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Abstract Background Stress Hyperglycemia Ratio (SHR) reflects the acute blood glucose variation in critically ill conditions. However, its prognostic value in chronic kidney disease (CKD) remains understudied. This study aimed to investigate the association between SHR and one-year mortality in CKD patients hospitalized in the Intensive Care Unit (ICU). Methods Patients with diagnosis of CKD in the Medical Information Mart for Intensive Care IV (MIMIC-IV) database were enrolled. Incidence of all-cause mortality within one-year follow-up was used as the primary endpoint. Results 1825 CKD patients were included in the study. A “U-shaped” relationship between SHR and one-year mortality as identified using multivariate restricted cubic spline (RCS) analysis. Then study population were categorized into three groups: Group 1 (SHR 0.95). Group 2 showed significantly better one-year outcomes compared to the other two groups (p = 0.0031). This survival benefit persisted across subgroup analyses stratified by age, sex, CKD stage, anemia and various clinical conditions. Conclusion SHR proved to be a meaningful biomarker for predicting one-year mortality in ICU-admitted CKD patients, with a “U-shaped” correlation. The identification of the optimal SHR range (0.70–0.95) provided clinicians with a valuable tool for detecting high-risk populations.

Background: Our previous research has shown that LKB1 in amniotic mesenchymal stem cells (MSCs) serves as a vital regulator of regulatory T cell differentiation and T cell proliferation, which may have a similar role in bone marrow MSCs (BMMSCs). Therefore, we investigated the role of LKB1 in BMMSCs for regulating CD4+ T cell proliferation in the bone micro-environment of AML. Methods: RT-PCR was used to assessed LKB1 expression in BMMSCs derived from AML patients and healthy controls. Subsequently, LKB1 was knocked down in the BMMSCs line HS-5 (HS-5-LKB1KD). Co-cultures in vitro were established to analyze the effect of HS-5-LKB1KD on CD4+ T cell. Flow cytometry was employed to measure PD-L1 and CD4+ T cell proliferation levels. Western blot was utilized to detect related proteins. Results: The expression of LKB1 in BMMSCs derived from AML patients was decreased. Knockdown of LKB1 in HS-5 resulted in upregulation of PD-L1 expression. Co-culture of peripheral blood CD4+ T cell with HS-5-LKB1KD exhibited reduced CD4+ T cell proliferation compared to co-culture with HS-5-LKB1con. Furthermore, blocking PD-L1 in the co-culture conditions could restore the reduced CD4+ T cell proliferation. Additionally, it was found that upregulation of the Wnt signaling pathway-related proteins following LKB1 knockdown in HS-5, indicating that downregulating LKB1 could promote PD-L1 expression through activation of the Wnt signaling pathway. Conclusions: The decreased expression of LKB1 in BMMSCs may activate the Wnt signaling pathway, leading to increased PD-L1 expression. This inhibited CD4+ T cell proliferation, which might lead to impaired anti-tumor immunity in AML patients and promote AML progression.

Hepatotoxicity is an significant side effect of doxorubicin (DOX), while astaxanthin (ASX) has the anti-liver injury biological functions. In this study, we utilized in vivo and in vitro methods to investigate the protective effect of ASX against DOX-induced hepatotoxicity and elucidate its potential mechanism. Our researchers measured liver injury indicators and the expression of ferroptosis-related protein (transferrin receptor 1 (TFRC), ferroportin 1 (FPN1), ferritin light chain (FTL), ferritin heavy chain-1 (FTH1), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11)) in rats and HepG2 cells. We found that ASX could effectively reduce ferroptosis level and relieve a range of DOX-caused manifestations of liver injury, including inflammation and oxidative damage. ASX may play the same role as ferroptosis inhibitor, Fer-1 and DFP, in this process. The findings demonstrated that the intervention with ASX ameliorated the DOX-induced liver injury by mitigating the DOX-induced ferroptosis through inhibiting iron accumulation.

Background: The effect of dietary antioxidant capacity on health has attracted increasing attention, but unequivocal evidence for its benefits on cardiovascular diseases is still lacking. Objectives: Our aim was to assess the association between composite dietary antioxidant index (CDAI) and Life’s Essential 8 (LE8), an evaluation indicator of cardiovascular health (CVH), in two large cohorts. Methods: The cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) 2005–2018 and Community Cohort Study on Specialized Nervous System Diseases (CCSNSD) 2018. The relationship between CDAI and CVH was studied by multinomial logistic regression, restricted cubic spline, subgroup and sensitivity analysis. Results: After adjusting for all potential confounding factors, it suggested that higher CDAI was positively associated with higher CVH (NHANES: OR Q4 vs. Q1 = 0.19, 95 % CI: 0.14–0.25; CCSNSD: OR Q4 vs. Q1 = 0.03, 95 % CI: 0.03–0.04). And a nonlinear dose–response relationship between CDAI and CVH was observed in two large cohorts. The robustness of the results was further demonstrated by sensitivity analysis. Among them, Mendelian randomization analysis showed that higher Vitamin C and Vitamin E intakes were causally associated with a lower risk of CVD. Moreover, there was a stronger positive correlation between the CDAI and CVH among individuals with lower socioeconomic status in both cohorts. Conclusion: Our findings demonstrated the potential benefit of dietary antioxidant intake in improving CVH. Besides, the relationship between CDAI and CVH may be influenced by income levels, highlighting the need for targeted interventions in populations with low income to increase CVH levels.

Abstract Polyamines, such as putrescine, spermidine, and spermine, are crucial for plant defense against both abiotic and biotic stresses. Putrescine is also known as a significant inducer of deoxynivalenol (DON) production in Fusarium graminearum, the primary causal agent of Fusarium head blight (FHB). However, the impact of other polyamines on DON production and whether modifying polyamine biosynthesis could improve wheat resistance to FHB are currently unknown. In this study, we demonstrate that key precursor components of putrescine synthesis, including arginine, ornithine, and agmatine, can induce DON production, albeit to a lesser extent than putrescine in trichothecene biosynthesis-inducing (TBI) culture under the same total nitrogen conditions. Intriguingly, spermidine and spermine, downstream products of putrescine in the polyamine biosynthesis pathway, do not induce DON production under the same conditions. Additionally, externally applying either spermidine or spermine to wheat heads significantly reduces the diseased spikelet number caused by F. graminearum. Furthermore, our results show that overexpression of the wheat spermidine synthase (SPDS) gene TaSPDS-7D1 significantly enhances the spermidine content and wheat resistance to FHB. In addition, the TaSPDS-7D1-overexpressing line OE3 exhibited a 1000-grain weight and plant height increase compared to the wild type. Our findings reveal that overexpression of the spermidine synthase gene can enhance wheat resistance to FHB without compromising wheat yield.

