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At present, more patients suffer from multiple chronic diseases. However, the hospital's existing chronic disease management is carried out according to the department. This means that a patient needs to go to more than one department for a chronic disease treatment. Therefore, this study proposes 6 dimensions (organizational management, medical service support, medical service, community alliance, self-management support, management information system) and 36 questions, to help evaluate the current chronic disease management system in China's large third-class hospitals. In this study, 143 survey samples from doctors and nurses were collected. A principal component analysis was used to extract three key elements of chronic disease management service delivery system (service management organization, management information system, medical core service). Then, multiple regression was used to establish the relationship model between the overall performance of the system and the main elements. Three key service nodes of the system (medical specialist support, patient tracking management and personalized intervention) were determined according to the weight of the regression model. The regression coefficients of the above three main elements show a similar impact on the overall performance of the system, but the key service nodes under each major element have relative differences, including medical specialist support, patient tracking management and personalized intervention. Finally, to establish a chronic disease management system with multiple departmental continuous care for chronic diseases, it is necessary to improve the chronic disease management system from three aspects of medical specialty support, patient tracking management and personalized intervention. This paper proposes corresponding improvement strategies.

Unlike other ubiquitin-like family members, UBL5 is structurally and functionally atypical, and a novel role in various biological processes and diseases has been discovered. UBL5 can stabilize the structure of the spliceosome, can promote post-transcriptional processing, and has been implicated in both DNA damage repair and protein unfolding reactions, as well as cellular mechanisms that are frequently exploited by viruses for their own proliferation during viral infections. In addition, UBL5 can inhibit viral infection by binding to the non-structural protein 3 of rice stripe virus and mediating its degradation. Therefore, UBL5 is an important link between viral infections and immunity, and its study will be beneficial for the prevention and treatment of viral infections in the future. However, a review of the current findings on the role of UBL5 in viral infection has not been undertaken. Therefore, in this review, we summarize the recent progress in understanding the functions of UBL5 and discuss its putative role in viral infections.

This paper provides a detailed analysis of the factors influencing the evolution of rural settlements, including natural environmental constraints, infrastructure, regional cultural inheritance and integration, urbanization and rural industrial transformation, land use refor- mation and innovation, rural household behavior conversion, macro-control policy factors, and so on. Based on differences between the ways and degree of effect on rural settlement evolution, these factors are classified into basic factors, new-type factors and mutation factors The drive of basic factors mainly focuses on the traditional inheritance of rural settlements, the new-type factors mainly affect rural settlement transition, and the mutation factors may bring about sudden changes. All these factors constitute a ＂three-wheel＂ driving mechanism for the evolution of rural settlements, and shape three typical driver paths： slow smooth path under the basic factors, new path to rapid development under the new-type factors, and the sudden change path under the mutation factors. The paper also investigates the overall situation of rural settlement evolution in the aspects of settlement system, settlement scale, settlement morphology, settlement function, settlement culture, settlement environment, etc. The general process of rural settlement evolution is divided into four stages： initial, transi- tional, developmental, and mature stages.

Background Foot-and-mouth disease (FMD) is a highly transmissible disease that leads to vast economic losses in many countries. Prevention using inactivated vaccines is one effective measure used to control FMD. Unfortunately, inactivated FMD vaccines provide only short-term protection and require a cold-chain system. In recent years, many studies have shown that layered double metal hydroxides (LDHs) carrying antigens can be used to strongly induce immune responses. In this study, LDH nanoparticles (NPs) were prepared by hydrothermal synthesis. LDH particle size, electric potential, and morphology were measured and observed. The adsorption capacity of LDH NPs to FMDV was tested. The effects of LDH as an adjuvant on inactivated FMDV vaccines were further evaluated and compared with commercial FMDV Montanide ISA-206 in BALB/C female mice and Yorkshire pigs. Results LDH NPs were successfully prepared with a uniform particle size of ~ 87.21 nm, regular edges, a loose hexagonal shape and positive zeta charge of 32 mV. The maximum absorption concentration was 0.16–0.31 μg FMDV/μg LDH. In the mouse experiment, antibody levels in group LDH + FMDV were significantly higher compared to group saline + FMDV ( P  < 0.01) from days 42–98 and were significantly higher to group ISA-206 + FMDV on day 56 post-immunization ( P  < 0.05). After day 14 post-immunization, IFN-γ content was significantly increased ( P  < 0.05). In the pig experiment, antibody levels in both the ISA-206 + FMDV and LDH + FMDV were positive and were significantly higher compared with the PBS group on day 7 ( P  < 0.005). Antibody levels in 90% pigs were positive on day 56 in the LDH group. The neutralizing antibody levels in the LDH and ISA-206 groups were significantly higher from days 7–28 compared to the PBS control group ( P  < 0.05). Thus, LDH NPs were effective at inducing an immune response against FMDV. Conclusions LDHs with a loose hexagonal shape and a positive charge were prepared and evaluated as adjuvant for FMD vaccine. It was demonstrated that LDHs can induce immune responses in mice and pigs. In addition, the LDHs produced antibodies continuously which may indicate a slow-release effect. The study shows that LDHs may act as a potentially useful FMDV adjuvant.

