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This study investigated the relationship between perceived social support and psychological resilience among university students while also exploring the mediating role of coping style and the moderating effect of perceived stress. The study collected data from 1356 university students, and a path analysis was used to test the proposed hypotheses. The results revealed that perceived social support had a significant positive effect on psychological resilience. Additionally, positive coping style partially mediated the relationship between perceived social support and psychological resilience. The study also found that the direct predictive effect of perceived social support on psychological resilience, as well as the mediating role of positive coping style, were both moderated by perceived stress. Specifically, the effect of perceived social support on psychological resilience was more significant among university students with lower perceived stress than among those with higher perceived stress. Our results underscore the importance of perceived social support, positive coping style, and perceived stress in promoting psychological resilience among Chinese university students.

Abstract Tensor networks are emerging architectures for implementing quantum classification models. The branching multi-scale entanglement renormalization ansatz (BMERA) is a tensor network known for its enhanced entanglement properties. This paper introduces a hybrid quantum-classical classification model based on BMERA and explores the correlation between circuit layout, expressiveness, and classification accuracy. Additionally, we present an autodifferentiation method for computing the cost function gradient, which serves as a viable option for other hybrid quantum-classical models. Through numerical experiments, we demonstrate the accuracy and robustness of our classification model in tasks such as image recognition and cluster excitation discrimination, offering a novel approach for designing quantum classification models.

Abstract Tissue regeneration technology has been rapidly developed and widely applied in tissue engineering and repair. Compared with traditional approaches like surgical treatment, the rising gene therapy is able to have a durable effect on tissue regeneration, such as impaired bone regeneration, articular cartilage repair and cancer-resected tissue repair. Gene therapy can also facilitate the production of in situ therapeutic factors, thus minimizing the diffusion or loss of gene complexes and enabling spatiotemporally controlled release of gene products for tissue regeneration. Among different gene delivery vectors and supportive gene-activated matrices, advanced gene/drug nanocarriers attract exceptional attraction due to their tunable physiochemical properties, as well as excellent adaptive performance in gene therapy for tissue regeneration, such as bone, cartilage, blood vessel, nerve and cancer-resected tissue repair. This paper reviews the recent advances on nonviral-mediated gene delivery systems with an emphasis on the important role of advanced nanocarriers in gene therapy and tissue regeneration.

Summary: Background: The survival rate of patients with distant metastasis (DM) of papillary thyroid carcinoma (PTC) is significantly reduced. It is of great significance to find an effective method for early prediction of the risk of DM for formulating individualized diagnosis and treatment plans and improving prognosis. Previous studies have significant limitations, and it is still necessary to develop new models for predicting the risk of DM of PTC. We aimed to develop and validate interpretable machine learning (ML) models for early prediction of DM in patients with PTC using a multicenter cohort. Methods: We collected data on patients with PTC who were admitted between June 2013 and May 2023. Data from 1430 patients at Yunnan Cancer Hospital (YCH) served as the training and internal validation set, while data from 434 patients at the First Affiliated Hospital of Kunming Medical University (KMU 1st AH) was used as the external test set. Nine ML methods such as random forest (RF) were used to construct the model. Model prediction performance was compared using evaluation indicators such as the area under the receiver operating characteristic curve (AUC). The SHapley Additive exPlanation (SHAP) method was used to rank the feature importance and explain the final model. Findings: Among the nine ML models, the RF model performed the best. The RF model accurately predicted the risk of DM in patients with PTC in both the internal validation of the training set [AUC: 0.913, 95% confidence interval (CI) (0.9075–0.9185)] and the external test set [AUC: 0.8996, 95% CI (0.8483–0.9509)]. The calibration curve showed high agreement between the predicted and observed risks. In the sensitivity analysis focusing on DM sites of PTC, the RF model exhibited outstanding performance in predicting “lung-only metastasis” showing high AUC, specificity, sensitivity, F1 score, and a low Brier score. SHAP analysis identified variables that contributed to the model predictions. An online calculator based on the RF model was developed and made available for clinicians at https://predictingdistantmetastasis.shinyapps.io/shiny1/. 11 variables were included in the final RF model: age of the patient with PTC, whether the tumor size is > 2 cm, whether the tumor size is ≤ 1 cm, lymphocyte (LYM) count, monocyte (MONO) count, monocyte/lymphocyte ratio (MLR), thyroglobulin (TG) level, thyroid peroxidase antibody (TPOAb) level, whether the T stage is T1/2, whether the T stage is T3/4, and whether the N stage is N0. Interpretation: On the basis of large-sample and multicenter data, we developed and validated an explainable ML model for predicting the risk of DM in patients with PTC. The model helps clinicians to identify high-risk patients early and provides a basis for individualized patient treatment plans. Funding: This work was supported by the National Natural Science Foundation of China (No. 81960426, 82360345 and 82001986), the Outstanding Youth Science Foundation of Yunnan Basic Research Project (No. 202401AY070001-316), Yunnan Province Applied and Basic Research Foundation (No. 202401AT070008), and Ten Thousand Talent Plans for Young Top-notch Talents of Yunnan Province.

