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Abstract Objectives To explore the role of nodule-pleural relationship, including nodule with pleural tail sign (PTS), nodule with pleural contact and nodule with pleural unrelated in CT-guided percutaneous transthoracic needle biopsy (PTNB)-induced pneumothorax, and whether employing different puncture routes has an impact on the incidence of pneumothorax in PTNB of nodules with PTS. Methods Between April 1, 2019, to June 30, 2021, 775 consecutive PTNB procedures of pulmonary nodules in the Peking University Cancer Hospital were retrospectively reviewed. The univariate and multivariate regression analysis were used to identify the risk factors for pneumothorax in PTNB. Results The nodule with pleural contact group has a lower incidence of pneumothorax than the nodule with PTS group (p = 0.001) and the nodule with pleural unrelated group (p = 0.002). It was observed that a higher incidence of pneumothorax caused by crossing PTS compared with no crossing PTS (p

Abstract Leukemia is a prevalent and widespread blood disease, and its early diagnosis is crucial for effective patient treatment. Diagnosing leukemia types heavily relies on pathologists’ morphological examination of blood cell images. However, this process is tedious and time-consuming, and the diagnostic results are subjective, leading to potential misdiagnosis and underdiagnosis. This paper proposes a blood cell image classification method that combines MAE with an enhanced Vision Transformer to tackle these challenges. Initially, pre-training occurs on two datasets, TMAMD and Red4, using the MAE self-supervised learning algorithm. Subsequently, the pre-training weights are transferred to our improved model.This paper introduces feature fusion of the outputs from each layer of the Transformer encoder to maximize the utilization of features extracted from lower layers, such as color, contour, and texture of blood cells, along with deeper semantic features. Furthermore, the dynamic margins for the subcenter Arcface Loss function are employed to enhance the model’s fine-grained feature representation by achieving inter-class dispersion and intra-class aggregation. Models trained using our method achieved state-of-the-art results on both the TMAMD dataset and Red4 dataset, with classification accuracies of 93.51% and 81.41%, respectively. This achievement is expected to be a valuable reference for physicians in their clinical diagnoses.

Abstract Background S100β is a biomarker of astroglial damage, the level of which is significantly increased following brain injury. However, the characteristics of S100β and its association with prognosis in patients with acute ischemic stroke following intravenous thrombolysis (IVT) remain unclear. Methods Patients in this multicenter prospective cohort study were prospectively and consecutively recruited from 16 centers. Serum S100β levels were measured 24 h after IVT. National Institutes of Health Stroke Scale (NIHSS) and hemorrhagic transformation (HT) were measured simultaneously. NIHSS at 7 days after stroke, final infarct volume, and modified Rankin Scale (mRS) scores at 90 days were also collected. An mRS score ≥ 2 at 90 days was defined as an unfavorable outcome. Results A total of 1072 patients were included in the analysis. The highest S100β levels (> 0.20 ng/mL) correlated independently with HT and higher NIHSS at 24 h, higher NIHSS at 7 days, larger final infarct volume, and unfavorable outcome at 3 months. The patients were divided into two groups based on dominant and non-dominant stroke hemispheres. The highest S100β level was similarly associated with the infarct volume in patients with stroke in either hemisphere (dominant: β 36.853, 95% confidence interval (CI) 22.659–51.048, P

Abstract Erythropoietin (EPO), expressed in red blood progenitor cells, primarily regulates erythropoiesis by binding to its receptor. Besides anemia, recent studies have identified new therapeutic indications for EPO that are not connected to red blood cell formation. Elevated EPO levels harm bone homeostasis in adult organisms and are associated with increased osteoclast; however, the underlying molecular mechanisms remain unclear. This study demonstrated that EPO enhanced osteoclast differentiation and bone resorption in vitro. We showed that EPO promoted osteoclast formation by up-regulating PPARγ expression through activating the Jak2/ERK signaling pathway. Consistently, PPARγ antagonists rescued the hyperactivation of osteoclasts due to EPO, while PPARγ agonists reversed the EMP9-mediated decrease in osteoclast differentiation. Further, exposing female mice to EPO for two months led to a decrease in bone mass and increased osteoclast numbers. The present results suggested that EPO promotes osteoclastogenesis by regulating the Jak2/ERK/ PPARγ signaling pathway. From a clinical perspective, the risk of compromised bone health should be considered when using EPO to treat anemia in post-operative patients with intertrochanteric fractures of the femur, as it could significantly impact the patient’s recovery and quality of life.

Abstract Background The purpose of this network meta-analysis was to assess the impact of different protective ventilatory strategies on postoperative pulmonary complications (PPCs). Methods Several databases were searched for randomized controlled trials (RCTs) that were published before October 2023 in a network meta-analysis. We assessed the effect of different lung-protective ventilation strategies on the incidence of PPCs using Bayesian network meta-analysis. Results We included 58 studies (11610 patients) in this meta-analysis. The network meta-analysis showed that low tidal volumes (LTVs) combined with iPEEP and recruitment manoeuvres (RM) was associated with significantly lower incidence of PPCs [HTVs: OR = 0.38, 95%CrI (0.19, 0.75), LTVs: OR = 0.33, 95%CrI (0.12, 0.82)], postoperative atelectasis[HTVs: OR = 0.2, 95%CrI (0.08, 0.48), LTVs: OR = 0.47, 95%CrI (0.11, 0.93)], and pneumonia[HTVs: OR = 0.22, 95%CrI (0.09, 0.48), LTVs: OR = 0.27, 95%CrI (0.08,0.89)] than was High tidal volumes (HTVs) or LTVs. LTVs combined with medium-to-high PEEP and RM were associated with significantly lower incidence of postoperative atelectasis, and pneumonia. Conclusion LTVs combined with iPEEP and RM decreased the incidence of PPCs, postoperative atelectasis, and pneumonia in noncardiac surgery patients. Individual PEEP-guided ventilation was the optimal lung protection ventilation strategy. The quality of evidence is moderate. Trial registration PROSPERO identifier CRD42023399485.

