Photoinduced Single Electron Reduction of the 4-O-5 Linkage in Lignin Models for C-P Coupling Catalyzed by Bifunctional N-Heterocyclic Carbenes.

Catalytic activation of Caryl-O bonds is considered as a powerful strategy for the production of aromatics from lignin. However, due to the high reduction potentials of diaryl ether 4-O-5 linkage models, their single electron reduction remains a daunting challenge. This study presents the blue light-induced bifunctional N-heterocyclic carbene (NHC)-catalyzed one-electron reduction of diaryl ether 4-O-5 linkage models for the synthesis of trivalent phosphines. The H-bond between the newly devised bifunctional NHC and diaryl ethers is responsible for the success of the single electron transfer. Furthermore, this approach demonstrates selective one-electron reduction of unsymmetric diaryl ethers, oligomeric phenylene oxide, and lignin model.

[Soil Cadmium Prediction and Health Risk Assessment of an Oasis on the Eastern Edge of the Tarim Basin Based on Feature Optimization and Machine Learning].

Soil heavy metal pollution poses a serious threat to food security, human health, and soil ecosystems. Based on 644 soil samples collected from a typical oasis located at the eastern margin of the Tarim Basin, a series of models, namely, multiple linear regression （LR）, neural network （BP）, random forest （RF）, support vector machine （SVM）, and radial basis function （RBF）, were built to predict the soil heavy metal content. The optimal prediction result was obtained and utilized to analyze the spatial distribution features of heavy metal contamination and relevant health risks. The outcomes demonstrated that： ① The average Cd content in the study area was 0.14 mg·kg-1, which was 1.17 times the soil background value of Xinjiang, making it the primary factor of soil heavy metal contamination in the area. Additionally, the carcinogenicity risk coefficients of Cd for both adults and children were less than 10-4, indicating that there were no significant long-term health risks for humans in the area. ② The estimation accuracies of the five inversion models were compared, and the validation set of the RF model had an R2 value of 0.763 7, which was the highest among the five models. Additionally, the RMSE, MAE, and MBE of the RF model were the smallest among the five models. Therefore, the predicted values of the RF model were most consistent with the measured values of the soil Cd content. The predicted map of soil Cd distribution derived from the RF model coincided best with the interpolation map. ③ The RF model outperformed the other four models in predicting health risks associated with the soil Cd element for both adults and children, resulting in better prediction results. Comparatively, the predicted values of the LR model in the validation set varied greatly, leading to unreliable results. It was demonstrated that the RF was the best model for predicting soil Cd content and evaluating health risks in the study area, considering its superior generalization capability and anti-overfitting ability.

AI-driven determination of active compounds and investigation of multi-pharmacological effects of Chrysanthemi Flos.

BACKGROUND: Chrysanthemi Flos as a medicine food homology species is widely used in the prevention and treatment of diseases, whereas comprehensive research of its active compounds related to multi-pharmacological effects remains limited. This study aimed to systematically explore the active compounds through artificial intelligence-based target prediction and activity evaluation. METHODS: The information on compounds in Chrysanthemi Flos was obtained from six cultivars containing Gongju, Chuju, Huaiju, Boju, Hangbaiju, and Fubaiju, using UPLC-Q-TOF/MS. The main differential metabolites in six cultivars were also screened through the PLS-DA model. Then the potential targets of differential compounds were predicted via the DrugBAN model. Enrichment and topological analysis of compound-target networks were performed to identify key pharmaceutical compounds. Subsequently, the pharmacological effects of predictively active compounds were confirmed in vitro. Based on the active compounds, the pharmacological activities of Chrysanthemi Flos from the six origins were also investigated and compared for the further evaluation of medicinal quality. RESULTS: A total of 155 secondary metabolites were obtained from Chrysanthemi Flos. Among them, 26 differential components were screened, and 9 key pharmacological compounds with 1141 targets were identified. Enrichment analysis indicated the main pharmacological effects of Chrysanthemi Flos related to inflammation, oxidative stress, and lipid metabolism. In addition, 9 key pharmaceutical compounds were evaluated in vitro experiments, indicating the significant therapeutic effect in regulating inflammation, oxidative stress, and lipid metabolism. CONCLUSION: This study successfully identified 9 key pharmaceutical compounds in Chrysanthemi Flos and predicted the pharmacodynamic advantages of six origins. The findings would provide improved guidance for the discovery of active constituents and the assessment of pharmacodynamic advantages of different geographical origins.

