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Background With the development of society and the improvement of people's living standards, health issues are receiving increasing attention. The aging population and the high incidence of chronic diseases have made health management an urgent problem that needs to be addressed. Primary healthcare institutions, as the "main battlefield" for residents' health, play a crucial role in health management. However, in the current implementation of health management, primary healthcare institutions still face numerous challenges, and their proactivity remains unclear. Objective To understand the current implementation status of health management in primary healthcare institutions in Shanghai and to discuss strategies for enhancing the implementation of proactive health-oriented health management. Methods From February 2023 to May 2023, a survey was conducted on 33 primary healthcare institutions in Shanghai. The survey aimed to understand the implementation of health management, assessment of high-risk factors and disease screening, execution of health education and information dissemination, coordination of health management resources and functional services, as well as the status of online health management services and health monitoring. Additionally, interviews were conducted with institution heads to gather information on implementation difficulties and suggestions. Results The research results showed that all participating institutions carried out health management for chronic disease patients, with 93.9% (31/33) covering key populations, 72.7% (24/33) involving rehabilitation populations, and 54.6% (18/33) including healthy populations. A total of 81.8% (27/33) of institutions utilized health data platforms, with the main functions including contract management, health record management, data querying, and health indicator management. Furthermore, 97.0% (32/33) of institutions conducted high-risk factor assessments and disease screenings, as well as follow-up, diagnosis, and management. The majority of institutions carried out health education and information dissemination activities through various platforms. Additionally, 87.9% (29/33) of institutions collaborated with other units to implement health management projects, providing diverse functional services. About 63.6% (21/33) of institutions offered online services, and 42.4% (14/33) were equipped with health monitoring devices. Managers believed that primary healthcare institutions and their staff have significant advantages in implementing proactive health-oriented management, but they also face challenges due to a lack of policy and financial support. Conclusion Primary healthcare institutions in Shanghai have made positive progress in implementing proactive health-oriented management. However, comprehensive measures are still needed to address existing challenges, in order to further improve the quality and efficiency of health management services and better meet the health needs of residents.

To improve people's health via meeting their growing health needs, the "Healthy China 2030" Planning Outline highlights the concept of protective care, and actively promotes the transformation from disease-centered care to human-centered care. There is still no a standard proactive care system. We summarized the essence, development status and significance of proactive care, then based on this, explored implementation strategies and assessment system regarding proactive care management conducted by community health institutions and community medical workers. We believe that community health institutions and community medical workers play an important role in the implementation of proactive care, and improving people's awareness of proactive care and self-health management ability via integrating proactive care into health management is of great significance to improve the national health level.

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a major health problem worldwide. Due to the fast emergence of SARS-CoV-2 variants, understanding the molecular mechanisms of viral pathogenesis and developing novel inhibitors are essential and urgent. Here, we investigated the potential roles of N6,2'-O-dimethyladenosine (m6Am), one of the most abundant modifications of eukaryotic messenger ribonucleic acid (mRNAs), in SARS-CoV-2 infection of human cells. Using genome-wide m6Am-exo-seq, RNA sequencing analysis, and Clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 genome editing, we demonstrate that phosphorylated C-terminal domain (CTD)-interacting factor 1 (PCIF1), a cap-specific adenine N6-methyltransferase, plays a major role in facilitating infection of primary human lung epithelial cells and cell lines by SARS-CoV-2, variants of concern, and other coronaviruses. We show that PCIF1 promotes infection by sustaining expression of the coronavirus receptors angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) via m6Am-dependent mRNA stabilization. In PCIF1-depleted cells, both ACE2/TMPRSS2 expression and viral infection are rescued by re-expression of wild-type, but not catalytically inactive, PCIF1. These findings suggest a role for PCIF1 and cap m6Am in regulating SARS-CoV-2 susceptibility and identify a potential therapeutic target for prevention of infection.

