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Eye fundus diseases, such as retinal degenerative diseases, which lead to blindness in ≈12% of individuals aged >65 years, cause permanent damage to retinal cells. The antioxidant quercetin (QC) is promising for the effective treatment of eye fundus diseases; however, its poor solubility and low retention rate often limit its clinical application. Herein, an in situ ophthalmic tethered gold yarnball (GY) that doubles as an ocular retention agent and QC reservoir to overcome low fundus drug retention is developed. After intravitreal injection, QC@GYs enhance retinal cell leakage and internal limiting membrane permeability, facilitating the partial penetration of QC@GYs into the intraretinal tissue. The combination of retina‐tethered QC@GY and first‐level sustained release reduces macular degeneration in vivo by effectively regulating oxidative stress. Furthermore, the sustained release of QC preserves the viability of retinal pigment epithelium cells, reduces apoptosis, and suppresses drusen formation. This preservation of retinal morphology and function maximizes the therapeutic impact while minimizing the need for frequent intraocular administration. Overall, the ophthalmic tethered GY platform is a versatile tool for retinal drug delivery for the treatment of eye fundus diseases. [ABSTRACT FROM AUTHOR]

Purpose: This study constructs an efficiency evaluation framework for assessing the human, structural and relational capital in the semiconductor industry of Taiwan. Furthermore, we analyze whether there are significant differences in efficiency across different levels concerning the industry supply chain (upstream, midstream and downstream), employee service tenure, capital scale and company establishment years. Design/methodology/approach: This study focuses on Taiwanese semiconductor companies, utilizing data sourced from the Taiwan Economic Journal (TEJ) Database for the period spanning 2017 to 2021, encompassing a total of five years. Due to the nondisclosure of intangible asset values by all companies, an effort was made to ensure a comparable baseline by excluding companies with incomplete or missing data. Finally, empirical analysis was conducted on a sample of 64 companies using the dynamic network data envelopment analysis method. Findings: (1) Overall efficiency demonstrates structural capital as the most prominent, followed by relational capital, while human capital shows relatively poorer efficiency. (2) To enhance the efficiency of intellectual capital, priority should be given to improving the efficiency of outputs related to intellectual property rights such as patents. (3) The midstream segment exhibits the best efficiency in both structural and relational capital. (4) Companies with longer employee service tenures exhibit superior efficiency in human capital in the long run. (5) Companies with extended establishment years and larger capital scales demonstrate superior efficiency in both human and structural capital. Originality/value: Reflecting on past literature, scholars have primarily focused on the relationship between intellectual capital and firm efficiency, often emphasizing the overall efficiency of intellectual capital. However, within organizations, human capital, structural capital, and relational capital are interrelated. This study, for the first time, assesses the efficiency of these three components within an organization. The research addresses the challenges in analyzing the efficiency of intellectual capital and introduces a highly contemporary approach – dynamic network data envelopment analysis (DNDEA). Using the semiconductor industry in Taiwan as a case study, this paper conducts empirical analysis in a captivating and worthy industry. Therefore, the ideas presented in this paper are original. [ABSTRACT FROM AUTHOR]

Stigma remains a significant barrier preventing individuals from seeking the support they need, particularly for individuals with East Asian heritages. To explore potential mechanisms, this study examined links from East Asian ideologies to mental health help‐seeking attitudes and peace of mind across five cultural groups: 322 respondents in China, 400 in Japan, 362 in Taiwan, 319 Asian Americans, and 688 white Americans. The three teachings of East Asia accounted for 31%–85% of the cross‐cultural differences in mental health attitudes and peace of mind. Empowering Confucian tenets (self‐cultivation, leading by example, and human heartedness), Taoism, and Buddhism all uniquely predicted greater peace of mind across most of the groups. Empowering Confucianism also predicted lower mental health stigma whereas Buddhism predicted greater stigma. Finally, Restrictive Confucian tenets (e.g., interpersonal harmony, propriety, and relational hierarchy) predicted greater stigma and lower peace of mind. Implications for addressing stigma/resistance within treatment and for promoting mental health across cultures are discussed. [ABSTRACT FROM AUTHOR]

This article presents a novel approach for detecting the folding angle (Of) of foldahle OLED TDDI panels using mutual capacitance driving. It offers the potential to reduce the number of module components, conserve space, and provide additional folding angle (Of) reference data for a wide range of applications. This method can be applied in self‐capacitive and mutual‐capacitive touch sensors, eliminating the need for additional sensors or design modifications. [ABSTRACT FROM AUTHOR]

Objectives: The Unified Flexibility and Mindfulness (UFM) model is a process-oriented multistage mechanistic model operationalizing the interplay between forms of mechanistic mindfulness and informed mindfulness, thereby representing holistic mindfulness as a set of interrelated processes and clarifying their links to well-being. Recent cross-sectional, correlational findings from a US sample supported the UFM model. The current study used data across 4 countries to link everyday aspects of Buddhism to components within the UFM model, thereby (1) extending work on the UFM model cross-culturally, (2) empirically tracing various aspects of mindfulness back to their origins, and (3) extending Buddhist psychology to embrace a broad operationalization of mindfulness within the Buddhism-Informed UFM (BI-UFM) model. Methods: A sample of 2091 online respondents (68% female, M = 32yo) drawn from 5 cultural groups (668 white Americans, 319 Asian Americans, 332 Chinese, 400 Japanese, 362 Taiwanese) completed the Three Teachings of East Asia (TTEA) inventory, the Multidimensional Psychological Flexibility Inventory (MPFI; a UFM measure), and measures of distress and well-being. Results: Confirmatory SEM analyses suggested that across random sample halves, culture groups, and Buddhists vs. non-Buddhists, key aspects of Buddhism (e.g., impermanence, meditation practice) were stably and consistently linked to greater mindful present moment awareness and decentering, which were in turn linked to value-driven behavior and well-being. Aspects of punishing karmic view were linked to higher distraction/inattention and defensively reacting to difficult experiences, which were in turn linked to aimless haphazard behavior and distress. Exploratory network analyses yielded comparable findings, highlighting the central nature of meditation practice and informed, value-driven behavior. The results more broadly supported the BI-UFM process model in which forms of mechanistic mindfulness were linked to greater informed mindfulness (e.g., decentering and value-driven behavior), highlighting possible paths toward cultivating holistic mindfulness, thereby promoting well-being. Conclusions: The current results support the BI-UFM model as a conceptual framework for understanding how Buddhist thought might shape the lives of individuals across the globe. [ABSTRACT FROM AUTHOR]

