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Abstract Background Bats (Order Chiroptera) are an important reservoir of emerging zoonotic microbes, including viruses of public health concern such as henipaviruses, lyssaviruses, and SARS-related coronaviruses. Despite the continued discovery of new viruses in bat populations, a significant proportion of these viral agents remain uncharacterized, highlighting the imperative for additional research aimed at elucidating their evolutionary relationship and taxonomic classification. Results In order to delve deeper into the viral reservoir hosted by bats, the present study employed Next Generation Sequencing (NGS) technology to analyze 13,105 swab samples obtained from various locations in China. Analysis of 378 sample pools revealed the presence of 846 vertebrate-associated viruses. Subsequent thorough examination, adhering to the International Committee on Taxonomy of Viruses (ICTV) criteria for virus classification, identified a total of 120 putative viral species with the potential to emerge as novel viruses, comprising a total of 294 viral strains. Phylogenetic analysis of conserved genomic regions indicated the novel virus exhibited a diverse array of viral lineages and branches, some of which displayed close genetic relationships to known human and livestock pathogens, such as poxviruses and pestiviruses. Conclusions This study investigates the breadth of DNA and RNA viruses harbored by bats, delineating several novel evolutionary lineages and offering significant contributions to virus taxonomy. Furthermore, the identification of hitherto unknown viruses with relevance to human and livestock health underscores the importance of this study in encouraging infectious disease monitoring and management efforts in both public health and veterinary contexts. Video Abstract

Abstract Health concerns about excess dietary salt have traditionally focused on its relationship with hypertension and the increased risk of cognitive impairment. However, research has often overlooked the unique health concerns and physiological differences between men and women, leading to gaps in knowledge, particularly regarding disease prevention and treatment strategies for women. The present study examined aged female rats over 12 weeks, using control, low, and high salt diets to mimic the post-menopausal phase in human females when cardiovascular risks typically increase. Cardiometabolic parameters and cognition were monitored. The findings revealed the impact of varying salt diets on blood lipids, blood pressure (BP) and heart rate (HR) levels and variability, anxiety, and cognition. Specifically, intake of a low-salt diet led to a significant reduction in BP levels but an increase in BP variability starting from the eighth week of the diet onset. Moreover, HR levels and variability were notably higher with the low-salt diet. Aged female rats exhibited increased anxiety on the low-salt diet at the fourth week, but the anxiety began to improve starting from the eighth week. Additionally, a trend suggested that the low salt intake worsened short-term memory while improving long-term memory. Furthermore, plasma lipids decreased significantly in aged female rats on a high-salt diet compared to those on a low-salt diet. The study provides valuable insights into the effects of salt intake on cardiometabolic parameters and cognitive function in aged female rats, highlighting the importance of considering sex-specific dietary guidelines for cardiometabolic and cognitive health.

A new species Serangium xinpingensis Huang & Wang, sp. nov. is described from Yunnan Province, China, as a newly discovered predator on Bemisia tabaci Gennadius (Hemiptera, Sternorrhyncha, Aleyrodidae). The new species is a valuable addition to the 14 species of this genus in China known before. A diagnosis, detailed description, including the structure of its immature stages, illustrations, and the distribution of the new species are provided.

Abstract Background Previous research has revealed the potential impact of circadian rhythms on pulmonary diseases; however, the connection between circadian rhythm-associated Thyrotroph Embryonic Factor (TEF) and Pulmonary Arterial Hypertension (PAH) remains unclear. We aim to assess the genetic causal relationship between TEF and PAH by utilizing two sets of genetic instrumental variables (IV) and publicly available Pulmonary Arterial Hypertension Genome-Wide Association Studies (GWAS). Methods Total of 23 independent TEF genetic IVs from recent MR reports and PAH GWAS including 162,962 European individuals were used to perform this two-sample MR study. Gain- and loss-of-function experiments were used to demonstrate the role of TEF in PAH. Results Our analysis revealed that as TEF levels increased genetically, there was a corresponding increase in the risk of PAH, as evidenced by IVW (OR = 1.233, 95% CI: 1.054–1.441; P = 0.00871) and weighted median (OR = 1.292, 95% CI for OR: 1.064–1.568; P = 0.00964) methods. Additionally, the up-regulation of TEF expression was associated with a significantly higher likelihood of abnormal circadian rhythm (IVW: P = 0.0024733, β = 0.05239). However, we did not observe a significant positive correlation between circadian rhythm and PAH (IVW: P = 0.3454942, β = 1.4980398). In addition, our in vitro experiments demonstrated that TEF is significantly overexpressed in pulmonary artery smooth muscle cells (PASMCs). And overexpression of TEF promotes PASMC viability and migratory capacity, as well as upregulates the levels of inflammatory cytokines. Conclusion Our analysis suggests a causal relationship between genetically increased TEF levels and an elevated risk of both PAH and abnormal circadian rhythm. Consequently, higher TEF levels may represent a risk factor for individuals with PAH.