The retrovirus human immunodeficiency virus-1 (HIV-1) is the causative agent of AIDS. Although treatment of HIV/AIDS with antiretroviral therapy provides suppression of viremia, latent reservoirs of integrated proviruses preclude cure by current antiviral treatments. Understanding the mechanisms of host-viral interactions may elucidate new treatment strategies. Here, we performed a CRISPR/Cas9 transcriptional activation screen using a high-complexity, genome-wide sgRNA library to identify cellular factors that inhibit HIV-1 infection of human CD4+ T cells. MT4 cells were transduced with a CRISPR/Cas9 sgRNA library and infected with nef-deficient HIV-1NL4-3 expressing ganciclovir-sensitive thymidine kinase, thus enabling selection of HIV-1-resistant cells for analysis of enriched sgRNAs. After validation of screen hits, multiple host factors essential for HIV-1 infection were identified, including SET (SET nuclear proto-oncogene) and ANP32A (acidic nuclear phosphoprotein 32A, PP32A), which together form a histone acetylase inhibitor complex. Using multiple human cell lines and peripheral blood mononuclear cells (PBMCs) from healthy donors and HIV-1-infected individuals, we demonstrate that SET depletion increased HIV-1 infectivity by augmenting DNA integration without significantly changing sites of integration. Conversely, SET overexpression decreased HIV-1 integration and infectivity. SET protein expression was significantly reduced in PBMCs from HIV-1-infected individuals and was downregulated by HIV-1 infection of healthy donor cells in vitro. Notably, HIV-1-induced downregulation of SET could be alleviated by inhibition of the protease granzyme A. Altogether, we have identified cellular inhibitors of HIV-1 infection on a genome-wide scale, which affords new insight into host-virus interactions and may provide new strategies for HIV-1 treatment.

N6,2'-O-dimethyladenosine (m6Am) is an abundant RNA modification located adjacent to the 5'-end of the mRNA 7-methylguanosine (m7G) cap structure. m6A methylation on 2'-O-methylated A at the 5'-ends of mRNAs is catalyzed by the methyltransferase Phosphorylated CTD Interacting Factor 1 (PCIF1). The role of m6Am and the function of PCIF1 in regulating host-pathogens interactions are unknown. Here, we investigate the dynamics and reprogramming of the host m6Am RNA methylome during HIV infection. We show that HIV infection induces a dramatic decrease in m6Am of cellular mRNAs. By using PCIF1 depleted T cells, we identify 2237 m6Am genes and 854 are affected by HIV infection. Strikingly, we find that PCIF1 methyltransferase function restricts HIV replication. Further mechanism studies show that HIV viral protein R (Vpr) interacts with PCIF1 and induces PCIF1 ubiquitination and degradation. Among the m6Am genes, we find that PCIF1 inhibits HIV infection by enhancing a transcription factor ETS1 (ETS Proto-Oncogene 1, transcription factor) stability that binds HIV promoter to regulate viral transcription. Altogether, our study discovers the role of PCIF1 in HIV-host interactions, identifies m6Am modified genes in T cells which are affected by viral infection, and reveals how HIV regulates host RNA epitranscriptomics through PCIF1 degradation.

