Design, synthesis and structure-activity relationship of novel 1,2,4-triazolopyrimidin-5-one derivatives targeting GABA and Na1.2 with antiepileptic activity.

A novel class of 7-phenyl-[1,2,4]triazol-5(4H)-one derivatives was designed and synthesized, and their in vivo anticonvulsant activities were evaluated using subcutaneous pentylenetetrazole (Sc-PTZ) and maximal electroshock (MES) tests. Compounds 3u, 4f and 4k exhibited significant anticonvulsant activities in the Sc-PTZ model with ED values of 23.7, 17.

Exploiting synthetic lethality in PDAC with antibody drug conjugates and ATR inhibition.

Pancreatic ductal adenocarcinoma (PDAC) remains a highly lethal malignancy with poor prognosis. Antibody-drug conjugates (ADCs) and their combinations with various anti-tumor drugs have made great progress. Camptothecin, and its derivatives (Dxd, SN-38 or exatecan) targeted TOP1 are effective payloads due to their potent anti-tumor activity.

Status Quo of Mental Health and Influencing Factors Among Older Adults in Different Living Situations: A Random Forest Analysis Based on CHARLS Data.

Purpose: To determine the status of depression and its key influencing factors among Chinese older adults in different living situations.

Method: Data of 7,092 older adults were obtained from the China Health and Retirement Longitudinal Survey. This study analyzed key variables influencing depressive symptoms using random forest modeling and logistic regression.

Hemodynamic analysis of left ventricular unloading with Impella versus IABP during VA-ECMO.

: The utilization of intra-aortic balloon pump (IABP) and Impella has been suggested as means of left ventricular unloading in veno-arterial extracorporeal membrane oxygenation (VA-ECMO) patients. This study aimed to assess the local hemodynamic alterations in VA-ECMO patients through simulation analyses. : In this study, a 0D-3D multiscale model was developed, wherein resistance conditions were employed to define the flow-pressure relationship.

Structured Liquid--Liquid Emulsion Stabilized by Surface-Engineered Liquid Metal Droplets as "Mutant" Pickering Emulsifiers.

Liquid metals (LMs), i.e., metals and alloys that exist in a liquid state at room temperature, have recently attracted considerable attention owing to their electronic and rheological properties useful in various cutting-edge technologies.

Spatial Scale Matters: Hydrolysis of Aryl Methyl Ethers over Zeolites.

The local environment of the active site, such as the confinement of hydronium ions within zeolite pores, significantly influences catalytic turnover, similar to enzyme functionality. This study explores these effects in the hydrolysis of guaiacols─lignin-derived compounds─over zeolites in water. In addition to the interesting catechol products, this reaction is advantageous for study due to its bimolecular hydrolysis pathway, which involves a single energy barrier and no intermediates, simplifying kinetic studies and result interpretation.

Inhibition of mitochondrial energy production leads to reorganization of the plant endomembrane system.

Mitochondria have generated the bulk of ATP to fuel cellular activities, including membrane trafficking, since the beginning of eukaryogenesis. How inhibition of mitochondrial energy production will affect the form and function of the endomembrane system and whether such changes are specific in today's cells remain unclear. Here, we treated Arabidopsis thaliana with antimycin A (AA), a potent inhibitor of the mitochondrial electron transport chain (mETC), as well as other mETC inhibitors and an uncoupler.

Central arterial stiffness in young adults with perinatal HIV exposure & infection.

Objective: To compare arterial stiffness between young adults with perinatally acquired HIV (YAPHIV) and young adults perinatally HIV exposed but uninfected (YAPHEU).

Design: Cross-sectional analysis of pulse wave velocity (PWV) measures among participants with echocardiography in the PHACS Cardiac Toxicity Substudy.

Methods: A total of 150 participants (95 YAPHIV, 55 YAPHEU, mean 23.

Nelonemdaz and Patients With Acute Ischemic Stroke and Mechanical Reperfusion: The RODIN Randomized Clinical Trial.

