The Shigella kinase effector OspG modulates host ubiquitin signaling to escape septin-cage entrapment.

Shigella flexneri is a Gram-negative bacterium causing severe bloody dysentery. Its pathogenesis is largely dictated by a plasmid-encoded type III secretion system (T3SS) and its associated effectors. Among these, the effector OspG has been shown to bind to the ubiquitin conjugation machinery (E2~Ub) to activate its kinase activity. However, the cellular targets of OspG remain elusive despite years of extensive efforts. Here we show by unbiased phosphoproteomics that a major target of OspG is CAND1, a regulatory protein controlling the assembly of cullin-RING ubiquitin ligases (CRLs). CAND1 phosphorylation weakens its interaction with cullins, which is expected to impact a large panel of CRL E3s. Indeed, global ubiquitome profiling reveals marked changes in the ubiquitination landscape when OspG is introduced. Notably, OspG promotes ubiquitination of a class of cytoskeletal proteins called septins, thereby inhibiting formation of cage-like structures encircling cytosolic bacteria. Overall, we demonstrate that pathogens have evolved an elaborate strategy to modulate host ubiquitin signaling to evade septin-cage entrapment.

Pre-treatment assessment of chemotherapy for cancer patients: a multi-site evidence implementation project of 74 hospitals in China.

BACKGROUND: Chemotherapy, whilst treating tumours, can also lead to numerous adverse reactions such as nausea and vomiting, fatigue and kidney toxicity, threatening the physical and mental health of patients. Simultaneously, misuse of chemotherapeutic drugs can seriously endanger patients' lives. Therefore, to maintain the safety of chemotherapy for cancer patients and to reduce the incidence of adverse reactions to chemotherapy, many guidelines state that a comprehensive assessment of the cancer patient should be conducted and documented before chemotherapy. This recommended procedure, however, has yet to be extensively embraced in Chinese hospitals. As such, this study aimed to standardise the content of pre-chemotherapy assessment for cancer patients in hospitals and to improve nurses' adherence to pre-chemotherapy assessment of cancer patients by conducting a national multi-site evidence implementation in China, hence protecting the safety of cancer patients undergoing chemotherapy and reducing the incidence of adverse reactions to chemotherapy in patients. METHODS: The national multi-site evidence implementation project was launched by a JBI Centre of Excellence in China and conducted using the JBI approach to evidence implementation. A pre- and post-audit approach was used to evaluate the effectiveness of the project. This project had seven phases: training, planning, baseline audit, evidence implementation, two rounds of follow-up audits (3 and 9 months after evidence implementation, respectively) and sustainability assessment. A live online broadcast allowed all participating hospitals to come together to provide a summary and feedback on the implementation of the project. RESULTS: Seventy-four hospitals from 32 cities in China participated in the project, four withdrew during the project's implementation, and 70 hospitals completed the project. The pre-and post-audit showed a significant improvement in the compliance rate of nurses performing pre-chemotherapy assessments for cancer patients. Patient satisfaction and chemotherapy safety were also improved through the project's implementation, and the participating nurses' enthusiasm and belief in implementing evidence into practice was increased. CONCLUSION: The study demonstrated the feasibility of academic centres working with hospitals to promote the dissemination of evidence in clinical practice to accelerate knowledge translation. Further research is needed on the effectiveness of cross-regional and cross-organisational collaborations to facilitate evidence dissemination.

High-sensitivity vector magnetic field sensor based on a V-shaped multimode-no-core-multimode fiber structure.

This work proposes and investigates a bent multimode-no-core-multimode optical fiber structure for vector magnetic field sensing applications. The bent no-core fiber (NCF) serves as the sensing area, and the gold film is deposited on its surface to excite the surface plasmon resonance effect. Due to the strong evanescent field of the unclad and bent NCF, the as-fabricated sensor exhibits a high sensitivity of 5630 nm/RIU in the refractive index range of 1.36-1.39. Magnetic fluid is employed as the magneto-sensitive material for magnetic field sensing, exhibiting a high magnetic field intensity sensitivity of 5.74 nm/mT and a high magnetic field direction sensitivity of 0.22 nm/°. The proposed sensor features a simple structure, low cost, point sensing, and excellent mechanical performance.

