Lin, L.-Y., Yu, W.-H., Lin, W.-P., Chen, C.-C., & Tu, Y.-F. (2022). Frontiers in Pediatrics, 10 Read this article

Early detection of developmental delays relies on the accuracy of the caregivers’ concerns of children’s developmental problems. The aim of this study was to investigate the agreement between the caregivers’ awareness of children’s developmental problems and professional identification. Caregivers of 1963 children (age range: 5–71 months; mean: 38.4 months) younger than 6 years old who were at risk of developmental delays and referred to the center for a comprehensive evaluation were enrolled in this study. The caregivers’ initial concerns of cognitive, speech/language, emotional/behavioral, motor and global development showed low agreement with the results of professional identification. The major disagreement was observed in the cognitive domain. Speech/language developmental concern was an important red-flag indicator of cognitive and emotional/behavioral developmental delays. The comorbid presence of ID, ASD, and ADHD was high in this study. Child’s age and mothers’ level of education were significant indicators for detecting the child’s developmental problems. It is recommended that assessing the cognitive developmental status is essential for all children in the identification process. Practitioners should not overlook caregivers' concern about speech/language and emotional/behavioral development. Transdisciplinary practitioners provide educational guidance to caregivers, especially in the domains of cognitive, speech/language, and emotional/behavioral development.

早期發現兒童發展遲緩取決於照顧者對兒童發展問題關注的準確性。本研究的目的是調查照顧者對兒童發展問題的認識與專業評估結果之間的一致性。本研究招募了 1963 名 6 歲以下兒童（年齡範圍：5-71 個月；平均：38.4 個月）的照顧者，這些兒童因發展遲緩的風險被轉介到中心進行全面評估。照顧者對兒童的認知、語言、情緒/行為、動作和整體發展遲緩問題的關注與專業鑑定結果的一致性較低，尤其是認知領域的一致性最低。語言發展問題是認知和情緒/行為發展遲緩的重要危險信號。研究中發現有很高的比率同時伴隨智能障礙、自閉症和注意力不足過動症的共病。兒童的年齡和母親的教育程度是檢測孩子發展問題的重要指標。建議在鑑定過程中評估所有兒童的認知發展狀態是不可少的。臨床工作者不應忽視照顧者對語言和情緒/行為發展的關注。跨領域專業人員需要為照顧者提供衛教資訊，特別是在認知、語言和情緒/行為發展領域。

Wang, X.-Y., Lin, J.-J., Lu, M.-K., Jang, F.-L., Tseng, H.-H., Chen, P.-S., Chen, P.-F., Chang, W.-H., Huang, C.-C., Lu, K.-M., Tan, H.-P., & Lin, S.-H. (2022). Schizophrenia, 8(1), 4. Read this article

Minor physical anomalies (MPAs) have been suggested as biomarkers and potential pathophysiological significance for schizophrenia. However, an integrated, clinically useful tool that used qualitative and quantitative MPAs to visualize and predict schizophrenia risk while characterizing the degree of importance of MPA items was lacking. We recruited a training set and a validation set to conduct logistic regression and Lasso regression to select the best parameters of MPAs and constructed nomograms. Two nomograms were built to show the weights of these predictors. The results of the validation dataset verified the efficacy of the nomograms with the area under the curve 0.84 and 0.85 in the logistic regression model and lasso regression model, respectively. This study provides an easy-to-use tool based on validated risk models of schizophrenia and reflects a divergence in development between schizophrenia patients and healthy controls (https://www.szprediction.net/).

在過往研究中細微體質特徵被認為是思覺失調症的生物標記，且有其潛在病理生理意義。然而，臨床缺乏用於測量思覺失調症風險的質性和量性細微體質特徵之整合工具。我們使用邏輯斯迴歸和Lasso迴歸來選擇最佳參數以nomogram視覺化方式來預測思覺失調症之風險。驗證數據集結果的兩種迴歸模型中曲線下面積分別為 0.84 和 0.85。本研究反應了思覺失調症患者與健康對照組的發展差異，並提供一種基於驗證思覺失調症風險模型的便利使用工具 (https://www.szprediction.net/)。

Hung, H.-Y., Cheng, K.-C., Kuo, P.-C., Chen, I.-T., Li, Y.-C., Hwang, T.-L., Lam, S.-H., & Wu, T.-S. (2022). Antioxidants, 11(2), 335. Read this article

Seven new anthraquinones with rare 2-isopropyldihydrofuran (1–3) and 2,2-dimethylpyrano (4–7) moieties together with thirty-four known compounds were isolated from the extracts of whole Hedyotis diffusa plants. Their structures were elucidated and established by various spectroscopic and spectrometric analytical methods. Among these isolates, selected compounds were examined for their anti-inflammatory activity. The results showed that rare substituted anthraquinones displayed potent inhibitory activity with IC50 values ranging from 0.15 ± 0.01 to 5.52 ± 1.59 µM on the N-formyl-methionyl-leucyl-phenylalanine/cytochalasin B (fMLP/CB)-induced superoxide anion generation and elastase release cellular models. Meanwhile, the proposed drug target of the active anthraquinone was studied by computer modeling. The binding affinity between the anti-inflammatory anthraquinone and elastase was evaluated by molecular docking. These results provided the scientific insight into the medicinal values of Hedyotis diffusa and vision of development as lead compounds. （Abstract, Antioxidants, 2022, 11(2), 335）

白花蛇舌草為常用的清熱解毒中草藥，本研究自全株植物之乙醇提取物中分離到41個天然化合物，其中新化合物1-3具有少見的2-isopropyldihydrofuran蒽醌骨架，而新化合物4-7具有2,2-dimethylpyrano蒽醌骨架，經由各種化學光譜和光譜分析方法對其結構進行了詳細的闡明和建立。在這些化合物中，篩選部分化合物進行抗發炎活性檢測，蒽醌類化合物對fMLP/CB誘導的超氧陰離子生成和彈性蛋白酶釋放具有很好的抑制活性，IC50 範圍在0.15 ± 0.01 ~ 5.52 ± 1.59 µM。同時，通過電腦模擬軟體，分子對接的方法研究抗發炎蒽醌與彈性蛋白酶的結合親和力推測。本研究結果為白花蛇舌草的藥用價值和蒽醌先導化合物的開發提供了部分科學依據。

Chen, B.-L., Cheng, Y.-Y., Lin, C.-Y., & Guo, H.-R. (2022). International Journal of Environmental Research and Public Health, 19(3), 1130. Read this article

Teachers are more likely to use a loud voice at work than the general working population, but few longitudinal studies have been conducted on their risk of voice disorders. The occurrence of voice disorders in private school teachers was assessed by using the Longitudinal Health Insurance Database 2000 of Taiwan. This study included private school teachers who were under 35 years old and newly employed between 2000 and 2010, and used workers with other occupations as the comparison cohort. After adjusting for age, sex, income, and comorbidities of sinusitis and laryngitis, private school teachers had a higher risk of developing voice disorders (hazard ratio [HR] = 1.58; 95% confidence intervals: 1.43–1.75). In addition, the finding that elementary and highschool teachers had a higher risk than college teachers (HR: 2.56 vs. 1.44) and the pattern of increases in cumulative incidence over time. The results support the causality between occupation and voice disorders in teachers.

教師是聲帶疾患高風險族群，但較少縱貫性研究佐證。本研究利用台灣健保資料庫2000年版的百萬歸人檔，篩選出2000年至2010年間年齡少於35歲的新進私立學校教師，觀察他們的聲帶疾患發生情形，並與其他整體職業族群相對照。在校正年齡、性別、收入以及鼻竇炎、喉炎後，發現私校教師有較高罹患聲帶疾病風險(相對風險1.58，95%信賴區間1.43~1.75)，且中小學較大專院校教師有更高風險(相對風險分別為2.56和1.44)，暗示較長授課時數與管教需求的教師有更高的風險，進一步確立教師工作與聲帶疾患的因果關係。

Wang, W.-M., Ou, H.-T., Wen, M.-J., Su, P.-F., Yang, C.-Y., Kuo, T.-H., Wang, M.-C., & Lin, W.-H. (2022). Scientific Reports, 12(1), 4177. Read this article

This study aimed to assess the impact of diabetic retinopathy (DR) severity on the incidence of major adverse cardiac events (MACE) and end-stage renal disease (ESRD) in T1D patients. Patients diagnosed with T1D between 1999 and 2013 were identified from patient-level data of Taiwan’s National Health Insurance Research database. A total of 1135 patients were included and classified into mild DR (n = 454), severe DR (n = 227), or non-DR (n = 454) by using propensity score matching. Multi-state model analyses, an extension of competing risk models with adjustment for transition-specific covariates for prediction of subsequent MACE and ESRD, were performed. MACE and ESRD risks were significantly higher in the severe DR patients; a 2.97-fold (1.73, 5.07) and 12.29-fold (6.50, 23.23) increase in the MACE risk among the severe DR patients compared to the mild DR and DR-free patients, respectively; and, a 5.91-fold (3.50, 9.99) and 82.31-fold (29.07, 233.04) greater ESRD risk of severe DR patients than that of the mild DR and DR-free groups, respectively (p < 0.001). Severity of DR was significantly associated with the late diabetes-related vascular events (i.e., MACE, ESRD) among T1D patients.

本研究目的在評估糖尿病視網膜病變 (DR) 嚴重程度對第一型糖尿病患者(T1D)患者主要不良心臟事件 (MACE) 和末期腎病變 (ESRD) 發生率的影響。研究對象為從台灣國民健康保險研究資料庫收錄1999年至2013年間被診斷患有T1D的病人，總共納入1135例患者，通過傾向評分匹配分為輕度DR（n = 454）、重度DR（n = 227）或無DR的對照組（n = 454）。進行了多狀態模型分析，本分析方式為競爭風險模型的擴展，並調整了特定過渡的協同變項，以預測隨後的MACE和ESRD。嚴重DR患者的MACE和ESRD風險顯著升高；與輕度DR和無DR患者相比，嚴重DR患者的MACE風險分別增加 2.97倍（1.73、5.07）和12.29倍（6.50、23.23）；並且嚴重DR患者的ESRD風險分別比輕度DR組和無DR組高5.91倍（3.50, 9.99）和82.31倍（29.07, 233.04）（p < 0.001）。DR的嚴重程度與T1D患者的晚期糖尿病相關血管事件（即MACE和ESRD）顯著相關。

Chu, C.-L., Chang, J.-Y., Chen, P.-Y., Wang, P.-Y., Hsu, S.-H., & Chou, D. (2022). Scientific Reports, 12(1), 959. Read this article

Horizontally stacked pure-Ge-nanosheet gate-all-around field-effect transistors were developed in this study. Large lattice mismatch Ge/Si multilayers were intentionally grown as the starting material rather than Ge/GeSi multilayers to acquire the benefits of the considerable difference in material properties of Ge and Si for realising selective etching. Additionally, dislocations were observed in suspended Ge nanosheets because of the absence of a Ge/Si interface and the disappearance of the dislocation-line tension force owing to the elongation of misfit dislocation at the interface. Forming gas annealing of the suspended Ge nanosheets resulted in a significant increase in the glide force compared to the dislocation-line tension force; the dislocations were easily removed because of this condition and the small size of the nanosheets. Based on this structure, a new mechanism of dislocation removal from suspended Ge nanosheet structures by annealing was described, which resulted in the structures exhibiting excellent gate control and electrical properties.

本研究目標乃開發一個水平堆疊的純鍺納米片柵環場效應晶體管。以大晶格錯位的Ge/Si多層作為起始材料，而非多層之Ge/GeSi。透過利用Ge和Si的材料性質有很大差異的好處，以實現選擇性蝕刻之目的。此外，由於沒有 Ge/Si 界面，並且於界面處錯位的拉申，使位錯線張力消失。與位錯線張力相比，懸浮鍺納米片的形成氣體退火導致滑動力顯著增加；由於這種條件和納米片的小尺寸，位錯很容易去除。基於這種結構，描述了一種通過退火從懸浮的鍺納米片結構中去除錯位的新機制，從而使結構表現出優異的柵極控制和電學性能。

Chen, H.-B. (2022). Scientific Reports, 12(1), 2869. Read this article

Hamiltonian ensemble (HE) is a novel approach to investigate the incoherent dynamical processes of quantum systems. It is particularly versatile in locally detecting bipartite quantum correlations and the characterization of the process nonclassicality. The HE theory is, in principle, applicable to very general unital dynamics; however, due to the technical difficulty imposed by the non-abelian algebraic structure underlying the HE, the results are exemplified under the frameworks of pure dephasing or isotropic depolarization. In this work, I achieve to circumvent the algebraic difficulty and go further beyond the aforementioned two frameworks, reaching the regime of anisotropic decoherence. A new type of HE of structural disorder in canonical form is studied. The disorder is categorized according to different levels of symmetry of its geometry. I have demonstrated four levels of symmetry, from the most symmetric case of spherical symmetry to the discrete type of simultaneous reflectional symmetries. This enables us to clearly distinguish how the different incoherent dynamical behaviors are caused by various types of symmetry breaking. These results significantly enhance the applicability the HE-simulation of open quantum systems.

