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IntroductionSeveral studies have reported on hepatitis E virus (HEV) prevalence in various regions of China, but the results vary widely. Herein, we conducted a systematic review and meta-analysis to assess the seroprevalence, RNA-positive rate, genotype distribution of HEV in China, and its risk factors.MethodsWe included 208 related studies involving 1,785,569 participants published between 1997 and 2022. Random-effects models were used to pool prevalence, and subgroup analyses were conducted by population, gender, age, study period, regions, and rural–urban distribution. The meta regression models and pooled odds ratios (OR) were performed to identify risk factors for HEV infections.ResultsThe pooled anti-HEV IgG, IgM, and Ag seroprevalence, and RNA detection rates in China from 1997 to 2022 were 23.17% [95% confidence interval (CI): 20.23–26.25], 0.73% (95% CI: 0.55–0.93), 0.12% (95% CI: 0.01–0.32), and 6.55% (95% CI: 3.46–12.05), respectively. The anti-HEV IgG seropositivity was higher in the occupational population (48.41%; 95% CI: 40.02–56.85) and older adult aged 50–59 years (40.87%; 95% CI: 31.95–50.11). The dominant genotype (GT) of hepatitis E in China was GT4. Notably, drinking non-tap water (OR = 1.82; 95% CI: 1.50–2.20), consumption of raw or undercooked meat (OR = 1.47; 95% CI: 1.17–1.84), and ethnic minorities (OR = 1.50; 95% CI: 1.29–1.73) were risk factors of anti-HEV IgG seroprevalence.DiscussionsOverall, the prevalence of hepatitis E was relatively high in China, especially among older adults, ethnic minorities, and humans with occupational exposure to pigs. Thus, there is a need for preventive measures, including HEV infection screening and surveillance, health education, and hepatitis E vaccine intervention in high-risk areas and populations.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42023397036.

ABSTRACT: The gut microbiota is known to have significant involvement in the regulation of lipogenesis and adipogenesis, yet the mechanisms responsible for this relationship remain poorly understood. The current study aims to provide insight into the potential mechanisms by which the gut microbiota modulates lipogenesis in chickens. Using chickens fed with a normal-fat diet (NFD, n = 5) and high-fat diet (HFD, n = 5), we analyzed the correlation between gut microbiota, cecal metabolomics, and lipogenesis by 16s rRNA sequencing, miRNA and mRNA sequencing as well as targeted metabolomics analysis. The potential metabolite/miRNA/mRNA axis regulated by gut microbiota was identified using chickens treated with antibiotics (ABX, n = 5). The possible mechanism of gut microbiota regulating chicken lipogenesis was confirmed by fecal microbiota transplantation (FMT) from chickens fed with NFD to chickens fed with HFD (n = 5). The results showed that HFD significantly altered gut microbiota composition and enhanced chicken lipogenesis, with a significant correlation between 3. Furthermore, HFD significantly altered the hepatic miRNA expression profiles and reduced the abundance of hepatic butyric acid. Procrustes analysis indicated that the HFD-induced dysbiosis of the gut microbiota might affect the expression profiles of hepatic miRNA. Specifically, HFD-induced gut microbiota dysbiosis may reduce the abundance of butyric acid and downregulate the expression of miR-204 in the liver. Multiomics analysis identified ACSS2 as a target gene of miR-204. Gut microbiota depletion by an antibiotic cocktail (ABX) showed a gut microbiota-dependent manner in the abundance of butyric acid and the expression of miR-204/ACSS2, which have been observed to be significantly correlated. Fecal microbiota transplantation from NFD chickens into HFD chickens effectively attenuated the HFD-induced excessive lipogenesis, elevated the abundance of butyric acid and the relative expression of miR-204, and reduced the expression of ACSS2 in the liver. Mechanistically, our results showed that the gut microbiota plays an antiobesity role by regulating the butyric acid/miR-204/ACSS2 axis in chickens. This work contributed to a better understanding of the functions of gut microbiota in regulating chicken lipogenesis.

Abstract Background Asthma is a heterogeneous disease with high morbidity. Advancement in high-throughput multi-omics approaches has enabled the collection of molecular assessments at different layers, providing a complementary perspective of complex diseases. Numerous computational methods have been developed for the omics-based patient classification or disease outcome prediction. Yet, a systematic benchmarking of those methods using various combinations of omics data for the prediction of asthma development is still lacking. Objective We aimed to investigate the computational methods in disease status prediction using multi-omics data. Method We systematically benchmarked 18 computational methods using all the 63 combinations of six omics data (GWAS, miRNA, mRNA, microbiome, metabolome, DNA methylation) collected in The Vitamin D Antenatal Asthma Reduction Trial (VDAART) cohort. We evaluated each method using standard performance metrics for each of the 63 omics combinations. Results Our results indicate that overall Logistic Regression, Multi-Layer Perceptron, and MOGONET display superior performance, and the combination of transcriptional, genomic and microbiome data achieves the best prediction. Moreover, we find that including the clinical data can further improve the prediction performance for some but not all the omics combinations. Conclusions Specific omics combinations can reach the optimal prediction of asthma development in children. And certain computational methods showed superior performance than other methods.

The overuse of nitrogen (N) fertilizer in fields has increased production costs and raised environmental concerns. Increasing the N use efficiency (NUE) of rice varieties is crucial for sustainable agriculture. Here we report the cloning and characterization of OsNPF3.1, a gene that controls rice NUE. An amino acid mutation in the OsNPF3.1 coding region caused different NUEs in wild and cultivated rice. OsNPF3.1, which is expressed mainly in the aerial parts of rice, also affects rice plant height, heading date, and thousand-grain weight. The OsNPF3.1 protein is located in the plasma membrane. When OsNPF3.1 was subjected to artificial selection, two naturally varying loci were associated with NUE, of which OsNPF3.1Chr6_8741040 differed between indica and japonica rice. OsNPF3.1 can be used as a new target gene for breeding rice varieties with high NUE.

This study aimed to compare the predictive value of six selected anthropometric indicators for benign prostatic hyperplasia (BPH). Males over 50 years of age who underwent health examinations at the Health Management Center of the Second Xiangya Hospital, Central South University (Changsha, China) from June to December 2020 were enrolled in this study. The characteristic data were collected, including basic anthropometric indices, lipid parameters, six anthropometric indicators, prostate-specific antigen, and total prostate volume. The odds ratios (ORs) with 95% confidence intervals (95% CIs) for all anthropometric parameters and BPH were calculated using binary logistic regression. To assess the diagnostic capability of each indicator for BPH and identify the appropriate cutoff values, receiver operating characteristic (ROC) curves and the related areas under the curves (AUCs) were utilized. All six indicators had diagnostic value for BPH (all P ≤ 0.001). The visceral adiposity index (VAI; AUC: 0.797, 95% CI: 0.759–0.834) had the highest AUC and therefore the highest diagnostic value. This was followed by the cardiometabolic index (CMI; AUC: 0.792, 95% CI: 0.753–0.831), lipid accumulation product (LAP; AUC: 0.766, 95% CI: 0.723–0.809), waist-to-hip ratio (WHR; AUC: 0.660, 95% CI: 0.609–0.712), waist-to-height ratio (WHtR; AUC: 0.639, 95% CI: 0.587–0.691), and body mass index (BMI; AUC: 0.592, 95% CI: 0.540–0.643). The sensitivity of CMI was the highest (92.1%), and WHtR had the highest specificity of 94.1%. CMI consistently showed the highest OR in the binary logistic regression analysis. BMI, WHtR, WHR, VAI, CMI, and LAP all influence the occurrence of BPH in middle-aged and older men (all P ≤ 0.001), and CMI is the best predictor of BPH.