Importance: Nelonemdaz selectively antagonizes the 2B subunit of the N-methyl-d-aspartate glutamate receptor and scavenges free radical species.

Objective: To evaluate whether nelonemdaz enhances the clinical outcomes of patients with acute ischemic stroke undergoing emergent reperfusion therapy.

Design, Setting, And Participants: This multicenter double-blind placebo-controlled randomized phase 3 trial (December 25, 2021, to June 30, 2023, in South Korea) recruited patients with acute ischemic stroke who met the following criteria: National Institutes of Health Stroke Scale score greater than or equal to 8, Alberta Stroke Program Early Computed Tomography score greater than or equal to 4, and endovascular thrombectomy within 12 hours after stroke onset.

Arabidopsis CIRP1 E3 ligase modulates drought and oxidative stress tolerance and reactive oxygen species homeostasis by directly degrading catalases.

Reactive oxygen species (ROS) plays critical roles in modulating plant growth and stress response and its homeostasis is fine tuned using multiple peroxidases. HO, a major kind of ROS, is removed rapidly and directly using three catalases, CAT1, CAT2, and CAT3, in Arabidopsis. Although the activity regulations of catalases have been well studied, their degradation pathway is less clear.

Enhanced ZBTB10 expression induced by betulinic acid inhibits gastric cancer progression by inactivating the ARRDC3/ITGB4/PI3K/AKT pathway.

Background: Gastric cancer (GC) ranks as the fourth leading cause of cancer-related deaths worldwide, with most patients diagnosed at advanced stages due to the absence of reliable early detection biomarkers.

Methods: RNA-sequencing was conducted to identify the differentially expressed genes between GC tissues and adjacent normal tissues. CCK8, EdU, colony formation, transwell, flow cytometry and xenograft assays were adopted to explore the biological function of ZBTB10 and betulinic acid (BA) in GC progression.

Platelet membrane-modified exosomes targeting plaques to activate autophagy in vascular smooth muscle cells for atherosclerotic therapy.

Atherosclerosis is one of the leading causes of ischemic cardiovascular disease worldwide. Recent studies indicated that vascular smooth muscle cells (VSMCs) play an indispensable role in the progression of atherosclerosis. Exosomes derived from mesenchymal stem cells (MSCs) have demonstrated promising clinical applications in the treatment of atherosclerosis.

Development and utilization of a multiplex PCR assay for detecting three feline enteroviruses.

Background: Feline diarrhea is a common digestive tract disease in clinical practice, with watery feces as the main clinical manifestation. There are numerous pathogenic factors causing feline diarrhea, among which viral infections are prevalent, and feline panleukopenia virus (FPV) is the most common pathogen. In recent years, a variety of novel viruses have been detected in the intestines of cats with diarrhea.

Hematopoietic stem cell transplantation and immunosuppressive therapy: implications of clonal haematopoiesis.

Aplastic anemia (AA) is a life-threatening bone marrow failure syndrome. The advent of next-generation sequencing (NGS) has shed light on the link between somatic mutations (SM) and the efficacy of immunosuppressive therapy (IST) in AA patients. However, the relationship between SM and hematopoietic stem cell transplantation (HSCT) has not been extensively explored.

A predictive model based on the gut microbiota improves the diagnostic effect in patients with rheumatoid arthritis.

Objectives: Rheumatoid arthritis (RA) is a chronic, destructive autoimmune disorder predominantly targeting the joints, with gut microbiota dysbiosis being intricately associated with its progression. The aim of the present study was to develop of effective early diagnostic methods for early RA based on gut microbiota.

Methods: A cohort comprising 262 RA patients and 475 healthy controls (HCs) was recruited.

Size-Dependent Separation of Extracellular Vesicle Subtypes with Exodisc Enabling Proteomic Analysis in Prostate Cancer.

