Insights into the transcriptomic heterogeneity of brain endothelial cells in normal aging and Alzheimer's disease.

Drug development for Alzheimer's disease Is extremely challenging, as demonstrated by the repeated failures of amyloid-β-targeted therapeutics and the controversies surrounding the amyloid-β cascade hypothesis. More recently, advances in the development of Lecanemab, an anti-amyloid-β monoclonal antibody, have shown positive results in reducing brain A burden and slowing cognitive decline in patients with early- stage Alzheimer's disease in the Phase III clinical trial (Clarity Alzheimer's disease). Despite these promising results, side effects such as amyloid-related imaging abnormalities (ARIA) may limit its usage.

Neuromodulation techniques for modulating cognitive function: enhancing stimulation precision and intervention effects.

Neuromodulation techniques effectively intervene in cognitive function, holding considerable scientific and practical value in fields such as aerospace, medicine, life sciences, and brain research. These techniques utilize electrical stimulation to directly or indirectly target specific brain regions, modulating neural activity and influencing broader brain networks, thereby regulating cognitive function. Regulating cognitive function involves an understanding of aspects such as perception, learning and memory, attention, spatial cognition, and physical function.

Arterial endothelial deletion of hereditary hemorrhagic telangiectasia 2/ causes epistaxis and cerebral microhemorrhage with aberrant arteries and defective smooth muscle coverage.

Hereditary Hemorrhagic Telangiectasia (HHT) is an autosomal dominant vascular disorder with manifestations including severe nose bleeding and microhemorrhage in brains. Despite being the second most common inherited bleeding disorder, the pathophysiological mechanism underlying HHT-associated hemorrhage is poorly understood. HHT pathogenesis is thought to follow a Knudsonian two-hit model, requiring a second somatic mutation for lesion formation.

Atomically intimate assembly of dual metal-oxide interfaces for tandem conversion of syngas to ethanol.

Selective conversion of syngas to value-added higher alcohols (containing two or more carbon atoms), particularly to a specific alcohol, is of great interest but remains challenging. Here we show that atomically intimate assembly of FeO-Rh-ZrO dual interfaces by selectively architecting highly dispersed FeO on ultrafine raft-like Rh clusters supported on tetragonal zirconia enables highly efficient tandem conversion of syngas to ethanol. The ethanol selectivity in oxygenates reached ~90% at CO conversion up to 51%, along with a markedly high space-time yield of ethanol of 668.

Discovery of Dual CDK6/BRD4 Inhibitor Inducing Apoptosis and Increasing the Sensitivity of Ferroptosis in Triple-Negative Breast Cancer.

Bromodomain-containing protein 4 (BRD4) is the most promising target for the treatment of triple-negative breast cancer (TNBC). However, its inherent resistant and acquired drug resistance limits its potential clinical application. Recently it has been shown that cyclin-dependent kinases 4/6 (CDK4/6) inhibitors can reincrease the sensitivity of TNBC cells to BRD4 inhibitors by combination therapy, so we designed a series of dual target CDK6/BRD4 inhibitors.

Effects of high fluoride and iodine combined exposure on thyroid nodules and goiter in school-age children in Jiangsu, China.

Introduction: With advancements in detection equipment and an increase in the frequency of examinations, thyroid nodules and goiter in children have garnered attention.

Objective: This study aims to determine the effects of high iodine and fluoride exposure on thyroid nodules and goiter in school-aged children.

Methods: We recruited children aged 8 to 12 from rural Jiangsu, China, based on the concentrations of iodine and fluoride in local drinking water and urine.

Multicolor Gold Clusterzyme-Enabled Construction of Ratiometric Fluorescent Sensor Array for Visual Biosensing.

The simultaneous detection of multiple bioanalytes with similar structures has been a long-standing challenge for biological research and disease diagnosis. Bioreceptor-inspired sensor arrays provide an attractive and competitive solution for addressing this challenge, but applying this technique to biosensing in practical application scenarios is complicated by many factors such as the lack of robust probes, interference from the biological matrix, and difficulty for on-site analysis. In this work, by taking advantage of the intrinsic fluorescence and enzyme-mimic properties of gold nanoclusters (AuNCs), we report the design of an innovative ratiometric sensor array toward enhanced fluorescent visual biosensing.

Development of gross motor skills in children under the age of 3 years: a decision tree approach.

Background: The early years of life are critical for gross motor development (GMD). This study utilized decision tree modeling to examine the influences on gross motor development in children under the age of 3 years and to rank the key factors affecting their development.

Methods: Based on randomized stratified sampling, 9,507 children aged 0-3 years in Shenzhen were included in this study.

EZH2 functional dichotomy in reactive oxygen species-stratified glioblastoma.

Background: EZH2, well-known for its canonical methyltransferase activity in transcriptional repression in many cancers including glioblastoma (GBM), has an understudied non-canonical function critical for sustained tumor growth. Recent GBM consortial efforts reveal complex molecular heterogeneity for which therapeutic vulnerabilities correlated with subtype stratification remain relatively unexplored. Current enzymatic EZH2 inhibitors (EZH2inh) targeting its canonical SET domain show limited efficacy and lack durable response, suggesting that underlying differences in the non-canonical pathway may yield new knowledge.

Polypharmacological Drug Design Guided by Integrating Phenotypic and Restricted Fragment Docking Strategies.

