LIM domain only 7 negatively controls nonalcoholic steatohepatitis in the setting of hyperlipidemia.

BACKGROUND AND AIMS: Hyperlipidemia has been extensively recognized as a high-risk factor for NASH; however, clinical susceptibility to NASH is highly heterogeneous. The key controller(s) of NASH susceptibility in patients with hyperlipidemia has not yet been elucidated. Here, we aimed to reveal the key regulators of NASH in patients with hyperlipidemia and to explore its role and underlying mechanisms. APPROACH AND RESULTS: To identify the predominant suppressors of NASH in the setting of hyperlipidemia, we collected liver biopsy samples from patients with hyperlipidemia, with or without NASH, and performed RNA-sequencing analysis. Notably, decreased Lineage specific Interacting Motif domain only 7 (LMO7) expression robustly correlated with the occurrence and severity of NASH. Although overexpression of LMO7 effectively blocked hepatic lipid accumulation and inflammation, LMO7 deficiency in hepatocytes greatly exacerbated diet-induced NASH progression. Mechanistically, lysine 48 (K48)-linked ubiquitin-mediated proteasomal degradation of tripartite motif-containing 47 (TRIM47) and subsequent inactivation of the c-Jun N-terminal kinase (JNK)/p38 mitogen-activated protein kinase (MAPK) cascade are required for the protective function of LMO7 in NASH. CONCLUSIONS: These findings provide proof-of-concept evidence supporting LMO7 as a robust suppressor of NASH in the context of hyperlipidemia, indicating that targeting the LMO7-TRIM47 axis is a promising therapeutic strategy for NASH.

Is cryoablation still suitable for advanced non-small cell lung cancer after failure of first-line chemotherapy? A multicenter, prospective, randomized-controlled trial of eighty-seven patients.

The aim of this study was to investigate the therapeutic effect of cryoablation treatment in advanced NSCLC patients who had failed first-line chemotherapy. Eighty-seven patients from ten hospitals in China were enrolled into the study, forty-four patients received cryoablation treatment plus basic treatment (experimental group), and forty-three patients had basic treatment alone (control group). Follow-up was performed once every three months until the end of the study or the death of the patient. The primary endpoints were overall and post-intervention survival; secondary endpoints included tumor markers, solid tumor efficacy, and symptom changes before and after treatment. There was no significant difference in median OS between the two groups of patients (9.0 months vs 11.2 months, P = 0.583). The disease control rate (DCR) and living quality of the experimental group was higher than that of the control group. In terms of OS, indiscriminate use of cryoablation for such patients was not beneficial, though it could improve symptoms of patients. Cryoablation had a significant effect on selected advanced NSCLC patients after the failure of first-line chemotherapy.

Cavin1 activates the Wnt/ß-catenin pathway to influence the proliferation and migration of hepatocellular carcinoma.

INTRODUCTION AND OBJECTIVES: Cavin1 is a cell membrane caveolin, with controversial function in different tumors. Meanwhile, the role of Cavin1 in hepatocellular carcinoma (HCC) progression remains unclear. In this study, we attempted to elucidate the significance of Cavin1 in HCC occurrence and progression. MATERIALS AND METHODS: Cavin1 content was examined in HCC tissues and paired adjacent normal liver tissues by qRT-PCR and IHC among 81 HCC patients. The Cavin1-mediated regulation of HCC proliferation and metastasis was assessed through in vitro and in vivo experiments. Finally, using GSEA, we found out Cavin1 could be a potential regulator of the Wnt pathway. The alterations of the Wnt pathway-related proteins were identified by Western Blot analysis. RESULTS: Cavin1 was lower expressed in HCC, which implied poor survival outcomes in HCC patients. Phenotypic experiments revealed that Cavin1 strongly suppressed HCC proliferation and migration in vitro and in vivo. Besides, altered epithelial-mesenchymal transition (EMT)-related protein expressions were detected. Based on our GSEA analysis, Cavin1 activated the Wnt pathway, and Western Blot analysis revealed diminished ß-catenin, c-Myc, and MMP9 contents upon Cavin1 overexpression. CONCLUSIONS: Cavin1 suppresses HCC progression by modulating HCC proliferation and migration via inhibiting the Wnt/ß-catenin axis activation.