Abstract Communication is crucial in constructing the relationship between students and advisers, ultimately bridging interpersonal interactions. Only a few studies however explore the communication between postgraduate students and advisers. To fill the gaps in the empirical researches, this study uses functional near-infrared spectroscopy (FNIRS) techniques to explore the neurophysiology differences in brain activation of postgraduates with different adviser-advise relationships during simulated communication with their advisers. Results showed significant differences in the activation of the prefrontal cortex between high-quality and the low-quality students during simulating and when communicating with advisers, specifically in the Broca's areas, the frontal pole, and the orbitofrontal and dorsolateral prefrontal cortices. This further elucidated the complex cognitive process of communication between graduate students and advisers.

Black tea's quality and flavor are largely influenced by its processing stages, which affect its volatile and non-volatile phytochemicals. This study aimed to optimized black tea manufacturing by investigating withering time, fermentation time, and temperature's impact on sensory quality. Using a U*15 (157) uniform design, optimal conditions were determined: 14 h of withering, 5.6 h of fermentation, and a 34 °C temperature. A verification experiment analyzed the volatile and non-volatile profiles. HPLC, GC–MS, and LC-MS revealed dynamic changes in phytochemicals. Among 157 VOCs and 2642 metabolites, 19 VOCs (VIP > 1.5) were crucial for aroma, while 50 (VIP > 1.5, p

Abstract Purpose To investigate the balance between post-treatment effect and continued nature growth after maxillary protraction treatment in patients with skeletal class III malocclusion. Methods 31 patients aged 8.79 ± 1.65 years with skeletal Class III malocclusion had been treated with maxillary protraction and the treatment lasted an average of 1.16 years. The average observation duration after treatment in the maxillary protraction group was 2.05 ± 0.39 years. In the control groups, a sample of 22 patients (9.64 ± 2.53 years) with untreated skeletal class III malocclusion and 24 patients (9.28 ± 0.96 years) with skeletal class I malocclusion were matched to the treatment group according to age, sex and observation period. The mean observation interval of the control groups was 2.39 ± 1.29 years in the class III group and 1.97 ± 0.49 years in the class I group. Results The active orthopedic treatment effect showed a opposite trend to the natural craniomaxillofacial growth effect after treatment in many aspects. In the observation duration of treatment group, decrease in ANB, Wits appraisal and BAr-AAr were statistically significant compared to class I control group (p 0.05), and overjet decreased significantly relative to both of the two control groups (P

Background: Globally, gastric cancer (GC) is recognized as the third leading cause of cancer-related deaths and the fifth most prevalent malignant disease. Multiple studies have indicated that Hedyotis diffusa Willd, in pinyin, called Bai Hua She Cao (BHSSC), a traditional Chinese medicine (TCM) is an herbal remedy for cancer treatment. However, the specific mechanisms underlying its anti-tumor properties and mode of action are still unclear. Methods: To determine the role of BHSSC in GC, candidate target genes were selected from The Encyclopedia of Traditional Chinese Medicine (ETCM) and analyzed using network pharmacology, bioinformatics, and experimental validation. Differentially expressed genes (DEGs) associated with gastric cancer were obtained from RNA sequencing (RNA-seq) data sourced from The Cancer Genome Atlas-Stomach adenocarcinoma (TCGA-STAD). The Reactome Pathway was examined using Analysis Tools, while KEGG pathways were analyzed using KOBAS. Gene Ontology (GO) evaluations were performed using WebGestalt and DAVID. The relationships between proteins were investigated using the STRING database. Furthermore, cell viability, colony formation, and cell migration ability were conducted in gastric cancer cells, BGC-823 and MGC-803. Results: Network pharmacology and bioinformatics analyses revealed a significant association between BHSSC and metabolic pathways. In vitro experiments demonstrated that BHSSC effectively suppressed gastric cancer cell proliferation and colony formation, inhibited cell migration, and activated the endoplasmic reticulum (ER) stress. Furthermore, it was found that enhancement of the expression of IRE1α and BIP is the mechanism by which BHSSC activates ER stress. Conclusions: The findings suggest that BHSSC exerts its effects through modulation of metabolic pathways, leading to the suppression of cell proliferation, inhibition of cell migration, and activation of the endoplasmic reticulum. These results provide valuable insights into the mechanisms underlying the therapeutic effects of BHSSC in GC and support its potential as a novel treatment option.