Background: Mesenchymal stem cells (MSCs) hold promise for cell-based therapy, yet the sourcing, quality, and invasive methods of MSCs impede their mass production and quality control. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) can be infinitely expanded, providing advantages over conventional MSCs in terms of meeting unmet clinical demands. Methods: The potential of MSC therapy for Leber's hereditary optic neuropathy (LHON) remains uncertain. In this study, we used HLA-homozygous induced pluripotent stem cells to generate iMSCs using a defined protocol, and we examined their therapeutic potential in rotenone-induced LHON-like models in vitro and in vivo. Results: The iMSCs did not cause any tumorigenic incidence or inflammation-related lesions after intravitreal transplantation, and they remained viable for at least nine days in the mouse recipient's eyes. In addition, iMSCs exhibited significant efficacy in safeguarding retinal ganglion cells (RGCs) from rotenone-induced cytotoxicity in vitro, and they ameliorated CGL+IPL layer thinning and RGC loss in vivo. Optical coherence tomography (OCT) and an electroretinogram demonstrated that iMSCs not only prevented RGC loss and impairments to the retinal architecture, but they also improved retinal electrophysiology performance. Conclusion: The generation of iMSCs via the HLA homozygosity of iPSCs offers a compelling avenue for overcoming the current limitations of MSC-based therapies. The results underscore the potential of iMSCs when addressing retinal disorders, and they highlight their clinical significance, offering renewed hope for individuals affected by LHON and other inherited retinal conditions. [ABSTRACT FROM AUTHOR]

The nucleotide‐binding and oligomerization domain, leucine‐rich repeats, and pyrin domain‐containing protein 3 (NLRP3) inflammasome plays a crucial role in innate immunity and is involved in the pathogenesis of autoinflammatory diseases. Glycolysis regulates NLRP3 inflammasome activation in macrophages. However, how lactic acid fermentation and pyruvate oxidation controlled by the mitochondrial pyruvate carrier (MPC) affect NLRP3 inflammasome activation and autoinflammatory disease remains elusive. We found that the inactivation of MPC with genetic depletion or pharmacological inhibitors, MSDC‐0160 or pioglitazone, increased NLRP3 inflammasome activation and IL‐1β secretion in macrophages. Glycolytic reprogramming induced by MPC inhibition skewed mitochondrial ATP‐associated oxygen consumption into cytosolic lactate production, which enhanced NLRP3 inflammasome activation in response to monosodium urate (MSU) crystals. As pioglitazone is an insulin sens MSDC‐itizer used for diabetes, its MPC inhibitory effect in diabetic individuals was investigated. The results showed that MPC inhibition exacerbated MSU‐induced peritonitis in diabetic mice and increased the risk of gout in patients with diabetes. Altogether, we found that glycolysis controlled by MPC regulated NLRP3 inflammasome activation and gout development. Accordingly, prescriptions for medications targeting MPC should consider the increased risk of NLRP3‐related autoinflammatory diseases. [ABSTRACT FROM AUTHOR]

In this paper, LCD in‐cell self‐capacitive sensor using 3D detection driving method for proximity 50mm is proposed. Based on self‐capacitive sensor and 3D detection driving method, proximity signal is 0.249pF in our simulation system. This paper also shows that the 50mm height slug can be detected with Novatek LCD TDDI NT36523 and PCB sensor board. [ABSTRACT FROM AUTHOR]

The fomite transmission of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) has drawn attention because of its highly contagious nature. Therefore, surfaces that can prevent coronavirus contamination are an urgent and unmet need during the coronavirus disease 2019 (COVID‐19) pandemic. Conventional surfaces are usually based on superhydrophobic or antiviral coatings. However, these coatings may be dysfunctional because of biofouling, which is the undesired adhesion of biomolecules. A superhydrophobic surface independent of the material content and coating agents may serve the purpose of antibiofouling and preventing viral transmission. Doubly reentrant topology (DRT) is a unique structure that can meet the need. This study demonstrates that the DRT surfaces possess a striking antibiofouling effect that can prevent viral contamination. This effect still exists even if the DRT surface is made of a hydrophilic material such as silicon oxide and copper. To the best of our knowledge, this work first demonstrates that fomite transmission of viruses may be prevented by minimizing the contact area between pathogens and surfaces even made of hydrophilic materials. Furthermore, the DRT geometry per se features excellent antibiofouling ability, which may shed light on the applications of pathogen elimination in alleviating the COVID‐19 pandemic. [ABSTRACT FROM AUTHOR]

In this paper, a wearable OLED in‐cell self‐capacitive sensor using machine learning algorithm for water‐proofing is proposed. This paper also shows the experiment and the test result. The result shows that the success rate of water‐proofing on bezel can be largely improved (from 30.7% to 77.1%) by machine learning method on the wearable device with Novatek TDDI NT38350. [ABSTRACT FROM AUTHOR]

In this paper, the self‐capacitive ring like touch sensor design and algorithm for OLED on‐cell touch panel is proposed by rearranging the touch sensor pad, and using hybrid algorithm to calculate touch position. Base on ring like touch sensor design and hybrid algorithm, we can improve the touch accuracy of ring region and realize sliding function on smart watch edge without real rotating bezel mechanical parts. [ABSTRACT FROM AUTHOR]

