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Abstract Suppression of Tumorigenicity 2 (ST2) is a member of the interleukin-1 receptor/ Toll-like receptor superfamily, and its specific ligand is Interleukin-33 (IL-33). IL-33/ ST2 signaling has been implicated in numerous inflammatory and allergic diseases, as well as in promoting malignant behavior of tumor cells and angiogenesis. However, the precise role of ST2 in gastric cancer angiogenesis remains incompletely elucidated. We observed a significant correlation between high expression of ST2 in gastric cancer tissues and poor prognosis, along with various clinicopathological features. In vitro experiments demonstrated that the IL-33/ ST2 axis activates the PI3K/AKT/NF-κB signaling pathway through TRAF6, thereby promoting VEGFA-mediated tumor angiogenesis; meanwhile sST2 acts as a decoy receptor to regulate the IL-33/ST2L axis. Consistent findings were also observed in subcutaneous xenograft tumor models in nude mice. Furthermore, we investigated the molecular mechanism by which IL-33 promotes ST2L expression in GC cells via upregulation of transcription factors YY1 and GATA2 through intracellular signaling pathways.

Abstract Ultrahigh-voltage electricity systems are a vital part of energy networks, often across wide regions passing through mountainous terrains. The instability of slopes forming tower foundations along transmission lines poses a large risk to the entire energy network. Moreover, the tower foundations along extra-high-voltage electricity transmission lines are a very special type of element that are also highly vulnerable to landslides. In this study, an integrative risk assessment framework, including a hazard assessment, vulnerability analysis for the specified element at risk, and consequence estimation, is proposed to quantify the direct and indirect risks of landslides to power transmission lines. The Yanzi landslide, where a tower of the major ultrahigh-voltage transmission line from Sichuan (western China) to Shanghai (eastern China) has just been constructed, is taken as a case study. The correlation between landslide displacement and tower structure tilting is studied. In terms of the precipitation return period, factors of safety, failure probability, and deformation are simulated. A physical vulnerability curve is fitted by assuming a Weibull relationship between the horizontal deformation (hazard intensity) of the landslide and the tower inclination ratio. The total risk is calculated as the sum of the direct and indirect losses, among which the potential indirect risk due to tower damage is much greater than the direct risk. This work demonstrates the importance of landslide treatment strategies along electricity transmission lines by considering the potential indirect risks. The risk assessment model of landslides affecting ultrahigh-voltage electricity transmission lines proposed in this study could be useful for other types of indirect landslide risk evaluations.

Abstract Background Although numerous studies have shown that bariatric surgery results in sustained weight loss and modifications in gut microbiota composition and cognitive function, the exact underlying mechanisms are unclear. This study aimed to investigate the effects of bariatric surgery on cognitive function through the microbiota-gut-brain axis (MGBA). Methods Demographic data, serum samples, fecal samples, cognitive assessment scales, and resting-state functional connectivity magnetic resonance imaging (rs-fMRI) scans were obtained from 39 obese patients before and after (6 months) laparoscopic sleeve gastrectomy (LSG). PCA analysis, OPLS-DA analysis, and permutation tests were used to conduct fecal 16 S microbiota profiling, serum metabolomics, and neuroimaging analyses, and a bariatric surgery-specific rs-fMRI brain functional connectivity network was constructed. Spearman correlation analysis and Co-inertia analysis were employed to correlate significant alterations in cognitive assessment scales and resting-state functional connectivity difference networks with differential serum metabolites and 16 S microbiota data to identify key gut microbiota and serum metabolic factors. Results LSG significantly reduced the weight of obese patients, with reductions of up to 28%. Furthermore, cognitive assessment scale measurements revealed that LSG enhanced cognitive functions, including memory (HVLT, p = 0.000) and executive function (SCWT, p = 0.008). Also, LSG significantly altered gut microbiota composition (p = 0.001), with increased microbial abundance and diversity (p 1). Spearman correlation analysis among cognitive assessment scales, gut microbiota species, and serum metabolites revealed correlations with 68 gut microbiota species and 138 serum metabolites (p

Abstract. Background:. Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented. Methods:. In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs). Results:. In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years. Conclusion:. These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.

Abstract Faults play a crucial role in shaping the formation and damage patterns of landslides in the mountainous region, particularly in Qinling-Daba (Qinba) area in China. On 6 October 2022, following a 4-day rainfall event totaling 221.5 mm, a landslide occurred in Hanwang Town, Shaanxi Province. The left boundary of the landslide coincided with a fault, which influence the formation and movement development of the landslide. To further understand and quantified the formation process and damage mechanism of the landslide, a comprehensive study was conducted, incorporating field investigations, local rainfall data, and various methods including unmanned aerial vehicles (UAVs), numerical simulations, and laboratory test. The results indicate that fault dictate the formation of the Lijiaping landslide by influencing the mechanical strength of the rock mass and the catchment topography in the landslide area. Due to fault, the rock mass in the landslide area is high fragmentation, with a softening coefficient of about 0.52. Weathering resulted in numerous residual and slope sediments in the landslide area, providing ample material for the landslide. Meanwhile, the fault activity led to a wedge-shaped topography in the landslide area, with an average Terrain Wetness Index (TWI) of 3.43, significantly higher than the Hanwang Township average of 1.47. This creates a hydrogeological structure favorable for landslides. Numerical simulations revealed that the maximum velocity of the landslide reached 5.05 m/s and the maximum displacement was 53.18 m, both occurring in the central part of the landslide. These findings offer crucial scientific insights for understanding and preventing similar geological hazards.

