Associations of 24-hour movement behaviors with emotional and behavioral problems among Chinese adolescents.

PURPOSE: The role of adherence to the recommendations for 24-hour movement behaviors (24-HMB), including physical activity (PA), screen time (ST), and sleep duration (SLP), in relation to emotional and behavioral problems in Chinese adolescents remains uncertain. This study aimed to investigate these associations and explore potential sex differences. METHODS: This school-based cross-sectional study included 15,071 Chinese adolescents with a mean age of 14.53 (SD: 1.65) years. Data on emotional and behavioral problems and 24-HMB (including PA, ST, and SLP) were collected. Analysis was performed using general linear mixed models, with additional sex-stratified analyses conducted. RESULTS: The number of 24-HMB recommendations met was negatively associated with total difficulties (ß estimate=-0.96, 95% CI: -1.07 to -0.85) and positively related to prosocial behavior (ß estimate = 0.41, 95% CI: 0.37 to 0.46) among adolescents. Compared with none of the recommendations met, meeting all recommendations (total difficulties: ß estimate=-2.98, 95% CI: -3.41 to -2.55; prosocial behaviors: ß estimate = 1.05, 95%CI: 0.87 to 1.24) demonstrated the strongest association with both difficulties and prosocial behaviors, followed by meeting recommendations for PA + ST (total difficulties: ß estimate=-2.15, 95% CI: -2.41 to -1.90; prosocial behaviors: ß estimate = 0.98, 95% CI: 0.87 to 1.09). These associations were consistently significant in both boys and girls. CONCLUSION: Adherence to more 24-HMB recommendations, particularly meeting all recommendations or combined PA + ST recommendations, could improve emotional and behavioral well-being among adolescent girls and boys. The significance of balanced movement behaviors for promoting adolescent mental health merits increased attention.

Tibial cortex transverse transport surgery improves wound healing in patients with severe type 2 DFUs by activating a systemic immune response: a cross-sectional study.

BACKGROUND: Tibial cortex transverse transport (TTT) surgery has become an ideal treatment for patients with type 2 severe diabetic foot ulcerations (DFUs) while conventional treatments are ineffective. Based on our clinical practice experience, the protective immune response from TTT surgery may play a role against infections to promote wound healing in patients with DFUs. Therefore, this research aimed to systematically study the specific clinical efficacy and the mechanism of TTT surgery. MATERIALS AND METHODS: Between June 2022 and September 2023, 68 patients with type 2 severe DFUs were enrolled and therapized by TTT surgery in this cross-sectional and experimental study. Major clinical outcomes including limb salvage rate and antibiotics usage rate were investigated. Ten clinical characteristics and laboratory features of glucose metabolism and kidney function were statistically analyzed. Blood samples from 6 key time points of TTT surgery were collected for label-free proteomics and clinical immune biomarker analysis. Besides, tissue samples from 3 key time points were for spatially resolved metabolomics and transcriptomics analysis, as well as applied to validate the key TTT-regulated molecules by RT-qPCR. RESULTS: Notably, 64.7% of patients did not use antibiotics during the entire TTT surgery. TTT surgery can achieve a high limb salvage rate of 92.6% in patients with unilateral or bilateral DFUs. Pathway analysis of a total of 252 differentially expressed proteins (DEPs) from the proteomic revealed that the immune response induced by TTT surgery at different stages was first comprehensively verified through multi-omics combined with immune biomarker analysis. The function of upward transport was activating the systemic immune response, and wound healing occurs with downward transport. The spatial metabolic characteristics of skin tissue from patients with DFUs indicated downregulated levels of stearoylcarnitine and the glycerophospholipid metabolism pathway in skin tissue from patients with severe DFUs. Finally, the expressions of PRNP (prion protein) to activate the immune response, PLCB3 (PLCB3, phospholipase C beta 3) and VE-cadherin to play roles in neovascularization, and PPDPF (pancreatic progenitor cell differentiation and proliferation factor), LAMC2 (laminin subunit gamma 2) and SPRR2G (small proline rich protein 2G) to facilitate the developmental process mainly keratinocyte differentiation were statistically significant in skin tissues through transcriptomic and RT-qPCR analysis. CONCLUSION: Tibial cortex transverse transport (TTT) surgery demonstrates favorable outcomes for patients with severe type 2 DFUs by activating a systemic immune response, contributing to anti-infection, ulcer recurrence, and the limb salvage rate for unilateral or bilateral DFUs. The specific clinical immune responses, candidate proteins, genes, and metabolic characteristics provide directions for in-depth mechanistic research on TTT surgery. Further research and public awareness are needed to optimize TTT surgery in patients with severe type 2 DFUs.