Wind is one of the cleanest renewable energy resources. Through the "Thousand Wind Turbines Project", Taiwan is planning to increase the proportion of power generation from renewable energy and has set a target of 5.7 GW for offshore wind by 2025. The effects of future offshore wind farms (OWFs) over the Taiwan Strait on the atmospheric environment have not been evaluated. This study examined the potential effects of proposed OWFs on the atmospheric environment if the OWFs had existed during Tropical Storm Haitang (2017) by using Weather Research and Forecasting (WRF) model. A small set of ensemble simulations was conducted for studying the sensitivity of the ambient conditions in the region to the wind farm locations, the number and density of the turbines, and the initial time of simulations. Following the landfall and northward movement of Tropical Storm Haitang, a series of complex interactions between the typhoon circulation and the wind farm emerged, including small time slots of wake effect and mountain blocking effect. The combination of these rapidly changing OWFs-related effects contributed to a weak reduction in precipitation (− 1.08 mm) and hub-height wind speed (− 0.25 m s−1), as well as minimal warming near the surface (+ 0.13 °C) over southern Taiwan. [ABSTRACT FROM AUTHOR]

Lappaol F (LAF), a natural lignan from Arctium lappa Linné (Asteraceae), inhibits tumour cell growth by inducing cell cycle arrest. However, its underlying anticancer mechanism remains unclear. The effects of LAF on the Hippo-Yes-associated protein (YAP) signalling pathway, which plays an important role in cancer progression, were explored in this study. Cervical (HeLa), colorectal (SW480), breast (MDA-MB-231) and prostate (PC3) cancer cell lines were treated with LAF at different concentrations and different durations. BALB/c nude mice bearing colon xenografts were intravenously injected with vehicle, LAF (10 or 20 mg/kg) or paclitaxel (10 mg/kg) for 15 days. The expression and nuclear localisation of YAP were analysed using transcriptome sequencing, quantitative PCR, western blotting and immunofluorescence. LAF suppressed the proliferation of HeLa, MDA-MB-231, SW480 and PC3 cells (IC50 values of 41.5, 26.0, 45.3 and 42.9 μmol/L, respectively, at 72 h), and this was accompanied by significant downregulation in the expression of YAP and its downstream target genes at both the mRNA and protein levels. The expression of 14-3-3σ, a protein that causes YAP cytoplasmic retention and degradation, was remarkably increased, resulting in a decrease in YAP nuclear localisation. Knockdown of 14-3-3σ with small interfering RNA partially blocked LAF-induced YAP inhibition and anti-proliferation effects. In colon xenografts, treatment with LAF led to reduced YAP expression, increased tumour cell apoptosis and tumour growth inhibition. LAF was shown to be an inhibitor of YAP. It exerts anticancer activity by inhibiting YAP at the transcriptional and post-translational levels. [ABSTRACT FROM AUTHOR]

In an article titled "Ophthalmic Tethered Gold Yarnball-Mediated Retained Drug Delivery for Eye Fundus Disease Treatment" published in Small Science, researchers developed a new method for delivering drugs to the eye. They created an ophthalmic tethered gold yarnball (GY) that acts as both a retention agent and a reservoir for the drug quercetin (QC). When injected into the eye, the QC@GYs improved the retention of the drug in the retina and allowed it to penetrate into the intra-retinal tissue. This research has potential implications for the treatment of eye fundus diseases. [Extracted from the article]

Nonmotor symptoms (NMSs) cause major burden in patients with Parkinson's disease (PD). Previous NMSs progression studies mostly focused on the prevalence. We conducted a longitudinal study to identify the progression pattern by the severity. PD patients recruited from the outpatient clinics of a tertiary medical center were evaluated by the Unified Parkinson's Disease Rating Scale and Non-Motor Symptoms Scale (NMSS). A retrospective study with three-step analysis was performed. Step 1, the NMSs severity was compared among patients stratified by disease duration every 2 years up to 10 years. Step 2, patients with repeated tests in 2 years were categorized into 4 groups by the diseased duration of every 5 years. Step 3, the NMSS score changes in 6 years follow-up were determined, and the dosage of anti-PD drugs was compared to the NMSs severity changes. 676 patients completed the step 1 analysis, which showed a trend of NMSs worsening but not significant until the disease duration longer than 4–6 years. Furthermore, the severity did not change between repeated evaluations in 2 years in all patients. The progression became apparent after 6 years. Individual symptoms had different progression patterns and the increment of medications was independent to NMSs evolution. We demonstrated the NMSs severity progression in Taiwanese PD patients and the independence of the medications and NMSs progression. [ABSTRACT FROM AUTHOR]

Objectives: Buddhism, Taoism, and Confucianism have influenced societies and shaped cultures as they have spread across the span of history and ultimately across the world. However, to date, the interrelated nature of their impacts has yet to be examined largely due to the lack of a measure that comprehensively assesses their various tenets. Building on a conceptual integration of foundational texts on each ideology as well as on recent measure development work (much of which is unpublished), the current studies developed a comprehensive measure of these ideologies (the Three Teachings of East Asia Inventory; TTEA) and validated it across four languages. Methods: A combined sample of 2,091 online respondents (Study 1: 322 Chinese respondents, Study 2: 400 Japanese respondents, Study 3: 362 Taiwanese respondents, Study 4: 688 White Americans and 319 Asian Americans) completed 25–35 min online survey in their preferred language: English, Traditional Mandarin, Simplified Mandarin, or Japanese. Results: Exploratory Factor Analyses within a 122-item pool identified 18 stable dimensions across all samples. Measurement invariance analyses identified the final 61-items of the TTEA inventory (demonstrating reasonable invariance across all languages), confirming 18 individual tenet subscales that organize into four higher-order composites: Buddhism, Taoism, Restrictive Confucianism, and Empowering Confucianism. A shorter 36-item version of the TTEA inventory was also developed. The TTEA scales demonstrated (1) acceptable internal consistency, (2) discriminant validity, and (3) incremental predictive validity for current life satisfaction and vitality. Conclusions: The TTEA inventory offers one of the first comprehensive, multilingual measures that will allow cross-cultural researchers to examine the influence of three related Eastern ideologies on societies across the world. [ABSTRACT FROM AUTHOR]

