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Summary: Calcitonin gene-related peptide (CGRP), a neuropeptide involved in nociceptor neuronal function, plays a critical role in mediating neuroinflammation and pain. In this study, we find that bladder group 2 innate lymphoid cells (ILC2s) function as primary producers of CGRP in the early phase of bacterial cystitis, contributing to increased inflammation, altered voiding behavior, and heightened pelvic allodynia. Furthermore, we demonstrate that interleukin (IL)-33, a cytokine secreted by urothelial cells, upregulates CGRP production by ILC2s in the bladder during uropathogenic Escherichia coli (UPEC) infection. Moreover, our research reveals that monocytes expressing high levels of receptor activity-modifying protein 1 (RAMP1), a CGRP receptor, mediate the pro-inflammatory effects of CGRP-producing ILC2s. In summary, our results underscore the significance of the immune cell-derived neuropeptides in the pathology of UPEC infection, suggesting a promising therapeutic approach targeting the IL-33-ILC2-CGRP axis for managing lower urinary tract symptoms in bacterial cystitis.

Abstract The correlation between liver disease and the progression of ulcerative colitis (UC) has remained elusive. In this study, it demonstrates that liver injury is intricately linked to the heightened severity of UC in patients, and causes more profound intestinal damage during DSS‐induced colitis in mice. Metabolomics analysis of plasma from liver cirrhosis patients shows liver injury compromising nicotinamide supply for NAD+ biosynthesis in the intestine. Subsequent investigation identifies intestinal group 2 innate lymphoid cells (ILC2s) are responsible for liver injury‐exacerbated colitis. Reconstitution of ILC2s or the restoration of NAD+ metabolism proves effective in relieving liver injury‐aggravated experimental colitis. Mechanistically, the NAD+ salvage pathway regulates gut ILC2s in a cell‐intrinsic manner by supporting the generation of succinate, which fuels the electron transport chain to sustaining ILC2s function. This research deepens the understanding of cellular and molecular mechanisms in liver disease‐UC interplay, identifying a metabolic target for innovative treatments in liver injury‐complicated colitis.

Abstract Background Talaromyces Marneffei (TM) is a rare opportunistic pathogen that mostly infects patients with low immunity compared to those with normal immunity. It may be related to immune deficiency or genetic factors. Objective To evaluate the gene mutation of a patient infected with TM in an endemic area with negative anti-interferon-γ autoantibodies, and negative human immunodeficiency virus (HIV) infection. Methods Extract deoxyribonucleic acid (DNA) samples from the patient's peripheral blood, detect the mutation gene by whole exome sequencing (WES), and carry out Sanger sequencing verification for the detected mutation gene. Results The authors detected a mutation in the IFNGR1 gene (NM_001363526.1) and validated the detected gene mutation using Sanger sequencing. The results showed a heterozygous mutation c.4C>T (p.L2F) located in the IFNGR1 gene (NM_001363526.1). Study limitations The mechanism of the IFNGR1 gene has not been further investigated in this study. Conclusions The IFNGR1 gene mutation may be a potential risk factor for TM infection, and the presence of anti-interferon-γ autoantibodies can aggravate disease symptoms.

BackgroundType 2 Diabetes Mellitus (T2D) and Osteoarthritis (OA) are both prevalent diseases that significantly impact the health of patients. Increasing evidence suggests that there is a big correlation between T2D and OA, but the molecular mechanisms remain elusive. The aims of this study are to investigate the shared biomarkers and potential molecular mechanisms in T2D combined with OA.MethodsT2D and OA-related differentially expressed genes (DEGs) were identified via bioinformatic analysis on Gene Expression Omnibus (GEO) datasets GSE26168 and GSE114007 respectively. Subsequently, extensive target prediction and network analysis were finished with Gene Ontology (GO), protein-protein interaction (PPI), and pathway enrichment with DEGs. The transcription factors (TFs) and miRNAs coupled in co-expressed DEGs involved in T2D and OA were predicted as well. The key genes expressed both in the clinical tissues of T2D and OA were detected with western blot and qRT-PCR assay. Finally, the most promising candidate compounds were predicted with the Drug-Gene Interaction Database (DGIdb) and molecular docking.ResultsIn this study, 209 shared DEGs between T2D and OA were identified. Functional analysis disclosed that these DEGs are predominantly related to ossification, regulation of leukocyte migration, extracellular matrix (ECM) structural constituents, PI3K/AKT, and Wnt signaling pathways. Further analysis via Protein-Protein Interaction (PPI) analysis and validation with external datasets emphasized MMP9 and ANGPTL4 as crucial genes in both T2D and OA. Our findings were validated through qRT-PCR and Western blot analyses, which indicated high expression levels of these pivotal genes in T2D, OA, and T2D combined with OA cases. Additionally, the analysis of Transcription Factors (TFs)-miRNA interactions identified 7 TFs and one miRNA that jointly regulate these important genes. The Receiver Operating characteristic (ROC) analysis demonstrated the significant diagnostic potential of MMP9 and ANGPTL4.Moreover, we identified raloxifene, ezetimibe, and S-3304 as promising agents for patients with both T2D and OA.ConclusionThis study uncovers the shared signaling pathways, biomarkers, potential therapeutics, and diagnostic models for individuals suffering from both T2D and OA. These findings not only present novel perspectives on the complex interplay between T2D and OA but also hold significant promise for improving the clinical management and prognosis of patients with this concurrent condition.

Abstract Pulmonary heart disease (PHD) involves altered structure and function of the right ventricle caused by an abnormal respiratory system that causes pulmonary hypertension. However, the association between changes in plasma proteomics and PHD remains unclear. Hence, we aimed to identify causal associations between genetically predicted plasma protein levels and PHD. Mendelian randomization was performed to test the target proteins associated with PHD. Summary statistics for the human plasma proteome and pulmonary heart disease were acquired from the UK Biobank (6038 cases and 426 977 controls) and the FinnGen study (6753 cases and 302 401 controls). Publicly available pQTLs datasets for human plasma proteins were obtained from a largescale genome‐wide association study in the INTERVAL study. The results were validated using a case–control cohort. We first enrolled 3622 plasma proteins with conditionally independent genetic variants; three proteins (histo‐blood group ABO system transferase, activating signal cointegration 1 complex subunit 1, and calcium/calmodulin‐dependent protein kinase I [CAMK1]) were significantly associated with the risk of pulmonary heart disease in the UK Biobank cohort. Only CAMK1 was successfully replicated (odds ratio: 1.1056, 95% confidence interval: 1.019–1.095, p = 0.0029) in the FinnGen population. In addition, the level of CAMK1 in 40 patients with PHD was significantly higher (p = 0.023) than that in the control group. This work proposes that CAMK1 is associated with PHD, underscoring the importance of the calcium signaling pathway in the pathophysiology to improve therapies for PHD.

Objective To explore the clinical significance of platelet-related parameters in children with chronic spontaneous urticaria (CSU). Methods Sixty-eight children with CSU and 68 children without CSU were enrolled. The differences in platelet-related parameters, including platelet count (PLT), mean platelet volume (MPV), and platelet distribution width (PDW), were compared between the two groups. The association of the disease course and disease severity with platelet-related parameters were analyzed in CSU children. Results PLT levels were significantly higher in children with CSU than in that without CSU (t=3.96, P0.05). However, the disease course correlated positively with MPV (r=0.26, P=0.034) and PDW (r=0.35, P=0.004), but not with PLT levels (r=0.02, P=0.875), in children with CSU.PLT levels negatively correlated with MPV (r=-0.41, P