Identification of flexible Pif1-DNA interactions and their impacts on enzymatic activities.

Flexible regions in biomolecular complexes, although crucial to understanding structure-function relationships, are often unclear in high-resolution crystal structures. In this study, we showed that single-molecule techniques, in combination with computational modeling, can characterize dynamic conformations not resolved by high-resolution structure determination methods. Taking two Pif1 helicases (ScPif1 and BsPif1) as model systems, we found that, besides a few tightly bound nucleotides, adjacent solvent-exposed nucleotides interact dynamically with the helicase surfaces. The whole nucleotide segment possessed curved conformations and covered the two RecA-like domains of the helicases, which are essential for the inch-worm mechanism. The synergetic approach reveals that the interactions between the exposed nucleotides and the helicases could be reduced by large stretching forces or electrostatically shielded with high-concentration salt, subsequently resulting in reduced translocation rates of the helicases. The dynamic interactions between the exposed nucleotides and the helicases underlay the force- and salt-dependences of their enzymatic activities. The present single-molecule based approach complements high-resolution structural methods in deciphering the molecular mechanisms of the helicases.

Preventing post-discharge suicides in psychiatric patients: insights from patients, lay healthcare supporters, and mental health professionals-a qualitative analysis.

BACKGROUND: Discharged psychiatric patients are at higher risk of suicide due to various risk factors in their lives compared to the general population. However, specific problems and needs of these patients after discharge remain unclear. This research constitutes a segment of a broader implementation study designed to formulate an interventional strategy targeting post-discharge suicide among Chinese psychiatric patients. The present study seeks to qualitatively investigate the problems and needs from the perspectives of patients, their lay healthcare supporters (LHSs), and mental health professionals (MPs), aiming to enhance the efficacy of the interventional strategy. METHODS: This study is part of a larger implementation study based on Shenzhen Kangning Hospital (SKH) in Shenzhen, Guangdong, China. Under the community-based participatory research framework, we recruited discharged psychiatric patients, their LHSs, and MPs as a collaborative community team, and we conducted individual in-depth interviews for patients and LSHs and focus group interviews with MPs. We utilized a thematic analysis approach to identify sub-themes and themes from interviews through systematically coding and analyzing the data. RESULTS: A total of 45 participants were recruited for interviews, comprising 17 patients, 8 LHSs, and 20 MPs. We conducted 25 individual in-depth interviews and 3 focus group interviews. Through the interviews, we identified three themes of post-discharge problems: problems related to self, family-related problems, societal and community-related problems. We also identified four themes related to reducing post-discharge suicide: proactive self-management, multifunctional relatives, multifunctional MP group, and a warm society. The tangible support from LHSs and emotional support from MPs are strongly emphasized. Follow-up interventions were identified as the most significant way to addressing these unmet needs. Instrumental support from the community and a caring and non-discriminatory environment for individuals with mental disorders are essential for reducing suicide risk. CONCLUSIONS: Establishing an integrated mental health care service network that connects psychiatric patients, LHSs, and MPs cross community and societal sectors, with patient-centered follow-up care at its core, is a practical approach to better address patients' needs and reduce post-discharge suicide. TRIAL REGISTRATION: Registration number: NCT04907669. Date of registration: May 26th,2021.

miRNA-383-5p Regulated Migration and Invasion of Tumor Cells by Inhibiting NCKAP1 Expression in Gastric Cancer.

Gastric cancer (GC) is the second deadliest disease in Asia, so it is crucial to find its promising therapeutic targets. The expression profile data of miR383-5p in the Cancer Genome Atlas (TCGA) were analyzed. The expression levels of miR383-5p in the collected clinical tissue samples and peripheral blood samples were examined by qPCR, and the relationship between its expression and the clinical data of patients was evaluated. MiR383-5p was overexpressed in the AGS cells, and cell biology assays, such as Transwell, were performed to detect the cell proliferation, migration, invasion and other cell biology abilities of miR383-5p. Target prediction and dual luciferase reporter gene assay were performed to find and validate the target genes of miR383-5p. The expression and activity of MMP and related proteins after overexpression of miR383-5p and NCKAP1 were detected by WB and gelatin zymography assay. The expression of miR383-5p was down-regulated in GC tissues, and its low expression was associated with lymph node metastasis. Restoration of miR383-5p expression in GC cells can inhibit the invasion and migration abilities of GC cells. MiR383-5p negatively regulated NCKAP1 through direct interaction with the 3'UTR sequence of NCKAP1. The overexpression of NCKAP1 can improve the migration and invasion abilities of GC cells, whereas overexpression of miR383-5p can inhibit growth of the aforementioned abilities of GC cells induced by NCKAP1 overexpression. The overexpression of NCKAP1 can increase the expression level and activity of MMP2, while the overexpression of miR383-5p can inhibit the increase of MMP2 expression level and activity in GC cells induced by NCKAP1 overexpression. NCKAP1 is a target gene of miR383-5p, and miR383-5p could be a valuable therapeutic target for stomach adenocarcinoma.