A single-blind study to investigate the effects of noisy galvanic vestibular stimulation (nGVS) in straight walking and 2 Hz head yaw walking for healthy and bilateral vestibular hypofunction (BVH) participants in light and dark conditions. The optimal stimulation intensity for each participant was determined by calculating standing stability on a force plate while randomly applying six graded nGVS intensities (0–1000 µA). The chest–pelvic (C/P) ratio and lateral deviation of the center of mass (COM) were measured by motion capture during straight and 2 Hz head yaw walking in light and dark conditions. Participants were blinded to nGVS served randomly and imperceivably. Ten BVH patients and 16 healthy participants completed all trials. In the light condition, the COM lateral deviation significantly decreased only in straight walking (p = 0.037) with nGVS for the BVH. In the dark condition, both healthy (p = 0.026) and BVH (p = 0.017) exhibited decreased lateral deviation during nGVS. The C/P ratio decreased significantly in BVH for 2 Hz head yaw walking with nGVS (p = 0.005) in light conditions. This study demonstrated that nGVS effectively reduced walking deviations, especially in visual deprived condition for the BVH. Applying nGVS with different head rotation frequencies and light exposure levels may accelerate the rehabilitation process for patients with BVH. Clinical Trial Registration This clinical trial was prospectively registered at www.clinicaltrials.gov with the Unique identifier: NCT03554941. Date of registration: (13/06/2018). [ABSTRACT FROM AUTHOR]

Pyrite catalyzes oxidation of various organic contaminants by dissolved oxygen (DO) under acidic conditions; however, the catalytic mechanism under alkaline conditions is still not clear. In this study, we observe increased oxidation rates of aniline with increasing pHs (7.0–11.0). Electron paramagnetic resonance (EPR) analysis and quenching experiments rule out contributions of •OH, O2•−, 1O2 and Fe (IV) to aniline oxidation and suggest that the Fe (III)–OOH peroxo and/or H2O2 are the primary oxidative species in the oxidation of aniline at pH 11.0. In addition, 200 mg L−1 H2O2 does not apparently increase the oxidation rate of aniline, which also rules out the predominant contribution of the produced H2O2 to aniline oxidation. We therefore suggest that the Fe (III)–OOH peroxo is indeed the primary oxidative species in the pyrite–DO system under alkaline conditions. Analyses of solid total organic carbon (TOC), gas chromatography–mass spectrometry and Fourier‐transform infrared spectroscopy further reveal that more than 83.3% aniline has been polymerized to polyaniline, instead of being mineralized into CO2 and H2O, indicating that H‐abstraction from aniline by the Fe (III)–OOH peroxo is an important step in the oxidation of aniline under alkaline conditions. This study provides new insight into the oxidative species in the pyrite–DO system, and opens a new door for organic degradations under alkaline conditions. [ABSTRACT FROM AUTHOR]

Bi2+xWO6 is a cost-effective and environmentally friendly photocatalyst that shows high reactivity in the oxidation of various contaminants under visible light. However, under alkaline conditions, the reactive oxidative species in the Bi2+xWO6 system are still not clear yet. In this study, it is observed that the oxidation rates of As(III) increase with increasing pH values in the Bi2.15WO6 system. Photoluminescence and the Mott–Schottky analyses confirm that OH− promotes the separation and transfer of photogenerated electron–hole pairs over Bi2.15WO6, thus facilitating the oxidation of As(III). Electron spin resonance spectra analysis and quenching experiments rule out contributions of •OH, O2˙−, 1O2 and superoxo species to As(III) oxidation and indicate that surface –OOH and/or H2O2 are indeed the predominant species under alkaline conditions. The improved production of H2O2 by H-donors such as glucose and phenol, as well as the UV-vis diffuse reflectance and Raman analyses, further confirms the formation of surface –OOH on Bi2.15WO6 under alkaline conditions. In the dark, the significant higher oxidation rate of As(III) by H2O2–Bi2.15WO6 than that by H2O2 alone reveals that surface −OOH, instead of H2O2, plays an important role in As(III) oxidation. This study enriches our understanding of the diversity of reactive oxygen species (ROS) in the Bi2.15WO6 system and gives new insight into the mechanism involved in the oxidation of As(III) under alkaline conditions. [ABSTRACT FROM AUTHOR]

Introduction: Nonmotor symptoms (NMSs) severely affect the daily quality of life of patients with Parkinson's disease (PD). Although many studies have documented the clinical characteristics of NMSs in PD patients, some issues remain unaddressed. The severity and gender distribution of NMSs in Asian and the Western patients differ. The correlations between clinical characteristics and NMS manifestations remain unclear. We studied these relationships in a large cohort of Taiwanese PD patients. Methods: Patients with PD were recruited from the outpatient clinic of a tertiary medical center and evaluated with standardized assessment protocols, including the NonMotor Symptoms Scale (NMSS), Unified Parkinson's Disease Rating Scale (UPDRS), Hoehn and Yahr (H&Y) scale, Mini-Mental Status Examination, and Montreal Cognitive Assessment. Results: Among 820 patients enrolled, 41.8% were female. The prevalence of the NMSs was 96.5%, with attention/memory (79.51%) being the most frequently involved domain. The mean severity score on the NMSS was 36.48 ± 34.30. Male patients reported higher NMS prevalence and severity than female patients, mostly in the gastrointestinal tract and urinary domains. We found that the severity of NMSs was correlated with disease duration, UPDRS Part III score, and H&Y stage. Conclusion: Although they exhibited similar NMS prevalence, Taiwanese PD patients reported less intense NMSs compared with those reported by Western patients. Furthermore, the NMS items our patients emphasized and gender discrepancies were distinct from those in Western studies. [ABSTRACT FROM AUTHOR]