哈密頓量系綜集合表示法是近年來新發展起來的工具，可用來研究量子系統的消相干動力學過程。當應用這個方法在局部地偵測量子關聯性、描述與量化消相干動力學過程中展現出的非古典性時又特別的有用。儘管本方法理論上可以廣泛應用在各類型的消相干動力學過程中，然而，由於本方法其內在的非阿貝爾代數結構之故，使得其廣泛應用性會遇到許多數學上的困難，致使目前大多數的工作僅用其來描述特定簡化類型的動力學過程，如純消相位過程或各向均勻去極化過程。在本工作中，我們成功克服一些數學代數結構方面的困難，突破以往的研究限制框架，達到各向非均勻去極化過程。因此這裡可以研究一種新類型的哈密頓量系綜集合，我們稱之為結構性的無序。這類結構性的無序可根據其無序分布的對稱性而加以有條理的分類與研究，讓我們可以了解不同的消相干行為是由甚麼類型的對稱性破缺引起。這些研究成果使的哈密頓量系綜集合理論的應用性可以更加廣泛。

Yen, P.-C., Chou, Y.-T., Li, C.-H., Sun, Z.-J., Wu, C.-H., Chang, Y.-F., Lu, F.-H., Yang, Y.-C., Chang, C.-J., & Wu, J.-S. (2022). Journal of Clinical Medicine, 11(5), 1445. Read this article

Liver fibrosis is associated with liver-related outcomes, yet often underdiagnosed in the primary care settings. Hyperuricemia is associated with non-alcoholic fatty liver disease (NAFLD), but the relationship between hyperuricemia and liver fibrosis remains unclear. Data on individuals without NAFLD is also limited. We investigated the association between hyperuricemia and liver fibrosis in subjects with and without NAFLD. This study recruited 11,690 relevant participants from a health-checkup center. Hyperuricemia was positively associated with significant liver fibrosis (p = 0.001) in the logistic regression. The positive association of hyperuricemia with significant liver fibrosis remained in subjects with NAFLD (p = 0.001), but not in subjects without NAFLD.

肝纖維化與肝相關的結果相關，但在基層醫療卻時常被忽略。高尿酸血症與非酒精性脂肪肝(NAFLD)有關，但與肝纖維化的關係仍未明。過去研究資料在沒有NAFLD的族群者資料有限。本篇研究探討在有無NAFLD的病人，其高尿酸血症及肝纖維化的相關性。此篇收錄11690位至健康檢查中心、符合收錄條件的成年人。經過邏輯式迴歸，高尿酸血症與顯著肝纖維化成正相關(p = 0.001)，且其正相關僅見於有NAFLD的族群，而不見於無NAFLD的族群。

Teng, Y. T., Chin, W. L., Chang, D. K., Chen, P. Y., & Chen, P. W. (2022). IEEE Access 10,2721-2728. Read this article

This work aims at optimizing the hardware implementation of the SubBytes and inverse SubBytes operations in the advanced encryption standard (AES). To this, the composite field arithmetic (CFA) is employed to optimize all building blocks in S-box (and inverse S-box) of SubBytes (and inverse SubBytes) transformation. A joint design of S-box and inverse S-box is also proposed to further enhance the area efficiency. Specifically, the area of multiplier in the Galois composite field, GF((22)2), is reduced. The squaring and multiplication with constant λ in GF((22)2) are combined and optimized as well. Moreover, the multiplicative inversion in GF((22)2) is manually optimized. Furthermore, the S-box and inverse S-box are combined and optimized using the pre_processing and post_processing modules. To increase the throughput, a balanced and pipelined architecture is derived. Using the proposed architecture, a throughput of 5.79 Gbps for the S-box can be achieved on Virtex-6 XC6VLX240T and 10% better than the conventional work. According to the ASIC implementation result, the proposed design can still achieve the highest area efficiency and approximately 30% better than conventional works using TSMC 90nm process.

這項工作旨在優化高級加密標準 (AES) 中SubBytes和反SubBytes操作的硬件實現。為此，採用複合域算法（CFA）優化SubBytes（和逆SubBytes）變換的S盒（和逆S盒）中的所有構建塊。還提出了S盒和逆S盒的聯合設計，以進一步提高面積效率。具體來說，伽羅瓦複合域中乘數的面積GF((22)2)減少了。 GF((22)2)中常數λ的平方和乘法也被組合和優化。此外，GF((22)2)中的乘法反元素是手動優化的。此外，使用 pre_processing 和 post_processing 模塊對S盒和逆S盒進行組合和優化。為了增加吞吐量，衍生出一種平衡的流水線架構。使用所提出的架構，S盒的吞吐量可以在 Virtex-6 XC6VLX240T 上實現 5.79 Gbps，比傳統工作高 10%。根據 ASIC 的實現結果，所提出的設計仍然可以達到最高的面積效率，並且比使用台積電 90nm 工藝的傳統作品好約 30%。

Chen, Y.-C., Lu, B.-Z., Shu, Y.-C., & Sun, Y.-T. (2022). Frontiers in Endocrinology, 12.2721-2728. Read this article

Aims: Diabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral vascular permeability (Ktrans) in the progression of type 2 diabetes mellitus (T2DM). Methods: Ktrans was crossectional measured in T2DM and non-diabetes groups with or without CSVD using dynamic contrast-enhanced MRI (DCE-MRI).Results: In all patients with T2DM, the Ktrans of white matter (WM) was increased, whereas the Ktrans of gray matter (GM) was increased only in T2DM with CSVD. The involvement of WM was earlier than GM and was prior to the CSVD features could be visualized on MRI. Among the commonly available four CSVD items of MRI, microbleeds was most sensitive, indicating the increased permeability in all patients. Increased Ktrans in T2DM was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces, in contrast to patients without diabetes. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs. Conclusions: This study highlights the early development of cerebral microangiopathy with increased BBB leakage in T2DM, prior to the CSVD features can be visualized on MRI. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.

Chen, K.-W., Bear, L., & Lin, C.-W. (2022). Sensors, 22(6),2331. Read this article

Electrocardiographic imaging (ECGi) reconstructs electrograms at the heart’s surface using the potentials recorded at the body’s surface. This is called the inverse problem of electrocardiography. This study aimed to improve on the current solution methods using machine learning and deep learning frameworks. Electrocardiograms were simultaneously recorded from pigs’ ventricles and their body surfaces. The Fully Connected Neural network (FCN), Long Short-term Memory (LSTM), Convolutional Neural Network (CNN) methods were used for constructing the model. A method is developed to align the data across different pigs. We evaluated the method using leave-one-out cross-validation. For the best result, the overall median of the correlation coefficient of the predicted ECG wave was 0.74. This study demonstrated that a neural network can be used to solve the inverse problem of ECGi with relatively small datasets, with an accuracy compatible with current standard methods.

心臟電位影像重建(Electrocardiographic imaging)是基於體表所測得之心電圖，重建心臟表面或內部的電位分佈的過程。此問題亦被稱為反向問題(Inverse Problem)。由於此問題在本質上無法得出唯一解，以及不容易針對體表與心臟間的電傳導性建模，目前針對此問題所發展出的方法，其準確度約0.7(所重建的心電圖與實際心電圖之間相關系數之中位數)。本研究嘗試使用神經網路解決此問題，以增加模型的準確度。本研究使用之兩組資料，一是來自於豬體表所量測之多個心電圖訊號，二是同時量測之豬心臟表面的心電圖。第一部分的研究，訓練與測試模型的資料皆來自同一之豬。所使用之神經網路有兩種。一是由數個全連接層(Fully Connected Layer FCN)所組成之神經網路，二是由長短期記憶(Long Short-Term Memory LSTM)神經網路所組成。第二部分的研究，我們將來源於不同的五隻豬之資料進行轉換，加以統合。接著我們使用卷積神經網絡(Convolutional Neural Network CNN)來建立模型。本研究使用留一驗證（leave-one-out cross-validation）作為模型準確度的驗證方法。若比較重建的心臟表面心電圖與實際心電圖，在第一部分研究中，使用全連接層FCN之部分，整體的相關系數之中位數以及前四分之一與後四分之一的數值為0.90 [0.68–0.96]。使用全連接層LSTM之部分則為0.82 [0.54–0.93]。在第二部分研究，使用CNN，整體的相關系數之中位數以及前四分之一與後四分之一的數值則為0.74 [0.22–0.89]。若比較重建的激發時間圖(activation map)，在第一部分研究中，使用全連接層FCN之部分，整體的相關系數之中位數以及前四分之一與後四分之一的數值為0.86 [0.61–0.93]。使用全連接層LSTM之部分則為0.52 [0.05–0.80]。在第二部分研究，使用CNN，整體的相關系數之中位數以及前四分之一與後四分之一的數值則為0.82 [0.67–0.93]。若比較激發點位置誤差(localization error)，在第一部分研究中，使用全連接層FCN之部分，整體的距離之中位數以及前四分之一與後四分之一的數值為10.4 [3.6–22.6] mm。使用全連接層LSTM之部分則為18.5 [6.4–41.5] mm。在第二部分研究，使用CNN，整體的相關系數之中位數以及前四分之一與後四分之一的數值則為9.3 [3.4–17.0] mm。本研究顯示，針對心臟電位影像重建，我們可以使用相對少量的資料解決。我們所達到的最佳結果為0.74(所重建的心電圖與實際心電圖之間相關系數之中位數)。此外，本研究也顯示並不需要精確的座標資訊來重建心電圖。針對模型的準確性而言，在不同的豬隻與不同的量測結果之歧異度仍然很大。這可能與資料量相對較小有關，這可以在第二部分研究中看到。其整體準確度較佳，可能與其整合了所有的資料，其資料量較第一部分多有關。臨床應用部分，此研究顯示可使用非侵入性的體表量測心電圖，來找尋心臟的電刺激源點。此資訊可用於心室早期收縮病人之治療。

Huang, Y.-H., & Wu, Y.-C. (2022). Polymers, 14(5),992. Read this article

This study aimed to explore a low cost and sustainable adsorbent to remove Sr2+ and Co2+ ions, which are major radioactive ions in nuclear wastewater. The material properties of the alkali-activated metakaoline as a function of soaking time at ambient temperature from 1 day to 7 days were examined by XRD, XRF, SEM, and solid-state NMR. Adsorption isotherms were used to evaluate the appropriate soaking time for optimal sorption performance for both Sr2+ and Co2+ ions. The alkali-activated metakaolin soaked for 3 days (BK3) presented the maximum adsorption capacities of 3.81 meq/g (167.5 mg/g) and 4.02 meq/g (118.5 mg/g) for Sr2+ and Co2+, respectively. The sorption mechanisms for Sr2+ and Co2+ in the BK3 sample were investigated, and the experimental results indicated that adsorption for Sr2+ was achieved via ion exchange. By contrast, surface complexation in combination with ion exchange contributed to the sorption mechanisms for the removal of Co2+. Competitive adsorption experiments revealed that the alkali-activated metakaolin favored the adsorption for divalent ions (i.e., Sr22+ and Co2+), and it was less effective for Cs+. Finally, the used adsorbent could be directly mineralized and vitrified by heat treatment to immobilize the Sr2+ and Co2+ ions.

本研究旨在開發具有量產潛力且符合永續發展的無機吸附劑，用於去除核廢水的Sr2+與Co2+放射性離子。使用天然高嶺土作為原料，在常溫下以氫氧化鈉進行鹼活化處理，觀察並討論不同鹼活化時間(1至7天)，對於高嶺土的結構變化情形。批次等溫吸附實驗確認，常溫鹼活化3天之樣品（BK3）對Sr2+與Co2+離子具有最高之吸附效率，分別為 3.81 meq/g (167.5 mg/g) 與4.02 meq/g (118.5 mg/g) 。研究結果亦指出，BK3樣品對Sr2+離子的吸附是由離子交換機制所主導，而對Co2+則是由表面錯合反應結合離子交換兩種機制綜合發生。競爭性離子吸附實驗發現，BK3樣品對於二價離子（Sr2+與Co2+）具有較高的選擇性吸附能力。本研究所合成之吸附劑以容易取得且價格低廉之天然礦物為原料，在常溫下即可獲得高效率之無機離子吸附劑，而完成離子吸附工作後之吸附劑廢料，可藉由熱處理將離子直接礦化於結構中，達到離子封存的目的，在核廢料處理的應用上具有高度潛力。

Li, C.-C., Hsu, J. C., Liang, F.-W., Chang, Y.-F., Chiu, C.-J., & Wu, C.-H. (2022). Aging, 14(5),2239-2251. Read this article

Osteoporotic fracture is a common public-health problem in ageing societies. Although post-fracture usage of osteoporosis medications may reduce mortality, recent results have been inconsistent. Participants aged 65 years old and older newly diagnosed with both osteoporosis and hip or vertebral fractures within 2009-2017 were recruited from Taiwan National Health Insurance Research Database. Osteoporosis medication exposure was calculated after the first-time ambulatory visit with newly diagnosed osteoporosis. Patients were followed until death or censored at the end of 2018. A total of 87,935 participants aged 65 years old and over (73.4% female), with a mean 4.13 follow-up years, were included. Taking medication was associated with significantly lower risk of mortality, even in the oldest-old adults, where a longer duration of taking osteoporosis medication was associated with lower all-cause mortality. Specific causes of mortality were also significantly lower for participants taking osteoporosis medication, such as cancer and cardiovascular disease. In conclusion, osteoporosis medication after hip or vertebral fracture may reduce mortality risk in older adults, notably in oldest-old adults. Encouraging the use of post-fracture osteoporosis medication in healthcare policies is warranted.