Background: A task assigned to space exploration satellites involves detecting the physical environment within a certain space. However, space detection data are complex and abstract. These data are not conducive for researchers' visual perceptions of the evolution and interaction of events in the space environment. Methods: A time-series dynamic data sampling method for large-scale space was proposed for sample detection data in space and time, and the corresponding relationships between data location features and other attribute features were established. A tone-mapping method based on statistical histogram equalization was proposed and applied to the final attribute feature data. The visualization process is optimized for rendering by merging materials, reducing the number of patches, and performing other operations. Results: The results of sampling, feature extraction, and uniform visualization of the detection data of complex types, long duration spans, and uneven spatial distributions were obtained. The real-time visualization of large-scale spatial structures using augmented reality devices, particularly low-performance devices, was also investigated. Conclusions: The proposed visualization system can reconstruct the three-dimensional structure of a large-scale space, express the structure and changes in the spatial environment using augmented reality, and assist in intuitively discovering spatial environmental events and evolutionary rules.

Abstract Background N6-methyladenosine (m6A) is dysregulated in various cancers, including colorectal cancer (CRC). Herein, we assess the diagnostic potential of peripheral blood (PB) m6A levels in CRC. Methods We collected PB from healthy controls (HCs) and patients with CRC, analyzed PB RNA m6A levels and the expression of m6A-related demethylase genes FTO and ALKBH5, cocultured CRC cells with PB mononuclear cells (PBMCs), and constructed an MC38 cancer model. Results PB RNA m6A levels were higher in the CRC than that in HCs. The area under the curve (AUC) of m6A levels (0.886) in the CRC was significantly larger compared with carbohydrate antigen 199 (CA199; 0.666) and carcinoembryonic antigen (CEA; 0.834). The combination of CEA and CA199 with PB RNA m6A led to an increase in the AUC (0.935). Compared with HCs, the expression of FTO and ALKBH5 was decreased in the CRC. After coculturing with CRC cells, the PBMCs RNA m6A were significantly increased, whereas the expression of FTO and ALKBH5 decreased. Furthermore, m6A RNA levels in the PB of MC38 cancer models were upregulated, whereas the expression of FTO and ALKBH5 decreased. Conclusions PB RNA m6A levels are a potential diagnostic biomarker for patients with CRC.

Abstract Background Long-term exposure of humans to air pollution is associated with an increasing risk of cardiovascular diseases (CVDs). Astaxanthin (AST), a naturally occurring red carotenoid pigment, was proved to have multiple health benefits. However, whether or not AST also exerts a protective effect on fine particulate matter (PM2.5)-induced cardiomyocyte damage and its underlying mechanisms remain unclear. Methods In vitro experiments, the H9C2 cells were subjected to pretreatment with varying concentrations of AST, and then cardiomyocyte injury model induced by PM2.5 was established. The cell viability and the ferroptosis-related proteins expression were measured in different groups. In vivo experiments, the rats were pretreated with different concentrations of AST for 21 days. Subsequently, a rat model of myocardial PM2.5 injury was established by intratracheal instillation every other day for 1 week. The effects of AST on myocardial tissue injury caused by PM2.5 indicating by histological, serum, and protein analyses were examined. Results AST significantly ameliorated PM2.5-induced myocardial tissue injury, inflammatory cell infiltration, the release of inflammatory factors, and cardiomyocyte H9C2 cell damage. Mechanistically, AST pretreatment increased the expression of SLC7A11, GPX4 and down-regulated the expression of TfR1, FTL and FTH1 in vitro and in vivo. Conclusions Our study suggest that ferroptosis plays a significant role in the pathogenesis of cardiomyocyte injury induced by PM2.5. AST may serve as a potential therapeutic agent for mitigating cardiomyocyte injury caused by PM2.5 through the inhibition of ferroptosis.

Abstract Background The primary objective of the research was to develop a method using radiomics-based computed tomography (CT) to predict muscle invasion in bladder cancer (BCa) before surgery. Methods A total of 269 patients with bladder cancer were divided into two groups; training group (n = 188 cases) and validation group (n = 81 cases). Radiomics characteristics were determined by analyzing the CT images of each patient. The least absolute shrinkage and selection operator (LASSO) technique was used for developing a radiomics signature. Furthermore, logistic regression (LR), the support vector machine (SVM), decision tree (DT), and Artificial Neural Network (ANN) models were applied to differentiate between non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Their performance was determined using the area under the receiver operating characteristic curve (AUC-ROC). In addition, accuracy, specificity, and sensitivity evaluations were also conducted. Results The radiomics signature was found to be successful in its prediction. A total of 1036 radiomics features were found in the 269 patients, and out of those, 16 were selected as the best predictors of radiomics features. The results revealed that the ANN classifier had the best performance, with a validation set accuracy of 0.950. Conclusions The current work used machine learning and radiomics techniques to successfully construct a prediction model for muscle invasion in bladder cancer. The ANN model produced significant outcomes that may be used in clinical diagnosis or therapy.

Biofilms account for a great deal of infectious diseases and contribute significantly to antimicrobial resistance. Efflux pumps confer antimicrobial resistance to microorganisms and involve multiple processes of biofilm formation. Efflux pump inhibitors (EPIs) are attracting considerable attention as a biofilm inhibition strategy. The regulatory functions of efflux pumps in biofilm formation such as mediating adherence, quorum sensing (QS) systems, and the expression of biofilm-associated genes have been increasingly identified. The versatile properties confer efflux pumps both positive and negative effects on biofilm formation. Furthermore, the expression and function of efflux pumps in biofilm formation are species-specific. Therefore, this review aims to detail the double-edged sword role of efflux pumps in biofilm formation to provide potential inhibition targets and give an overview of the effects of EPIs on biofilm formation.