Polypharmacological drugs are of great value for treating complex human diseases by the combinative modulation of several biological targets. However, multitarget drug design with more than two targets is challenging and generally discovered by serendipity. Herein, a restricted fragment docking (RFD) computational method combined with a phenotypic discovery approach was developed for rational polypharmacological drug design.

GeneRaMeN enables integration, comparison, and meta-analysis of multiple ranked gene lists to identify consensus, unique, and correlated genes.

High-throughput experiments often produce ranked gene outputs, with forward genetic screening being a notable example. While there are various tools for analyzing individual datasets, those that perform comparative and meta-analytical examination of such ranked gene lists remain scarce. Here, we introduce Gene Rank Meta Analyzer (GeneRaMeN), an R Shiny tool utilizing rank statistics to facilitate the identification of consensus, unique, and correlated genes across multiple hit lists.

A predictive model for stunting among children under the age of three.

Background: In light of the global effort to eradicate stunting in childhood, the objective of this research endeavor was to assess the prevalence of stunting and associated factors, simultaneously construct and validate a risk prediction model for stunting among children under the age of three in Shenzhen, China.

Methods: Using the stratified random sampling method, we selected 9,581 children under the age of three for research and analysis. The dataset underwent a random allocation into training and validation sets, adhering to a 8:2 split ratio.

Breaking the Conversion-Selectivity Trade-Off in Methanol Synthesis from CO Using Dual Intimate Oxide/Metal Interfaces.

The selective hydrogenation of carbon dioxide (CO) to value-added chemicals, e.g., methanol, using green hydrogen retrieved from renewable resources is a promising approach for CO emission reduction and carbon resource utilization.

Research on the economic effects of housing support expenditures under the perspective of consumption heterogeneity: Evidence from China.

What kind of impact does the government's housing support expenditure have on residents' consumption? This is a topic that deserves in-depth study and is of practical significance. This study constructs provincial equilibrium panel data based on China's guaranteed housing construction and financial expenditures on housing support data from 1999-2009 and 2000-2021. It applies the systematic GMM method to estimate the impact of government housing support expenditures on residents' consumption.

Simultaneous Targeting of NQO1 and SOD1 Eradicates Breast Cancer Stem Cells via Mitochondrial Futile Redox Cycling.

Triple-negative breast cancer (TNBC) contains the highest proportion of cancer stem-like cells (CSC), which display intrinsic resistance to currently available cancer therapies. This therapeutic resistance is partially mediated by an antioxidant defense coordinated by the transcription factor NRF2 and its downstream targets that include NAD(P)H quinone oxidoreductase 1 (NQO1). In this study, we identified the antioxidant enzymes NQO1 and superoxide dismutase 1 (SOD1) as therapeutic vulnerabilities of ALDH+ epithelial-like CSCs and CD24-/loCD44+/hi mesenchymal-like CSCs in TNBC.

Systemic immune inflammation index and all-cause mortality in chronic kidney disease: A prospective cohort study.

Background: The aim of this study was to investigate the association between systemic immune-inflammation index (SII) and all-cause mortality in individuals with chronic kidney disease (CKD).

Patients And Methods: This prospective cohort study was carried out among 9303 participants with CKD from the National Health and Nutrition Examination Survey cycles spanning 1999 to 2018. The mortality data were ascertained by linking participant records to the National Death Index up to December 31, 2019.

Immunotherapy for Pulmonary Arterial Hypertension: From the Pathogenesis to Clinical Management.

Pulmonary hypertension (PH) is a progressive cardiovascular disease, which may lead to severe cardiopulmonary dysfunction. As one of the main PH disease groups, pulmonary artery hypertension (PAH) is characterized by pulmonary vascular remodeling and right ventricular dysfunction. Increased pulmonary artery resistance consequently causes right heart failure, which is the major reason for morbidity and mortality in this disease.

Guest-Induced Helical Superstructure from a Gold Nanocluster-Based Supramolecular Organic Framework Enables Efficient Catalysis.

Mimicking hierarchical assembly in nature to exploit atomically precise artificial systems with complex structures and versatile functions remains a long-standing challenge. Herein, we report two single-crystal supramolecular organic frameworks (MSOF-4 and MSOF-5) based on custom-designed atomically precise gold nanoclusters Au(4-Mpy)(PPh), showing distinct and intriguing host-guest adaptation behaviors toward 1-/2-bromopropane (BPR) isomers. MSOF-4 exhibits topology and cylindrical channels with 4-mercaptopyridine (4-Mpy) ligands matching well with guest 1-BPR.

Species sensitivity distribution for nonylphenol: Acute toxicity and ecological risk in Bohai Region.

Nonylphenol (NP), a main byproduct of nonylphenol polyethoxylates (NPEs) degradation, is prevalent across diverse environmental settings. Given its widespread presence, evaluating the ecological risks associated with NP in coastal waters and sediments is essential for the protection of the marine environment. This study evaluates the acute toxicity of NP on ten representative aquatic species from the Bohai Sea, determining the Aquatic Life Criteria (ALC) through two distinct methods.

The Emerging Role of Ferroptosis in EBV-Associated Cancer: Implications for Cancer Therapy.

Ferroptosis is a novel and iron-dependent form of programmed cell death, which has been implicated in the pathogenesis of various human cancers. EBV is a well-recognized oncogenic virus that controls multiple signaling pathways within the host cell, including ferroptosis signaling. Recent studies show that inducing ferroptosis could be an efficient therapeutic strategy for EBV-associated tumors.