Tazarotene-induced gene 1 (TIG1) encodes a protein that is a retinoid-regulated tumor suppressor. TIG1 is expressed in most normal tissues, and downregulation of TIG1 expression in multiple cancers is caused by promoter hypermethylation. Kazal-type serine protease inhibitor-2 (SPINK2) is a serine protease inhibitor, and the SPINK protein family has been shown to inhibit the expression of urokinase-type plasminogen activator (uPA). In addition, increased levels of uPA and the uPA receptor were observed in testicular cancer tissues. This study demonstrated that TIG1 interacts with SPINK2 in NT2/D1 testicular carcinoma cells. TIG1 and SPINK2 were highly expressed in normal testis tissues, while low expression levels of TIG1 and SPINK2 were found in testicular cancer tissues. TIG1 inhibited cell invasion, migration, and epithelial–mesenchymal transition (EMT) of NT2/D1 cells. SPINK2 enhanced TIG1-regulated uPA activity and EMT suppression, while silencing SPINK2 alleviated TIG1-mediated EMT regulation, cell migration, and invasion. Therefore, the results suggest that the interaction between TIG1 and SPINK2 plays an important role in the inhibition of testicular cancer cell EMT, and suppression is mediated through downregulation of the uPA/uPAR signaling pathway. [ABSTRACT FROM AUTHOR]

Phospholipase A and acyltransferase 4 (PLAAT4) is a member of the HREV107 tumor suppressor gene family. The expression of PLAAT4 has been shown to induce cell death; however, the underlying mechanism remains unknown. Here, we found that RPLP0, a ribosomal protein, can interact with PLAAT4, as determined by yeast two-hybrid screening, coimmunoprecipitation, and colocalization. The level of RPLP0 was suppressed in HtTA cervical cancer cells expressing PLAAT4. In PLAAT4-expressing or RPLP0-silenced cells, decreased cell viability and cell proliferation combined with increased cell death were observed. Furthermore, the levels of cell cycle-associated proteins and anti-apoptotic proteins decreased in PLAAT4-expressing or RPLP0-silenced cells. Similar patterns of cell viability and expression levels of cell-cycle-associated proteins and apoptosis-related proteins were observed in PLAAT4-expressing and RPLP0-knockdown cells, indicating that RPLP0 deficiency might be involved in PLAAT4-mediated growth inhibition and cellular apoptosis. [ABSTRACT FROM AUTHOR]

Object: The purpose of this study was to evaluate the clinical effectiveness of telemedicine on changes in body mass index for overweight and obese people as well as for diabetes and hypertension patients.Methods: A systematic review of articles published before 31 August 2014, was conducted using searches of Medline, Cochrane Library, EMBASE, and CINAHL Plus. The inclusion criteria were randomised controlled trials that compared telemedicine interventions with usual care or standard treatment in adults and reported a change in body mass index. A meta-analysis was conducted for eligible studies, and the primary outcome was a change in body mass index. Subgroup analysis was performed for the type of telemedicine, main purpose of intervention, and length of intervention.Results: Twenty-five randomised controlled trials comprising 6253 people were included in the qualitative and quantitative analyses. The length of intervention ranged from nine weeks to two years. The meta-analysis revealed significant differences in body mass index changes (pooled difference in means = -0.49, 95% confidence interval -0.63 to -0.34, p < 0.001) between the telemedicine and control groups. The subgroup analyses found that either Internet-based or telephone-based intervention was associated with greater changes in body mass index than in controls. Telemedicine intervention was effective in improving body mass index whether it was used for diabetes control, hypertension control, weight loss, or increasing physical activity and was also effective for people with and without diabetes or hypertension. However, only interventions with a duration ≥ 6 months significantly decreased body mass index compared to controls.Conclusion: Both patients with chronic disease and overweight/obese people could benefit from telemedicine interventions. We suggest that an effective telemedicine approach should be longer than six months and emphasise the importance of post-interventional follow-ups. [ABSTRACT FROM AUTHOR]

The activation of hepatic stellate cells (HSCs) is an important step in the progress of liver fibrosis. Fibrosis can be impeded by HSC reversion to a quiescent state or HSC clearance through apoptosis. To investigate the apoptotic effects of hsian‐tsao (Mesona procumbens Hemsl) on human HSCs, the expression levels of cleaved caspase‐3, p38, and c‐Jun N‐terminal kinase (JNK) were assessed using Western blotting, and the caspase‐3 activity was measured using caspase‐3/CPP32 colorimetric assay kit. Hsian‐tsao extract (HTE) increased the activity of caspase‐3 and the level of activated caspase‐3, indicating the activation of apoptosis. The intracellular reactive oxygen species (ROS) level increased in a dose‐dependent manner. This increase was prevented by an antioxidant, suggesting that HTE induces ROS accumulation. In addition, we found that HTE induced the phosphorylation of the mitogen‐activated protein kinases JNK and p38. These collective data indicate that HTE induces apoptosis via ROS production through the p38, JNK, and caspase‐3‐dependent pathways. HTE may decrease HSC activation in liver fibrosis and may have a therapeutic potential. [ABSTRACT FROM AUTHOR]

Ebastine is a second-generation histamine H1 receptor antagonist that is used to attenuate allergic inflammation. Ebastine has also shown to affect hair loss; however, the immunoregulatory effect of ebastine cannot completely exclude the possibility of spontaneous hair regrowth in ebastine-treated mice. In this study, we examined the effects of ebastine on the growth of human follicle dermal papilla cells (HFDPC) using a WST-1 cell proliferation assay and a bromodeoxyuridine incorporation assay. Ebastine was shown to significantly increase the proliferation of HFDPC. The expression levels of cell-cycle regulatory proteins and an antiapoptotic protein were increased in ebastine-treated HFDPC. Furthermore, elevated expression levels of phospho-AKT and phospho-p44/42 extracellular signal-regulated kinase (ERK) were observed in ebastine-treated HFDPC. Ebastine-mediated HFDPC growth was completely reversed by blocking ERK kinase. The results from our present study suggest that the regulation of HFDPC proliferation by ebastine might be directly involved in hair regrowth through the ERK signaling pathway. [ABSTRACT FROM AUTHOR]

