Developmental Programming: Differing impact of prenatal testosterone and prenatal bisphenol-A -treatment on hepatic methylome in female sheep.

Steroid hormones are integral to pregnancy and fetal development, regulating processes such as metabolism, inflammation, and immune responses. Excessive prenatal steroid exposure, through lifestyle choices or environmental chemicals, can lead to metabolic dysfunctions in offspring. The research focuses on how exposure to testosterone (T) and bisphenol A (BPA) affects the liver's DNA methylome, a key component of the epigenome influencing long-term health.

Copy number loss Of APP cause thoracic aortic dissection.

Thoracic aortic dissection (TAD) is a leading cause of sudden cardiovascular death. Although a limited number of copy number variations (CNVs) have been reported in small cohorts of patients with hereditary TAD or sporadic aortic dissection, a comprehensive investigation and functional validation of CNVs in sporadic TAD using large-scale whole genome sequencing (WGS) data remain lacking. To address this gap, we conducted whole genome sequencing in two independent case-control studies, involving 257 patients with sporadic TAD and 132 controls.

Structure-Based Discovery of Quinazolin-2-amine Derivatives as Potent ROR1 Pseudokinase Inhibitors with and Efficacy against Triple-Negative Breast Cancer.

As a kind of pseudokinase, although ROR1 lacks the ATP catalytic activity similar to that of classical kinases, it has been proven to play a crucial role in the occurrence and development of triple-negative breast cancer (TNBC). Through structure-based drug design strategy, we have discovered novel quinolin-2-amine ROR1 inhibitor which exhibited excellent binding activity to ROR1 ( = 0.052 μM) and antiproliferative against breast cancer cells (IC = 0.

The hot air circulation ventilation composting system removes antibiotic resistance genes through competitive inhibition by core bacteria.

Livestock manure is a significant reservoir of antibiotic resistance genes (ARGs). Aerobic composting technology can produce mature compost while effectively removing ARGs. In this study, we developed an energy-saving and emission-reducing hot air circulating ventilated composting technology (HACV), which had no adverse effects on the composting process or compost maturity.

Integration of Transcriptomic and Single-Cell Data to Uncover Senescence- and Ferroptosis-Associated Biomarkers in Sepsis.

Sepsis is a life-threatening condition characterized by organ dysfunction due to an imbalanced immune response to infection, with high mortality. Ferroptosis, an iron-dependent cell death process, and cellular senescence, which exacerbates inflammation, have recently been implicated in sepsis pathophysiology. Weighted gene co-expression network analysis (WGCNA) was used to identify ferroptosis- and senescence-related gene modules in sepsis.

Developmental programming: mechanisms of early exposure to real-life chemicals in biosolids on offspring ovarian dynamics†.

Female reproductive capacity is shaped by ovarian reserve and patterns of follicle development. Ovarian reserve depletion occurs by follicle activation and atresia, which are affected by environmental chemicals (ECs). Because humans are simultaneously exposed to hundreds of ECs, real-life exposure models are essential to assess patterns of atresia after EC exposure.

The relationship between hemoglobin, albumin, lymphocyte, and platelet (HALP) score and 28-day mortality in patients with sepsis: a retrospective analysis of the MIMIC-IV database.

Background: In recent years, the hemoglobin, albumin, lymphocyte, and platelet (HALP) score has emerged as a potential marker of immunological and nutritional status. This study aimed to evaluate the association between the HALP score and prognosis in patients with sepsis.

Methods: This retrospective cohort study analyzed sepsis patients using clinical data from the Medical Information Mart for Intensive Care IV (MIMIC-IV) database.

HACD2 Promotes Pancreatic Cancer Progression by Enhancing PKM2 Dissociation From PRKN in a Dehydratase-Independent Manner.