Abstract Chronic kidney disease (CKD) has historically been a significant global health concern, profoundly impacting both life and well-being. In the process of CKD, with the gradual loss of renal function, the incidence of various life-threatening complications, such as cardiovascular diseases, cerebrovascular accident, infection and stroke, is also increasing rapidly. Unfortunately, existing treatments exhibit limited ability to halt the progression of kidney injury in CKD, emphasizing the urgent need to delve into the precise molecular mechanisms governing the occurrence and development of CKD while identifying novel therapeutic targets. Renal fibrosis, a typical pathological feature of CKD, plays a pivotal role in disrupting normal renal structures and the loss of renal function. Ferroptosis is a recently discovered iron-dependent form of cell death characterized by lipid peroxide accumulation. Ferroptosis has emerged as a potential key player in various diseases and the initiation of organ fibrosis. Substantial evidence suggests that ferroptosis may significantly contribute to the intricate interplay between CKD and its progression. This review comprehensively outlines the intricate relationship between CKD and ferroptosis in terms of iron metabolism and lipid peroxidation, and discusses the current landscape of pharmacological research on ferroptosis, shedding light on promising avenues for intervention. It further illustrates recent breakthroughs in ferroptosis-related regulatory mechanisms implicated in the progression of CKD, thereby providing new insights for CKD treatment. Video Abstract

Abstract Aims Apolipoproteins have been reported to be involved in many cardiovascular diseases. The aim of our study was to investigate the prognostic value of apolipoprotein B (ApoB) to apolipoprotein A‐I (ApoA‐I) ratio (ApoB/ApoA‐I) in patients with heart failure (HF). Methods and results We randomly assigned 2400 HF patients into the training cohort (n = 1400) and the validation cohort (n = 1000). Using a receiver operating characteristic curve, we identified the optimal cut‐off value of the ApoB/ApoA‐I in the training cohort as 0.69, which was further validated in the validation cohort. A propensity score matching (PSM) analysis was conducted to eliminate the imbalance in the baseline characteristics of the high and low ApoB/ApoA‐I group. A total of 2242 HF patients were generated in the PSM cohort. We also validated our results with an independent cohort (n = 838). Univariate and multivariate analyses were conducted to explore the independent prognostic value of ApoB/ApoA‐I in the training cohort (n = 1400), the validation cohort (n = 1000), the PSM cohort (n = 2242), and the independent cohort (n = 838). Patients with high ApoB/ApoA‐I ratio had significantly poorer prognosis compared with those with low ApoB/ApoA‐I ratio in the training cohort, the validation cohort, the PSM cohort, and the independent cohort (P

Abstract Objective ST-segment myocardial infarction (STEMI) is a time-sensitive emergency. This study screened the favorable factors for the survival of STEMI patients with medium- and high-risk thrombolysis in myocardial infarction (TIMI) scores. Methods According to the TIMI scores at admission, 433 STEMI patients were retrospectively and consecutively selected and allocated into low-/medium-/high-risk groups, with their general information/blood routine/biochemical indicators/coagulation indicators documented. The factors influencing the in-hospital survival of STEMI patients were analyzed using univariate and multivariate logistic regression analyses. Moreover, the predictive value of favorable factors was analyzed by receiver operating characteristics (ROC) curve, and patients were assigned into high/low level groups based on the cut-off value of these factors, with their in-hospital survival rates compared. Results The in-hospital survival rate of the medium-/high-risk groups was lower than that of the low-risk group. Emergency percutaneous coronary intervention (PCI), lymphocyte (LYM), total protein (TP), albumin (ALB), and sodium (Na) were independent favorable factors for in-hospital survival in the medium-/high-risk groups. Besides, LYM > 1.275 × 109/L, TP > 60.25 g/L, ALB > 34.55 g/L, and Na > 137.9 mmo1/L had auxiliary predictive value for the survival of STEMI patients with medium-/high-risk TIMI scores. Patients with high levels of LYM, TP, ALB, and Na exhibited higher in-hospital survival rates than patients with low levels. Conclusion For STEMI patients with medium- and high-risk TIMI scores, accepting emergency PCI and normal levels of LYM, TP, ALB, and Na were more conducive to in-hospital survival.

To explore the effects of yeast fermentation on deodorization and flavor enhancement of Seriola lalandi roe, the nutritional value of Seriola lalandi roe were studied in this paper at first, and then high sugar type instant dry yeast was selected as the fermenting agent, the optimal fermentation process conditions were optimized by single-factor experimental analysis according to the sensory score, pH and total acid content. Fresh fish roe and unfermented fish roe were used as controls to analyze the difference in sensory quality, free amino acids and volatile flavor composition of the fermented fish roe. The results showed that, the Seriola lalandi roe was rich in polyunsaturated fatty acids, zinc and selenium elements, and had high nutritional value. The best deodorization effect by 1.5% yeast inoculum, 5% sucrose addition, 1.5 h fermentation time and 28 ℃ fermentation temperature. The contents of sweet amino acids and umami amino acids in fermented roe increased significantly（P

The activation of brown adipose tissue by cold exposure in paternal mice has been reported to improve the metabolic health of offspring. Notably, dietary components for activating BAT have drawn considerable attention owing to their high feasibility for human trials. Therefore, here the potential metabolic improving effects of dietary capsaicin intervention on diet-induced obese paternal mice and their offspring were measured. The results support that paternal preconceptional capsaicin intervention not only elicited the anticipated enhancement of brown fat activity in obese paternal mice, but also improved the metabolic profiles in male offspring evidenced by their elevated resistance to high-fat diet challenge. Moreover, changes in sperm DNA methylation and small non-coding RNA profile were noted in paternal mice with capsaicin intervention, though additional investigation is needed to further delve into the mechanisms. In summary, paternal dietary intervention activating BAT could represent a promising strategy for enhancing the metabolic health of offspring.

ObjectiveTo investigate the association between the dietary intake of linoleic acid (LA) and alpha linolenic acid (ALA) with mortality outcomes in patients with diabetes.Participants3,112 U.S. adults aged≥20 years.SettingBasic information was collected at baseline of the National Health and Nutrition Examination Survey (NHANES). Serum CRP (mg/dL), total protein (g/L), waist circumference (cm), fasting blood glucose (mmol/L), white blood cell count, serum LDL-C, and serum HDL-C were also measured. Daily diets were also recorded using a 24-hour dietary review to produce the individuals’ intake of LA and ALA. The association between tertiles of LA and ALA intake with mortality was analyzed by weighted Cox models adjusted for the main confounders.Main outcome measuresThe study included 3,112 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2008. Death outcomes were ascertained by linkage to the database records through 31 December 2015.ResultsSubjects with a high intake of LA (T3) had 17% [hazard ratio (HR) 0.83, 95% CI 0.70 to 0.99) and 48% (HR=0.52, 0.35 to 0.80)] reductions in all-cause mortality and cardiovascular mortality, respectively, compared with subjects with lowest intake (T1). Similar results were observed for ALA, HR of cardiovascular mortality was 0.55 (0.38 to 0.81) and for all-cause mortality was 0.85 (0.69 to 1.04) comparing the highest to lowest intake tertiles.ConclusionHigher intakes of LA and ALA were inversely associated with CVD and all-cause deaths in patients with diabetes. Proper dietary intakes of LA and ALA could contribute to the cardiovascular health and the long-term survival of patients with diabetes.

Abstract The aim of this study was to investigate the association between serum albumin to serum creatinine ratio (sACR) and the prognosis of heart failure (HF). In this single‐center prospective cohort study, a total of 2625 patients with HF were enrolled between March 2012 and June 2017. All patients were divided into three groups according to the tertiles of sACR. Of 2625 patients, the mean age was 57.0 ± 14.3 years. During a median follow‐up time of 23 months, 666 end point events occurred. Prognosis analysis indicated that the lowest sACR was significantly associated with higher mortality risk of HF (hazard ratio [HR] = 1.920, 95% confidence interval [CI] = 1.585–2.326, p

Gel materials, especially hydrogels and aerogels, have been materials of interest in adsorption technology research in recent years [...]

Probiotics have become increasingly recognized for their potential health-promoting properties; however, the viability of probiotics can be affected by storage and transportation processes as well as the stressful environment of the human digestive tract, preventing them from achieving effective concentration (107 CFU/mL). In this regard, the embedding technology of probiotics provides an effective protection method. Dextran-based water in water (W/W) emulsion loaded with Lactobacillus plantarum was used as spinning solution to prepare Lactobacillus plantarum-loaded electrospun fibers. The structure of the W/W emulsion and the electrospun fibers was charactered. Lactobacillus plantarum were uniformly embedded in the internal phase of the W/W emulsion and the loading efficiency was 9.70 ± 0.40 log CFU/g. After 240 min digestion in the gastrointestinal tract, and temperature treatment in 65 °C and 72 °C, the loaded probiotics maintained high activity. Even after 5 days of storage in room temperature and 4 °C, the loaded probiotic activity levels remained high, with counts >8 log CFU/g. These results suggest that probiotics encapsulated by emulsion electrospinning could be potentially delivered in a novel food delivery system used in the future food industry.