Legionella pneumophila exploits the endo-lysosomal network for phagosome biogenesis by co-opting SUMOylated Rab7.

Legionella pneumophila strains harboring wild-type rpsL such as Lp02rpsLWT cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of extensive lysosome damage and apoptosis. The bacterial factor directly responsible for inducing such cell death and the host factor involved in initiating the signaling cascade that leads to lysosome damage remain unknown. Similarly, host factors that may alleviate cell death induced by these bacterial strains have not yet been investigated. Using a genome-wide CRISPR/Cas9 screening, we identified Hmg20a and Nol9 as host factors important for restricting strain Lp02rpsLWT in BMDMs. Depletion of Hmg20a protects macrophages from infection-induced lysosomal damage and apoptosis, allowing productive bacterial replication. The restriction imposed by Hmg20a was mediated by repressing the expression of several endo-lysosomal proteins, including the small GTPase Rab7. We found that SUMOylated Rab7 is recruited to the bacterial phagosome via SulF, a Dot/Icm effector that harbors a SUMO-interacting motif (SIM). Moreover, overexpression of Rab7 rescues intracellular growth of strain Lp02rpsLWT in BMDMs. Our results establish that L. pneumophila exploits the lysosomal network for the biogenesis of its phagosome in BMDMs.

Phytochemicals derived from Nicotiana tabacum L. plant contribute to pharmaceutical development.

The Nicotiana tabacum L. plant, a medicinal resource, holds significant potential for benefiting human health, as evidenced by its use in Native American and ancient Chinese cultures. Modern medical and pharmaceutical studies have investigated that the abundant and distinctive function metabolites in tobacco including nicotine, solanesol, cembranoid diterpenes, essential oil, seed oil and other tobacco extracts, avoiding the toxic components of smoke, mainly have the anti-oxidation, anti-lipid production, pro-lipid oxidation, pro-insulin sensitivity, anti-inflammation, anti-apoptosis and antimicrobial activities. They showed potential pharmaceutical value mainly as supplements or substitutes for treating neurodegenerative diseases including Alzheimer's and Parkinson's disease, inflammatory diseases including colitis, arthritis, sepsis, multiple sclerosis, and myocarditis, and metabolic syndrome including Obesity and fatty liver. This review comprehensively presents the research status and the molecular mechanisms of tobacco and its metabolites basing on almost all the English and Chinese literature in recent 20 years in the field of medicine and pharmacology. This review serves as a foundation for future research on the medicinal potential of tobacco plants.

CircALMS1 Alleviates Pulmonary Microvascular Endothelial Cell Dysfunction in Pulmonary Hypertension.

BACKGROUND: Circular RNAs can serve as regulators influencing the development of pulmonary hypertension (PH). However, their function in pulmonary vascular intimal injury remains undefined. Thus, we aimed to identify specifically expressed circular RNAs in pulmonary microvascular endothelial cells (PMECs) under hypoxia and PH. METHODS AND RESULTS: Deep RNA sequencing and quantitative real-time polymerase chain reaction revealed that circALMS1 (circular RNA Alstrom syndrome protein 1) was reduced in human PMECs under hypoxia (P<0.0001). Molecular biology and histopathology experiments were used to elucidate the roles of circALMS1 in regulating PMEC dysfunction among patients with PH. The circALMS1 expression was decreased in the plasma of patients with PH (P=0.0315). Patients with lower circALMS1 levels had higher risk of death (P=0.0006). Moreover, the circALMS1 overexpression of adeno-associated viruses improved right ventricular function and reduced pulmonary vascular remodeling in monocrotaline-PH and sugen/hypoxia-PH rats (P<0.05). Furthermore, circALMS1 overexpression promoted apoptosis and inhibited PMEC proliferation and migration under hypoxia by directly downregulating miR-17-3p (P<0.05). Dual luciferase assay confirmed the direct binding of circALMS1 to miR-17-3p and miR-17-3p binding to its target gene YT521-B homology domain-containing family protein 2 (YTHDF2) (P<0.05). The YTHDF2 levels were also downregulated in hypoxic PMECs (P<0.01). The small interfering RNA YTHDF2 reversed the effects of miR-17-3p inhibitors on PMEC proliferation, migration, and apoptosis. Finally, the results indicated that, although YTHDF2, as an N(6)-methyladenosine reader protein, contributes to the degradation of many circular RNAs, it could not regulate the circALMS1 levels in PMECs (P=0.9721). CONCLUSIONS: Our study sheds new light on circALMS1-regulated dysfunction of PMECs by the miR-17-3p/YTHDF2 pathway under hypoxia and provides insights into the underlying pathogenesis of PH.