Introduction ST-segment elevation myocardial infarction (STEMI) with high thrombus burden is associated with a poor prognosis. Manual aspiration thrombectomy reduces coronary vessel distal embolisation, improves microvascular perfusion and reduces cardiovascular deaths, but it promotes more strokes and transient ischaemic attacks in the subgroup with high thrombus burden. Intrathrombus thrombolysis (ie, the local delivery of thrombolytics into the coronary thrombus) is a recently proposed treatment approach that theoretically reduces thrombus volume and the risk of microvascular dysfunction. However, the safety and efficacy of intrathrombus thrombolysis lack sufficient clinical evidence.Methods and analysis The intrAThrombus Thrombolysis versus aspiRAtion thrombeCTomy during prImary percutaneous coronary interVEntion trial is a multicentre, prospective, open-label, randomised controlled trial with the blinded assessment of outcomes. A total of 2500 STEMI patients with high thrombus burden who undergo primary percutaneous coronary intervention will be randomised 1:1 to intrathrombus thrombolysis with a pierced balloon or upfront routine manual aspiration thrombectomy. The primary outcome will be the composite of cardiovascular death, recurrent myocardial infarction, cardiogenic shock, heart failure readmission, stent thrombosis and target-vessel revascularisation up to 180 days.Ethics and dissemination The trial was approved by Ethics Committees of China-Japan Friendship Hospital (2022-KY-013) and all other participating study centres. The results of this trial will be published in peer-reviewed journals.Trial registration number NCT05554588.

Abstract Objective Chronic kidney disease (CKD) patients with coronary artery disease (CAD) in the intensive care unit (ICU) have higher in-hospital mortality and poorer prognosis than patients with either single condition. The objective of this study is to develop a novel model that can predict the in-hospital mortality of that kind of patient in the ICU using machine learning methods. Methods Data of CKD patients with CAD were extracted from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database. Boruta algorithm was conducted for the feature selection process. Eight machine learning algorithms, such as logistic regression (LR), random forest (RF), Decision Tree, K-nearest neighbors (KNN), Gradient Boosting Decision Tree Machine (GBDT), Support Vector Machine (SVM), Neural Network (NN), and Extreme Gradient Boosting (XGBoost), were conducted to construct the predictive model for in-hospital mortality and performance was evaluated by average precision (AP) and area under the receiver operating characteristic curve (AUC). Shapley Additive Explanations (SHAP) algorithm was applied to explain the model visually. Moreover, data from the Telehealth Intensive Care Unit Collaborative Research Database (eICU-CRD) were acquired as an external validation set. Results 3590 and 1657 CKD patients with CAD were acquired from MIMIC-IV and eICU-CRD databases, respectively. A total of 78 variables were selected for the machine learning model development process. Comparatively, GBDT had the highest predictive performance according to the results of AUC (0.946) and AP (0.778). The SHAP method reveals the top 20 factors based on the importance ranking. In addition, GBDT had good predictive value and a certain degree of clinical value in the external validation according to the AUC (0.865), AP (0.672), decision curve analysis, and calibration curve. Conclusion Machine learning algorithms, especially GBDT, can be reliable tools for accurately predicting the in-hospital mortality risk for CKD patients with CAD in the ICU. This contributed to providing optimal resource allocation and reducing in-hospital mortality by tailoring precise management and implementation of early interventions.

Abstract Objective Chinese diabetes society has published the new diagnostic criteria for diabetes in China (2020 edition). We aimed to investigate the predictive value of new diabetes-diagnosed criteria for cardiovascular diseases (CVD). Methods A total of 5884 individuals from the China Health and Retirement Longitudinal Study in 2011 and 2018 were enrolled. Baseline characteristics and outcome data were compared. The association between diabetes diagnosed by two criteria and future CVD was identified by Kaplan–Meier curves, Cox regression analyses, and receiver-operating characteristic analyses. Delong’s test was conducted to compare the predictive value for future CVD between diabetes diagnosed by the 2020 edition and diabetes diagnosed by the previous version. Results After multivariate adjustment, both diabetes diagnosed by the 2020 edition and diabetes diagnosed by the previous edition is associated with CVD (HR 1.607, 95% CI 1.221–2.115, P

ABSTRACT Anthracnose diseases caused by Colletotrichum species are among the most common fungal diseases. These symptoms typically manifest as dark, sunken lesions on leaves, stems, and fruit. In China, mango anthracnose seriously affects fruit yield and quality. Genome sequencing of several species shows the presence of mini-chromosomes. These are thought to contribute to virulence, but their formation and activity remain to be fully elucidated. Here, we assembled 17 Colletotrichum genomes (16 isolated from mango plus one from persimmon) through PacBio long-read sequencing. Half of the assembled scaffolds had telomeric repeats at both ends indicating full-length chromosomes. Based on comparative genomics analysis at interspecies and intraspecies levels, we identified extensive chromosomal rearrangements events. We analyzed mini-chromosomes of Colletotrichum spp. and found large variation among close relatives. In C. fructicola, homology between core chromosomes and mini-chromosomes suggested that some mini-chromosomes were generated by recombination of core chromosomes. In C. musae GZ23-3, we found 26 horizontally transferred genes arranged in clusters on mini-chromosomes. In C. asianum FJ11-1, several potential pathogenesis-related genes on mini-chromosomes were upregulated, especially in strains with highly pathogenic phenotypes. Mutants of these upregulated genes showed obvious defects in virulence. Our findings provide insights into the evolution and potential relationships to virulence associated with mini-chromosomes. IMPORTANCE Colletotrichum is a cosmopolitan fungal genus that seriously affects fruit yield and quality of many plant species. Mini-chromosomes have been found to be related to virulence in Colletotrichum. Further examination of mini-chromosomes can help us elucidate some pathogenic mechanisms of Colletotrichum. In this study, we generated novel assemblies of several Colletotrichum strains. Comparative genomic analyses within and between Colletotrichum species were conducted. We then identified mini-chromosomes in our sequenced strains systematically. The characteristics and generation of mini-chromosomes were investigated. Transcriptome analysis and gene knockout revealed pathogenesis-related genes located on mini-chromosomes of C. asianum FJ11-1. This study represents the most comprehensive investigation of chromosome evolution and potential pathogenicity of mini-chromosomes in the Colletotrichum genus.