IPF-related new macrophage subpopulations and diagnostic biomarker identification - combine machine learning with single-cell analysis.

Idiopathic pulmonary fibrosis (IPF) is a chronic disease of unknown etiology that lacks a specific treatment. In IPF, macrophages play a key regulatory role as a major component of the lung immune system, especially during inflammation and fibrosis. However, our understanding of the cellular heterogeneity and molecular characterization of macrophages in IPF, as well as their relevance in the clinical setting, is relatively limited. In this study, we analyzed in-depth single-cell transcriptome sequencing (scRNA-seq) data from lung tissues of IPF patients, identified macrophage subpopulations in IPF, and probed their molecular characteristics and biological functions. hdWGCNA identified co-expressed gene modules of a subpopulation of IPF-associated macrophages (IPF-MΦ), and probed the IPF-MΦ by a machine-learning approach. hdWGCNA identified a subpopulation of IPF-associated macrophage subpopulations and probed the IPF-MΦ signature gene (IRMG) for its prognostic value, and a prediction model was developed on this basis. In addition, IPF-MΦ was obtained after recluster analysis of macrophages in IPF lung tissues. Coexpressed gene modules of IPF-MΦ were identified by hdWGCNA. Then, a machine learning approach was utilized to reveal the characteristic genes of IPF-MΦ, and a prediction model was built on this basis. In addition, we discovered a type of macrophage unique to IPF lung tissue named ATP5-MΦ. Its characteristic gene encodes a subunit of the mitochondrial ATP synthase complex, which is closely related to oxidative phosphorylation and proton transmembrane transport, suggesting that ATP5-MΦ may have higher ATP synthesis capacity in IPF lung tissue. This study provides new insights into the pathogenesis of IPF and provides a basis for evaluating disease prognosis and predictive medicine in IPF patients.

Spatial accessibility and inequality analysis of rabies-exposed patients to rabies post-exposure prophylaxis clinics in Guangzhou City, China.

BACKGROUND: The incidence of rabies exposure is high and increasing in China, leading to an urgent demand of rabies post-exposure prophylaxis (PEP) clinics for the injured. However, the spatial accessibility and inequality of rabies-exposed patients to rabies PEP clinics is less known in China. METHODS: Based on rabies exposure data, PEP clinic data, and resident travel origin-destination (OD) matrix data in Guangzhou City, China, we first described the incidence of rabies exposure in Guangzhou from 2020 to 2022. Then, the Gaussian two-step floating catchment area method (2SFCA) was used to analyze the spatial accessibility of rabies-exposed patients to rabies PEP clinics in Guangzhou, and the Gini coefficient and Moran's I statistics were utilized to evaluate the inequality and clustering of accessibility scores. RESULTS: From 2020 to 2022, a total of 524,160 cases of rabies exposure were reported in Guangzhou, and the incidence showed a significant increasing trend, with an average annual incidence of 932.0/100,000. Spatial accessibility analysis revealed that the overall spatial accessibility scores for three scenarios (threshold of driving duration [d0] = 30 min, 45 min, and 60 min) were 0.30 (95% CI: 0.07, 0.87), 0.28 (95% CI: 0.11, 0.53) and 0.28 (95% CI: 0.14, 0.44), respectively. Conghua, Huangpu, Zengcheng and Nansha districts had the higher accessibility scores, while Haizhu, Liwan, and Yuexiu districts exhibited lower spatial accessibility scores. The Gini coefficient and Moran's I statistics showed that there were certain inequality and clustering in the accessibility to rabies PEP clinics in Guangzhou. CONCLUSIONS: This study clarifies the heterogeneity of spatial accessibility to rabies PEP clinics, and provide valuable insights for resource allocation to achieve the WHO target of zero human dog-mediated rabies deaths by 2030.