Integrated network pharmacology and phosphoproteomic analyses of Baichanting in Parkinson's disease model mice.

The incidence rate of Parkinson's disease (PD) is increasing yearly. Neuronal apoptosis caused by abnormal protein phosphorylation is closely related to the pathogenesis of Parkinson's disease. At present, few PD-specific apoptosis pathways have been revealed. To investigate the effect of Baichanting (BCT) on apoptosis from the perspective of protein phosphorylation, α-syn transgenic mice were selected to observe the behavioral changes of the mice, and the apoptosis of substantia nigra cells were detected by the HE method and TUNEL method. Network pharmacology combined with phosphorylation proteomics was used to find relevant targets for BCT treatment of PD and was further verified by PRM and western blotting. BCT improved the morphology of neurons in the substantia nigra and reduced neuronal apoptosis. The main enriched pathways in the network pharmacology results were apoptosis, the p53 signaling pathway and autophagy. Western blot results showed that BCT significantly regulated the protein expression levels of BAX, Caspase-3, LC3B, P53 and mTOR and upregulated autophagy to alleviate apoptosis. Using phosphorylated proteomics and PRM validation, we found that Pak5, Grin2b, Scn1a, BcaN, L1cam and Braf are closely correlated with the targets of the web-based pharmacological screen and may be involved in p53/mTOR-mediated autophagy and apoptosis pathways. BCT can inhibit the activation of the p53/mTOR signaling pathway, thereby enhancing the autophagy function of cells, and reducing the apoptosis of neurons which is the main mechanism of its neuroprotective effect.

Characteristics and influencing factors of anticipated HIV stigma among HIV-negative/unknown MSM in China: A regression mixture model.

BACKGROUND: Anticipated HIV stigma among men who have sex with men's (MSM) has a severe negative effect on their physical and mental health wellbeing and hence requires specific attention. The current study aims to identify the characteristics and the psychosocial influencing factors of anticipated HIV stigma in MSM using regression mixture model (RMM) and to determine the cut-off point of the seven-item Anticipated HIV Stigma Questionnaire (AHSQ) using the receiver operating characteristic (ROC) analysis. METHODS: A cross-sectional study was conducted among HIV-negative/unknown MSM from Blued online platform in China from December 16th, 2020 to March 1st, 2021, enrolling 1394 participants. Data were collected on demographic characteristics, perceived social support, anticipated HIV stigma, depressive symptoms, and HIV knowledge. Latent profile analysis was performed to identify different profiles of anticipated HIV stigma level. Chi-square test, analysis of variance, and RMM analysis were conducted to explore the influencing factors in different profiles. ROC analyses were carried out to identify the cut-off value of anticipated stigma. RESULTS: Among the participants, three profiles of anticipated stigma were identified: "low anticipated HIV stigma" (12.0%), "moderate anticipated HIV stigma" (52.1%), and "severe anticipated HIV stigma" (35.9%). RMM analysis showed that higher income and higher levels of knowledge were positively associated with moderate anticipated HIV stigma, whereas full-time job and social support were negatively associated with moderate anticipated HIV stigma; higher income, depressive symptoms, and knowledge were positively associated with severe anticipated HIV stigma, whereas minor ethnicity and social support were negatively associated with severe anticipated HIV stigma. ROC curve of the AHSQ showed that the optimal cut-off value of ≥16 could indicate positive anticipated HIV stigma. CONCLUSION: The study focuses on the level of anticipated HIV stigma and its psycho-socio influencing factors among HIV-negative/unknown MSM. It provides evidence for implementing relevant psychological interventions to HIV-negative/unknown MSM.

Integration of 16S rRNA sequencing and metabolomics to investigate the modulatory effect of ginsenoside Rb1 on atherosclerosis.