Abstract Objective We aimed to investigate the effect of the triglyceride glucose (TyG) index on the association between diabetes and cardiovascular disease (CVD). Methods Data from 6,114 individuals were extracted and analyzed from the China Health and Retirement Longitudinal Survey (CHARLS) from 2011 to 2018. Logistic regression analyses were conducted to assess the relationship between diabetes and CVD across the various TyG index groups. The statistical method of subgroup analysis was used to determine the correlation between diabetes and CVD for each TyG index group by sex, history of hypertension and dyslipidemia, smoking, and drinking. Results Diabetes was positively associated with CVD risk after adjustment in 2011(odds ratio (OR) 1.475, 95% CI 1.243–1.752, P

To clarify the effect of copper powder morphology on the microstructure and properties of copper matrix bulk composites reinforced with Ni-doped graphene, spherical and dendritic copper powders were selected to fabricate the Ni-doped graphene reinforced copper matrix bulk composites. The Ni-doped graphene were synthesized by hydrothermal reduction method, followed by mixing with copper powders, and then consolidated by spark plasma sintering. It is found that the Ni-doped graphene are well bonded with the dendritic copper powder, whereas Ni-doped graphene are relatively independent on the spherical copper powder. The copper base bulk composite prepared by the dendritic copper powder has better properties than that prepared by spherical copper powder. At 0.5wt.% Ni-doped graphene, the dendritic copper base bulk composite has a good combination of hardness, electrical conductivity and yield strength, which are 81.62 HV, 87.93% IACS and 164 MPa, respectively.

Abstract Mitogen-activated protein kinase (MAPK) cascades are activated by external stimuli and convert signals to cellular changes. Individual MAPKs have been characterized in a number of plant pathogenic fungi for their roles in pathogenesis and responses to biotic or abiotic stresses. However, mutants deleted of all the MAPK genes have not been reported in filamentous fungi. To determine the MAPK-less effects in a fungal pathogen, in this study we generated and characterized mutants deleted of all three MAPK genes in the wheat scab fungus Fusarium graminearum. The Gpmk1 mgv1 Fghog1 triple mutants had severe growth defects and was non-pathogenic. It was defective in infection cushion formation and DON production. Conidiation was reduced in the triple mutant, which often produced elongated conidia with more septa than the wild-type conidia. The triple mutant was blocked in sexual reproduction due to the loss of female fertility. Lack of any MAPKs resulted in an increased sensitivity to various abiotic stress including cell wall, osmotic, oxidative stresses, and phytoalexins, which are likely related to the defects of the triple mutant in environmental adaptation and plant infection. The triple mutant also had increased sensitivity to the biocontrol bacterium Bacillus velezensis and fungus Clonostachys rosea. In co-incubation assays with B. velezensis, the Gpmk1 mgv1 Fghog1 mutant had more severe growth limitation than the wild type and was defective in conidium germination and germ tube growth. In confrontation assays, the triple mutant was defective in defending against mycoparasitic activities of C. rosea and the latter could grow over the mutant but not wild-type F. graminearum. RNA-seq and metabolomics analyses showed that the MAPK triple mutant was altered in the expression of many ATP-binding cassette (ABC) and major facilitator superfamily (MFS) transporter genes and the accumulation of metabolites related to arachidonic acid, linoleic acid, and alpha-linolenic acid metabolisms. Overall, as the first study on mutants deleted of all three MAPKs in fungal pathogens, our results showed that although MAPKs are not essential for growth and asexual reproduction, the Gpmk1 mgv1 Fghog1 triple mutant was blocked in plant infection and sexual reproductions. It also had severe defects in responses to various abiotic stresses and bacterial- or fungal-fungal interactions.

Small extracellular vesicles (sEVs) are recognized as promising detection biomarkers and attractive delivery vehicles, showing great potential in diagnosis and treatment of diseases. However, the applications of sEVs are usually restricted by their poor secretion amount from donor cells under routine cell culture conditions, which is especially true for mesenchymal stem cells (MSCs) due to their limited expansion and early senescence. Here, a microfluidic device is proposed for boosting sEV secretion from MSCs derived from human fetal bone marrow (BM-MSCs). As the cells rapidly pass through a microfluidic channel with a series of narrow squeezing ridges, mechanical stimulation permeabilizes the cell membrane, thus promoting them to secrete more sEVs into extracellular space. In this study, the microfluidic device demonstrates that mechanical-squeezing effect could increase the secretion amount of sEVs from the BM-MSCs by approximately 4-fold, while maintaining cellular growth state of the stem cells. Further, the secreted sEVs are efficiently taken up by immortalized human corneal epithelial cells and accelerate corneal epithelial wound healing in vitro, indicating that this technique wound not affect the functionality of sEVs and demonstrating the application potentials of this technique.

BackgroundOvarian cancer (OC) is the most lethal gynecologic malignancy, yet the clinical results for OC patients are still variable. Therefore, we examined how elafin expression affects the patients’ prognoses and immunotherapy responses in OC, which may facilitate treatment selection and improve prognosis.MethodsThe elafin mRNA expression profile was downloaded from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus. Elafin’s prognostic potential and its relationship with clinical variables were investigated using Kaplan–Meier survival curves, time-dependent receiver operating characteristic curves as well as univariate and multivariate Cox regression models. As validation, protein expression in the tumor and adjacent tissues of OC patients was investigated by using immunohistochemistry (IHC). Comprehensive analyses were then conducted to explore the correlation between immune infiltration and elafin expression.ResultsA higher mRNA expression of elafin was associated with an unfavorable prognosis in TCGA cohort and was validated in GSE31245 and IHC. Moreover, elafin was indicated as an independent risk factor for OC. A significantly higher protein expression of elafin was detected in the adjacent tissues of OC patients with shorter overall survival (OS). The immune-related pathways were mainly enriched in the high-elafin-mRNA-expression group. However, the mRNA expression of elafin was favorably correlated with indicators of the immune filtration and immunotherapy response, which also proved better immunotherapy outcomes.ConclusionThe high elafin expression was associated with an unfavorable OS, while it also indicated better immunotherapy responses. Thus, the detection of elafin is beneficial to diagnosis and treatment selection.

In situ transcriptomics maps RNA expression patterns across intact tissues taking our understanding of gene expression to a new level. Here, the authors present a computational method that uncovers gene expression, cell niche, and tissue region patterns from 2D and 3D spatial transcriptomics.