We present a case of superior vena cava syndrome caused by thoracic tumor with initial presentation of diffuse skin swelling. A 62-year-old female presented with facial erythema, swelling and itching for 6 months, with aggravation for 5 days. Dermatological examination showed diffuse edematous erythema on the face, with unclear boundary, fading under pressure, tight feeling of touch, nonpitting edema of the neck and upper limbs. The patient was diagnosed as allergic dermatitis in other hospital. Following the treatments with antiallergic and other symptomatic treatment, pruritus was slightly improved, but the erythema and swelling of the face were not significantly improved, and gradually aggravated. Chest multislice helieal CT showed soft tissue masses on the mediastinum and right hilum. The lesions were considered as malignant lesions involved the superior vena cava, atrium and right pleura. Formation of tumor thrombus in superior vena cava and its branches, right atrium, right superior pulmonary vein and left atrium were also seen. Diagnosis: thoracic tumors complicated with superior vena cava syndrome. Due to the concerns of medical cost and surgical risks, the patient did not receive further treatment in our hospital and was lost to follow-up.

Abstract Antimicrobial peptides (AMPs) are important mediators of intestinal immune surveillance. However, the regional heterogeneity of AMPs and its regulatory mechanisms remain obscure. Here, we clarified the regional heterogeneity of intestinal AMPs at the single-cell level, and revealed a cross-lineages AMP regulation mechanism that bile acid dependent transcription factors (BATFs), NR1H4, NR1H3 and VDR, regulate AMPs through a ligand-independent manner. Bile acids regulate AMPs by perturbing cell differentiation rather than activating BATFs signaling. Chromatin accessibility determines the potential of BATFs to regulate AMPs at the pre-transcriptional level, thus shaping the regional heterogeneity of AMPs. The BATFs-AMPs axis also participates in the establishment of intestinal antimicrobial barriers of fetuses and the defects of antibacterial ability during Crohn’s disease. Overall, BATFs and chromatin accessibility play essential roles in shaping the regional heterogeneity of AMPs at pre- and postnatal stages, as well as in maintenance of antimicrobial immunity during homeostasis and disease.

Abstract Aims Dilated cardiomyopathy (DCM) belongs to the common types of cardiomyopathies. The pathogenesis remains unclear despite the fact that various genes have been found associated with DCM. MMP2 is a zinc‐dependent and calcium‐containing secreted endoproteinases, which could cleave a broad spectrum of substrates including extracellular matrix components and cytokines. It has proved to play an important role in the cardiovascular diseases. This study aimed to investigate the potential role of MMP2 gene polymorphisms in DCM susceptibility and prognosis in a Chinese Han population. Methods and results A total of 600 idiopathic DCM patients and 700 healthy controls were enrolled. Patients with contact information were followed up for a median period of 28 months. Three tagged single nucleotide polymorphisms (rs243865, rs2285052, and rs2285053) in the promoter of MMP2 gene were genotyped. A series of function analysis were conducted to illuminate the underlying mechanism. The frequency of rs243865‐C allele was increased in DCM patients when compared with healthy controls (P = 0.001). Genotypic frequencies of rs243865 were associated with the susceptibility of DCM in the codominant, dominant, and overdominant models (P

Colon cancer is increasing worldwide and is commonly regarded as hormone independent, yet recent reports have implicated sex hormones in its development. Nevertheless, the role of hormones from the hypothalamus–hypophysis axis in colitis-associated colorectal cancer (CAC) remains uncertain. In this study, we observed a significant reduction in the expression of the oxytocin receptor (OXTR) in colon samples from both patient with colitis and patient with CAC. To investigate further, we generated mice with an intestinal-epithelium-cell-specific knockout of OXTR. These mice exhibited markedly increased susceptibility to dextran-sulfate-sodium-induced colitis and dextran sulfate sodium/azoxymethane-induced CAC compared to wild-type mice. Our findings indicate that OXTR depletion impaired the inner mucus of the colon epithelium. Mechanistically, oxytocin was found to regulate Mucin 2 maturation through β1-3-N-acetylglucosaminyltransferase 7 (B3GNT7)-mediated fucosylation. Interestingly, we observed a positive correlation between B3GNT7 expression and OXTR expression in human colitis and CAC colon samples. Moreover, the simultaneous activations of OXTR and fucosylation by l-fucose significantly alleviated tumor burden. Hence, our study unveils oxytocin’s promising potential as an affordable and effective therapeutic intervention for individuals affected by colitis and CAC.

Abstract Background Measurement of the Chinese burden of disease with disability-adjusted life-years (DALYs) requires disability weight (DW) that quantify health losses for all non-fatal consequences of disease and injury. The Global Burden of Disease (GBD) 2013 DW study indicates that it is limited by lack of geographic variation in DW data and by the current measurement methodology. We aim to estimate DW for a set of health states from major diseases in the Wuhan population. Methods We conducted the DW measurement study for 206 health states through a household survey with computer-assisted face-to-face interviews and a web-based survey. Based on GBD 2013 DW study, paired comparison (PC) and Population health equivalence (PHE) method was used and different PC/PHE questions were randomly assigned to each respondent. In statistical analysis, the PC data was analyzed by probit regression. The probit regression results will be anchored by results from the PHE data analyzed by interval regression on the DW scale units between 0 (no loss of health) and 1 (loss equivalent to death). Results A total of 2610 and 3140 individuals were included in the household and web-based survey, respectively. The results from the total pooled data showed health state “mild anemia” (DW = 0.005, 95% UI 0.000–0.027) or “allergic rhinitis (hay fever)” (0.005, 95% UI 0.000–0.029) had the lowest DW and “heroin and other opioid dependence, severe” had the highest DW (0.699, 95% UI 0.579–0.827). A high correlation coefficient (Pearson’s r = 0.876; P

Piezocatalysis, a heterogeneous catalytic technique, leverages the periodic electric field changes generated by piezoelectric materials under external forces to drive carriers for the advanced oxidation of organic pollutants. Antibiotics, as emerging trace organic pollutants in water sources, pose a potential threat to animals and drinking water safety. Thus, piezoelectric catalysis can be used to degrade trace organic pollutants in water. In this work, BaTiO3 and La-doped BaTiO3 were synthesized using an improved sol–gel–hydrothermal method and used as piezocatalytic materials to degrade sulfadiazine (SDZ) with ultrasound activation. High-crystallinity products with nano cubic and spherical morphologies were successfully synthesized. An initial concentration of SDZ ranging from 1 to 10 mg/L, a catalysis dosage range from 1 to 2.5 mg/mL, pH, and the background ions in the water were considered as influencing factors and tested. The reaction rate constant was 0.0378 min−1 under the optimum working conditions, and the degradation efficiency achieved was 89.06% in 60 min. La-doped BaTiO3 had a better degradation efficiency, at 14.98% on average, compared to undoped BaTiO3. Further investigations into scavengers revealed a partially piezocatalytic process for the degradation of SDZ. In summary, our work provides an idea for green environmental protection in dealing with new types of environmental pollution.

To implement state policies of zero-markup drug policy and medical service fee adjustment for public hospitals, this study constructed game models of the pharmaceutical supply chain, consisting of a drug supplier and a public hospital. The study obtained the optimal medical service level and pricing under the new state drug policies. In addition, it analyzed the impacts of the degree of public benefit of hospitals on the medical service level, the medical service price, and the drug price. Finally, from the perspective of cooperation between drug suppliers and public hospitals, the specialized coordination contract was designed to maximize overall social welfare. This study found an anomalous but meaningful conclusion: in the background of the zero-markup drug policy, a higher public benefit of hospitals could increase the drug prices, but it could reduce the medical service prices further to cut down on the overall treatment fees for the patients. The novel coordination contract can optimize the pharmaceutical supply chain and achieve a win-win situation for the drug suppliers, public hospitals, and patients. When the public benefit of hospitals is higher, the profit of a decentralized decision-making supply chain is greater than a centralized one, while the pharmaceutical supply chain will not coordinate itself.