Recently, studies have revealed the prognostic value of 5-methylcytosine (m5C) in clear cell renal cell carcinoma (ccRCC). However, the role of m5C methylation in ccRCC immune infiltration and the immunotherapeutic response remains unknown. Based on the mRNA expressions of 14 m5C regulators, we evaluated the m5C modification patterns of 530 tumor samples from the TCGA-ccRCC database. We used the principal component analysis (PCA) algorithm to construct individual patient m5Cscores to facilitate individual analysis of m5C modification patterns in ccRCC patients. We finally defined three different m5C modification patterns. Different clinical features and immune heterogeneity existed among the three patterns, and their immune infiltration characteristics could correspond to different immune phenotypes, including the immune-inflamed, immune-excluded, and immune-desert phenotype. We designed the m5Cscore calculated by the PCA algorithm to measure individual patients’ m5C modification patterns. The low m5Cscore group presented with a positive prognosis, increased TMB, and immune activation. Additionally, low m5Cscore patients showed an increased response to immune checkpoint inhibitors. We further the value of the m5Cscore in predicting OS verified in four other tumor cohorts. Our findings revealed that m5C methylation modifications are essential in regulating ccRCC immune infiltration. Assessing single ccRCC patients’ m5C modification patterns can fully improve our comprehension of tumor immune characteristics and be used to provide effective personalized immunotherapy strategies for clinical use.

Objectives: Influenza vaccination is an effective method for preventing influenza virus infection. Herein, we performed a meta-analysis to quantify global influenza vaccination rates (IVRs) and the factors influencing its uptake in the general population, individuals with chronic diseases, pregnant women, and healthcare workers. Methods: Related articles were obtained from online databases and screened according to the inclusion criteria. The pooled IVRs were calculated using the random effects model. Subgroup analyses and multivariate meta-regression were performed to determine the factors associated with influenza vaccine uptake. Results: We included 522 studies from 68 countries/regions. Most studies were conducted in the European region (247 studies), followed by the Western Pacific (135 studies) and American regions (100 studies). The IVRs with 95% confidence intervals (CIs) in the general population were lower (24.96%, 23.45%-26.50%) than in individuals with chronic diseases (41.65%, 40.08%-43.23%), healthcare workers (36.57%, 33.74%-39.44%), and pregnant women (25.92%, 23.18%-28.75%). The IVRs in high-income countries/regions were significantly higher than that in middle-income countries/regions. A free national or regional vaccination policy, perception of influenza vaccine efficacy and disease severity, a recommendation from healthcare workers, and having a history of influenza vaccination were positive factors for vaccine uptake (P

Background: It is well known that appropriate mechanical stimulation benefits tendon-bone (T-B) healing, however, the mechanisms behind this are still uncovered completely. Here, we aimed to explore whether the IL-4/JAK/STAT signaling pathway mediated macrophage polarization was involved in mechanical stimulation induced T-B healing. Method: C57BL/6 mice rotator cuff (RC) repair model was established, and the mice were randomly allocated to the following group. 1. Mice were allowed for free cage activities after surgery (FC group); 2. Mice received treadmill running initiated on postoperative day 7 (TR group); 3. Mice only received a local injection of hydrogel containing IL-4 neutralizing antibody without postoperative intervention (FC ​+ ​AF-404-SP group); 4. Mice received a local injection of hydrogel containing IL-4 neutralizing antibody and postoperative treadmill running (TR ​+ ​AF-404-SP group). The expression of IL-4 within supraspinatus tendon (SST) enthesis was measured by Enzyme-linked immunosorbent assay (ELISA). In addition, the activation of JAK/STAT signaling pathway in macrophages and identification of macrophage phenotype at the RC insertion site was detected by Flow cytometry and qRT-PCR. T-B healing quality in this RC repair model was evaluated by histological staining, Micro-computed tomography (Micro-CT) scanning, and biomechanical testing. Result: In this study, using the RC repair model, we confirmed that generation of IL-4, activation of the JAK/STAT signaling pathway in macrophages, the ability of macrophages to polarize towards M2 subtype, and T-B healing quality were significantly enhanced in TR group compared to FC group. When comparing FC ​+ ​AF-404-SP group with TR ​+ ​AF-404-SP group, it was found that the mechanical stimulation induced this effect was depleted following the blockade of the IL-4/JAK/STAT signaling pathway. Conclusion: Our finding suggested that mechanical stimulation could accelerate T-B healing via activating the IL-4/JAK/STAT signaling pathway that modulates macrophages to polarize towards M2 subtype. The translational potential of this article: This is the first study to reveal a significant role of mechanical stimulation in the IL-4/JAK/STAT signaling pathway activation and macrophage polarization during RC T-B healing, which highlights the IL-4/JAK/STAT signaling pathway as a potential target to mediate macrophage M2 polarization and improves T-B healing for RC repair.

Abstract Background Rotavirus is the leading global pathogen of diarrhea-associated mortality and poses a great threat to public health in all age groups. This study aimed to explore the global burden and 30-year change patterns of rotavirus infection-associated deaths. Methods Based on the Global Burden of Disease 2019 Study (GBD 2019), we analyzed the age-standardized death rate (ASDR) of rotavirus infection by sex, geographical region, and sociodemographic index (SDI) from 1990 to 2019. A Joinpoint regression model was used to analyze the global trends in rotavirus infection over the 30 years, SaTScan software was used to detect the spatial and temporal aggregations, and a generalized linear model to explore the relationship between sociodemographic factors and death rates of rotavirus infection. Results Globally, rotavirus infection was the leading cause of diarrheal deaths, accounting for 19.11% of deaths from diarrhea in 2019. Rotavirus caused a higher death burden in African, Oceanian, and South Asian countries in the past three decades. The ASDR of rotavirus declined from 11.39 (95% uncertainty interval [95% UI] 5.46–19.48) per 100,000 people in 1990 to 3.41 (95% UI 1.60–6.01) per 100,000 people in 2019, with an average annual percentage change (AAPC) (− 4.07%, P

Abstract The tumor microenvironment plays an important role in various processes, including tumorigenesis, cancer progression, and metastasis. Immune signatures have been identified and verified for use in diagnosis and prognosis prediction. We used single-sample Gene Set Enrichment Analysis to evaluate tumor immune cell infiltration score (TIICs) and verify their prognostic significance in both training and validation cohorts and using this information to build a prognostic model. A total of 1281 samples were obtained for further evaluation of the immune enrichment scores of 28 immune cells, showing that Th17 cell contributed most significantly to survival. Using the median TIICs as a cutoff to divide the samples into two groups, we found that the high-TIICs group was associated with favorable outcomes in both the training and validation sets. We then constructed a prognostic model to predict the 6, 8, and 10-year survival outcomes. Further analysis showed that immune score and tumor purity were higher in the high-TIICs group, while the matrix score was lower in this group. Forty-two differentially expressed genes were identified between the two groups. This new prognostic model based on immune cell infiltration indicates the potential for TIICs in predicting prognosis and as targets for treatment.

Abstract Background As the most common renal malignancy, kidney renal clear cell carcinoma (KIRC) has a high prevalence and death rate as well as a poor response to treatment. Developing an efficient prognostic model is essential for accurately predicting the outcome and therapeutic benefit of KIRC patients. Methods Gene expression profiles of podocyte‐associated genes (PAGs) were obtained from The Cancer Genome Atlas and GEO datasets. Cox regression and Lasso regression analyses were then used for filtering prognosis‐associated PAGs. Risk score (RS) was computed from these genetic characteristics. Kaplan–Meier analysis and receiver operating characteristic (ROC) curves were applied for ascertaining the prognostic value. Stratified analysis was used to sufficiently validate model performance. Concordance index was used to compare the predictive ability of different models. Immuno‐infiltration analysis and immunophenoscore were utilized for the prediction of patient reaction to immune checkpoint inhibitors (ICIs). Results WT1, ANLN, CUBN, OSGEP, and RHOA were significantly associated with KIRC prognosis. Prognostic analysis indicated that high‐RS patients have a significantly poorer outcome. Cox regression analysis demonstrated a potential for RS to be an independent prognostic factor. Pathway enrichment results indicated a lower enrichment of cancer‐related biological pathways in the low‐RS subgroup. Immune infiltration analysis and IPS demonstrated greater responsiveness to ICIs in the high RS group. Conclusions This podocyte‐associated KIRC prognostic model can effectively predict KIRC prognosis and immunotherapy response, which may help to provide clinicians with more effective treatment strategies.

