Targeting endothelial SMAD4 ameliorates endothelial dysfunction in hypertensive mice.

Objective: Endothelial dysfunction is a key contributor to hypertension, and dysregulation of TGF-β/BMP signaling pathways exacerbates vascular pathogenesis. However, the precise role of SMAD4 in the development of vascular inflammation and dysfunction in hypertension remains poorly understood.

Methods: Tie2-Cre/ERT2 system was used to generate an endothelial-specific Smad4 knockout mouse.

Instant Energy Barrier Modulation in Bistable Robotic Grippers for Compliant Triggering and Powerful Grasping.

Bistable structures, which leverage mechanical instability, have emerged as a promising paradigm in the development of robotic grippers, providing advantages including rapid response and low energy consumption. A critical limitation of existing bistable grippers, however, lies in their invariable energy barriers, which hinder the balance between compliant triggering and powerful grasping. In this study, we propose a bistable robotic gripper capable of in situ energy barrier modulation, inspired by the adaptive seed dispersal behavior of pods.

Dietary inflammatory index and Alzheimer's disease mortality in a prospective cohort.

Objective: This study examined the relationship between the Dietary Inflammatory Index (DII) and Alzheimer's disease (AD) mortality in US adults.

Methods: Data from 45,093 participants in the 1988-2014 National Health and Nutrition Examination Survey (NHANES) were analyzed, with mortality follow-up through December 2019. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95 % confidence intervals (CIs) for AD mortality.

Vitamin D receptor upregulation promotes ferroptosis-related salivary hyposecretion caused by Sod1 knockout in female mice.

Oxidative stress is a key factor in reducing salivary flow and damaging salivary gland tissues, and females are more likely to experience saliva hyposecretion than males, with the underlying mechanism not elucidated. To investigate the potential link between salivary gland function and systemic oxidative stress, we employed a superoxide dismutase 1 gene (Sod1) knockout (SKO) mouse model to simulate elevated endogenous oxidative stress. Concurrent with increased endogenous reactive oxygen species (ROS) levels, we observed reduced salivary production, increased vitamin D receptor (VDR) expression, and altered gene expression profiles associated with ferroptosis, inflammation, and circadian regulation.

Improvement of Cardiovascular Risk Factors by Genistein Supplementation: A Systematic Review and Meta-Analysis in Diverse Population-Based RCTs.

Genistein[5,7-dihydroxy-3-(4-hydroxyphenyl)chromen-4-one] is a phytoestrogens known to positively impact various cardiovascular disease (CVD) risk factors. However, not all studies have yielded consistent results, and existing meta-analyses have not comprehensively addressed all CVD risk factors. We conducted a systematic search of the PubMed, ISI Web of Science, Embase, and Cochrane Library databases up to June 2024, following PRISMA 2020 guidelines.

Protective association between dietary phytosterol intake and cardiovascular health: an analysis of the UK Biobank cohort.

: Cardiovascular diseases (CVDs) remain a leading cause of morbidity and mortality worldwide, with dietary interventions showing promise in reducing CVD risk factors. Phytosterols (PSs) in plant-based foods may reduce CVD risk by lowering low-density lipoprotein cholesterol. However, the relationship between dietary PS intake and CVD outcomes remains inconclusive.

Noncoding variation near UBE2E2 orchestrates cardiometabolic pathophenotypes through polygenic effectors.

Mechanisms underpinning signals from genome-wide association studies remain poorly understood, particularly for noncoding variation and for complex diseases such as type 2 diabetes mellitus (T2D) where pathogenic mechanisms in multiple different tissues may be disease driving. One approach is to study relevant endophenotypes, a strategy we applied to the UBE2E2 locus where noncoding single nucleotide variants (SNVs) are associated with both T2D and visceral adiposity (a pathologic endophenotype). We integrated CRISPR targeting of SNV-containing regions and unbiased CRISPR interference (CRISPRi) screening to establish candidate cis-regulatory regions, complemented by genetic loss of function in murine diet-induced obesity or ex vivo adipogenesis assays.

Effects of phytosterol supplementation on lipid profiles and apolipoproteins: A meta-analysis of randomized controlled trials.

Background: The use of phytosterols and phytostanols (PS) as food supplements to control plasma cholesterol concentrations has recently received attention as its efficacy has been endorsed by scientific authorities and leading guidelines. However, the effects of phytosterols on lipid profiles and atherosclerosis remain incomplete and controversial. This study aims to investigate the effects of PS supplementation on lipid profiles and apolipoproteins in adults based on a systematic review of the literature and a meta-analysis of randomized controlled trials (RCTs).

Effects of three flavonoids on the metabolism of lenvatinib.

Lenvatinib is a first-line therapy for the treatment of hepatocellular carcinoma (HCC), an active multi-target tyrosine kinase inhibitor (TKI). The interaction between Traditional Chinese Medicine (TCM) and chemicals has increasingly become a research hotspot. The objective of this study was to pinpoint the effects of three flavonoids on the metabolism of lenvatinib.

Effects of two commonly used antidepressants amitriptyline and fluoxetine on the pharmacokinetics of abrocitinib in rats.

Abrocitinib is approved to treat moderate-to-severe atopic dermatitis and eliminated mainly through cytochrome P450 (CYP450) enzyme. Two commonly used antidepressants, amitriptyline and fluoxetine, could inhibit the activities of CYP2C19 and CYP3A4. In this study, we developed a new and quick ultra performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method for quantitatively analyzing the plasma concentration of abrocitinib, and further investigated the effects of amitriptyline or fluoxetine on the pharmacokinetics of abrocitinib in rats.