Abstract Patients with inflammatory bowel disease (IBD) always suffer from severe abdominal pain and appear to be at high risk for colorectal cancer. Recently, the co-delivery of targeted drugs and gut microbiota has developed into an attractive strategy. A new strategy using gut microbiota fermentation to overcome the interspace diffuse resistance from the mucus layer to control drug release in inflammatory bowel sites (IBS sites) has not yet been available. Here, we designed an alginate hydrogel microsphere encapsulating bifidobacterium (Bac) and drug-modified nanoscale dietary fibers (NDFs). The hydrogel microsphere is responsible for protecting drugs from acidic and multi-enzymatic environments and delivering drugs to the colorectum. Subsequently, the fermentation of Bac by digesting NDFs and proteins as carbon and nitrogen sources can promote drug release and play a probiotic role in the gut microbiota. In vitro evidence indicated that small-sized NDF (NDF-1) could significantly promote short-chain fatty acid (SCFA) expression. Notably, NDF-1 hydrogel microspheres showed a boost release of 5-ASA in the IBS sites, resulting in the amelioration of gut inflammation and remodeling of gut microbiota in chronic colitis mice. This study developed a controlled release system based on microbial fermentation for the treatment of IBD.

Abstract Respiratory syncytial virus (RSV) and human metapneumovirus (HMPV) are related RNA viruses responsible for severe respiratory infections and resulting disease in infants, elderly, and immunocompromised adults1–3. Therapeutic small molecule inhibitors that bind to the RSV polymerase and inhibit viral replication are being developed, but their binding sites and molecular mechanisms of action remain largely unknown4. Here we report a conserved allosteric inhibitory site identified on the L polymerase proteins of RSV and HMPV that can be targeted by a dual-specificity, non-nucleoside inhibitor, termed MRK-1. Cryo-EM structures of the inhibitor in complexes with truncated RSV and full-length HMPV polymerase proteins provide a structural understanding of how MRK-1 is active against both viruses. Functional analyses indicate that MRK-1 inhibits conformational changes necessary for the polymerase to engage in RNA synthesis initiation and to transition into an elongation mode. Competition studies reveal that the MRK-1 binding pocket is distinct from that of a capping inhibitor with an overlapping resistance profile, suggesting that the polymerase conformation bound by MRK-1 may be distinct from that involved in mRNA capping. These findings should facilitate optimization of dual RSV and HMPV replication inhibitors and provide insights into the molecular mechanisms underlying their polymerase activities.

Abstract Cancer exerts a multitude of effects on metabolism, including the reprogramming of cellular metabolic pathways and alterations in metabolites that facilitate inappropriate proliferation of cancer cells and adaptation to the tumor microenvironment. There is a growing body of evidence suggesting that aberrant metabolites play pivotal roles in tumorigenesis and metastasis, and have the potential to serve as biomarkers for personalized cancer therapy. Importantly, high-throughput metabolomics detection techniques and machine learning approaches offer tremendous potential for clinical oncology by enabling the identification of cancer-specific metabolites. Emerging research indicates that circulating metabolites have great promise as noninvasive biomarkers for cancer detection. Therefore, this review summarizes reported abnormal cancer-related metabolites in the last decade and highlights the application of metabolomics in liquid biopsy, including detection specimens, technologies, methods, and challenges. The review provides insights into cancer metabolites as a promising tool for clinical applications.

Over the past decades, many forests have been converted to monoculture plantations, which might affect the soil microbial communities that are responsible for governing the soil biogeochemical processes. Understanding how reforestation efforts alter soil prokaryotic microbial communities will therefore inform forest management. In this study, the prokaryotic communities were comparatively investigated in a secondary Chinese fir forest (original) and a reforested Chinese fir plantation (reforested from a secondary Chinese fir forest) in Southern China. The results showed that reforestation changed the structure of the prokaryotic community: the relative abundances of important prokaryotic families in soil. This might be caused by the altered soil pH and organic matter content after reforestation. Soil profile layer depth was an important factor as the upper layers had a higher diversity of prokaryotes than the lower ones (p < 0.05). The composition of the prokaryotic community presented a seasonality characteristic. In addition, the results showed that the dominant phylum was Acidobacteria (58.86%) with Koribacteraceae (15.38%) as the dominant family in the secondary Chinese fir forest and the reforested plantation. Furthermore, soil organic matter, total N, hydrolyzable N, and NH4+−N were positively correlated with prokaryotic diversity (p < 0.05). Also, organic matter and NO3-−N were positively correlated to prokaryotic abundance (p < 0.05). This study demonstrated that re-forest transformation altered soil properties, which lead to the changes in microbial composition. The changes in microbial community might in turn influence biogeochemical processes and the environmental variables. The study could contribute to forest management and policy-making.