Background: Cellular senescence is pivotal in the occurrence and progression of atrial fibrillation (AF). This study aimed to identify senescence-related genes that could be potential therapeutic biomarkers for AF. Methods: AF-related differentially expressed genes (DEGs) were identified using the Gene Expression Omnibus dataset. Weighted gene co-expression network analysis (WGCNA) was used to analyze important modules and potential hub genes. Integrating senescence-related genes, potential biomarkers were identified. Their differential expression levels were then validated in human atrial tissue, HL-1 cells, and Angiotensin II-infused mice. Finally, molecular docking analysis was conducted to predict potential interactions between potential biomarkers and the senolytic drug Navitoclax. Results: We identified seven genes common to AF-related DEGs and senescence-related genes. Three significant modules were selected from WGCNA analysis. Taken together, three senescence-related genes (ETS1, SP1, and WT1) were found to be significantly associated with AF. Protein-protein interaction network analysis revealed biological connections among the predicted target genes of ETS1, SP1, and WT1. Notably, ETS1, SP1, and WT1 exhibited significant differential expression in clinical samples as well as in vitro and in vivo models. Molecular docking revealed favorable binding affinity between senolytic Navitoclax and these potential biomarkers. Conclusions: This study highlights ETS1, SP1, and WT1 as crucial senescence-related genes associated with AF, offering potential therapeutic targets, with supportive evidence of binding affinity with senolytic Navitoclax. These findings provide novel insights into AF pathogenesis from a senescence perspective.

Abstract Mounting clinical evidence suggests that a comprised intestinal barrier contributes to the progression of nonalcoholic steatohepatitis (NASH); nevertheless, the precise mechanism remains elusive. This study unveils a significant upregulation of nuclear receptor‐binding SET domain protein 2 (NSD2) in the intestines of obese humans and mice subjected to a high‐fat cholesterol diet (HFCD). Intestine‐specific NSD2 knockout attenuated the progression of intestinal barrier impairment and NASH, whereas NSD2 overexpression exacerbated this progression. Mechanistically, NSD2 directly regulates the transcriptional activation of Ern1 by demethylating histone H3 at lysine 36 (H3K36me2), thus activating the ERN1–JNK axis to intensify intestinal barrier impairment and subsequently foster NASH progression. These findings elucidate the crucial role of NSD2‐mediated H3K36me2 in intestinal barrier impairment, suggesting that targeting intestinal NSD2 can represent a novel therapeutic approach for NASH.

PreambleRobotic magnetic navigation (RMN)-guided catheter ablation (CA) technology has been used for the treatment of cardiac arrhythmias for almost 20 years. Various studies reported that RMN allows for high catheter stability, improved lesion formation and a superior safety profile. So far, no guidelines or recommendations on RMN-guided CA have been published.PurposeThe aim of this consensus paper was to summarize knowledge and provide recommendations on management of arrhythmias using RMN-guided CA as treatment of atrial fibrillation (AF) and ventricular arrhythmias (VA).MethodologyAn expert writing group, performed a detailed review of available literature, and drawing on their own experience, drafted and voted on recommendations and summarized current knowledge and practice in the field. Recommendations on RMN-guided CA are presented in a guideline format with three levels of recommendations to serve as a reference for best practices in RMN procedures. Each recommendation is accompanied by supportive text and references. The various sections cover the practical spectrum from system and patient set-up, EP laboratory staffing, combination of RMN with fluoroscopy and mapping systems, use of automation features and ablation settings and targets, for different cardiac arrhythmias.ConclusionThis manuscript, presenting the combined experience of expert robotic users and knowledge from the available literature, offers a unique resource for providers interested in the use of RMN in the treatment of cardiac arrhythmias.