Abstract Abnormal SUMOylation is implicated in non-alcoholic fatty liver disease (NAFLD) progression. Forkhead box protein A1 (FoxA1) has been shown to protect liver from steatosis, which was down-regulated in NAFLD. This study elucidated the role of FoxA1 deSUMOylation in NAFLD. NAFLD models were established in high-fat diet (HFD)-induced mice and palmitate acid (PAL)-treated hepatocytes. Hepatic steatosis was evaluated by biochemical and histological methods. Lipid droplet formation was determined by BODIPY and Oil red O staining. Target molecule levels were analyzed by RT-qPCR, Western blotting, and immunohistochemistry staining. SUMOylation of FoxA1 was determined by Ni-NTA pull-down assay and SUMOylation assay Ultra Kit. Protein interaction and ubiquitination were detected by Co-IP. Gene transcription was assessed by ChIP and dual luciferase reporter assays. Liver FoxA1 knockout mice developed severe liver steatosis, which could be ameliorated by sirtuin 6 (Sirt6) overexpression. Nutritional stresses reduced Sumo2/3-mediated FoxA1 SUMOylation at lysine residue K6, which promoted lipid droplet formation by repressing fatty acid β-oxidation. Moreover, Sirt6 was a target gene of FoxA1, and Sirt6 transcription activity was restrained by deSUMOylation of FoxA1 at site K6. Furthermore, nutritional stresses-induced deSUMOylation of FoxA1 promoted the ubiquitination and degradation of FoxA1 with assistance of murine double minute 2 (Mdm2). Finally, activating FoxA1 SUMOylation delayed the progression of NAFLD in mice. DeSUMOylation of FoxA1 at K6 promotes FoxA1 degradation and then inhibits Sirt6 transcription, thereby suppressing fatty acid β-oxidation and facilitating NAFLD development. Our findings suggest that FoxA1 SUMOylation activation might be a promising therapeutic strategy for NAFLD.

This is the third paper in the series Catalogue of fungi in China that aims to systematically and promptly publish Chinese fungal species. In this paper of the series, we focus on macrofungi from the southern border area of Xizang, a previously less concerned region. A total of 15 new species in six orders, 11 families, and 12 genera from Agaricomycetes, Basidiomycota are described. Both morphological and phylogenetic analyses support the identity of these new species and their taxonomic placements. In addition, one new combination Trechispora cryptomerioides is proposed. We hope that the third paper in the series Catalogue of fungi in China will draw more attention to reporting Chinese fungal diversity in the border areas of Xizang and other special geographic regions besides the aim of this series itself.

Traditional treatments against advanced non-small cell lung cancer (NSCLC) with high morbidity and mortality continue to be dissatisfactory. Given this situation, there is an urgent requirement for alternative modalities that provide lower invasiveness, superior clinical effectiveness, and minimal adverse effects. The combination of photodynamic therapy (PDT) and immunotherapy gradually become a promising approach for high-grade malignant NSCLC. Nevertheless, owing to the absence of precise drug delivery techniques as well as the hypoxic and immunosuppressive characteristics of the tumor microenvironment (TME), the efficacy of this combination therapy approach is less than ideal. In this study, we construct a novel nanoplatform that indocyanine green (ICG), a photosensitizer, loads into hollow manganese dioxide (MnO2) nanospheres (NPs) (ICG@MnO2), and then encapsulated in PD-L1 monoclonal antibodies (anti-PD-L1) reprogrammed exosomes (named ICG@MnO2@Exo-anti-PD-L1), to effectively modulate the TME to oppose NSCLC by the synergy of PDT and immunotherapy modalities. The ICG@MnO2@Exo-anti-PD-L1 NPs are precisely delivered to the tumor sites by targeting specially PD-L1 highly expressed cancer cells to controllably release anti-PD-L1 in the acidic TME, thereby activating T cell response. Subsequently, upon endocytic uptake by cancer cells, MnO2 catalyzes the conversion of H2O2 to O2, thereby alleviating tumor hypoxia. Meanwhile, ICG further utilizes O2 to produce singlet oxygen (1O2) to kill tumor cells under 808 nm near-infrared (NIR) irradiation. Furthermore, a high level of intratumoral H2O2 reduces MnO2 to Mn2+, which remodels the immune microenvironment by polarizing macrophages from M2 to M1, further driving T cells. Taken together, the current study suggests that the ICG@MnO2@Exo-anti-PD-L1 NPs could act as a novel drug delivery platform for achieving multimodal therapy in treating NSCLC.