Intercellular adhesion molecule–1 (ICAM1) is crucial to the development and progression of atherosclerosis. Recent genome-wide association studies (GWAS) have revealed that single nucleotide polymorphisms (SNPs) in two of the nuclear factor-κB (NF-κB) pathway genes, NFKBIK and RELA, are associated with soluble ICAM1 (sICAM1) levels. However, neither of these two gene variants is found in the Asian populations. This study aimed to elucidate whether other candidate gene variants involved in the NF-κB pathway may be associated with sICAM1 levels in Taiwanese. After excluding carriers of the ICAM1 rs5491-T allele, three SNPs in the ICAM1 gene and eight SNPs in six of the NF-κB pathway genes (NFKB1, PDCD11, TNFAIP3, NKAPL, IKBKE, and PRKCB) were analyzed for their association with sICAM1 levels in 480 individuals. Our data showed that two SNPs, rs5498 of ICAM1 and rs1635 of NKAPL, were significantly associated with sICAM1 levels (P = 0.002 and 0.004, respectively) in the Taiwanese population. Using a multivariate analysis, rs5498 and rs1635 as well as the previously reported ABO genotypes and rs12051272 of the CDH13 gene were independently associated with sICAM1 levels (P = 0.001, 0.001, 0.006 and 0.031, respectively). An analysis with combined risk alleles of four candidate SNPs in the ICAM1, NKAPL, ABO, and CDH13 genes showed an increase in sICAM1 levels with added numbers of risk alleles and weighted genetic risk score. Our findings thus expanded the repertoire of gene variants responsible for the regulation of sICAM1 levels in the Asian populations. [ABSTRACT FROM AUTHOR]

aimed to investigate the mortality rate after falls of rural and non-rural older people and to explore the risk factors of mortality after falls among older people. Patients and methods: This population-based case–control study identified two groups from a nationwide claim database (National Health Insurance Research Database in Taiwan): a rural group and a non-rural group, which included 3,897 and 5,541 older people, respectively, who were hospitalized for accidental falls (The International Classification of Diseases, Ninth Revision, Clinical Modification: E880–E888) during 2006–2009. Both groups were followed up for 4 years after falls. Four-year cumulative all-cause mortality rate after falls was calculated, and the demographic factor, comorbidity, and medications were considered as the potential risk factors of mortality after falls. Results: The rural group had a significantly higher frequency of fall-related hospitalizations (7.4% vs 4.3%, P<0.001), but a lower 4-year cumulative all-cause mortality rate after falls than the non-rural group (8.8% vs 23.4%, P<0.001). After adjusting for age, gender, comorbidity, and medication use, the rural group had a significantly lower risk of mortality after falls than the non-rural group (adjusted odds ratio =0.32, 95% confidence interval =0.28–0.37, P<0.001). Age, gender, place of residence, comorbidity, number of medications, and inappropriate medication use were independent risk factors of mortality after falls. Conclusion: The rural older people had a higher frequency of fall-related hospitalizations but lower mortality after falls than the non-rural older people. Fall prevention programs should be adjusted for difference in place of residence. [ABSTRACT FROM AUTHOR]

Recent phylodynamic studies have focused on using tree topology patterns to elucidate interactions among the epidemiological, evolutionary, and demographic characteristics of infectious agents. However, because studies of viral phylodynamics tend to focus on epidemic outbreaks, tree topology signatures of tissue-tropism pathogens might not be clearly identified. Therefore, this study used a novel Bayesian evolutionary approach to analyze the A24 variant of coxsackievirus (CV-A24v), an ocular-tropism agent of acute hemorrhagic conjunctivitis. Analyses of the 915-nucleotide VP1 and 690-nt 3Dpol regions of 21 strains isolated in Taiwan and worldwide during 1985–2010 revealed a clear chronological trend in both the VP1 and 3Dpol phylogenetic trees: the emergence of a single dominant cluster in each outbreak. The VP1 sequences included three genotypes: GI (prototype), GIII (isolated 1985–1999), and GIV (isolated after 2000); no VP1 sequences from GII strains have been deposited in GenBank. Another five genotypes identified in the 3Dpol region had support values >0.9. Geographic and demographic transitions among CV-A24v clusters were clearly identified by Bayes algorithm. The transmission route was mapped from India to China and then to Taiwan, and each prevalent viral population declined before new clusters emerged. Notably, the VP1 and 3Dpol genes had high nucleotide sequence similarities (94.1% and 95.2%, respectively). The lack of co-circulating lineages and narrow tissue tropism affected the CV-A24v gene pool. [ABSTRACT FROM AUTHOR]

Dengue virus (DV) causes a non-specific febrile illness known as Dengue fever (DF), and a severe life-threatening illness, Dengue hemorrhagic fever/Dengue shock syndrome (DHF/DSS). Hemostatic changes induced by this virus involve three main factors: thrombocytopenia, endothelial cell damage, and significant abnormalities of the coagulation and fibrinolysis systems. The pathogenesis of bleeding in DV infections remains unknown. In this article, we focused on the DV activating endothelial cells and altering the parameters of hemostasis system. The expression of hemostasis-related factors, Thrombomodulin, TF, TFPI, t-PA, and PAI-1, in DV-infected cells were determined by RT-PCR. Flow cytometry analysis and immunofluorescence staining confirmed that the expression levels of TM in the DV-infected HMEC-1 and THP-1 cells were increased. In addition, the purified recombinant domain III of the envelope glycoprotein of DV (EIII) could induce the expression of TM in the HMEC-1 cells and THP-1 cells. The TM expression induced by DV or EIII in the endothelial cells and monocytic cells suggests that the EIII of DV plays an important role in the pathogenesis of DHF/DSS. [ABSTRACT FROM AUTHOR]