Abstract Background The alveolar epithelial type II cell (AT2) and its senescence play a pivotal role in alveolar damage and pulmonary fibrosis. Cell circadian rhythm is strongly associated with cell senescence. Differentiated embryonic chondrocyte expressed gene 1 (DEC1) is a very important circadian clock gene. However, the role of DEC1 in AT2 senescence and pulmonary fibrosis was still unclear. Results In this study, a circadian disruption model of light intervention was used. It was found that circadian disruption exacerbated pulmonary fibrosis in mice. To understand the underlying mechanism, DEC1 levels were investigated. Results showed that DEC1 levels increased in lung tissues of IPF patients and in bleomycin-induced mouse fibrotic lungs. In vitro study revealed that bleomycin and TGF-β1 increased the expressions of DEC1, collagen-I, and fibronectin in AT2 cells. Inhibition of DEC1 mitigated bleomycin-induced fibrotic changes in vitro and in vivo. After that, cell senescence was observed in bleomycin-treated AT2 cells and mouse models, but these were prevented by DEC1 inhibition. At last, p21 was confirmed having circadian rhythm followed DEC1 in normal conditions. But bleomycin disrupted the circadian rhythm and increased DEC1 which promoted p21 expression, increased p21 mediated AT2 senescence and pulmonary fibrosis. Conclusions Taken together, circadian clock protein DEC1 mediated pulmonary fibrosis via p21 and cell senescence in alveolar epithelial type II cells.

Objective The relationship between vitiligo and cardiovascular diseases remains controversial. This study aimed to systematically review the evidence comparing cardiovascular disease risk factors between patients with vitiligo and controls and to perform a meta-analysis of the results.Data sources A comprehensive database search was performed for all studies in PubMed, EMBASE, and Cochrane Central Register databases from inception to November, 2023. The main keywords used were vitiligo, hypertension, diabetes, hyperlipidemia, metabolic syndrome, obesity, smoking, alcohol consumption, C-reactive protein, and homocysteine.Study selection Only observational studies and no randomized controlled trials were included. Of the 1269 studies initially selected, the full texts of 108 were assessed for eligibility, and 74 were ultimately included in the analysis.Data extraction and synthesis Three reviewers independently extracted the following data: study design, number and characteristics of participants, inclusion indicators, and disease duration. A meta-analysis of the single-group rates was performed for the diabetes, hypertension, hyperlipidemia, and obesity groups. Random-effects or fixed-effects models were used to calculate the sample-size weighted averages for the indicators included in the studies.Main outcomes and measures The primary outcomes were co-morbidity analysis and co-morbidity rates of vitiligo with metabolic syndrome, obesity, hyperlipidemia, hypertension, and diabetes mellitus. Secondary outcomes were factors associated with vitiligo and cardiovascular disease.Results This meta-analysis concluded that comorbidities in patients with vitiligo included metabolic syndrome, diabetes, obesity, hyperlipidemia, and hypertension, with comorbidity rates of 28.3%, 6.0%, 38.5%, 43.0%, and 15.8%, respectively. Simultaneously, we showed that the vitiligo group differed significantly from the control group in the following aspects: fasting blood glucose, insulin, systolic and diastolic blood pressure, total cholesterol, triglycerides, low-density lipoprotein, high-density lipoprotein, homocysteine, C-reactive protein, smoking, and alcohol consumption. However, no significant differences were observed between the vitiligo and control groups in terms of waist circumference, body mass index, or phospholipid levels.Limitations The vast majority of the studies were from Eastern countries; therefore, extrapolation of these results to Western populations is questionable. The significant heterogeneity may be due to different protocols, doses, durations, center settings, population registries, etc., which severely compromise the validity of the results.Conclusion This study summarized not only the factors associated with, but also those not associated with, cardiovascular disease in patients with vitiligo. This study provides a foundation for the prevention and treatment of cardiovascular disease in patients with vitiligo.

Abstract Severe trauma could induce sepsis due to the loss of control of the infection, which may eventually lead to death. Accurate and timely diagnosis of sepsis with severe trauma remains challenging both for clinician and laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis. We compared the diagnostic characteristics of routinely used biomarkers of sepsis alone and in combination, trying to define a biomarker panel to predict sepsis in severe patients. This prospective observational study included patients with severe trauma (Injury severity score, ISS = 16 or more) in the emergency intensive care unit (EICU) at a university hospital. Blood samples were collected and plasma levels of procalcitonin (PCT), C-reactive protein (CRP), interleukin-6 (IL-6) and serum amyloid A (SAA) were measured using commercial enzyme linked immunosorbent assay (ELISA) kits. A total of 100 patients were eligible for analysis. Of these, 52 were diagnosed with sepsis. CRP yielded the highest discriminative value followed by PCT. In multiple logistic regression, SAA, CRP, and PCT were found to be independent predictors of sepsis. Bioscore which was composed of SAA, CRP, and PCT was shown to be far superior to that of each individual biomarker taken individually. Therefore, compared with single markers, the biomarker panel of PCT, CRP, and SAA was more predictive of sepsis in severe polytrauma patients.

Abstract COVID-19 increased global mortality in 2019. Cystitis became a contributing factor in SARS-CoV-2 and COVID-19 complications. The complex molecular links between cystitis and COVID-19 are unclear. This study investigates COVID-19-associated cystitis (CAC) molecular mechanisms and drug candidates using bioinformatics and systems biology. Obtain the gene expression profiles of IC (GSE11783) and COVID-19 (GSE147507) from the Gene Expression Omnibus (GEO) database. Identified the common differentially expressed genes (DEGs) in both IC and COVID-19, and extracted a number of key genes from this group. Subsequently, conduct Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis on the DEGs. Additionally, design a protein–protein interaction (PPI) network, a transcription factor gene regulatory network, a TF miRNA regulatory network, and a gene disease association network using the DEGs. Identify and extract hub genes from the PPI network. Then construct Nomogram diagnostic prediction models based on the hub genes. The DSigDB database was used to forecast many potential molecular medicines that are associated with common DEGs. Assess the precision of hub genes and Nomogram models in diagnosing IC and COVID-19 by employing Receiver Operating Characteristic (ROC) curves. The IC dataset (GSE57560) and the COVID-19 dataset (GSE171110) were selected to validate the models' diagnostic accuracy. A grand total of 198 DEGs that overlapped were found and chosen for further research. FCER1G, ITGAM, LCP2, LILRB2, MNDA, SPI1, and TYROBP were screened as the hub genes. The Nomogram model, built using the seven hub genes, demonstrates significant utility as a diagnostic prediction model for both IC and COVID-19. Multiple potential molecular medicines associated with common DEGs have been discovered. These pathways, hub genes, and models may provide new perspectives for future research into mechanisms and guide personalised and effective therapeutics for IC patients infected with COVID-19.