Background: /aims: Atherosclerosis (AS) is the common pathological basis of a variety of cardiovascular diseases (CVD), and has become the main cause of human death worldwide, and the incidence is increasing and younger trend. Ginsenoside Rb1 (Rb1), an important monomer component of the traditional Chinese herb ginseng, known for its ability to improve blood lipid disorders and anti-inflammatory. In addition, Rb1 was proved to be an effective treatment for AS. However, the effect of Rb1 on AS remains to be elucidated. The aim of this study was to investigate the mechanisms of Rb1 in ameliorating AS induced by high-fat diet (HFD). Materials and methods: In this study, we developed an experimental AS model in Sprague-Dawley rats by feeding HFD with intraperitoneal injection of vitamin D3. The potential therapeutic mechanism of Rb1 in AS rats was investigated by detecting the expression of inflammatory factors, microbiome 16S rRNA gene sequencing, short-chain fatty acids (SCFAs) targeted metabolomics and untargeted metabolomics. Results: Rb1 could effectively alleviate the symptoms of AS and suppress the overexpression of inflammation-related factors. Meanwhile, Rb1 altered gut microbial composition and concentration of SCFAs characterized by Bacteroidetes, Actinobacteria, Lactobacillus, Prevotella, Oscillospira enrichment and Desulfovibrio depletion, accompanied by increased production of acetic acid and propionic acid. Moreover, untargeted metabolomics showed that Rb1 considerably improved faecal metabolite profiles, particularly arachidonic acid metabolism and primary bile acid biosynthesis. Conclusion: Rb1 ameliorated the HFD-induced AS, and the mechanism is related to improving intestinal metabolic homeostasis and inhibiting systemic inflammation by regulating gut microbiota.

The role of immune cells and inflammation in pulmonary hypertension: mechanisms and implications.

Pulmonary hypertension (PH) is a malignant disease with progressive increase of pulmonary vascular pressure, which eventually leads to right heart failure. More and more evidences show that immune cells and inflammation play an important role in the occurrence and development of PH. In the context of pulmonary vascular diseases, immune cells migrate into the walls of the pulmonary vascular system. This leads to an increase in the levels of cytokines and chemokines in both the bloodstream and the surrounding tissues of the pulmonary vessels. As a result, new approaches such as immunotherapy and anti-inflammatory treatments are being considered as potential strategies to halt or potentially reverse the progression of PH. We reviewed the potential mechanisms of immune cells, cytokines and chemokines in PH development. The potential relationship of vascular cells or bone morphogenetic protein receptor 2 (BMPR2) in immune regulation was also expounded. The clinical application and future prospect of immunotherapy were further discussed.

Legionella metaeffector MavL reverses ubiquitin ADP-ribosylation via a conserved arginine-specific macrodomain.

ADP-ribosylation is a reversible post-translational modification involved in various cellular activities. Removal of ADP-ribosylation requires (ADP-ribosyl)hydrolases, with macrodomain enzymes being a major family in this category. The pathogen Legionella pneumophila mediates atypical ubiquitination of host targets using the SidE effector family in a process that involves ubiquitin ADP-ribosylation on arginine 42 as an obligatory step. Here, we show that the Legionella macrodomain effector MavL regulates this pathway by reversing the arginine ADP-ribosylation, likely to minimize potential detrimental effects caused by the modified ubiquitin. We determine the crystal structure of ADP-ribose-bound MavL, providing structural insights into recognition of the ADP-ribosyl group and catalytic mechanism of its removal. Further analyses reveal DUF4804 as a class of MavL-like macrodomain enzymes whose representative members show unique selectivity for mono-ADP-ribosylated arginine residue in synthetic substrates. We find such enzymes are also present in eukaryotes, as exemplified by two previously uncharacterized (ADP-ribosyl)hydrolases in Drosophila melanogaster. Crystal structures of several proteins in this class provide insights into arginine specificity and a shared mode of ADP-ribose interaction distinct from previously characterized macrodomains. Collectively, our study reveals a new regulatory layer of SidE-catalyzed ubiquitination and expands the current understanding of macrodomain enzymes.

Neural stem cell-derived exosomes regulate cell proliferation, migration, and cell death of brain microvascular endothelial cells via the miR-9/Hes1 axis under hypoxia.