Chest trauma clinical practice guideline protects against delirium in patients with rib fractures.

Introduction: Traumatic rib fractures present a considerable risk to patient well-being, contributing to morbidity and mortality in trauma patients. To address the risks associated with rib fractures, evidence-based interventions have been implemented, including effective pain management, pulmonary hygiene, and early walking. Vancouver General Hospital, a level 1 trauma center in British Columbia, Canada, developed a comprehensive multidisciplinary chest trauma clinical practice guideline (CTCPG) to optimize the management of patients with rib fractures. This prospective cohort study aimed to assess the impact of the CTCPG on pain management interventions and patient outcomes. Methods: The study involved patients admitted between January 1, 2021 and December 31, 2021 (post-CTCPG cohort) and a historical control group admitted between November 1, 2018 and December 31, 2019 (pre-CTCPG cohort). Patient data were collected from patient charts and the British Columbia Trauma Registry, including demographics, injury characteristics, pain management interventions, and relevant outcomes. Results: Implementation of the CTCPG resulted in an increased use of multimodal pain therapy (99.4% vs 96.1%; p=0.03) and a significant reduction in the incidence of delirium in the post-CTCPG cohort (OR 0.43, 95% CI 0.21 to 0.80, p=0.0099). There were no significant differences in hospital length of stay, ICU (intensive care unit) days, non-invasive positive pressure ventilation requirement, ventilator days, pneumonia incidence, or mortality between the two cohorts. Discussion: Adoption of a CTCPG improved chest trauma management by enhancing pain management and reducing the incidence of delirium. Further research, including multicenter studies, is warranted to validate these findings and explore additional potential benefits of the CTCPG in the management of chest trauma patients. Level of evidence: IIb.

Non-invasive screening of bladder cancer using digital microfluidics and FLIM technology combined with deep learning.

Non-invasive screening for bladder cancer is crucial for treatment and postoperative follow-up. This study combines digital microfluidics (DMF) technology with fluorescence lifetime imaging microscopy (FLIM) for urine analysis and introduces a novel non-invasive bladder cancer screening technique. Initially, the DMF was utilized to perform preliminary screening and enrichment of urine exfoliated cells from 54 participants, followed by cell staining and FLIM analysis to assess the viscosity of the intracellular microenvironment. Subsequently, a deep learning residual convolutional neural network was employed to automatically classify FLIM images, achieving a three-class prediction of high-risk (malignant), low-risk (benign), and minimal risk (normal) categories. The results demonstrated a high consistency with pathological diagnosis, with an accuracy of 91% and a precision of 93%. Notably, the method is sensitive for both high-grade and low-grade bladder cancer cases. This highly accurate non-invasive screening method presents a promising approach for bladder cancer screening with significant clinical application potential.

Potential regulator of meat quality in geese: C1QTNF1 implications on cell proliferation and muscle growth.

Goose creates important economic value depending on their enrich nutrients of meat. Our previous study investigates potential candidate genes associated with variations in meat quality between Xianghai Flying (XHF) Goose and Zi Goose through genomic and transcriptome integrated analysis. Screening of 5 differential expression candidate genes related to muscle development identified by the FST, XP-EHH and RNA-seq in breast muscle from various geese. Among them, C1QTNF1 (C1q and TNF related protein 1), a gene of unknown function in goose, which observed mutations in coding sequence regions in sequencing data. Its function was explored after overexpression and knockdown which designed depending on the genetic sequence of the goose, respectively. Results showed that over-expression of C1QTNF1 significantly enhances cell proliferation and viability. In addition, the expression levels of the fusion marker gene Myomaker and the differentiation marker gene MyoD are significantly upregulated in cells. Knock-down C1QTNF1 leads to down regulated Myomaker and MyoD which involved muscle formation. But, the expression level of muscle atrophy marker MuRF is not significantly changed among different transfection groups. Since protein structures and interactions are closely related to their functions, we further analyzed the C1QTNF1 for physicochemical properties, structural predictions, protein interactions and homology. It can be reasonably inferred that C1QTNF1 has a similar effect to collagen, which may affect muscle development. In summary, we first speculate that C1QTNF1 may play an important regulatory role in muscle growth and development and thereby contributes to the further understanding of the genetic mechanisms that underlie meat quality traits of goose.