AbstractBackground We discovered that vitiligo was associated with sexual dysfunction in clinical diagnosis and treatment; however, no further analysis had been performed due to a lack of data.Objective This study aimed to clarify the relationship between vitiligo and sexual dysfunction.Methods We searched six databases (PubMed, Embase, Cochrane, China National Knowledge Infrastructure, China Science and Technology Journal, and Wanfang Data Knowledge Service Platform) for nearly 40 years.Results According to the search strategy, 91 relevant studies were retrieved, of which 4 were included in the analysis. The Arizona Sexual Experience Scale (ASEX) score (mean difference [MD] 4.96, 95% confidence interval [CI] 2.78–7.13, p

Abstract Background The advancement of single-cell sequencing has progressed our ability to solve biological questions. Cell type annotation is of vital importance to this process, allowing for the analysis and interpretation of enormous single-cell datasets. At present, however, manual cell annotation which is the predominant approach remains limited by both speed and the requirement of expert knowledge. Methods To address these challenges, we constructed a hierarchically organized marker map through manually curating over 26,000 cell marker entries from about 7000 publications. We then developed WISE, a weighted and integrated gene set enrichment method, to integrate the prevalence of canonical markers and ordered differentially expressed genes of specific cell types in the marker map. Benchmarking analysis suggested that our method outperformed state-of-the-art methods. Results By integrating the marker map and WISE, we developed a user-friendly and convenient web server, ACT ( http://xteam.xbio.top/ACT/ or http://biocc.hrbmu.edu.cn/ACT/ ), which only takes a simple list of upregulated genes as input and provides interactive hierarchy maps, together with well-designed charts and statistical information, to accelerate the assignment of cell identities and made the results comparable to expert manual annotation. Besides, a pan-tissue marker map was constructed to assist in cell assignments in less-studied tissues. Applying ACT to three case studies showed that all cell clusters were quickly and accurately annotated, and multi-level and more refined cell types were identified. Conclusions We developed a knowledge-based resource and a corresponding method, together with an intuitive graphical web interface, for cell type annotation. We believe that ACT, emerging as a powerful tool for cell type annotation, would be widely used in single-cell research and considerably accelerate the process of cell type identification.

Abstract This study aims to investigate the effects of hyperthermia on intestinal microecology, immune function, and progression-free survival of patients with advanced unresectable lung adenocarcinoma. A total of twenty patients with lung adenocarcinoma in the study group received the advanced standard first-line treatment protocol, which included pemetrexed + cisplatin combined with sintilimab immunotherapy and hyperthermia. Additionally, twenty patients with lung adenocarcinoma in the control group received the advanced standard first-line treatment protocol, which included pemetrexed + cisplatin combined with sintilimab immunotherapy. The T-lymphocyte subpopulation and CD4/CD8 cell ratio of each sample were detected using flow cytometry. The intestinal flora was evaluated using 16S rRNA gene sequencing. The study observed the changes in the abundance, distribution, composition, and structure of fecal gut microorganisms before and after the treatment in both groups of patients. Significant differences were observed in the intestinal flora between the two groups. The patients in the study group showed improved immunity after treatment, whereas there was no significant change in the immunity of the control group before and after treatment. However, the difference in progression-free survival between the two groups was not statistically significant. Hyperthermia has a significant impact on improving the microecology of intestinal flora and the immunity of patients, but it does not have a significant effect on prolonging the progression-free survival of patients.

Abstract Objective This systematic review and meta-analysis study aimed to evaluate the effectiveness of probiotics supplementation on glycaemic control in patients with type 2 diabetes mellitus (T2DM) based on the data from the randomised clinical trials (RCTs). Methods PubMed, Web of Sciences, Embase, and Cochrane Library were searched from the inception to October 2022, and RCTs about probiotics and T2DM were collected. The standardised mean difference (SMD) with 95% confidence interval (CI) was used to estimate the effects of probiotics supplementation on glycaemic control related parameters, e.g. fasting blood glucose (FBG), insulin, haemoglobin A1c (HbA1c), and homeostasis model of assessment of insulin resistance (HOMA-IR). Results Thirty RCTs including 1,827 T2MD patients were identified. Compared with the placebo group, the probiotics supplementation group had a significant decrease in the parameters of glycaemic control, including FBG (SMD = − 0.331, 95% CI − 0.424 to − 0.238, P effect

The construction of an integrated national strategic system and capability is an essential goal of implementing the strategy of military-civilian integration in the contemporary era. And the collaborative innovation of military-civilian S&T is an inevitable choice to achieve this goal. Due to the dynamic, complex, and stochastic characteristics of military-civilian S&T collaborative innovation, the level of S&T innovation is highly volatile. This paper takes the internal and external stochastic disturbance factors of military-civilian S&T collaborative innovation as the perspective, studies the strategy selection problem of military-civilian S&T collaborative innovation under military domination, constructs a differential game model to explore the innovation strategies under the non-cooperative model without military subsidies, the non-cooperative model with military subsidies, and the collaborative model. Finally, we use numerical experiments to verify the validity of the conclusions. The study shows that: (1) Within a reasonable range of values of the benefit distribution coefficient, the system can achieve the Pareto optimum, and the collaborative model is conducive to improving the S&T innovation level and the optimum benefit level of the system. (2) Military subsidies can increase the benefits of the system and the parties involved to achieve Pareto improvement. (3) The level of S&T innovation under the collaborative model has dynamic evolutionary characteristics of maximum expectation and variance. As the intensity of disturbance increases, the stability of the system may be destroyed. Risk-averse civil enterprises prefer the cooperative mode, whereas risk-averse civil enterprises prefer the non-cooperative model.