Magnesium alloy is one of the most widely used lightweight structural materials, and the development of high strength-toughness magnesium alloy is an important research field at present and even in the future. The preparation process parameters of magnesium alloy directly affect the microstructure of the magnesium alloy, and then determine the properties of the magnesium alloy. The cooling rate has important effects on the microstructure and properties of the magnesium alloy, and is an important preparation process parameter that cannot be ignored. Both the cooling rate from liquid phase to solid phase and the cooling rate of the magnesium alloy after heat treatment will change the microstructure of the magnesium alloy. Furthermore, the properties of magnesium alloy will be affected. In this paper, the effects of cooling rate on the solidification behavior, the rheological behavior, the change of microstructure (the solid solution of alloying elements in matrix, the composition, size, distribution and morphology of second phase, the diffusion and segregation of alloying elements, the grain size, the formation and morphology of dendrite, etc.), and the effects of cooling rate of magnesium alloy after heat treatment on the microstructure and stress distribution are reviewed. The reasons for the divergence about the influence of cooling rate on the microstructure of magnesium alloy are analyzed in detail. The effects of cooling rate on the mechanical properties, corrosion resistance and oxidation resistance of magnesium alloy are also analyzed and discussed deeply. Finally, the new methods and approaches to study the effects of cooling rate on the microstructure and properties of magnesium alloy are prospected.

Abstract Autophagy is closely related to the occurrence and development of human malignancies; however, the detailed mechanisms underlying autophagy in cervical cancer require further investigation. Previously, we found that the ectopic expression of NCAPH, a regulatory subunit of condensed protein complexes, significantly enhanced the proliferation of tumor cells; however, the underlying mechanisms were unclear. Here, we revealed that NCAPH is a novel autophagy-associated protein in cervical cancer that promotes cell proliferation by inhibiting autophagosome formation and reducing autophagy, with no effect on the cell cycle, apoptosis, or aging. Tripartite motif-containing protein 21 (TRIM21) is well known to be involved in inflammation, autoimmunity and cancer, mainly via its E3 ubiquitin ligase activity. Mass spectrometry and immunoprecipitation assays showed that TRIM21 interacted with NCAPH and decreased the protein stability of NCAPH via ubiquitination at the K11 lysine residue. Structural domain mutation analysis revealed that TRIM21 combined with NCAPH through its PRY/SPRY and CC domains and accelerated the degradation of NCAPH through the RING domain. Furthermore, TRIM21 promoted autophagosome formation and reduced cell proliferation by inhibiting NCAPH expression and the downstream AKT/mTOR pathway in cervical cancer cells. Immunohistochemical staining revealed that the protein expression of TRIM21 was negatively correlated with that of NCAPH and positively correlated with that of beclin-1 in cervical cancer tissues. Therefore, we provide evidence for the role of the TRIM21-NCAPH axis in cervical cancer autophagy and proliferation and the involvement of the AKT/mTOR signaling pathway in this process. These results deepen our understanding of the carcinogenesis of cervical cancer, broaden the understanding of the molecular mechanisms of TRIM21 and NCAPH, and provide guidance for individualized treatment of cervical cancer in the future.

Inflammatory bowel diseases (IBD), comprising ulcerative colitis (UC) and Crohn's disease (CD), are complex chronic inflammatory intestinal conditions with a multifaceted pathology, influenced by immune dysregulation and genetic susceptibility. The challenges in understanding IBD mechanisms and implementing precision medicine include deciphering the contributions of individual immune and non-immune cell populations, pinpointing specific dysregulated genes and pathways, developing predictive models for treatment response, and advancing molecular technologies. Single-cell RNA sequencing (scRNA-seq) has emerged as a powerful tool to address these challenges, offering comprehensive transcriptome profiles of various cell types at the individual cell level in IBD patients, overcoming limitations of bulk RNA sequencing. Additionally, single-cell proteomics analysis, T-cell receptor repertoire analysis, and epigenetic profiling provide a comprehensive view of IBD pathogenesis and personalized therapy. This review summarizes significant advancements in single-cell sequencing technologies for enhancing our understanding of IBD, covering pathogenesis, diagnosis, treatment, and prognosis. Furthermore, we discuss the challenges that persist in the context of IBD research, including the need for longitudinal studies, integration of multiple single-cell and spatial transcriptomics technologies, and the potential of microbial single-cell RNA-seq to shed light on the role of the gut microbiome in IBD.

In this study, an ultra-high strength Mg-13Gd-4Y–0Zn-0.5Zr (wt.%) alloy with tensile yield strength (TYS) of 456 MPa and ultimate tensile strength (UTS) of 486 MPa was prepared by using different pre-heat parameters and subsequent final-heat treatment combined with backward extrusion (BE) deformation process. It was shown that the pre-heat teratment could significantly enhance the UTS and TYS of the secondary backward extruded (BEed) alloy compared with none treatment. The reason was that the pre-heat treatment promoted the particle stimulated nucleation (PSN) mechanism and continuous dynamic recrystallization (CDRX), significantly increasing the fraction of dynamic recrystallization (DRX). The strengthening of the secondary BEed alloy was attributed to the unique microstructure characteristics: (I) the fine DRXed grains pinned by dynamic precipitates, (II) the dense dynamic precipitation phases, (III) the effect of the fine-grain strengthening. However, the overly densely distributed second phase, which increased the local dislocation density due to the narrower spacing, made it difficult to prevent crack propagation and caused premature fracture of the alloy. In addition, the subsequent final-heat treatment also facilitated the precipitation of the second phases of the secondary BEed alloys and brought in the ultra-high mechanical properties.