A study on the configuration of factors influencing overweight and obesity in adolescents based on fuzzy set qualitative comparative analysis.

OBJECTIVE: Overweight and obesity among adolescents are grave public health issues around the world. Although the conditions that contribute to obesity have been extensively researched, little is known about how multiple conditions interact to cause overweight and obesity. The current study intends to investigate the histomorphic configuration pathways of several conditions of adolescent overweight and obesity by gender. METHOD: The data came from a social survey conducted in June 2021 in Changchun, Jilin Province, China. The sample collected was 14-year-old adolescents, including 167 boys and 137 girls. The school physicians examined the participants' weight and height, and questionnaires were used to collect risk indicators from adolescents, such as sleep duration, electronic screens times, consumption of sugary drinks and fried foods, and physical activity. Simultaneously, a Fuzzy Qualitative Comparative Analysis will be performed to investigate the combinations of diverse conditions. RESULT: We found that there is no determining necessary condition that, once present, directly determines that an individual is in a state of overweight and obesity. Simultaneously, this study revealed nine alternative configurational paths of overweight and obesity in teenagers of different genders, with a concordance of 0.805 for six male groupings and 0.916 for three female groupings. The outcomes of overweight obesity in adolescents under different genders are similar but not identical. CONCLUSION: This study examined the interactions of a number of conditions from the individual, behavioral, learning and living environment that led to the same overweight obese outcome among adolescents of different genders. Our research will be useful to policymakers in that interventions should take into account the combined effects of a number of different aspects rather than focusing on a single factor that causes overweight and obesity.

Miniaturized Electrochemical Sensing Platforms for Quantitative Monitoring of Glutamate Dynamics in the Central Nervous System.

Glutamate is one of the most important excitatory neurotransmitters within the mammalian central nervous system. The role of glutamate in regulating neural network signaling transmission through both synaptic and extra-synaptic paths highlights the importance of the real-time and continuous monitoring of its concentration and dynamics in living organisms. Progresses in multidisciplinary research have promoted the development of electrochemical glutamate sensors through the co-design of materials, interfaces, electronic devices, and integrated systems. This review summarizes recent works reporting various electrochemical sensor designs and their applicability as miniaturized neural probes to in vivo sensing within biological environments. We start with an overview of the role and physiological significance of glutamate, the metabolic routes, and its presence in various bodily fluids. Next, we discuss the design principles, commonly employed validation models/protocols, and successful demonstrations of multifunctional, compact, and bio-integrated devices in animal models. The final section provides an outlook on the development of the next generation glutamate sensors for neuroscience and neuroengineering, with the aim of offering practical guidance for future research.

A "Two-Part" Resonance Circuit Based Detachable Sweat Patch for Noninvasive Biochemical and Biophysical Sensing.

Wearable electronics play important roles in noninvasive, continuous, and personalized monitoring of multiple biosignals generated by the body. To unleash their full potential for next-generation human centered bio-integrated electronics, the wireless sensing capability is a desirable feature. However, state-of-the-art wireless sensing technologies exploit rigid and bulky electronic modules for power supply, signal generation, and data transmission. This study reports a battery-free device technology based on a "two-part" resonance circuit model with modularized, physically separated, and detachable functional units for magnetic coupling and biosensing. The resulting platform combines advantages of electronics and microfluidics with low cost, minimized form factors, and improved performance stability. Demonstration of a detachable sweat patch capable of simultaneous recording of cortisol concentration, pH value, and temperature highlights the potential of the "two-part" circuit for advanced, transformative biosensing. The resulting wireless sensors provide a new engineering solution to monitoring biosignals through intimate and seamless integration with skin surfaces.