3-Hydroxyacyl-CoA dehydratase 2 (HACD2), an obesity-related gene involved in the elongation of long-chain fatty acids, is highly expressed in pancreatic cancer (PC) and is associated with patient prognosis. Interestingly, the study reveals that HACD2 mediated the proliferation of PC cells in a dehydratase-independent manner, affecting the downstream glycolytic pathway. Mechanistically, HACD2 promotes PC cells proliferation by binding to E3 ubiquitin-protein ligase parkin (PRKN) and enhancing pyruvate kinase PKM (PKM2) dissociation from PRKN, resulting in reduced ubiquitination of PKM2 and increased dimerization of PKM2, which subsequently promote c-Myc expression and tumor growth.

Early prediction of post-pancreatectomy acute pancreatitis after pancreaticoduodenectomy based on serum C-reactive protein.

Background: Post-pancreatectomy acute pancreatitis (PPAP) is an early acute inflammatory process of the pancreatic remnant that is associated with a series of downstream pancreas-specific complications. This study aimed to investigate the relationship between postoperative serum C-reactive protein (CRP) levels and the occurrence of PPAP after pancreaticoduodenectomy (PD).

Methods: Consecutive patients who underwent PD between January 1, 2020, and May 31, 2022, were retrospectively analyzed.

Nanosized κ-Carbide and B2 Boosting Strength Without Sacrificing Ductility in a Low-Density Fe-32Mn-11Al Steel.

High-performance lightweight materials are urgently needed because of energy savings and emission reduction. Here, we design a new steel with a low density of 6.41 g/cm, which is a 20% weight reduction compared to the conventional steel.

Developmental programming: preconceptional and gestational exposure of sheep to biosolids on offspring ovarian dynamics†.

Developmental exposure to environmental chemicals perturbs establishment and maintenance of the ovarian reserve across the reproductive lifetime, leading to premature follicle depletion and ovarian aging. Considering humans are exposed to a complex mixture of environmental chemicals, real-life models assessing their cumulative impact on the ovarian reserve are needed. Biosolids are a source of a real-life mixture of environmental chemicals.

The proinflammatory status, based on preoperative interleukin-6, predicts postpancreatectomy acute pancreatitis and associated postoperative pancreatic fistula after pancreaticoduodenectomy.

Background And Aim: Early predictors of morbidity after pancreaticoduodenectomy (PD) can guide tailored postoperative management. Preoperative inflammatory data in patients who underwent PD remained poorly studied in investigating the clinical significance of predicting postpancreatectomy acute pancreatitis (PPAP) and PPAP-associated postoperative pancreatic fistula (POPF).

Methods: The clinical data of 467 patients receiving PD between January 2020 and December 2022 were retrospectively reviewed.

Metabolomic and transcriptomic analyses reveal the mechanism of polysaccharide and secondary metabolite biosynthesis in Bletilla striata tubers in response to shading.

Polysaccharides and various secondary metabolites are the major bioactive ingredients in Bletilla striata tubers and their biosynthesis and accumulation are influenced by light intensity. However, the mechanisms underlying shading effects remain largely unknown. In the present study, we used a combined analysis of the physiology, metabolome, and transcriptome to investigate the physiological activities and bioactive component accumulation of B.

Design, synthesis, and biological evaluation of imidazolylacetophenone oxime derivatives as novel brain-penetrant agents for Alzheimer's disease treatment.

Alzheimer's disease (AD, also known as dementia) has become a serious global health problem along with population aging, and neuroinflammation is the underlying cause of cognitive impairment in the brain. Nowadays, the development of multitarget anti-AD drugs is considered to be one effective approach. Imidazolylacetophenone oxime ethers or esters (IOEs) were multifunctional agents with neuroinflammation inhibition, metal chelation, antioxidant and neuroprotection properties against Alzheimer's disease.

ROCK1 regulates glycolysis in pancreatic cancer via the c-MYC/PFKFB3 pathway.

Background: Dysregulation of Rho-associated coiled coil-containing protein kinases (ROCKs) is involved in the metastasis and progression of various malignant tumors. However, how one of the isomers, ROCK1, regulates glycolysis in tumor cells is incompletely understood. Here, we attempted to elucidate how ROCK1 influences pancreatic cancer (PC) progression by regulating glycolytic activity.