Abstract Background Patients with pulmonary arterial hypertension (PAH) exhibit a distinct gut microbiota profile; however, the causal association between gut microbiota, associated metabolites, and PAH remains elusive. We aimed to investigate this causal association and to explore whether dietary patterns play a role in its regulation. Methods Summary statistics of gut microbiota, associated metabolites, diet, and PAH were obtained from genome-wide association studies. The inverse variance weighted method was primarily used to measure the causal effect, with sensitivity analyses using the weighted median, weighted mode, simple mode, MR pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger methods. A reverse Mendelian randomisation analysis was also performed. Results Alistipes (odds ratio [OR] = 2.269, 95% confidence interval [CI] 1.100–4.679, P = 0.027) and Victivallis (OR = 1.558, 95% CI 1.019–2.380, P = 0.040) were associated with an increased risk of PAH, while Coprobacter (OR = 0.585, 95% CI 0.358–0.956, P = 0.032), Erysipelotrichaceae (UCG003) (OR = 0.494, 95% CI 0.245–0.996, P = 0.049), Lachnospiraceae (UCG008) (OR = 0.596, 95% CI 0.367–0.968, P = 0.036), and Ruminococcaceae (UCG005) (OR = 0.472, 95% CI 0.231–0.962, P = 0.039) protected against PAH. No associations were observed between PAH and gut microbiota-derived metabolites (trimethylamine N-oxide [TMAO] and its precursors betaine, carnitine, and choline), short-chain fatty acids (SCFAs), or diet. Although inverse variance-weighted analysis demonstrated that elevated choline levels were correlated with an increased risk of PAH, the results were not consistent with the sensitivity analysis. Therefore, the association was considered insignificant. Reverse Mendelian randomisation analysis demonstrated that PAH had no causal impact on gut microbiota-derived metabolites but could contribute to increased the levels of Butyricicoccus and Holdemania, while decreasing the levels of Clostridium innocuum, Defluviitaleaceae UCG011, Eisenbergiella, and Ruminiclostridium 5. Conclusions Gut microbiota were discovered suggestive evidence of the impacts of genetically predicted abundancy of certain microbial genera on PAH. Results of our study point that the production of SCFAs or TMAO does not mediate this association, which remains to be explained mechanistically.

Using data independent acquisition (DIA) proteomics, the composition and biological functions of differentially expressed proteins in raw milk during cold storage at 4 ℃ for up to 6 days were investigated. A total of 902 proteins were detected. Among them, 70 and 71 differentially expressed proteins were selected during the early (day 0 vs day 3) and late (day 3 vs day 6) stages of refrigeration, respectively. The differentially expressed proteins played an important role in the response to nerve growth factors and the regulation of cells and tissues at the early stage of refrigeration, and were mainly involved in the biological processes of cells. At the late stage of refrigeration, the differentially expressed proteins could regulate the metabolic processes of carbohydrate and RNA, and mainly participated in the sugar metabolic pathways. Protein-protein interaction (PPI) network analysis indicated that cell division control protein 42 homolog (CDC42) was the hub node protein for both refrigeration periods, which was closely related to phagocytosis. These findings revealed the compositional changes and functional diversity of functions in raw milk proteins during refrigeration, which will provide a theoretical basis for the cold storage of raw milk and be of great significance for the quality control of raw milk.