Coronavirus disease 2019 (COVID-19) is caused by SARS-CoV-2 and has spread across the globe. SARS-CoV-2 is a highly infectious virus with no vaccine or antiviral therapy available to control the pandemic; therefore, it is crucial to understand the mechanisms of viral pathogenesis and the host immune responses to SARS-CoV-2. SARS-CoV-2 is a new member of the betacoronavirus genus like other closely related viruses including SARS-CoV and Middle East respiratory syndrome coronavirus (MERS-CoV). Both SARS-CoV and MERS-CoV have caused serious outbreaks and epidemics in the past eighteen years. Here, we report that one of the interferon-stimulated genes (ISGs), cholesterol 25-hydroxylase (CH25H), is induced by SARS-CoV-2 infection in vitro and in COVID-19-infected patients. CH25H converts cholesterol to 25-hydrocholesterol (25HC) and 25HC shows broad anti-coronavirus activity by blocking membrane fusion. Furthermore, 25HC inhibits USA-WA1/2020 SARS-CoV-2 infection in lung epithelial cells and viral entry in human lung organoids. Mechanistically, 25HC inhibits viral membrane fusion by activating the ER-localized acyl-CoA:cholesterol acyltransferase (ACAT) which leads to the depletion of accessible cholesterol from the plasma membrane. Altogether, our results shed light on a potentially broad antiviral mechanism by 25HC through depleting accessible cholesterol on the plasma membrane to suppress virus-cell fusion. Since 25HC is a natural product with no known toxicity at effective concentrations, it provides a potential therapeutic candidate for COVID-19 and emerging viral diseases in the future.

We perform a CRISPR-Cas9 genome-wide screen in glioblastoma stem cells and identify integrin αvβ5 as an internalization factor for Zika virus (ZIKV). Expression of αvβ5 is correlated with ZIKV susceptibility in various cells and tropism in developing human cerebral cortex. A blocking antibody against integrin αvβ5, but not αvβ3, efficiently inhibits ZIKV infection. ZIKV binds to cells but fails to internalize when treated with integrin αvβ5-blocking antibody. αvβ5 directly binds to ZIKV virions and activates focal adhesion kinase, which is required for ZIKV infection. Finally, αvβ5 blocking antibody or two inhibitors, SB273005 and cilengitide, reduces ZIKV infection and alleviates ZIKV-induced pathology in human neural stem cells and in mouse brain. Altogether, our findings identify integrin αvβ5 as an internalization factor for ZIKV, providing a promising therapeutic target, as well as two drug candidates for prophylactic use or treatments for ZIKV infections.

Background: Coronavirus disease (COVID)-19 can lead to chronic lung damage and respiratory issues, potentially increasing surgical difficulty and risk for patients with non-small-cell lung cancer (NSCLC). However, the impacts of a COVID-19 history on early outcomes in NSCLC patients remain controversial. Objectives: To evaluate the effect of COVID-19 history on early outcomes in NSCLC patients and identify high-risk groups undergoing radical resection based on the largest Chinese multi-center real-world data to date. Design: Multi-center retrospective cohort study. Methods: NSCLC patients with (POCVD group) or without (NCVD group) a history of COVID-19 who underwent radical surgery at six institutions from January 2022 to January 2024 were retrospectively reviewed from a prospectively maintained database. Propensity-score matching (PSM) was utilized to minimize patient selection bias. Results: Out of 7932 cases included, PSM resulted in 3021 cases per group. The two groups were comparable regarding the proportion of male patients (52.0% vs 51.6%) and those aged ⩾70 years (13.3% vs 13.8%). Although the two groups had comparable incidences of complications with Clavien-Dindo grades ⩾II (13.0% vs 14.4%, p = 0.117), the POCVD group had longer surgical durations (120.87 ± 40.23 min vs 110.74 ± 38.76 min, mean difference (95% confidence interval (CI) = 10.13 (8.138–12.122)) and higher rates of respiratory complications than the NCVD group. Subgroup logistic regression analysis indicated that patients aged ⩾70 years (odds ratio (OR) (95% CI) = 1.322 (1.022–1.876)) and those with a smoking history (OR (95% CI) = 1.235 (1.008–1.543)) had an increased risk of developing complications with Clavien-Dindo grades ⩾II. Further analysis confirmed that these high-risk patients experienced extended surgical durations, longer chest tube drainage, and prolonged postoperative hospital stay, along with increased postoperative respiratory complications following COVID-19. Conclusion: Generally, radical resection is safe for NSCLC patients with a COVID-19 history. However, these patients experienced prolonged surgical durations and a higher incidence of postoperative respiratory complications compared to those without a COVID-19 history. In addition, individuals aged ⩾70 years or with a smoking history faced elevated surgical risks following COVID-19. Plain language summary: Analyzing the impact of COVID-19 history on early outcomes and identifying high-risk groups among non-small cell lung cancer patients undergoing radical resection Aim and Purpose Research Question: Does a COVID-19 history affect the early outcomes of radical surgery (lobectomy/bi-lobectomy/pneumectomy) in patients with non-small cell lung cancer (NSCLC)? Hypothesis: Patients with a COVID-19 history face elevated surgical risks compared to those without. Objective: To understand how past COVID-19 infection impacts early outcomes in NSCLC patients undergoing surgery and to identify high-risk groups. Background Why This Study: COVID-19 can cause long-term lung damage, making surgery riskier for NSCLC. However, it's unclear how past COVID-19 infection affects NSCLC patients receiving surgery. Importance: The research helps to understand the additional risks for NSCLC patients with a COVID-19 history based on the largest cohort to date, aiming to improve their surgical outcomes. Method and Design Research Design: Multi-center retrospective cohort study. Methods and Participants: 7932 NSCLC patients undergoing radical surgery between January 2022 and January 2024 were included and divided into two groups: those with a COVID-19 history (POCVD group) and those without (NCVD group). Result and Importance Findings: 1. The POCVD group had longer surgical durations and higher rates of respiratory complications compared to the NCVD group. 2. The POCVD and NCVD groups were associated with a comparable incidence of postoperative complications with Clavien-Dindo grades ⩾II. 3. The elderly (aged ⩾70 years) and smokers were at higher risk for complications post-COVID-19. Implications: While surgery is generally safe for NSCLC patients with a COVID-19 history, they do face increased risks and complications. This highlights the need for special care and monitoring for older patients and those with smoking histories. Key Message: NSCLC patients with a COVID-19 history can safely undergo radical surgery, but they may experience longer surgical durations and more postoperative respiratory complications, especially the elderly and smokers. [ABSTRACT FROM AUTHOR]