Bladder cancer is a major public health problem in the world, and is one of the most common malignant tumors in the genito-urinary system. Due to its high incidence and mortality, it remains a serious threat to human health. In recent years, related researches on the occurrence of bladder cancer found a certain connection between the expression level of circRNA and development of bladder cancer. circRNA can accomplish the purpose of promoting or inhibiting the occurrence and progression of bladder cancer by affecting the expression of related miRNA and mRNA. Higher expression levels of some circRNAs such as circITCH, circACVR2A, circPICALM, and circZKSCAN1 demonstrate an improved prognostic survival of patients with bladder cancer. Higher expression of circBPTF and circPRMT5 correlated with worse prognosis in bladder cancer patients. This article highlights a relationship between CircRNA and bladder cancer.

Abstract Background Fine particulate matter (PM2.5) is associated with increased incidence and severity of asthma. PM2.5 exposure disrupts airway epithelial cells, which elicits and sustains PM2.5-induced airway inflammation and remodeling. However, the mechanisms underlying development and exacerbation of PM2.5-induced asthma were still poorly understood. The aryl hydrocarbon receptor nuclear translocator-like protein 1 (BMAL1) is a major circadian clock transcriptional activator that is also extensively expressed in peripheral tissues and plays a crucial role in organ and tissue metabolism. Results In this study, we found PM2.5 aggravated airway remodeling in mouse chronic asthma, and exacerbated asthma manifestation in mouse acute asthma. Next, low BMAL1 expression was found to be crucial for airway remodeling in PM2.5-challenged asthmatic mice. Subsequently, we confirmed that BMAL1 could bind and promote ubiquitination of p53, which can regulate p53 degradation and block its increase under normal conditions. However, PM2.5-induced BMAL1 inhibition resulted in up-regulation of p53 protein in bronchial epithelial cells, then increased-p53 promoted autophagy. Autophagy in bronchial epithelial cells mediated collagen-I synthesis as well as airway remodeling in asthma. Conclusions Taken together, our results suggest that BMAL1/p53-mediated bronchial epithelial cell autophagy contributes to PM2.5-aggravated asthma. This study highlights the functional importance of BMAL1-dependent p53 regulation during asthma, and provides a novel mechanistic insight into the therapeutic mechanisms of BMAL1. Graphic abstract Video Abstract

Objectives To classify subgroups of cancer-related symptoms in patients with multiple myeloma (MM) during treatment and examine between-group differences in demographic and clinical characteristics in addition to functional status.Design Cross-sectional survey study.Setting Haematology department of two tertiary hospitals affiliated with Guilin Medical University in China.Participants Using a convenience sampling method, questionnaires were distributed to patients with MM visiting two hospitals in Guilin, China.Interventions The patients were categorised into subgroups based on cancer-related symptoms using a latent class analysis. An analysis of covariance was performed to examine how demographic and clinical characteristics and functional status differed among the subgroups.Results In total, 216 patients completed the survey, with an average age of 60.3 years. A three-class solution was identified: low symptom burden group (class 1, 36.6%), moderate symptom burden group (class 2, 34.2%) and high symptom burden group (class 3, 29.2%). Patients with low monthly family income (OR=3.14, p=0.010) and complications of MM bone disease (OR=2.95, p=0.029) were more likely to belong to class 2. The predictors of high-burden symptoms were treated with painkillers, antidepressants or hypnotic drugs (OR=3.68, p=0.012) and

Objective To investigate the effect of LINGO-1 shRNA (LV) and neurotrophic factors cocktail (NTFs,NTFcocktail) encapsulated by Pluronic F-127(PF-127)hydrogel (PF-127-LV-NTFs)three-dimensional(3D) composite scaffolds on the proliferation and differentiation of rat neural stem cells. Methods The LV was constructed and infected with NSCs at different MOI. RT-qPCR and Western blot were used to detect the expression of LINGO-1 in NSCs. Brain derived neurotropic factor(BDNF), neurotrophin-3(NT-3), platelet-derived growth factor(PDGF),insulin-like growth factor 1(IGF-1), epidermat growth factor(EGF), basic fibroblast growth factor(bFGF) and glial cell derived neurotrophic factor(GDNF) were prepared as NTFs. The LV and NTFs were mixed with PF-127 and divided into different groups to culture NSCs. CCK-8 was used to detect the cell viability of NSCs, the survival rate of NSCs was detected by LIVE/DEAD staining, and immunofluorescence staining was used to detect the proliferation and differentiation of NSCs. Results The optimal MOI for LV was 5. CCK-8 assay results showed that there was no significant difference in the survival rate of NSCs. The LIVE/DEAD and Nestin immune-fluorescence staining results showed that compared with control, the survival rate of NSCs and the proportion of neuron differentiation positive were the highest in PF-127+LV+NTF group(P＜0.01). Conclusions PF-127-LV-NTFs 3D composite scaffold is favouring to support the proliferation and the directional differentiation of NSCs of rat.