Rotator cuff (RC) attaches to humerus across a triphasic yet continuous tissue zones (bone-fibrocartilage-tendon), termed “enthesis”. Regrettably, rapid and functional enthesis regeneration is challenging after RC tear. The existing grafts bioengineered for RC repair are insufficient, as they were engineered by a scaffold that did not mimic normal enthesis in morphology, composition, and tensile property, meanwhile cannot simultaneously stimulate the formation of bone-fibrocartilage-tendon tissues. Herein, an optimized decellularization approach based on a vacuum aspiration device (VAD) was developed to fabricate a book-shaped decellularized enthesis matrix (O-BDEM). Then, three recombinant growth factors (CBP-GFs) capable of binding collagen were synthesized by fusing a collagen-binding peptide (CBP) into the N-terminal of BMP-2, TGF-β3, or GDF-7, and zone-specifically tethered to the collagen of O-BDEM to fabricate a novel scaffold (CBP-GFs/O-BDEM) satisfying the above-mentioned requirements. After ensuring the low immunogenicity of CBP-GFs/O-BDEM by a novel single-cell mass cytometry in a mouse model, we interleaved urine-derived stem cell-sheets into this CBP-GFs/O-BDEM to bioengineer an enthesis-like graft. Its high-performance on regenerating enthesis was determined in a canine model. These findings indicate this CBP-GFs/O-BDEM may be an excellent scaffold for constructing enthesis-like graft to patch large/massive RC tears, and provide breakthroughs in fabricating graded interfacial tissue.

Mapping higher order chromatin architecture is important. Here the authors use long sequencing reads to map genome-wide multi-way contacts and investigate higher order chromatin organisation; they use hypergraph theory for data representation and analysis, and apply this to different cell types.

Background: After anterior cruciate ligament (ACL) reconstruction in clinic, firm and rapid integration of the grafted tendon into the bone tunnel remains a challenge. Exosomes from hypoxia-treated stem cells are beneficial for promoting angiogenesis and then coupling with osteogenesis. Therefore, exosomes from hypoxia-cultured bone-marrow mesenchymal stem cells (Hypo-Exos) may be a cell-free therapy for enhancing graft-bone incorporation after ACL reconstruction. Methods: Exosomes from normoxia-cultured bone-marrow mesenchymal stem cells (Norm-Exos) or Hypo-Exos were respectively cultured with human umbilical vein endothelial cells (HUVECs) for in-vitro evaluating their functions in HUVECs proliferation, migration, and tube formation. A total of 87 rats with single-bundle ACL reconstructions in the right knee were randomly allocated into 3 different treatments: phosphate-buffered saline (PBS) with the adhesive hydrogel injection as control (Ctrl), Norm-Exos with the adhesive hydrogel injection (Norm-Exos), and Hypo-Exos with the adhesive hydrogel injection (Hypo-Exos). At postoperative weeks 2, 4, or 8, the ACL graft-bone integrations were evaluated. Results: Hypo-Exos was a better stimulator for in-vitro HUVECs proliferation, migration, and tube formation compared to PBS or Norm-Exos. Hypo-Exos within the adhesive hydrogel could be sustained-released at least 14 days around the peri-graft site. Radiologically, at week 4 or 8, femoral or tibial bone tunnel areas (BTA), as well as bone volume/total volume ratio (BV/TV) of the femoral or tibial peri-graft bone in the Hypo-Exos group, improved significantly better than these parameters of the Ctrl and Norm-Exos groups (P

N6-methyladenosine (m6A) is the most prevalent internal modification found in both mRNA and lncRNA. It exerts reversible regulation over RNA function and affects RNA processing and metabolism in various diseases, especially tumors. The m6A binding protein, hnRNPA2B1, is extensively studied as a member of the heterogeneous nuclear ribonucleoprotein (hnRNP) protein family. It is frequently dysregulated and holds significant importance in multiple types of tumors. By recognizing m6A sites for variable splicing, maintaining RNA stability, and regulating translation and transport, hnRNPA2B1 plays a vital role in various aspects of tumor development, metabolism, and regulation of the immune microenvironment. In this review, we summarized the latest research on the functional roles and underlying molecular mechanisms of hnRNPA2B1. Moreover, we discussed its potential as a target for tumor therapy.

Nitrogen is essential for crop production. It is a critical macronutrient for plant growth and development. However, excessive application of nitrogen fertilizer is not only a waste of resources but also pollutes the environment. An effective approach to solving this problem is to breed rice varieties with high nitrogen use efficiency (NUE). In this study, we performed a genome-wide association study (GWAS) on 419 rice landraces using 208,993 single nucleotide polymorphisms (SNPs). With the mixed linear model (MLM) in the Tassel software, we identified 834 SNPs associated with root surface area (RSA), root length (RL), root branch number (RBN), root number (RN), plant dry weight (PDW), plant height (PH), root volume (RL), plant fresh weight (PFW), root fractal dimension (RFD), number of root nodes (NRN), and average root diameter (ARD), with a significant level of p < 2.39×10–7. In addition, we found 49 SNPs that were correlated with RL, RBN, RN, PDW, PH, PFW, RFD, and NRN using genome-wide efficient mixed-model association (GEMMA), with a significant level of p < 1×10–6. Additionally, the final results for eight traits associated with 193 significant SNPs by using multi-locus random-SNP-effect mixed linear model (mrMLM) model and 272 significant SNPs associated with 11 traits by using IIIVmrMLM. Within the linkage intervals of significantly associated SNP, we identified eight known related genes to NUE in rice, namely, OsAMT2;3, OsGS1, OsNR2, OsNPF7.4, OsPTR9, OsNRT1.1B, OsNRT2.3, and OsNRT2.2. According to the linkage disequilibrium (LD) decay value of this population, there were 75 candidate genes within the 150-kb regions upstream and downstream of the most significantly associated SNP (Chr5_29804690, Chr5_29956584, and Chr10_17540654). These candidate genes included 22 transposon genes, 25 expressed genes, and 28 putative functional genes. The expression levels of these candidate genes were measured by real-time quantitative PCR (RT-qPCR), and the expression levels of LOC_Os05g51700 and LOC_Os05g51710 in C347 were significantly lower than that in C117; the expression levels of LOC_Os05g51740, LOC_Os05g51780, LOC_Os05g51960, LOC_Os05g51970, and LOC_Os10g33210 were significantly higher in C347 than C117. Among them, LOC_Os10g33210 encodes a peptide transporter, and LOC_Os05g51690 encodes a CCT domain protein and responds to NUE in rice. This study identified new loci related to NUE in rice, providing new genetic resources for the molecular breeding of rice landraces with high NUE.

BackgroundAn accurate assessment of current trends in cardiovascular risks could inform public health policy. This study aims to determine 20-year trends in the prevalence of elevated cardiovascular risk and its risk factors' control among US adults.MethodsIn this serial cross-sectional analysis of 23,594 adults, aged 40–79 years, without clinical atherosclerotic cardiovascular disease (ASCVD) in the National Health and Nutrition Examination Survey from 2001 to 2020, we calculated the prevalence of elevated cardiovascular risk (10-year ASCVD risk ≥ 7.5%) for all participants and subgroups with their risk factors controlled for diabetes, hypertension, or dyslipidemia.ResultsThe age- and sex-adjusted prevalence of elevated cardiovascular risk slightly decreased from 41.5% (95% CI, 39.7–43.3%) in 2001–2004 to 38.6% (95% CI, 36.1–41.1%) in 2017–2020 (P for trend = 0.169) while the respective sex-adjusted prevalence significantly increased from 34.4% (95% CI, 32.8–36.0%) to 39.5% (95% CI, 37.0–42.0%; P for trend

Recent advances in biological technologies, such as multi-way chromosome conformation capture (3C), require development of methods for analysis of multi-way interactions. Hypergraphs are mathematically tractable objects that can be utilized to precisely represent and analyze multi-way interactions. Here we present the Hypergraph Analysis Toolbox (HAT), a software package for visualization and analysis of multi-way interactions in complex systems.