ABSTRACTEvidence showed that air pollution was associated with an increased risk of tuberculosis (TB). This study aimed to study the impact of long-term exposure to ambient particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) on the acquisition of LTBI and on the risk of subsequent active disease development among rural older adults from a multicentre cohort, which have not yet been investigated to date. A total of 4790 older adults were included in a population-based, multicentre, prospective cohort study (LATENTTB-NSTM) from 2013 to 2018. The level of long-term exposure to PM2.5 for each participant was assessed by aggregating satellite-based estimates. Logistic regression and time-varying Cox proportional hazards models with province-level random intercepts were employed to assess associations of long-term exposures to PM2.5 with the risk of LTBI and subsequent development of active TB, respectively. Out of 4790 participants, 3284 were LTBI-free at baseline, among whom 2806 completed the one-year follow-up and 127 developed newly identified LTBI. No significant associations were identified between PM2.5 and the risk of LTBI. And among 1506 participants with LTBI at baseline, 30 active TB cases were recorded during the 5-year follow-up. Particularly, an increment of 5 μg/m3 in 2-year moving averaged PM2.5 was associated with a 50.6% increased risk of active TB (HR = 1.506, 95% CI: 1.161-1.955). Long-term air pollution might be a neglected risk factor for active TB development from LTBI, especially for those living in developing or less-developed areas where the air quality is poor.

Introduction The presence of perioperative insomnia is common but yet often overlooked among cancer survivors. Non-pharmaceutical therapies have shown promise in treating cancer-related insomnia during the perioperative period; however, the existing evidence from various studies remains inconsistent. Therefore, this study aims to systematically review and assess the effectiveness of a wide range of non-pharmaceutical interventions during perioperative period for cancer-related insomnia. Findings from this study will help to make evidence-based treatment decisions.Methods and analysis A comprehensive electronic search will be conducted to identify relevant articles from multiple databases, including PubMed, MEDLINE, Embase, Web of Science, Cochrane Central Register of Controlled Trials and Chinese literature databases such as CNKI, VIP, Wanfang from inception to 1 December 2023. Language restrictions will not be imposed to ensure inclusivity. The change of the Pittsburgh Sleep Quality Index or the Insomnia Severity Index from baseline will be used as the primary outcome of the study. Studies using these as secondary outcomes are also acceptable. Pairwise meta-analysis and network meta-analysis will be conducted using Stata V.15.0 software. The Cochrane collaboration tool for assessing the Risk of Bias and Risk of Bias in Non-randomised Studies of Interventions will be used for risk and bias assessment. Additionally, the Grading of Recommendations, Assessment, Development and Evaluation scale will be employed to evaluate the quality of the evidence.Ethics and dissemination Ethical approval is not required for this study since it involves the analysis of existing studies. The anticipated results will be disseminated through publication in a peer-reviewed journal.PROSPERO registration number CRD42023437356.

Objective To investigate the correlation between mildly elevated pulmonary artery systolic pressure (PASP) on echocardiography and mortality, as well as long-term changes in PASP.Design Retrospective cohort study.Setting Shanghai, China, a single centre.Participants A total of 910 patients were enrolled in this study. From January to June 2016, 1869 patients underwent echocardiography at the Zhongshan Hospital affiliated with Fudan University. Patients with malignant tumours, previous heart or other solid organ transplantation, previous or scheduled ventricular assist device implantation, severe kidney dysfunction (uraemia and patients on dialysis) and a life expectancy of less than 1 year for any medical condition were excluded.Interventions No interventions were done.Primary and secondary outcome measures The predictors of death in patients with mild echocardiographic pulmonary hypertension were analysed using univariate and multivariate Cox regression analyses. Paired t-tests were used to calculate changes in the PASP values at baseline and follow-up for different patient groups.Results The 5-year survival of patients was 93.2%. Patients were grouped according to whether they had combined organic heart disease (OHD). The PASP value was an independent predictor of all-cause mortality in patients with OHD, with each 1 mm Hg increase associated with an HR of 1.02 (95% CI: 1.01–1.03, p=0.038) but not in patients without OHD. Of the total, 46% (419/910) of the patients with 5–6 years of echocardiography were investigated for changes in the PASP value. We found significant PASP reduction in patients without OHD (42.8±2.4 mm Hg vs 39.3±8.2 mm Hg, p