Abstract Malus sieversii, commonly known as wild apples, represents a Tertiary relict plant species and serves as the progenitor of globally cultivated apple varieties. Unfortunately, wild apple populations are facing significant degradation in localized areas due to a myriad of factors. To gain a comprehensive understanding of the nutrient status and spatiotemporal variations of M. sieversii, green leaves were collected in May and July, and the fallen leaves were collected in October. The concentrations of leaf nitrogen (N), phosphorus (P), and potassium (K) were measured, and the stoichiometric ratios as well as nutrient resorption efficiencies were calculated. The study also explored the relative contributions of soil, topographic, and biotic factors to the variation in nutrient traits. The results indicate that as the growing period progressed, the concentrations of N and P in the leaves significantly decreased (P P > N. The resorption efficiencies were mainly regulated by nutrient concentrations in fallen leaves. A robust spatial dependence was observed in leaf nutrient concentrations during all periods (70.1–97.9% for structural variation), highlighting that structural variation, rather than random factors, dominated the spatial variation. Nutrient resorption efficiencies (NRE, PRE, and KRE) displayed moderate structural variation (30.2–66.8%). The spatial patterns of nutrient traits varied across growth periods, indicating they are influenced by multifactorial elements (in which, soil property showed the highest influence). In conclusion, wild apples manifested differentiated spatiotemporal variability and influencing factors across various leaf nutrient traits. These results provide crucial insights into the spatiotemporal patterns and influencing factors of leaf nutrient traits of M. sieversii at the permanent plot scale for the first time. This work is of great significance for the ecosystem restoration and sustainable management of degrading wild fruit forests.

Abstract Glioma is the most common malignant tumor in the central nervous system, and its unique pathogenesis often leads to poor treatment outcomes and prognosis. In 2021, the World Health Organization (WHO) divided gliomas into five categories based on their histological characteristics and molecular changes. Non-coding RNA is a type of RNA that does not encode proteins but can exert biological functions at the RNA level, and long non-coding RNA (lncRNA) is a type of non-coding RNA with a length exceeding 200 nt. It is controlled by various transcription factors and plays an indispensable role in the regulatory processes in various cells. Numerous studies have confirmed that the dysregulation of lncRNA is critical in the pathogenesis, progression, and malignancy of gliomas. Therefore, this article reviews the proliferation, apoptosis, invasion, migration, angiogenesis, immune regulation, glycolysis, stemness, and drug resistance changes caused by the dysregulation of lncRNA in gliomas, and summarizes their potential clinical significance in gliomas.

Abstract The characteristic features of the rheumatoid arthritis (RA) microenvironment are synovial inflammation and hyperplasia. Therefore, there is a growing interest in developing a suitable therapeutic strategy for RA that targets the synovial macrophages and fibroblast-like synoviocytes (FLSs). In this study, we used graphene oxide quantum dots (GOQDs) for loading anti-arthritic sinomenine hydrochloride (SIN). By combining with hyaluronic acid (HA)-inserted hybrid membrane (RFM), we successfully constructed a new nanodrug system named HA@RFM@GP@SIN NPs for target therapy of inflammatory articular lesions. Mechanistic studies showed that this nanomedicine system was effective against RA by facilitating the transition of M1 to M2 macrophages and inhibiting the abnormal proliferation of FLSs in vitro. In vivo therapeutic potential investigation demonstrated its effects on macrophage polarization and synovial hyperplasia, ultimately preventing cartilage destruction and bone erosion in the preclinical models of adjuvant-induced arthritis and collagen-induced arthritis in rats. Metabolomics indicated that the anti-arthritic effects of HA@RFM@GP@SIN NPs were mainly associated with the regulation of steroid hormone biosynthesis, ovarian steroidogenesis, tryptophan metabolism, and tyrosine metabolism. More notably, transcriptomic analyses revealed that HA@RFM@GP@SIN NPs suppressed the cell cycle pathway while inducing the cell apoptosis pathway. Furthermore, protein validation revealed that HA@RFM@GP@SIN NPs disrupted the excessive growth of RAFLS by interfering with the PI3K/Akt/SGK/FoxO signaling cascade, resulting in a decline in cyclin B1 expression and the arrest of the G2 phase. Additionally, considering the favorable biocompatibility and biosafety, these multifunctional nanoparticles offer a promising therapeutic approach for patients with RA. Graphical abstract

In this study, the effect of heat treatment on the microstructure and mechanical properties of 2209 duplex stainless steel fabricated by wire arc additive was analyzed. It was found that solution treatment at 1100°C for 2 hours and tempering at 300°C for 2 hours can effectively improve the grain inhomogeneity of 2209 duplex stainless steel, eliminate γ2 and harmful brittle phases, and take into account the mechanical properties and corrosion resistance. Compared with the original deposition state, the hardness and yield strength increased by 10% and 31.8% to 245.6 HV and 499.7 MPa, which meet the requirements of engineering propellers. Electron back-scattered diffraction studies showed that the grains became refined and austenite maintained //Z orientation after solution heat treatment. Many small-angle grain boundaries were present in both the original sample and the solid solution, but further tempering transformed the small-angle grain boundaries into large-angle grain boundaries.