Polycystic ovary syndrome (PCOS) exerts negative effects on females of childbearing age. It is important to identify more suitable models for fundamental research on PCOS. We evaluated animal models from a novel perspective with the aim of helping researchers select the best model for PCOS. RNA sequencing was performed to investigate the mRNA expression profiles in the ovarian tissues of mice with dehydroepiandrosterone (DHEA) plus high-fat diet (HFD)-induced PCOS. Meanwhile, 14 datasets were obtained from the Gene Expression Omnibus (GEO), including eight studies on humans, three on rats and three on mice, and genes associated with PCOS were obtained from the PCOSKB website. We compared the consistency of each animal model and human PCOS in terms of DEGs and pathway enrichment analysis results. There were 239 DEGs shared between prenatally androgenized (PNA) mice and PCOS patients. Moreover, 1113 genes associated with PCOS from the PCOSKB website were identified among the DEGs of PNA mice. A total of 134 GO and KEGG pathways were shared between PNA mice and PCOS patients. These findings suggest that the PNA mouse model is the best animal model to simulate PCOS.

Evidence on the health benefits of vitamin C supplementation in highly polluted areas has not been evaluated. We aimed to evaluate whether dietary vitamin C supplementation can improve vascular health linked to particulate matter (PM) exposure. A randomised double-blind crossover trial involving 58 health young adults was performed in Shijiazhuang, China in 2018. All subjects were randomly assigned to the vitamin C supplementation group (2000 mg/d) or placebo group for a week alternating with a 2 week washout period. Fifteen circulating biomarkers were measured. Linear mixed-effect model was applied to evaluate the effect of vitamin C supplementation on health outcomes. The average concentrations of PM2.5 and PM10 were 164.91 and 327.05 μg/m3, respectively. Vitamin C supplementation was significantly associated with a 19.47% decrease in interleukin-6 (IL-6), 17.30% decrease in tumour necrosis factor-a (TNF-α), 34.01% decrease in C-reactive protein (CRP), 3.37% decrease in systolic blood pressure (SBP) and 6.03% decrease in pulse pressure (PP). Furthermore, glutathione peroxidase (GSH-Px) was significantly increased by 7.15%. Sex-subgroup analysis showed that vitamin C significantly reduced TNF-α by 27.85% in male participants and significantly increased APOB by 6.28% and GSH-Px by 14.47% only in female participants. This study indicated that vitamin C supplementation may protect vascular vessels against PM exposure among healthy young adults in China.

BackgroundOvarian cancer (OC) is one of the most lethal gynecologic malignancies and a leading cause of death in the world. Thus, this necessitates identification of prognostic biomarkers which will be helpful in its treatment.MethodsThe gene expression profiles from The Cancer Genome Atlas (TCGA) and GSE31245 were selected as the training cohort and validation cohort, respectively. The Kaplan–Meier (KM) survival analysis was used to analyze the difference in overall survival (OS) between high and low RB transcriptional corepressor 1 (RB1) expression groups. To confirm whether RB1 was an independent risk factor for OC, we constructed a multivariate Cox regression model. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways enrichment analyses were conducted to identify the functions of differentially expressed genes (DEGs). The associations of RB1 with immune infiltration and immune checkpoints were studied by the Tumor Immune Estimation Resource (TIMER 2.0) and the Gene Expression Profiling Interactive Analysis (GEPIA). The immunohistochemistry (IHC) was performed to compare the expression level of RB1 in normal tissues and tumor samples, and to predict the prognosis of OC.ResultsThe KM survival curve of the TCGA indicated that the OS in the high-risk group was lower than that in the low-risk group (HR = 1.61, 95% CI: 1.28-2.02, P = 3×10-5), which was validated in GSE31245 (HR = 4.08, 95% CI: 1.21–13.74, P = 0.01) and IHC. Multivariate Cox regression analysis revealed that RB1 was an independent prognostic biomarker (HR = 1.66, 95% CI: 1.31-2.10, P = 2.02×10-5). Enrichment analysis suggested that the DEGs were mainly involved in cell cycle, DNA replication, and mitochondrial transition. The infiltration levels of fibroblast, neutrophil, monocyte and macrophage were positively correlated with RB1. Furthermore, RB1 was associated with immune checkpoint molecules (CTLA4, LAG3, and CD274). The IHC staining revealed higher expression of RB1 in tumor tissues as compared to that in normal tissues (P = 0.019). Overexpression of RB1 was associated with poor prognosis of OC (P = 0.01).ConclusionThese findings suggest that RB1 was a novel and immune-related prognostic biomarker for OC, which may be a promising target for OC treatment.

AimsSesamin, the main lignin constituent of sesame, plays a pivotal role in regulating physical state. Some studies have evidenced that the supplementation of sesamin may decrease cardiovascular disease risk. The goal of this systematic review was to summarize evidence of the effects of sesamin supplementation on obesity, blood pressure, and lipid profile in humans by performing a meta-analysis of randomized controlled trials.Data SynthesisFive databases (PubMed, Cochrane Library, EMBASE, Web of Science, and Scopus) were searched electronically from inception to July 2021 to identify randomized controlled trials that assessed the impact of sesamin on obesity, blood pressure, and lipid profile. Weighted mean difference (WMD) and standard deviation (SD) were used to present the major outcomes.ConclusionsSeven trials (n = 212 participants) were included in the overall analysis. Results showed that sesamin supplementation caused a great reduction in TC (WMD: -10.893 mg/dl, 95% CI: −19.745 to −2.041, p = 0.016), LDL-c (WMD: -8.429 mg/dl, 95% CI: −16.086 to −0.771, p = 0.031), and SBP (WMD: −3.662 mmHg, 95% CI: −6.220 to −1.105, p = 0.005), whereas it had no effect on HDL-c, TG, DBP, or weight. Subgroup analysis showed that duration, parallel design, and unhealthy status can affect TC, LDL-c, and SBP evidently. We did not discover a strong link between indicators’ changes and duration of supplementation. Sesamin can be used as an obtainable dietary supplement to improve blood pressure and blood lipids, and further as a health product to prevent cardiovascular diseases.