Background: Inflammatory bowel disease (IBD) is a chronic disease with an unclear pathogenesis for which successful treatments are still lacking. It has been reported that procyanidin, a natural antioxidant, relieves colitis, but the specific mechanism is elusive. Purpose: Our present study was designed to investigate the effects of procyanidin on colitis and the regulation of the M1 macrophage phenotype and related signaling pathways. Methods: In vivo, we used two classic colitis models to observe the effect of procyanidin on macrophage polarization. In vitro, we further validated the therapeutic effect of procyanidin in the RAW264.7 cell line and peritoneal macrophages. Results: The current findings provide new evidence that procyanidin ameliorated dextran sulfate sodium (DSS)-induced colitis by preventing the polarization of macrophages to the M1 type and downregulating the levels of proinflammatory factors in cells. We also showed that procyanidin prevented lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines and the activation of proinflammatory macrophages, which was achieved by activating the STAT3 and NF-κB pathways. Conclusions: This is the first study to demonstrate that procyanidin alleviates experimental colitis by inhibiting the polarization of proinflammatory macrophages. These data reveal new ideas for the pathogenesis and treatment of inflammatory diseases.

The occurrence of antibiotics in agricultural soils has raised concerns due to their potential risks to ecosystems and human health. However, a comprehensive understanding of antibiotic accumulation, distribution, and potential risks to terrestrial ecosystems on a global scale is still limited. Therefore, in this study, we evaluated the accumulation of antibiotics and their potential risks to soil microorganisms and plants, and highlighted the driving factors of antibiotic accumulation in agricultural soils based on 134 peer-reviewed studies (between 2000 and 2022). The results indicated that 56 types of antibiotics were detected at least once in agricultural soils with concentrations ranging from undetectable to over 7000 µg/kg. Doxycycline, tylosin, sulfamethoxazole, and enrofloxacin, belonging to the tetracyclines, macrolides, sulfonamides, and fluoroquinolones, respectively, were the most accumulated antibiotics in agricultural soil. The accumulation of TCs, SAs, and FQs was found to pose greater risks to soil microorganisms (average at 29.3%, 15.4%, and 21.8%) and plants (42.4%, 26.0%, and 38.7%) than other antibiotics. East China was identified as a hot spot for antibiotic contamination due to high levels of antibiotic concentration and ecological risk to soil microorganisms and plants. Antibiotic accumulation was found to be higher in vegetable fields (245.5 µg/kg) and orchards (212.4 µg/kg) compared to croplands (137.2 µg/kg). Furthermore, direct land application of manure resulted in a greater accumulation of TCs, SAs, and FQs accumulation in soils than compost fertilization. The level of antibiotics decreased with increasing soil pH and organic matter content, attributed to decreasing adsorption and enhancing degradation of antibiotics. In conclusion, this study highlights the need for further research on the impacts of antibiotics on soil ecological function in agricultural fields and their interaction mechanisms. Additionally, a whole-chain approach, consisting of antibiotic consumption reduction, manure management strategies, and remediation technology for soil contaminated with antibiotics, is needed to eliminate the potential environmental risks of antibiotics for sustainable and green agriculture.

Aiming at the problem of fuzzy selection basis of dual-structure slope simulation calculation parameters and the complicated force and deformation of the slope body in the supporting process. The study relies on the treatment project of the right side slope of the K5 + 220-K5 + 770 section of the TJ1A section of the Jiangwen Expressway. The slope is a gravel soil-weathered bedrock dual structure slope, which is referred to as Hetangba slope in the study. Use Midas/GTS NX to build a trial calculation model. A new method for checking simulation parameters of deep displacement monitoring data is proposed. The superposition calculation method of pore water pressure is proposed to realize the slope stress-seepage coupling. The analysis method of slope excavation and support process is put forward. The analysis shows that the most dangerous working condition in the slope excavation and support process is the second-level excavation. When there is a local displacement and plastic strain concentration area on the slope, the reference significance of the extreme value and the safety factor is reduced. Compared with the application of pore water pressure and no pore water pressure, there is no obvious change in the position of the extreme value of horizontal displacement and plastic strain in working conditions 2–8, but the extreme value changes are different. The slope safety factor of working conditions 2–8 is reduced. The continuous distribution zone of plastic strain inside the slope disappeared in condition 7. There is a very small unstable area on the top of the third-level slope of working conditions 9–11. The research results have great theoretical guiding significance for the measurement and control simulation and early warning analysis of the dual structure slope construction process.

Abstract Background Endometrial cancer (EC) is a common malignant tumor in women with increasing mortality. The prognosis of EC is highly heterogeneous which needs more effective biomarkers for clinical decision. Here, we reported the effect of autophagy-related genes (ARGs) on the prognosis of EC. Methods The expression data of EC tissues and adjacent non-tumor samples were available from the TCGA dataset and 232 autophagy-related genes were from The Human Autophagy Database. A prognostic ARGs risk model was further constructed by using LASSO-Cox regression, and its prognostic and predictive value were evaluated by nomogram. Further functional analysis was conducted to reveal a significant signaling pathway. Results A total of 45 differentially expressed ARGs were obtained, including 18 upregulated and 27 downregulated genes. Eleven ARGs (BID, CAPN2, CDKN2A, DLC1, GRID2, IFNG, MYC, NRG3, P4HB, PTK6, and TP73) were finally selected to build ARGs risk. This signature could well distinguish between the high- and low-risk patients (survival analysis: P = 1.18E-10; AUC: 0.733 at 1 year, 0.795 at 3 years, and 0.823 at 5 years). Furthermore, a nomogram was plotting to predict the possibility of overall survival and suggested good value for clinical utility. Conclusion We established an eleven-ARG signature, which was probably effective in the prognostic prediction of patients with EC.

ABSTRACT Mesomycoplasma hyopneumoniae is the etiological agent of mycoplasmal pneumonia of swine (MPS), which causes substantial economic losses to the world’s swine industry. Moonlighting proteins are increasingly being shown to play a role in the pathogenic process of M. hyopneumoniae. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH), a key enzyme in glycolysis, displayed a higher abundance in a highly virulent strain of M. hyopneumoniae than in an attenuated strain, suggesting that it may have a role in virulence. The mechanism by which GAPDH exerts its function was explored. Flow cytometry and colony blot analysis showed that GAPDH was partly displayed on the surface of M. hyopneumoniae. Recombinant GAPDH (rGAPDH) was able to bind PK15 cells, while the adherence of a mycoplasma strain to PK15 was significantly blocked by anti-rGAPDH antibody pretreatment. In addition, rGAPDH could interact with plasminogen. The rGAPDH-bound plasminogen was demonstrated to be activated to plasmin, as proven by using a chromogenic substrate, and to further degrade the extracellular matrix (ECM). The critical site for GAPDH binding to plasminogen was K336, as demonstrated by amino acid mutation. The affinity of plasminogen for the rGAPDH C-terminal mutant (K336A) was significantly decreased according to surface plasmon resonance analysis. Collectively, our data suggested that GAPDH might be an important virulence factor that facilitates the dissemination of M. hyopneumoniae by hijacking host plasminogen to degrade the tissue ECM barrier. IMPORTANCE Mesomycoplasma hyopneumoniae is a specific pathogen of pigs that is the etiological agent of mycoplasmal pneumonia of swine (MPS), which is responsible for substantial economic losses to the swine industry worldwide. The pathogenicity mechanism and possible particular virulence determinants of M. hyopneumoniae are not yet completely elucidated. Our data suggest that GAPDH might be an important virulence factor in M. hyopneumoniae that facilitates the dissemination of M. hyopneumoniae by hijacking host plasminogen to degrade the extracellular matrix (ECM) barrier. These findings will provide theoretical support and new ideas for the research and development of live-attenuated or subunit vaccines against M. hyopneumoniae.