Transcriptome Study of rd1Mouse Brain and Association with Parkinson's Disease.

Degeneration of the retina is intrinsically associated with the pathogenesis and progression of neurodegenerative diseases. However, the cellular and molecular mechanisms underlying the association between neurodegeneration and retinal degeneration are still under exploration due to the complexity of the connectivity network of the nervous system. In this study, RNA-seq data from the brains of model retinitis pigmentosa (RP) mice and previously studied Parkinson's disease (PD) mice were analyzed to explore the commonalities between retinal degenerative and neurodegenerative diseases. Differentially expressed genes in RP were compared with neurodegenerative disease-related genes and intersecting genes were identified, including Cnr1 and Septin14. These genes were verified by quantitative real-time reverse transcription PCR and Western blotting experiments. The key proteins CNR1 and SEPTIN14 were found to be potential cotherapeutic targets for retinal degeneration and neurodegenerative disease. In conclusion, understanding the commonalities between retinal degenerative diseases and neurodegenerative processes in the brain will not only facilitate the interpretation of the underlying pathomechanisms but also contribute to early diagnosis and the development of new therapeutic strategies.

[Clinical Significance of Serum ADA Combined with GLB, CREA, ß2-MG and HGB in Newly Diagnosed Multiple Myeloma].

OBJECTIVE: To investigate the role of serum adenosine deaminase (ADA) combined with globulin (GLB), creatinine (CREA), ß2-microglobulin (ß2-MG) and hemoglobin (HGB) in the initial screening of multiple myeloma (MM), in order to reduce missed diagnosis and misdiagnosis of MM. METHODS: A retrospective analysis was performed on 62 newly diagnosed multiple myeloma (NDMM) patients who were admitted to the Department of Hematology of the First Affiliated Hospital of Chengdu Medical College from April 2018 to December 2021, and 33 patients with benign hematologic diseases and 30 healthy subjects were selected as the control group. The expression of ADA in pan-cancer was analyzed using TCGA and GTEx databases. The general data and laboratory indicators of the subjects were collected, and the differences of ADA activity and other laboratory indicators in each group were compared. The relationship between serum ADA activity and clinical data of NDMM patients was analyzed. The changes of ADA activity before and after chemotherapy in NDMM patients and the differences of ADA activity in NDMM patients with different DS and ISS stages were compared. Multivariate logistic regression was used to analyze the risk factors of NDMM. The receiver operating characteristic(ROC) curve was used to evaluate the diagnostic efficacy of ADA and other laboratory indicators in MM. Bioinformatics method was used to analyze the co-expression networks and enrichment pathways of ADA. RESULTS: ADA level was significantly upregulated in tissues of 14 types of cancer in TCGA database, and ADA was highly expressed in 11 types of cancer in TCGA combined with GTEx databases. The serum levels of ADA, GLB, uric acid (UA), cystatin C (CysC) and ß2-MG in the NDMM group were significantly higher than those in benign hematologic disease group and healthy control group ( P < 0.05), while the levels of ALB and the value of albumin to globulin ratio (A∶G) in the NDMM group were significantly lower than those in the other two groups ( P < 0.001). There were significant differences in DS stage (P =0.036), ISS stage (P =0.019) and the levels of CREA (P =0.036), UA (P =0.034), ß2-MG (P =0.019) in NDMM patients with different ADA activity levels. After primary chemotherapy, ADA activity and ß2-MG concentration were decreased in NDMM patients ( P < 0.01). The comparison results of patients in different stages showed that ADA activity of patients in DS stage I+II was significantly lower than that of patients in DS stage III (P <0.05), and ADA activity of patiens in ISS stage I+II was significantly lower than that of patients in ISS stage III ( P < 0.01). Multivariate logistic regression analysis showed that increased GLB, increased ADA activity, increased CREA, increased ß2-MG and decreased HGB were independent risk factors for NDMM. The area under the curve (AUC) of ADA in the diagnosis of MM was 0.847, and the AUC of ADA combined with GLB, CREA, ß2-MG and HGB in the diagnosis of MM was 0.940. The results of co-expression network and enrichment pathway analysis showed that ADA bounded to 20 proteins and it was significantly associated with the metabolic pathways of purine, pyrimidine, nicotinate and nicotinamide. CONCLUSION: The detection of ADA activity in serum is of positive significance for the auxiliary diagnosis, therapeutic evaluation and monitoring the progress of NDMM patients. ADA combined with GLB, CREA, ß2-MG and HGB can improve the detection rate of MM, and reduce missed diagnosis and misdiagnosis to a certain extent.