The human papillomavirus (HPV) vaccine reduces the prevalence of genital warts and the cancers they are associated with in males. However, the vaccination of males has always been neglected. Here, we performed a meta-analysis to comprehend the acceptability of the HPV vaccine in men and the factors impacting vaccination intentions. We searched PubMed, Web of Science, Embase, Ovid, CNKI, and Wan Fang up to 5 July 2023 for studies that reported HPV vaccine acceptance among men. A random effects model was used to obtain the pooled acceptance rate, and subgroup analysis was performed. Then, the influencing factors of HPV vaccination in males were analyzed. A total of 57 studies with 32,962 samples were included in the analysis. The overall acceptance rate of the HPV vaccine in general men was 47.04% (95% confidence interval [95%CI]: 39.23–54.93%), and 62.23% (95% CI: 52.93–71.10%) among those whose sexual orientation contained men. HPV vaccine acceptance rates differed significantly between the two populations (p = 0.01). The population with a medical background (46.23%, 95% CI: 40.28–52.24%) was more willing to be vaccinated. In comparison to the employed population (66.93%, 95% CI: 48.79–82.81%) and the unemployed (68.44%, 95% CI: 52.82–82.23%), vaccination acceptance rates were lower among students (47.35%, 95% CI: 37.00–57.81%) (p = 0.04). The most significant barriers to vaccination were perceived low risk of infection for themselves (45.91%, 95% CI: 31.73–60.43%), followed by vaccine cost (43.46%, 95% CI: 31.20–56.13%). Moreover, the recommendations from medical professionals (60.90%, 95%CI: 44.23–76.37%) and sexual partners (60.09%, 95%CI: 27.11–88.67%) were significant factors in promoting vaccination. Overall, acceptance of the HPV vaccine among general men was at a lower level, despite being slightly higher among men with a same-sex orientation. Popularizing knowledge about diseases and vaccines, encouraging medical professionals to recommend vaccines to men, or reducing the cost of vaccines may promote HPV vaccination.

【Objective】The differences in leaf nutrient content and nutrient resorption efficiency of different canopies of A. montana forest were analyzed, and the relationship between A. montana leaf nutrient resorption efficiency and nutrient contents in leaves and soil was studied.【Method】The Aleurites montana forest, planted after the coniferous forests with low production being cut down and cultivated as ecological forest conforming to the nature, was taken as test materials. The contents of nitrogen (N), phosphorus (P), potassium (K), calcium (Ca) and magnesium (Mg) in leaves of the upper and lower canopies of A. montana were determined in the peak vegetative period (July) and the defoliating period (October).【Result】The macronutrients N, P, K, Ca and Mg in senescent leaves were significantly lower than those in mature leaves and there was no nutrient enrichment in senescent leaves. The N contents of mature and senescent leaves in the upper canopy were significantly higher than those in the lower canopy. The K content in mature leaves of upper layer was significantly higher than that in the lower canopy. Ca resorption efficiency was significantly lower than that of other nutrients, with only 14.935 (±3.191) %. In addition, the resorption efficiency of Mg in the lower canopy was significantly higher than that in the upper canopy. There was no significant difference in the resorption efficiencies of other nutrients between upper and lower canopies. There was a significant negative correlation between K resorption efficiency and K content in mature and senescent leaves, and a significant positive correlation between Ca resorption efficiency and Ca content in mature leaves. There was a significant positive correlation between N resorption efficiency and soil hydrolyzed nitrogen. The K resorption efficiency was negatively correlated with soil total K content, but positively correlated with soil available K content.【Conclusion】The nutrient contents in senescent leaves of A. montana were significant lower than those in mature leaves, and there was a certain correlation between nutrient resorption efficiency and nutrients in leaves and soil. The study results could provide a scientific basis for further exploring the nutrient cycling mechanism of ecological public welfare forests.

Abstract Background The TetR (tetracycline repressor) family is one of the major transcription factor families that regulate expression of genes involved in bacterial antimicrobial resistance systems. NCgl0886 protein, designated as AtsR, is a member of the TetR family identified in Corynebacterium glutamicum, which is conserved in several species of the genera Corynebacterium, also including the well-known pathogen C. diphtheriae. AtsR is located at no far upstream of the identically oriented ncgl0884 gene, encoding a putative multidrug efflux pump protein, and in the same operon with ncgl0887, encoding a resistance, nodulation and cell division (RND) superfamily drug exporter. However, the role of AtsR is not clearly understood. Results Here we showed that dimeric AtsR directly repressed the expression of the ncgl0887-atsR operon, as well as indirectly controlled the ncgl0884 transcription. Antibiotics and toxic compounds induced the expression of ncgl0887-atsR operon. A perfect palindromic motif (5΄-TGCAA-N2-TTGCA-3΄; 12 bp) was identified in the upstream region of ncgl0887-atsR operon. Electrophoretic mobility shift assays (EMSAs) demonstrated specific binding of AtsR to this motif, and hydrogen peroxide (H2O2) blocked binding. H2O2 oxidized cysteine residues to form Cys123-Cys187 intermolecular disulfide bonds between two subunits in AtsR dimer, which altered its DNA-binding characteristics and caused its dissociation, thereby leading to derepression of the drug efflux protein. Deletion of ncgl0884 and ncgl0887 increased the susceptibilities of C. glutamicum for several toxic compounds, but overexpression of atsR decreased the drug tolerance of C. glutamicum. Conclusions Our study revealed that AtsR was a redox regulator that sensed oxidative stress via thiol modification. The results obtained here will contribute to our understanding of the drug response mechanism not only in C. glutamicum but also in the related bacteria C. diphtheriae.

Abstract The β2-adrenergic receptor (β2AR) is a G protein-coupled receptor (GPCR) that mediates the majority of cellular responses to external stimuli. Aberrant expression of β2AR results in various pathophysiological disorders, including tumorigenesis, but little is known about its role in liver regeneration. This study aims to investigate the impact and the underlying mechanism of β2AR in liver regeneration. Here, we found that β2AR was upregulated during liver regeneration induced by 70% PH. Deletion of β2AR in mice resulted in 62% mortality 2 days post-PH, decreased proliferative marker expression and impaired liver function throughout regeneration. Moreover, AAV8-mediated overexpression of β2AR in hepatocytes accelerated the regeneration process and increased target gene expression. Mechanistically, β2AR recruited G-protein-coupled receptor kinase 2 (GRK2) to the membrane and then formed a complex with c-met to transactivate c-met signaling, which triggered downstream extracellular regulated protein kinase (ERK) signaling activation and nuclear translocation. Inhibition of c-met with SU11274 or ERK with U0126 decreased β2AR overexpression-induced hepatocyte proliferation. Our findings revealed that β2AR might act as a critical mediator regulating liver regeneration by crosstalk with c-met and activation of ERK signaling.

Abstract Composites that can rapidly self-healing their structure and function at room temperature have broad application prospects. However, in view of the complexity of composite structure and composition, its self-heal is facing challenges. In this article, supramolecular effect is proposed to repair the multistage structure, mechanical and thermal properties of composite materials. A stiff and tough supramolecular frameworks of 2-[[(butylamino)carbonyl]oxy]ethyl ester (PBA)–polydimethylsiloxane (PDMS) were established using a chain extender with double amide bonds in a side chain to extend prepolymers through copolymerization. Then, by introducing the copolymer into a folded graphene film (FGf), a highly thermally conductive composite of PBA–PDMS/FGf with self-healing capacity was fabricated. The ratio of crosslinking and hydrogen bonding was optimized to ensure that PBA–PDMS could completely self-heal at room temperature in 10 min. Additionally, PBA–PDMS/FGf exhibits a high tensile strength of 2.23 ± 0.15 MPa at break and high thermal conductivity of 13 ± 0.2 W m−1 K−1; of which the self-healing efficiencies were 100% and 98.65% at room temperature for tensile strength and thermal conductivity, respectively. The excellent self-healing performance comes from the efficient supramolecular interaction between polymer molecules, as well as polymer molecule and graphene. This kind of thermal conductive self-healing composite has important application prospects in the heat dissipation field of next generation electronic devices in the future.