BackgroundChronic kidney disease (CKD) patients have a high prevalence of coronary artery disease and a high risk of cardiovascular events. The present study assessed the value of the CHA2DS2-VASc score for predicting mortality among hospitalized acute coronary syndrome (ACS) patients with CKD.MethodsThis was a retrospective cohort study that included CKD patients who were hospitalized for ACS from January 2015 to May 2020. The CHA2DS2-VASc score for each eligible patient was determined. Patients were stratified into two groups according to CHA2DS2-VASc score:

Abstract Aims Elderly patients with heart failure (HF) are associated with frequent all‐cause readmission or death. The present study sought to develop an accurate and easy‐to‐use model to predict all‐cause readmission or death risk in Chinese elderly patients with HF. Methods and results This was a prospective cohort study in patients with HF aged 65 or older. Demographic, co‐morbidity, laboratory, and medication data were collected. A Cox regression model was used to identify factors for the prediction of readmission or death at 30 days and 1 year. A nomogram was developed with bootstrap validation. Of the included 854 patients, the cumulative all‐cause readmission and mortality rates were 10.5% and 11.6% at 30 days and 34.9% and 19.7% at 1 year, respectively. The independent risk factors associated with both 30 day and 1 year readmission or death were older age, stroke, diastolic blood pressure 400 pg/mL (all P

Heart failure (HF) is a major global healthcare problem accounting for substantial deterioration of prognosis. As a complex clinical syndrome, HF often coexists with multi-comorbidities of which cognitive impairment (CI) is particularly important. CI is increasing in prevalence among patients with HF and is present in around 40%, even up to 60%, of elderly patients with HF. As a potent and independent prognostic factor, CI significantly increases the hospitalization and mortality and decreases quality of life in patients with HF. There has been a growing awareness of the complex bidirectional interaction between HF and CI as it shares a number of common pathophysiological pathways including reduced cerebral blood flow, inflammation, and neurohumoral activations. Research that focus on the precise mechanism for CI in HF is still ever insufficient. As the tremendous adverse consequences of CI in HF, effective early diagnosis of CI in HF and interventions for these patients may halt disease progression and improve prognosis. The current clinical guidelines in HF have begun to emphasize the importance of CI. However, nearly half of CI in HF is underdiagnosed, and few recommendations are available to guide clinicians about how to approach CI in patients with HF. This review aims to synthesize knowledge about the link between HF and cognitive dysfunction, issues pertaining to screening, diagnosis and management of CI in patients with HF, and emerging therapies for prevention. Based on data from current studies, critical gaps in knowledge of CI in HF are identified, and future research directions to guide the field forward are proposed.

Altered expression levels of the proteins that regulate N6-methyladenosine (m6A) RNA methylation, including methyltransferase-like 14 (METTL14), are associated with cancer development. Based on our analysis of m6A methylation regulators using The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets, we focused on the regulatory role of METTL14 in ovarian cancer. We performed bioinformatics and survival analyses with these datasets and also used METTL14-overexpressing SKOV-3 ovarian cancer cells for in vitro studies. Trophinin associated protein (TROAP) siRNA and treatment with or without actinomycin D was used in the cells for qRT-PCR, western blot, cDNA microarray, cell viability, colony formation, luciferase gene reporter, methylated RNA immunoprecipitation (MeRIP)-qPCR, total RNA methylation, and RNA stability assays. Additionally, ovarian cancer and normal tissue samples were analyzed by immunohistochemistry, qRT-PCR, and western blot assays. The TCGA and GEO data confirmed copy number variations (CNVs) of these m6A RNA methylation regulators in ovarian cancer tissues. Furthermore, reduced METTL14 expression was associated with alterations in CNVs as well as poor patient survival in ovarian cancer. Moreover, the METTL14 and m6A RNA methylation levels were both significantly reduced in ovarian cancer tissues than in normal tissues. Restoration of METTL14 expression suppresses ovarian cancer cell proliferation by inhibition of TROAP expression. Further in vivo and in vitro experiments confirmed that METTL14 is a negative regulator of ovarian cancer cell proliferation via TROAP expression and that m6A RNA methylation regulates TROAP mRNA stability. In conclusion, METTL14 overexpression decreased ovarian cancer proliferation by inhibition of TROAP expression via an m6A RNA methylation-dependent mechanism.

ObjectiveOur study aims to investigate the role of the ABO blood group in the development and severity of coronary artery disease (CAD) in end-stage renal disease (ESRD) patients with dialysis.MethodsA total of 408 ESRD patients with dialysis between January 2010 and December 2020 were enrolled including 204 patients diagnosed with CAD undergoing coronary angiography for the first time, and baseline characteristics as well as Gensini score (GS) were collected. Logistic regression analysis and linear regression analysis were performed to evaluate the relation of ABO blood types to the risk and severity of CAD, respectively.ResultsBlood group O frequency was significantly low in dialysis ESRD patients with CAD (25 vs. 38.24%) compared with the non-CAD patients and multivariable logistic regression showed blood group O was negatively associated with the risk of CAD [adjusted odds ratio (OR) = 0.33, 95% CI = 0.19–0.60, p < 0.001] as well as the GS tertiles (adjusted OR = 0.23, 95% CI = 0.11–0.49, p < 0.001) compared with A blood group. Blood group A, B, and AB were positively associated with the high Gensini tertile compared with O blood group (adjusted OR = 4.26, 95% CI = 2.03–8.93, p < 0.001; adjusted OR = 2.39, 95% CI = 1.11–5.13, p < 0.05; adjusted OR = 4.33, 95% CI = 1.40–13.35, P < 0.05). Similarly, multivariable linear regression results revealed O blood type was negatively associated with the GS (β = −26.129, 95% CI = −40.094 to −12.164, p < 0.001).ConclusionThis case-control study demonstrated that blood group O was a potential independent protective factor for the risk and severity of CAD in ESRD patients with dialysis.