Human iPSC-derived liver co-culture spheroids to model liver fibrosis.

The lack of adequate humanin vitromodels that recapitulate the cellular composition and response of the human liver to injury hampers the development of anti-fibrotic drugs. The goal of this study was to develop a human spheroid culture model to study liver fibrosis by using induced pluripotent stem cell (iPSC)-derived liver cells. iPSCs were independently differentiated towards hepatoblasts (iHepatoblasts), hepatic stellate cells (iHSCs), endothelial cells (iECs) and macrophages (iMΦ), before assembly into free floating spheroids by culturing cells in 96-well U-bottom plates and orbital shaking for up to 21 days to allow further maturation. Through transcriptome analysis, we show further maturation of iECs and iMΦ, the differentiation of the iHepatoblasts towards hepatocyte-like cells (iHeps) and the inactivation of the iHSCs by the end of the 3D culture. Moreover, these cultures display a similar expression of cell-specific marker genes (CYP3A4, PDGFRß, CD31andCD68) and sensitivity to hepatotoxicity as spheroids made using freshly isolated primary human liver cells. Furthermore, we show the functionality of the iHeps and the iHSCs by mimicking liver fibrosis through iHep-induced iHSC activation, using acetaminophen. In conclusion, we have established a reproducible human iPSC-derived liver culture model that can be used to mimic fibrosisin vitroas a replacement of primary human liver derived 3D models. The model can be used to investigate pathways involved in fibrosis development and to identify new targets for chronic liver disease therapy.

ZmABF4-ZmVIL2/ZmFIP37 module enhances drought tolerance in maize seedlings.

Drought, as a primary environmental factor, imposes significant constraints on developmental processes and productivity of plants. PHDs were identified as stress-responsive genes in a wide range of eukaryotes. However, the regulatory mechanisms governing PHD genes in maize under abiotic stress conditions are still largely unknown and require further investigation. Here, we identified a mutant, zmvil2, in the EMS mutant library with a C to T mutation in the exon of the Zm00001d053875 (VIN3-like protein 2, ZmVIL2), resulting in premature termination of protein coding. ZmVIL2 belongs to PHD protein family. Compared to WT, zmvil2 mutant exhibited increased sensitivity to drought stress. Consistently, overexpression of ZmVIL2 enhances drought resistance in maize. Y2H, BiFC, and Co-IP experiments revealed that ZmVIL2 directly interacts with ZmFIP37 (FKBP12-interacting protein of 37). zmfip37 knockout mutants also exhibit decreased drought tolerance. Interestingly, we demonstrated that ZmABF4 directly binds to the ZmVIL2 promoter to enhance its activity in yeast one hybrid (Y1H), electrophoretic mobility shift assay (EMSA) and dual luciferase reporter assays. Therefore, we uncovered a novel model ZmABF4-ZmVIL2/ZmFIP37 that promotes drought tolerance in maize. Overall, these findings have enriched the knowledge of the functions of PHD genes in maize and provides genetic resources for breeding stress-tolerant maize varieties.

Effect of Different Staining Methods on Brain Cryosections.

Staining frozen sections is often required to distinguish cell types for spatial transcriptomic studies of the brain. The impact of the staining methods on the RNA integrity of the cells becomes one of the limitations of spatial transcriptome technology with microdissection. However, there is a lack of systematic comparisons of different staining modalities for the pretreatment of frozen sections of brain tissue as well as their effects on transcriptome sequencing results. In this study, four different staining methods were analyzed for their effect on RNA integrity in frozen sections of brain tissue. Subsequently, differences in RNA quality in frozen sections under different staining conditions and their impact on transcriptome sequencing results were assessed by RNA-seq. As one of the most commonly used methods for staining pathological sections, HE staining seriously affects the RNA quality of frozen sections of brain tissue. In contrast, the homemade cresyl violet staining method developed in this study has the advantages of short staining time, low cost, and less RNA degradation. The homemade cresyl violet staining proposed in this study can be applied instead of HE staining as an advance staining step for transcriptome studies in frozen sections of brain tissue. In the future, this staining method may be suitable for wide application in brain-related studies of frozen tissue sections. Moreover, it is expected to become a routine step for staining cells before sampling in brain science.

