Incorporation of a rigid 1,3-diketone-containing fragment led to significantly improved AXL inhibitory activity: design, synthesis, and SAR of the anilinopyrimidine AXL inhibitors.

Overexpressed AXL kinase is involved in various human malignancies, which incurs tumor progression, poor prognosis, and drug resistance. Suppression of the aberrant AXL axis with genetic tools or small-molecule inhibitors has achieved valid antitumor efficacies in both preclinical studies and clinical antitumor campaigns. Herein we will report the design, synthesis, and structure-activity relationship (SAR) exploration of a series of anilinopyrimidine type II AXL inhibitors.

Epidemiology and Antimicrobial Resistance of Stenotrophomonas maltophilia in China, 2014-2021.

Introduction: Stenotrophomonas maltophilia is an opportunistic pathogen associated with various nosocomial infections and is known for its intrinsic multidrug resistance. This study aims to provide a comprehensive overview of the epidemiology and resistance patterns of S. maltophilia in China from 2014 to 2021.

Plant Coumarin Metabolism-Microbe Interactions: An Effective Strategy for Reducing Imidacloprid Residues and Enhancing the Nutritional Quality of Pepper.

Imidacloprid (IMI) stress positively correlates with the potential of coumarins to alleviate abiotic stress. However, little is known about the pathways and mechanisms by which coumarin reduces the IMI residue by regulating plant secondary metabolism and plant-microbe interactions. This study examined the impact of coumarin on the uptake, translocation, and metabolism of IMI in pepper plants by modulating the signal molecule levels and microbial communities in the rhizosphere and phyllosphere.

Novel PD-L1/VISTA Dual Inhibitor as Potential Immunotherapy Agents.

Inhibiting the activity of immune checkpoint proteins to reignite the antitumor activity of immune cells has emerged as a pivotal strategy. PD-L1 and VISTA, as critical proteins governing immune regulation, are concurrently upregulated under conditions such as hypoxia. Through a rational drug design process, , a dual-target inhibitor for PD-L1 and VISTA is identified.

Machine Learning Boosted Entropy-Engineered Synthesis of CuCo Nanometric Solid Solution Alloys for Near-100% Nitrate-to-Ammonia Selectivity.

Nanometric solid solution alloys are utilized in a broad range of fields, including catalysis, energy storage, medical application, and sensor technology. Unfortunately, the synthesis of these alloys becomes increasingly challenging as the disparity between the metal elements grows, due to differences in atomic sizes, melting points, and chemical affinities. This study utilized a data-driven approach incorporating sample balancing enhancement techniques and multilayer perceptron (MLP) algorithms to improve the model's ability to handle imbalanced data, significantly boosting the efficiency of experimental parameter optimization.

Size-adjustable High-Entropy Alloy Nanoparticles as an Efficient Platform for Electrocatalysis.

The high entropy alloy (HEA) possesses distinctive thermal stability and electronic characteristics, which exhibits substantial potential for diverse applications in electrocatalytic reactions. However, accurately controlling the size of HEA still remains a challenge, especially for the ultrasmall HEA nanoparticles. Herein, we firstly calculate and illustrate the size impact on the electronic structure of HEA and the adsorption energies of crucial intermediates in typical electrocatalytic reactions, such as the hydrogen evolution reaction (HER), oxygen reduction reaction (ORR), CO2 electroreduction (CO2RR) and NO3- electroreduction (NO3RR).

Existence and significance of anti-HLA-C autoantibodies to primary and persistent platelet transfusion refractoriness in patients with hematologic disorders: a retrospective study from a single centre.

Objectives: Platelet transfusion refractoriness (PTR) is a frustrating clinical problem, and primary and persistent (P/P) PTR who experienced persistent PTR since the first transfusion was failed to be well recognized. This study aims to investigate the incidence and risk factors for P/P PTR.

Methods: Patients with hematologic disorders who underwent HLA high-resolution genotyping and donor-specific HLA antibody or panel reactive antibody (PRA) testing between January 2019 and March 2023 were reviewed.

Extraction and biological activities of polysaccharides and saponins from : a review.

(), a perennial woody plant of the Araliaceae family, is extensive in Northeast China. Esteemed for both its medicinal and edible qualities in the Changbai Mountain region, its primary components include polysaccharides, saponins, and flavonoids. displays numerous pharmacological effects, such as cardiovascular protection, anti-tumour, anti-fatigue, and hypoglycaemic properties.

Photocatalytic Oxidative Coupling of Methane to Ethane Using CO2 as a Soft Oxidant Over the Au/TiO2-Vo Nanosheets.