ObjectivesEvidence of the relationship between android fat mass and gynoid fat mass with the mortality prediction is still limited. Current study analyzed the NHANES database to investigate the relationship between android fat mass, gynoid fat mass and CVD, with all-cause mortality.MethodThe study subjects were NHANES participants over 20 years old, two indicators of regional body composition, android fat and gynoid fat were measured by Dual Energy x-ray Absorptiometry (DEXA). The other various covariates data obtained from the NHANES questionnaire and laboratory measurements, including age, gender, education, race/ethnicity, uric acid, total serum cholesterol, albumin, Vitamin C, folate, alcohol drinking, smoking status, history of diabetes, and hypertension. Mortality status was ascertained from a linked mortality file prepared by the National Center for Health Statistics. The study population was divided quartiles based on the distribution of android fat mass and gynoid fat mass. The relationship between these two indicators with cardiovascular and all-cause mortality was investigated by using Cox regression. The covariates age, gender, smoking status, drinking status, history of diabetes, and history of hypertension were stratified.ResultsIn the fully adjusted model, Q3 had the lowest HR in android fat mass and gynoid fat mass. When examining the relationship between android fat mass and CVD mortality, current smokers and drinkers had the lowest CVD risk in Q2 [smoking: 0.21 (0.08, 0.52), drinking: 0.14 (0.04, 0.50)]. In diabetic patients, compared with Q1, other groups with increased android fat mass can significantly reduce the risk of CVD [Q4: 0.17 (0.04, 0.75), Q3: 0.18 (0.03, 1.09), Q2: 0.27 (0.09, 0.83)]. In ≥60 years old and female, the greater the gynoid fat mass, the smaller the HR of all-cause mortality [Q4 for ≥60 years old: 0.57 (0.33, 0.96), Q4 for female: 0.37 (0.23, 0.58)]. People

Thin film nano-composite polyamide (TFN PA) total heat exchange membranes (THEMs) containing ZIF-7, ZIF-8, ZIF-9 and ZIF-67 particles (PTs) introduced during interface polymerization process were prepared. A novel integrated online testing system was established to simultaneously evaluate their CO2 and moisture exchange rates as well as energy recovery efficiencies. ZIF PTs added in water phase improved the CO2 barrier property of the THEMs due to their good dispersion in water, the coordination of the excess cations on their surfaces with the –NH2 groups of MPD from the PA matrix and partially by increasing the PA layer thickness. Addition of ZIF PTs in organic phase showed variety of effects on the CO2 barrier property of the THEMs depending on their dispersion, structure rigidity, and interaction with the PA polymer matrix. Adding 0.01 g/144 cm2 of ZIF-67 in aqueous phase and 0.02 g/144 cm2 of ZIF-9 in organic phase could form TFN membranes with improved CO2 barrier property without sacrificing energy recovery efficiencies. ZIF-9 addition in organic phase formed ZIF/PA TFN THEMs with the highest total heat recovery rates of 72% and lowest on-line CO2 exchange rates of 1.7%. The newly obtained online CO2 exchange rates (hCO2) were found to have good correlation with the off-line CO2 permeance values (PERCO2), ηCO2 = ln (PERCO2)%-0.005, with a high Pearson's R value of 0.9914. There was also a linear correlation between the permeation selectivity obtained online (DSH2O/CO2) and calculated offline (ISH2O/CO2), ISH2O/CO2 = 0.289*DSH2O/CO2+14.4, with an excellent Pearson's R values of 0.9942. The integrated testing system could give more realistic evaluation for novel THEMs with a lot less efforts.

Abstract Mycoplasma hyorhinis may cause systemic inflammation of pigs, typically polyserositis and arthritis, and is also associated with several types of human cancer. However, the pathogenesis of M. hyorhinis colonizing and breaching the respiratory barrier to establish systemic infection is poorly understood. Glycolytic enzymes are important moonlighting proteins and virulence-related factors in various bacteria. In this study, we investigated the functions of a glycolytic critical enzyme, enolase in the infection and systemic spread of M. hyorhinis. Bacterial surface localization of enolase was confirmed by flow cytometry and colony hybridization assay. Recombinant M. hyorhinis enolase (rEno) was found to adhere to pig kidney (PK-15) cells, and anti-rEno serum significantly decreased adherence. The enzyme was also found to bind host plasminogen and fibronectin, and interactions were specific and strong, with dissociation constant (K D) values of 1.4 nM and 14.3 nM, respectively, from surface plasmon resonance analysis. Activation of rEno-bound plasminogen was confirmed by its ability to hydrolyze plasmin-specific substrates and to degrade a reconstituted extracellular matrix. To explore key sites during these interactions, C-terminal lysine residues of enolase were replaced with leucine, and the resulting single-site and double-site mutants show significantly reduced interaction with plasminogen in far-Western blotting and surface plasmon resonance tests. The binding affinities of all mutants to fibronectin were reduced as well. Collectively, these results imply that enolase moonlights as an important adhesin of M. hyorhinis, and interacts with plasminogen and fibronectin. The two lysine residues in the C-terminus are important binding sites for its multiple binding activities.

The stress and deformation response characteristics of the support structure in the process of excavation and support of circular sand foundation pit are complex. The existing research results lack a general analysis method for the mutual check between the field monitoring data and the numerical simulation results. This research relies on the excavation and support project of a circular foundation pit in the sandy soil layer of the west anchorage of Humen Second Bridge. The force and deformation characteristics of foundation pit soil are monitored and structure is supported during construction. A new method for checking simulation parameters based on the excursion monitoring data of the diaphragm wall is proposed. The modeling and calculation theory of foundation pit excavation and support process is established. The superposition calculation of pore water pressure is used to realize the foundation pit seepage-stress coupling. The effects of steady-state seepage conditions on the equivalent strain of foundation pit soil, the displacement of the diaphragm wall, and the axial force of the lining are compared and analyzed. The stress and deformation mechanism of the soil layer and supporting structure during the excavation and support of a circular foundation pit in the sand layer is obtained.

IntroductionThe evidence on eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) intake status and long-term mortality among people with diabetes is scarce. This study aimed to investigate the relationship between EPA and DHA intakes with all-cause and cause-specific mortality in adults with diabetes.MethodsThis study included 2,991 adults with diabetes from the National Health and Nutrition Examination Survey (NHANES) 1999–2008. Death outcomes were ascertained by linkage to the database records through 31 December 2015. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for mortality from all causes, cardiovascular disease (CVD), and coronary heart disease (CHD) in patients with diabetes.ResultsAmong 2,991 patients with diabetes, the mean age was 61.9 years (55.2% males). During the mean follow-up duration of 9.4 years, a total of 1,091 deaths were documented, of which 273 were due to CVD, including 227 CHD deaths. EPA and DHA intakes were associated with lower mortality risks, especially that of CVD. After adjusting for demographic, major lifestyle factors, overall dietary intake patterns, and history of hypertension and dyslipidemia, the multivariable HRs (95% CIs) of mortality risk comparing Q4 to Q1 of EPA intake were 0.55 (0.33–0.92; P-trend = 0.019) for CHD, 0.55 (0.36–0.83; P-trend = 0.005) for CVD, and 0.91 (0.70–1.18; P-trend = 0.264) for all-cause. The respective HRs (95% CIs) comparing Q4 to Q1 of DHA were 0.60 (0.37–0.98; P-trend = 0.051) for CHD, 0.58 (0.38–0.89; P-trend = 0.014) for CVD, and 0.92 (0.72–1.18; P-trend = 0.481) for all-cause. In subgroup analysis, we found that the association trends of EPA and DHA intakes with death risk remained robust among patients with diabetes, especially among those who are old, female, those with higher BMI, and dyslipidemia patients with CVD and CHD.DiscussionIn the USA, higher EPA and DHA intakes were associated with a lower risk of CHD and CVD mortality in patients with diabetes. Our study supports the benefits of adequate EPA and DHA intakes in promoting the health of patients with diabetes.