骨鬆性骨折是高齡化社會中常見的公共衛生問題。儘管骨折後使用骨質疏鬆症藥物可能會降低死亡率，但最近的研究結果並不一致。本研究從台灣全民健保資料庫中篩選2009~2017年間新診斷骨質疏鬆症且髖部或脊椎骨折的65歲及以上參與者，並追蹤至2018年。骨鬆藥物暴露是從第一次門診開立骨鬆藥物後開始計算。共計87,935名65歲及以上的參與者（73.4%為女性）進入本研究，平均追蹤時間為4.13年。研究結果顯示，使用骨鬆藥物可顯著降低骨鬆骨折後的全死因死亡率，即使是85歲以上的老人。使用骨鬆藥物的時間越長，死亡風險越小。而使用骨鬆藥物亦可顯著降低骨鬆骨折後的常見死因死亡率，如癌症和心血管疾病。因此，鼓勵在醫療政策中，在骨鬆骨折後使用骨鬆藥物是必要的。

Hsieh, Y.-P., Chen, K.-C., Chen, M.-Y., Huang, L.-Y., Su, A.-Y., Chiang, W.-F., Huang, W.-T., & Huang, T.-T. (2022). International Journal of Molecular Sciences , 23(9), 4495. Read this article

Oral squamous cell carcinoma (OSCC) accounts for over 90% of oral cancers and causes considerable morbidity and mortality. Epigenetic deregulation is a common mechanism underly- ing carcinogenesis. DNA methylation deregulation is the epigenetic change observed during the transformation of normal cells to precancerous and eventually cancer cells. This study investigated the DNA methylation patterns of PTK6 during the development of OSCC. Bisulfite genomic DNA sequencing was performed to determine the PTK6 methylation level. OSCC animal models were established to examine changes in PTK6 expression in the different stages of OSCC development. The DNA methylation of PTK6 was decreased during the development of OSCC. The mRNA and protein expression of PTK6 was increased in OSCC cell lines compared with human normal oral keratinocytes. In mice, the methylation level of PTK6 decreased after treatment with 4-nitroquinoline 1-oxide and arecoline, and the mRNA and protein expression of PTK6 was increased. PTK6 hypomethylation can be a diagnostic marker of OSCC. Upregulation of PTK6 promoted the proliferation, migration, and invasion of OSCC cells. PTK6 promoted carcinogenesis and metastasis by increasing STAT3 phosphorylation and ZEB1 expression. The epigenetic deregulation of PTK6 can serve as a biomarker for the early detection of OSCC and as a treatment target.

蛋白質酪氨酸激酶6表觀基因體調控失調促進口腔鱗狀細胞癌的癌變
口腔鱗狀細胞癌佔所有口腔癌類型的90%以上，並且會導致相當高的死亡率。表觀基因體調控異常是常見的致癌機制。DN甲基化調控異常會使正常細胞轉化為癌前病變細胞最終轉變成癌細胞。在本研究中，調查了口腔鱗狀細胞癌發展過程中PTK6的DNA甲基化調控。在此研究中，透過亞硫酸氫鹽基因組DNA測序來確定PTK6甲基化水平。以及建立口腔鱗狀細胞癌動物模型來檢查，在口腔鱗狀細胞癌不同階段中PTK6的表達差異。在口腔鱗狀細胞癌的發展過程中，PTK6 的DNA甲基化顯著降低。與人類正常口腔角質細胞相比，口腔鱗狀細胞癌細胞株中PTK6的mRNA和蛋白質表達顯著增加。在動物模型中，利用4-硝基喹啉1-氧化物和檳榔鹼處理後，PTK6的甲基化水平顯著降低，而PTK6的mRNA和蛋白表達顯著增加。從這些結果可以發現，PTK6低甲基化可以作為口腔鱗狀細胞癌的診斷標誌物。在口腔鱗狀細胞癌中， PTK6的表現增加促進了口腔鱗狀細胞癌細胞的增殖、遷移和侵襲。 PTK6通過增加STAT3磷酸化和ZEB1表達促進癌變和轉移。 PTK6的表觀遺傳失調可作為早期檢測OSCC的生物標誌物和治療標的。

Chen, W.-L., & Chuang, H.-S. (2022). Biosensors , 12(6), 362. Read this article

Brownian motion, which is a natural phenomenon, has attracted numerous researchers and received extensive studies over the past decades. The effort contributes to the discovery of optical diffusometry, which is commonly used for micro/nano particle sizing. However, the analysis uncertainty caused by the coupling relationship among particle diameter, temperature, and fluid viscosity usually poses a barrier to precise measurement. Preventing random background noise becomes the key to achieving a high level of accuracy in diffusometry detection. Recently, Janus particles have become known as an ideal tool for resolving the rotational Brownian motion. Followed by our previous study, the rotational Brownian motion and the translational Brownian motion can be separately measured using the Janus particles. Accordingly, a simple self-viscosity and temperature-compensated technique based on the delicate removal of temperature and fluid viscosity variations through particle tracking was first proposed in this study. Consequently, the translational Brownian motion was expressed in terms of particle trajectory, whereas the rotational Brownian motion was expressed in terms of the blinking signal from the Janus particles. The algorithm was verified simulatively and experimentally in temperature (10 °C to 40 °C) and viscosity-controlled (1 mPa·s to 5 mPa·s) fields. In an evaluation of biosensing for a target protein, IFN-γ, the limit of detection of the proposed self-compensated diffusometry reached 0.45 pg/mL, whereas its uncertainties of viscosity and temperature were 96 and 15-fold lower than the pure the rotational Brownian motion counterpart, respectively. The results indicated the low-uncertainty and high-accuracy biosensing capability resulting from the self-viscosity and temperature-compensated technique. This research will provide a potential alternative to future similar bead-based immunosensing, which requires ultra-high stability and sensitivity.

布朗運動是一種自然現象，在過去的數十年裡，吸引了相當多的科研人員投入研究，而這一連串的努力最終也促成了光學擴散儀的發展。光學擴散儀通常用於奈/微米粒子粒徑的測定；然而，由於粒徑、液體溫度和粘度之間具有相互耦合關系，因此易引起分析不確定性，對精確測量構成阻礙。為此，降低背景雜訊便成為擴散測量法實現高精確度的首要關鍵。近來，雙性粒子已成為量化旋轉布朗運動的一項理想工具。根據我們之前的研究，旋轉布朗運動和位移布朗運動皆可以透過雙性粒子分別測定。因此，本研究提出了一種簡單的自我黏度和溫度補償技術，希望透過追蹤粒子巧妙去除流體溫度和黏度變化的影響。原則上，位移布朗運動可由粒子軌跡來顯示，而旋轉布朗運動則用雙性粒子的閃爍信號來表示。該演算法已在控制溫度（10 °C至40 °C）和黏度（1 mPa·s至5 mPa·s）範圍內成功地進行了模擬和實驗驗證。最後，我們還利用一種指標蛋白，IFN-γ，來評估本技術在生物感測方面的效果。結果顯示檢測極限可達到0.45 pg/mL，而黏度和溫度的不確定性分別比單純利用旋轉布朗運動的方法低了將近96倍和15倍。這些結果顯示，本研究中的自我黏度和溫度補償技術具有低不確定性和高精度的生物感測能力。這項研究預期可為未來需要超高穩定性和靈敏度之類似微珠免疫感測應用提供一個潛在的替代方案。

Shah, P., & Chen, C.-S. (2022). International Journal of Molecular Sciences , 23(2), 712. Read this article

Cell-penetrating peptides (CPPs) have distinct properties to translocate across cell envelope. The key property of CPPs to translocation with attached molecules has been utilized as vehicles for the delivery of several potential drug candidates that illustrate the significant effect in in-vitro experiment but fail in in-vivo experiment due to selectively permeable nature of cell envelop. Penetratin, a well-known CPP identified from the third α-helix of Antennapedia homeodomain of Drosophila, has been widely used and studied for the delivery of bioactive molecules to treat cancers, stroke, and infections caused by pathogenic organisms. Few studies have demonstrated that penetratin directly possesses antimicrobial activities against bacterial and fungal pathogens; however, the mechanism is unknown. In this study, we have utilized the power of high-throughput Saccharomyces cerevisiae proteome microarrays to screen all the potential protein targets of penetratin. Saccharomyces cerevisiae proteome microarrays assays of penetratin followed by statistical analysis depicted 123 Saccharomyces cerevisiae proteins as the protein targets of penetratin out of ~5800 Saccharomyces cerevisiae proteins. To understand the target patterns of penetratin, enrichment analyses were conducted using 123 protein targets. In biological process: ribonucleoprotein complex biogenesis, nucleic acid metabolic process, actin filament-based process, transcription, DNA-templated, and negative regulation of gene expression are a few significantly enriched terms. Cytoplasm, nucleus, and cell-organelles are enriched terms for cellular component. Protein-protein interactions network depicted ribonucleoprotein complex biogenesis, cortical cytoskeleton, and histone binding, which represent the major enriched terms for the 123 protein targets of penetratin. We also compared the protein targets of penetratin and intracellular protein targets of antifungal AMPs (Lfcin B, Histatin-5, and Sub-5). The comparison results showed few unique proteins between penetratin and AMPs. Nucleic acid metabolic process and cellular component disassembly were the common enrichment terms for penetratin and three AMPs. Penetratin shows unique enrichment items that are related to DNA biological process. Moreover, motif enrichment analysis depicted different enriched motifs in the protein targets of penetratin, LfcinB, Histatin-5, and Sub-5.

細胞穿透胜肽(CPP)有跨越細胞膜的明顯特性，CPP和附著分子有跨細胞膜的關鍵特性被用來運送許多具有潛力的藥物，在體外試驗有顯著效果，但在體內試驗失敗是因為有細胞膜的選擇性通透關係。Penetratin是一種著名的CPP源自於觸角族同域的黑腹果蠅的第三阿法-螺旋，被廣泛利用或研究在傳遞生物活性分子以治療癌症、中風、和由致病微生物所引起的感染。少許研究有說明penetratin擁有對抗細菌與真菌病原體的活性；然而這個機轉是未知的。在此研究中，我們使用高通量釀酒酵母菌蛋白質微陣列的技術來分析在penetratin潛在所攻擊的目標蛋白。運用釀酒酵母菌微陣列分析penetratin，並進行統計分析，其中約5800個釀酒酵母的蛋白質中有123個是penetratin的目標蛋白。為了瞭解penertratin的目標蛋白特性，此123種目標蛋白被進行富集分析。在生物程序方面：核蛋白複合物生物產生、核酸代謝過程、肌動蛋白纖維-基本過程、轉譯、DNA-模板、基因表現的負控制都是一些顯著富集的特性。細胞質、細胞核、胞器都是這些蛋白質富集的細胞部位。蛋白質和蛋白質相互作用分析描述這123 蛋白質的特性在於核蛋白複合物的生物產生、皮質細胞骨架和組蛋白結合方式，他們代表123種penetratin目標蛋白的主要富集的特性。我們也比較penetratin目標蛋白和其他抗真菌AMPs（Lfcin B, Histatin-5, and sub-5)細胞內的目標蛋白。比較結果顯示penetratin和AMPs間有少許獨特的蛋白質。核酸代謝和細胞成份分解是pentratin和三種AMPs 共同的富集特性。Penetratin 獨特富集的項目和DNA生物過程有關。此外，基序豐富度分析結果得知penetratin ,Lfcin B,Histatin-5,and Sub-5目標蛋白中，有不同富集的基序。

Ma, C.-H., Yang, H.-L., Huang, Y.-T., Wu, Z.-X., Cheng, H.-C., Chou, W.-C., Hung, C.-H., & Tsai, K.-L. (2022). Annals of Medicine , 54(1), 1320-1327. Read this article

Vertebral compression fractures (VCFs) often occur in patients with osteoporosis. These fractures can also lead to postural changes. Several studies have shown that patients with vertebral compression fractures have a restrictive pattern in their pulmonary function. Percutaneous vertebroplasty (PVP) is the standard treatment for vertebral compression fractures, with the benefits of pain relief and enhancement of vertebral stability for partially collapsed vertebral bodies. However, the effects of PVP on short-term recovery of respiratory performance have not been investigated. Therefore, this study aimed to examine the changes in pulmonary function, respiratory muscle strength, maximal voluntary ventilation (MVV), and chest mobility in patients with vertebral compression fractures after PVP. We recruited 32 VCF patients. Four time points were measured: before and after PVP and 1 and 3 weeks after PVP. Chest expansion and back pain improved at each time point after PVP. MVV showed significant progress at both 1 and 3 weeks after discharge. Forced expiratory volume in 1 second (FEV1) and maximal inspiratory muscle strength significantly improved one week after discharge. Taking all the data together, PVP can resolve severe back pain and provide excellent improvements in MVV and chest mobility in patients with vertebral compression fractures.

脊椎椎體壓迫性骨折經常發生在骨質疏鬆症患者身上。這些骨折可能導致姿勢變化。多項研究指出，脊椎椎體壓迫性骨折患者的肺功能存在限制性模式。經皮椎體成形術是脊椎椎體壓迫性骨折的標準治療方法，具有緩解疼痛和增強部分塌陷椎體的椎體穩定性的好處。然而，尚未研究驗證對經皮椎體成形術呼吸性能短期恢復的影響。因此，本研究旨在驗證經皮椎體成形術後對脊椎椎體壓迫性骨折患者肺功能、呼吸肌力量、最大自主通氣量和胸部活動度的變化。我們招募了 32 名脊椎椎體壓迫性骨折患者。測量了四個時間點：經皮椎體成形術前和之後以及經皮椎體成形術後1和3週。經皮椎體成形術後每個時間點的胸脹和背痛都有所改善。 最大自主通氣量在出院後 1 周和 3 週均顯示出顯著進展。出院一周後，1秒用力呼氣量最大吸氣肌力顯著改善。綜合所有數據，經皮椎體成形術不僅可以解決嚴重的背痛，還可以顯著改善脊椎椎體壓迫性骨折患者的最大自主通氣量和胸部活動度。

You, B., Lu, J.-Y., Chen, P.-L., Hung, T.-Y., & Yu, C.-P. (2022). Materials , 15(5), 1871. Read this article

Metal-hole-supported terahertz (THz) waves through the structure of a metal-wire-woven hole array (MWW-HA) present high-frequency-passed transmittance spectra of one plasmonic metamaterial with artificial plasmonic frequencies, which are inversely proportional to metal-hole widths. For the transmitted THz waves of MWW-HA, transverse-electric (TE) and transverse-magnetic (TM) waveguide modes mix within a symmetric metal-hole boundary. THz resonance waves transversely crossing the holes of MWW-HA are experimentally characterized with spectral peaks in the frequency range of 0.1–2 THz that are correlated with aperture sizes, unit-cell-hole widths, metal-wire thicknesses, and wire-bending angles. The metal-hole-transported resonance waves of MWW-HA are dominated by TE waveguide modes instead of TM ones because a hole width of MWW-HA is approximate to the half wavelength of a resonance wave. The round metal edges of the woven metal wires can minimize the effective optical length of a thick metal hole to transmit THz resonance waves, thereby resulting the smallest rotation angle of linear polarization and high transmittance up to 0.94. An MWW-HA structure is therefore reliable for supporting metal-hole resonance waves with low resistance, whereas a metal-slab-perforated hole array cannot achieve the same result.