Mulberry flavonoids can modulate the composition of rumen microbiota in ruminants to improve nutrient digestibility, owing to their strong biological activities. This study aimed to explore the effect of mulberry leaf flavonoids (MLF) on rumen bacteria, fermentation kinetics, and metagenomic functional profile in water buffalo. Forty buffaloes (4 ± 1 lactations) with almost same body weight (av. 600 ± 50 Kg) and days in milk (90 ± 20 d) were randomly allocated to four treatments having different levels of MLF: 0 g/d (control), 15 g/d (MLF15), 30 g/d (MLF30), and 45 g/d (MLF45) supplemented in a basal diet. After 35 days of supplementation, rumen contents were collected to determine rumen fermentation parameters. The 16S rRNA gene sequencing was performed to elucidate rumen bacteria composition. The obtained taxonomic data were analyzed to explore the rumen bacteriome and predict the associated gene functions and metabolic pathways. Results demonstrated a linear increase (p < 0.01) in rumen acetate, propionate, and total VFAs in the MLF45 group as compared to control. No effect of treatment was observed on rumen pH and butyrate contents. Acetate to propionate ratio in the MLF45 group linearly and quadratically decreased (p = 0.001) as compared to MLF15 and control groups. Similarly, MLF45 linearly increased (p < 0.05) the microbial protein (MCP) and NH3-N as compared to other treatments. Treatment adversely affected (p < 0.01) almost all alpha diversity parameters of rumen bacteria except Simpson index. MLF promoted the abundance of Proteobacteria while reducing the relative abundances of Actinobacteria, Acidobacteria, Chloroflexi, and Patescibacteria. The MLF supplementation tended to substantially reduce (0.05 < p < 0.1) the abundance of Actinobacteria, and Patescibacteria while completely eliminating Acidobacteria (p = 0.029), Chloroflexi (p = 0.059), and Gemmatimonadetes (p = 0.03) indicating the negative effect of flavonoids on the growth of these bacteria. However, MLF45 tended to substantially increase (p = 0.07) the abundance (~21.5%) of Acetobacter. The MLF treatment exhibited negative effect on five genera by significantly reducing (Sphingomonas) or eliminating (Arthobactor, unclassified_c__Actinobacteria, norank_c__Subgroup_6, norank_o__Saccharimonadales, and Nocardioides) them from the rumen microbiota. Pearson correlation analysis revealed 3, 5 and 23 positive correlations of rumen bacteria with milk yield, rumen fermentation and serum antioxidant parameters, respectively. A positive correlation of MCP was observed with three bacterial genera (Acetobacter, Enterobacter, and Klebsiella). The relative abundance of Pseudobutyrivibrio and Empedobacter also showed a positive correlation with the ruminal acetate and propionate. The present study indicated 45 g/d as an appropriate dose of MLF which modulated rumen bacteria and its functional profile in water buffalo.

Abstract Background Antiangiogenic therapy has increasingly become an important strategy for the treatment of colorectal cancer. Recent studies have shown that the tumour microenvironment (TME) promotes tumour angiogenesis. Bufalin is an active antitumour compound whose efficacy has been indicated by previous studies. However, there are very few studies on the antiangiogenic effects of bufalin. Methods Herein, human umbilical vein endothelial cell (HUVEC) tube formation, migration and adhesion tests were used to assess angiogenesis in vitro. Western blotting and quantitative PCR were used to detect relevant protein levels and mRNA expression levels. A subcutaneous xenograft tumour model and a hepatic metastasis model were established in mice to investigate the influence of bufalin on angiogenesis mediated by the TME in vivo. Results We found that angiogenesis mediated by cells in the TME was significantly inhibited in the presence of bufalin. The results demonstrated that the proangiogenic genes in HUVECs, such as VEGF, PDGFA, E-selectin and P-selectin, were downregulated by bufalin and that this downregulation was mediated by inhibition of the STAT3 pathway. Overexpression of STAT3 reversed the inhibitory effects of bufalin on angiogenesis. Furthermore, there was little reduction in angiogenesis when bufalin directly acted on the cells in the tumour microenvironment. Conclusion Our findings demonstrate that bufalin suppresses tumour microenvironment-mediated angiogenesis by inhibiting the STAT3 signalling pathway in vascular endothelial cells, revealing that bufalin may be used as a new antiangiogenic adjuvant therapy medicine to treat colorectal cancer.

Mechanical nociception is an evolutionarily conserved sensory process required for the survival of living organisms. Previous studies have revealed much about the neural circuits and sensory molecules in mechanical nociception, but the cellular mechanisms adopted by nociceptors in force detection remain elusive. To address this issue, we study the mechanosensation of a fly larval nociceptor (class IV da neurons, c4da) using a customized mechanical device. We find that c4da are sensitive to mN-scale forces and make uniform responses to the forces applied at different dendritic regions. Moreover, c4da showed a greater sensitivity to localized forces, consistent with them being able to detect the poking of sharp objects, such as wasp ovipositor. Further analysis reveals that high morphological complexity, mechanosensitivity to lateral tension and possibly also active signal propagation in dendrites contribute to the sensory features of c4da. In particular, we discover that Piezo and Ppk1/Ppk26, two key mechanosensory molecules, make differential but additive contributions to the mechanosensitivity of c4da. In all, our results provide updates into understanding how c4da process mechanical signals at the cellular level and reveal the contributions of key molecules.

Abstract So far, the identification and determination of flavor additives in food has gained extensive attention in the area of food safety. However, it remains a big challenge for simultaneous detection of diverse flavor agents. In this work, a novel gas chromatography method coupled with ultrasound-microwave synergistic extraction was developed for simultaneous detection of five flavor compounds, including butyl butyrate, menthol, methyl salicylate, eugenol and vanilline. In this strategy, ultrasound-microwave synergistic extraction was used to extract the five flavoring agents from chewing gum. The effects of extractants, solid-liquid ratio, extraction time and microwave power on extraction yield were researched by using orthogonal test. After the optimization of programme temperature and splitless injection, the five flavoring agents were well separated and simultaneously detected with wide linear ranges, low limits of detection, high accuracy and good repeatability. Therefore, this proposed method would hold great promise for assay application on the food safety.