Abstract Hepatic ischemia–reperfusion (IR) injury remains a common issue lacking effective strategy and validated pharmacological targets. Here, using an unbiased metabolomics screen, this study finds that following murine hepatic IR, liver 3‐hydroxyanthranilic acid (3‐HAA) and quinolinic acid (QA) decline while kynurenine and kynurenic acid (KYNA) increase. Kynurenine aminotransferases 2, functioning at the key branching point of the kynurenine pathway (KP), is markedly upregulated in hepatocytes during ischemia, shifting the kynurenine metabolic route from 3‐HAA and QA to KYNA synthesis. Defects in QA synthesis impair de novo nicotinamide adenine dinucleotide (NAD) biosynthesis, rendering the hepatocytes relying on the salvage pathway for maintenance of NAD and cellular antioxidant defense. Blocking the salvage pathway following IR by the nicotinamide phosphoribosyltransferase inhibitor FK866 exacerbates liver oxidative damage and enhanced IR susceptibility, which can be rescued by the lipid peroxidation inhibitor Liproxstatin‐1. Notably, nicotinamide mononucleotide administration once following IR effectively boosts NAD and attenuated IR‐induced oxidative stress, inflammation, and cell death in the murine model. Collectively, the findings reveal that metabolic rewiring of the KP partitions it away from NAD synthesis in hepatic IR pathophysiology, and provide proof of concept that NAD augmentation is a promising therapeutic measure for IR‐induced liver injury.

Acute kidney injury (AKI), one of the most prevalent clinical diseases with a high incidence rate worldwide, is characterized by a rapid deterioration of renal function and further triggers the accumulation of metabolic waste and toxins, leading to complications and dysfunction of other organs. Multiple pathogenic factors, such as rhabdomyolysis, infection, nephrotoxic medications, and ischemia-reperfusion injury, contribute to the onset and progression of AKI. However, the detailed mechanism remains unclear. Ferroptosis, a recently identified mechanism of nonapoptotic cell death, is iron-dependent and caused by lipid peroxide accumulation in cells. A variety of studies have demonstrated that ferroptosis plays a significant role in AKI development, in contrast to other forms of cell death, such as apoptosis, necroptosis, and pyroptosis. In this review, we systemically summarized the definition, primary biochemical mechanisms, key regulators and associated pharmacological research progress of ferroptosis in AKI. We further discussed its therapeutic potential for the prevention of AKI, in the hope of providing a useful reference for further basic and clinical studies.

ObjectiveThe potential effects of pulmonary dysfunction on cardiovascular diseases (CVD) and all-cause mortality are receiving attention. The current study aimed to explore whether reduced lung function predicts CVD and all-cause mortality in people with diabetes.MethodsA total of 1,723 adults with diabetes (mean age 60.2 years) were included in the National Health and Nutrition Examination Survey (NHANES III). Death outcomes were ascertained by linkage to the database records through 31 December 2015. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for coronary heart disease (CHD), CVD, and all-cause mortalities. We conducted stratified analyses based on age, body mass index (BMI), history of hypertension, and dyslipidemia.ResultsDuring a mean follow-up of 14.62 years (25,184 person-year), a total of 1,221 deaths were documented, of which 327 were CHD, 406 were CVD, and 197 were cancer. After multi-factor adjustment, participants with lower FEV1 and FVC had a higher risk of CHD, CVD, and all-cause mortality. This association was also found in lower FVC and a higher risk of cancer mortality [HR: 3.85 (1.31–11.32); P for trend = 0.040], but the association of FEV1 was attenuated after adjustment for covariates [HR:2.23 (0.54–9.17); P for trend = 0.247]. In subgroup analysis, we found that the adverse associations of FEV1 and FVC with CVD mortality were observed in subgroups of age, BMI, and history of hypertension and dyslipidemia.ConclusionDeclined lung function was associated with a higher risk of CVD and all-cause mortality in people with diabetes. Lung function tests, especially FEV1 and FVC, should be encouraged to provide prognostic and predictive information for the management of CVD and all-cause mortality in patients with diabetes.

Actinic keratosis (AK) is a common precancerous skin lesion with significant harm, and it is often confused with non-actinic keratoses (NAK). At present, the diagnosis of AK mainly depends on clinical experience and histopathology. Due to the high difficulty of diagnosis and easy confusion with other diseases, this article aims to develop a convolutional neural network that can efficiently, accurately, and automatically diagnose AK. This article improves the MobileNet model and uses the AK and NAK images in the HAM10000 dataset for training and testing after data preprocessing, and we performed external independent testing using a separate dataset to validate our preprocessing approach and to demonstrate the performance and generalization capability of our model. It further compares common deep learning models in the field of skin diseases (including the original MobileNet, ResNet, GoogleNet, EfficientNet, and Xception). The results show that the improved MobileNet has achieved 0.9265 in accuracy and 0.97 in Area Under the ROC Curve (AUC), which is the best among the comparison models. At the same time, it has the shortest training time, and the total time of five-fold cross-validation on local devices only takes 821.7 s. Local experiments show that the method proposed in this article has high accuracy and stability in diagnosing AK. Our method will help doctors diagnose AK more efficiently and accurately, allowing patients to receive timely diagnosis and treatment.

Abstract The current study was aimed to explore the beneficial effects of polysaccharides isolated from Laminaria japonica (LP) on gestational diabetes mellitus (GDM) mice. The obtained results demonstrated that the LP improved serum biochemical index, body weight index, and glucose tolerance. Furthermore, the evidence also suggested that the beneficial effects of LP might be attributed to the alternation in gut microbiota by LP supplementation. Particularly, the Turicibacter, a short‐chain fatty acids‐producing bacterium, was found to be up‐regulated. In conclusion, the obtained results indicated that the LP might serve as prebiotic, and might have a great potential to be used as food supplementation for GDM patients.

Abnormal activation of the innate and adaptive immune systems has been observed in inflammatory bowel disease (IBD) patients. Anxiety and depression increase the risk of IBD by activating the adaptive immune system. However, whether anxiety affects innate immunity and its impact on IBD severity remains elusive. This study investigated the mechanism by which anxiety contributes to IBD development in a murine model of acute wrap restraint stress (WRS). Here, we found that anxiety-induced overactivation of group 2 innate lymphoid cells (ILC2) aggravated colonic inflammation. Overactivation of the hypothalamic–pituitary–adrenal (HPA) axis is a hallmark of the physiological change of anxiety. Corticosterone (CORT), a stress hormone, is a marker of HPA axis activation and is mainly secreted by HPA activation. We hypothesized that the overproduction of CORT stimulated by anxiety exacerbated colonic inflammation due to the abnormally elevated function of ILC2. The results showed that ILC2 secreted more IL-5 and IL-13 in the WRS mice than in the control mice. Meanwhile, WRS mice experienced more body weight loss, shorter colon length, higher concentrations of IL-6 and TNF-α, more severely impaired barrier function, and more severe inflammatory cell infiltration. As expected, the serum corticosterone levels were elevated after restraint stress. Dexamethasone (DEX) was then injected to mimic HPA axis activation induced CORT secretion. DEX injection can also stimulate ILC2 to secrete more type II cytokines and exacerbate oxazolone (OXA) induced colitis. Blocking the IL-13/STAT6 signaling pathway alleviated colitis in WRS and DEX-injected mice. In conclusion, the overactivation of ILC2 induced by CORT contributed to the development of OXA-induced colitis in mice.

Mycoplasma hyopneumoniae is the etiological agent of swine enzootic pneumonia (EP), which resulting in considerable economic losses in pig farming globally. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) is a major tool for gene expression studies. However, no internal reference genes for normalization of RT-qPCR data of M. hyopneumoniae have been reported. The aim of this study was to screen the most stable genes for RT-qPCR analysis in M. hyopneumoniae under different conditions. Therefore, a total of 13 candidate internal reference genes (rpoC, Lipo, sgaB, oppB, hypo621, oppF, gyrB, uvrA, P146, prfA, proS, gatB, and hypo499) of M. hyopneumoniae filtered according to the reported quantitative proteomic analysis and the 16S rRNA internal reference gene frequently used in other bacteria were selected for RT-qPCR analysis. The mRNAs from different virulence strains (168, 168 L, J, NJ, and LH) at five different growth phases were extracted. The corresponding cycle threshold (Ct) values of the 25 reverse transcribed cDNAs using the 14 candidate genes were determined. Different internal reference genes or combinations were then screened for expression stability analysis using various statistical tools and algorithms, including geNorm, BestKeeper, and NormFinder software, to ensure the reliability of the analysis. Through further comprehensive evaluation of the RefFinder software, it is concluded that the gatB gene was the most suitable internal reference gene for samples of the different virulence strains in different growth phases for M. hyopneumoniae, followed by prfA, hypo499, and gyrB.