此研究發表以金屬線編織網的孔洞結構所傳輸的兆赫電磁波，發現具有電漿人造結構的高頻通過頻譜特徵與類似金屬電漿頻率的截止頻率表現，此高通頻譜與其截止頻率反比於編織網孔洞尺寸，由於金屬孔洞的二維對稱性，編織網孔洞內的兆赫電磁波是由橫向電波與橫向磁波，所混合而成的波導電場模態，此混合電場是經由橫向共振模式通過金屬編織網，其頻譜所展現的穿透率尖峰現象，是因為此兆赫頻率符合電磁波在金屬孔洞內的共振尺寸條件，包括孔徑尺寸、單元體結構寬度、金屬線徑與金屬線曲折角度等，並且經由共振過程的縱向消逝波，將0.1–2 THz兆赫波能量傳遞到出射端面，此外，經由調查比較穿透頻譜頻率與金屬孔洞寬度，證實橫向電波控制整體金屬編織網的穿透頻譜特徵，另外，金屬線的圓形狀表面可以縮減兆赫共振波傳輸的光學厚度，造成最低幅度的極化偏離表現，此實驗研究觀察最高穿透率可以達到0.94左右，不同於平板式金屬孔洞陣列的兆赫波穿透特性，此研究成功證實金屬編織孔洞陣列，不但能夠共振傳輸兆赫電磁波，還可以表現低損耗、保持極化偏振的特殊表現。

Chou, C.-Y., Cheng, W.-F., Chen, M.-Y., Lin, H., Ho, C.-M., Hung, Y.-C., Huang, L.-W., Wang, P.-H., Yu, M.-H., & Huang, Y.-F. (2022). Cancers , 14(7), 1746. Read this article

This large-scale study aimed to determine the long-term influences of potential prognostic predictors and progression-free interval (PFI) criteria for grading platinum-sensitivity in ovarian clear cell carcinoma (OCCC). We retrospectively reviewed the medical records of OCCC patients presenting at nine tertiary centres (1995–2015), and evaluated patient characteristics, therapeutic factors, clinical outcomes, and hazard ratios for disease progression and death. We enrolled 536 patients (median follow-up, 36.6 months) and developed newly defined distributions of PFIs (seven and 14 months) for grading platinum sensitivity. In the multivariate model, preoperative CA125 levels and chemoresponse independently predicted early-stage progression-free survival (PFS) risk. Post-progression cytoreduction correlated with reduced mortality risk. No unfavourable outcomes were observed with respect to coexisting endometriosis, fertility-sparing strategies, or platinum-based regimens. Cancers 2022, A PFI of ＜ 7 months, the strongest predictor of both post-progression mortality and second relapse risks, correlated with chemo-resistance, advanced tumour stage, and shortened post-progression survival. Chemotherapy regimens commonly used in front-line or relapse settings were limited in improving prognoses, especially in the advanced-stage cohort. Clinical trials of novel targeted agents and／or innovative biomarkers for chemoresistance should be comprehensively investigated and offered early to advanced-stage patients or those with OCCC progression occurring within seven months after receiving chemotherapy.

卵巢癌死亡率在婦女癌症死因中名列前茅，其中卵巢亮細胞癌是一種特殊難治的亞型。此協作研究目的在提供台灣大規模亮細胞癌臨床個案特性及治療相關之長期預後因子，以及開發鉑敏感分級的新穎臨床標準。研究設計為以九家醫學中心回溯性收集1995年至2015年診斷為卵巢亮細胞癌病人之詳細臨床資訊及分析病人特性與治療相關之復發或死亡風險。最後共收集536位病人，中位追蹤期為36.6個月。資料分析也發現無惡化期間採用＜7個月為鉑抗藥性、7-14個月為部分鉑抗藥性、及>14個月為鉑敏感性作為亮細胞癌之鉑敏感分級的新穎臨床標準，有別於常見之漿液型癌以6及12個月做為切點。多變數分析發現早期亮細胞癌的治療前CA125及對化學治療反應可做為無惡化存活期之獨立預測因子;首次疾病惡化後的減癌手術則可降低死亡率。亮細胞癌旁同時有子宮內膜異位存在、生育功能保留手術、或鉑藥物合併如paclitaxel或cyclophosphamide，則對早期癌病預後沒有明顯影響。我們發現，無惡化期間＜7個月是預測疾病惡化或死亡風險上，同時也是預測第二次疾病惡化上的獨立風險因子。檢測無惡化期間＜7個月的角色，的確也與化學治療抗藥性及晚期癌病明顯相關、並有較短的首次復發後之存活期。我們觀察到，尤其是晚期亮細胞癌病人，以鉑化合物併用他種化學治療藥物類別治療，無論是第一線時或是復發時使用，對於提升存活期的效果相當有限。因此未來應該在晚期、或第一次復發若在首次化療結束後＜7個月內就被發現之卵巢亮細胞癌族群，就應該鼓勵進入臨床試驗，以探討新穎生物鉑抗藥性指標或採用特殊標靶治療的策略，或能提升這種具鉑抗藥性卵巢癌患者的存活。

Chang, Y.-H., Yen, C.-H., Lai, C.-C., Lai, H.-Y., & Hung, H.-Y. (2022). Pharmaceuticals , 15(4), 449. Read this article

Although the population with nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) is increasing, there is still no medicine indicated for treating these diseases clinically. Therefore, a new drug to overcome NAFLD and NASH is in urgent need. Capillarisin, a 2-phenoxychromone isolated from Artemisia capillaris Thunb., is well-known for its liver-protective effects. Thus, a series of 2-phenoxychromones was prepared and evaluated for its protective activity against lipid droplet formation in oleic acid (OA)-treated Huh7 cells. The results showed that modification of trimethoxy groups on the phenyl ring possessed better inhibitory properties compared to other functional groups on the same ring. Surprisingly, the compounds with a hydroxy group at the C-5 position of the chromone exhibited apparent cytotoxicity. Finally, the active compound, 5,7-dimethoxy-2-(3,4,5-trimethoxyphenoxy)-chromen-4-one, with an IC50 value of 32.2 ± 2.1 μM against lipid accumulation and no significant cytotoxicity, reduced the accumulation of lipid droplets by up-regulating peroxisome proliferator-activated receptor gamma coactivator 1α (PGC1α) to facilitate the catabolism of fat, which shows promise for further optimization to manage NAFLD and NASH.

雖然酒精性肝炎跟非酒精性肝炎的盛行率有增加的趨勢，但臨床上並沒有治療的藥物。因此，開發治療酒精性肝炎跟非酒精性肝炎的新藥有其急迫性。茵陳色原酮為分離自茵陳蒿植物且具有2-苯氧基色原酮結構的化合物，其保肝作用是已為人知曉的。因此，一系列具有2-苯氧基色原酮結構的衍生物就被製備出來並測試其在Huh-7肝癌細胞株上對於油酸誘導的脂肪累積的保護效果。結果顯示化學修飾在苯環上具有三個甲氧基的化合物比起其他的官能基修飾具有較高的抑制油滴累積的能力。令人驚訝的是在五號位置上有羥基的結構表現出明顯的細胞毒性。最後，最有效的化合物表現出抑制脂肪累積的百分之五十的濃度32.3 μM且沒有明顯的細胞毒性，此作用透過轉錄輔助活化因子(PGC1α)來促進脂肪的代謝。這個研究結果對於未來繼續開發治療酒精性肝炎跟非酒精性肝炎非常的有幫助。

Lin, M.-W., Fang, S.-Y., Hsu, J.-Y. C., Huang, C.-Y., Lee, P.-H., Huang, C.-C., Chen, H.-F., Lam, C.-F., & Lee, J.-S. (2022). Frontiers in Neuroscience , 16. Read this article

Mitochondrial dysfunction is a hallmark of secondary neuroinflammatory responses and neuronal death in spinal cord injury (SCI). Even though mitochondria-based therapy is an attractive therapeutic option for SCI, the efficacy of transplantation of allogeneic mitochondria in the treatment of SCI remains unclear. Herein, we determined the therapeutic effects of mitochondrial transplantation in the traumatic SCI rats. Compressive SCI was induced by applying an aneurysm clip on the T10 spinal cord of rats. A 100-μg bolus of soleus-derived allogeneic mitochondria labeled with fluorescent tracker was transplanted into the injured spinal cords. The results showed that the transplanted mitochondria were detectable in the injured spinal cord up to 28 days after treatment. The rats which received mitochondrial transplantation exhibited better recovery of locomotor and sensory functions than those who did not. Both the expression of dynamin-related protein 1 and severity of demyelination in the injured cord were reduced in the mitochondrial transplanted groups. Mitochondrial transplantation also alleviated SCI-induced cellular apoptosis and inflammation responses. These findings suggest that transplantation of allogeneic mitochondria at the early stage of SCI reduces mitochondrial fragmentation, neuroapoptosis, neuroinflammation, and generation of oxidative stress, thus leading to improved functional recovery following traumatic SCI.

嚴重脊髓損傷後會造成永久性的神經功能障礙，在臨床上至今仍沒有有效的治療方法，不僅影響患者個人身體和心理，對負擔照顧責任的家屬與社會帶來相當大的負荷；因為細胞在死亡前都會發生粒線體功能障礙，如何提升粒線體功能一直是研究的重要方向，本篇論文驗證移植健康的粒線體在外傷性脊髓損傷的治療成效，因為粒線體可用自體採集，沒有免疫排斥性，可以很快進入臨床試驗，我們希望對脊髓損傷提出一個全新的治療方式，為脊髓損傷病人提供一個希望。

Hsu, C.-K., Cheng, N.-Y., Yang, C.-C., Yen, Y.-Y., & Tseng, S.-H. (2022). Scientific Reports , 12(1), 7469. Read this article

Currently, there are already commercial systems, such as the Courage+Khazaka Corneometer and Mexameter that measure skin capacitance and optical reflectance, for conveniently quantifying the status of skin barrier function and erythema of skin. Despite numerous comparisons of the Courage+Khazaka system with the PASI scoring system, they are rarely compared on parity with diffuse reflectance spectroscopy (DRS) based systems. In this study, we employed a custom-built DRS system shown to be able to determine the skin water-protein binding status and the hemoglobin concentration, and we performed cross-validation of the DRS measurement results with the readings derived from the Corneometer and Mexameter as well as a portion of the PASI scores. We conclude that the DRS method could be a valuable addition to existing skin capacitance/reflectance measurement systems and the PASI scoring system toward achieving a more efficient and objective clinical psoriasis vulgaris severity evaluation.

目前，已經有商業系統，例如 Courage+Khazaka Corneometer 和 Mexameter 測量皮膚電容和光學反射率，可以方便地量化皮膚屏障功能和皮膚紅斑的狀態。有不少過往文獻針對Courage+Khazaka 系統與 PASI 評分系統進行比較，但很少有文獻將上述系統與漫反射光譜 (DRS) 系統進行比較。在這項研究中，我們使用了一個自製的 DRS 系統，該系統能夠確定皮膚水蛋白結合狀態和血紅蛋白濃度；並且我們使用 Corneometer 和 Mexameter 的讀數、 DRS 測量結果、以及部分 PASI 分數，進行了交叉驗證分析。我們最後得出結論，DRS量測方法可有效補強現有皮膚電容/反射率測量系統和 PASI 評分系統的量測結果，以實現更有效和客觀的臨床乾癬嚴重程度評估。

Chang, J.-H., & Weng, H.-C. (2022). Knowledge-Based Systems , 108837. Read this article

Large labeled datasets represent human labor’s costly consumption of resources. Therefore, semi-supervised learning leverages a large amount of unlabeled data to improve the training results in limited labels. Many methods of semi-supervised learning utilize diverse data augmentations to improve model learning and the classification rule from these changes, requiring models to spend a lot of time to adapt to the changes. Besides, reducing the noise in trained unlabeled data is also an issue that is often discussed in semi-supervised learning so that the inference from error predictions can be reduced. It may define that the data, of which the probability predicted from the model is higher than a threshold, as confident and then only train on those high-confidence unlabeled data so that the model avoids the influence from deviation of the error caused by unlabeled data predictions. However, it also leads to the fact that many unlabeled data cannot be effectively used. Thus, this study proposes a semi-supervised framework, including Attention Consistency (AC) and One Supervised (OS) algorithms, which improves efficiency and performance of the model learning by guiding the model to pay attention to classified features and judging whether the model cannot be effectively trained in existing reliable data. This way, the model fully uses unlabeled data to train. The experiment results and comparisons show that similar results can be reached using other methods within a shorter training process. This paper also analyzes the distribution of feature results and proposes a new measurement to find out distribution information.
Keywords: Deep learning, Semi-supervised learning, Attention consistency, Reliable data

充分使用可靠數據和注意力一致性進行半監督學習
大型標記數據集代表了人類勞動力對資源的高成本消耗。因此，半監督學習利用大量未標記的數據來改善有限標籤的訓練結果。許多半監督學習方法利用不同的數據增強來改進模型學習和這些變化的分類規則，需要模型花費大量時間來適應這些變化。此外，減少訓練的未標記數據中的噪聲也是半監督學習中經常討論的問題，從而可以減少錯誤的預測推斷。可以將模型預測的概率高於某個閾值定義為置信度，然後只對那些置信度高的未標註數據進行訓練，從而避免模型因未標註數據導致的誤差偏差影響預測。然而，這也導致許多未標記的數據無法被有效使用。因此，本研究提出了一種半監督框架，包括注意力一致性Attention Consistency (AC) 和單監督One Supervised (OS) 算法，通過引導模型注意分類特徵並判斷模型是否不能識別來提高模型學習的效率和性能且在現有的可靠數據中得到有效的培訓。如此一來，模型完全使用未標記的數據進行訓練。實驗結果和比較表明，使用其他方法可以在較短的訓練過程中達到類似的結果。本文還分析了特徵結果的分佈，並提出了一種新的度量來找出分佈資訊。

Kuo, Y.-R., Cheng, T.-A., Chou, P.-H., Liu, Y.-F., Chang, C.-J., Chuang, C.-F., Su, P.-F., Lin, R.-M., & Lin, C.-L. (2022). Journal of Clinical Medicine, 11(3), 708. Read this article

Background: Vertebral compression fractures, resulting in significant pain and disability, commonly occur in elderly osteoporotic patients. However, the current literature lacks long-term follow-up information related to image parameters and bone formation following vertebroplasty.Purpose: To evaluate new bone formation after vertebroplasty and the long-term effect of vertebroplasty.Methods: A total of 157 patients with new osteoporotic compression fractures who underwent vertebroplasty were retrospectively analyzed. The image parameters, including wedge angles, compression ratios, global alignment, and new bone formation, were recorded before and after vertebroplasty up to three years postoperatively.Results: The wedge angle improved and was maintained for 12 months. The compression ratios also improved but gradually deteriorated during the follow-up period. New bone formation was found in 40% of the patients at 36 months, and the multivariate analysis showed that this might have been related to the correction of the anterior compression ratio. Conclusions: Vertebroplasty significantly restored the wedge angles and compression ratios up to one year postoperatively, and new bone formation was noted on plain radiographs, which increased over time. Last, the restoration of vertebral parameters may contribute to new bone formation.