Background Hypoxemia is the most common adverse reaction during sedated hysteroscopy. Obesity is a risk factor for hypoxemia. For hysteroscopy, propofol is the most commonly used sedative. However, it can cause dose-dependent respiratory depression. This drawback has driven the search for sedatives with less respiratory depressant effects. Remimazolam is a new benzodiazepine drug with several advantages, including minimal impact on the respiratory and circulatory systems. This study aims to compare remimazolam and propofol in terms of safety and efficacy in patients with overweight or obesity who are undergoing sedated hysteroscopy. Methods This prospective, single-center, randomized, single-blind, controlled clinical trial will be conducted to examine the effect of remimazolam on the incidence of severe hypoxemia in patients with overweight or obesity. Patients ( n  = 600) scheduled to undergo sedated hysteroscopy will be randomly assigned to either the control or experimental group and will be sedated using propofol or remimazolam, respectively. Discussion The main objective of this study is to determine whether remimazolam can reduce the incidence of severe hypoxemia in patients with overweight or obesity during hysteroscopy. The results of this study are expected to provide evidence on the safety and efficacy of remimazolam in patients with overweight or obesity, which will enhance patient comfort and safety during sedated hysteroscopy. Trial registration ClinicalTrials.gov NCT06187896. Registered on January 3, 2024.

The Coronavirus Disease 2019 (COVID-19) caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is a global pandemic that seriously threatens health and socioeconomic development, but the existed antiviral drugs and vaccines still cannot yet halt the spread of the epidemic. Therefore, a comprehensive and profound understanding of the pathogenesis of SARS-CoV-2 is urgently needed to explore effective therapeutic targets. Here, we conducted a multiomics study of SARS-CoV-2-infected lung epithelial cells, including transcriptomic, proteomic, and ubiquitinomic. Multiomics analysis showed that SARS-CoV-2-infected lung epithelial cells activated strong innate immune response, including interferon and inflammatory responses. Ubiquitinomic further reveals the underlying mechanism of SARS-CoV-2 disrupting the host innate immune response. In addition, SARS-CoV-2 proteins were found to be ubiquitinated during infection despite the fact that SARS-CoV-2 itself didn’t code any E3 ligase, and that ubiquitination at three sites on the Spike protein could significantly enhance viral infection. Further screening of the E3 ubiquitin ligases and deubiquitinating enzymes (DUBs) library revealed four E3 ligases influencing SARS-CoV-2 infection, thus providing several new antiviral targets. This multiomics combined with high-throughput screening study reveals that SARS-CoV-2 not only modulates innate immunity, but also promotes viral infection, by hijacking ubiquitination-specific processes, highlighting potential antiviral and anti-inflammation targets.