Abstract Objective This study aims to elucidate the functional role of IQGAP1 phosphorylation modification mediated by the SOX4/MAPK1 regulatory axis in developing pancreatic cancer through phosphoproteomics analysis. Methods Proteomics and phosphoproteomics data of pancreatic cancer were obtained from the Clinical Proteomic Tumor Analysis Consortium (CPTAC) database. Differential analysis, kinase-substrate enrichment analysis (KSEA), and independent prognosis analysis were performed on these datasets. Subtype analysis of pancreatic cancer patients was conducted based on the expression of prognostic-related proteins, and the prognosis of different subtypes was evaluated through prognosis analysis. Differential analysis of proteins in different subtypes was performed to identify differential proteins in the high-risk subtype. Clinical correlation analysis was conducted based on the expression of prognostic-related proteins, pancreatic cancer typing results, and clinical characteristics in the pancreatic cancer proteomics dataset. Functional pathway enrichment analysis was performed using GSEA/GO/KEGG, and most module proteins correlated with pancreatic cancer were selected using WGCNA analysis. In cell experiments, pancreatic cancer cells were grouped, and the expression levels of SOX4, MAPK1, and the phosphorylation level of IQGAP1 were detected by RT-qPCR and Western blot experiments. The effect of SOX4 on MAPK1 promoter transcriptional activity was assessed using a dual-luciferase assay, and the enrichment of SOX4 on the MAPK1 promoter was examined using a ChIP assay. The proliferation, migration, and invasion functions of grouped pancreatic cancer cells were assessed using CCK-8, colony formation, and Transwell assays. In animal experiments, the impact of SOX4 on tumor growth and metastasis through the regulation of MAPK1-IQGAP1 phosphorylation modification was studied by constructing subcutaneous and orthotopic pancreatic cancer xenograft models, as well as a liver metastasis model in nude mice. Results Phosphoproteomics and proteomics data analysis revealed that the kinase MAPK1 may play an important role in pancreatic cancer progression by promoting IQGAP1 phosphorylation modification. Proteomics analysis classified pancreatic cancer patients into two subtypes, C1 and C2, where the high-risk C2 subtype was associated with poor prognosis, malignant tumor typing, and enriched tumor-related pathways. SOX4 may promote the occurrence of the high-risk C2 subtype of pancreatic cancer by regulating MAPK1-IQGAP1 phosphorylation modification. In vitro cell experiments confirmed that SOX4 promoted IQGAP1 phosphorylation modification by activating MAPK1 transcription while silencing SOX4 inhibited the proliferation, migration, and invasion of pancreatic cancer cells by reducing the phosphorylation level of MAPK1-IQGAP1. In vivo, animal experiments further confirmed that silencing SOX4 suppressed the growth and metastasis of pancreatic cancer by reducing the phosphorylation level of MAPK1-IQGAP1. Conclusion The findings of this study suggest that SOX4 promotes the phosphorylation modification of IQGAP1 by activating MAPK1 transcription, thereby facilitating the growth and metastasis of pancreatic cancer.

Abstract Metabolic reprogramming has become increasingly important in tumor biology research. The glucose metabolic pathway is a major energy source and is often dysregulated in breast cancer. DAB2IP is widely reported to be a tumor suppressor that acts as a scaffold protein to suppress tumor malignancy in breast cancer. Interestingly, DAB2IP has also been found to be a potential regulator of glucose uptake; however, the exact mechanism remains unclear. In this study, we found that DAB2IP inhibited glucose uptake under hypoxia conditions in breast cancer cells by suppressing HIF-1α signals. Mechanically, DAB2IP interacted with the E3 ubiquitin ligase STUB1 via its PER domain, thus triggering STUB1 mediated HIF-1α ubiquitylation and degradation, and inhibit glucose metabolism and tumor progression. Deleting the PER domain abrogated the DAB2IP-related inhibitory effects on glucose uptake, intracellular ATP production, and lactic acid production in breast cancer cells. These findings elucidate the biological roles of DAB2IP in cancer-related glucose metabolism as well as a novel mechanism by which STUB1-driven HIF-1α ubiquitylated degradation is regulated in breast cancer.

Abstract Purpose As future physicians, medical students have experienced tremendous pressure during the ongoing COVID-19 pandemic, which is associated with a high risk of depression and anxiety. We aimed to investigate an overview of the prevalence of anxiety and depression among medical students in various countries during the global COVID-19 pandemic, and discuss associated stressors. Methods We systematically searched CINAHL, EMBASE, MEDLINE, PubMed, and Web of Science for relevant articles from December 1, 2019 to March 15, 2023. We performed meta-analysis using a random-effects model with REML method to calculate the pooled prevalence of anxiety and depression. Begg’s and Egger’s tests were used to identify the potential risk of publication bias. Meta-regression was used to explore potential sources of heterogeneity. Results We identified 130 studies reporting anxiety and depression among 132,068 medical students during the COVID-19 pandemic. Eight screening tools were identified for anxiety and six for depression. The pooled prevalence of mental health outcomes for anxiety and depression was 45% (95% confidence interval [CI], 40%–49%) and 48% (95% CI, 43%–52%), respectively. The pooled prevalence of mental health outcomes for moderate and severe anxiety and moderate and severe depression was 28% (95% CI, 24%–32%) and 30% (95% CI, 26%–35%), respectively. There was high heterogeneity between studies, with I2 ranging from 99.58%–99.66%. Continent and survey date were included in the meta-regression model. The results of meta-regression revealed that medical students in Asia had a lower prevalence of anxiety, and depression than those in other regions. The survey date (from February to June, 2020) showed a significantly positive correlation with the prevalence of anxiety and depression. Conclusions We demonstrated the global prevalence of anxiety and depression among medical students during the COVID-19 pandemic. The data highlight that medical students worldwide are at high risk of experiencing anxiety and depression. The reported stressors can be categorized into personal, academic, environmental and cultural, and pandemic factors. Schools and institutions should ensure optimal alternative learning environments for uninterrupted provision of medical education. The appropriate authorities should prioritize the provision of adequate protection for medical students and establish policies to promote new methods of training and education during a disaster, such as via distance learning.