Abstract Background To describe the current status of standardized patient (SP) practice in mainland China. Methods We conducted a nationwide survey in 2016. One hundred and eighty-three SP educators (SPEs) responded to the questionnaire, representing 80 medical centers from 25 provinces in mainland China. All of these centers were affiliated with China Standardized Patients Practice Teaching Guidance. In the survey, we assessed the methods of SPs’ recruitment, hourly wage, how SPs were used and challenges of SP role. We also compared these data among the 4 different regions in China. Results In mainland China, the most frequent range of SPs’ age was between 30 and 40 years (24.8%). The SPs were usually recruited by recommendations from the SPEs or a current SP (43.8%), as well as advertising in the hospitals (43.8%). The mean hourly wage was US$12.60 for teaching activities and US$18.82 for medical examinations. The median frequency for training SPs was 12.9 times per year. The SPs were used in areas such as internal medicine (89.6%), surgery (79.2%) and pediatrics (56.3%). The most challenging parts for the SPs were to remember all of the key points of the cases (51.9%) and portraying the emotions of the case (51.9%). Almost half of the SPs reported that, when interacting with medical students, they had difficulty in providing feedback in consistent with students’ learning objectives. SPs’ gender, age, rewards and scenarios playing were different significantly among the 4 geographic regions in China (P

Abstract. Background:. To prevent risk of life-threatening stent thrombosis, all patients need to undergo dual antiplatelet therapy (DAPT) for at least 6 weeks to 12 months after stent implantation. If DAPT is continued during noncardiac surgery, there is a risk of severe bleeding at the surgical site. Our study was to assess the risk of bleeding in patients with continued DAPT during orthopedic surgery. Methods:. The clinical data of 78 patients with coronary heart disease who underwent orthopedic surgery from February 2006 to July 2018 were retrospectively analyzed. Prior to orthopedic surgery, DAPT was continued in 16 patients (group I), 24 patients were treated with single antiplatelet therapy (group II), and 26 patients received low-molecular-weight heparin therapy for more than 5 days after the discontinuation of all antiplatelet therapies (group III). Twelve patients were excluded, as they had undergone minimally invasive surgery such as transforaminal endoscopy and vertebroplasty. The perioperative blood loss of each patient was calculated using Nadler's formula and Gross’ formula. The intraoperative bleeding volume, total volume of intraoperative bleeding in addition to postoperative drainage, and total blood loss were compared between groups. The level of significance was set at P 0.05). Six patients experienced postoperative cardiovascular complications due to the delayed restart of antiplatelet therapy; one of these patients in group III died from myocardial infarction. Conclusions:. Continued DAPT or single antiplatelet treatment during orthopedic surgery does not increase the total intraoperative and perioperative bleeding compared with switching from antiplatelet therapy to low-molecular-weight heparin. However, the discontinuation of antiplatelet therapy increases the risk of serious cardiac complications.

Background: Pleural fibrosis is defined as excessive depositions of matrix components that result in pleural tissue architecture destruction and dysfunction. In severe cases, the progression of pleural fibrosis leads to lung entrapment, resulting in dyspnea and respiratory failure. However, the mechanism of pleural fibrosis is poorly understood. Methods: miR-4739 levels were detected by miRNA array and real-time PCR. Real-time PCR, western blotting and immunofluorescence were used to identify the expression profile of indicators related to fibrosis. Target gene of miR-4739 and promoter activity assay was measured by using dual-luciferase reporter assay system. In vivo, pleural fibrosis was evaluated by Masson staining and miR-4739 level was detected by In situ hybridization histochemistry. Findings: We found that bleomycin induced up-regulation of miR-4739 in pleural mesothelial cells (PMCs). Over-regulated miR-4739 mediated mesothelial-mesenchymal transition and increased collagen-I synthesis in PMCs. Investigation on the clinical specimens revealed that high levels of miR-4739 and low levels of bone morphogenetic protein 7 (BMP-7) associated with pleural fibrosis in patients. Then we next identified that miR-4739 targeted and down-regulated BMP-7 which further resulted in unbalance between Smad1/5/9 and Smad2/3 signaling. Lastly, in vivo studies revealed that miR-4739 over-expression induced pleural fibrosis, and exogenous BMP-7 prevented pleural fibrosis in mice. Interpretation: Our data indicated that miR-4739 targets BMP-7 which mediates pleural fibrosis. The miR-4739/BMP-7 axis is a promising therapeutic target for the disease. Fund: The National Natural Science Foundation of China. Keywords: Pleural fibrosis, Pleural mesothelial cells (PMCs), miR-4739, BMP-7, Mesothelial-mesenchymal transition (MMT)

Pleural fibrosis is defined as an excessive deposition of extracellular matrix that results in destruction of the normal pleural tissue architecture and compromised function. Tuberculous pleurisy, asbestos injury, and rheumatoid pleurisy are main causes of pleural fibrosis. Pleural mesothelial cells (PMCs) play a key role in pleural fibrosis. However, detailed mechanisms are poorly understood. Serine/arginine-rich protein SRSF6 belongs to a family of highly conserved RNA-binding splicing-factor proteins. Based on its known functions, SRSF6 should be expected to play a role in fibrotic diseases. However, the role of SRSF6 in pleural fibrosis remains unknown. In this study, SRSF6 protein was found to be increased in cells of tuberculous pleural effusions (TBPE) from patients, and decellularized TBPE, bleomycin, and TGF-β1 were confirmed to increase SRSF6 levels in PMCs. In vitro, SRSF6 mediated PMC proliferation and synthesis of the main fibrotic protein COL1A2. In vivo, SRSF6 inhibition prevented mouse experimental pleural fibrosis. Finally, activated SMAD2/3, increased SOX4, and depressed miRNA-506-3p were associated with SRSF6 upregulation in PMCs. These observations support a model in which SRSF6 induces pleural fibrosis through a cluster pathway, including SRSF6/WNT5A and SRSF6/SMAD1/5/9 signaling. In conclusion, we propose inhibition of the splicing factor SRSF6 as a strategy for treatment of pleural fibrosis.