Abstract 360-degree videos have become increasingly popular with the application of virtual reality (VR) technology. To encode such kind of videos with ultra-high resolution, an efficient and real-time video encoder becomes a key requirement. The Versatile Video Coding (VVC) standard has good coding performance. However, it has pretty high computational complexity which increasing the application cost of 360-degree videos. Among them, the decision of the quadtree with nested multi-type tree (QTMT) partitioning structure is one of the time-consuming procedures. In this paper, based on the characteristics of 360-degree video with Equirectangular projection (ERP) format, the empirical variogram combined with Mahalanobis distance is introduced to measure the difference between the horizontal and vertical directions of the CU, and a fast partition algorithm is proposed. The experimental results show that the algorithm saves 32.13% of the coding time with only an increase of 0.66% in BDBR.

【Objective】Rice blast is an important limiting factor in rice production. Exploring and utilizing resistant genes is an important guarantee for achieving high and stable yield of rice. Previous studies have shown that rice blast resistance-related microRNA osa-miR-21 may regulate rice blast resistance by targeting the polyamine oxidase gene OsPAO4. However, the function of Polyamine Oxidases (PAOs) in rice disease resistance has not been reported. In order to further explore the possible biological function of OsPAO4 gene in rice disease resistance, the CRISPR/Cas9 editing technology was used for site-specific editing of ospao4 gene mutants and the edited offspring were also analyzed.【Method】A 20-bp editing target was designed in the second exon of OsPAO4, and the nucleotide fragments of the target was cloned into pRGEB32 vector to obtain OsPAO4 editing vector. Then, the rice Pik-H4 NIL callus was transformed by Agrobacterium-mediated method. Positive transgenic plants were obtained by regeneration culture and hygromycin detection, PCR and sequence analysis were performed on the DNA sequences near the target site in the T0 generation plants.【Result】The results show that the OsPAO4 gene was successfully edited and finally 25 transgenic-positive plants were obtained, and various mutation types were produced in the T0 generation, including 3 homozygous mutants, 18 heterozygous mutants and 4 nonedited plants. In addition, the glume color of the heterozygous mutation ospao4-8 of the T0 generation changed from purple to dark gray, and the activity of catalase (CAT) in the mutants was increased. It was predicted that OsPAO4 might participate in the basis immunization process.【Conclusion】A variety of ospao4 mutants were created in this study, and it was preliminarily determined that OsPAO4 might participate in the regulation of rice immune process, which laid an important foundation for further revealing the specific biological function and molecular regulation mechanism of OsPAO4 gene.

The objective of the study is to investigate the effect of theabrownin on the immunohistochemistry of brain tissue in aging mice, screen the differential metabolites and analyze the metabolic pathways involved. A mouse aging model was established by subcutaneous injection of D-galactose in mice. Immunohistochemical and UHPLC-QE-MS metabolomics techniques were used to detect brain samples of normal control mice, D-galactose model mice and theabrownin-treated (pretreatment and treatment) mice. The results showed that the areal density of choline acetyltransferase positive expression was significantly increased (P

BackgroundThe prognosis of ST-segment elevation myocardial infarction (STEMI) is closely linked to left ventricular ejection fraction (LVEF). In contrast to primary percutaneous coronary intervention (PPCI), thrombolysis-transfer PCI (TTPCI) is influenced by multiple factors that lead to heterogeneity in cardiac function and prognosis. The aim of this study is to develop a nomogram model for predicting early LVEF in STEMI patients with TTPCI, based on routine indicators at admission.MethodWe retrospectively reviewed data from patients diagnosed with STEMI at five network hospitals of our PCI center who performed TTPCI as door-to-balloon time (the interval between arrival at the hospital and intracoronary balloon inflation) over 120 min, from February 2018 to April 2022. Categorical variables were analyzed using Pearson χ2 tests or Fisher exact tests, while Student's t-test or Mann–Whitney U-test was used to compare continuous variables. Subsequently, independent risk factors associated with reduced LVEF one week after TTPCI were identified through comprehensive analysis by combining All-Subsets Regression with Logistic Regression. Based on these indicators, a nomogram model was developed, and validated using the area under the receiver operating characteristic (ROC) curve and the Bootstrap method.ResultsA total of 288 patients were analyzed, including 60 with LVEF