Prediction of Transcription Factor Binding Sites on Cell-Free DNA Based on Deep Learning.

Transcription factors (TFs) are important regulatory elements for vital cellular activities, and the identification of transcription factor binding sites (TFBS) can help to explore gene regulatory mechanisms. Research studies have proved that cfDNA (cell-free DNA) shows relatively higher coverage at TFBS due to the protection by TF from degradation by nucleases and short fragments of cfDNA are enriched in TFBS. However, there are still great difficulties in the noninvasive identification of TFBSs from experimental techniques. In this study, we propose a deep learning-based approach that can noninvasively predict TFBSs of cfDNA by learning sequence information from known TFBSs through convolutional neural networks. Under the addition of long short-term memory, our model achieved an area under the curve of 84%. Based on this model to predict cfDNA, we found consistent motifs in cfDNA fragments and lower coverage occurred upstream and downstream of these cfDNA fragments, which is consistent with a previous study. We also found that the binding sites of the same TF differ in different cell lines. TF-specific target genes were detected from cfDNA and were enriched in cancer-related pathways. In summary, our method of locating TFBSs from plasma has the potential to reflect the intrinsic regulatory mechanism from a noninvasive perspective and provide technical guidance for dynamic monitoring of disease in clinical practice.

Contribution of diversity of social participation on the mental health of humanitarian migrants during resettlement.

AIMS: By the end of 2022, an estimated 108.4 million individuals worldwide experienced forced displacement. Identifying modifiable factors associated with the mental illness of refugees is crucial for promoting successful integration and developing effective health policies. This study aims to examine the associations between the changes in the diversity of social participation and psychological distress among refugees throughout the resettlement process, specifically focusing on gender differences. METHODS: Utilizing data from three waves of a longitudinal, nationally representative cohort study conducted in Australia, this study involved 2399 refugees interviewed during Wave 1, 1894 individuals interviewed during Wave 3 and 1881 respondents during Wave 5. At each wave, we assessed psychological distress and 10 types of social participation across 3 distinct dimensions, including social activities, employment and education. The primary analysis employed mixed linear models and time-varying Cox models. Gender-stratified analyses and sensitivity analyses were performed. RESULTS: Refugees engaging in one type or two or more types of social participation, compared with those not engaging in any, consistently had lower psychological distress scores (ß = -0.62 [95% confidence interval (CI), -1.07 to -0.17] for one type of social participation; ß = -0.57 [95% CI, -1.04 to -0.10] for two or more types of social participation) and a reduced risk of experiencing psychological distress (hazard ratio [HR] = 0.81 [95% CI, 0.65-0.99] for one type of social participation; HR = 0.77 [95% CI, 0.61-0.97] for two or more types of social participation) during the resettlement period. When stratifying the results by gender, these associations in the adjusted models only remained significant in male refugees. Moreover, three specific types of social participation, namely sporting activities, leisure activities and current employment status, were most prominently associated with a reduced risk of psychological distress. CONCLUSIONS: The findings of this cohort study suggest that social participation was consistently associated with reduced risks of psychological distress among male refugees during resettlement. These findings highlight the significance of promoting meaningful social participation and interaction may be an effective strategy to improve the mental health of refugees and facilitate their successful integration into society, especially among male refugees.

Gut microbiota derived from fecal microbiota transplantation enhances body weight of Mimas squabs.