IntroductionTriclosan (TCS), a widely prescribed broad-spectrum antibacterial agent, is an endocrine-disrupting chemical. The relationship and biological mechanisms between TCS exposure and breast cancer (BC) are disputed. We aimed to examine the correlation between urinary TCS exposure and BC risk and estimated the mediating effects of oxidative stress and relative telomere length (RTL) in the above association.MethodsThis case-control study included 302 BC patients and 302 healthy individuals in Wuhan, China. We detected urinary TCS, three common oxidative stress biomarkers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α), 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], and RTL in peripheral blood mononuclear cells.ResultsSignificant associations were observed between log-transformed urinary concentrations of TCS, 8-OHdG, HNE-MA, 8-isoPGF2α, RTL, and BC risk, with the odds ratios (95% confidence intervals) being 1.58 (1.32–1.91), 3.08 (1.55–6.23), 3.39 (2.45–4.77), 3.99 (2.48–6.54), and 1.67 (1.35–2.09), respectively. Continuous TCS exposure was significantly positively correlated with RTL, HNE-MA, and 8-isoPGF2α (all p

BackgroundLittle is known about the role of interleukin (IL) in patients with acute myocardial infarction (MI), especially soluble IL-2 receptor (sIL-2R) and IL-8. We aim to evaluate, in MI patients, the predictive value of serum sIL-2R and IL-8 for future major adverse cardiovascular events (MACEs), and compare them with current biomarkers reflecting myocardial inflammation and injury.MethodsThis was a prospective, single-center cohort study. We measured serum concentrations of IL-1β, sIL-2R, IL-6, IL-8 and IL-10. Levels of current biomarkers for predicting MACEs were measured, including high-sensitivity C reactive protein, cardiac troponin T and N-terminal pro-brain natriuretic peptide. Clinical events were collected during 1-year and a median of 2.2 years (long-term) follow-up.ResultsTwenty-four patients (13.8%, 24/173) experienced MACEs during 1-year follow-up and 40 patients (23.1%, 40/173) during long-term follow-up. Of the five interleukins studied, only sIL-2R and IL-8 were independently associated with endpoints during 1-year or long-term follow-up. Patients with high sIL-2R or IL-8 levels (higher than the cutoff value) had a significantly higher risk of MACEs during 1-year (sIL-2R: HR 7.7, 3.3–18.0, p

Upward diffusing methane in gas hydrate geological systems is consumed in the sediment and water column by a series of biogeochemical reactions, which not only affect living foraminifera but also lead to early diagenetic alteration of buried foraminiferal tests. Previous studies of the impact of methane release events on fossil foraminifera focused mainly on carbon and oxygen isotopes, with little attention given to other geochemical proxies to date. Here, we examine the test wall microstructure and analyze the elemental and stable carbon-oxygen isotopic compositions of buried foraminifera from gas hydrate-bearing sediments at Site GMGS2-16 in the northern South China Sea. Our results show that diagenetic alteration of foraminiferal tests at Site GMGS2-16 is mainly linked to high-Mg calcite overgrowths. Test δ13C covaries negatively with the degree of diagenetic alteration (based on petrographic characteristics) but positively with Mg/Ca ratios. With increasing diagenetic alteration, Ba/Ca, Mn/Ca, Fe/Ca, Mo/Ca, U/Ca, V/Ca, Ni/Ca and Co/Ca also generally increase, but Sr/Ca and Cu/Ca exhibit variable changes. We infer that foraminiferal tests are highly susceptible to alteration by methane-bearing fluids, and that the elemental ratios of diagenetically altered tests are potentially reliable proxies for paleo-methane release events. At Site GMGS2-16, the overall pattern of diagenetic alteration of foraminiferal tests records frequent vertical fluctuations of the sulfate-methane transition zone (SMTZ) caused by variable fluid flux and methane release rates, with two discrete large-scale methane release events having maximum ages of ~0.47 ka and ~170 ka.

Paraneoplastic pemphigus (PNP) is a rare life-threatening disease which always associated with an underlying neoplasm. Tumor-related PNP most commonly precedes the detection of a hematological malignancy, with some cases seen during disease remission following cytotoxic drug therapy or radiotherapy. The lung is the most frequently-involved site in PNP, second only to the eyes, and involvement is seen in 59.2% to 92.8% of PNP cases. Bronchiolitis obliterans (BO) is the end stage of respiratory involvement and is regarded as life-threatening. The key point in treatment of PNP is to control the associated underlying hematologic neoplasia. High-dose systemic corticosteroids combined with other immunosuppressants are considered the first line of treatment. Other therapies that have shown beneficial effects include plasmapheresis, intravenous immunogloblin (IVIG), and more recently, daclizumab, alemtuzumab, and rituximab. There is no effective treatment for BO with PNP, and suppression of the cellular immune response may be necessary. Patients with PNP-BO associated with lymphoma mostly die within approximately 1 year. Herein, we reported a patient who diagnosed with PNP-BO concurrent with chronic lymphocytic leukemia. He was successful treated with ibrutinib and had achieved the longest survival which suggested that ibrutinib may be the best treatment choice for such patient.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease involving multiple organs. It is often called “immortal cancer” due to the difficulties in disease treatment. As the cornerstone of immune regulation, the programmed cell death protein 1 (PD-1) has been extensively studied in the context of chronic inflammation due to its ability of regulating immune response and immunosuppression. Recently, more and more studies on rheumatic immune related complications have also focused on PD-1 and proposed that the use of PD-1 agonist could inhibit the activation of lymphocytes and alleviate SLE disease activity. In this review, we summarized the role of PD-1 in SLE, implicating its potential application as a biomarker to predict SLE disease activity; we also proposed that the combination of PD-1 agonist and low-dose IL-2 may have better therapeutic efficacy, shining light on a new direction for developing specific treatment approaches.

Abstract The controllability of the microstructure of a compressed hierarchical building block is essential for optimizing a variety of performance parameters, such as thermal management. However, owing to the strong orientation effect during compression molding, optimizing the alignment of materials perpendicular to the direction of pressure is challenging. Herein, to illustrate the effect of the ordered microstructure on heat dissipation, thermally conductive carbon‐based materials are fabricated by tailoring dense, orientation–tunable, and interleaved structures. Vertically aligned carbon nanotube arrays (VACNTs) interconnected with graphene films (GF) are prepared as a 3D core‐ordered material to fabricate compressed building blocks of O–VA–GF and S–VA–GF. Leveraging the densified interleaved structure offered by VACNTs, the hierarchical O–VA–GF achieves excellent through‐plane (41.7 W m−1 K−1) and in‐plane (397.9 W m−1 K−1) thermal conductivities, outperforming similar composites of S–VA–GF (through‐plane: 10.3 W m−1 K−1 and in‐plane: 240.9 W m−1 K−1) with horizontally collapsed carbon nanotubes. As heat dissipation plates, these orderly assembled composites yield a 144% and 44% enhancement in the cooling coefficient compared with conventional Si3N4 for cooling high‐power light‐emitting diode chips.