Comparison of clinical and echocardiographic outcomes between mini-thoracotomy transatrial LuX-Valve transcatheter and surgical tricuspid valve replacement.

Background and aims: Transcatheter tricuspid valve replacement (TTVR) has recently emerged as a novel therapeutic approach for managing severe tricuspid regurgitation (TR). However, surgical tricuspid valve replacement (STVR) continues to be the predominant treatment modality. There are limited comparative data on both procedures. This study aimed to compare clinical and echocardiographic outcomes between patients who underwent mini-thoracotomy transatrial LuX-Valve TTVR and those who underwent STVR. Methods: This study prospectively collected patients with severe TR who underwent TTVR (n = 29) or isolated STVR (n = 59) at Wuhan Union Hospital from 2019 to 2022. All TTVR patients received the LuX-Valve via a mini-thoracotomy and transatrial approach. The clinical and echocardiographic outcomes were compared at 30-day and one-year follow-ups. Results: At baseline, patients with LuX-Valve TTVR had higher surgical risk scores and a greater proportion of right ventricular dysfunction compared with STVR. In the early postoperative period, the STVR group had a greater decrease in right ventricular function. Hospital length of stay (LOS), intensive care unit LOS, total procedure time, and tracheal intubation time were shorter in the TTVR than in the STVR group. The incidence of postoperative paravalvular leaks was higher among patients who underwent TTVR. Compared to the STVR group, the pacemaker implantation rate was lower in the TTVR group. During follow-up, the peak tricuspid valve velocity and mean gradient in the TTVR group were consistently lower than those in the STVR group. There was similar mortality between TTVR and STVR at 30-day and one-year follow-ups. Conclusions: The mini-thoracotomy transatria LuX-Valve TTVR has a higher incidence of paravalvular leaks and a lower rate of pacemaker implantation than STVR, with similar 30-day and one-year mortality rates. In some respects, mini-thoracotomy transatrial LuX-Valve TTVR may be a feasible and safe treatment option for specific populations, or it could potentially serve as an alternative therapy to supplement conventional STVR. Further follow-up is required to assess differences in long-term clinical outcomes and valve durability.

Trideuteromethylthiolation through Reaction of Arynes, S-Methyl-d3 Sulfonothioate with Sulfonamides or Amides: Access to Trideuteromethylated Sulfilimines.

A direct and practical three-component tandem reaction of arynes, S-methyl-d3 sulfonothioate with sulfonamides or amides is developed. The reaction is highly efficient and chemoselective, which allows mild synthesis of trideuteromethylated sulfilimines with broad substrate scope and good functional group compatibility, giving the products in good to excellent yields with 92%-99% deuterium incorporation. Mechanism studies disclosed sulfenamide that generated in situ is the key intermediate for the reaction. This protocol provides potential method for introduction of -SCD3 moiety for deuteration of marked drugs and drug candidates containing sulfilimine skeleton.

Gut microbiota modulating intestinal stem cell differentiation.

Proliferation and differentiation of intestinal stem cell (ISC) to replace damaged gut mucosal epithelial cells in inflammatory states is a critical step in ameliorating gut inflammation. However, when this disordered proliferation continues, it induces the ISC to enter a cancerous state. The gut microbiota on the free surface of the gut mucosal barrier is able to interact with ISC on a sustained basis. Microbiota metabolites are able to regulate the proliferation of gut stem and progenitor cells through transcription factors, while in steady state, differentiated colonocytes are able to break down such metabolites, thereby protecting stem cells at the gut crypt. In the future, the gut flora and its metabolites mediating the regulation of ISC differentiation will be a potential treatment for enteropathies.

Antibacterial activity and mechanism of chelerythrine against Streptococcus agalactiae.