ObjectiveThis study aimed to evaluate the feasibility of a hybrid Glubran-supported single-Proglide technique for large bore femoral access closure during percutaneous access endovascular aneurysm repair (EVAR).MethodsA retrospective cohort study was performed for all percutaneous EVARs at our center from January 2023 to June 2023. All patients received the hybrid Glubran-supported single-Proglide technique involving a mixture of surgical glue and Lipiodol injection after single suture placement for femoral access closure. Technical success was defined as achieving complete hemostasis without a bailout strategy. Vascular complications and bleeding were defined by Valve Academic Research Consortium-3 (VARC-3) criteria. Vascular access changes and 30-day mortality were recorded.ResultsThe technique success rate for the entire study population was 100% (55 femoral access in 37 patients; median age: 72; 78% males). The mean sheath size was 20.4 ± 2.3F. The mean manual compression time was 3.5 ± 1.4 min, the mean hemostasis time was 9.0 ± 2.5 min, and the mean procedural time was 103.9 ± 34.7 min. One patient (1.6%) developed an access site infection and recovered conservatively. No VARC-3 vascular complications and access changes were observed. No 30-day mortality happened.ConclusionsThe hybrid Glubran-supported single-Proglide technique is feasible for large bore access closure during EVAR and may be a viable alternative; however, larger prospective studies are required to confirm its efficacy.

Introduction Patients with breast cancer often suffer from depressive symptoms throughout various stages of cancer, significantly impacting their quality of life and treatment outcomes. Non-pharmaceutical interventions such as psychotherapy, mind–body therapies and physical exercise have shown effectiveness in addressing cancer-related depression. However, the efficacy and safety of different non-pharmacological interventions remain a topic of debate. Therefore, to provide an objective assessment and comparison of the impact of different non-pharmaceutical interventions on depression, we will conduct a network meta-analysis (NMA) to explore the effects of different non-pharmaceutical interventions on reducing depressive symptoms among patients with breast cancer.Methods and analysis We will search nine Chinese and English-language databases, from database inception to 31 July 2023, for randomised controlled trials published in Chinese or English. The English-language databases are PubMed, Medline, Embase, Web of Science and Cochrane Central Register of Controlled Trials, and the Chinese databases are CBM, CNKI, VIP and Wanfang. Two independent researchers will perform information extraction from eligible articles. The primary outcome will be the changes in depressive symptoms, while the secondary outcome will include adverse events. STATA V.15.0 will be used to conduct paired meta-analysis and NMA. Grading of Recommendations Assessment, Development and Evaluation will be used to assess the quality of evidence, and the Cochrane tool for assessing the risks of bias in randomised trials V.2 will be used for risk of bias assessment.Ethics and dissemination The study does not require ethical approval as it will analyse data from existing studies. It is expected that the results of the study will be published in peer-reviewed journals and presented at relevant conferences.PROSPERO registration number CRD42023450494.

Abstract Sirtuins, which are NAD+-dependent class III histone deacetylases, are involved in various biological processes, including DNA damage repair, immune inflammation, oxidative stress, mitochondrial homeostasis, autophagy, and apoptosis. Sirtuins are essential regulators of cellular function and organismal health. Increasing evidence suggests that the development of age-related diseases, including kidney diseases, is associated with aberrant expression of sirtuins, and that regulation of sirtuins expression and activity can effectively improve kidney function and delay the progression of kidney disease. In this review, we summarise current studies highlighting the role of sirtuins in renal diseases. First, we discuss sirtuin family members and their main mechanisms of action. We then outline the possible roles of sirtuins in various cell types in kidney diseases. Finally, we summarise the compounds that activate or inhibit sirtuin activity and that consequently ameliorate renal diseases. In conclusion, targeted modulation of sirtuins is a potential therapeutic strategy for kidney diseases. Video Abstract

Traffic signal control is an important part of intelligent transportation. Efficient traffic signal control strategies not only alleviate traffic congestion, improve vehicle traffic efficiency, but also reduce exhaust pollution during the waiting period. The traditional multiple intersection signal light control method are generally faced with passive control and can not adapt to complex changes. In view of this, the study first combines reinforcement learning and Markov decision to construct a signal control problem model for multiple intersections. Secondly, deep Q-learning networks are introduced for decision solving, and multi-head attention mechanisms and graph convolutional networks are further introduced for optimization and improvement. Finally, a spatial lightweight model for multiple intersection adaptive graph convolution is proposed. The experimental results show that the maximum throughput of the multi-intersection adaptive control model can reach 195 vehicles/min, the shortest queue length is 4.31 vehicles, the shortest average delay is 1.23 minutes, the shortest average travel time is 2.07 minutes, and the attention value of adjacent intersections is close to 80%. The average green wave time under this model is 4 minutes, and the longest green wave section can reach 5 minutes. It can be seen that the new multi-intersection signal adaptive control model proposed in this study has advantages and feasibility compared with similar methods in various indexes, and can provide new ideas and methods for the further development of traffic signal automatic control technology.