Lycopene from tomatoes and tomato products exerts renoprotective effects by ameliorating oxidative stress, apoptosis, pyroptosis, fibrosis, and inflammatory injury in calcium oxalate nephrolithiasis: the underlying mechanisms.

Several mechanisms underlying nephrolithiasis, one of the most common urological diseases, involve calcium oxalate formation, including oxidative stress, inflammatory reactions, fibrosis, pyroptosis, and apoptosis. Although lycopene has strong antioxidant activity, its protective effects against CaOx-induced injury have not yet been reported. This study aimed to systematically investigate the protective effects of lycopene and explore its mechanisms and molecular targets.

Qbnb: An innovative C2B2C2B2C e-commerce mode for integrated on-demand services.

The traditional supply-side-driven e-commerce modes provide consumers with massive amounts of structured information about goods and services. Due to the lack of a tailor-made ability to describe, explain, and accurately understand unstructured service demands, existing technologies and service modes still struggle to fully explore, articulate, and meet the personalized, high-quality, and urgent service demands of the disadvantaged groups in e-commerce. This paper innovatively proposes the concept of "integrated services on demand" and develops its C2B2C2B2C-based "Qbnb" e-commerce mode, operation mechanism and intermediary platform architecture.

Variation in and risk of cardiovascular disease in the UK Biobank.

Background: Cardiovascular disease (CVD) is an escalating global health crisis, contributing significantly to worldwide mortality and morbidity. Dyslipidemia stands as a critical risk factor for CVD. Vascular endothelial growth factor A () is pivotal in angiogenesis and represents a clinical target for CVD intervention.

Effects of dietary fibers or probiotics on functional constipation symptoms and roles of gut microbiota: a double-blinded randomized placebo trial.

Dietary fibers/probiotics may relieve constipation via optimizing gut microbiome, yet with limited trial-based evidences. We aimed to evaluate the effects of formulas with dietary fibers or probiotics on functional constipation symptoms, and to identify modulations of gut microbiota of relevance. We conducted a 4-week double-blinded randomized placebo-controlled trial in 250 adults with functional constipation.

Next-Day Medical Activities Recommendation Model with Double Attention Mechanism Using Generative Adversarial Network.

Medical activities recommendation is a key aspect of an intelligent healthcare system, which can assist doctors with little clinical experience in clinical decision making. Medical activities recommendation can be seen as a kind of temporal set prediction. Previous studies about them are based on Recurrent Neural Network (RNN), which does not incorporate personalized medical history or differentiate between the impact of medical activities.

Effects of tongue hair flexural deformation on viscous fluid transport by bees.

A bee's tongue is coated in dynamic hairs that gradually unfold to entrain the viscid nectar, during which hairs inevitably deflect as a result of fluid drag. The hair deflection induced decline in nectar capture rate may be a coupled elastoviscous problem and remains poorly understood. Here we employed geometric beam theory coupled with the effective viscous force to derive a dynamic model for a rotary tongue hair deflection in a viscous fluid.

Self-supervised graph neural network with pre-training generative learning for recommendation systems.

The case assignment system is an essential system of case management and assignment within the procuratorate and is an important aspect of judicial fairness and efficiency. However, existing methods mostly use manual or random case assignment, which leads to unbalanced case distribution. Moreover, the relationship between prosecutors and case categories usually shows a power-law distribution in real-world data.

Dual-level diagnostic feature learning with recurrent neural networks for treatment sequence recommendation.

In recent years, the massive electronic medical records (EMRs) have supported the development of intelligent medical services such as treatment recommendations. However, existing treatment recommendations usually follow the traditional sequential recommendation strategies, ignoring the partial temporality of the practical process and the patient's diagnostic features. To this end, in this paper, we propose a new Dual-level Diagnostic Feature Learning with Recurrent Neural Network for treatment sequence recommendation (DDFL-RNN), where the dual-level diagnostic features including patients' historical medical records and current treatment results.

The Effect of Single-Dose Ougan Juice Application on the Pharmacokinetics of Erlotinib.

The aim of our study was to investigate the effects of single-dose Ougan (Citrus reticulata cv. Suavissima) juice application on the pharmacokinetics of erlotinib in vivo. Twelve Sprague-Dawley rats were randomly divided into the Ougan juice and control groups ( = 6 each).

Pharmacokinetics of 10-Hydroxy Mesaconitine in Rat Plasma by Ultra-Performance Liquid Chromatography-Tandem Quadrupole Mass Spectrometry.

Mesaconitine is the predominant active ingredient in Debx. The compound 10-hydroxy mesaconitine is one known metabolite of mesaconitine and is toxic. In order to better understand its pharmacokinetics, UPLC-MS/MS was used in this paper to measure the concentration of 10-hydroxy mesaconitine in the plasma of rats after oral (5 mg/kg) and intravenous (0.

Co-benefits of carbon and pollution control policies on air quality and health till 2030 in China.

Facing the dual challenges of climate change and air pollution, China has made great efforts to explore the co-control strategies for the both. We assessed the benefits of carbon and pollution control policies on air quality and human health, with an integrated framework combining an energy-economic model, an air quality model and a concentration-response model. With a base year 2015, seven combined scenarios were developed for 2030 based on three energy scenarios and three end-of-pipe control ones.