Abstract Double-suction centrifugal pumps have been applied extensively in many areas, and the significance of pressure fluctuations inside these pumps with large power is becoming increasingly important. In this study, a double-suction centrifugal pump with a high-demand for vibration and noise was redesigned by increasing the flow uniformity at the impeller discharge, implemented by combinations of more than two parameters. First, increasing the number of the impeller blades was intended to enhance the bounding effect that the blades imposed on the fluid. Subsequently, increasing the radial gap between the impeller and volute was applied to reduce the rotor-stator interaction. Finally, the staggered arrangement was optimized to weaken the efficacy of the interference superposition. Based on numerical simulation, the steady and unsteady characteristics of the pump models were calculated. From the fluctuation analysis in the frequency domain, the dimensionless pressure fluctuation amplitude at the blade passing frequency and its harmonics, located on the monitoring points in the redesigned pumps (both with larger radial gap), are reduced a lot. Further, in the volute of the model with new impellers staggered at 12°, the average value for the dimensionless pressure fluctuation amplitude decreases to 6% of that in prototype pump. The dimensionless root-mean-square pressure contour on the mid-span of the impeller tends to be more uniform in the redesigned models (both with larger radial gap); similarly, the pressure contour on the mid-section of the volute presents good uniformity in these models, which in turn demonstrating a reduction in the pressure fluctuation intensity. The results reveal the mechanism of pressure fluctuation reduction in a double-suction centrifugal pump, and the results of this study could provide a reference for pressure fluctuation reduction and vibration performance reinforcement of double-suction centrifugal pumps and other pumps.

Abstract Aims Our objective was to investigate the association of common variants in the coding region of advanced glycosylation end‐product specific receptor (RAGE) and the prognosis of heart failure (HF). Methods and results A total of 3394 HF patients were continuously enrolled from January 2009 to August 2018 with a median follow‐up of 20.4 months. Additionally, 2861 healthy subjects also participated in the study. By sequencing these two groups, we identified a common functional missense variant rs2070600 in the coding region of RAGE, which showed a significant association with the prognosis of HF [hazard ratio = 0.53, 95%, confidence interval (CI) = 0.30–0.94, P = 0.03], but no association with the risk of HF (odds ratio = 0.52, 95%, CI = 0.66–1.04, P = 0.106). A series of functional assays revealed that rs2070600‐A, but not ‐G allele, suppressed the expression of RAGE protein by facilitating the binding of miR‐125a‐3p. Furthermore, the RAGE messenger RNA levels of human peripheral blood lymphocytes were reduced in subjects with the rs2070600‐AA genotype compared with subjects with the rs2070600‐GG or ‐AG genotypes. Additionally, our Western blot results from human heart tissue showed increased RAGE expression in HF samples compared with that in healthy donors. Conclusions Our results demonstrate that the common missense variant rs2070600‐A allele is associated with a reduced risk of cardiovascular death and cardiac transplantation by facilitating the binding of miR‐125a‐3p.

As a major component of the enteroendocrine system, enterochromaffin (EC) cells play a key role in ulcerative colitis (UC). However, the scarcity of EC cells has limited the investigation of their function. In this study, we applied digital spatial profiling to acquire transcriptomic data for EC cells and other epithelial cells from colonoscopic biopsy samples from eight patients with UC and seven healthy controls. Differential expression analysis, gene set enrichment analysis, and weighted gene coexpression network analysis were performed to identify differentially expressed genes and pathways and coexpression networks. Results were validated using an online dataset obtained by single-cell RNA sequencing, along with immunofluorescence staining and quantitative real-time PCR. In healthy participants, 10 genes were significantly enriched in EC cells, functionally concentrated in protein and bioamine synthesis. A coexpression network containing 17 hub genes, including TPH1, CHGA, and GCLC, was identified in EC cells. In patients with UC, EC cells gained increased capacity for protein synthesis, along with novel immunological functions such as antigen processing and presentation, whereas chemical sensation was downregulated. The specific expression of CHGB and RGS2 in EC cells was confirmed by immunofluorescence staining. Our results illuminate the transcriptional signatures of EC cells in the human colon. EC cells’ newly observed functional shift from sensation to secretion and immunity indicates their pivotal role in UC.

Background: Stroke is the predominant cause of death worldwide. We aimed to investigate the association of serum beta-2 microglobulin (β2M) concentrations with risk of stroke and all-cause mortalities in a cohort study. Methods: Overall, 4914 U.S. adults (mean age = 63.0 years, 44.3% male) were recruited from the National Health and Nutrition Examination Survey (NHANES Ⅲ). During a median follow-up of 19.4 years, 254 stroke deaths and 3415 all-cause deaths were identified by the National Center for Health Statistics. The associations of β2M with stroke and all-cause mortalities were investigated by using weighted Cox proportional hazard regression models. Results: β2M was positively associated with stroke and all-cause mortality in unadjusted models and multivariable-adjusted models. The multivariable HR (95% CI) for stroke mortality in Q5 VS Q1 of serum β2M concentrations was 3.45 (1.33–8.91; p for trend = 0.001) and that for all-cause mortality was 3.95 (3.05–5.12; p for trend < 0.001). In subgroup analyses, the association of β2M and stroke mortality did not vary by different levels of sociodemographic and general stroke risk factors (p interaction > 0.05). In addition, the magnitude of positive association between β2M with all-cause mortality did vary by age, ratio of family income to poverty, smoking status, and history of hypertensive (p interaction < 0.05). Conclusions: Our findings suggest that support that β2M may be a marker of stroke and all-cause mortality, which provides a new perspective for the study of cerebrovascular health and long-term survival in the future.

Among patients with diabetes mellitus, limited studies have investigated the relationship between anthropometric parameters and cardiovascular disease (CVD), with all-cause mortality. We examined the associations of arm circumference (AC), arm-to-waist ratio (AC/WC), and CVD, with all-cause mortality among patients with diabetes. This is a cohort study of 5497 diabetic individuals aged 20 or over who were recruited in the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2014. Cox proportional hazards regression models were used to analyze the associations between AC, AC/WC, and CVD, with all-cause mortality. We also conducted stratified analyses and explored the possible non-linear relation by restricted cubic splines. During a median follow-up of 7.2 years, there were 271 and 1093 cases of CVD and all-cause death. The multivariable adjusted hazard ratios (HRs) with 95% confidence intervals (Cis) of CVD mortality in Q2, Q3, and Q4 groups compared with Q1 group were 0.37 (0.22, 0.62), 0.24 (0.12, 0.48), 0.18 (0.07, 0.46) for AC, and 0.18 (0.07, 0.46), 0.34 (0.20, 0.60), 0.28 (0.15, 0.53) for AC/WC. Similar results were observed in the analysis for all-cause mortality risk. AC and AC/WC were both inversely associated with CVD and all-cause mortality among individuals with diabetes. It is important to pay attention to these anthropometric parameters of diabetic patients.