OBJECTIVE: Compared to Mimas pigeons, Shiqi pigeons exhibit greater tolerance to coarse feeding because of their abundant gut microbiota. Here, to investigate the potential of utilizing intestinal flora derived from Shiqi pigeons, the intestinal flora and body indices of Mimas squabs were evaluated after fecal microbiota transplantation (FMT) from donors. METHODS: A total of 90 one-day-old squabs were randomly divided into the control group (CON), the low-concentration group (LC) and the high-concentration group (HC): gavaged with 200 µL of bacterial solution at concentrations of 0, 0.1, and 0.2 g/15 mL, respectively. RESULTS: The results suggested that FMT improved the body weight of Mimas squabs in the HC and LC groups (p<0.01), and 0.1 g/15 mL was the optimal dose during FMT. After 16S rRNA sequencing was performed, compared to those in the CON group, the abundance levels of microflora, especially Lactobacillus, Muribaculaceae, and Megasphaera (p<0.05), in the FMT-treated groups were markedly greater. Random forest analysis indicated that the main functions of key microbes involve pathways associated with metabolism, further illustrating their important role in the host body. CONCLUSION: FMT has been determined to be a viable method for augmenting the weight and intestinal microbiota of squabs, representing a unique avenue for enhancing the economic feasibility of squab breeding.

Evaluation of AlphaFold2 Structures for Hit Identification across Multiple Scenarios.

The introduction of AlphaFold2 (AF2) has sparked significant enthusiasm and generated extensive discussion within the scientific community, particularly among drug discovery researchers. Although previous studies have addressed the performance of AF2 structures in virtual screening (VS), a more comprehensive investigation is still necessary considering the paramount importance of structural accuracy in drug design. In this study, we evaluate the performance of AF2 structures in VS across three common drug discovery scenarios: targets with holo, apo, and AF2 structures; targets with only apo and AF2 structures; and targets exclusively with AF2 structures. We utilized both the traditional physics-based Glide and the deep-learning-based scoring function RTMscore to rank the compounds in the DUD-E, DEKOIS 2.0, and DECOY data sets. The results demonstrate that, overall, the performance of VS on AF2 structures is comparable to that on apo structures but notably inferior to that on holo structures across diverse scenarios. Moreover, when a target has solely AF2 structure, selecting the holo structure of the target from different subtypes within the same protein family produces comparable results with the AF2 structure for VS on the data set of the AF2 structures, and significantly better results than the AF2 structures on its own data set. This indicates that utilizing AF2 structures for docking-based VS may not yield most satisfactory outcomes, even when solely AF2 structures are available. Moreover, we rule out the possibility that the variations in VS performance between the binding pockets of AF2 and holo structures arise from the differences in their biological assembly composition.

The Impact of Blood Sample Processing on Ribonucleic Acid (RNA) Sequencing.

In gene quantification and expression analysis, issues with sample selection and processing can be serious, as they can easily introduce irrelevant variables and lead to ambiguous results. This study aims to investigate the extent and mechanism of the impact of sample selection and processing on ribonucleic acid (RNA) sequencing. RNA from PBMCs and blood samples was investigated in this study. The integrity of this RNA was measured under different storage times. All the samples underwent high-throughput sequencing for comprehensive evaluation. The differentially expressed genes and their potential functions were analyzed after the samples were placed at room temperature for 0h, 4h and 8h, and different feature changes in these samples were also revealed. The sequencing results showed that the differences in gene expression were higher with an increased storage time, while the total number of genes detected did not change significantly. There were five genes showing gradient patterns over different storage times, all of which were protein-coding genes that had not been mentioned in previous studies. The effect of different storage times on seemingly the same samples was analyzed in this present study. This research, therefore, provides a theoretical basis for the long-term consideration of whether sample processing should be adequately addressed.

Effects of chronic stress on cancer development and the therapeutic prospects of adrenergic signaling regulation.

Long-term chronic stress is an important factor in the poor prognosis of cancer patients. Chronic stress reduces the tissue infiltration of immune cells in the tumor microenvironment (TME) by continuously activating the adrenergic signaling, inhibits antitumor immune response and tumor cell apoptosis while also inducing epithelial-mesenchymal transition (EMT) and tumor angiogenesis, promoting tumor invasion and metastasis. This review first summarizes how adrenergic signaling activates intracellular signaling by binding different adrenergic receptor (AR) heterodimers. Then, we focused on reviewing adrenergic signaling to regulate multiple functions of immune cells, including cell differentiation, migration, and cytokine secretion. In addition, the article discusses the mechanisms by which adrenergic signaling exerts pro-tumorigenic effects by acting directly on the tumor itself. It also highlights the use of adrenergic receptor modulators in cancer therapy, with particular emphasis on their potential role in immunotherapy. Finally, the article reviews the beneficial effects of stress intervention measures on cancer treatment. We think that enhancing the body's antitumor response by adjusting adrenergic signaling can enhance the efficacy of cancer treatment.