Summary: The spliceosomal snRNP cores, each comprised of a snRNA and a seven-membered Sm ring (D1/D2/F/E/G/D3/B), are assembled by twelve chaperoning proteins in human. However, only six assembly-assisting proteins, ICln and the SMN complex (SMN/Gemin2/Gemin6-8), have been found in Schizosaccharomyces pombe (Sp). Here, we used recombinant proteins to reconstitute the chaperone machinery and investigated the roles of these proteins systematically. We found that, like the human system, the assembly in S. pombe requires ICln and the SMN complex sequentially. However, there are several significant differences. For instance, h_F/E/G forms heterohexamers and heterotrimers, while Sp_F/E/G only forms heterohexamers; h_Gemin2 alone can bind D1/D2/F/E/G, but Sp_Gemin2 cannot. Moreover, we found that Sp_Gemin2 is essential using genetic approaches. These mechanistic studies reveal that these six proteins are necessary and sufficient for Sm core assembly at the molecular level, and enrich our understanding of the chaperone systems in species variation and evolution.

Abstract Aim The aim of this study was to explore the mediating role of perceived social support in the association between perceived stress and job burnout in midwives. Design A descriptive, cross‐sectional online survey. Methods Using the stratified cluster sampling method, 329 midwives in 20 hospitals in China were selected as the participants. They completed self‐report assessment measures of job burnout, perceived stress and perceived social support. Results 63.5% of the participants had job burnout. Perceived stress was negatively associated with social support (r = −.350, p

Abstract Heat stress has multiple potential effects on the brain, such as neuroinflammation, neurogenesis defects, and cognitive impairment. β-hydroxybutyric acid (BHBA) has been demonstrated to play neuroprotective roles in various models of neurological diseases. In the present study, we investigated the efficacy of BHBA in alleviating heat stress-induced impairments of adult hippocampal neurogenesis and cognitive function, as well as the underlying mechanisms. Mice were exposed to 43 ℃ for 15 min for 14 days after administration with saline, BHBA, or minocycline. Here, we showed for the first time that BHBA normalized memory ability in the heat stress-treated mice and attenuated heat stress-impaired hippocampal neurogenesis. Consistently, BHBA noticeably improved the synaptic plasticity in the heat stress-treated hippocampal neurons by inhibiting the decrease of synapse-associated proteins and the density of dendritic spines. Moreover, BHBA inhibited the expression of cleaved caspase-3 by suppressing endoplasmic reticulum (ER) stress, and increased the expression of brain-derived neurotrophic factor (BDNF) in the heat stress-treated hippocampus by activating the protein kinase B (Akt)/cAMP response element binding protein (CREB) and methyl-CpG binding protein 2 (MeCP2) pathways. These findings indicate that BHBA is a potential agent for improving cognitive functions in heat stress-treated mice. The action may be mediated by ER stress, and Akt-CREB-BDNF and MeCP2 pathways to improve adult hippocampal neurogenesis and synaptic plasticity.

IntroductionMicroorganisms play an important role in the multifunctionality of soil ecosystems. Soil microbial diversity and functions have a great impact on plant growth and development. The interactions between tea trees and soil microbiota can be linked with planting patterns and management strategies, whose effects on soil microbial community structure and metabolites are still unclear.MethodsHere we used amplicon sequencing and metabolomic analysis to investigate the differences in soil microbial composition and metabolites among three tea production systems: organic, non-organic, and intercropping.ResultsWe detected significant differences among the three systems and found that Firmicutes, Proteobacteria, Acidobacteriota, Actinobacteriota and Chloroflexi were the main bacteria in the three soil groups, although they varied in relative abundance. Acidobacteria bacterium increased significantly in the organic and intercropping groups. For fungi, Ascomycota and Basidiomycota were the main differential fungal phyla. Fungi alpha-diversity in the non-organic group was significantly higher than that in the other two groups, and was correlated with multiple soil physical and chemical factors. Moreover, network analysis showed that bacteria and fungi were strongly correlated. The changes in soil microorganisms caused by management and planting patterns may affect soil quality through corresponding changes in metabolites. Metabolomic analysis showed differences in metabolite composition among different groups. It was also found that the arachidonic acid metabolic pathway was affected by changes in soil microorganisms, and may further affect soil quality in an essential manner.DiscussionPlanting patterns and management strategies may significantly affect soil microorganisms and therefore metabolites. Changes in soil microorganisms, especially in fungi, may alter soil quality by affecting soil physicochemical properties and metabolites. This study will provide new insights into soil quality monitoring from a microbiological perspective.