Streptococcus agalactiae (S.agalactiae), also known as group B Streptococcus (GBS), is a highly infectious pathogen. Prolonged antibiotic usage leads to significant issues of antibiotic residue and resistance. Chelerythrine (CHE) is a naturally occurring benzophenidine alkaloid and chelerythrine chloride (CHEC) is its hydrochloride form with diverse biological and pharmacological activities. However, the antibacterial mechanism of CHEC against GBS remains unclear. Thus, this study aims to investigate the in vitro antibacterial activity of CHEC on GBS and elucidate its underlying mechanism. The antibacterial effect of CHEC on GBS was assessed using inhibitory zone, minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC) assays, as well as by constructing a time-kill curve. The antibacterial mechanism of CHEC was investigated through techniques such as scanning electron microscopy (SEM) and transmission electron microscopy (TEM), measurement of alkaline phosphatase (AKP) activity, determination of Na+ K+, Ca2+ Mg2+-adenosine triphosphate (ATP) activity, observation of membrane permeability, and analysis of intracellular reactive oxygen species (ROS) and mRNA expression levels of key virulence genes. The results demonstrated that the inhibition zone diameters of CHEC against GBS were 14.32 mm, 12.67 mm, and 10.76 mm at concentrations of 2 mg/mL, 1 mg/mL, and 0.5 mg/mL, respectively. The MIC and MBC values were determined as 256 µg/mL and 512 µg/mL correspondingly. In the time-kill curve, 8 × MIC, 4 × MIC and 2 × MIC CHEC could completely kill GBS within 24 h. SEM and TEM analyses revealed significant morphological alterations in GBS cells treated with CHEC including shrinkage, collapse, and leakage of cellular fluids. Furthermore, the antibacterial mechanism underlying CHEC's efficacy against GBS was attributed to its disruption of cell wall integrity as well as membrane permeability resulting in extracellular release of intracellular ATP, AKP, Na+ K+, Ca2+ Mg2+. Additionally CHEC could increase the ROS production leading to oxidative damage and downregulating mRNA expression levels of key virulence genes in GBS cells. In conclusion, CHEC holds potential as an antimicrobial agent against GBS and further investigations are necessary to elucidate additional molecular mechanisms.

Multi-Source Feature-Fusion Method for the Seismic Data of Cultural Relics Based on Deep Learning.

The museum system is exposed to a high risk of seismic hazards. However, it is difficult to carry out seismic hazard prevention to protect cultural relics in collections due to the lack of real data and diverse types of seismic hazards. To address this problem, we developed a deep-learning-based multi-source feature-fusion method to assess the data on seismic damage caused by collected cultural relics. Firstly, a multi-source data-processing strategy was developed according to the needs of seismic impact analysis of the cultural relics in the collection, and a seismic event-ontology model of cultural relics was constructed. Additionally, a seismic damage data-classification acquisition method and empirical calculation model were designed. Secondly, we proposed a deep learning-based multi-source feature-fusion matching method for cultural relics. By constructing a damage state assessment model of cultural relics using superpixel map convolutional fusion and an automatic data-matching model, the quality and processing efficiency of seismic damage data of the cultural relics in the collection were improved. Finally, we formed a dataset oriented to the seismic damage risk analysis of the cultural relics in the collection. The experimental results show that the accuracy of this method reaches 93.6%, and the accuracy of cultural relics label matching is as high as 82.6% compared with many kinds of earthquake damage state assessment models. This method can provide more accurate and efficient data support, along with a scientific basis for subsequent research on the impact analysis of seismic damage to cultural relics in collections.

A counter-gravity casting system for in situ high-speed synchrotron x-ray imaging characterization.

Counter-gravity casting (CGC) aims to eliminate turbulent melt flow and defect formation during filling and subsequent solidification by pushing high-temperature melt into the mold cavity against gravity with regulated pressure. However, limited by the opaqueness of molten metals and the complexity of the CGC apparatus, it is extremely difficult to directly quantify the high-velocity mold filling and pressurized solidification in real-time. Here, we report the design and characterization of a CGC system capable of in situ monitoring of mold filling and subsequent solidification processes in the synchrotron beamlines by deploying a high-energy, high-speed synchrotron x-ray imaging technique. The high-velocity melt flow and dendrite growth during pressurized solidification have been quantified for systematical process parameter analysis by investigating time-resolved x-ray images of an exemplary Al-Cu alloy. The high-speed imaging results demonstrate that the in situ CGC system provides a useful way to better understand the fundamentals of mold filling, pressurized solidification, and experimental inputs for high-fidelity modeling in scientific and industrial applications.

Engineering cyanobacteria as a new platform for producing taxol precursors directly from carbon dioxide.