BACKGROUND: Our previous study found that mouse embryonic neural stem cell (NSC)-derived exosomes (EXOs) regulated NSC differentiation via the miR-9/Hes1 axis. However, the effects of EXOs on brain microvascular endothelial cell (BMEC) dysfunction via the miR-9/Hes1 axis remain unknown. Therefore, the current study aimed to determine the effects of EXOs on BMEC proliferation, migration, and death via the miR-9/Hes1 axis. METHODS: Immunofluorescence, quantitative real-time polymerase chain reaction, cell counting kit-8 assay, wound healing assay, calcein-acetoxymethyl/propidium iodide staining, and hematoxylin and eosin staining were used to determine the role and mechanism of EXOs on BMECs. RESULTS: EXOs promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. The overexpression of miR-9 promoted BMEC proliferation and migration and reduced cell death under hypoxic conditions. Moreover, miR-9 downregulation inhibited BMEC proliferation and migration and also promoted cell death. Hes1 silencing ameliorated the effect of amtagomiR-9 on BMEC proliferation and migration and cell death. Hyperemic structures were observed in the regions of the hippocampus and cortex in hypoxia-induced mice. Meanwhile, EXO treatment improved cerebrovascular alterations. CONCLUSION: NSC-derived EXOs can promote BMEC proliferation and migration and reduce cell death via the miR-9/Hes1 axis under hypoxic conditions. Therefore, EXO therapeutic strategies could be considered for hypoxia-induced vascular injury.

Identification of an angiogenesis-related risk score model for survival prediction and immunosubtype screening in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is an incurable B-cell malignancy, but with the emergence of immunotherapy, a potential cure is hopeful. The individualized interaction between the tumor and bone marrow (BM) microenvironment determines the response to immunotherapy. Angiogenesis is a constant hallmark of the BM microenvironment in MM. However, little is known about the potency ability of angiogenesis-associated genes (AAGs) to regulate the immune microenvironment of MM patients. METHODS: We comprehensively dissected the associations between angiogenesis and genomic landscapes, prognosis, and the immune microenvironment by integrating 36 AAGs. Immunohistochemistry was performed to verify the correlation between angiogenic factor expression and patient prognosis. Single-sample gene set enrichment analysis was applied to quantify the relative abundance of 28 infiltrating cells. The AAG score was constructed using the least absolute shrinkage and selection operator Cox regression model. RESULTS: Angiogenesis was closely correlated with MM patient prognosis, and the mutation intensity of the AAGs was low. Immunohistochemistry confirmed that high microvessel density predicted poor prognosis. Three AAG clusters and two gene clusters with distinct clinical outcomes and immune characteristics were identified. The established AAG_score model performed well in predicting patient prognosis and active immunotherapy response. The high-AAG_score subgroup was characterized by reduced immune cell infiltration, poor prognosis, and inactive immunotherapy response. Multivariate analyses indicated that the AAG_score was strongly robust and independent among the prognostic variables. CONCLUSION: This study revealed that angiogenesis is significantly related to MM patient prognosis and immune phenotype. Evaluating the AAG signature was conducive to predicting patient response to immunotherapy and guiding more efficacious immunotherapy strategies.

Impact of different sequential triple oral combination therapies based selexipag on outcomes in pulmonary arterial hypertension.

BACKGROUND: While the GRIPHON study and others have confirmed the efficacy and safety of selexipag with single, dual, and initial triple combination therapy for patients with pulmonary arterial hypertension (PAH), multicenters studies concerning diverse triple oral combination therapies based on selexipag are limited. HYPOTHESIS: This study was conducted to evaluate the effects of various sequential triple oral combination therapies on PAH outcomes. METHODS: A retrospective study was carried out involving 192 patients from 10 centers, who were receiving sequential triple oral combination therapy consisting of an endothelin receptor antagonist (ERA), a phosphodiesterase 5 inhibitor (PDE5i)/riociguat and selexipag. Clinical parameters, event-free survival, and all-cause survival were assessed and analyzed at baseline and posttreatment. RESULTS: Among the 192 patients, 37 were treated with ERA + riociguat + selexipag, and 155 patients received ERA + PDE5i + selexipag. Both sequential triple oral combination therapies improved the World Health Organization functional class and raised the count of low-risk parameters. As a result of the larger patients' population in the ERA + PDE5i + selexipag group, these individuals exhibited significant increases in 6-minute walking distance (6MWD), pulmonary arterial systolic pressure, pulmonary arterial pressure, right ventricle, and eccentricity index, and significant decreases in N-terminal probrain natriuretic peptide after 6 months of treatment. Nevertheless, both sequential triple oral combination therapy groups demonstrated similar shifts in these clinical parameters between baseline and 6 months. Baseline 6MWD and mean pulmonary arterial pressure were independent predictors of survival in patients undergoing ERA + PDE5i + selexipag therapy. Importantly, no significant differences were found in 6-month event-free survival and all-cause survival between two groups. CONCLUSIONS: Different oral sequential triple combination therapies based on selexipag could comparably improve outcomes in patients with PAH.