背景：脊椎椎體壓迫性骨折多見於老年骨質疏鬆患者，可能導致嚴重的疼痛和殘疾。然而對於使用椎體成型術治療脊椎椎體壓迫性骨折後，長期的影像與椎體內新生骨形成的情形，目前仍無足夠文獻佐證。目的：評估椎體成型術後，脊椎骨癒合情形與在長期追蹤X光影像上的改善幅度。方法：針對157例過去因骨質疏鬆相關之脊椎椎體壓迫性骨折患者，接受椎體成型術後進行影像學的回顧性分析。將經椎體成型術患者，術前及術後追蹤的X光影像分階段檢視，依序從術前片至術後三年的影像，影像分析內容包括椎體楔狀角、壓迫比率、整體排列和新生骨之生長比率。結果：經椎體成型術後椎體楔狀角得到改善，並維持了12個月。術後椎體壓迫比率也有所改善，但在分析術前至術後三年的影像，觀察到壓迫比率有隨時間惡化的跡象。40% 的患者在手術後36 個月時發現新生骨形成，多變量分析顯示這可能與矯正前壓迫比率有關。結論：椎體成形術顯著恢復了椎體楔狀角和術後椎體壓迫比率，且時間可達一年之久；另外透過影像可觀察到新生骨的形成，隨著時間的推移而增加。最後，椎體參數的改善幅度可能與骨癒合情形有相關性。

Kuo, J.-H., Ubeda Herrera, J. J., Liu, C.-Y., Lee, T.-H., Strong, C., Lin, C.-Y., Chang, Y.-H., Lin, Y.-C., Hsieh, Y.-P., & Tsai, M.-C. (2022). [Original Research]. Frontiers in Public Health, 10. Read this article

Self-image reflects overall self-acceptance in developing adolescents. Using a representative cohort of Taiwanese youth, this study aims to explore the relationship between weight status, pubertal timing, athletic competence, and adolescent self-image. Data come from the Taiwan Youth Project that comprised a longitudinal cohort of adolescents (N = 2690, 51% males, Mage = 13.3 ± 0.5 years) surveyed annually from seventh grade. Self-image was measured by perceived satisfaction with appearance and physique. Pubertal timing was defined using the Pubertal Developmental Scale. Athletic competence was assessed by experiences with participation in competitive sports and self-perceived talent for sports. In order to test for mediating roles of pubertal timing and athletic competence, Hayes' PROCESS macro on SPSS was conducted. The boot-strapped 95% confidence intervals indicated significant mediating effects of pubertal timing (β = −0.008, [−0.015, −0.001]) and athletic competence (β = −0.006, [−0.011, −0.002]) in the link between BMI and self–image in females. Moreover, BMI at baseline were associated with long-term self-image in males (β = −0.037, [−0.057, −0.017]) and females (β = 0.132, [0.073, 0.190]). Understanding the mediating factors may help enhance adolescents' self-image by providing guidance on healthy weight and physical activity behaviors according to different stages of pubertal progression.

自我意象反映了青少年時期的整體自我接納程度。本研究探討台灣青少年BMI、青春期歷程、運動能力和青少年自我意象之間的關係。數據來自台灣青年計畫，該研究包含從七年級開始每年的縱向數據（N = 2690，51% 男性，Mage = 13.3 ± 0.5 歲）。自我意像是透過對外表和體格的滿意度來衡量，青春期歷程使用青春期發育量表來定義，運動能力採用參加體育競賽的經歷和自我認知的體育天賦來評估。為了檢驗青春期歷程和運動能力的中介作用，我們在SPSS 運用Hayes' PROCESS macro。女性的青春期歷程 (β = -0.008, [-0.015, -0.001]) 和運動能力 (β = -0.006, [-0.011, -0.002]) 在BMI及自我意象間具有顯著的中介作用。此外，青春期的BMI 與男性 (β = -0.037, [-0.057, -0.017]) 和女性 (β = 0.132, [0.073, 0.190]) 的長期自我意象相關。因此，根據青春期的不同階段，提供健康體重和運動的指導，有助於提升青少年的自我意象。

Barceló, J., Sheen, G. C.-H., Tung, H. H., & Wu, W.-C. (2022). Social Science & Medicine, 310, 115278. Read this article

In “Vaccine Nationalism Among the Public: Cross-country Experimental Evidence of Own-country Bias Towards COVID-19 Vac- cination” (joint with Joan Barceló, Hans H. Tung, and Wen-Chin Wu; published in Social Science & Medicine), we administered an experiment requesting 15,000 adult citizens across 14 individual countries from around the world to assess 450,000 profiles of vaccines that randomly varied across seven attributes. We showed that, beyond vaccine fundamentals such as efficacy rate and duration of the protection, citizens systematically favored vaccines developed and produced in their own country of residence. The extent of preference in favor of vaccines developed and produced within the national borders is particularly large among citizens who identify more strongly with their nation, suggesting nationalism plays a role in explaining the bias in favor of vaccines developed and produced locally. This public opinion bias on vaccine preferences has significant theoretical and practical implications.

在 “Vaccine Nationalism Among the Public: A Cross-country Experi- mental Evidence of Own-country Bias towards COVID-19 Vaccination”這篇文章中，我們使用聯合分析法(conjoint analysis)進行了一個包含台灣日韓美中英法等、橫跨十四個國家的大規模問卷實驗，我們的實驗結果發現，民眾在進行疫苗選擇時，除了疫苗的保護力、保護力持續期間長短等疫苗的基本特質外，在控制其他條件下，民眾還會特別偏好自己國家所研發的疫苗。

Cheng, H.-T., Huang, M.-S., & Hsu, S.-W. (2022). ACS Omega, 7(34), 30622-30631. Read this article

Here, we fabricate heterogeneous nanocrystals by integrating seed-mediated and plasmon-mediated photochemistry. Using metal nanocrystals as seed crystals, bimetallic nanocrystals can be generated by depositing or reducing guest metal nanocrystals on the host seed crystals, and semiconductor-metal nanocrystals can be generated by sulfidation on the surface of metal nanocrystals. Since plasmonic nanocrystals act as seeds for bicomponent nanocrystal synthesis, plasmonic-induced "hot electrons" around the seeds can be used to accelerate the formation rate of bicomponent nanocrystals, leading to changes in nanocrystal morphology. This new synthetic method should enable the fabrication of a variety of multicomponent nanocrystals with desirable functionalities for potential applications such as photocatalysts, chemical/biosensors, and biomedicine.

在這裡，我們通過整合種子介導和等離子體介導的光化學來製造異質奈米晶體。 以金屬奈米晶體作為晶種，可以通過在晶種上沉積或還原第二種金屬奈米晶體生成雙奈米晶體，通過在金屬奈米晶體表面進行硫化反應生成半導體-金屬奈米晶體。 由於等離子體奈米晶體作為雙成分奈米晶體合成的晶種，故於晶種周圍的等離子體誘導“熱電子”可用於加速雙成分奈米晶體的形成速度，從而導致奈米晶體之形態的變化。 這種新的合成方法可用於製造各種具有理想功能的多成分奈米晶體，用於各式潛在的應用，例如光催化劑、化學/生物傳感器和生物醫學等。

Mao, L.-K., Huang, M.-H., Lai, C.-H., Sun, Y.-N., & Chen, C.-Y. (2022). Diagnostics, 12(8), 1913. Read this article

In intensive care units, after endotracheal intubation, the position of the endotracheal tube (ETT) should be checked to avoid complications. The malposition can be detected by the distance between the ETT tip and the Carina (ETT–Carina distance). However, it struggles with a limited performance for two major problems, i.e., occlusion by external machine and poor chest radiograph quality. While previous studies addressed these problems, they always suffered from manual intervention requirements. Therefore, this paper aimed to locate the ETT tip and the Carina more accurately for detecting the malposition without manual intervention. The proposed architecture was composed of “Fully Convolutional One-Stage Object Detection”, a Coarse-to-Fine Attention module, and a segmentation branch. Moreover, a post-process algorithm was adopted to refine the detection results. With the dataset provided by National Cheng Kung University Hospital, the accuracy of detecting the malposition achieved 88.82%, and the ETT–Carina distance errors were less than 5.333 ± 6.240 mm.

本篇論文的目標，是在無需人工模板的情況下更準確地定位「氣管導管末端」和「氣管隆突」以檢測導管錯位。本篇論文提出來的架構由「一階全卷積目標檢測器」、「由粗到細的注意力模塊」和「掩碼分支」所組成，並透過後處理改善定位的結果。最後，基於成功大學附設醫院提供的資料集，本篇論文在預測錯位上的準確度為88.82%，在預測導管末端到氣管隆突的距離的誤差為5.333 ± 6.240 mm，優於現有的方法。

Ni, Y. T., Nguyen, D. N., Liao, F. K., Kao, T. C., & Chen, C. Y. (2022). IEEE Access, 10, 59373-59382. Read this article

In this paper, novel hard-decision iterative decoding algorithms for binary Reed-Muller (RM) codes are presented. First, two algorithms are devised based on the majority-logic decoding algorithm with reliability measures of the received sequence. The bit-flipping (BF) and the normalized bit-flipping (NBF) decoding algorithms are hard-decision decoding algorithms. According to the updated hard reliability measures, the BF and NBF algorithms flip one bit of the received hard-decision sequence at a time in each iteration. The NBF decoding algorithm performs better than the BF decoding algorithm by normalizing the reliability measures of the information bits. Moreover, the BF and NBF algorithms are modified to flip multiple bits in one iteration to reduce the average number of iterations. The modified decoding algorithms are called the multiple-bits-flipping (MBF) algorithm and the normalized multiple-bits-flipping (NMBF) algorithm, respectively. The proposed algorithms have low computational complexities and can converge rapidly after a small number of iterations.

在此研究中，我們提出了里德穆勒碼全新的疊代解碼演算法。我們利用可靠度量測以及多數決解碼原理來進行解碼。透過疊代的方式更新位元的可靠度，並在每次疊代中翻轉接收序列的一個位元。此外，我們透過正規化可靠度量測值來增進解碼的效能。我們更進一步提出翻轉多個位元的作法，來加速疊代演算法的過程，可藉由較少的疊代次數來獲得相近的效能。

Chen, B.-Y., Hsu, C.-C., Chen, Y.-Z., Lin, J.-J., Tseng, H.-H., Jang, F.-L., Chen, P.-S., Chen, W.-N., Chen, C.-S., & Lin, S.-H. (2022). Brain, Behavior, and Immunity, 106, 11-20. Read this article

Schizophrenia (SZ) is influenced by genetic and environmental factors, and associated with chronic neuroinflammation. If the symptoms express after adolescence, environmental impacts are more substantial, and the disease is defined as adult-onset schizophrenia (AOS). Effects of environmental factors on antibody responses such as Escherichia coli (E. coli) to immunoglobulin G (IgG) and immunoglobulin M (IgM) might increase the severity of symptoms in SZ via the gut-brain axis. The purpose of this study is to reveal antibody profiles of SZ against bacterial protein antigens. We analyzed the IgG and IgM antibodies using E. coli proteome microarrays from 80 SZ patients and 40 healthy controls (HC). We identified the protein yjjU, livG and ftsE can form the best combination panel to classify IgG in AOS vs HC with accuracy of 0.8. Also, these antigens are enriched in ABC transporter related domains, including human ABCB1 protein. The findings suggest that AOS had different immunoglobulin production compared to early-onset schizophrenia (EOS) and HC.