Local characteristics of molecular epidemiolgy of Acinetobacter baumannii in Jilin province (northeast China).

A. Baumannii is an opportunistic nosocomial pathogen which has severe antibiotic resistance. However, the epidemiology is less clearly understood in Jilin province and China. Thus, 89 A. baumannii isolates from a single hospital in Jilin province between 2013-2017 were performed by MLST. In order to better understanding of the epidemiology of Jilin isolates, Chinese strains originated from other domestic regions and worldwide isolates in MLST database were analyzed by silico phylogenetic tools together. A total of 22 STs in Jilin were identified, and 10 STs were found to be novel. The top three predominant sequence types are ST195 (n = 34, 38.2%), ST208 (n = 14, 15.7%) and ST540 (n = 13, 14.6%). ST369 is predicted to be group founder and ST195, ST540 are subgroup founders of the majority STs in Jilin Province. Some newly discovered singletons showed close relationship with strains from other countries, which suggest that nation-cross transmission is one of important origin of Jilin strains. The majority of Jilin STs showed clonality and close relationship with the majorities from other regions of China. But occupation of individual STs in Jilin were different from that of other domestic regions. The aggregation trend and genetic relationship proved that predominant Jilin STs continue to mutate during transmission. Drug resistance facilitated transmission of Jilin A.baumannii isolates because more than 94% of isolates are resistant to at least one carbapenem and the STs with strong resistance to carbapenems usually has more isolates. In conclusion, high diversity and different occupation of STs, and occupation of novel STs proved that epidemiology of A. baumannii in Jilin has special regional characteristics, and drug resistance facilitated transmission of domestic strains and foreign strains.

Short- and Long-Term Outcomes of Indocyanine Green Fluorescence Navigation- Versus Conventional-Laparoscopic Hepatectomy for Hepatocellular Carcinoma: A Propensity Score-Matched, Retrospective, Cohort Study.

BACKGROUND: Indocyanine green (ICG) fluorescence imaging technology is increasingly widely used in laparoscopic hepatectomy. However, whether it can provide long-term survival benefits to patients with liver malignancies remains unclear. This study investigated the clinical effect of laparoscopic hepatectomy for hepatocellular carcinoma (HCC) using ICG imaging technology. METHODS: We retrospectively analyzed HCC patients who underwent laparoscopic hepatectomy at Zhongnan Hospital of Wuhan University from January 2016 to December 2020. Propensity score matching (PSM) was used to match patients undergoing ICG fluorescence navigation laparoscopic hepatectomy (ICG-FNLH) with those undergoing conventional laparoscopic hepatectomy (CLH) in a 1:1 ratio to minimize the influence of confounding factors. We compared perioperative status and long-term prognosis between the two groups and performed multivariate analysis to identify risk factors associated with overall survival and recurrence-free survival. RESULTS: The original cohort consisted of 141 patients, with 50 patients in each group (100 patients in total) after PSM. The anatomical liver resection rate, R0 resection rate, and resection margin distance in the ICG-FNLH group were higher than those in the CLH group. The intraoperative blood loss was lower than that in the CLH group. The recurrence-free survival and overall survival of the ICG-FNLH group were better than those of the CLH group. ICG-FNLH improved the recurrence-free survival of HCC patients (hazard ratio [HR] = 2.165, 95% confidence interval [CI]: 1.136-4.127, P = 0.024). CONCLUSIONS: Compared with CLH, ICG-FNLH can improve the recurrence-free survival rate of patients with hepatocellular carcinoma and may help to improve the long-term prognosis of patients.

Detection of methyltransferase activity and inhibitor screening based on rGO-mediated silver enhancement signal amplification strategy.