Herein, we first report a photocatalytic OCM using CO2 as a soft oxidant for C2H6 production under mild conditions, where an efficient photocatalyst with unique interface sites is constructed to facilitate CO2 adsorption and activation, while concurrently boosting CH4 dissociation. As a prototype, the Au quantum dots anchored on oxygen-deficient TiO2 nanosheets are fabricated, where the Au-Vo-Ti interface sites for CO2 adsorption and activation are collectively disclosed by in situ Kelvin probe force microscopy, quasi in situ X-ray photoelectron spectroscopy and theoretical calculations. Compared with single metal site, the Au-Vo-Ti interface sites exhibit the lower CO2 adsorption energy and decrease the energy barrier of the *CO2 hydrogenation step from 1.

Manipulating Interphase Chemistry for Aqueous Zn Stabilization: The Role of Supersaturation.

The limited cycling durability of Zn anode, attributed to the absence of a robust electrolyte-derived solid electrolyte interphase (SEI), remains the bottleneck for the practical deployment of aqueous zinc batteries. Herein, we highlight the role of local supersaturation in governing the fundamental crystallization chemistry of Zn4SO4(OH)6·xH2O (ZSH) and propose a subtle supersaturation-controlled morphology strategy to tailor the interphase chemistry of Zn anode. By judiciously creating local high-supersaturation environment with organic caprolactam to manipulate the precipitation manner of zinc sulfate hydroxide (ZSH), lattice-lattice matched heterogeneous nucleation of ZSH (001) and Zn (002) is realized in aqueous ZnSO4, producing a dense, pseudo-coincidence interface capable of functioning as decent SEI.

Aneurysm Is Restricted by CD34 Cell-Formed Fibrous Collars Through the PDGFRb-PI3K Axis.

Aortic aneurysm is a life-threatening disease caused by progressive dilation of the aorta and weakened aortic walls. Its pathogenesis involves an imbalance between connective tissue repair and degradation. CD34 cells comprise a heterogeneous population that exhibits stem cell and progenitor cell properties.

Action Potential Firing Patterns Regulate Dopamine Release via Voltage-Sensitive Dopamine D2 Autoreceptors in Mouse Striatum In Vivo.

Dopamine (DA) in the striatum is vital for motor and cognitive behaviors. Midbrain dopaminergic neurons generate both tonic and phasic action potential (AP) firing patterns in behavior mice. Besides AP numbers, whether and how different AP firing patterns per se modulate DA release remain largely unknown.

The antiarthritic effect of CBR-470-1 in hypoxic environment is to increase the level of NOD-like receptor family pyrin domain containing 3 ubiquitination by decreasing phosphoglycerate kinase 1 activity.

Background: Hypoxia can affect the occurrence and development of inflammation in humans, but its effects on the disease progression of osteoarthritis (OA) remain unclear. Synovial macrophages play an essential role in the progression of arthritis. Specifically, the activation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) in macrophages induces the secretion of a series of inflammatory factors, accelerating the progression of OA.

Deficiency of ATF3 facilitates both angiotensin II-induced and spontaneously formed aortic aneurysm and dissection development by activating cGAS-STING pathway.

Background: Sporadic aortic aneurysm and dissection (AAD) is a critical condition characterised by the progressive loss of vascular smooth muscle cells (VSMCs) and the breakdown of the extracellular matrix. However, the molecular mechanisms responsible for the phenotypic switch and loss of VSMCs in AAD are not fully understood.

Methods And Results: In this study, we employed a discovery-driven, unbiased approach.

Single-Cell Transcriptomics Uncovers Core Signature for Regulating Mitochondrial Homeostasis During Testicular Ageing.

Testicular ageing is accompanied by a series of morphological changes, while the features of mitochondrial dysfunction remain largely unknown. Herein, we observed a range of age-related modifications in testicular morphology and spermatogenic cells, and conducted single-cell RNA sequencing on young and old testes in Drosophila. Pseudotime trajectory revealed significant changes in germline subpopulations during ageing.

Non-surgery strategy versus hepatectomy in hepatocellular carcinoma patients with complete response after conversion therapy: a meta-analysis.

Background: There is ongoing debate surrounding the optimal therapeutic strategy for hepatocellular carcinoma (HCC) patients achieving complete response (CR) after conversion therapy. This meta-analysis compares the prognostic outcomes of non-surgery strategies with hepatectomy.

Methods: The systematic searches were conducted up to April 11, 2024, across PubMed, Embase, Web of Science, and the Cochrane Library, analyzing progression-free survival (PFS) and overall survival (OS).

Reduced gut microbiota diversity in ulcerative colitis patients with latent tuberculosis infection during vedolizumab therapy: insights on prophylactic anti-tuberculosis effects.