This study was aimed to evaluate the potential of a herbal mixture (HM) to improve production performance, rumen fermentation, and milk fatty acid profile in water buffaloes. Sixteen Murrah buffaloes (in four groups) were fed for 10 weeks with the same basal diet supplemented with 0 (control); 20 (HM20), 30 (HM30), and 40 (HM40) g/buffalo per day. The herbal mixture contained an equal quantity of black pepper (fruit), ginger (tubers), cinnamon (bark), peppermint (leaves), ajwain (seeds) and garlic (bulbs). After two weeks of adaptation, daily milk yield, and weekly milk composition were recorded. On the last day of the experiment, rumen contents were collected to determine rumen fermentation parameters and bacterial diversity through 16S rRNA sequencing. Results revealed no effect of treatment on dry matter intake (DMI), rumen fermentation parameters, and daily milk yield. However, milk fat (%) showed a tendency to increase (p = 0.07) in HM20 as compared with the control group. A significant increase in mono and polyunsaturated fatty acids (C14:1, C16:1, C18:2n6 and C18:3) whereas a decrease in saturated fatty acids (C18:0) in milk was observed in HM20 as compared with the control group. No significant change in bacterial diversity parameters (alpha and beta diversity) was observed in response to the treatment. Despite the substantial variation observed in the relative abundance of bacteria among treatment groups, no significant effect of treatment was observed when compared with the control group. Correlation analysis revealed several positive and negative correlations of rumen bacteria with rumen volatile fatty acids (VFA) and milk yield traits. Bacterial genera including Succinivibrionaceae, Butyrivibrio, Pseudobutyrivibrio, and Lachnospiraceae showed a positive correlation with VFA and milk yield traits. Overall, we observed 52 positive and 10 negative correlations of rumen bacteria with milk fatty acid contents. Our study revealed the potential of the herbal mixture at a lower supplemental level (20 g/day) to increase milk fat (%) and unsaturated fatty acid content in buffalo.

Heterodimeric motor organization of kinesin-II is essential for its function in anterograde IFT in ciliogenesis. However, the underlying mechanism is not well understood. In addition, the anterograde IFT velocity varies significantly in different organisms, but how this velocity affects ciliary length is not clear. We show that in Chlamydomonas motors are only stable as heterodimers in vivo, which is likely the key factor for the requirement of a heterodimer for IFT. Second, chimeric CrKinesin-II with human kinesin-II motor domains functioned in vitro and in vivo, leading to a ~ 2.8 fold reduced anterograde IFT velocity and a similar fold reduction in IFT injection rate that supposedly correlates with ciliary assembly activity. However, the ciliary length was only mildly reduced (~15%). Modeling analysis suggests a nonlinear scaling relationship between IFT velocity and ciliary length that can be accounted for by limitation of the motors and/or its ciliary cargoes, e.g. tubulin.

Abstract. Lung cancer is a leading cause of cancer-related deaths worldwide. It mainly consists of 2 histological types: small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC, including squamous cell carcinoma and adenocarcinoma). The present study aimed to assess the role of serum progastrin-releasing peptide (ProGRP), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) and their combinations in the histological diagnosis of lung cancer (specially SCLC), which is of great importance for the initiation of treatment and prognostic implications. Serum ProGRP, NSE, and CEA were determined by the electrochemiluminescence immunoassay (ECLIA) in 66 patients with SCLC, 73 with adenocarcinoma, 44 with squamous cell carcinoma, 45 with non-malignant pulmonary diseases, and 50 healthy controls. Receiver operating characteristic curves were constructed to compare the predictive ability of each biochemical marker and their combined detection models to discriminate among the patients with lung cancers of different histological groups, benign pulmonary diseases and healthy individuals. In the ECLIA detection system, ProGRP showed the sensitivity and specificity for SCLC diagnosis were 71.2% and 91.1% to 93.2%, respectively. Among the markers, the largest area under the ROCs was for ProGRP in discriminating SCLC from benign pulmonary diseases, squamous cell carcinoma and adenocarcinoma (0.815, 0.859, and 0.835, respectively), which indicated that ProGRP was the most efficient marker for identifying SCLC. Besides, ProGRP and NSE exhibited almost equivalent diagnostic performance in discriminating SCLC from benign diseases. As for squamous cell carcinoma, we recommended proGRP, while for adenocarcinoma, the combination of proGRP and CEA was preferred. Remarkably, when ProGRP ≤ 66 pg/mL, CEA was of great value in diagnosing SCLC and adenocarcinoma. If CEA ≤ 5 ng/mL, the patient was at higher risk for SCLC, whereas the patient was more likely to be diagnosed with adenocarcinoma. Our study provided promising information about the diagnostic values of serum ProGRP, NSE, CEA in distinguishing SCLC from benign pulmonary diseases and NSCLC, which was of crucial clinical significance in the early diagnosis and therapy of SCLC.