透過全基因體大腸桿菌晶片剖析思覺失調症蛋白質抗體圖譜
思覺失調症常受遺傳和環境因素的影響，並與慢性神經炎症有關。若疾病症狀於青春期之後才展現，則環境有較大的影響，遂被定義為成人型思覺失調症。另一方面，環境因素對於免疫球蛋白 G (IgG) 和免疫球蛋白 M (IgM) 等抗體反應，可能會透過腸腦軸來加劇思覺失調症症狀程度。故本研究的目的為揭示思覺失調症針對細菌蛋白抗原的抗體圖譜。本研究利用 80 名思覺失調症患者和 40 名健康者的大腸桿菌蛋白質晶片，並分析其 IgG 和 IgM 抗體差異。我們辨識出蛋白質 yjjU、livG 和 ftsE 可以形成最佳鑑別組合，並能將成人型思覺失調症患者與健康者中的 IgG 進行分類，其準確度為 0.8。此外，這些抗原亦與富含 ABC 轉運蛋白相關結構有所關聯，其中包含人類 ABCB1 蛋白。研究結果顯示，與早發性思覺失調症和健康者相比，成人型思覺失調症會產生不同的免疫球蛋白表現。

Wang, L.-C., Wu, S.-R., Yao, H.-W., Ling, P., Perng, G.-C., Chiu, Y.-C., Hsu, S.-M., & Chen, S.-H. (2022). PLOS Pathogens, 18(8), e1010692. Read this article

Herpes simplex virus 1 (HSV-1)-induced encephalitis is the most common cause of sporadic, fatal encephalitis in humans. HSV-1 has at least 10 different envelope glycoproteins, which can promote virus infection. The ligands for most of the envelope glycoproteins and the significance of these ligands in virus-induced encephalitis remain elusive. Here, we show that glycoprotein E (gE) binds to the cellular protein, annexin A1 (Anx-A1) to enhance infection. Anx-A1 can be detected on the surface of cells permissive for HSV-1 before infection and on virions. Suppression of Anx-A1 or its receptor, formyl peptide receptor 2 (FPR2), on the cell surface and gE or Anx-A1 on HSV-1 envelopes reduced virus binding to cells. Importantly, Anx-A1 knockout, Anx-A1 knockdown, or treatments with the FPR2 antagonist reduced the mortality and tissue viral loads of infected mice. Our results show that Anx-A1 is a novel enhancing factor of HSV-1 infection. Anx-A1-deficient mice displayed no evident physiology and behavior changes. Hence, targeting Anx-A1 and FPR2 could be a promising prophylaxis or adjuvant therapy to decrease HSV-1 lethality.

單純疱疹病毒第一型(Herpes simplex virus 1; HSV-1)引起的腦炎為最常見的散發性、致死性腦炎。病毒具有十種以上可幫助感染的膜蛋白，但大部分膜蛋白於細胞上的配體，及此配體於腦炎中所扮演的腳色仍然不明。本篇研究指出膜蛋白E(glycoprotein E; gE)與細胞蛋白annexin A1 (Anx-A1)結合並增加病毒感染，Anx-A1可在未受感染的容許細胞表面以及病毒顆粒上被偵測到，抑制細胞表面的Anx-A1或其受體formyl peptide receptor 2 (FPR2)，以及在病毒顆粒上的gE或Anx-A1皆可降低病毒與細胞的結合。剔除或減少Anx-A1於小鼠的表現，或者給予感染小鼠FPR2拮抗劑有效減少小鼠的死亡率以及組織病毒量。結果顯示Anx-A1是一過去未發現的，可增加單純疱疹病毒第一型感染的細胞因子。Anx-A1全身剔除小鼠並無明顯生理或行為異常，因此針對單純疱疹病毒第一型引起的腦炎，Anx-A1或FPR2的抑制療法可作為預防或者輔助療法使用。

Wu, Y.-C., Chen, C.-Y., Chang, C.-S., Li, C.-C., Wang, R.-H., Sun, Z.-J., Wu, C.-H., & Chang, Y.-F. (2022). Journal of Clinical Medicine, 11(17), 5035. Read this article

Osteoporotic vertebral fracture is so called “silent fracture”. Two-third of vertebral fractures are under-diagnosed due to no obvious symptom in clinical practice. As previous studies, numerous approved agents are available to treat osteoporosis effectively. However, a treatment gap exists due to under diagnosis and low treatment rate. There were few studies focused on factors associated with outpatient visits and osteoporosis treatment after vertebral fracture. We would evaluate the factors associated with outpatient visits after vertebral fracture from subjects of Tianliao study between 2009 and 2010. Furthermore, information about outpatient visits and osteoporosis medication prescriptions were derived from National Health Insurance Research database.

骨鬆性脊椎骨折常被稱為沉默的骨折，臨床上三分之二的脊椎骨折常因沒有明顯症狀而未即時診斷治療。治療骨鬆性脊椎骨折目前雖然有許多有效的藥物，然而若病人未認知脊椎骨折後治療之重要性，當然也就不會回診治療而造成治療上的缺口。目前僅有少數研究探討影響脊椎骨折後回診治療之相關因子。因此本研究利用2009及2010年田寮研究之65歲以上新診斷脊椎骨折之受試者，同時串接健保資料庫評估其脊椎骨折後回診之有無、回診間隔時間長短、及是否接受骨鬆藥物治療，探討影響脊椎骨折後回診及藥物治療之相關因子。

Chen, P.-S., Feng, W.-H., Tsai, T.-H., Hong, Y.-K., Lee, A.-S., Chang, K.-C., Chung, H.-C., Liu, Y.-W., Hsieh, C.-C., Fang, Y.-H., Yang, P.-J., Luo, C.-Y., Liu, P.-Y., Cheng, T.-L., & Li, Y.-H. (2022). Scientific Reports, 12(1), 10532. Read this article

Tumor endothelial marker 1 (TEM1) is a transmembrane glycoprotein that appears on mesenchymal lineage-derived cells during embryogenesis, but its expression greatly reduces after birth. Re-upregulation of TEM1 is found in tumor angiogenesis, organ fibrosis and wound healing indicating its potential role in tissue remodeling and repair. The expression level and function of TEM1 in adult heart are unknown. In explanted hearts from heart failure (HF) patients received cardiac transplantation, immunofluorescence staining showed TEM1 was expressed in cardiomyocytes (CMs) and cardiac fibroblasts. Bioinformatics analysis showed TEM1 upregulation in mouse heart after coronary ligation. Cardiac TEM1 expression was reconfirmed in mouse HF induced by coronary ligation or doxorubicin injection. TEM1 expression increased in cultured CMs stimulated with mechanical stretch, doxorubicin and hypoxia. Further studies showed recombinant TEM1 (rTEM1) was a functional protein that influenced cell behaviors of CMs. It directly activated Erk and Akt through interaction with PDGF receptor. TEM1lacZ/lacZ mice had less collagen deposition and worse cardiac function than wild type mice. These results indicate that TEM1 expression increases in the heart after cardiac injury and works as a functional protein that participates in cardiac remodeling.

腫瘤內皮標誌物1 (TEM1)是一種醣基化穿膜蛋白，在胚胎發育過程中出現在間質衍生細胞上，但在出生後其表現量大大降低。但在腫瘤血管生成、器官纖維化和傷口癒合中發現 TEM1的表現量會重新上升，顯示TEM1在組織重塑和修復方面有其潛在作用。TEM1在成人心臟中的表現量和功能尚不清楚。在接受心臟移植的心衰竭 (HF)患者的移植心臟中，免疫螢光染色顯示TEM1會表現在心肌細胞和心臟纖維母細胞中。生物信息分析顯示冠狀動脈結紮手術後的小鼠心臟TEM1量會上升。在冠狀動脈結紮或阿黴素注射誘導心衰竭的小鼠心臟中再次證實TEM1會表現。用機械拉伸、阿黴素和缺氧刺激下培養的心肌細胞中TEM1的表現量同樣會增加。進一步的研究顯示重組TEM1 (rTEM1)是具有功能性的蛋白，會影響心肌細胞的細胞行為。它通過與PDGF受體相互作用直接活化Erk和Akt。與正常小鼠相比，TEM1lacZ/lacZ基因轉殖小鼠的膠原蛋白沉積更少，心臟功能更差。這些結果表明，心臟損傷後心臟TEM1的表現量增加，同時TEM1是一種會參與心臟重塑的功能性蛋白。

Tien, S.-M., Chang, P.-C., Lai, Y.-C., Chuang, Y.-C., Tseng, C.-K., Kao, Y.-S., Huang, H.-J., Hsiao, Y.-P., Liu, Y.-L., Lin, H.-H., Chu, C.-C., Cheng, M.-H., Ho, T.-S., Chang, C.-P., Ko, S.-F., Shen, C.-P., Anderson, R., Lin, Y.-S., Wan, S.-W., & Yeh, T.-M. (2022). PLOS Pathogens, 18(4), e1010469. Read this article

Dengue virus (DENV) which infects about 390 million people per year in tropical and subtropical areas manifests various disease symptoms, ranging from fever to life-threatening hemorrhage and even shock. To date, there is still no effective treatment for DENV disease, but only supportive care. DENV nonstructural protein 1 (NS1) has been shown to play a key role in disease pathogenesis. Recent studies have shown that anti-DENV NS1 antibody can provide disease protection by blocking the DENV-induced disruption of endothelial integrity. We previously demonstrated that anti-NS1 monoclonal antibody (mAb) protected mice from all four serotypes of DENV challenge. Here, we generated humanized anti-NS1 mAbs and transferred them to mice after DENV infection. The results showed that DENV-induced prolonged bleeding time and skin hemorrhage were reduced, even several days after DENV challenge. Mechanistic studies showed the ability of humanized anti-NS1 mAbs to inhibit NS1-induced vascular hyperpermeability and to elicit Fc-dependent complement-mediated cytolysis as well as antibody-dependent cellular cytotoxicity of cells infected with four serotypes of DENV. These results highlight humanized anti-NS1 mAb as a potential therapeutic agent in DENV infection.

人源化抗登革病毒非結構性蛋白1單株抗體在老鼠模式之治療效益
每年登革熱病毒在熱帶和亞熱帶地區造成大約3.9億人感染；感染後表現出各種症狀，從自限性的發燒到危及生命的嚴重登革疾病，而嚴重登革疾病通常都需要在醫院進行護理。迄今，我們僅有賴支持性療法提供登革的患者，而非有效的藥物治療。近期，登革的非結構性蛋白1 (nonstructural protein 1, NS1) 已被證明在登革疾病致病機制中扮演重要角色。而抗登革非結構性蛋白1抗體可透過阻擋登革病毒所引發的內皮細胞完整性破損而提供保護力。我們先前的研究發現抗登革非結構性蛋白1單株抗體 (monoclonal antibodies, mAbs) 針對四型登革病毒在小鼠中皆可提供保護力。因此在本研究中，我們製備了人源化 (humanized) 抗 NS1單株抗體並在將它送到被登革病毒感染的老鼠體內。結果顯示人源化抗 NS1單株抗體的治療益處不僅在降低病毒量和 NS1 濃度方面，而且還可以減少登革病毒所導致的出血時間延長及皮膚出血，甚至是感染後期皆有效。體外機制研究顯示降低NS1 誘導的血管通透性以維持內皮完整性，並且增加被登革病毒感染細胞的細胞溶解以消除病毒。綜合以上，人源化抗 NS1單株抗體為可能的治療性藥品並向臨床應用發展。

Yang, L.-X., Liu, Y.-C., Cho, C.-H., Chen, Y.-R., Yang, C.-S., Lu, Y.-L., Zhang, Z., Tsai, Y.-T., Chin, Y.-C., Yu, J., Pan, H.-M., Jiang, W.-R., Chia, Z.-C., Huang, W.-S., Chiu, Y.-L., Sun, C.-K., Huang, Y.-T., Chen, L.-M., Wong, K.-T., . . . Liu, T.-M. (2022). Journal of Nanobiotechnology, 20(1), 311. Read this article

The development of optical organic nanoparticles (NPs) is desirable and widely studied. However, most organic dyes are water-insoluble such that the derivatization and modification of these dyes are difficult. Herein, we demonstrated a simple platform for the fabrication of organic NPs designed with emissive properties by loading ten different organic dyes into water-soluble polymer nanosponges composed of poly(styrene-altmaleic acid) (PSMA). This packaging strategy includes commercial dyes and our newly synthesized organic dyes (> 85% loading) designed for OPVs, DSSCs, and OLEDs applications preventing their spontaneous aggregation in aqueous solutions and improving their biocompatibility. These low-cytotoxicity organic NPs exhibited tunable fluorescence from visible to NIR emission for cellular imaging and biological tracking in vivo. Moreover, PSMA NPs loaded with designed NIR-dyes were also performed photodynamic therapy for the photolysis of cancer cells under 808 nm laser excitation. Indeed, our work demonstrates a facile approach for increasing the biocompatibility and stability of organic dyes by loading them into water-soluble polymer-based carriers, providing a new perspective of organic optoelectronic materials in biomedical theranostic applications.

光學有機奈米粒子被廣泛研究發展且持續有高應用需求。然而大多數有機染料是不溶於水的，而直接對這些染料進行衍生化或改質是很困難與麻煩的。本篇研究展示了一個簡單的平台，可將十種不同的有機染料加載到由聚(苯乙烯-馬來酸)(PSMA)組成的水溶性聚合物奈米海綿中，來製造具有螢光與光動力特性的有機光學奈米粒子。這種裝載策略包括一般商品化的螢光染劑和我們為太陽能電池應用設計新合成OPV、DSSC 和 OLED類型的有機染劑可達> 85%的負載量，並防止它們在水溶液中自發聚集與提高染劑的生物相容性。這些低細胞毒性有機奈米粒子具有從可見光到近紅外的螢光範圍，可用於活體多光子細胞成像和生物追踪。此外，亦可搭載NIR染料在 808 nm雷射激發下對小鼠膀胱癌細胞進行進行光動力療法，有效提升腫瘤鼠的生存率。我們的研究揭示了一種通用且簡單的裝載平台，能將不同結構的有機染料高效率加載到水溶性聚合物的載體中，提高有機染料的生物相容性和穩定性，為有機光電材料在生物醫學治療診斷應用中提供了新的視角。

Chang, C.-S., Liu, I. T., Liang, F.-W., Li, C.-C., Sun, Z.-J., Chang, Y.-F., Chao, T.-H., & Wu, C.-H. (2022). Scientific Reports, 12(1), 7912. Read this article

To determine whether body composition indices interact with age and gender as a predictor of all-cause mortality, 1,200 participants at least 40 years of age were recruited in 2009 and 2010. A multi-frequency bioelectrical impedance analysis device was used to measure each participant’s body composition indices, including the fat mass index (FMI), fat free mass index (FFMI), skeletal muscle mass index (SMMI), and visceral fat area index (VFAI). A baseline questionnaire was used to collect demographic information about lifestyle habits, socioeconomic status, and medical conditions. All claimed records of death from 2009 to 2018 in the National Health Insurance Research Databank were identified. The all-cause mortality rate was 8.67% after a mean follow-up period of 5.86±2.39 person-years. The Cox proportional hazard model analysis showed significantly negative associations between FFMI or SMMI with all-cause mortality in the total group and those aged > = 65 y/o. The FFMI and SMMI were negative predictors of mortality in both genders. The FMI and VFAI were positive predictors of mortality exclusively in females. In conclusion, the SMMI is a better predictor of mortality than the BMI, FMI, and FFMI, especially in older adults. A higher fat mass or visceral fat distribution may predict higher mortality in females.