Continuous blood exchange in rats as a novel approach for experimental investigation.

Blood exchange therapy, specifically Whole blood exchange (WBE), is increasingly being utilized in clinical settings to effectively treat a range of diseases. Consequently, there is an urgent requirement to establish convenient and clinically applicable animal models that can facilitate the exploration of blood exchange therapy mechanisms. Our study conducted continuous WBE in rats through femoral and tail vein catheterization using dual-directional syringe pumps.

Efficacy of fresh frozen plasma transfusion in decompensated cirrhosis patients with coagulopathy admitted to ICU: a retrospective cohort study from MIMIC-IV database.

We aimed to explore the association between FFP transfusion and outcomes of DC patients with significant coagulopathy. A total of 693 DC patients with significant coagulopathy were analyzed with 233 patients per group after propensity score matching (PSM). Patients who received FFP transfusion were matched with those receiving conventional therapy via PSM.

Inhibiting autophagy enhanced mitotic catastrophe-mediated anticancer immune responses by regulating the cGAS-STING pathway.

Given the limitations of the response rate and efficacy of immune checkpoint inhibitors (ICIs) in clinical applications, exploring new therapeutic strategies for cancer immunotherapy is necessary. We found that 5-(3,4,5-trimethoxybenzoyl)-4-methyl-2-(p-tolyl)imidazole (BZML), a microtubule-targeting agent, exhibited potent anticancer activity by inducing mitotic catastrophe in A549/Taxol and L929 cells. Nuclear membrane disruption and nuclease reduction provided favorable conditions for cGAS-STING pathway activation in cells with mitotic catastrophe.

Experimental Investigation on the Pyrolysis and Conversion Characteristics of Organic-Rich Shale by Supercritical Water.

Organic-rich shale oil reservoirs with low-medium maturity have attracted increasing attention because of their enormous oil and gas potential. In this work, a series of experiments on pyrolysis of the particle and core samples were carried out in a self-made supercritical water pyrolysis apparatus to evaluate the feasibility and benefits of supercritical water in promoting the transformation efficiency and oil yield of the low-medium maturity organic-rich shale. Core samples had a mass loss of 8.

TP53 missense mutation reveals gain-of-function properties in small-sized KRAS transformed pancreatic ductal adenocarcinoma.

Background: Although the molecular features of pancreatic ductal adenocarcinoma (PDAC) have been well described, the impact of detailed gene mutation subtypes on disease progression remained unclear. This study aimed to evaluate the impact of different TP53 mutation subtypes on clinical characteristics and outcomes of patients with PDAC.

Methods: We included 639 patients treated with PDAC in Ruijin Hospital affiliated to Shanghai Jiaotong University School of Medicine between Jan 2019 and Jun 2021.

Radiomics nomogram for prediction of glypican-3 positive hepatocellular carcinoma based on hepatobiliary phase imaging.

Introduction: The hepatobiliary-specific phase can help in early detection of changes in lesion tissue density, internal structure, and microcirculatory perfusion at the microscopic level and has important clinical value in hepatocellular carcinoma (HCC). Therefore, this study aimed to construct a preoperative nomogram for predicting the positive expression of glypican-3 (GPC3) based on gadoxetic acid-enhanced (Gd-EOB-DTPA) MRI hepatobiliary phase (HBP) radiomics, imaging and clinical feature.

Methods: We retrospectively included 137 patients with HCC who underwent Gd-EOB-DTPA-enhanced MRI and subsequent liver resection or puncture biopsy at our hospital from January 2017 to December 2021 as training cohort.

Ovarian follicle size or growth rate can both be determinants of ovulatory follicle selection in mice†.

The endocrinology regulating ovulation of the desired number of oocytes in the ovarian cycle is well described, particularly in mono-ovulatory species. Less is known about the characteristics that make one follicle suitable for ovulation while most other follicles die by atresia. Bromodeoxyuridine (BrdU) injection was used to characterize granulosa cell proliferation rates in developing ovarian follicles in the estrous cycle of mice.