To improve urban seismic resilience, a reasonable seismic retrofitting scheme for buildings is required. Urban cities contain a large number of buildings, making it challenging to precisely assess the seismic retrofitting benefits of each one. This paper proposes a cost–benefit assessment framework that takes into account seismic risk, seismic damage, retrofit costs, economic losses, and cost–benefit analyses for the city-scale seismic retrofitting of buildings. The proposed framework adopts readily available building parameters, including the number of stories, construction year, total height, structural type, floor area, and response spectrum for structural design. It makes use of empirical seismic retrofitting models and a newly developed story-level seismic loss assessment method combining the physical mechanism and empirical loss ratios. For city-scale cost–benefit analysis, the framework can strike a good balance between data accessibility, computational workload, level of result details, and result accuracy. It can adapt nimbly to earthquake-induced indirect losses and budgetary constraints on retrofitting. The analysis of 98,618 buildings in Xi’an city, China, is carried out. The findings indicate that, when potential indirect economic loss ratios of buildings are neglected, the retrofitting benefits of unreinforced masonry and old buildings are the most significant.

Background: The relationship between cardiac functions and the fatal outcome of coronavirus disease 2019 (COVID-19) is still largely underestimated. We aim to explore the role of heart failure (HF) and NT-proBNP in the prognosis of critically ill patients with COVID-19 and construct an easy-to-use predictive model using machine learning.Methods: In this multicenter and prospective study, a total of 1,050 patients with clinical suspicion of COVID-19 were consecutively screened. Finally, 402 laboratory-confirmed critically ill patients with COVID-19 were enrolled. A “triple cut-point” strategy of NT-proBNP was applied to assess the probability of HF. The primary outcome was 30-day all-cause in-hospital death. Prognostic risk factors were analyzed using the least absolute shrinkage and selection operator (LASSO) and multivariate logistic regression, further formulating a nomogram to predict mortality.Results: Within a 30-day follow-up, 27.4% of the 402 patients died. The mortality rate of patients with HF likely was significantly higher than that of the patient with gray zone and HF unlikely (40.8% vs. 25 and 16.5%, respectively, P < 0.001). HF likely [Odds ratio (OR) 1.97, 95% CI 1.13–3.42], age (OR 1.04, 95% CI 1.02–1.06), lymphocyte (OR 0.36, 95% CI 0.19–0.68), albumin (OR 0.92, 95% CI 0.87–0.96), and total bilirubin (OR 1.02, 95% CI 1–1.04) were independently associated with the prognosis of critically ill patients with COVID-19. Moreover, a nomogram was developed by bootstrap validation, and C-index was 0.8 (95% CI 0.74–0.86).Conclusions: This study established a novel nomogram to predict the 30-day all-cause mortality of critically ill patients with COVID-19, highlighting the predominant role of the “triple cut-point” strategy of NT-proBNP, which could assist in risk stratification and improve clinical sequelae.

Background: Breast cancer (BRCA) is one of the most common cancers in women worldwide and a leading cause of death from malignancy. This study was designed to identify a novel biomarker for prognosticating the survival of BRCA patients. Methods: The prognostic potential of eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) was assessed using RNA sequencing (RNA-seq) data from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) as training cohort and validation set, respectively. The functional enrichment analysis of differentially expressed genes (DEGs) was performed. The relationship between EIF4G1 and tumor microenvironment (TME) was analyzed. Immunotherapy responses were explored by the immunophenoscores (IPS) and tumor immune dysfunction and exclusion (TIDE) score. The Connectivity Map (CMap) was used to discover potentially effective therapeutic molecules against BRCA. Immunohistochemistry (IHC) was applied to compare the protein levels of EIF4G1 in normal and cancer tissues and to verify the prognostic value of EIF4G1. Results: BRCA patients with increased expression of EIF4G1 had a shorter overall survival (OS) in all cohorts and results from IHC. EIF4G1-related genes were mainly involved in DNA replication, BRCA metastasis, and the MAPK signaling pathway. Infiltration levels of CD4+-activated memory T cells, macrophages M0, macrophages M1, and neutrophils were higher in the EIF4G1 high-expression group than those in the EIF4G1 low-expression group. EIF4G1 was positively correlated with T cell exhaustion. Lower IPS was revealed in high EIF4G1 expression patients. Five potential groups of drugs against BRCA were identified. Conclusion: EIF4G1 might regulate the TME and affect BRCA metastasis, and it is a potential prognostic biomarker and therapeutic target for BRCA.

The high electron mobility transistor (HEMT)-based biosensors are highly competitive in the ultimate application of portable and point-of-care testing. Herein, we have demonstrated highly sensitive and real-time detection of cardiac troponin I (cTnI), a biomarker for the diagnosis of acute myocardial infarction (AMI) using AlGaAs/GaAs HEMT-based biosensors. The device has achieved a lower detection limit of 1 pg/ml in the buffer solution and less than 30 s response time, which demonstrated significant promise in the early diagnosis and screening of AMI. In addition, our results are consistent with the enzyme-linked immunosorbent assay according to the AMI patient’s blood test results. Furthermore, by comparing the two HEMT structures, we also calculated the equilibrium dissociation constant (KD) of the cTnI and cTnI antibody and analyzed the sensing mechanism. The results show that this method is very promising for early diagnosis of AMI.

Histone acetylation, balanced by histone acetyltransferase (HAT) and histone deacetylase (HDAC) complexes, affects dynamic transitions of chromatin structure to regulate transcriptional accessibility. However, little is known about the interplay between HAT and HDAC complexes in Fusarium graminearum, a causal agent of Fusarium Head Blight (FHB) that uniquely contains chromosomal regions enriched for house-keeping or infection-related genes. In this study, we identified the ortholog of the human inhibitor of growth (ING1) gene in F. graminearum (FNG1) and found that it specifically interacts with the FgEsa1 HAT of the NuA4 complex. Deletion of FNG1 led to severe growth defects and blocked conidiation, sexual reproduction, DON production, and plant infection. The fng1 mutant was normal in H3 acetylation but significantly reduced in H4 acetylation. A total of 34 spontaneous suppressors of fng1 with faster growth rate were isolated. Most of them were still defective in sexual reproduction and plant infection. Thirty two of them had mutations in orthologs of yeast RPD3, SIN3, and SDS3, three key components of the yeast Rpd3L HDAC complex. Four mutations in these three genes were verified to suppress the defects of fng1 mutant in growth and H4 acetylation. The rest two suppressor strains had a frameshift or nonsense mutation in a glutamine-rich hypothetical protein that may be a novel component of the FgRpd3 HDAC complex in filamentous fungi. FgRpd3, like Fng1, localized in euchromatin. Deletion of FgRPD3 resulted in severe growth defects and elevated H4 acetylation. In contract, the Fgsds3 deletion mutant had only a minor reduction in growth rate but FgSIN3 appeared to be an essential gene. RNA-seq analysis revealed that 48.1% and 54.2% of the genes with altered expression levels in the fng1 mutant were recovered to normal expression levels in two suppressor strains with mutations in FgRPD3 and FgSDS3, respectively. Taken together, our data showed that Fng1 is important for H4 acetylation as a component of the NuA4 complex and functionally related to the FgRpd3 HDAC complex for transcriptional regulation of genes important for growth, conidiation, sexual reproduction, and plant infection in F. graminearum.

