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Abstract The removal and discharge of coal powders from coalbed methane wellbore is the key to maintaining continuous production. For this reason, based on the submerged jet theory, the force and migration starting conditions of coal powder particles deposited at the bottom of the coalbed methane well are analyzed by analyzing the cohesiveness of coal powders, and a model for the starting and migration of coal powders at the bottom of the well under submerged jet conditions is established; Considering the adhesion between coal dust, the adhesion coefficient is used to characterize the adhesion between particles, a mechanical model of coal dust particles deposited at the bottom of the well is established, and the corresponding calculation formula for the outlet flow rate of the coal dust cleaning nozzle is derived. The fluid mechanics parameters of the bottom of the well coal dust cleaning under different conditions are obtained, and the numerical simulation method is used to simulate the whole process of jet flushing of the bottom of the well coal dust deposited, and the effect of the bottom of the well jet flushing of coal dust deposits is analyzed, providing a theoretical basis for the bottom of the well coal dust flushing process.

ABSTRACT Background The toxicity and drug resistance associated with oxaliplatin (L‐OHP) limit its long‐term use for colorectal cancer (CRC) patients. p53 mutation is a common genetic trait of CRC. PRIMA‐1met (APR‐246, eprenetapopt) restores the DNA‐binding capacity of different mutant P53 proteins. PRIMA‐1met has progressed to the Phase III clinical trial. Our study explores the combination therapy of PRIMA‐1met and L‐OHP for CRC with different p53 status. Methods Cell viability was assessed with Cell Counting Kit‐8 (CCK‐8) assay and combination index (CI) was calculated using The Chou‐Talalay method. We also employed wound healing assay and colony formation assay to determine the effect of L‐OHP, PRIMA‐1met and their combination. Weighted gene co‐expression network analysis (WGCNA) of RNA‐seq data was conducted to identify key modules and central genes related to different treatment modalities. Xenograft CRC mouse model was used to assess the combination treatment in vivo. Results Our findings showed heightened cytotoxicity and inhibition of migration, and colony formation in CRC cells treated with both drugs, irrespective of p53 status, presenting a promising avenue for addressing L‐OHP resistance and toxicity. RNA‐seq analysis revealed differential responses between p53‐wide type HCT116 and p53‐mutant DLD‐1 cells, with pathway alterations implicated in tumorigenesis. WGCNA identified key modules and hub genes associated with combination therapy response. In vivo studies demonstrated enhanced efficacy of combined therapy over PRIMA‐1met alone, while mitigating L‐OHP‐induced toxicity. Conclusions In summary, our research reveals the differential molecular mechanisms of combined PRIMA‐1met and L‐OHP in CRC with wild type p53 and mutant p53. Our data not only demonstrate that this combined regimen exerts synergistic anti‐CRC effect in vitro and in vivo, but also suggest the benefit of PRIMA‐1met on prevention of L‐OHP‐related side effects. These findings underscore the clinical potential of PRIMA‐1met‐L‐OHP combination therapy in CRC, offering enhanced efficacy and reduced toxicity, warranting further clinical investigation.

Central precocious puberty (CPP) is an endocrine disease in children, characterized by rapid genital development and secondary sexual characteristics before the age of eight in girls and nine in boys. The premature activation of the hypothalamic-pituitary-gonadal axis (HPGA) limits the height of patients in adulthood and is associated with a higher risk of breast cancer. How to prevent and improve the prognosis of CPP is an important problem. Vitamin D receptor (VDR) is widely expressed in the reproductive system, participates in the synthesis and function of regulatory sex hormones, and affects the development and function of gonads. In addition, gut microbiota plays an important role in human health by mainly regulating metabolites, energy homeostasis, and hormone regulation. This review aims to clarify the effect of vitamin D deficiency on the occurrence and development of CPP and explore the role of gut microbiota in it. Although evidence on the interaction between vitamin D deficiency, gut microbiota, and sexual development remains limited, vitamin D supplementation and gut microbiota interventions offer a promising, non-invasive strategy for managing CPP.