The toxicity response of the electrochemical signal of the cell to the drug metabolized by the S9 system.

The electrochemical detection method of cytotoxicity using intracellular purines as biomarkers has shown great potential for in vitro drug toxicity evaluation. However, no electrochemical detection system based on an in vitro drug metabolism mechanism has been devised. In this paper, electrochemical voltammetry was used to investigate the effect of the S9 system on the electrochemical behavior of HepG2 cells, and benzo[a]pyrene, fluoranthene, and pyrene were employed to investigate the sensitivity of electrochemical signals of cells to the cytotoxicity of drugs metabolized by the S9 system. The results showed that, within 8 h of exposure to the S9 system, the electrochemical signal of HepG2 cells at 0.7 V did not alter noticeably. The levels of xanthine, guanine, hypoxanthine, and adenine in the cells were not significantly altered. Compared with the absence of S9 system metabolism, benzo[a]pyrene and fluoranthene processed by the S9 system decreased the electrochemical signal of the cells in a dose-dependent manner, while pyrene did not change it appreciably. HPLC also revealed that benzo[a]pyrene and fluoranthene metabolized by the S9 system decreased the intracellular purine levels, whereas pyrene had no effect on them before and after S9 system metabolism. The cytotoxicity results of the three drugs examined by electrochemical voltammetry and MTT assay showed a strong correlation and good agreement. The S9 system had no effect on the intracellular purine levels or the electrochemical signal of cells. When the drug was metabolized by the S9 system, variations in cytotoxicity could be precisely detected by electrochemical voltammetry.

Enhanced sensitivity of temperature and magnetic field sensor based on FPIs with Vernier effect.

A kind of temperature and magnetic field sensor using Fabry-Perot interferometers (FPIs) and Vernier effect to enhance sensitivity is proposed. The sensor structure involves filling the FP air cavities with polydimethylsiloxane (PDMS) and magnetic fluid (MF) to create the PDMS and MF cavities for temperature and magnetic field detection, respectively. The two cavities are reflective structures, which are interconnected in series through a fiber-optic circulator. Experimental data demonstrates that the Vernier effect effectively enhances the sensor sensitivity. The average temperature sensitivity of the sensor is 26765 pm/°C within the range of 35∼39.5°C. The magnetic field intensity sensitivity is obtained to be -2245 pm/mT within the range of 3∼11 mT. The sensitivities of the temperature and magnetic field using the Vernier effect are about five times larger than those of the corresponding single FP cavity counterparts.

Prevalence and influencing factors of PTSD symptoms among healthcare workers: A multicenter cross-sectional study during the surge period of the COVID-19 pandemic since December 2022 in the Chinese mainland.

BACKGROUND: China has experienced a surge period of COVID-19 pandemic since December 2022. Healthcare workers (HCWs) were exposed to huge workload under high risk of being infected, and significant levels of trauma, which might cause Post-traumatic Stress Disorders (PTSD) symptoms in HCWs. OBJECTIVES: To identify the prevalence of PTSD symptoms among HCWs in the Chinese mainland during the surge period of the COVID-19 pandemic; to explore their psycho-social factors of PTSD symptoms. METHODS: A multicenter cross-sectional study was conducted among HCWs in Chinese mainland from January 5 to February 9, 2023, covering seven geographical regions. 6552 participants were recruited by convenience sampling. Data were collected on demographic characteristics, work-related factors, and psychological factors by online questionnaires. Univariate analysis and binary logistic regression were used to determine the influencing factors of PTSD symptoms. RESULTS: The prevalence of PTSD symptoms among HCWs was 37.49 %. A higher level of mindfulness, resilience, and perceived social support were protective factors. Female gender, nurses, higher educational attainment, married status, more working years, higher perceived risk of contracting COVID-19 due to work, and higher perceived work intensity were risk factors. CONCLUSION: High prevalence of PTSD symptoms among HCWs necessitates psychological interventions. Tailored interventions, designed by professional psychiatrists, should be tailored to address the stressors. A comprehensive approach, incorporating mindfulness, resilience-building, and perceived social support enhancement, is vital to bolster the mental well-being of HCWs exposed to traumatic events, thus mitigating the impact of PTSD effectively. Additionally, it is essential to provide support to HCWs with other potential risk factors.