Background Patients with non-small cell lung cancer (NSCLC) who develop brain metastases (BM) have a poor prognosis. This study aimed to construct a clinical prediction model to determine the overall survival (OS) of NSCLC patients with BM. Methods A total of 300 NSCLC patients with BM at the Yunnan Cancer Centre were retrospectively analysed. The prediction model was constructed using the least absolute shrinkage and selection operator-Cox regression. The bootstrap sampling method was employed for internal validation. The performance of our prediction model was compared using recursive partitioning analysis (RPA), graded prognostic assessment (GPA), the update of the graded prognostic assessment for lung cancer using molecular markers (Lung-molGPA), the basic score for BM (BSBM), and tumour-lymph node-metastasis (TNM) staging. Results The prediction models comprising 15 predictors were constructed. The area under the curve (AUC) values for the 1-year, 3-year, and 5-year time-dependent receiver operating characteristic (curves) were 0.746 (0.678–0.814), 0.819 (0.761–0.877), and 0.865 (0.774–0.957), respectively. The bootstrap-corrected AUC values and Brier scores for the prediction model were 0.811 (0.638–0.950) and 0.123 (0.066-0.188), respectively. The time-dependent C-index indicated that our model exhibited significantly greater discrimination compared with RPA, GPA, Lung-molGPA, BSBM, and TNM staging. Similarly, the decision curve analysis demonstrated that our model displayed the widest range of thresholds and yielded the highest net benefit. Furthermore, the net reclassification improvement and integrated discrimination improvement analyses confirmed the enhanced predictive power of our prediction model. Finally, the risk subgroups identified by our prognostic model exhibited superior differentiation of patients’ OS. Conclusion The clinical prediction model constructed by us shows promise in predicting OS for NSCLC patients with BM. Its predictability is superior compared with RPA, GPA, Lung-molGPA, BSBM, and TNM staging.

BackgroundThe immune responses to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are crucial in maintaining a delicate balance between protective effects and harmful pathological reactions that drive the progression of coronavirus disease 2019 (COVID-19). T cells play a significant role in adaptive antiviral immune responses, making it valuable to investigate the heterogeneity and diversity of SARS-CoV-2-specific T cell responses in COVID-19 patients with varying disease severity.MethodsIn this study, we employed high-throughput T cell receptor (TCR) β repertoire sequencing to analyze TCR profiles in the peripheral blood of 192 patients with COVID-19, including those with moderate, severe, or critical symptoms, and compared them with 81 healthy controls. We specifically focused on SARS-CoV-2-associated TCR clonotypes.ResultsWe observed a decrease in the diversity of TCR clonotypes in COVID-19 patients compared to healthy controls. However, the overall abundance of dominant clones increased with disease severity. Additionally, we identified significant differences in the genomic rearrangement of variable (V), joining (J), and VJ pairings between the patient groups. Furthermore, the SARS-CoV-2-associated TCRs we identified enabled accurate differentiation between COVID-19 patients and healthy controls (AUC > 0.98) and distinguished those with moderate symptoms from those with more severe forms of the disease (AUC > 0.8). These findings suggest that TCR repertoires can serve as informative biomarkers for monitoring COVID-19 progression.ConclusionsOur study provides valuable insights into TCR repertoire signatures that can be utilized to assess host immunity to COVID-19. These findings have important implications for the use of TCR β repertoires in monitoring disease development and indicating disease severity.

Management of hypertension and prevention of cognitive decline are challenging public health problems. However, the effects of exergame intervention on blood pressure (BP) remain to be explored, and whether exergame intervention is an effective alternative to traditional physical exercise intervention for older adults with hypertension remains to be demonstrated. This study aimed to explore the effectiveness of moderate-intensity exergame intervention and bicycle exercise training on BP and executive function in older hypertensive patients. A total of 128 participants were randomly assigned to the exergame intervention group (n = 41), bicycle exercise intervention group (n = 44), and control group (n = 43). The intervention groups exercised for 60 min, 3 times per week, for 16 weeks, while the control group maintained their normal lifestyle. The results revealed that there were no significant differences between two intervention groups and control group in systolic BP and diastolic BP changes (ps > 0.05). Both intervention groups demonstrated significant improvements in working memory when compared with control group (exergame intervention group: −461.9 ms, p = 0.025; bicycle exercise intervention group: −470.1 ms, p = 0.021). There were no significant differences in systolic BP, diastolic BP, or working memory between the two intervention groups after 16 weeks of training (ps > 0.05). No difference in inhibition or cognitive flexibility was observed between the intervention and control groups (ps > 0.05). The current results showed that moderate-intensity exergame intervention did not produce significant benefits in reducing BP, but yielded similar beneficial effects in working memory to that of bicycle exercise intervention. More studies are needed on whether exergame intervention has the potential to be a promising supplemental therapeutic tool for older adults with hypertension.