Taxol serves as an efficient natural anticancer agent with extensive applications in the treatment of diverse malignancies. Although advances in synthetic biology have enabled the de novo synthesis of taxol precursors in various microbial chassis, the total biosynthesis of taxol remains challengable owing to the restricted oxidation efficiency in heterotrophic microbes. Here, we engineered Synechocystis sp. PCC 6803 with modular metabolic pathways consisting of the methylerythritol phosphate pathway enzymes and taxol biosynthetic enzymes for production of taxadiene-5α-ol (T5α-ol), the key oxygenated intermediate of taxol. The best strain DIGT-P560 produced up to 17.43 mg/L of oxygenated taxanes and 4.32 mg/L of T5α-ol. Moreover, transcriptomic analysis of DIGT-P560 revealed that establishing a oxygenated taxane flux may enhance photosynthetic electron transfer efficiency and central metabolism in the engineered strain to ameliorate the metabolic disturbances triggered by the incorporation of exogenous genes. This is the first demonstration of photosynthetic production of taxadiene-5α-ol from CO2 in cyanobacteria, highlighting the broad prospects of engineered cyanobacteria as bio-solar cell factories for valuable terpenoids production and expanding the ideas for further rational engineering and optimization.

Reconstitution of the Multiple Myeloma Microenvironment Following Lymphodepletion with BCMA CAR-T Therapy.

PURPOSE: To investigate the remodeling of multiple myeloma (MM) microenvironment after BCMA-targeted chimeric antigen receptor T cell (CAR-T) therapy. EXPERIMENTAL DESIGN: We performed single-cell RNA sequencing (scRNA-seq) on paired bone marrow specimens (n = 14) from 7 MM patients before (i.e., baseline, 'day -4') and after (i.e., 'day 28') post-lymphodepleted BCMA CAR-T therapy. RESULTS: Our analysis revealed heterogeneity in gene expression profiles among MM cells, even those harboring the same cytogenetic abnormalities. The best overall responses (BORs) of patients over the 15-month follow-up are positively correlated with the abundance and targeted cytotoxic activity of CD8+ effector CAR-T cells on day 28 after CAR-T cell infusion. Additionally, favorable responses are associated with attenuated immunosuppression mediated by regulatory T cells (Tregs), enhanced CD8+ effector T cell cytotoxic activity, and elevated type 1 conventional dendritic cell (cDC1) antigen presentation ability. DC re-clustering inferred intramedullary-originated cDC3s with extramedullary migration. Cell-cell communication network analysis indicated BCMA CAR-T therapy mitigates BAFF/GALECTIN/MK pathway-mediated immunosuppression and activates MIF pathway-mediated anti-MM immunity. CONCLUSIONS: Our study sheds light on MM microenvironment dynamics after BCMA CAR-T therapy, offering clues for predicting treatment responsivity.

Mechanism and therapeutic potential of traditional Chinese medicine extracts in sepsis.

Sepsis is a complex syndrome characterized by multi-organ dysfunction, due to the presence of harmful microorganisms in blood which could cause mortality. Complications associated with sepsis involve multiple organ dysfunction. The pathogenesis of sepsis remains intricate, with limited treatment options and high mortality rates. Traditional Chinese medicine (TCM) has consistently demonstrated to have a potential on various disease management. Its complements include reduction of oxidative stress, inhibiting inflammatory pathways, regulating immune responses, and improving microcirculation. Traditional Chinese medicine can mitigate or even treat sepsis in a human system. This review examines progress on the use of TCM extracts for treating sepsis through different pharmacological action and its mechanisms. The potential targets of TCM extracts and active ingredients for the treatment of sepsis and its complications have been elucidated through molecular biology research, network pharmacology prediction, molecular docking analysis, and visualization analysis. Our aim is to provide a theoretical basis and empirical support for utilizing TCM in the treatment of sepsis and its complications while also serving as a reference for future research and development of sepsis drugs.

CRISPR/Cas9-mediated Nap knockout affects female reproduction and egg shape in Bombyx mori.

Insect reproductive capacity can affect effective pest control and infertility studies and has become an important focus in recent molecular genetic research. Nucleosome assembly protein (Nap) is highly conserved across multiple species and is involved in forming the sperm nucleus in many species. We used clustered regularly interspaced palindromic repeats/Cas9 technology to knockout BmNap in Bombyx mori and observed that the mutations caused female infertility, whereas male fertility was not affected. BmNap mutants grew and mated normally; however, female mutants laid smaller eggs that could not be fertilised and did not hatch. In addition, female sterility produced by the mutation could be inherited stably via male mutants; therefore, Nap could be used as a potential target for lepidopteran pest control through population regulation. In the current study, we elucidated a new function of BmNap, increased the understanding of the oogenesis regulation network in Lepidoptera and promoted the development of insect sterility technologies.

The Lipid-Metabolism-Associated Anti-Obesity Properties of Rapeseed Diacylglycerol Oil.