Chikungunya virus (CHIKV) is a reemerging arbovirus causing disease on a global scale, and the potential for its epidemics remains high. CHIKV has caused millions of cases and heavy economic burdens around the world, while there are no available approved antiviral therapies to date. In this study, nifuroxazide, an FDA-approved antibiotic for acute diarrhea or colitis, was found to significantly inhibit a variety of arboviruses, although its antiviral activity varied among different target cell types. Nifuroxazide exhibited relatively high inhibitory efficiency in yellow fever virus (YFV) infection of the hepatoma cell line Huh7, tick-borne encephalitis virus (TBEV) and west nile virus (WNV) infection of the vascular endothelial cell line HUVEC, and CHIKV infection of both Huh7 cells and HUVECs, while it barely affected the viral invasion of neurons. Further systematic studies on the action stage of nifuroxazide showed that nifuroxazide mainly inhibited in the viral replication stage. In vivo, nifuroxazide significantly reduced the viral load in muscles and protected mice from CHIKV-induced footpad swelling, an inflammation injury within the arthrosis of infected mice. These results suggest that nifuroxazide has a potential clinical application as an antiviral drug, such as in the treatment of CHIKV infection.

The successful application of primordial germ cells (PGCs) is an ideal method for generating gene-edited birds. However, barriers to efficient DNA transfection in PGCs lead to low transfection efficiency, limiting the generation of genetically modified chickens. The current study utilized chemical transfection and electroporation methods to determine the optimal transfection conditions for the PGC line under feeder- and serum-free medium. Among the tested methods, the Lonza electroporation system exhibited the highest transduction efficiency, with a previously unreported rate of 71.13 ± 1.26%. Optimal transfection conditions were achieved using 4 µg of DNA and 100 µL of EntransterTM-E in 1 × 106 PGCs. Furthermore, the optimal electroporation conditions resulted in low cell death and normal expression of pluripotency-related genes, highlighting the low cytotoxicity. The resulting electroporation models were then used to deliver the enhanced green fluorescent protein (EGFP) gene to the Z chromosome with a Cas9-gRNA plasmid, achieving a 7-day insertion efficiency of 14.63 ± 1.07%. Our study highlights the vast potential of electroporation technology for the transfection of PGCs.

The emergence of significant arboviruses and their spillover transmission to humans represent a major threat to global public health. No approved drugs are available for the treatment of significant arboviruses in circulation today. The repurposing of clinically approved drugs is one of the most rapid and promising strategies in the identification of effective treatments for diseases caused by arboviruses. Here, we screened small-molecule compounds with anti-tick-borne encephalitis virus, West Nile virus, yellow fever virus and chikungunya virus activity from 2580 FDA-approved drugs. In total, 60 compounds showed antiviral efficacy against all four of the arboviruses in Huh7 cells. Among these compounds, ixazomib and ixazomib citrate (inhibitors of 20S proteasome β5) exerted antiviral effects at a low-micromolar concentration. The time-of-drug-addition assay suggested that ixazomib and ixazomib citrate disturbed multiple processes in viruses’ life cycles. Furthermore, ixazomib and ixazomib citrate potently inhibited chikungunya virus replication and relieved virus-induced footpad swelling in a mouse model. These results offer critical information which supports the role of ixazomib as a broad-spectrum agent against arboviruses.

Despite nationwide control efforts, central China experiences persistently high annual PM2.5 concentrations (~50 μg/m3), which are particularly severe in January (exceeding 110 μg/m3). This study employs an integrated approach combining a Multiple Linear Regression (MLR) model derived from random forest analysis with the WRF-CMAQ chemical transport modeling system to quantitatively disentangle the driving factors of PM2.5 concentrations in central China. Key findings reveal significant spatiotemporal heterogeneity in anthropogenic contributions, evidenced by consistently higher north–south gradients in regression residuals (reflecting emission impacts), linked to spatially varying industrial and transportation influences. Critically, the reduction in anthropogenic impacts over six years was substantially smaller in winter (January: 27 to 23 μg/m3) compared to summer (15 to −18 μg/m3, July), highlighting the profound role of emissions in driving severe January pollution events. Furthermore, WRF-CMAQ simulations demonstrated that adverse meteorological conditions in January 2020 counteracted emission controls, causing a net increase in PM2.5 of +13 μg/m3 relative to 2016, thereby offsetting ~68% of the reductions achieved through emission abatement (−19 μg/m3). Significant regional transport, especially affecting northern and central Henan, further weakened local control efficacy. These quantitative insights into the mechanisms of PM2.5 pollution, particularly the counteracting effects of meteorology on emission reductions in critical winter periods, provide a vital scientific foundation for designing more effective and targeted air quality management strategies in central China.