Background: Non-syndromic oligodontia is characterized by the absence of six or more permanent teeth, excluding third molars, and can have aesthetic, masticatory, and psychological consequences. Previous studies have shown that PAX9 is associated with autosomal dominant forms of oligodontia but the precise molecular mechanisms are still unknown.Methods: Whole-exome and Sanger sequencing were performed on a cohort of approximately 28 probands with NSO, for mutation analysis. Bioinformatic analysis was performed on the potential variants. Immunofluorescence assay, western blotting, and qPCR were used to explore the preliminary functional impact of the variant PAX9 proteins. We reviewed PAX9-related NSO articles in PubMed to analyze the genotype-phenotype correlations.Results: We identified three novel PAX9 variants in Chinese Han families: c.152G>T (p.Gly51Val), c.239delC (p.Thr82Profs*3), and c.409C>T (q.Gln137Ter). In addition, two previously reported missense variants were identified: c.140G>C (p.Arg47Pro) and c.146C>T (p.Ser49Leu) (reference sequence NM_006194.4). Structural modeling revealed that all missense variants were located in the highly conserved paired domain. The other variants led to premature termination of the protein, causing structural impairment of the PAX9 protein. Immunofluorescence assay showed abnormal subcellular localizations of the missense variants (R47P, S49L, and G51V). In human dental pulp stem cells, western blotting and qPCR showed decreased expression of PAX9 variants (c.140G>C, p.R47P, and c.152G>T, p.G51V) compared with the wild-type group at both the transcription and translation levels. A review of published papers identified 64 PAX9 variants related to NSO and found that the most dominant feature was the high incidence of missing upper second molars, first molars, second premolars, and lower second molars.Conclusion: Three novel PAX9 variants were identified in Chinese Han families with NSO. These results extend the variant spectrum of PAX9 and provide a foundation for genetic diagnosis and counseling.

Abstract Colorectal cancer (CRC) is the most common human digestive malignancy with a poor prognosis; the pathophysiology of colon cancer involves multiple linkages of regulatory networks. Recently, thrombospondin 2 (THBS2) has been extensively studied for its role in cancer progression. In this study, we evaluated the expression of THBS2 in CRC tissues and studied the possible mechanism by which THBS2 regulates CRC progression. Our results showed that the upregulation of THBS2 in CRC tissues and CRC cell lines and high expression of THBS2 was correlated with poor overall survival. The in vitro experimental data showed that THBS2 overexpression promoted CRC cell growth, invasion, and migration, while THBS2 inhibition exerted tumor‐suppressive actions on CRC cells. THBS2 knockdown suppressed the activity of Wnt/β‐catenin signaling. Collectively, the results implied that THBS2 exerted promotional effects on CRC cell proliferation, invasion, and migration, partly by modulating the Wnt/β‐catenin signaling pathway.

The intricate regulatory process governing rice immunity against the blast fungus Magnaporthe oryzae remains a central focus in plant–pathogen interactions. In this study, we investigated the important role of Osa-miR11117, an intergenic microRNA, in regulating rice defense mechanisms. Stem-loop qRT-PCR analysis showed that Osa-miR11117 is responsive to M. oryzae infection, and overexpression of Osa-miR11117 compromises blast resistance. Green fluorescent protein (GFP)-based reporter assay indicated OsPAO4 is one direct target of Osa-miR11117. Furthermore, qRT-PCR analysis showed that OsPAO4 reacts to M. oryzae infection and polyamine (PA) treatment. In addition, OsPAO4 regulates rice resistance to M. oryzae through the regulation of PA accumulation and the expression of the ethylene (ETH) signaling genes. Taken together, these results suggest that Osa-miR11117 is targeting OsPAO4 to regulate blast resistance by adjusting PA metabolism and ETH signaling pathways.

Introduction: The COVID-19 global pandemic is far from ending. There is an urgent need to identify applicable biomarkers for early predicting the outcome of COVID-19. Growing evidences have revealed that SARS-CoV-2 specific antibodies evolved with disease progression and severity in COIVD-19 patients. Objectives: We assumed that antibodies may serve as biomarkers for predicting the clinical outcome of hospitalized COVID-19 patients on admission. Methods: By taking advantage of a newly developed SARS-CoV-2 proteome microarray, we surveyed IgG responses against 20 proteins of SARS-CoV-2 in 1034 hospitalized COVID-19 patients on admission and followed till 66 days. The microarray results were further correlated with clinical information, laboratory test results and patient outcomes. Cox proportional hazards model was used to explore the association between SARS-CoV-2 specific antibodies and COVID-19 mortality. Results: Nonsurvivors (n = 955) induced higher levels of IgG responses against most of non-structural proteins than survivors (n = 79) on admission. In particular, the magnitude of IgG antibodies against 8 non-structural proteins (NSP1, NSP4, NSP7, NSP8, NSP9, NSP10, RdRp, and NSP14) and 2 accessory proteins (ORF3b and ORF9b) possessed significant predictive power for patient death, even after further adjustments for demographics, comorbidities, and common laboratory biomarkers for disease severity (all with p trend

