Kaempferol alleviates myocardial ischemia injury by reducing oxidative stress via the HDAC3-mediated Nrf2 signaling pathway.

Introduction: Kaempferol (KAE) is a flavonoid found in various plants. Recent studies showed that high dietary intake of KAE was associated with a lower risk of myocardial infarction; however, the cardioprotective mechanism of KAE remains unknown.

Objectives: To determine the effect of KAE on cardiac injury in isoproterenol (ISO)-induced rats and cobalt chloride (CoCl)-treated cardiomyocytes, and the underlying mechanisms.

The C57BL/6N mouse substrain is a viable model of elastase-induced abdominal aortic aneurysm.

Aim: Compared with the C57BL/6N substrain, the C57BL/6J substrain is more susceptible to the angiotensin II (Ang II)-induced development of dissected abdominal aortic aneurysms (AAAs). The aim of this study was to elucidate whether the widely used C57BL/6N mouse substrain is as susceptible as the C57BL/6J mouse substrain to porcine pancreatic elastase (PPE) infusion-induced experimental nondissected AAA development.

Methods: Experimental nondissected AAAs were induced in C57BL/6J and C57BL/6N mice via transient aortic luminal infusion of PPE.

Multi-objective optimization design of low-power-driven, large-flux, and fast-response three-stage valve.

Intrinsically safe solenoids drive solenoid valves in coal mining equipment. The low power consumption of these solenoids limits the response time of the solenoid valves. Additionally, the low viscosity and high susceptibility to dust contamination of the emulsion fluid often lead to leakage and sticking of hydraulic valves.

Intracellular spatial transcriptomic analysis toolkit (InSTAnT).

Imaging-based spatial transcriptomics technologies such as Multiplexed error-robust fluorescence in situ hybridization (MERFISH) can capture cellular processes in unparalleled detail. However, rigorous and robust analytical tools are needed to unlock their full potential for discovering subcellular biological patterns. We present Intracellular Spatial Transcriptomic Analysis Toolkit (InSTAnT), a computational toolkit for extracting molecular relationships from spatial transcriptomics data at single molecule resolution.

Association of non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) and gallstones among US adults aged ≤ 50 years: a cross-sectional study from NHANES 2017-2020.

Background: The chronic digestive condition gallstones is quite common around the world, the development of which is closely related to oxidative stress, inflammatory response and abnormalities of lipid metabolism. In the last few years, as a novel biomarker of lipid metabolism, the non-high-density lipoprotein cholesterol to high-density lipoprotein cholesterol ratio (NHHR) has garnered significant interest. However, its relationship with gallstones has not been studied yet.

LARP7 Contributes to Glucose-Induced Cardiac Dysfunction, Apoptosis and Fibrosis by Inhibiting the Degradation of STING.

Background: Diabetic cardiomyopathy (DCM) is an important cause of heart failure in diabetic patients. The aim of this study was to investigate the pathogenesis of DCM and to identify potential therapeutic targets.

Methods: A mouse model of type 1 DCM was constructed by continuous intraperitoneal injection of streptozotocin (STZ).

Nonparametric empirical Bayes biomarker imputation and estimation.

Biomarkers are often measured in bulk to diagnose patients, monitor patient conditions, and research novel drug pathways. The measurement of these biomarkers often suffers from detection limits that result in missing and untrustworthy measurements. Frequently, missing biomarkers are imputed so that down-stream analysis can be conducted with modern statistical methods that cannot normally handle data subject to informative censoring.

A metabolomics pipeline highlights microbial metabolism in bloodstream infections.

The growth of antimicrobial resistance (AMR) highlights an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although severe infections profoundly alter host metabolism, prior studies have largely ignored microbial metabolism in this context. Here, we describe an iterative, comparative metabolomics pipeline to uncover microbial metabolic features in the complex setting of a host and apply it to investigate gram-negative bloodstream infection (BSI) in patients.

Urotensin II receptor deficiency ameliorates ligation-induced carotid intimal hyperplasia partially through the RhoA-YAP1 pathway.

Intimal hyperplasia (IH) is a common pathological feature of vascular proliferative diseases, such as atherosclerosis and restenosis after angioplasty. Urotensin II (UII) and its receptor (UTR) are widely expressed in cardiovascular tissues. However, it remains unclear whether the UII/UTR system is involved in IH.

Diabetic status aggravates atherosclerosis in aged ApoE mice.

Streptozocin (STZ) aggravates diabetic atherosclerosis in aged ApoE mice. (A). Study design: ApoE mice were given STZ (50 mg/kg/day) or vehicle by intraperitoneal injection for five days consecutively to induce diabetes.

The incidence rate and histological characteristics of intimal hyperplasia in elastase-induced experimental abdominal aortic aneurysms in mice.

Intimal hyperplasia (IH) is a negative vascular remodeling after arterial injury. IH occasionally occurs in elastase-induced abdominal aortic aneurysm (AAA) mouse models. This study aims to clarify the incidence and histological characteristics of IH in aneurysmal mice.

Mechanism of Artemisia annua L. in the treatment of acute myocardial infarction: network pharmacology, molecular docking and in vivo validation.

This study was to evaluate the potential mechanism of action of Artemisia annua L. (A. annua) in the treatment of acute myocardial infarction (AMI) using network pharmacology, molecular docking and in vivo experiments.