To investigate the effects of rapeseed diacylglycerol oil (RDG) intake on lipid accumulation and metabolism in C57BL/6J mice, obese mice were fed a high-fat diet in which 45% of the total energy content came from RDG (RDGM group) or rapeseed triacylglycerol oil (RTGM group). This diet intervention was conducted for 12 weeks following the establishment of the obese mouse model. By the end of the experiment, the serum glucose levels of the mice in the RTGM and RDGM groups were 13.0 ± 1.3 mmol/L and 9.7 ± 1.5 mmol/L, respectively. Meanwhile, the serum triglyceride level in the RDGM group was 26.3% lower than that in the RTGM group. The weight-loss effect in the RDGM group was accompanied by a significant decrease in the white adipose tissue (WAT) index. The RDG intervention did not significantly change the antioxidant and anti-inflammatory properties of the rapeseed oil in vivo. The RDG diet improved the liver lipid metabolism abnormalities induced by a high-fat diet, leading to decreased liver damage index values (AST and ALT). Additionally, compared to that in the RTGM group, the expression of the adipogenic genes PPAR-γ and DGAT decreased in both the liver and intestine by 21.7% and 16.7% and by 38.7% and 47.2%, respectively, in the RDGM group. Further, most lipolytic genes in BAT showed no significant change after the RDG intervention. This implies that RDG regulates lipid metabolism by altering the expression of adipogenic genes in the liver, intestine, and adipose tissue, thereby reducing the accumulation of WAT. Furthermore, the RDG diet enhanced gut flora diversity, increasing the relative levels of unclassified Muribaculaceae and decreasing the levels of Dubosiella and Faecalibaculum in the mouse gut, potentially accelerating lipid metabolism. Thus, a three-month RDG diet intervention in obese mice exhibited benefits in regulating the somatotype, serum obesity-related indices, gut flora structure, and lipid metabolism in the adipose tissue, liver, and intestine.

Current syphilis infection in virally suppressed people living with HIV: a cross-sectional study in eastern China.

Background: Antiretroviral therapy (ART) has been shown to reduce human immunodeficiency virus (HIV) viral replication and ultimately achieve viral suppression and eliminate HIV transmission. However, little is known about the impact of viral suppression on high-risk behaviors and sexually transmitted infections (STIs). Objective: This study aimed to assess the rates of current syphilis infection in virally suppressed people living with HIV (PLWH) and whether with the duration of ART can reduce the current syphilis infection in eastern China. Method: We conducted a cross-sectional survey of PLWH in Zhejiang Province, China, in 2022. PLWH who were on ART >6 months and were virally suppressed (viral load <50 copies/mL) were included in the study. Data were collected from the National Epidemiological Database of Zhejiang Province and all participants were tested for viral load and current syphilis. Multivariable logistic regression was used to identify risk factors associated with current syphilis infection. Result: A total of 30,744 participants were included in the analysis. 82.7% of participants were male, the mean age was 44.9 ± 14.1 years, 84.9% had received ART in a hospital setting, the mean time on ART was 5.9 ± 3.1 years and 5.6% of participants were infected with current syphilis. Multivariable logistic regression showed that being male [adjusted odds ratio (aOR): 2.12, 95% confidence interval (CI): 1.69-2.66], high level of education (aOR: 1.23, 95% CI: 1.02-1.49), homosexual route of HIV infection (aOR: 1.80, 95% CI: 1.60-2.04), non-local registered residence (aOR: 1.29, 95% CI: 1.11-1.51), had history of STIs before HIV diagnosis (aOR: 1.95, 95 % CI: 1.75-2.18) and treatment provided by a municipal hospital (aOR: 2.16, 95% CI: 1.31-3.55) were associated with increased risk of current syphilis infection. Being married (aOR: 0.67, 95% CI: 0.58-0.76) was associated with a decreased risk of current syphilis infection. Conclusion: Our findings revealed a high rate of current syphilis infection among virally suppressed PLWH in eastern China. Duration of ART did not reduce the prevalence of current syphilis infection. Targeted interventions to reduce current syphilis infection should be prioritized for subgroups at higher risk.

Risk Factors of Sarcopenia in COPD Patients: A Meta-Analysis.