HuangQi ChiFeng decoction maintains gut microbiota and bile acid homeostasis through FXR signaling to improve atherosclerosis.

Huangqi Chifeng Decoction (HQCFT), a traditional Chinese medicine preparation, has long been used to treat cardiovascular and cerebrovascular diseases. However, the mechanism of the beneficial effect of HQCFT on atherosclerosis remains to be explored. In this work, to investigate the effects of HQCFT on bile acid (BA) metabolism and the gut microbiome in atherosclerosis, ApoE-/- mice were fed a with high-fat diet for 16 weeks to establish the AS model. HQCFT(1.95 g kg-1 and 3.9 g kg-1 per day) was administered intragastrically for 8 weeks to investigate the regulatory effects of HQCFT on gut microbiota and bile acid metabolism and to inhibit the occurrence and development of AS induced by a high-fat diet. Histopathology, liver function and blood lipids were used to assess whether HQCFT can reduce plaque area, regulate lipid levels and alleviate liver steatosis in AS mice. In addition, 16S rDNA sequencing was used to screen the gut microbiota structure, and ultrahigh-performance liquid chromatography-tandem mass spectrometry (UPLC‒MS/MS) was used to determine the bile acid profile. The mRNA and protein expression levels of bile acid metabolism were detected by RT‒PCR and WB to find the potential correlation. Results: HQCFT can regulate gut microbiota disorders, which was achieved by increasing gut microbiota diversity and altering Proteobacteria, Desulfobacterota, Deferribacteres, Rodentibacter, Parasutterella, and Mucispirillum interference abundance to improve AS-induced gut microbiota. HQCFT can also adjust the content of bile acids (TCA, LCA, DCA, TDCA, TLCA, UDCA, etc.), regulate bile acid metabolism, relieve liver fat accumulation, and inhibit the process of AS. In addition, HQCFT can restore the abnormal metabolism of bile acid caused by AS by regulating the expression of farnesoid X receptor (FXR), liver X receptor α (LXRα), ABCA1, ABCG1 and CYP7A1. Conclusion: HQCFT may play a part in the prevention of atherosclerosis by inhibiting the FXR/LXRα axis, increasing the expression of CYP7A1 in the liver, and regulating the interaction between the gut microbiota and bile acid metabolism.

Legionella pneumophila exploits the endo-lysosomal network for phagosome biogenesis by co-opting SUMOylated Rab7.

L. pneumophila strains harboring wild-type rpsL such as Lp02rpsLWT cannot replicate in mouse bone marrow-derived macrophages (BMDMs) due to induction of extensive lysosome damage and apoptosis. The mechanism of this unique infection-induced cell death remains unknown. Using a genome-wide CRISPR/Cas9 screening, we identified Hmg20a and Nol9 as host factors important for restricting strain Lp02rpsLWT in BMDMs. Depletion of Hmg20a protects macrophages from infection-induced lysosomal damage and apoptosis, allowing productive bacterial replication. The restriction imposed by Hmg20a was mediated by repressing the expression of several endo-lysosomal proteins, including the small GTPase Rab7. We found that SUMOylated Rab7 is recruited to the bacterial phagosome via SulF, a Dot/Icm effector that harbors a SUMO-interacting motif (SIM). Moreover, overexpression of Rab7 rescues intracellular growth of strain Lp02rpsLWT in BMDMs. Our results establish that L. pneumophila exploits the lysosomal network for the biogenesis of its phagosome in BMDMs.