Kernel Cox partially linear regression: Building predictive models for cancer patients' survival.

Wide heterogeneity exists in cancer patients' survival, ranging from a few months to several decades. To accurately predict clinical outcomes, it is vital to build an accurate predictive model that relates the patients' molecular profiles with the patients' survival. With complex relationships between survival and high-dimensional molecular predictors, it is challenging to conduct nonparametric modeling and irrelevant predictors removing simultaneously.

Identification and targeting of microbial putrescine acetylation in bloodstream infections.

The growth of antimicrobial resistance (AMR) has highlighted an urgent need to identify bacterial pathogenic functions that may be targets for clinical intervention. Although severe bacterial infections profoundly alter host metabolism, prior studies have largely ignored alterations in microbial metabolism in this context. Performing metabolomics on patient and mouse plasma samples, we identify elevated levels of bacterially-derived -acetylputrescine during gram-negative bloodstream infections (BSI), with higher levels associated with worse clinical outcomes.

C-reactive protein deficiency ameliorates experimental abdominal aortic aneurysms.

Background: C-reactive protein (CRP) levels are elevated in patients with abdominal aortic aneurysms (AAA). However, it has not been investigated whether CRP contributes to AAA pathogenesis.

Methods: CRP deficient and wild type (WT) male mice were subjected to AAA induction via transient intra-aortic infusion of porcine pancreatic elastase.

Mediator subunit MED1 deficiency prevents carbon tetrachloride-induced hepatic fibrosis in mice.

Mediator subunit mediator 1 (MED1) mediates ligand-dependent binding of the mediator coactivator complex to various nuclear receptors and plays a critical role in embryonic development, lipid and glucose metabolism, liver regeneration, and tumorigenesis. However, the precise role of MED1 in the development of liver fibrosis has been unclear. Here, we showed that MED1 expression was increased in livers from nonalcoholic steatohepatitis (NASH) patients and mice and positively correlated with transforming growth factor β (TGF-β) signaling and profibrotic factors.

Deficiency of protein inhibitor of activated STAT3 exacerbates atherosclerosis by modulating VSMC phenotypic switching.

Background And Aims: Phenotypic switching of vascular smooth muscle cells (VSMCs) plays an essential role in the development of atherosclerosis. Protein inhibitor of activated STAT (Pias) regulates VSMCs phenotype via acting as sumo E3 ligase to promote protein sumoylation. Our previous study indicated that Pias3 expression decreased in atherosclerotic lesions.

Hepatic transcriptome signatures in mice and humans with nonalcoholic fatty liver disease.

Background: Nonalcoholic fatty liver disease (NAFLD) is the main reason for cirrhosis and hepatocellular carcinoma. As a starting point for NAFLD, the treatment of nonalcoholic fatty liver (NAFL) is receiving increasing attention. Mice fed a high-fat diet (HFD) and hereditary leptin deficiency (ob/ob) mice are important NAFL animal models.

A homozygous missense mutation in the fibroblast growth factor 5 gene is associated with the long-hair trait in Angora rabbits.

Background: Rabbits are well-domesticated animals. As a crucial economic animal, rabbit has been successfully bred into wool-use, meat-use and fur-use breeds. Hair length is one of the most economically important traits affecting profitability in wool rabbits.

Single-cell dissection of aggression in honeybee colonies.

Understanding how genotypic variation results in phenotypic variation is especially difficult for collective behaviour because group phenotypes arise from complex interactions among group members. A genome-wide association study identified hundreds of genes associated with colony-level variation in honeybee aggression, many of which also showed strong signals of positive selection, but the influence of these 'colony aggression genes' on brain function was unknown. Here we use single-cell (sc) transcriptomics and gene regulatory network (GRN) analyses to test the hypothesis that genetic variation for colony aggression influences individual differences in brain gene expression and/or gene regulation.

Mechanisms and efficacy of metformin-mediated suppression of established experimental abdominal aortic aneurysms.

Objective: Metformin treatment attenuates experimental abdominal aortic aneurysm (AAA) formation, as well as reduces clinical AAA diameter enlargement in patients with diabetes. The mechanisms of metformin-mediated aneurysm suppression, and its efficacy in suppressing established experimental aneurysms, remain uncertain.

Methods: Experimental AAAs were created in male C57BL/6J mice via intra-aortic infusion of porcine pancreatic elastase.

Treatment With Small Molecule Inhibitors of Advanced Glycation End-Products Formation and Advanced Glycation End-Products-Mediated Collagen Cross-Linking Promotes Experimental Aortic Aneurysm Progression in Diabetic Mice.

Background Although diabetes attenuates abdominal aortic aneurysms (AAAs), the mechanisms by which diabetes suppresses AAAs remain incompletely understood. Accumulation of advanced glycation end- (AGEs) reduces extracellular matrix (ECM) degradation in diabetes. Because ECM degradation is critical for AAA pathogenesis, we investigated whether AGEs mediate experimental AAA suppression in diabetes by blocking AGE formation or disrupting AGE-ECM cross-linking using small molecule inhibitors.

Power of testing for exposure effects under incomplete mediation.

Mediation analysis studies situations where an exposure may affect an outcome both directly and indirectly through intervening variables called mediators. It is frequently of interest to test for the effect of the exposure on the outcome, and the standard approach is simply to regress the latter on the former. However, it seems plausible that a more powerful test statistic could be achieved by also incorporating the mediators.