The isolation of a virus using cell culture to observe its cytopathic effects (CPEs) is the main method for identifying the viruses in clinical specimens. However, the observation of CPEs requires experienced inspectors and excessive time to inspect the cell morphology changes. In this study, we utilized artificial intelligence (AI) to improve the efficiency of virus identification. After some comparisons, we used ResNet-50 as a backbone with single and multi-task learning models to perform deep learning on the CPEs induced by influenza, enterovirus, and parainfluenza. The accuracies of the single and multi-task learning models were 97.78% and 98.25%, respectively. In addition, the multi-task learning model increased the accuracy of the single model from 95.79% to 97.13% when only a few data of the CPEs induced by parainfluenza were provided. We modified both models by inserting a multiplexer and de-multiplexer layer, respectively, to increase the correct rates for known cell lines. In conclusion, we provide a deep learning structure with ResNet-50 and the multi-task learning model and show an excellent performance in identifying virus-induced CPEs. [ABSTRACT FROM AUTHOR]

The late-onset type of Fabry disease (FD) with GLA IVS4 + 919G > A mutation has been shown to lead to cardiovascular dysfunctions. In order to eliminate variations in other aspects of the genetic background, we established the isogenic control of induced pluripotent stem cells (iPSCs) for the identification of the pathogenetic factors for FD phenotypes through CRISPR/Cas9 genomic editing. We adopted droplet digital PCR (ddPCR) to efficiently capture mutational events, thus enabling isolation of the corrected FD from FD-iPSCs. Both of these exhibited the characteristics of pluripotency and phenotypic plasticity, and they can be differentiated into endothelial cells (ECs). We demonstrated the phenotypic abnormalities in FD iPSC-derived ECs (FD-ECs), including intracellular Gb3 accumulation, autophagic flux impairment, and reactive oxygen species (ROS) production, and these abnormalities were rescued in isogenic control iPSC-derived ECs (corrected FD-ECs). Microarray profiling revealed that corrected FD-derived endothelial cells reversed the enrichment of genes in the pro-inflammatory pathway and validated the downregulation of NF-κB and the MAPK signaling pathway. Our findings highlighted the critical role of ECs in FD-associated vascular dysfunctions by establishing a reliable isogenic control and providing information on potential cellular targets to reduce the morbidity and mortality of FD patients with vascular complications. [ABSTRACT FROM AUTHOR]

(1) Background: Antifolate methotrexate (MTX) is the most common disease-modifying antirheumatic drug (DMARD) for treating human rheumatoid arthritis (RA). The mitochondrial-produced formate is essential for folate-mediated one carbon (1C) metabolism. The impacts of MTX on formate homeostasis in unknown, and rigorously controlled kinetic studies can greatly help in this regard. (2) Methods: Combining animal model (8-week old female C57BL/6JNarl mice, n = 18), cell models, stable isotopic tracer studies with gas chromatography/mass spectrometry (GC/MS) platforms, we systematically investigated how MTX interferes with the partitioning of mitochondrial and cytosolic formate metabolism. (3) Results: MTX significantly reduced de novo deoxythymidylate (dTMP) and methionine biosyntheses from mitochondrial-derived formate in cells, mouse liver, and bone marrow, supporting our postulation that MTX depletes mitochondrial 1C supply. Furthermore, MTX inhibited formate generation from mitochondria glycine cleavage system (GCS) both in vitro and in vivo. Folinate selectively rescued 1C metabolic pathways in a tissue-, cellular compartment-, and pathway-specific manner: folinate effectively reversed the inhibition of mitochondrial formate-dependent 1C metabolism in mouse bone marrow (dTMP, methionine, and GCS) and cells (dTMP and GCS) but not methionine synthesis in liver/liver-derived cells. Folinate failed to fully recover hepatic mitochondrial-formate utilization for methionine synthesis, suggesting that the efficacy of clinical folinate rescue in MTX therapy on hepatic methionine metabolism is poor. (4) Conclusion: Conducting studies in mouse and cell models, we demonstrate novel findings that MTX specifically depletes mitochondrial 1C supply that can be ameliorated by folinate supplementation except for hepatic transmethylation. These results imply that clinical use of low-dose MTX may particularly impede 1C metabolism via depletion of mitochondrial formate. The MTX induced systematic and tissue-specific formate depletion needs to be addressed more carefully, and the efficacy of folinate with respect to protecting against such depletion deserves to be evaluated in medical practice. [ABSTRACT FROM AUTHOR]

The sudden outbreak of 2019 novel coronavirus (2019-nCoV, later named SARS-CoV-2) in Wuhan, China, which rapidly grew into a global pandemic, marked the third introduction of a virulent coronavirus into the human society, affecting not only the healthcare system, but also the global economy. Although our understanding of coronaviruses has undergone a huge leap after two precedents, the effective approaches to treatment and epidemiological control are still lacking. In this article, we present a succinct overview of the epidemiology, clinical features, and molecular characteristics of SARS-CoV-2. We summarize the current epidemiological and clinical data from the initial Wuhan studies, and emphasize several features of SARS-CoV-2, which differentiate it from SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV), such as high variability of disease presentation. We systematize the current clinical trials that have been rapidly initiated after the outbreak of COVID-19 pandemic. Whereas the trials on SARS-CoV-2 genome-based specific vaccines and therapeutic antibodies are currently being tested, this solution is more long-term, as they require thorough testing of their safety. On the other hand, the repurposing of the existing therapeutic agents previously designed for other virus infections and pathologies happens to be the only practical approach as a rapid response measure to the emergent pandemic, as most of these agents have already been tested for their safety. These agents can be divided into two broad categories, those that can directly target the virus replication cycle, and those based on immunotherapy approaches either aimed to boost innate antiviral immune responses or alleviate damage induced by dysregulated inflammatory responses. The initial clinical studies revealed the promising therapeutic potential of several of such drugs, including favipiravir, a broad-spectrum antiviral drug that interferes with the viral replication, and hydroxychloroquine, the repurposed antimalarial drug that interferes with the virus endosomal entry pathway. We speculate that the current pandemic emergency will be a trigger for more systematic drug repurposing design approaches based on big data analysis. [ABSTRACT FROM AUTHOR]