Abstract Background A possible relationship between periodontitis and Alzheimer’s disease (AD) has been reported. However, there is limited information on the association between the Porphyromonas gingivalis (P. gingivalis) periodontal infection and the pathological features of AD. The hypothesis that P. gingivalis periodontal infection may cause cognitive impairment via age-dependent neuroinflammation was tested. Results Thirty 4-week-old (young) female C57BL/6 J mice were randomly divided into two groups, the control group and the experimental group. Thirty 12-month-old (middle-aged) were grouped as above. The mouth of the mice in the experimental group was infected with P. gingivalis. Morris water maze(MWM) was performed to assess the learning and memory ability of mice after 6 weeks. Moreover, the expression levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the mice brain tissues were determined by Quantitative real-time polymerase chain reaction (qRT-PCR), Enzyme Linked Immunosorbent Assay(ELISA) and immunohistochemistry. Our results showed that the learning and memory abilities of the middle-aged P. gingivalis infected mice were impaired. Moreover, the expression levels of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the brain tissues of the middle-aged P. gingivalis infected mice were increased. Conclusions These results suggest that P. gingivalis periodontal infection may cause cognitive impairment via the release of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β in the brain tissues of middle-aged mice.

Fusarium head blight caused by Fusarium graminearum is an important disease of wheat and barley. Previous studies have showed that all three MAP kinase genes, MGV1, FgHOG1, and GPMK1, are involved in regulating hyphal growth, sexual reproduction, plant infection, and stress responses in this pathogen. To determine the relationship between the Mgv1 and FgHog1 pathways, in this study, we generated and characterized the mgv1 Fghog1 double mutant. Deletion of FgHOG1 partially rescued the defects of the mgv1 mutant in vegetative growth and cell wall integrity but had no effects on its defects in plant infection and DON production. The mgv1 Fghog1 mutant grew faster and was more tolerant to cell wall stressors than the mgv1 mutant. Swollen compartments and cell burst were observed frequently in the mgv1 mutant but rarely in the mgv1 Fghog1 mutant when treated with fungicide fludioxonil or cell wall stressor Congo red. Conversely, the deletion of MGV1 also alleviated the hyperosmotic sensitivity of the Fghog1 mutant in vegetative growth. TGY assays indicated increased phosphorylation of FgHog1 in the mgv1 mutant, and TEY assays further revealed elevated activation of Gpmk1 in the mgv1 Fghog1 double mutant, particularly under cell wall stress conditions. Overall, our data showed that deletion of FgHOG1 partially suppressed the defects of the mgv1 mutant, possibly by affecting genes related to cell wall integrity and osmoregulation via the over-activation of Gpmk1 MAP kinase and avoiding intracellular turgor elevation.

Circulating T follicular helper (cTfh) cells are known to be involved in numerous immune-mediated diseases, but their pathological role in psoriasis is less fully investigated. Herein, we aimed to identify whether cTfh cells contributed to the pathogenesis of psoriasis. The frequency and function of cTfh cells were compared between patients with psoriasis vulgaris and healthy controls, and the infiltration of Tfh cells was detected between lesional and nonlesional skin tissues of psoriasis patients. Moreover, the dynamic change of cTfh cells before and after acitretin treatment was evaluated. Our results showed both increased frequency and activation (indicated by higher expression of ICOS, PD-1, HLA-DR, and Ki-67 and increased production of IL-21, IL-17, and IFN-γ) of cTfh cells in psoriasis patients. Compared with nonlesional skin tissues of psoriasis patients, the number of infiltrated Tfh cells was significantly increased in psoriasis lesions. In addition, positive correlations between the percentage of cTfh, functional markers on cTfh cells in peripheral blood and disease severity were noted. Furthermore, the frequency of cTfh cells and the levels of cytokines secreted by cTfh cells were all significantly decreased after 1-month treatment.

AIMS: MicroRNAs (miRNAs) play important roles in the pathogenesis of cardiovascular diseases. Circulating miRNAs were recently identified as biomarkers for various physiological and pathological conditions. In this study, we aimed to identify the circulating miRNA fingerprint of vulnerable coronary artery disease (CAD) and explore its potential as a novel biomarker for this disease. METHODS AND RESULTS: The Taqman low-density miRNA array and coexpression network analyses were used to identify distinct miRNA expression profiles in the plasma of patients with typical unstable angina (UA) and angiographically documented CAD (UA group, n = 13) compared to individuals with non-cardiac chest pain (control group, n = 13). Significantly elevated expression levels of miR-106b/25 cluster, miR-17/92a cluster, miR-21/590-5p family, miR-126*, and miR-451 were observed in UA patients compared to controls. These findings were validated by real-time PCR in another 45 UA patients, 31 stable angina patients, and 37 controls. In addition, miR-106b, miR-25, miR-92a, miR-21, miR-590-5p, miR-126* and miR-451 were upregulated in microparticles (MPs) isolated from the plasma of UA patients (n = 5) compared to controls (n = 5). Using flow cytometry and immunolabeling, we further found that Annexin V(+) MPs were increased in the plasma samples of UA patients compared to controls, and the majority of the increased MPs in plasma were shown to be Annexin V(+) CD31(+) MPs. The findings suggest that Annexin V(+) CD31(+) MPs may contribute to the elevated expression of the selected miRNAs in the circulation of patients with vulnerable CAD. CONCLUSION: The circulating miRNA signature, consisting of the miR-106b/25 cluster, miR-17/92a cluster, miR-21/590-5p family, miR-126* and miR-451, may be used as a novel biomarker for vulnerable CAD. TRIAL REGISTRATION: Chinese Clinical Trial Register, ChiCTR-OCH-12002349.