Abstract Atomic clocks with higher frequency stability and accuracy than traditional space-borne atomic clocks are the cornerstone of long-term autonomous operation of space-time-frequency systems. We proposed a space cold atoms clock based on an intracavity cooling scheme, which captures cold atoms at the center of a microwave cavity and then executes in situ interactions between the cold atoms and microwaves. As a result of the microgravity environment in space, the cold atoms can interact with the microwaves for a longer time, which aids in realizing a high-precision atomic clock in space. This paper presents the overall design, operational characteristics, and reliability test results of the space atomic clock based on the intracavity cooling scheme designed for the operation onboard the China space station. In addition, the engineering prototype performance of the space cold atoms microwave clock is also presented. The ground test results for the clock show a fractional frequency stability of 1.1 × 10−12 τ−1/2 reaching 2.5 × 10−15 at 200,000 s, providing solid technical and data support for its future operation in orbit.

In order to investigate the effect of long-term consumption of yak milk on the intestinal flora and metabolism and to explore the correlation between acclimation to monodiet and yak milk intake in high-altitude pastoral areas, this study used metagenomics and metabolomics to evaluate the gut microbial community structure and metabolites of mice fed yak milk or Holstein cow milk. Results showed that compared with the control group (normal saline solution), at the phylum level, ingestion of yak milk improved the relative abundance of Actinobacteria (33.27%), Bacteroidetes (24.31%) and Verrucomicrobia (11.08%), while ingestion of Holstein cow milk increased the relative abundance of Firmicutes (43.74%) and Bacteroidetes (24.75%). At the genus level, yak milk consumption increased the relative abundance of Ackermania (11.80%), Bacteroides (6.09%) and Limosilactobacillus (4.77%), while Holstein cow milk consumption increased the relative abundance of Lactobacillus (28.62%), Duncaniella (6.15%) and Limosilactobacillus (6.49%). Both yak and Holstein cow milk up-regulated carbohydrate and nucleotide metabolism. Furthermore, yak milk significantly up-regulated amino acid metabolism, cofactor and vitamin metabolism, energy metabolism, the biosynthesis of secondary metabolites, and the biosynthesis and metabolism of peptidoglycan. Metabolomics revealed that yak milk increased the contents of metabolites such as VB1, (+/-) 12 (13)-DiHOME, coenzyme Q2 and sulfonymethazine, as well as steroid hormone biosynthesis, cofactor biosynthesis, 2-oxyarboxylate metabolism, VB6 metabolism and phenylalanine metabolism in mice. Investigation of intestinal tissue morphology showed that the intestinal wall became thicker with increasing diversity and richness of the gut microbiota and the intestinal villi became longer and denser without deformity or breakage. In conclusion, yak milk has a positive effect on the intestinal flora and metabolism in mice, and this study provides a scientific basis for further development and utilization of yak milk.

Objective To explore the clinical efficacy of transcranial magnetic stimulation combined with mirror visual feedback training system in the treatment of unilateral neglect after stroke. Methods A total of 60 post-stroke unilateral neglect patients in the rehabilitation medicine department of Shanghai Tongren Hospital from January 2021 to December 2022 were selected as the study objects.They were divided into control group and combined group by random number table method,with 30 cases in each group.The control group received transcranial magnetic stimulation therapy,and the combined group received transcranial magnetic stimulation combined mirror visual feedback training.Montreal cognitive assessment(MoCA) scale score,Chinese behavioral inattention test-Hong Kong(CBIT-HK) score,Catherine-Bogo Scale(CBS),and Modified Barthel index(MBI) score were compared between the two groups before treatment and 4 weeks after treatment. Results After treatment,MoCA score,CBIT-HK score and MBI score in combined group were higher than those in control group(P

Abstract Background Appropriate communication with dental patients enhances treatment outcomes and patient satisfaction. Implementing simulated patient interviews courses can improve patient-centered care and reduce conflict during clerkship training. Therefore, this study explored the relationship among student participation in a situational simulation course (SSC), academic performance, clerkship performance, and objective structured clinical examination (OSCE) performance. Methods This study was conducted with a sample of fifth-year dental students undergoing clerkship training. After implementing a situational simulation course to investigate the relationship among participation in SSC, academic performance, clerkship performance, and OSCE performance, a path analysis model was developed and tested. Results Eighty-seven fifth-year dental students were eligible for the SSC, and most (n = 70, 80.46%) volunteered to participate. The path analysis model revealed that academic performance had a direct effect on OSCE performance (β = 0.281, P = 0.003) and clerkship performance (β = 0.441, P

Increasing researches reveal gut microbiota was associated with the development of tuberculosis (TB). How to prevent or reduce Mycobacterium tuberculosis colonization in the lungs is a key measure to prevent TB. However, the data on gut microbiota preventing Mycobacterium colonization in the lungs were scarce. Here, we established the clindamycin-inducing intestinal microbiome dysbiosis and fecal microbial transplantation models in mice to identify gut microbiota’s effect on Mycobacterium’s colonization in the mouse lungs and explore its potential mechanisms. The results showed that clindamycin treatment altered the diversity and composition of the intestinal bacterial and fungal microbiome, weakened the trans-kingdom network interactions between bacteria and fungi, and induced gut microbiome dysbiosis in the mice. Gut microbiota dysbiosis increases intestinal permeability and enhances the susceptibility of Mycobacterium colonization in the lungs of mice. The potential mechanisms were gut microbiota dysbiosis altered the lung transcriptome and increased Nos2 expression through the ‘gut–lung axis’. Nos2 high expression disrupts the intracellular antimicrobial and anti-inflammatory environment by increasing the concentration of nitric oxide, decreasing the levels of reactive oxygen species and Defb1 in the cells, and promoting Mycobacteria colonization in the lungs of mice. The present study raises a potential strategy for reducing the risks of Mycobacteria infections and transmission by regulating the gut microbiome balance.