In the general population, there is little evidence of a link between blood urea nitrogen (BUN) and long-term mortality. The goal of this study was to explore whether higher BUN concentration is a predictor of cardiovascular disease (CVD) and all-cause mortality. From 1999 to 2006, the National Health and Nutrition Examination Survey (NHANES) included 17,719 adult individuals. Death outcomes were ascertained by linkage to the database records through 31 December 2015. The Cox proportional hazard regression model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) for CVD and all-cause mortality in individuals. We also performed stratified analyses based on age, gender, drinking, smoking, history of hypertension and diabetes. During a mean follow-up 11.65 years, a total of 3628 deaths were documented, of which 859 were due to CVD. Participants with higher BUN had a higher risk of CVD and all-cause death compared to those with lower BUN. After multifactor adjustment for demographics, major lifestyle factors, and hypertension and diabetes history, higher BUN levels compared with lower levels were significantly associated with higher risk of CVD (HR: 1.48 [1.08, 2.02], P-trend < 0.001) and all-cause mortality (HR: 1.48 [1.28, 1.72], P-trend < 0.001). In subgroup analyses, we found that the trend in the association of BUN with the risk of death remained strong in female subjects. Greater BUN levels were linked to higher CVD and all-cause mortality in the NHANES of American adults. The importance of BUN in predicting death is supported by our research.

Background: Mutations in genes encoding sarcomere and cytoskeletal proteins are major causes of primary dilated cardiomyopathy (DCM). Likewise, ischemic myocardial injury is a major cause of secondary cardiac remodeling, which, in a subset, is severe and resembles DCM. The latter is referred to as ischemic dilated cardiomyopathy (IDCM). We postulated the presence of pathogenic and likely pathogenic variants (PVs and LPVs, respectively) in genes known to cause primary DCM might predispose the heart to severe cardiac dilatation and dysfunction post myocardial ischemic injury, i.e., IDCM.Methods: We performed whole-exome sequencing in 1,041 patients with primary DCM, 215 patients with IDCM, and 414 healthy controls. Indices of cardiac size and function were similar between those with primary and ischemic DCM. PVs and LPVs, including the truncating variants in 36 genes known to cause primary DCM were identified and compared among the three groups.Results: Pathogenic variants and LPVs were detected in 266 individuals, comprised of 215/1,041 (20.7%) patients with DCM, 27/215 (12.6%) patients with IDCM, and 24/414 (5.8%) control individuals. PVs and LPVs in the TTN gene were the most common and detected in 130/1,041 (12.5%) of patients with DCM, 15/215 (7.0%) of cases with IDCM, and 10/414 (2.4%) control individuals. Of 135 TTNtv, 118 involved exons that were >90% spliced in. These variants were found in 120/1,041 (11.5%) of DCM patients, 6/215 (2.8%) of IDCM cases, and only in 1/414 (0.2%) of the control population (p < 0.001 among the three groups).Conclusions: Pathogenic variants and LPVs in genes known to cause primary DCM are enriched in patients with IDCM, suggesting that such variants function as susceptibility alleles for cardiac dilatation and dysfunction in post myocardial ischemic injury. Thus, IDCM shares a partial genetic etiology with the primary DCM.

Limited evidence investigated the combined influence of early-adulthood weight change and later physical activity on the risk of cardiovascular (CVD) and all-cause mortality. The aim of this study is to explore the associations of early-adulthood weight change and later physical activity with CVD and all-cause mortality. This is a cohort study of 23,193 US adults aged 40 to 85 years from the National Health and Nutrition Examination Survey (NHANES) 1999 to 2014. Cox proportional hazards regression was used to calculate hazard ratios (HRs) with 95% confidence intervals (CIs) of CVD and all-cause mortality associated with early-adulthood weight change and later physical activity. During a median follow-up of 9.2 years, there were 533 and 2734 cases of CVD and all-cause deaths. Compared with being physically inactive, the HRs of the CVD mortality of being physically active were 0.44 (0.26 to 0.73), 0.58 (0.19 to 1.82), 0.38 (0.17 to 0.86) and 0.46 (0.21 to 1.02) among individuals with stable normal, stable obese, non-obese to obese and maximum overweight early-adulthood weight change patterns. Using stable normal patterns that were physically active later as the reference, other early-adulthood weight change patterns did not show a significantly higher risk of CVD mortality when participants were physically active in later life; later physically inactive participants had a significantly increased risk of CVD mortality, with HRs of 2.17 (1.30 to 3.63), 5.32 (2.51 to 11.28), 2.59 (1.29 to 5.18) and 2.63 (1.32 to 5.26) in the stable normal, stable obese, non-obese to obese and maximum overweight groups, respectively. Similar results can be seen in the analyses for all-cause mortality. Our findings suggest that inadequate physical activity worsens the negative impact of unhealthy early-adulthood weight change patterns, which is worthy of being noted in the improvement of public health.

Background Visceral hypersensitivity is a common symptom in patients with post-infectious irritable bowel syndrome (PI-IBS), and change of the microbiota is a vital etiological factor of it. Clostridium butyricum (C. butyricum) is one of the probiotics which is reported as the active components in the treatment of IBS, especially IBS with diarrhea. Citrobacter rodentium (C. rodentium) is an enteropathogenic bacteria which can produce self-limiting colitis in mice, which have been used to produce a PI-IBS-like mice model. Whether C. butyricum could influence the visceral hypersensitivity and gut microbiota of PI-IBS is still unknown. Our study aimed to examine whether the intervention of C. butyricum or antibiotics could affect the etiology of visceral hypersensitivity. Methods C57BL/6 male mice were gavaged with the C. rodentium to induce a infective colitis. The C. butyricum and antibiotic compound were used to intervene the infected mice 3 days later. A 9-day chronic water avoidance stress (WAS) process was implemented to help induce the visceral hypersensitivity. The abdominal withdrawal reflex (AWR) score was assayed to indicate the visceral hypersensitivity of different groups. On the 7th, 14th, and 30th days after infection, mice feces were collected and high-throughput sequencing was carried out to analyze their gut microbiota. Results Combined, the C. rodentium infection plus chronic stress (WAS) could induce the visceral hypersensitivity in mice. Treatment of the C. butyricum after C. rodentium infection could relieve visceral hypersensitivity of mice, while no difference was observed in the antibiotic treatment group. The gut microbiota diversity of C. rodentium infected mice was similar to the uninfected mice, while there were different microbial communities structure between them. The Shannon and Chao indexes significantly decreased in the antibiotic treatment group compared to other groups at 7th, 14th, and 30th days post-infection, while treatment of C. butyricum could maintain the indexes within normal range. At day 14 after infection, the structure of microbiota headed towards normality after the C. butyricum treatment. After the WAS, the Shannon and Chao indexes of the control group decreased and the structure of microbiota changed. The C. butyricum treatment could prevent these changes of the gut microbiota induced by WAS. Conclusion C. butyricum could relieve the visceral hypersensitivity in mice induced by C. rodentium infection plus chronic stress. It could also remodel the microbiota change caused by the infection and chronic stress. It may be a more effective treatment strategy for PI-IBS than antibiotics.

Background: Common variants may contribute to the variation of prognosis of heart failure (HF) among individual patients, but no systematical analysis was conducted using transcriptomic and whole exome sequencing (WES) data. We aimed to construct a genetic risk score (GRS) and estimate its potential as a predictive tool for HF-related mortality risk alone and in combination with traditional risk factors (TRFs).Methods and Results: We reanalyzed the transcriptomic data of 177 failing hearts and 136 healthy donors. Differentially expressed genes (fold change >1.5 or

Nonbacterial prostatitis has been reported to be associated with reduced zinc intake, but the role of zinc remains unclear. Here, oyster hydrolysate-zinc complex (OH-Zn) was prepared to attenuate rat prostatitis. We found using dynamic light scattering and energy-dispersive X-ray analysis that OH-Zn was a nanostructure complex (49.06 ± 0.26 nm) with a prominent signal of zinc. Fourier transform infrared spectroscopy illustrated that OH-Zn was formed via interactions among zinc ions, amino nitrogen atoms and carboxyl oxygen. OH-Zn treatment significantly reduced the prostatic index value, prostatic specific antigen, tumor necrosis factor-alpha, interleukin-1 beta, malonaldehyde, prostatic acid phosphatase, and acid phosphatase in prostatitis rats. OH-Zn increased the levels of superoxide dismutase, glutathione and serum zinc concentration in prostatitis rats relative to the control group. Moreover, histological analyses revealed OH-Zn prevented the carrageen-induced pathological morphology of the prostate. Therefore, OH-Zn might be a preferable paradigm to ameliorate prostatitis as a novel zinc supplement.