The antagonistic transcription factors, EspM and EspN, regulate the ESX-1 secretion system in M. marinum.

Bacterial pathogens use protein secretion systems to transport virulence factors and regulate gene expression. Among pathogenic mycobacteria, including Mycobacterium tuberculosis and Mycobacterium marinum, the ESAT-6 system 1 (ESX-1) secretion is crucial for host interaction. Secretion of protein substrates by the ESX-1 secretion system disrupts phagosomes, allowing mycobacteria cytoplasmic access during macrophage infections. Deletion or mutation of the ESX-1 system attenuates mycobacterial pathogens. Pathogenic mycobacteria respond to the presence or absence of the ESX-1 system in the cytoplasmic membrane by altering transcription. Under laboratory conditions, the EspM repressor and WhiB6 activator control transcription of specific ESX-1-responsive genes, including the ESX-1 substrate genes. However, deleting the espM or whiB6 gene does not phenocopy the deletion of the ESX-1 substrate genes during macrophage infection by M. marinum. In this study, we identified EspN, a critical transcription factor whose activity is masked by the EspM repressor under laboratory conditions. In the absence of EspM, EspN activates transcription of whiB6 and ESX-1 genes during both laboratory growth and macrophage infection. EspN is also independently required for M. marinum growth within and cytolysis of macrophages, similar to the ESX-1 genes, and for disease burden in a zebrafish larval model of infection. These findings suggest that EspN and EspM coordinate to counterbalance the regulation of the ESX-1 system and support mycobacterial pathogenesis.IMPORTANCEPathogenic mycobacteria, which are responsible for tuberculosis and other long-term diseases, use the ESX-1 system to transport proteins that control the host response to infection and promote bacterial survival. In this study, we identify an undescribed transcription factor that controls the expression of ESX-1 genes and is required for both macrophage and animal infection. However, this transcription factor is not the primary regulator of ESX-1 genes under standard laboratory conditions. These findings identify a critical transcription factor that likely controls expression of a major virulence pathway during infection, but whose effect is not detectable with standard laboratory strains and growth conditions.

Psychological status of residents at the onset of nationwide COVID-19 lockdown in low- and medium-risk areas of China.

The coronavirus disease 2019 (COVID-19), a dual threat to public physical and mental health, prompted an investigation into the psychological well-being of residents in low- to medium-risk areas of China during the initial stages of the pandemic. We administered WeChat-based questionnaire surveys and employed chi-square tests and multiple logistic regression to analyze correlations between residents' age, gender, education, symptoms, COVID-19 close contact history, information sources, and anxiety, depression, and attitudes toward lockdown measures. We received 10,433 valid questionnaires, revealing 26% anxiety and 19.5% depression. Support for lockdown measures reached 98.2%. Factors such as female gender, self-diagnosed pneumonia symptoms, close contact history, and higher education levels increased anxiety risk. Having a doctorate posed a severe anxiety risk, at 4.5 times (P = .019, 95% CI 1.29-15.73). Older age acted as a protective factor, reducing severe anxiety risk to 0.98 and 0.22 times (P < .001, 95% CI 0.14-0.34). Females with a master degree or below and those receiving COVID-19 information from multiple channels faced higher depression risk. Pneumonia symptoms were a risk for all anxiety and depression degrees. Attitudes toward lockdown measures had no significant impact on psychological status, nor did any of the analyzed factors affect residents' overall attitude toward lockdown. Our findings underscore the need for increased psychological counseling, particularly for young females with lower educational backgrounds or self-suspected infection symptoms, to mitigate mild to moderate anxiety and depression in future epidemics or pandemics. The public, especially those of working age with doctorates or higher education, bears the highest risk of severe anxiety. Lockdown measures enjoy strong support in low- to medium-risk areas of China.