DNA methylation refers to the chemical modification process of obtaining a methyl group by the covalent bonding of a specific base in DNA sequence with S-adenosyl methionine (SAM) as a methyl donor under the catalysis of methyltransferase (MTase), which is related to the occurrence of multiple diseases. Therefore, the detection of MTase activity is of great significance for disease diagnosis and drug screening. Because reduced graphene oxide (rGO) has a unique planar structure and remarkable catalytic performance, it is not clear whether rGO can rapidly catalyze silver deposition as an effective way of signal amplification. However, in this study, we were pleasantly surprised to find that using H2O2 as a reducing agent, rGO can rapidly catalyze silver deposition, and its catalytic efficiency of silver deposition is significantly better than that of GO. Therefore, based on further verifying the mechanism of catalytic properties of rGO, we constructed a novel electrochemical biosensor (rGO/silver biosensor) for the detection of dam MTase activity, which has high selectivity and sensitivity to MTase in the range of 0.1 U/mL to 10.0 U/mL, and the detection limit is as low as 0.07 U/mL. Besides, this study also used Gentamicin and 5-Fluorouracil as inhibitor models, confirming that the biosensor has a good application prospect in the high-throughput screening of dam MTase inhibitors.

Prognostic Significance of Advanced Lung Cancer Inflammation Index, a Nutritional and Inflammation Index, in Patients With Gastrointestinal Cancers: A Meta-analysis.

Previous studies have investigated the prognostic value of the advanced lung cancer inflammation index (ALI) in gastrointestinal (GI) cancers; however, the results are controversial. This meta-analysis aimed to evaluate the prognostic and clinicopathological role of ALI in patients with GI cancers. A systematic search of electronic databases was conducted to evaluate the prognostic and clinicopathological value of ALI in GI cancers. Nine studies comprising 3,750 patients were included in this meta-analysis. The pooled results showed that a low ALI was significantly associated with worse overall survival (OS, hazard ratio [HR] = 1.95, 95% confidence interval [CI] = 1.53-2.47, P < 0.001, I2 = 63.9%) and disease-free survival/relapse-free survival (DFS/RFS, HR = 1.49, 95% CI = 1.28-1.73, P < 0.001, I2 = 0%) in patients with GI cancers. In addition, decreased ALI correlated with the depth of tumor invasion and presence of distant metastasis and tended to be associated with male sex, high carcinoembryonic antigen levels, lymph node metastasis, and right-sided colon cancer. Low ALI was associated with adverse OS and DFS/RFS in patients with GI cancer. In addition, decreased ALI also correlated with clinicopathological factors, indicating higher stage of the malignancy.

Association Between the Awareness of Antiretroviral Drugs-Related Services and Drug Accessibility During the COVID-19 Pandemic Among Patients Undergoing Antiretroviral Therapy: A Cross-Sectional Study.

In a cross-sectional survey from 21 February to 6 March, 2020, we analyzed the awareness and utilization of antiretroviral drugs (ARVs)-related services among people living with HIV during the COVID-19 pandemic in Guangzhou, China. In addition, a subgroup analysis was performed among those who needed to go to hospital to access their drugs, and we explored the association between the awareness of ARVs-related services and the accessibility of ARVs. Of 375 participants, 89.9% were aware of drug-borrowing service, 90.7% were aware of drug-delivery service and 86.9% were aware of information-assistance service. Knowing about the drug-borrowing service or the information-assistance service, knowing about at least two services and knowing about all of the three services were all positively associated with ARVs accessibility. In addition, 35 (39.3%) of those who had acquired their drugs on time received them via the drug-delivery service. To some extent, the three ARVs-related services have alleviated the difficulties in accessing ARVs during the pandemic, especially the drug-delivery service.

Application value of high-frequency ultrasonography in endoscopic retrograde appendicitis therapy for pediatric acute appendicitis.