Soil water content plays an important role in crop production, especially in the main rice production areas of China. The temporal stability of soil water content was studied in a paddy field of Taihu Lake region, southeast China. There were two treatments in this experiment, one was mulch with rice straw and the other was without mulch. Soil water content of the two treatments was monitored at the interval of 10 days by the Time Domain Reflectometer probes which were installed in situ, and measured both at 14 and 33 cm soil layers. The data were evaluated by temporal stability methods and Spearman's correlation. Results showed that mulching with rice straw proved to be efficient in retaining the soil water at the 14 cm soil layer. Based on the relative difference method, the representative positions of the experiment field were identified, which accurately represented the field-mean soil water at the experiment field was detected in terms of root mean square error, less than 2.18%. The Spearman's correlation values were high, which indicates temporal dependence along the experiment period. The data of soil water temporal stability could provide scientific basis for adequate water management in paddy field. HIGHLIGHTS The deeper the soil layer, the better the temporal stability of soil moisture.; Temporal stability of soil moisture affects agricultural production.; The temporal stability of soil moisture can provide information in large area.; Straw mulching had significant effect on temporal stability of soil surface water.; The use of field water stability can reduce the number of observations required for soil water management.;

Abstract Objective To evaluate the effect of continuous traction with a combined adjustable Halo-pelvic fixation brace on the cervical spine alignment in patients with severe rigid spinal deformity and analyze its related factors. Methods We conducted a retrospective cohort study of 21 patients with severe rigid spinal deformity treated in our department between 2015 and 2019. All subjects received combined adjustable Halo-pelvic fixation brace traction before secondary orthopedic surgery. The influence of the Halo-pelvic fixation brace on the cervical spine alignment was evaluated by measuring the parameters of lateral cervical X-ray at three time points: before traction, at the end of traction, and 6 months after orthopedic surgery. The correlation between parameter changes and total traction duration was analyzed to explore factors influencing cervical alignment. Results The C2L-C7L angle was 22.40 ± 15.91° before traction, which decreased to 5.91 ± 6.78° at the end of traction but increased to 14.51 ± 10.07° after orthopedic surgery (BT vs ET p

Abstract Background This is the first study to explore the potential functions and expression patterns of RNA N6-methyladenosine (m6A) and potential related genes in preeclampsia. Methods We identified two m6A modification patterns through unsupervised cluster analysis and validated them by principal component analysis. We quantified the relative abundance of specific infiltrating immunocytes using single-sample gene set enrichment analysis (ssGSEA) and the Wilcoxon test. To screen hub genes related to m6A regulators, we performed weighted gene coexpression network analysis. Functional enrichment analysis was conducted for differential signalling pathways and cellular processes. Preeclampsia patients were grouped by consensus clustering based on differentially expressed hub genes and the relationship between different gene-mediated classifications and clinical features. Results Two m6A clusters in preeclampsia, cluster A and cluster B, were determined based on the expression of 17 m6A modification regulators; ssGSEA revealed seven significantly different immune cell subtypes between the two clusters. A total of 1393 DEGs and nine potential m6A-modified hub genes were screened. We divided the patients into two groups based on the expression of these nine genes. We found that almost all the patients in m6A cluster A were classified into hub gene cluster 1 and that a lower gestational age may be associated with more m6A-associated events. Conclusions This study revealed that hub gene-mediated classification is consistent with m6A modification clusters for predicting the clinical characteristics of patients with preeclampsia. Our results provide new insights into the molecular mechanisms of preeclampsia.

Abstract Background Chronic hepatitis B virus (HBV) infection is characterized by the presence of dysfunctional exhausted CD8+ T cells that hamper viral control. We investigated the phenotypic heterogeneity of exhausted CD8+ T cells in HBV carriers. Methods We enrolled 31 HBV carriers and 23 healthy controls (HCs) in our study. Peripheral blood mononuclear cells (PBMCs) were isolated, and flow cytometry was used to determine the phenotypic distribution of CD8+ T cell subsets. Expression of cytokines such as TNF-α and IFN-γ was detected by quantitative reverse transcription–PCR, a fluorescence flow cytometry-based immunomicrobead assay and flow cytometry. Results There were no significant differences in the baseline characteristics between the 31 HBV carriers and the 23 sex- and age-matched HCs. CD8+ T cells exhibited higher levels of inhibitory receptors (TIM3 and PD1) in the HBV carriers than in the HCs (P

Drought stress under a changing climate can significantly affect agricultural production. Simulation of soil water dynamics in field conditions becomes necessary to understand changes of soil water conditions to develop irrigation guidelines. In this study, three models including Auto-Regressive Integrated Moving Average (ARIMA), Back-Propagation Artificial Neural Network (BP-ANN), and Least Squares Support Vector Machine (LS-SVM) were used to simulate the soil water content in the 0–14 cm and 14–33 cm soil layers across the Taihu Lake region of China. Rainfall, evaporation, temperature, humidity and wind speed that affect soil water content changes were considered in the BP-ANN and LS-SVM, but not in ARIMA. The results showed that the variability of soil water content in the 0–14 cm soil layer was greater than that in 14–33 cm. Correlation coefficients (r) of soil water content between simulations and observations were highest (0.9827) using LS-SVM in the 14–33 cm soil layer, while they were the lowest (0.7019) using ARIMA in the 0–14 cm soil layer; but no significant difference in r values was observed between the two soil layers with the BP-ANN model. Compared with the other two models, the LS-SVM model seems to be more accurate for forecasting the dynamics of soil moisture. The results suggested that agro-climatic data can be used to predict the severity of soil drought stress and provide guidance for irrigation to increase crop production in the Taihu Lake region of China. HIGHLIGHTS To understand the dynamics of soil water in the Taihu Lake region of China.; The simulation accuracy of LS-SVM was the highest.; To predict the trend of soil water content in the study area.;

Abstract Pathological cardiac hypertrophy is a process of abnormal remodeling of cardiomyocytes in response to pressure overload or other stress stimuli, resulting in myocardial injury, which is a major risk factor for heart failure, leading to increased morbidity and mortality. General control nonrepressed protein 5 (GCN5)/lysine acetyltransferase 2 A, a member of the histone acetyltransferase and lysine acetyltransferase families, regulates a variety of physiological and pathological events. However, the function of GCN5 in pathological cardiac hypertrophy remains unclear. This study aimed to explore the role of GCN5 in the development of pathological cardiac hypertrophy. GCN5 expression was increased in isolated neonatal rat cardiomyocytes (NRCMs) and mouse hearts of a hypertrophic mouse model. GCN5 overexpression aggravated the cardiac hypertrophy triggered by transverse aortic constriction surgery. In contrast, inhibition of GCN5 impairs the development of pathological cardiac hypertrophy. Similar results were obtained upon stimulation of NRCMs (having GCN5 overexpressed or knocked down) with phenylephrine. Mechanistically, our results indicate that GCN5 exacerbates cardiac hypertrophy via excessive activation of the transforming growth factor β-activated kinase 1 (TAK1)-c-Jun N-terminal kinase (JNK)/p38 signaling pathway. Using a TAK1-specific inhibitor in rescue experiments confirmed that the activation of TAK1 is essential for GCN5-mediated cardiac hypertrophy. In summary, the current study elucidated the role of GCN5 in promotion of cardiac hypertrophy, thereby implying it to be a potential target for treatment.

Three dimensional (3D) porous nanostructures assembled by low-dimensional nanomaterials are widely applied in gas sensor according to porous structure which can facilitate the transport of gas molecules. In this work, fish-scale-like porous SnO2 nanomaterials assembled from ultrathin nanosheets with thickness of 16.8 nm were synthesized by a facile hydrothermal route. Then Ag nanoparticles were decorated on the surface of SnO2 nanosheets via one-step method to improve their gas-sensing performances. The sensing properties of pristine SnO2 and Ag/SnO2 nanosheets were investigated intensively. After decorating with Ag nanoparticles, the characteristics of SnO2 based sensor for triethylamine detection were significantly improved. Especially, the Ag/SnO2 based sensor with Ag content of 2 at% exhibited the highest triethylamine sensing sensitivity at optimum work temperature of 170 °C. The improved sensing properties of Ag/SnO2 sensors were attributed to the sensitizing actions of Ag nanoparticles as well as the unique hierarchical porous architecture.