Abstract The purpose of this study was to compare the ability of 18F-FDG PET/CT and contrast-enhanced MRI (CEMRI) to detect and grade venous tumour thrombus (VTT) and venous bland thrombus (VBT) in RCC and assess invasion of the venous wall by VTT. The PET/CT and CEMRI data of 41 patients with RCC were retrieved. The difference in maximum standardized uptake value (SUVmax) between VTT and VBT was analysed. According to their pathological diagnosis, the patients were divided into those with and without venous wall invasion. The PET/CT and CEMRI features, including the SUVmax of the primary lesion and VTT, maximum venous diameter, complete occlusion of the vein by VTT, and VTT morphology, were compared between the two groups. All 41 patients had VTT, and eleven of the 41 patients had VBT. The mean SUVmax of the VTT (6.33 ± 4. 68, n = 41) was significantly higher than that of the VBT (1.37 ± 0.26, n = 11; P

Abstract Background Allergic rhinitis (AR) is an immunoglobulin E (IgE)-mediated inflammatory response. Persistent allergic rhinitis (PAR) is a subtype of AR, but the treatment of PAR is still a problem. Acupuncture is used as an alternative therapy for AR in clinical practice. The aim of this study is to evaluate the effectiveness of acupuncture therapy combined with fluticasone propionate nasal spray in comparison to fluticasone propionate nasal spray alone in the relief of symptoms for PAR. Methods This study is a multicenter, single-blind, randomized controlled trial. A total of 260 eligible patients will be randomly assigned into the treatment group or the control group. The treatment group will receive the nasal fluticasone propionate combined with acupuncture, and the control group will receive fluticasone propionate nasal spray alone for 6 weeks. The primary outcome is the change in the Reflective Total Nasal Symptom Score (rTNSS) from baseline to the end of treatment, and the Total Non Nasal Symptom Score (TNNSS), reflective total ocular symptom score (rTOSS), Rhinitis Quality of Life Questionnaire (RQLQ), use of antiallergic drugs, and the Rhinitis Control Assessment Test (RCAT) are used as secondary outcomes. The participants will be followed up for another 24 weeks after treatment. Discussion This clinical trial will be able to provide high level evidence on the acupuncture therapy combined with fluticasone propionate nasal spray in the treatment of PAR. Trial registration ISRCTN Registry, ID: ISRCTN44040506 . Registered on 22 July 2020.

Sex differences are evident in the incidence and mortality of diverse cancers. With the development of personalized approaches in cancer treatment, the impact of sex differences has not been systematically incorporated into preclinical and clinical cancer research. The molecular mechanisms underlying sex differences in cancer have not been elucidated. Here, we developed the first database of Sex Differences in Cancer (SDC), a web-based public database that integrates resources from multiple databases, including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression Project (GTEx), UCSC Xena, Broad Institute Cancer Cell Line Encyclopedia (CCLE), Genomics of Drug Sensitivity in Cancer (GDSC). SDC contains 27 types of cancers, 6 types of molecular data, more than 10,000 donors, 977 cancer cell lines were used to analyze sex differences among cancers. It provides five main modules: Survival and phenotype, Molecular differences, Signatures and pathways, Therapy response, Download. Users can download the all the visualized results and raw data after analysis. Collectively, SDC is the first integrated database to analyze sex differences in cancer on the web server, which will strengthen our understanding of the role of sex in cancers. It is implemented in Shiny-server and freely available for public use at http://sdc.anticancer.xyz.

Abstract Rational design of hierarchically structured electrocatalysts is particularly important for electrocatalytic oxygen reduction reaction (ORR). Here, ZIF‐67 crystals are stringed on core–shell Ag@C nanocables using a coordination‐modulated process. Upon pyrolysis, Ag@C strings of Co nanoparticles embedded with three‐dimensional porous carbon with beads‐on‐string hierarchical structures are developed. Due to the advantages of the rich electrochemical active sites of Co‐based “beads” and the efficient electron transfer pathways via Ag@C “strings,” the resultant NH3–Ag@C@Co–N–C‐700 catalyst shows an improved electrocatalytic activity toward ORR. NH3–Ag@C@Co–N–C‐700 shows a high onset potential of 0.99 V versus RHE, a high half‐wave potential of 0.88 V versus RHE, and a large limiting current of 5.8 mA cm−2, which are better than those of commercial Pt/C electrocatalysts. Additionally, the NH3–Ag@C@Co–N–C‐700 catalyst shows high stability and preeminent methanol tolerance, which makes NH3–Ag@C@Co–N–C‐700 a promising catalyst for oxygen electrocatalysis in fuel cell applications.