IntroductionRespiratory Syncytial Virus (RSV) is a significant cause of respiratory illnesses worldwide, particularly in infants and elderly individuals. Despite the burden RSV imposes, effective preventive measures are limited. The research application of adeno-associated virus (AAV) in vaccine platforms has been expanding, and its potential in prevention and treatment has garnered much attention.MethodsIn this study, we explored the potential application of a recombinant adeno-associated virus 5 (rAAV5) vector-based RSV vaccine, focusing on the expression of the pre-fusion (Pre-F) protein structure. Through intramuscular immunization in mice. The immunogenicity of the vaccine was evaluated in Balb/c mice immunized intramuscularly and intranasal, respectively.ResultsThe rAAV5-RSV-Fm vaccine demonstrated positive humoral and induced antibody titers against RSV strains A and B for up to 120 days post-immunization. Notably, intranasal administration also elicited protective antibodies. Characterization studies confirmed the ability of the vac-cine to express the Pre-F protein and its superior immunogenicity compared to that of full-length F protein.ConclusionThese findings underscore the potential application of rAAV5 vector platforms in RSV vaccine development and further investigation into their protective efficacy is warranted.

A 56-year-old man with a 5-year history of paroxysmal palpitations, which have worsened over the past year, was diagnosed with atrial fibrillation. During evaluation, transesophageal echocardiography revealed a left atrium (LA) tumoral mass attached to the atrial septal fossa ovale, with intra-tumoral blood flow and blood stream draining from the mass. Both coronary computed tomography angiography and coronary angiography demonstrated a coro-cameral fistula connection between the left circumflex artery (LCX) branch and the LA. In addition, they showed feeding arteries of the mass arising from the LCX. The patient underwent surgical resection of the LA mass and repair of the coronary artery fistula. Intraoperative exploration revealed a 1.7 cm × 1.0 cm jelly-like, brittle LA mass and confirmed a rupture of the supplying artery, leading to a coronary artery–left atrial fistula. Surgical ligation was executed to ensure complete sealing of the supplying coronary branch within the atrial septum. Histopathological examination confirmed the diagnosis of left atrial myxoma. The 6-month follow-up indicated no recurrence of the myxoma and restoration of sinus rhythm after radiofrequency ablation. In the literature, cases of a left circumflex artery branch–left atrial fistula due to rupture of the artery supplying a left atrial myxoma are rare.

The treatment of internal hemorrhage remains challenging due to the current limited antibacterial capability, hemostatic efficacy, and biocompatibility of hemostatic materials. The TEMPO-oxidized cellulose nanofibers/collagen/chitosan (TCNF/COL/CS) hemostatic aerogel was developed in this work by physically encasing COL in a sandwich structure and electrostatically self-assembling polyanionic TCNF with polycationic CS. In vitro coagulation experiments revealed the favorable procoagulant properties of TCNF/COL/CS along with high adhesion to erythrocytes and platelets. TCNF/COL/CS significantly increased the hemostatic efficacy by 59.8 % and decreased blood loss by 62.2 % in the liver injury model when compared to Surgicel®, the most frequently used hemostatic material. Furthermore, it demonstrated outstanding biodegradability both in vitro and in vivo, and a substantial increase in resistance (96.8 % against E. coli and 95.4 % against S. aureus) compared to TCNF. The significant hemostatic and biodegradable characteristics of TCNF/COL/CS can be ascribed to its interconnected porous structure, increased porosity, and efficient water absorption, along with the synergistic effect of the three constituents. The TCNF/COL/CS aerogel shows significant potential to control internal bleeding. A novel plant-derived nanocellulose composite aerogel has been described here for the first time; it has outstanding antibacterial characteristics, higher biocompatibility, and outstanding hemostatic characteristics in vivo.

AML is a malignant tumor derived from the hematopoietic system, which has a poor prognosis and its incidence is increasing recent years. LncRNAs bind to miRNAs as competitive endogenous RNAs to regulate the occurrence and progression of AML， with IL-6R playing a crucial role in hematological malignancies. However, the mechanism by which noncoding RNAs regulate IL6R expression in AML remains unclear. This study found that the AC010247.2/miR-125b-5p axis promotes AML progression by regulating IL-6R expression. Specifically, knocking down or inhibiting AC010247.2 and miR-125b-5p affected IL6R and its downstream genes. Mechanistically, AC010247.2 acts as a ceRNA for miR-125b-5p, influencing IL-6R expression. Additionally, AC010247.2's regulation of AML progression partially depends on miR-125b-5p. Notably, the AC010247.2/miR-125b-5p/IL6R axis serves as a better polygenic diagnostic marker for AML. Our study identifies a key ceRNA regulatory axis that modulates IL6R expression in AML, providing a reliable multigene diagnostic method and potential therapeutic target.