BACKGROUND: Endoscopic retrograde appendicitis therapy (ERAT) is a new method of treating acute appendicitis that has emerged in recent years in children, but the application of radiological examination in the diagnosis and treatment of pediatric diseases is greatly limited. Therefore, high-frequency ultrasonography imaging has attracted more and more attention because of its advantages such as non-invasiveness, no radiation, and a simpler procedure. This study aims to explore the application value of high-frequency ultrasonography in ERAT for pediatric acute appendicitis. METHODS: A retrospective analysis was conducted on 136 children admitted to our hospital from January 2020 to October 2021 who were definitively diagnosed with acute appendicitis and underwent endoscopic retrograde intra-appendiceal irrigation treatment under the guidance of high-frequency ultrasonography. They were divided into the preschool age group (< 6 years) and school age group (≥ 6 years) according to age. Before the operation and at 1-2 days after ERAT, the external diameter of the appendix, as well as the thickness of the intestinal wall, mucosal layer, and muscular layer in each group were measured by high-frequency ultrasonography and recorded in detail. During the operation, a stent was placed under real-time guidance, and the situation in the cavity was observed. The clinical data of the two groups of children before and after the operation were collected, and the recurrence status after treatment was followed up. RESULTS: Endoscopic treatment was completed in 131 patients with a success rate of 96.32%. There was no significant difference between the two groups in appendix diameter, intestinal wall, or muscular layer after the operation when compared to those before the operation (p > 0.05), but there was a significant difference in the mucosal thickness after operation when compared to before the operation (p < 0.05). Abdominal pain in the two groups was significantly relieved immediately after the operation, and the white blood cell count returned to normal, with a significant difference before and after the ERAT operation (p < 0.05). CONCLUSION: Endoscopic intra-appendiceal irrigation under the guidance of high-frequency ultrasonography is a real-time and convenient method that is safe and effective in treating pediatric acute appendicitis.

Behavioral and psychosocial factors and their effects on insomnia among people undergoing entry quarantine in hotels during COVID-19 pandemic: a cross-sectional study in Guangzhou, China.

BACKGROUND: The COVID-19 pandemic continues to impact global health and China requires a 14-day quarantine for individuals on flights with positive COVID-19 cases. This quarantine can impact mental well-being, including sleep. This study aims to examine the impact of psychosocial and behavioral factors on insomnia among individuals undergoing quarantine in hotels. METHODS: This study was a cross-sectional survey carried out in Guangzhou, China. The data was gathered through online questionnaires distributed to international passengers who arrived in Guangzhou on flights and were required to undergo a 14-day quarantine in hotels arranged by the local government. The questionnaires were sent to the participants through the government health hotline "12,320." RESULTS: Of the 1003 passengers who were quarantined, 6.7% reported significant anxiety and 25.0% had varying degrees of insomnia. Anxiety was positively associated with insomnia (ß = 0.92, P < 0.001), while collectivism (ß = -0.07, P = 0.036), indoor exercise (ß = -0.50, P < 0.001), and the perceived people orientation of the public health service (ß = -0.20, P = 0.001) were negatively associated with insomnia. The study also identified moderating effects, such that a higher sense of collectivism, a greater frequency of indoor exercise, and a higher perception of the people-oriented of the public health service were associated with a lower impact of anxiety on insomnia. These moderating effects were also observed in participants with varying degrees of insomnia. CONCLUSIONS: This study reveals that a proportion of people undergoing entry quarantine experience insomnia and confirms how psychosocial and behavioral factors can alleviate insomnia in this population.

Association of childhood threat and deprivation with depressive symptoms and the moderating role of current economic status among middle-aged and older adults in China.

PURPOSE: To investigate the independent impact of threat-related and deprivation-related adverse childhood experiences (ACEs) on depressive symptoms among middle-aged and older adults, and to evaluate the moderating role of current economic status in these associations. METHODS: This cross-sectional study included 11,048 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study. We captured five threat-related ACEs and five deprivation-related ACEs by questionnaires. Depressive symptoms were assessed using the 10-item Centre for Epidemiological Studies Depression Scale. Current economic status was reflected by annual per capita household consumption expenditure. We performed logistic regression analyses to evaluate the independent association of childhood threat and deprivation with depressive symptoms, and conducted stratified analyses and tests for interaction to explore the moderation effect of current economic status in such associations. RESULTS: Compared with the nonexposed group, the experience of both childhood threat and deprivation were independently associated with greater risks of depressive symptoms later in life (odds ratio [OR] 1.75, 95% CI 1.49-2.05 for ≥ 2 threat-related ACEs; OR 2.02, 95% CI 1.67-2.43 for ≥ 2 deprivation-related ACEs). High current economic status significantly ameliorated the impact of childhood deprivation, but not threat, on depressive symptoms (P value for interaction 0.038). CONCLUSIONS: Both threat-related and deprivation-related ACEs were associated with the risk of depressive symptoms among middle-aged and older adults, while current economic status was a significant moderator in such risks only for childhood deprivation. The findings implied that prioritising targeted interventions for individuals with ACEs, especially for childhood deprivation victims who were economically disadvantaged in adulthood, may help mitigate depressive symptoms in later life.