Abstract Systolic blood pressure variability (SBPV) is associated with outcome in acute ischemic stroke. Remote ischemic conditioning (RIC) has been demonstrated to be effective in stroke and may affect blood pressure. Relationship between SBPV and RIC treatment after stroke warrants investigation. A total of 1707 patients from per-protocol analysis set of RICAMIS study were included. The SBPV was calculated based on blood pressure measured at admission, Day 7, and Day 12. (I) To investigate the effect of SBPV on efficacy of RIC in stroke, patients were divided into High and Low categories in each SBPV parameter. Primary outcome was excellent functional outcome at 90 days. Compared with Control, efficacy of RIC in each category and interaction between categories were investigated. (II) To investigate the effect of RIC treatment on SBPV, SBPV parameters were compared between RIC and Control groups. Compared with Control, a higher likelihood of primary outcome in RIC was found in high category (max–min: adjusted risk difference [RD] = 7.2, 95% CI 1.2–13.1, P = 0.02; standard deviation: adjusted RD = 11.5, 95% CI 1.6–21.4, P = 0.02; coefficient of variation: adjusted RD = 11.2, 95% CI 1.4–21.0, P = 0.03). Significant interaction of RIC on outcomes were found between High and Low standard deviations (adjusted P

Abstract Objective We performed a post hoc exploratory analysis of Remote Ischemic Conditioning for Acute Moderate Ischemic Stroke (RICAMIS) to determine whether hypertension history and baseline systolic blood pressure (SBP) affect the efficacy of remote ischemic conditioning (RIC). Methods Based on the full analysis set of RICAMIS, patients were divided into hypertension versus non‐hypertension group, or

Abstract Background Centella Asiatica has been shown to have beneficial value for the treatment of tumors. However, its active ingredients and molecular mechanisms of action have not been fully elucidated. Pectic polysaccharides are the primary active components from medicinal plants. Moreover, these polysaccharides are regarded as potential inhibitors of galectins, such as galectin-1, -3, -7, that generally promote tumor growth. Nevertheless, detailed structural analysis of pectic polysaccharides from Centella Asiatica is sorely lacking, as is knowledge of their interactions with galectins. Methods Water-soluble pectic polysaccharides (WCAP) isolated from Centella Asiatica were purified into two homogeneous fractions (WCAP-A2b and WCAP-A5b) by a combination of anion-exchange and gel-permeation chromatography. Monosaccharide composition, FT-IR, NMR and enzymatic analyses were used to characterize their structural features. Furthermore, the interactions between galectin-1, -3, -7 and a series of these polysaccharides, including two pectin fractions and their structural domains produced by enzymatic hydrolysis, were evaluated by using hemagglutination and biolayer interferometry. Results WCAP-A2b and WCAP-A5b have weight averaged molecular weights of 30.0 kDa and 34.0 kDa, respectively, and both polysaccharides consist of rhamnogalacturonan I (RG-I), rhamnogalacturonan II (RG-II) and homogalacturonan (HG) domains, with mass ratios of 1.3: 1.0: 1.4 and 1.1: 1.0: 2.4, respectively. Their RG-I domains contain arabinan, galactan, and/or arabinogalactan, along with neutral sugar side chains that are more prevalent in WCAP-A2b than in WCAP-A5b. Hemagglutination and biolayer interferometry binding assays indicate that galectin-3 vis-à-vis galectin-1 and -7, binds strongly to the RG-I domain (likely via its neutral side chains) in WCAP-A5b, thereby inhibiting galectin-3-mediated cell–cell interactions. Conclusions Our study provides structural information on pectin polysaccharides from Centella Asiatica. Results suggest that RG-I domains from WCAP-A5b and WCAP-A2b may be developed as potential inhibitors of galectin-3-mediated cell–cell adhesion and tumor growth. Graphical Abstract

