The non-structural protein 5A (NS5A) is a hepatitis C virus (HCV) protein indispensable for the viral life cycle. Many prior papers have pinpointed several serine residues in the low complexity sequence I region of NS5A responsible for NS5A phosphorylation; however, the functions of specific phosphorylation sites remained obscure. Using phosphoproteomics, we identified three phosphorylation sites (serines 222, 235, and 238) in the NS5A low complexity sequence I region. Reporter virus and replicon assays using phosphorylation-ablated alanine mutants of these sites showed that Ser-235 dominated over Ser-222 and Ser-238 in HCV replication. Immunoblotting using an Ser-235 phosphorylation-specific antibody showed a time-dependent increase in Ser-235 phosphorylation that correlated with the viral replication activity. Ser-235 phosphorylated NS5A co-localized with double-stranded RNA, consistent with its role in HCV replication. Mechanistically, Ser-235 phosphorylation probably promotes the replication complex formation via increasing NS5A interaction with the human homologue of the 33-kDa vesicle-associated membrane protein-associated protein. Casein kinase I␣ (CKI␣) directly phosphorylated Ser-235 in vitro. Inhibition of CKI␣ reduced Ser-235 phosphorylation and the HCV RNA levels in the infected cells. We concluded that NS5A Ser-235 phosphorylated by CKI␣ probably promotes HCV replication via increasing NS5A interaction with the 33-kDa vesicle-associated membrane protein-associated protein.Chronic HCV 2 infection affects 130 -170 million people worldwide (1). The infection is often asymptomatic until development of severe liver diseases, including fibrosis, cirrhosis, and hepatocellular carcinoma, making chronic HCV infection the most common cause of liver transplant (2). HCV is an enveloped virus with a positive, single-stranded RNA genome encoding three structural (core, E1, and E2) and seven non-structural (p7, NS2, NS3, NS4A, NS4B, NS5A, and NS5B) proteins (1). The structural proteins together with the host membranes make up the viral particles, whereas the non-structural proteins are required for a complete life cycle. Already, there are several approved highly efficient HCV antivirals targeting non-structural proteins, including NS3/4A protease inhibitors (boceprevir, telaprevir, and simeprevir) and an NS5B RNA-dependent RNA polymerase inhibitor (sofosbuvir) (3). However, their high costs prohibit their accessibility to most patients (4). New competitive alternatives are desirable.NS5A is a multitasking protein required for the HCV life cycle and thus a good antiviral target (5). It is a phosphoprotein that appears as two bands at 56 and 58 kDa on immunoblots, respectively, referred to as hypophosphorylated (p56) and hyperphosphorylated (p58) NS5A (6). NS5A interacts with many viral and host proteins and participates in various aspects of the viral life cycle (7). For example, NS5A was reported to interact with the hVAP-A protein that takes part in the replication protein complex formation (8 -10). NS5A mutatio...

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The emergence of Coronavirus disease 2019 (COVID-19) had rapidly spread since FEB/MAR 2020. Policy to prevent transmission of COVDI-19 resulted in multi-dimensional impact on social interaction. We aimed to develop a beneficial survey tool with favorable quality and availability, the Societal Influences Survey Questionnaire (SISQ), to evaluate social influences on people during this pandemic. The SISQ was developed with 15 items and 4-point Likert scales consisting of five factors. These include social distance, social anxiety, social desirability, social information, and social adaptation. Construct validity and reliability were performed to verify the SISQ. A total of 1912 Taiwanese were recruited. The results demonstrated that the SISQ has acceptable reliability, with Cronbach’s alphas ranging between 0.57 and 0.76. The SISQ accounted for 58.86% and satisfied the requirement of Kaiser–Mayer–Olkinvalues (0.78) and significant Bartlett’s Test of sphericity. Moreover, the confirmatory factor analysis fit indices also indicated the adequacy of the model. As for multiple comparison, females scored higher than males in factor of social distance. Unemployed participants and those without partners scored higher in several domains of factors. The survey method and survey instrument prove reliable and valuable, also providing different categories of assessment results regarding social influences and their impacts. Further studies are warranted to extend the applicability of SISQ.

Elsevier has created a COVID-19 resource centre with free information in English and Mandarin on the novel coronavirus COVID-19. The COVID-19 resource centre is hosted on Elsevier Connect, the company's public news and information website. Elsevier hereby grants permission to make all its COVID-19-related research that is available on the COVID-19 resource centre-including this research content-immediately available in PubMed Central and other publicly funded repositories, such as the WHO COVID database with rights for unrestricted research re-use and analyses in any form or by any means with acknowledgement of the original source. These permissions are granted for free by Elsevier for as long as the COVID-19 resource centre remains active.

The apo epsilon4 allele was not associated with MDD in this study. However, the finding of a lower frequency of the apo epsilon2 allele in MDD could lead to the conclusion that the apo epsilon2 allele likely provides a protective effect against MDD in the Taiwanese population.

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BackgroundThe purpose of this study was to investigate the relationship among work stress, sex life satisfaction, and mental health of married nurses. Demographic information, work stress, sex life satisfaction, sexual desire and mental health measured using the Chinese Health Questionnaire, data were collected from 100 married nurses in Taiwan.FindingsSex life satisfaction and age were negatively correlated, but sex life satisfaction and sexual desire were positively correlated. The mental health of over-committed nursing staff was not affected. Higher reward for effort was positively correlated with sex life satisfaction.ConclusionsNo matter whether job stress was high or low, receiving a higher reward for effort led to better sex life satisfaction, which had a satisfying positive effect on the nurses' lives. To improve nursing care quality at the hospital, nursing administrators should assist nurses in confronting work stress via positive adjustment, which is associated with the nurses’ sexual harmony, and quality of life.

Priapism is a urologic emergency, and a urologic consultation should be obtained as early as possible. Its etiologies are numerous and diverse. Patients who use antipsychotic drugs should be informed about the complications of priapism, especially those patients with a history of prolonged erections associated with other alpha-adrenergic blocking agents or a history of sickle cell disease. If antipsychotic medication is considered to be needed in the treatment of patients with a history of priapism, physicians should select a drug with a low peripheral alpha-adrenergic blocking property. Physicians should be aware of this rare but potentially serious complication of antipsychotic drugs. Early intervention and appropriate treatment are essential to prevent permanent impotence and other serious complications.