Abstract Poly-L-lactic acid (PLLA) is considered to be a promising candidate material for biodegradable vascular scaffolds (BVS) in percutaneous coronary intervention (PCI). But, PLLA-BVS also faces the challenge of thrombosis (ST) and in-stent restenosis (ISR) caused by in-stent neo-atherosclerosis (ISNA) associated with inflammatory reactions in macrophage-derived foam cells. Our previous studies have confirmed that curcumin alleviates PLLA-induced injury and inflammation in vascular endothelial cells, but it remains unclear whether curcumin can alleviate the effect of inflammatory reactions in macrophage-derived foam cells while treated with degraded product of PLLA. In this study, PLLA-BVS was implanted in the porcine coronary artery to examine increased macrophages and inflammatory cytokines such as NF-κb and TNF-α by histology and immunohistochemistry. In vitro, macrophage-derived foam cells were induced by Ox-LDL and observed by Oil Red Staining. Foam cells were treated with pre-degraded PLLA powder, curcumin and PPARγ inhibitor GW9662, and the expression of IL-6, IL-10, TNF-α, NF-κb, PLA2 and PPARγ were investigated by ELISA or RT-qPCR. This study demonstrated that the macrophages and inflammatory factors increased after PLLA-BVS implantation in vivo, and foam cells derived from macrophages promoted inflammation by products of PLLA degradation in vitro. This present study was found that the inflammation of foam cells at the microenvironment of PLLA degraded products were significantly increased, and curcumin can attenuate the inflammation caused by the PLLA degradation via PPARγ signal pathway. In addition, curcumin should be further studied experimentally in vivo experiments on animal models as a potential therapeutic to reduce ISNA of PLLA-BVS. Graphical abstract

With the rapid growth of traffic demand for vehicular data transmissions, the limited cellular band becomes a constraint to meet the needs of all cellular-vehicle-to-everything (C-V2X) users. In this paper, we investigate an efficient clustering-based spectrum resource management scheme for dynamic heterogeneous vehicular networks. Due to the frequent changes of channel state information (CSI) caused by high mobility of vehicles, the traditional radio resource management scheme based on complete CSI is no longer applicable. To solve this problem, we consider different quality of service (QoS) requirements for vehicular communications and propose an optimization problem for C-V2X networks. The proposed dynamic vehicular optimization strategy is carried out on the vehicle-to-vehicle (V2V) and vehicle-to-infrastructure (V2I) links, which can construct a more realistic two-way lane in actual communication environments. We also propose a low-complexity vehicle matching algorithm based on large-scale fading to improve the stability of communication links. The desirable performance is confirmed by computer simulations.

Pyroptosis, a form of inflammatory programmed cell death, is accompanied by inflammation and participate in the body's immune response. The expression of pyroptosis-related genes (PRGs) is associated with tumor prognosis in ovarian cancer (OC), but it is still unknown whether pyroptosis can affect tumor immune microenvironment (TME) of OC. Based on 30 PRGs, we comprehensively assessed the pyroptosis patterns by using PRGscore and correlated them with TME features in 474 OC patients. Finally, we identified three pyroptosis modification patterns and TME immune characteristics of these patterns were in response to three immune phenotypes (immune-desert, immune-inflamed, and immune-excluded phenotypes). PRGscore can predict patient survival, staging, grading, and immunotherapy efficacy. Low PRGscore was associated with better survival advantage and increased mutation burden. Low PRGscore patients showed significantly better therapeutic effects and clinical results in chemotherapy and immunotherapy. Besides, the capability of PRGscore in predicting prognosis and immunotherapy sensitivity was further verified in other three tumor cohorts. In conclusion, the comprehensive assessment of OC pyroptosis modifications can help enhancing our understanding of TME immune infiltration and provide better personalized treatment tactics for OC patients.

Abstract It is well known that the Doppler frequency shift contains the emitter location information. The problem of emitter location based on frequency of arrival (FOA) measurements of multiple moving observers is focussed. In contrast to most relevant works, the newly proposed positioning methods consider the influence of signal frequency deviation due to source instability and present two mathematical models of the frequency deviation. The first model assumes that the frequency offset is a small random parameter. A two‐stage closed‐form location method (called method a) is proposed. In stage 1, a set of pseudo‐linear equations are established according to the geometric relationship between the observers and emitter, so as to obtain an intermediate estimate of source position. Stage 2 returns to the original FOA measurement model and uses the estimation result in stage 1 to construct the second set of pseudo‐linear equations, yielding the final positioning result. The second model assumes that the signal frequency deviation is a large deterministic parameter. We propose an alternative two‐stage localisation method (called method b). In stage 1, a decoupling optimisation algorithm is developed based on the pseudo‐linear equations derived in stage 1 of method a, and intermediate estimates of the source position and frequency deviation are obtained successively. Stage 2 returns to the original FOA measurement model again and forms the second set of pseudo‐linear equations, yielding the final closed‐form solutions of emitter position and frequency offset. Both methods are proved analytically to achieve the Cramér–Rao bound (CRB) under the moderate noise level. Simulation results demonstrate the superior performance of the new methods.

BackgroundRecently studies have identified a critical role for interferon regulatory factor (IRF) in modulating tumour immune microenvironment (TME) infiltration and tumorigenesis.MethodsBased on IRF1-9 expression profiles, we classified all ccRCC samples into three molecular subtypes (clusters A-C) and characterized the prognosis and immune infiltration of these clusters. IRFscore constructed by principal component analysis was performed to quantify IRF-related subtypes in individual patients.ResultsWe proved that IRFscore predicted multiple patient characteristics, with high IRFscore group having poorer prognosis, suppressed TME, increased T-cell exhaustion, increased TMB and greater sensitivity to anti- PD-1/CTLA-4 therapies. Furthermore, analysis of metastatic ccRCC (mccRCC) molecular subtypes and drug sensitivity proved that low IRFscore was more sensitive to targeted therapies. Moreover, IRFscore grouping can be well matched to the immunological and molecular typing of ccRCC. qRT-PCR showed differential expression of IRFs in different cell lines.ConclusionsEvaluating IRF-related molecular subtypes in individual ccRCC patients not only facilitates our understanding of tumour immune infiltration, but also provides more effective clinical ideas for personalised treatment.

Methanococcus is a genus of well-characterized mesophilic and hydrogenotrophic methanogens with a robust genetic system. Commonly found in tidal marshes, they compete with sulfate- and iron-reducing bacteria for hydrogen gas (H2) and formate, their two major energy sources. They are characterized by rapid growth in mineral medium and requirements for marine levels of salts for optimal growth. Genetic tools developed over the last twenty years include improvements in shuttle vectors for production of recombinant proteins and CRISPR systems for mutagenesis as well as a variety of marker proteins for studies of gene expression. These tools have enabled functional characterization of the genome, including regulation of the transcriptome and proteome, mapping of transcription start and termination sites, and identification of essential genes. Metabolic and gene regulatory network models have been created. This foundation in the basic biology of Methanococcus provides an opportunity for development of biotechnological applications of these hydrogenotrophic methanogens.

Docynia delavayi (Franch.) Schneid is an evergreen tree with multiple benefits and high development and utilization value. The fruit is consumed as fresh and dry fruit, juices, and other products. However, it is unknown the chemical changes that occur upon fruit maturation. The metabolite content of unripe and ripe fruit was examined using UPLC-MS/MS technology based on a broadly targeted metabolome. We identified 477 metabolites, of which 130 differed between ripe and unripe fruit. These compounds are primarily involved in the biosynthesis of secondary metabolites, such as pantothenic acid, flavonoids, and amino acids. Moreover, in ripe fruit, there are 94 metabolites that are upregulated, particularly flavonoids and terpenoids. In comparison, compounds associated with sour flavors (amino acids, phenolic acids, organic acids) are down-regulated. Remarkably, these metabolites have a strong relationship with the medicinal properties of D. delavayi. This study provides a global perspective of the D. delavayi fruit metabolome and a comprehensive analysis of metabolomic variations during fruit development, thereby increasing the knowledge of the metabolic basis of important fruit quality traits in D. delavayi fruit.