Background Musculoskeletal (MSK) disorders, affecting billions of people worldwide, pose significant challenges to the healthcare system and require effective management models. The rapid development of digital healthcare technologies (DHTs) has revolutionized the healthcare industry. DHT-based interventions have shown promising clinical benefits in managing MSK disorders, alleviating pain, and improving functional impairment. There is, however, no bibliometric analysis of the overall trends on this topic. Methods We extracted all relevant publications from the Web of Science Core Collection (WoSCC) database until April 30, 2023. We performed bibliometric analysis and visualization using CiteSpace, VOSviewer, and R software. Annual trends of publications, countries/regions distributions, funding agencies, institutions, co-cited journals, author contributions, references, core journals, and keywords and research hotspots were analyzed. Results A total of 6810 papers were enrolled in this study. Publications have increased drastically from 16 in 1995 to 1198 in 2022, with 4067 articles published in the last five years. In all, 53 countries contributed with publications to this research area. The United States, the United Kingdom, and China were the most productive countries. Harvard University was the most contributing institution. Regarding keywords, research focuses include artificial intelligence, deep learning, machine learning, telemedicine, rehabilitation, and robotics. Conclusion The COVID-19 pandemic has further accelerated the adoption of DHTs, highlighting the need for remote care options. The analysis reveals the positive impact of DHTs on improving physician productivity, enhancing patient care and quality of life, reducing healthcare expenditures, and predicting outcomes. DHTs are a hot topic of research not only in the clinical field but also in the multidisciplinary intersection of rehabilitation, nursing, education, social and economic fields. The analysis identifies four promising hotspots in the integration of DHTs in MSK pain management, biomechanics assessment, MSK diagnosis and prediction, and robotics and tele-rehabilitation in arthroplasty care.

Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases and is known to induce endoplasmic reticulum (ER) stress, which alters cellular homeostasis and metabolic processes. While ER stress is implicated in HCV-related diseases, its precise role remains unclear. This study identifies fibroblast growth factor 21 (FGF21) as a key host factor significantly upregulated by HCV infection. Mechanistic analyses reveal that the activation of the FGF21 promoter by HCV is primarily mediated by the transcription factor ATF4, which is upregulated through the phosphorylation of eIF2α induced by ER stress. Additionally, CREBH activation further enhances ATF4 expression, contributing to increased FGF21 levels. TRIB3, upregulated by ATF4, acts as a negative regulator of FGF21 expression. The study also identifies FGF21-dependent upregulation of SOCS2 and TRIM31 in HCV-infected cells. SOCS2 contributes to the suppression of type 1 interferon signaling, aiding viral persistence, while TRIM31 promotes the degradation of the tumor suppressor protein TSC, activating the mTORC1 pathway and potentially promoting liver cell proliferation. These findings suggest that FGF21 upregulation in HCV-infected cells may play a role in both immune response regulation and cell proliferation, contributing to sustained viral infection and disease progression.

BackgroundSurgical patients often experience intraoperative hypothermia or hyperthermia. However, the relationship of intraoperative hypothermia and hyperthermia with postoperative pulmonary infection (PPI) and surgical site infection (SSI) is unclear. Here, we conducted a retrospective cohort study to address these issues.MethodsAdult patients who underwent major non-cardiac surgery under general anesthesia were eligible for the study and were recruited. Three indices of core body temperature under hypothermia (37.3°C) were calculated as mentioned in the following: absolute value (0C), duration of exposure (min), and area under the curve (AUC,°C× min). The outcomes were in-hospital PPI and SSI. The risk-adjusted association of intraoperative hypothermia and hyperthermia with PPI and SSI was determined.ResultsThe absolute value (the nadir value of hypothermia and the peak value of hyperthermia) was not associated with PPI and SSI. PPI was associated with (1) duration: hypothermia >90 min [adjusted odds ratio (aOR): 1.425, 95% confidence interval (CI): 1.131–1.796] and hyperthermia >75 min (aOR: 1.395, 95%CI: 1.208–1.612) and (2) AUC: hypothermia >3,198 (aOR: 1.390, 95%CI: 1.128–1.731) and hyperthermia >7,945 (aOR: 2.045, 95%CI: 1.138–3.676). SSI was associated with (1) duration: hypothermia > 195 min (aOR: 2.900, 95%CI: 1.703–4.937) and hyperthermia >75 min (aOR: 1.395, 95%CI: 1.208–1.612) and (2) AUC: hypothermia >6,946 (aOR: 2.665, 95%CI: 1.618–4.390), hyperthermia >7,945 (aOR: 2.619, 95%CI: 1.625–4.220). Interactions were not observed between hyperthermia and hypothermia on the outcomes.ConclusionsIt was observed that intraoperative hypothermia and hyperthermia are associated with postoperative pulmonary infection and surgical site infection in major non-cardiac surgery.

Summary: The interaction between prostate cancer (PCa) cells and prostate stromal cells fosters an immunosuppressive tumor microenvironment (TME) that promotes tumor growth and immune evasion. However, the specific signaling pathways involved remain unclear. We identified a key mechanism involving the CXCL5/CXCR2 and LIF/LIFR pathways, which create a feedforward loop that enhances neuroendocrine differentiation (NED) in PCa cells and upregulates WNT1-inducible signaling pathway protein 1 (WISP1) in both cell types. WISP1 upregulation is essential for inducing immune checkpoints and immunosuppressive cytokines via LIF/LIFR signaling and STAT3 phosphorylation. This process leads to increased neuroendocrine markers, immune checkpoints, cell proliferation, and migration. Notably, WISP1 levels in patient sera correlate with PCa progression, suggesting its potential as a biomarker. Our findings elucidate the mechanisms by which reciprocal communication between PCa cells and stromal cells contributes to the formation of an immunosuppressive TME, driving the malignant progression of PCa and highlighting potential targets for therapeutic intervention.