[This corrects the article DOI: 10.1371/journal.ppat.1003231.].

Contractile injection systems (CISs), one of the most important bacterial secretion systems that transport substrates across the membrane, are a collection of diverse but evolutionarily related macromolecular devices. Numerous effector proteins can be loaded and injected by this secretion complex to their specific destinations. One group of CISs called extracellular CIS (eCIS) has been proposed as secretory molecules that can be released from the bacterial cytoplasm and attack neighboring target cells from the extracellular environment. This makes them a potential delivery vector for the transportation of various cargos without the inclusion of bacterial cells, which might elicit certain immunological responses from hosts. We have demonstrated that the Photorhabdus virulence cassette (PVC), which is a typical eCIS, could be applied as an ideal vector for the translocation of proteinaceous cargos with different physical or chemical properties. Here, we describe the in-depth purification protocol of this mega complex from Escherichia coli. The protocol provided is a simpler, faster, and more productive way of generating the eCIS complexes than available methodologies reported previously, which can facilitate the subsequent applications of these nanodevices and other eCIS in different backgrounds.

Abstract Inflammation contributes to development of idiopathic pulmonary arterial hypertension (IPAH), and tumor biomarkers can reflect inflammatory and immune status. We aimed to determine the value of tumor biomarkers in IPAH comprehensively. We enrolled 315 patients with IPAH retrospectively. Tumor biomarkers were correlated with established indicators of pulmonary hypertension severity. Multivariable Cox regression found that AFP (hazard ratio [HR]: 1.587, 95% confidence interval [CI]: 1.014–2.482, p = 0.043) and CA125 (HR: 2.018, 95% CI: 1.163–3.504, p = 0.013) could independently predict prognosis of IPAH. The changes of AFP over time were associated with prognosis of patients, each 1 ng/mL increase in AFP was associated with 5.4% increased risk of clinical worsening (HR: 1.054, 95% CI: 1.001–1.110, p = 0.046), enabling detection of disease progression. Moreover, beyond well‐validated PH biomarkers, CA125 was still of prognostic value in the low‐risk patients (HR: 1.014, 95% CI: 1.004–1.024, p = 0.004), allowing for more accurate risk stratification and prediction of disease outcomes. AFP and CA125 can serve for prognosis prediction, risk stratification, and dynamic monitor in patients with IPAH.

Abstract Bats, recognized as considerable reservoirs for coronaviruses (CoVs), serve as natural hosts for several highly pathogenic CoVs, including SARS-CoV and SARS-CoV-2. Investigating the bat CoV community provides insights into the origin for highly pathogenic CoVs and highlights bat CoVs with potential spillover risks. This study probes the evolution, recombination, host range, geographical distribution, and cross-species transmission characteristics of bat CoVs across China and its associated CoVs in other regions. Through detailed research on 13,064 bat samples from 14 provinces of China, 1141 CoV strains are found across 10 subgenera and one unclassified Alpha-CoV, generating 399 complete genome sequences. Within bat CoVs, 11 new CoV species are identified and 425 recombination events are detected. Bats in southern China, particularly in Yunnan province, exhibit a pronounced diversity of CoVs. Limited sampling and low detection rates exist for CoVs in Myotacovirus, Nyctacovirus, Hibecovirus, Nobecovirus in China. The genus Myotis is highlighted as a potential ancestral host for Alpha-CoV, with the genus Hipposideros suggested as a likely progenitor host for bat-associated Beta-CoV, indicating the complexity of cross-species transmission dynamics. Through the comprehensive analysis, this study enriches the understanding of bat CoVs and offers a valuable resource for future research.