Background: The gut microbiota plays a pivotal role in ulcerative colitis (UC) development. This study explores the impact of latent tuberculosis infection (LTBI) on the gut microbiota in UC and assesses changes during vedolizumab treatment, investigating prophylactic anti-tuberculosis therapy.

Results: This cohort study included adult patients with UC receiving vedolizumab treatment at Jinhua Hospital, Zhejiang University from April 2021 to December 2022.

Influencing factors of elderly hospitalized psychiatric patients complicated with physical disease: a cross-sectional study of 332 patients in Guangzhou China.

Objective: To investigate the influencing factors of the number of physical diseases in elderly hospitalized psychiatric patients.

Methods: A total of 332 hospitalized elderly patients with mental illness were enrolled in this study. The number of combined physical diseases was divided into three groups, which were 0, 1 ~ 2, and ≥ 3.

Development of a set of indicators for the quality of chronic pain management in Chinese community-dwelling older adults: a Delphi study.

Background: Standardized and systematic quality assessments of chronic pain management, particularly among older adult populations, are lacking in resource-limited community settings. A specific set of indicators to evaluate the quality of chronic pain management in this population has yet to be developed. Therefore, the present study constructed a set of indicators to assess the quality of chronic pain management in Chinese community-dwelling older adults, providing a standardized reference and guidance for community health centers to manage chronic pain in this population.

Efficacy and safety of aspirin in preventing venous thromboembolism after hip arthroplasty for femoral neck fracture: a noninferiority prospective cohort study.

Background: Venous thromboembolism (VTE) is a common complication after hip arthroplasty. Here, we investigated the clinical efficacy and safety of prophylactic aspirin vs. conventional therapy in hip arthroplasty for femoral neck fracture.

ENPP2 promotes progression and lipid accumulation via AMPK/SREBP1/FAS pathway in chronic lymphocytic leukemia.

Background: Disorders of lipid metabolism are critical factors in the progression of chronic lymphocytic leukemia (CLL). However, the characteristics of lipid metabolism and related regulatory mechanisms of CLL remain unclear.

Methods: Hence, we identified altered metabolites and aberrant lipid metabolism pathways in patients with CLL by ultra-high-performance liquid chromatography-mass spectrometry-based non-targeted lipidomics.

Puerarin Protects Myocardium From Ischaemia/Reperfusion Injury by Inhibiting Ferroptosis Through Downregulation of VDAC1.

Despite improvements in interventional techniques leading to faster myocardial reperfusion postmyocardial infarction, there has been a significant rise in the occurrence of myocardial ischaemia/reperfusion injury (MI/RI). A deeper understanding of the underlying mechanisms of MI/RI could offer a crucial approach to reducing myocardial damage and enhancing patient outcomes. This study examined the myocardial protective properties of puerarin (PUE) in the context of MI/RI using hypoxia/reoxygenation (H/R) or ischaemia/reperfusion (I/R) injury models were employed in H9c2 cells and C57BL/6 mice.

Investigations on mineralogical characteristics and feasibility of coal gangue as a concrete aggregate from guizhou province, China.

Coal gangue (CG) is an industrial solid waste produced by coal mining and separation that is considered to have a significant effect on the soil or water environment when exposed to the air, exacerbating ecological pollution. The comprehensive utilization of CG has always been a difficult problem due to the complex mineralogical characteristics. Producing concrete aggregates with CG is an effective strategy for utilising CG resources synthetically.

Association between the triglyceride to high-density lipoprotein cholesterol ratio and type 2 diabetes mellitus in non-alcoholic fatty liver disease.

This study evaluated the ability of the triglyceride (TG) to high-density lipoprotein cholesterol (TG/HDL-C) ratio to identify individuals at risk of type 2 diabetes mellitus (T2DM) in the non-alcoholic fatty liver disease (NAFLD) population. We retrospectively studied 4,769 patients with NAFLD from the Affiliated Hospital of Hangzhou Normal University (2020-2023). Binary logistic regression models were used to evaluate the association between the TG/HDL-C ratio and lipid parameters with T2DM.

Identification of shared genetic etiology of cardiovascular and cerebrovascular diseases through common cardiometabolic risk factors.

Cardiovascular diseases (CVDs) and cerebrovascular diseases (CeVDs) are closely related vascular diseases, sharing common cardiometabolic risk factors (RFs). Although pleiotropic genetic variants of these two diseases have been reported, their underlying pathological mechanisms are still unclear. Leveraging GWAS summary data and using genetic correlation, pleiotropic variants identification, and colocalization analyses, we identified 11 colocalized loci for CVDs-CeVDs-BP (blood pressure), CVDs-CeVDs-LIP (lipid traits), and CVDs-CeVDs-cIMT (carotid intima-media thickness) triplets.