Electric field stimulation is known to affect various cellular processes, including cell fate specification and differentiation, particularly towards neuronal lineages. This makes it a promising therapeutic strategy to stimulate regeneration of neuronal tissues. Retinal ganglion cells (RGCs) is a type of neural cells of the retina responsible for transduction of visual signals from the retina to the brain cortex, and is often degenerated in various blindness-causing retinal diseases. The organic photovoltaic materials such as poly-3-hexylthiophene (P3HT) can generate electric current upon illumination with light of the visible spectrum, and possesses several advantageous properties, including light weight, flexibility and high biocompatibility, which makes them a highly promising tool for electric stimulation of cells in vitro and in vivo. In this study, we tested the ability to generate photocurrent by several formulations of blend (bulk heterojunction) of P3HT (which is electron donor material) with several electron acceptor materials, including Alq3 and bis(10-hydroxybenzo[h]quinolinato)beryllium (Bebq2). We found that the photovoltaic device based on bulk heterojunction of P3HT with Bebq2 could generate photocurrent when illuminated by both green laser and visible spectrum light. We tested the growth and differentiation capacity of human induced pluripotent stem cells (hiPSC)-derived RGCs when grown in interface with such photostimulated device, and found that they were significantly increased. The application of P3HT:Bebq2-formulation of photovoltaic device has a great potential for developments in retinal transplantation, nerve repair and tissue engineering approaches of treatment of retinal degeneration. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is the eye disease with the highest epidemic incidence, and has great impact on the aged population. Wet-type AMD commonly has the feature of neovascularization, which destroys the normal retinal structure and visual function. So far, effective therapy options for rescuing visual function in advanced AMD patients are highly limited, especially in wet-type AMD, in which the retinal pigmented epithelium and Bruch's membrane structure (RPE-BM) are destroyed by abnormal angiogenesis. Anti-VEGF treatment is an effective remedy for the latter type of AMD; however, it is not a curative therapy. Therefore, reconstruction of the complex structure of RPE-BM and controlled release of angiogenesis inhibitors are strongly required for sustained therapy. The major purpose of this study was to develop a dual function biomimetic material, which could mimic the RPE-BM structure and ensure slow release of angiogenesis inhibitor as a novel therapeutic strategy for wet AMD. We herein utilized plasma-modified polydimethylsiloxane (PDMS) sheet to create a biomimetic scaffold mimicking subretinal BM. This dual-surface biomimetic scaffold was coated with laminin and dexamethasone-loaded liposomes. The top surface of PDMS was covalently grafted with laminin and used for cultivation of the retinal pigment epithelial cells differentiated from human induced pluripotent stem cells (hiPSC-RPE). To reach the objective of inhibiting angiogenesis required for treatment of wet AMD, the bottom surface of modified PDMS membrane was further loaded with dexamethasone-containing liposomes via biotin-streptavidin linkage. We demonstrated that hiPSC-RPE cells could proliferate, express normal RPE-specific genes and maintain their phenotype on laminin-coated PDMS membrane, including phagocytosis ability, and secretion of anti-angiogenesis factor PEDF. By using in vitro HUVEC angiogenesis assay, we showed that application of our membrane could suppress oxidative stress-induced angiogenesis, which was manifested in decreased secretion of VEGF by RPE cells and suppression of vascularization. In conclusion, we propose modified biomimetic material for dual delivery of RPE cells and liposome-enveloped dexamethasone, which can be potentially applied for AMD therapy. [ABSTRACT FROM AUTHOR]

Several efforts have been made on the development of bioscaffolds including the polydimethylsiloxane (PDMS) elastomer for supporting cell growth into stable sheets. However, PDMS has several disadvantages, such as intrinsic surface hydrophobicity and mechanical strength. Herein, we generated a novel PDMS-based biomimetic membrane by sequential modifications of the PMDS elastomer with graphene oxide (GO) and addition of a hexagonal micropillar structure at the bottom of the biomembrane. GO was initially homogenously mixed with pure PDMS and then was further coated onto the upper surface of the resultant PDMS. The elastic modulus and hydrophilicity were significantly improved by such modifications. In addition, the development of hexagonal micropillars with smaller diameters largely improved the ion permeability and increased the motion resistance. We further cultured retinal pigment epithelial (RPE) cells on the surface of this modified PDMS biomembrane and assayed its biocompatibility. Remarkably, the GO incorporation and coating exhibited beneficial effect on the cell growth and the new formation of tight junctions in RPE cells. Taken together, this GO-modified PDMS scaffold with polyhexagonal micropillars may be utilized as an ideal cell sheet and adaptor for cell cultivation and can be used in vivo for the transplantation of cells such as RPE cells. [ABSTRACT FROM AUTHOR]

The optimal viewing distance (OVD) of high resolution autostereoscopic 3D mobile display is obtained by using flexible liquid crystal display, which is thin and light-weight. In this article, two types of 3D-display are proposed by 10.1 inch plastic switching cell and 4.3 inch plastic parallax barrier, respectively. [ABSTRACT FROM AUTHOR]

10.1 inch prototype flexible switchable liquid crystal (LC) cell was successfully obtained using sheet-to-sheet (S2S) with low temperature manufacturing process and also applied in autostereoscopic three-dimensional (3D) display. Systematically change of plastic barrier layer substrates resulted in different reliability performance will be discussed in this paper. [ABSTRACT FROM AUTHOR]