Adherence to Antiretroviral Therapy and Its Predictive Factors Among People Living with HIV in China: A Behavioral Theory-Based Prospective Cohort Study.

BACKGROUND: Free antiretroviral therapy (ART) has been expanded to all people living with HIV (PLWH) in China since 2016, and adherence to ART has been shown to be the primary determinant of viral suppression. This study aimed to investigate the ART adherence and its associated factors among PLWH in China in the context of a scaling-up of treatment policy. METHOD: A prospective cohort study was conducted from June 2016 to May 2018 in Guangzhou, China. A total of 400 eligible participants were recruited from the Guangzhou Eighth People's hospital in Guangzhou, China. The Theory of Planned Behavior and the Behavioral Maintenance Theory were applied to guide the questionnaire design. Participants were invited to completed self-administered questionnaire at baseline and months 3 and 6 post-baseline. Logistic regression models were fitted to explore factors associated with ART adherence. RESULTS: Of the 400 participants, the prevalence of optimal ART adherence was 83.6% at month 3 and 83.3% at month 6. The baseline attitude (ORa = 1.11, P < 0.05), behavioral intention (ORa = 1.90, P < 0.05), and outcome expectations (ORa = 1.09, P < 0.001) predicted ART adherence at month 3 in adjusted analyses, but only outcome expectations (ORa = 1.09, P < 0.01) remained significant in the final multivariate model. At month 3, negative experiences (ORa = 0.62, P < 0.05) were the only predictor of adherence at month 6. CONCLUSION: Approximately 15% of participants reported suboptimal ART adherence. The developments of tailored interventions that target factors such as outcome expectations at baseline and negative experiences during treatment are warranted.

The effects of COVID-19 event strength on job burnout among primary medical staff.

BACKGROUND: As a global pandemic, The Corona Virus Disease 2019 (COVID-19) has brought significant challenges to the primary health care (PHC) system. Health professionals are constantly affected by the pandemic's harmful impact on their mental health and are at significant risk of job burnout. Therefore, it is essential to gain a comprehensive understanding of how their burnout was affected. The study aimed to examine the relationship between COVID-19 event strength and job burnout among PHC providers and to explore the single mediating effect of job stress and work engagement and the chain mediating effect of these two variables on this relationship. METHODS: Multilevel stratified convenience sampling method was used to recruit 1148 primary medical staff from 48 PHC institutions in Jilin Province, China. All participants completed questionnaires regarding sociodemographic characteristics, COVID-19 event strength, job stress, work engagement, and job burnout. The chain mediation model was analyzed using SPSS PROCESS 3.5 Macro Model 6. RESULTS: COVID-19 event strength not only positively predicted job burnout, but also indirectly influenced job burnout through the mediation of job stress and work engagement, thereby influencing job burnout through the "job stress → work engagement" chain. CONCLUSIONS: This study extends the application of event systems theory and enriches the literature about how the COVID-19 pandemic impacted PHC medical staff job burnout. The findings derived from our study have critical implications for current and future emergency response and public policy in the long-term COVID-19 disease management period.

Mismatch sensing by nucleofilament deciphers mechanism of RecA-mediated homologous recombination.

Recombinases polymerize along single-stranded DNA (ssDNA) at the end of a broken DNA to form a helical nucleofilament with a periodicity of ∼18 bases. The filament catalyzes the search and checking for homologous sequences and promotes strand exchange with a donor duplex during homologous recombination (HR), the mechanism of which has remained mysterious since its discovery. Here, by inserting mismatched segments into donor duplexes and using single-molecule techniques to catch transient intermediates in HR, we found that, even though 3 base pairs (bp) is still the basic unit, both the homology checking and the strand exchange may proceed in multiple steps at a time, resulting in ∼9-bp large steps on average. More interestingly, the strand exchange is blocked remotely by the mismatched segment, terminating at positions ∼9 bp before the match-mismatch joint. The homology checking and the strand exchange are thus separated in space, with the strand exchange lagging behind. Our data suggest that the strand exchange progresses like a traveling wave in which the donor DNA is incorporated successively into the ssDNA-RecA filament to check homology in ∼9-bp steps in the frontier, followed by a hypothetical transitional segment and then the post-strand-exchanged duplex.