本研究目的在瞭解身體組成指標如何在與年齡與性別的互動下成為全死因死亡率的關係。於2009年到2010年間，共收錄四十歲以上1200位受試者參與研究。使用多頻率生物電阻分析儀測量每位受試者的身體組成指標，包括脂肪量指標(fat mass index, FMI)、除脂肪量指標(fat free mass index, FFMI)、骨骼肌肉量指標(skeletal muscle mass index, SMMI)以及內臟脂肪區域指標(visceral fat area index, VFAI)。使用基礎問卷收集受試者的基本地域資料包含生活習慣、社經地位以及身體健康狀況等。所有死亡發生記錄的資料來自2009年到2018年間國家健康保險研究資料庫。研究結果發現，經過平均5.86±2.39人年的追蹤後，受試者的全死因死亡率為8.67%。利用Cox proportional hazard model分析發現在所有受試者以及大於65歲以上族群，FFMI或SMMI與全死因脂肪率呈現有意義的負相關性。男女性受試者FFMI 以及SMMI 皆為死亡的負向預測因子，FMI 與VFAI 則僅在女性族群為正向的死亡預測因子。總結來說，相較於BMI、FMI 以及FFMI 而言，SMMI是最佳的死亡預測因子，此現象在老年族群更為明顯。女性有較高的脂肪量或內臟脂肪分布則可能有較高的死亡率。

Yang, S.-M., Yen, H.-K., & Lu, K.-C. (2022). Nanomaterials, 12(6), 897. Read this article

In this study, indium tin oxide nanowires (ITO NWs) with high density and crystallinity were synthesized by chemical vapor deposition (CVD) method via vapor-liquid-solid (VLS) route; the NWs were decorated with silver on the surface by an electrochemical method. The ITO NWs possessed great morphologies with length of 5~10 μm and an average diameter of 58.1 nm. The room temperature photoluminescence (PL) studies show that the ITO NWs were of visible light-emitting properties, and there were a large number of oxygen vacancies on the surface. The successful modification of Ag was confirmed by TEM, XRD and XPS. PL analysis reveals that there was an extra Ag signal at around 1.895 eV, indicating the potential application of Ag-ITO NWs as na-noscale optical materials. Electrical measurements show that more Ag-nanoparticles on the surface of ITO NWs contributed to higher resistivity, demonstrating the change of the electron transmission channel of the Ag-ITO NWs. ITO NWs and Ag-ITO NWs are expected to enhance the performance of electronic and optoelectronics devices.

本研究中，我們透過化學氣相沉積法以汽-液-固的成長路線製備出具有高密度與高結晶度的氧化銦錫(ITO)奈米線，並以電化學法在表面修飾銀奈米粒子。PL分析指出修飾銀後的ITO奈米線在1.85eV附近有一個Ag的訊號，說明其光學應用的可能性。電性量測顯示ITO奈米線表面的銀奈米顆粒會提高奈米線電阻率，說明奈米線的電子傳輸通道產生變化。這些研究結果可證實ITO奈米線與修飾銀的ITO奈米線具備電子與光電元件應用的未來及可能性。

Yu, Y.-W., Tan, C.-H., Su, H.-C., Chien, C.-Y., Sung, P.-S., Lin, T.-Y., Lee, T.-L., & Yu, R.-L. (2022). Frontiers in Aging Neuroscience, 14. Read this article

Mini-mental status examination (MMSE) and Montreal Cognitive Assessment (MoCA) are commonly used clinical tools to screen for cognitive impairment in patients with Parkinson's disease (PD). We developed the Parkinson's Disease Social Functioning Scale (PDSFS) and demonstrated good psychometric properties for assessing social functioning in patients with PD. This study validates and simplifies commonly used clinical assessment tools and develops a comprehensive test of cognitive and social functioning to aid in detecting PD with mild cognitive impairment (PD-MCI) and PD with dementia (PDD). We found that the cut-off score of the short MMSE to detect PD-MCI is 26 points, while the cut-off scores of the MoCA to detect PD-MCI and PDD are 23 and 18, respectively. The short version of the MoCA includes three sub-tests: visuospatial/executive, memory subtest, and orientation sense, with a total score of 16 points. The cut-off scores for detecting PD-MCI and PDD were 9 and 7 points. The abbreviated version of the PDSFS includes the subscales of family life, hobbies, and self-care, with 27 points and a cut-off score of 25 points for PD-MCI. The comprehensive test comprises a simplified version of the MoCA and a simplified version of the PDSFS, with a total score of 43 points. We have simplified validation and simplified commonly used tests, and comprehensive tests can be helpful in the detection of PD-MCI and PDD.

簡短智能測驗(Mini-mental status examination)和蒙特利爾智能測驗(Montreal Cognitive Assessment)是臨床上常用於篩檢巴金森氏病患者（巴病）認知障礙的工具。我們發展了巴金森氏病社會功能量表(Parkinson's Disease Social Functioning Scale)且證實具良好的心理計量特性，可用於評估巴病患者的社會功能。本研究檢驗並簡化常用的臨床評估工具，發展兼顧認知與社會功能的綜合測驗。我們發現簡短智能測驗偵測巴病合併輕度認知障礙症的切截分數為26分，而蒙特利爾智能測驗偵測巴病合併輕度認知障礙症與巴病合併失智症的切截分數分別為23與18分。簡短版蒙特利爾智能測驗包含視覺空間/執行、記憶分測驗、定向感三個分測驗，滿分為16分，偵測巴病合併輕度認知障礙症與合併失智症的切截分數為9分與7分。簡版巴病社會功能量表包含家庭生活、嗜好與自理分量表，滿分為27分，巴病合併輕度認知障礙症的切截分數為25分。綜合測驗由簡版蒙特利爾智能測驗與簡版巴病社會功能量表組成，滿分為43分，偵測巴病合併輕度認知障礙症與合併失智症的切截分數為35分與30分。我們簡化了驗證並簡化了常用的測驗，且綜合測驗可助益於偵測巴病合併輕度認知障礙症與巴病合併失智症。

Tsai, Y.-Y., Chen, Y.-C., Zhao, C.-G., & Hwang, I.-S. (2022). Frontiers in Physiology, 13. Read this article

Background: Stroboscopic vision (SV), intermittent visual blocking, has recently been incorporated into postural training in rehabilitation. This study investigated interactions of postural fluctuation dynamics and cortical processing for the elderly during stabilometer stance with SV. Methods: Thirty-five healthy elderly maintained an upright stance on a stabilometer. Along with postural fluctuation dynamics, EEG relative power and EEG-EEG connectivity were used to contrast neuromechanical controls of stabilometer stance with SV and full-vision. Results: Compared with the full-vision, SV led to greater postural fluctuations with lower sample entropy and mean frequency (MF). SV also reduced regional power in the mid-frontal theta cluster, which was correlated to SV-dependent changes in the size of postural fluctuations. SV also enhanced the alpha band supra-threshold connectivity in the visual dorsal and frontal-occipital loops of the right hemisphere, and the supra-threshold connectivity from Fp2 positively related to variations in the MF of postural fluctuations. Conclusion: SV adds challenge to postural regulation on the stabilometer, with the increasing regularity of postural movements and fewer corrective attempts to achieve the postural goal. The elderly shift over-reliance on visual inputs for posture control with more non-visual awareness, considering deactivation of the dorsal visual stream and visual error processing.

老年人站立於不穩定平面對於閃頻視覺產生姿勢搖晃適應與大腦皮質反應背景:視覺閃頻是一種間歇性阻斷視覺訊息的方式，近來年被用來復健訓練姿勢平衡。本研究探討老年人站立在搖晃的平衡板，閃頻視覺導致大腦處理改變與姿勢晃動之間的相互關聯。方法: 35位健康的老年人(年齡: 65.8 ± 2.8 歲，男:女 = 16: 19)。他們維持靜止站立在平衡板，有閃頻視覺和全視線(控制組)兩種視覺狀態。姿勢晃動程度由平衡板動態晃動參數分析。不同區域腦波相對活化程度與成對腦電極的連結性與姿勢晃動程度表現關聯性。結果:發現閃頻視覺較全視線狀態使姿勢平衡晃動的幅度變大、較規律且平均頻率變低。閃頻視線也使中間額葉區域的theta頻功率活性變小，此改變也跟閃頻視線造成的姿勢平衡晃動變大有顯著相關。閃頻視線強化了在alpha頻帶的背側視覺與右側額葉枕葉連結性，其中Fp2連結性改變與閃頻導致的姿勢晃動平均頻率降低有顯著正相關。結論: 閃頻視覺增加了在平衡板姿勢調控的困難度，所以姿勢晃動變得較規律且較低的修正頻率。老年人原本依賴視覺訊息來控制姿勢。閃頻視覺*讓老年人大腦降低背側視覺流的活化，降低視覺錯誤處理來降低對視覺的依賴。

Wang, L.-C., Tsai, H.-P., Chen, S.-H., & Wang, S.-M. (2022). [Review]. Frontiers in Pharmacology, 13. Read this article

Neonatal infection with nonpolio enteroviruses (EVs) causes nonspecific febrile illnesses and even life-threatening multiorgan failure. Hepatitis, which often results in hepatic necrosis followed by disseminated intravascular coagulopathy, is one of the most severe and frequent fatal neonatal EV infection complications. Coxsackievirus B (CVB) 1–5 and many echoviruses have been most commonly identified. Neonatal EV infection treatment has usually involved initial supportive care. Studies for CVB and echovirus infection treatments were developed for more than thirty years. Intravenous immunoglobulin and pleconaril therapy was performed in some clinical trials. Additionally, other studies demonstrated antiviral and/or anti-inflammatory pathogenesis mechanisms of neonatal EV hepatitis in in vitro or in vivo models. These treatments represented promising options for the clinical practice of neonatal EV hepatitis. However, further investigation is needed to elucidate the whole therapeutic potential and safety problems.

新生兒感染非小兒麻痺症腸病毒，大都會引起輕症，如非專一性發熱，但也會導致危急生命的多重器官衰竭。肝炎是新生兒腸病毒感染後，最常發生與最嚴重的併發症之一，會造成肝臟壞死及後續的彌散性血管內凝集。克沙奇病毒B 1-5型和許多伊科病毒是最常被鑑定出的。新生兒腸病毒感染後，經常使用支持性治療為主，治療克沙奇病毒及伊科病毒的研究已經發展超過30年，靜脈免疫球蛋白注射和pleconaril已被使用於一些臨床試驗中，此外，其他研究也朝向在細胞或活體中，探討抗病毒及抗發炎對於新生兒腸病毒肝炎的機制，這些研究代表在臨床上針對新生兒腸病毒肝炎有力的正面選項，然而，需要更進一步研究，來闡明完整的治療潛力以及安全性問題。

Hsiao, H.-T., Wang, J. C.-F., & Wu, S.-N. (2022). Biomedicines, 10(6), 1318. Read this article

Vortioxetine (VOR) is recognized to exert antidepressant actions. However, whether this drug modifies ionic currents in excitable cells remains unclear. The aim of this study was to explore the electrophysiological effects of VOR and other related compounds in pituitary GH3 cells and in Neuro-2a cells. VOR suppressed the delayed-rectifier K+ current (IK(DR)) in a concentration-, time-, and state-dependent manner. Effective IC50 values needed to inhibit peak and sustained IK(DR) were computed to be 31.2 and 8.5 μM, respectively, while the KD value estimated from minimal binding scheme was 7.9 μM. Cell exposure to serotonin (10 μM) alone failed to alter IK(DR), while fluoxetine (10 μM), a compound structurally similar to VOR, mildly suppressed current amplitude. VOR has been previously demonstrated to have an agonistic or antagonistic effect on HT receptors. Propranolol is an inhibitor of β-adrenergic and 5-HT receptors and risperidone can suppress dopamine receptors. In continued presence of VOR, neither further addition of propranolol nor risperidone reversed VOR-mediated inhibition of IK(DR). Increasing VOR concentration not only depressed IK(DR) conductance but also shifted toward the hyperpolarized potential. As the VOR concentration was raised, the recovery of IK(DR) block became slowed. The IK(DR) activated by a downsloping ramp was suppressed by its presence. The inhibition of IK(DR) by a train pulse was enhanced during exposure to VOR. In Neuro-2a cells, this drug decreased IK(DR). Overall, inhibitory effects of VOR on ionic currents might constitute another underlying mechanism of its actions.