Background: Functional dyspepsia (FD) is a common upper gastrointestinal disorder worldwide, but the current treatments for FD are still unsatisfactory. The aims of this study were to investigate the efficacy and safety of Qi-Zhi-Wei-Tong granules in patients with postprandial distress syndrome (PDS)-predominant FD. Methods: The study was conducted as a randomized, double-blinded, multicenter, placebo-controlled design in 197 patients with PDS. All participants received placebo treatment for 1 week. Patients whose total symptom score decreased by

Background: Etomidate (R-1-[1-ethylphenyl] imidazole-5-ethyl ester) is a widely used anesthetic drug that had been reported to contribute to cognitive deficits after general surgery. However, its underlying mechanisms have not been fully elucidated. In this study, we aimed to explore the neurobiological mechanisms of cognitive impairments that caused by etomidate. Methods: A total of 30 Sprague-Dawley rats were used and divided into two groups randomly to receive a single injection of etomidate or vehicle. Then, the rats′ spatial memory ability and neuronal survival were evaluated using the Morris water maze test and Nissl staining, respectively. Furthermore, we analyzed levels of oxidative stress, as well as cyclic adenosine 3′,5′-monophosphate response element-binding (CREB) protein phosphorylation and immediate early gene (IEG, including Arc, c-fos, and Egr1) expression levels using Western blot analysis. Results: Compared with vehicle-treated rats, the etomidate-treated rats displayed impaired spatial learning (day 4: 27.26 ± 5.33 s vs. 35.52 ± 3.88 s, t = 2.988, P = 0.0068; day 5: 15.84 ± 4.02 s vs. 30.67 ± 4.23 s, t = 3.013, P = 0.0057; day 6: 9.47 ± 2.35 s vs. 25.66 ± 4.16 s, t = 3.567, P = 0.0036) and memory ability (crossing times: 4.40 ± 1.18 vs. 2.06 ± 0.80, t = 2.896, P = 0.0072; duration: 34.00 ± 4.24 s vs. 18.07 ± 4.79 s, t = 3.023, P = 0.0053; total swimming distance: 40.73 ± 3.45 cm vs. 27.40 ± 6.56 cm, t = 2.798, P = 0.0086) but no neuronal death. Furthermore, etomidate did not cause oxidative stress or deficits in CREB phosphorylation. The levels of multiple IEGs (Arc: vehicle treated rats 100%, etomidate treated rats 86%, t = 2.876, P = 0.0086; c-fos: Vehicle treated rats 100%, etomidate treated rats 72%, t = 2.996, P = 0.0076; Egr1: Vehicle treated rats 100%, etomidate treated rats 58%, t = 3.011, P = 0.0057) were significantly reduced in hippocampi of etomidate-treated rats. Conclusion: Our data suggested that etomidate might induce memory impairment in rats via inhibition of IEG expression.

Background: Healthcare-associated pneumonia (HCAP) is associated with drug-resistant pathogens and high mortality, and there is no clear evidence that this is due to inappropriate antibiotic therapy. This study was to elucidate the clinical features, pathogens, therapy, and outcomes of HCAP, and to clarify the risk factors for drug-resistant pathogens and prognosis. Methods: Retrospective observational study among hospitalized patients with HCAP over 10 years. The primary outcome was 30-day all-cause hospital mortality after admission. Demographics (age, gender, clinical features, and comorbidities), dates of admission, discharge and/or death, hospitalization costs, microbiological results, chest imaging studies, and CURB-65 were analyzed. Antibiotics, admission to Intensive Care Unit (ICU), mechanical ventilation, and pneumonia prognosis were recorded. Patients were dichotomized based on CURB-65 (low- vs. high-risk). Results: Among 612 patients (mean age of 70.7 years), 88.4% had at least one comorbidity. Commonly detected pathogens were Acinetobacter baumannii, Pseudomonas aeruginosa, and coagulase-negative staphylococci. Initial monotherapy with β-lactam antibiotics was the most common initial therapy (50%). Mean age, length of stay, hospitalization expenses, ICU admission, mechanical ventilation use, malignancies, and detection rate for P. aeruginosa, and Staphylococcus aureus were higher in the high-risk group compared with the low-risk group. CURB-65 ≥3, malignancies, and mechanical ventilation were associated with an increased mortality. Logistic regression analysis showed that cerebrovascular diseases and being bedridden were independent risk factors for HCAP. Conclusion: Initial treatment of HCAP with broad-spectrum antibiotics could be an appropriate approach. CURB-65 ≥3, malignancies, and mechanical ventilation may result in an increased mortality.

Background: It is still a challenge for the cardiac surgeons to achieve adequate revascularization for diffused coronary artery disease (CAD). Coronary endarterectomy (CE) offers an alternative choice of coronary artery reconstruction and revascularization. In this study, short-term result of CE combined with coronary artery bypass graft (CABG) was discussed in the treatment for the diffused CAD. Methods: From January 2012 to April 2014, 221 cases of CABG were performed by the same surgeon in our unit. Among these cases, 38 cases of CE + CABG were performed, which was about 17.2% (38/221) of the cohort. All these patients were divided into two groups: CE + CABG group (Group A) and CABG alone group (Group B). All clinical data were compared between the two groups, and postoperative complications and in-hospital mortality were analyzed. The categorical and continuous variables were analyzed by Chi-square test and Student′s t-test respectively. Results: Diabetes mellitus, hypertension, hyperlipidemia, and peripheral vascular disease were more common in group A. In this cohort, a total of 50 vessels were endarterectomized. Among them, CE was performed on left anterior descending artery in 11 cases, on right coronary artery in 29 cases, on diagonal artery in 3 cases, on intermediate artery in 2 cases, on obtuse marginal artery in 5 cases. There was no hospital mortality in both groups. The intro-aortic balloon pump was required in 3 cases in Group A (3/38), which was more often than that in Group B (3/183). At the time of follow-up, coronary computed tomography angiogram showed all the grafts with CE were patent (50/50). There is no cardio-related mortality in both groups. All these patients were free from coronary re-intervention. Conclusions: Coronary endarterectomy + CABG can offer satisfactory result for patients with diffused CAD in a short-term after the operation.