Data transformation of the reference soil organic matter (SOM) decomposition rates (kref), often derived as turnover times or in alternative formats, is commonly used to develop ecological models for projecting the persistence of SOM. However, the effects of reciprocal or logarithmic transformation of kref on model performance and edaphic‐climatic patterns remain uncertain. Here, we convert published kref values into reciprocal or logarithmic formats and establish machine learning models between the transformed kref and edaphic‐climatic predictors. We show that models trained with the transformed kref exhibit a 11.6%−68.4% reduction in performance upon re‐conversion to kref compared to those trained with the original kref. The variable importance analysis identifies distinct key predictors governing the original kref and its transformed counterparts. This suggests that data transformation alters the relative significance of predictors without necessarily improving kref prediction performance. Consequently, our study underscores the importance of directly focusing on the original values rather than alternative representations when dissecting a given variable's patterns and mechanisms in ecological modeling. Core Ideas: Data transformation caused reduced predictive performance upon re‐conversion to kref compared to the original kref.Models trained with data transformation exhibited divergent edaphic‐climatic controls for different formatted kref.This study underscores the importance of directly focusing on original values rather than alternative representations. Plain Language Summary: The first‐order model is commonly used to simulate the dynamics of soil organic matter decomposition. The reference decomposition rates (kref) in the first‐order model are usually transformed into reciprocal or logarithmic formats, which may affect model performance as well as the regulatory patterns of edaphic‐climatic factors. In this study, we investigated the effects of data transformation on predictive performance and variable importance. We found that models trained with transformed kref exhibited reduced performance upon re‐conversion to kref, compared to those trained with the original kref. In addition, data transformation altered the distribution and range of the dependent variable, leading to divergent controlling roles of explanatory variables pertaining to models trained with different formatted kref. Our study underscores the need to apply models directly to the original variables rather than their transformed representations. [ABSTRACT FROM AUTHOR]