BackgroundSerum creatinine (Cr)- and cystatin C (CysC)-based indices have been suggested as alternative markers for sarcopenia, but their predictive value for sarcopenia risk is uncertain, which was investigated in the present study in the Chinese population with the middle and older ages.MethodsData from the China Health and Retirement Longitudinal Study (CHARLS) were collected in the 2011 and 2015 waves. All participants were free of sarcopenia at the baseline. Sarcopenia was diagnosed when low muscle mass and grip strength or low physical performance were present. Four indices were computed: predictive skeletal muscle mass index (pSMI), total-body muscle mass (TBMM), creatinine-to-cystatin C ratio (CCR), and sarcopenia index (SI). Restricted cubic splines and logistic regression models were used to assess the effects of these indices on sarcopenia risk.ResultsAmong 4,527 participants without sarcopenia at the baseline (2011), the median age was 58 year-old (IQR: 52–65), with 52.7% women. Followed up in year 2015, the incidence of sarcopenia was 20.8 per 1,000 person-years (376/4,527). Neither CCR nor SI showed linear or non-linear associations with the risk of subsequent sarcopenia. However, a decrease in pSMI and TBMM was significantly associated with an increased risk of sarcopenia [adjusted per-SD decrease OR, 2.93; 95% CI, 2.09–4.13, p

Ferroptosis, a distinct form of non-apoptotic cell death characterized by iron dependency and lipid peroxidation, is increasingly linked to various pathological conditions in pregnancy and liver diseases. It plays a critical role throughout pregnancy, influencing processes such as embryogenesis, implantation, and the maintenance of gestation. A growing body of evidence indicates that disruptions in these processes can precipitate pregnancy-related disorders, including pre-eclampsia (PE), gestational diabetes mellitus (GDM), and intrahepatic cholestasis of pregnancy (ICP). Notably, while ICP is primarily associated with elevated maternal serum bile acid levels, its precise etiology remains elusive. Oxidative stress induced by bile acid accumulation is believed to be a significant factor in ICP pathogenesis. Similarly, the liver’s susceptibility to oxidative damage underscores the importance of lipid metabolism dysregulation and impaired iron homeostasis in the progression of liver diseases such as alcoholic liver disease (ALD), non-alcoholic fatty liver disease (NAFLD), cholestatic liver injury, autoimmune hepatitis (AIH), acute liver injury, viral hepatitis, liver fibrosis, and hepatocellular carcinoma (HCC). This review discusses the shared signaling mechanisms of ferroptosis in gestational and hepatic diseases, and explores recent advances in understanding the mechanisms of ferroptosis and its potential role in the pathogenesis of gestational and hepatic disorders, with the aim of identifying viable therapeutic targets.

In this research, configuration optimization was conducted for FDSHX (fan duct surface heat exchanger) that is a new type of heat exchanger adopted in aero-engine heat management in recent years. Firstly, a method of Taguchi-ANFIS (Taguchi-Adaptive Neuro-Fuzzy Inference System), which can reduce training data volume utilizing orthogonal experimental matrix, was proposed to construct a rapid response mathematical model between three configuration parameters, including fin pitch, fin thickness, and oil passages number, and two design indicators, including heat transfer capacity and operating weight, based on the data prepared by an experimental validated FDSHX heat transfer capacity calculation method using heat transfer unit simulation. Secondly, a hybrid method of NSGA II-IWO (Non-dominated Sorting Genetic Algorithm II-Invasive Weed Optimization), which can simultaneously obtain the strong abilities of exploration and escaping from trap into local optima, was proposed to drive the constructed response mathematical model to enhance heat transfer through adjusting the three configuration parameters. Optimization comparison was performed between NSGA II-IWO and four classic optimization algorithms including GA (Genetic Algorithm), IWO (Invasive Weed Optimization), CA (Cultural Algorithm), and HS (Harmony Search). This research provides an integrated solution to help mechanical engineers improve the applicability and reasonableness of FDSHX design.