Abstract Background Although visceral leishmaniasis (VL) was largely brought under control in most regions of China during the previous century, VL cases have rebounded in western and central China in recent decades. The aim of this study was to investigate the epidemiological features and spatial–temporal distribution of VL in mainland China from 2004 to 2019. Methods Incidence and mortality data for VL during the period 2004–2019 were collected from the Public Health Sciences Data Center of China and annual national epidemic reports of VL, whose data source was the National Diseases Reporting Information System. Joinpoint regression analysis was performed to explore the trends of VL. Spatial autocorrelation and spatial–temporal clustering analysis were conducted to identify the distribution and risk areas of VL transmission. Results A total of 4877 VL cases were reported in mainland China during 2004–2019, with mean annual incidence of 0.0228/100,000. VL incidence showed a decreasing trend in general during our study period (annual percentage change [APC] = −4.2564, 95% confidence interval [CI]: −8.0856 to −0.2677). Among mainly endemic provinces, VL was initially heavily epidemic in Gansu, Sichuan, and especially Xinjiang, but subsequently decreased considerably. In contrast, Shaanxi and Shanxi witnessed significantly increasing trends, especially in 2017–2019. The first-level spatial–temporal aggregation area covered two endemic provinces in northwestern China, including Gansu and Xinjiang, with the gathering time from 2004 to 2011 (relative risk [RR] = 13.91, log-likelihood ratio [LLR] = 3308.87, P

Abstract Heat and stress transfer at an interface are crucial for the contact‐based tactile sensing to measure the temperature, morphology, and modulus. However, fabricating a smart sensing material that combines high thermal conductivity, elasticity, and good adhesion is challenging. In this study, a composite is fabricated using a directional template of vertically aligned folded graphene (VAFG) and a copolymer matrix of poly‐2‐[[(butylamino)carbonyl]oxy]ethyl ester and polydimethylsiloxane, vinyl‐end‐terminated polydimethylsiloxane (poly(PBAx‐ran‐PDMS)). With optimized chemical cross‐linking and supermolecular interactions, the poly(PBA‐ran‐PDMS)/VAFG exhibits high thermal conductivity (15.49 W m−1 K−1), an high elastic deformation, and an interfacial adhesion of up to 6500 N m−1. Poly(PBA‐ran‐PDMS)/VAFG is highly sensitive to temperature and pressure and demonstrates a self‐learning capacity for manipulator applications. The smart manipulator can distinguish and selectively capture unknown materials in the dark. Thermally conductive, elastic, and adhesive poly(PBA‐ran‐PDMS)/VAFG can be developed into core materials in intelligent soft robots.

BackgroundLeukemia caused by occupational risk is a problem that needs more attention and remains to be solved urgently, especially for acute lymphoid leukemia (ALL), acute myeloid leukemia (AML), and chronic lymphoid leukemia (CLL). However, there is a paucity of literature on this issue. We aimed to assess the global burden and trends of leukemia attributable to occupational risk from 1990 to 2019.MethodsThis observational trend study was based on the Global Burden of Disease (GBD) 2019 database, the global deaths, and disability-adjusted life years (DALYs), which were calculated to quantify the changing trend of leukemia attributable to occupational risk, were analyzed by age, year, geographical location, and socio-demographic index (SDI), and the corresponding estimated annual percentage change (EAPC) values were calculated.ResultsGlobal age-standardized DALYs and death rates of leukemia attributable to occupational risk presented significantly decline trends with EAPC [−0.38% (95% CI: −0.58 to −0.18%) for DALYs and −0.30% (95% CI: −0.45 to −0.146%) for death]. However, it was significantly increased in people aged 65–69 years [0.42% (95% CI: 0.30–0.55%) for DALYs and 0.38% (95% CI: 0.26–0.51%) for death]. At the same time, the age-standardized DALYs and death rates of ALL, AML, and CLL were presented a significantly increased trend with EAPCs [0.78% (95% CI: 0.65–0.91%), 0.87% (95% CI: 0.81–0.93%), and 0.66% (95% CI: 0.51–0.81%) for DALYs, respectively, and 0.75% (95% CI: 0.68–0.82%), 0.96% (95% CI: 0.91–1.01%), and 0.55% (95% CI: 0.43–0.68%) for death], respectively. The ALL, AML, and CLL were shown an upward trend in almost all age groups.ConclusionWe observed a substantial reduction in leukemia due to occupational risks between 1990 and 2019. However, the people aged 65–69 years and burdens of ALL, AML, and CLL had a significantly increased trend in almost all age groups. Thus, there remains an urgent need to accelerate efforts to reduce leukemia attributable to occupational risk-related death burden in this population and specific causes.

BackgroundMetabolic and energy disorders are considered central to the etiology of diabetic cardiomyopathy (DCM). Sodium-glucose cotransporter-2 inhibitors (SGLT2i) can effectively reduce the risk of cardiovascular death and heart failure in patients with DCM. However, the underlying mechanism has not been elucidated.MethodsWe established a DCM rat model followed by treatment with empagliflozin (EMPA) for 12 weeks. Echocardiography, blood tests, histopathology, and transmission electron microscopy (TEM) were used to evaluate the phenotypic characteristics of the rats. The proteomics and metabolomics of the myocardium in the rat model were performed to identify the potential targets and signaling pathways associated with the cardiovascular benefit of SGLT2i.ResultsThe diabetic rat showed pronounced DCM characterized by mitochondrial pleomorphic, impaired lipid metabolism, myocardial fibrosis, and associated diastolic and systolic functional impairments in the heart. To some extent, these changes were ameliorated after treatment with EMPA. A total of 43 proteins and 34 metabolites were identified as targets in the myocardium of diabetic rats treated with EMPA. The KEGG analysis showed that arachidonic acid is associated with the maximum number of related pathways and may be a potential target of EMPA treatment. Fatty acid (FA) metabolism was enhanced in diabetic hearts, and the perturbation of biosynthesis of unsaturated FAs and arachidonic acid metabolism was a potential enabler for the cardiovascular benefit of EMPA.ConclusionSGLT2i ameliorated lipid accumulation and mitochondrial damage in the myocardium of diabetic rats. The metabolomic and proteomic data revealed the potential targets and signaling pathways associated with the cardiovascular benefit of SGLT2i, which provides a valuable resource for the mechanism of SGLT2i.

Background and purposeIt is crucial to evaluate the efficacy, recurrence, and metastasis of liver tumors after clinical treatment. This study aimed to investigate the value of Introvoxel Incoherent Motion (IVIM) imaging in the evaluation of rabbit VX2 liver tumors treated with Transcatheter Arterial Embolization (TAE) combined with apatinib.MethodsTwenty rabbit VX2 liver tumor models were established and randomly divided into either the experimental group (n=15) or the control group (n=5). The experimental group was treated with TAE combined with oral apatinib after successful tumor inoculation, while no treatment was administered following inoculation in the control group. IVIM sequence scan was performed in the experimental group before treatment, at 7 and 14 days after treatment. All rabbits were sacrificed after the last scan of the experimental group. Marginal tissues from the tumors of both groups were excised for immunohistochemical analysis to observe and compare the expression of microvessel density (MVD). The alterations of IVIM-related parameters of tumor tissues in the experimental group, including Apparent Diffusion Coefficient (ADC), True Diffusion Coefficient (D), Pseudodiffusion Coefficient (D*), and Perfusion Fraction (f) were compared at different periods, and the correlation between these parameters and MVD was analyzed.ResultsAfter treatment, ADC and D values significantly increased, whereas D* and f values both decreased, with statistically significant differences.(P0.05).ConclusionIVIM imaging can be employed to evaluate the efficacy of TAE combined with apatinib in rabbit VX2 liver tumors. Alterations in D and f values were closely related to the MVD of liver tumor tissues.

Researching the aluminum molten salt system has always been challenging because of the high temperature and significant corrosion seen in the aluminum electrolysis industry. This paper employs ab initio molecular dynamics simulations to investigate the ionic structure and transport features of the K3AlF6-2.2NaF-AlF3 molten system. The findings indicate that the primary Al-F complex ion species present in K-rich molten salts are [AlF4]−, [AlF5]2−, and [AlF6]3−. The fluorine atom located at the bridge site constitutes around 3% of the overall composition, suggesting a rather modest degree of polymerization for the ionic structure. The relative diffusion rates of the ions in the system are as follows: sodium (Na) has the highest diffusion ability, followed by potassium (K), fluoride (F), and aluminum (Al). With the increase in K3AlF6 concentration, the distribution and diffusion coefficient of complex ions in the melt change, resulting in a decrease in the transport performance of the entire system. These fundamental research findings can contribute to the optimization of the aluminum electrolysis industry in the future.