Vortioxetine (簡稱VOR)被認為具有抗憂鬱作用。然而此藥物是否能在激活細胞中改變離子電流還尚不清楚。此研究的目的是探討VOR在腦下垂體中GH3細胞及Neuro-2a細胞上的電生理效應。VOR在濃度上，時間長度、及狀態上的方面抑制內向延遲的整流鉀離子電流(IK(DR))。所需要抑制持續內向延遲的整流鉀離子電流(IK(DR))或峰值達到百分之五十的有效的VOR濃度值經過計算為31.2毫莫耳及8.5毫莫耳，而在極少結合的狀態時其相關解離常數的值為7.9毫莫耳。細胞暴露於血清素(10毫莫耳)中不會改變內流鉀離子電流，而當結構相似於VOR的藥物fluoxetine在10毫莫耳濃度時對內流鉀離子電流的幅度會輕微的抑制。在以前的研究VOR對5-羥色胺受體有相當的作用，而propranolol是5-羥色胺受體和β-adrenergic的抑制劑，而risperidone能對多巴胺受體有抑制作用。在始終有VOR的環境下加入propranolol或是risperidone都不會改變VOR作用的抑制內向延遲的整流鉀離子電流(IK(DR))。在實驗中增加VOR的濃度不僅會減少內向延遲的整流鉀離子電流(IK(DR))的導電性也會讓反應曲線向左偏移亦即是向過極化電壓的移動。隨著VOR的濃度增加，內向延遲的整流鉀離子電流(IK(DR))阻斷後的恢復時間變慢。在持續性的脈衝抑制了內向延遲的整流鉀離子電流(IK(DR))，在VOR存在時其抑制現象會被加強。在Neuro-2a細胞VOR這個藥會減少內向延遲的整流鉀離子電流(IK(DR))。因此由整個實驗而言，VOR在兩種細胞的電生理作用其在經細胞膜對離子流的抑制性調節作用，可能就是其在藥理作用的分子機制，在抗憂鬱作用及神經退化性疾病的治療的機轉。

Lin, C.-h., & Liu, F.-Y. (2022). Scientific Reports, 12(1), 15101. Read this article

A computational method, dubbed the simplified unit-cell micromechanics model, is generalized and applied to establish the effective nonlinear responses of three-phase magnetoelectric composites that are composed of two distinct magnetostrictive and piezoelectric phases embedded in elastic polymer matrices. To obtain effective nonlinear responses, a mathematical linearization is first introduced to perform the constitutive linearization for the nonlinear materials, and the resulting constitutive equations are then unified and nested into the micromechanics model followed by iterations in order to minimize errors from the linearization process. Numerical results are first validated against limited experimental measurements available in the literature. Parametric studies are then conducted in order to reveal the effect of phase constitutive laws, volume fractions, and geometries on the overall nonlinear responses of there-phase magnetoelectric composites. The contributions of this work complement those of earlier studies that prevalently devoted to two-phase magnetoelectric composites and linear magneto-electro-elastic coupled responses only.

一個數學模型，命名為『單位晶格微觀力學模型』，已被廣義化，並應用於模擬由壓電材料、磁致伸缩材料及高分子材料，所組成的三相磁電複合材料的有效非線性響應。為了得到有效非線性響應，首先利用一個數學線性化的方法將非線性本構方程式線性化，再者將線性化後的方程式結合單位晶格微觀力學模型，最後利用疊代法將線性化後所產生的預測誤差最小化，以求得有效非線性響應之數值解。研究結果顯示，1)本研究所提出的數學模型與實驗數據非常吻合，2)三相磁電複合材料的有效非線性響應，受到材料本構律、體積分率及幾何形狀顯著的影響。本研究成果可以補足現今磁電複合材料的研究大多僅僅注重兩相材料及線性響應。

Kuo, Y.-Z., Kang, Y.-R., Chang, W.-L., Sim, L. C.-L., Hsieh, T.-C., Chang, C.-H., Wang, Y.-C., Tsai, C.-J., Huang, L.-C., Tsai, S.-T., & Wu, L.-W. (2022). Cellular Oncology. Read this article

Although YAP1 and TAZ are believed to be equivalent downstream effectors of the Hippo pathway, differential expression of YAP1 or TAZ suggests distinct functions during cancer progression. The exact role of YAP1 and TAZ in esophageal cancer, the 6th leading cancer-related mortality in the world, remains elusive. Following manipulation of YAP1 or/and TAZ expression, we subjected these manipulated cells to proliferation, migration, invasion, and xenograft tumorigenesis assays. We found that YAP1 functions as a tumor suppressor whereas TAZ exerted pro-tumor functions in esophageal cancer cells. We also found a significant increase in TAZ mRNA expression upon YAP1 depletion, but not vice versa, despite the downregulation of CTGF and CYR61, shared targets of YAP1 and TAZ, in xenografted tissue cells. In addition to transcriptional regulation, YAP1-mediated TAZ expression was found to occur via protein synthesis. Restored TAZ expression mitigated YAP1-mediated suppression of cellular behavior. By contrast, TAZ silencing reduced the promoting effect exerted by YAP1 depletion on cellular behaviors. The observed anti-tumor function of YAP1 was further supported by a better overall survival among esophageal cancer patients with a high YAP1 expression. We conclude that YAP1 functions as a suppressor and negatively regulates pro-tumor TAZ expression via transcriptional and translational control in esophageal cancer.

雖然YAP1和TAZ被認為是Hippo pathway的等效下游因子，但YAP1或TAZ的差異表達暗喻癌症進展過程中功能的不同。YAP1和TAZ在世界上癌症死亡率排名第六食道癌中的確切機轉仍然不清楚。在對YAP1或TAZ的表達進行單次或雙重改變後，對這些表現量改變的細胞進行增殖，遷移，侵襲和異種移植腫瘤的相關細胞與藥物處理的實驗。我們發現YAP1具有腫瘤抑制因數的功能，而TAZ在食道癌細胞有促腫瘤功能。我們還發現，削弱YAP1表現時會單向的增加TAZ mRNA表達。除了轉錄調控外，還發現YAP1介導所抑制TAZ表達也會透過抑制該蛋白質的合成。同時回復的TAZ表達會減輕YAP1介導的細胞行為的抑制。削弱TAZ的表現則會降低YAP1耗盡對細胞行為所誘發的促進作用。此外透過分析人類TCGA的食道癌患者其YAP1或TAZ mRNA與病人癒後的相關性，發現在高YAP1表達的食道癌患者有較好的總生存率。總言之，YAP1具有抑制食道癌生長轉移的功能，並且會通過轉錄和翻譯控制在食道癌細胞中負調節具促癌功能的TAZ基因的表達。

Escalante, J., Chen, W.-H., Tabatabaei, M., Hoang, A. T., Kwon, E. E., Andrew Lin, K.-Y., & Saravanakumar, A. (2022). Renewable and Sustainable Energy Reviews, 169, 112914. Read this article

As a sustainable and renewable energy source, biomass has piqued interest in generating bioenergy and biofuels over recent years. Pyrolysis characteristics of different feedstock samples can be analyzed and examined through thermogravimetric analysis (TGA). TGA has been an essential tool and widely used to investigate the thermal characteristics of a substance under heating environments, such as thermodegradation dynamics and kinetics. Studying the potential of waste biomass for generating sustainable bioenergy carves a pathway into a circular bioeconomy regime, and can help tackle our heavy reliance on nonrenewable energy sources. This study aims to give a deep insight into the wide use of TGA in aiding in the research and development of pyrolysis of different waste biomass sources. The thermal characteristics portrayed by different biomass wastes through TGA are discussed. The effects of significant pyrolysis operating parameters are also illustrated. A more comprehensive understanding of evolved products during the pyrolysis stage can be gained by combining TGA with other analytical methods. Overall, an in-depth literature review helps identify current trends and technological improvements (i.e., integrating artificial intelligence) of TGA use with pyrolysis.

作為一種再生能源，近年來生質物製造成生質能及生質燃料已經引起了人們高度的興趣。不同原料樣品的熱解特性可以藉由熱重分析進行分析和檢驗。熱重分析一直是不可或缺的工具，廣泛用於研究物質在加熱環境下的熱特性，例如熱降解動力學和動力學。由於永續生質能源的潛力，研究生質廢棄物開啟了通往循環生物經濟的途徑，並有助於解決我們對非再生能源的嚴重依賴。本研究旨在深入了解熱重分析在幫助研究和開發不同生質廢棄物來源的熱解方面的廣泛應用。說明通過描繪的不同生物質廢物的熱特性。還說明了重要熱解操作參數的影響。通過將熱重分析與其他分析方法的結合，可以更全面地了解熱解階段的衍生產物。整體而言，深入的文獻回顧有助於確定熱重分析使用與熱解的當前趨勢和技術（例如人工智慧）改進。

Chang, Y. S., Hou, S. Y., Yu, S. S., Tsai, S. Y., Chen, Y. Y., Hsu, L. J., Tsai, P. J., Lin, H. K., Lin, C. H., & Tsai, Y. S. (2022). Theranostics, 12(13), 5803-5819. Read this article

Bronchopulmonary dysplasia (BPD) remains one of the greatest challenges in the field of neonatology. To date, systemic corticosteroids remain one of the few proven treatments for BPD. This study was to investigate the effects of postnatal short course Dex exposure on brown adipose tissue. We found that postnatal Dex treatment induced growth retardation, BAT whitening, UCP1 downregulation and cold intolerance in neonatal rats. BAT mitochondria were damaged, and autophagosome clearance was inhibited. AMPK activators could partially rescue thesedamages.

早產兒慢性肺疾病仍然是新生兒科領域中最具挑戰的難題之一。全身性類固醇至今仍是少數證實有效可以治療或預防慢性肺疾病的藥物。我們的研究發現產後類固醇的使用會導致新生幼鼠生長遲滯、棕色脂肪白化、產熱蛋白UCP1的表現量下降與及不耐寒冷的現象。其棕色脂肪內的粒線體受損，自噬作用也會受到影響。使用AMPK活化劑可以部分挽救類固醇造成的棕色脂肪損傷。

Ko, P.-Y., Hsu, C.-C., Chen, S.-Y., Kuo, L.-C., Su, W.-R., Jou, I.-M., Su, F.-C., & Wu, P.-T. (2022). International Journal of Molecular Sciences, 23(17), 9760. Read this article

Although the combination of steroid and hyaluronic acid was thought to provide rapid pain relief and functional improvement in osteoarthritis, there is little evidence that these two combinations can treat tendinopathy. This study demonstrates that a specific ratio of steroid and hyaluronic acid formulation can improve tendinopathy through anti-apoptosis, anti-senescence and changing senescence-related secretory phenotypes without cytotoxicity. This study provides a possible approach to treat tendinopathy by using a specific combination of two known agents.

儘管認為類固醇和玻尿酸的組合治療能快速的在退化性關節炎達到疼痛緩解及功能性改善，然而，很少有證據證實這兩種組合能治療肌腱病變。本研究顯示特殊比例的類固醇和玻尿酸配方可以經由抗細胞凋零、抗老化及改變老化相關分泌表型來達到改善肌腱病變的目的，且不具有細胞毒性。本研究提供了一種可能的方法藉由使用兩種已知藥物的特殊組合來治療肌腱病變。

Li, C. J., Tsai, H. W., Chen, Y. L., Wang, C. I., Lin, Y. H., Chu, P. M., Chi, H. C., Huang, Y. C., & Chen, C. Y. (2023). J Hepatocell Carcinoma, 10, 123-138. Read this article

Hepatocellular carcinoma (HCC) accounts for 80% of all liver cancers and is the 2nd leading cause of cancer-related death in Taiwan. Various factors, including rapid cell growth, a high recurrence rate and drug resistance, make HCC difficult to cure. Moreover, the survival rate of advanced HCC patients treated with systemic chemotherapy remains unsatisfactory. Hence, the identification of novel molecular targets and the underlying mechanisms of chemoresistance in HCC and the development more effective therapeutic regimens are desperately needed. We found that protein tyrosine phosphatase IVA3 (PTP4A3) in the cisplatin/doxorubicin-resistant microarray was closely associated with the overall and recurrence-free survival rates of HCC patients. Furthermore, PTP4A3 was highly expressed in tumor tissues versus adjacent normal tissues from HCC patients. In addition, we evaluated the IL-6-associated signaling pathway involving STAT3 and JAK2, and the levels of p-STAT3, p-JAK2, STAT3 and JAK2 were obviously reduced with cisplatin or doxorubicin treatment in HCC cells. Collectively, we suggest that cisplatin or doxorubicin decreases HCC cell viability via downregulation of PTP4A3 expression through the IL-6R-JAK2-STAT3 cascade. Therefore, emerging evidence provides a deep understanding of the roles of PTP4A3 in HCC cisplatin/doxorubicin chemoresistance, which can be applied to develop early diagnosis strategies and reveal prognostic factors to establish novel targeted therapeutics to specifically treat HCC.

肝細胞癌占了所有肝癌的80%，在台灣是死亡率第二的癌症。很多因素導致肝細胞癌難以治癒，如快速生長，高度復發及藥物抗藥性。而且肝細胞癌較後期的病人經過全身系統性化療治療後，其存活率並沒有有效改善，因此，鑑定新穎的分子、探討產生化療抗藥性的機制、以及發展有效的治療方式是非常需要的。我們透過DNA微陣列(microarray)，發現PTP4A3跟整體存活率及無復發存活率有高度相關，且PTP4A3高度表現在臨床肝細胞癌組織中。我們分析與IL-6相關的訊息傳導分子，像是p-STAT3、STAT3、p-JAK2、JAK2在肝細胞癌的表現都會被cisplatin 及doxorubicin抑制。整體來說，我們發現cisplatin 及doxorubicin會透過IL-6R-JAK2-STAT3訊息傳導路徑去降低PTP4A3的表現，進而抑制肝細胞癌細胞的存活率。因此，這篇提供了PTP4A3在cisplatin/doxorubicin化療藥物抗藥性的肝細胞癌中所扮演的角色，期望進一步發展出具早期診斷以及預後的分子，建立在肝細胞癌中，新的標靶藥物治療的分子。