Maize is an imperative crop around the globe, and it provides several essential nutrients to humans and animals. Environmental changes seriously affect growth and productivity. Drought stress is one of the most important abiotic stresses, reducing maize growth and yield and threatening global food security. For decades, breeders have been trying to improve maize's ability to counter the toxic effects of drought stress. Drought tolerance is controlled by many genes and it complicates molecular breeding. The use of conventional breeding methods limited the development of drought tolerance in maize because of the complex nature of this trait. Hence, maize breeders have shifted their focus towards improvement of drought tolerance in maize at molecular level. Different molecular tools like quantitative trait loci (QTL) mapping, genome-wide-association-studies (GWAS), transcriptome analysis, transcription factor (TFs) analysis, and CRISPR/Cas9 have played a vital role in gene’s identification and their use in molecular breeding. These genomic regions have been proven very effective, and more studies are being conducted to increase their efficiency; however, the improvement level is limited because of the complex genetic mechanism of drought tolerance. Different review articles have been published on this aspect; however, a comprehensive and updated overview of drought tolerance needs to be included. The current review highlights the role of diverse molecular techniques to improve drought tolerance in maize. This review article will enhance the interest of researchers working on the genetic improvement of maize.

Abstract Background Bawei Chenxiang Wan (BCW) is among the most effective and widely used therapies for coronary heart disease and angina pectoris in Tibet. However, whether it confers protection through a right-ventricle (RV) myocardial metabolic mechanism is unknown. Methods Male Sprague–Dawley rats were orally administrated with BCW, which was injected concurrently with a bolus of Sugen5416, and subjected to hypoxia exposure (SuHx; 5000 m altitude) for 4 weeks. Right ventricular hypertrophy (RVH) in high-altitude heart disease (HAHD) was assessed using Fulton’s index (FI; ratio of RV to left ventricle + septum weights) and heart-weight-to-body-weight ratio (HW/BW). The effect of therapeutic administration of BCW on the RVH hemodynamics was assessed through catheterization (mean right ventricular pressure and mean pulmonary artery pressure (mRVP and mPAP, respectively)). Tissue samples were used to perform histological staining, and confirmatory analyses of mRNA and protein levels were conducted to detect alterations in the mechanisms of RVH in HAHD. The protective mechanism of BCW was further verified via cell culture. Results BCW considerably reduced SuHx-associated RVH, as indicated by macro morphology, HW/BW ratio, FI, mPAP, mRVP, hypertrophy markers, heart function, pathological structure, and myocardial enzymes. Moreover, BCW can alleviate the disorder of glucose and fatty acid metabolism through upregulation of carnitine palmitoyltransferase1ɑ, citrate synthase, and acetyl-CoA and downregulation of glucose transport-4, phosphofructokinase, and pyruvate, which resulted in the reduced levels of free fatty acid and lactic acid and increased aerobic oxidation. This process may be mediated via the regulation of sirtuin 3 (SIRT3)-hypoxia-inducible factor 1α (HIF1α)-pyruvate dehydrogenase kinase (PDK)/pyruvate dehydrogenase (PDH) signaling pathway. Subsequently, the inhibition of SIRT3 expression by 3-TYP (a selective inhibitor of SIRT3) can reverse substantially the anti-RVH effect of BCW in HAHD, as indicated by hypertrophy marker and serum myocardial enzyme levels. Conclusions BCW prevented SuHx-induced RVH in HAHD via the SIRT3-HIF1ɑ-PDK/PDH signaling pathway to alleviate the disturbance in fatty acid and glucose metabolism. Therefore, BCW can be used as an alternative drug for the treatment of RVH in HAHD.

In recent years, cyclic sulfone compounds, a subset of biologically active heterocyclic compounds, have gained considerable attention due to their potential in the development of novel active pharmaceutical ingredients. This review focuses on identifying simple, mild, environmentally friendly, and efficient synthesis methods. Various catalytic approaches for the synthesis of cyclic sulfone compounds are systematically reviewed, highlighting their advantages and potential applications in pharmaceutical development.