Objective: Sarcopenia is a common complication of COPD associated with an age-related reduction in skeletal muscle mass associated with decreased muscle strength and / or reduced mobility. The incidence of sarcopenia in patients with COPD is twice that of non-COPD patients and is associated with poor prognosis, this study aimed to investigate the influencing factors of sarcopenia in COPD patients. Methods: Selected studies from PubMed, Embase, Web of Science, Cochrane Library, Wanfang, Wanfang, CNKI, CBM, and Wanfang databases as of November 12023. Patients aged 18 were selected; data were then independently extracted by two reviewers using a standard data collection form. Results: In total, 17 articles reporting on 5408 patients were included. Age (OR = 1.083; 95% CI, 1.024-1.145), ALB (OR = 0.752; 95% CI, 0.724-0.780), BMI(OR = 0.701; 95% CI, 0.586-0.838), smoking (OR = 1.859; 95% CI, 1.037-3.334), diabetes (OR = 1.361; 95% CI, 1.095-1.692), qi deficiency (OR = 9.883; 95% CI, 2.052, 47.593), GOLD C (OR =2.232; 95% CI, 1.866, 2.670) and GOLD D (OR = 2.195; 95% CI, 1.826-2.637) were factors affecting muscle loss in COPD patients. Conclusion: Sarcopenia is more prevalent in patients with COPD. Age, body mass index, smoking, diabetes mellitus, qi deficiency, ALB, and GOLD grade were the contributing factors for sarcopenia in patients with chronic obstructive pulmonary disease. In the future, medical staff should not only pay attention to the early screening of sarcopenia in high-risk groups, but also provide relevant prevention information.

Identification and validation of basement membrane-related genes predicting prognosis and immune infiltration associated with bladder cancer.

Bladder cancer (BC) is fatal during muscle invasion and treatment progress is limited. In this study, we aimed to construct and validate basement membrane (BM)-associated gene prognosis to predict BC progression and tumor immune infiltration correlation. We choreographed BM-related genes in the Cancer Genome Atlas (TCGA) database using COX regression and least absolute shrinkage and selection operator (LASSO) analysis, and the predictive value of BM-related genes was further validated by the GSE32548, GSE129845, and immunohistochemistry staining. All analyses were performed with R-version 4.2.2, and its appropriate packages. Three genes were identified to construct a gene signature to predictive of BC prognosis. We divided the TCGA database into 2 groups, and patients in the high-risk group had worse overall survival (OS) than those in the low-risk group. In GSE32548, we confirmed that patients in the high-risk group had a poorer prognosis compared to those in the low-risk group in terms of OS. Immunohistochemical staining of EPEMP1, GPC2, and ITGA3 showed significantly higher expression at the protein level in BC tissues than in normal tissues. The Spearman analysis showed risk score was positively correlated with B cell naïve, Macrophages M2, and Mast cells resting. stromal score, immune score, and ESTIMATE scores were significantly higher in the high-risk group. drugs sensitivity analysis showed IC50 of Cisplatin, Gemcitabine, and Methotrexate in the high-risk group was significantly higher than that in the low-risk group. We identified 3 prognostic genes from a novel perspective of BM genes as effective risk stratification tools for BC patients.

Depressive symptoms and its multifaceted associated factors among young men who have sex with men facing the dual threats of COVID-19 and mpox in China.

INTRODUCTION: The COVID-19 pandemic has significantly impacted the mental health of human beings since 2020, especially the young people and the pre-existing marginalized groups such as men who have sex with men (MSM). During the COVID-19 pandemic, the multi-country outbreak of mpox in 2022 additionally posed a significant stress on the most-affected communities (i.e., MSM). This study investigated the level of depressive symptoms and its multifaceted associated factors among Chinese young men who have sex with men (YMSM) in this unique period. METHODS: In September 2022, a large-scale cross-sectional survey was conducted among YMSM aged 18-29 years across six representative provinces in China. Hierarchical regression analysis was performed to test the various types of associated factors of depressive symptoms. RESULTS: Among the 2493 participants, 65.6 % (n = 1638) reported mild to severe depressive symptoms. The hierarchical regression analysis identified that depressive symptoms was significantly positively associated with unemployment, having substance use in the past 6 months, a higher level of MSM self-stigma, incompletion of COVID-19 vaccination, greater mpox risk perception, and presence of mpox related-like symptoms. LIMITATIONS: This study used the facility-based sampling method to recruit the participants, which may lead to selection bias. CONCLUSIONS: Chinese YMSM faced significant mental health challenges during the concurrent epidemics of COVID-19 and mpox, which was associated with their socio-economic status, risk behaviors, stigma, and multiple diseases-related variables. Proactive measures may hold promise as effective strategies for mitigating mental distress among marginalized groups during public health crises.