Extracellular vesicles (EVs) are emerging as crucial biomarkers in cancer diagnostics and therapeutics with their heterogeneity presenting both challenges and opportunities in prostate cancer research. However, existing methods for isolating and characterizing EV subtypes have been limited by inefficient separation and inadequate proteomic analysis. Here we show an optimized centrifugal microfluidic device, Exodisc, that efficiently isolates large quantities of EV subtypes from particle-enriched medium, enabling comprehensive proteomic analysis of small (EV-S, 20-200 nm) and large (EV-L, >200 nm) EVs.

Glucose Metabolic Abnormalities and Their Interaction With Defective Phosphate Homeostasis in Tumor-induced Osteomalacia.

Context: Phosphate homeostasis was compromised in tumor-induced osteomalacia (TIO) due to increased fibroblast growth factor 23 (FGF23) secretion. Nevertheless, the glucose metabolic profile in TIO patients has not been investigated.

Objectives: This work aimed to clarify the glucose metabolic profiles in TIO patients and explore their interaction with impaired phosphate homeostasis.

An InDel variant in the promoter of the NAC transcription factor MdNAC18.1 plays a major role in apple fruit ripening.

A complex regulatory network governs fruit ripening, but natural variations and functional differentiation of fruit ripening genes remain largely unknown. Utilizing a genome-wide association study (GWAS), we identified the NAC family transcription factor MdNAC18.1, whose expression is closely associated with fruit ripening in apple (Malus × domestica Borkh.

Ultrarapid and efficient sequestration of iodate and iodide with a pillar[5]arene-based cationic polymeric network.

A macrocycle-based approach to the construction of a cationic polymeric network with pillar[5]arene as the node for efficient sequestration of hazardous IO and I is presented. Ultrafast kinetics ( 4 min) were achieved along with excellent adsorption capacities for both IO (456 mg g) and I (370 mg g), good selectivity, and outstanding reusability. This work showcases the merits of pillar[5]arene as nodes in cationic adsorption materials in the removal of anionic iodine species.

Inhibiting NLRP3 enhances cellular autophagy induced by outer membrane vesicles from .

The bacterium is able to invade lung epithelial cells and survive intracellularly. During this process, it secretes outer membrane vesicles (OMVs), however, it is currently unclear how OMVs from (PA-OMVs) affect lung epithelial cells and their impact on oxidative stress, autophagy, and other physiological activities of lung epithelial cells. In this study, we found that PA-OMVs activated oxidative stress and autophagy in cells.

Investigation of Pyrrole Analogues Inhibition on Mpro by Spectroscopic Analysis, Molecular Docking and Enzyme Activity.

The main protease (Mpro) is a cysteine enzyme and represents a vital target for antiviral drug screening. In this work, Twenty-five pyrrole derivatives were synthesized and screened by enzyme activity experiments. Results indicate that six pyrrole derivatives can bind to Mpro and have inhibitory effect on Mpro.

Solvent-Free Artificial Light-Harvesting System in a Fluid Donor with Highly Efficient Förster Resonance Energy Transfer.

Multi-step Förster resonance energy transfer (FRET) plays a vital role in photosynthesis. While the energy transfer efficiency (Φ) of a naturally occurring system can reach 95%, that of most artificial light-harvesting systems (ALHSs) is still limited. Herein, we propose a strategy to construct highly efficient ALHSs using a blue-emitting, supercooled ionic compound of naphthalimide (NPI) as the donor, a green-emitting BODIPY derivate as a relay acceptor, and a commercially available, red-emitting dye [rhodamine B (RhB)] as the final acceptor.

Sabatier Principle Inspired Bifunctional Alloy Interface for Stable and High-Depth Discharging Zinc Metal Anodes.

Achieving stable Zn anodes is essential for advancing high-performance Zn metal batteries. Here, we propose a Sabatier principle inspired bifunctional transition-metal (TM) interface to enable homogeneous Zn dissolution during discharging and dendrite-free Zn deposition during charging. Among various TM-coated Zn (TM@Zn) electrodes, Cu@Zn exhibits the highest reversibility and structural stability, attributed to the optimal interaction between Cu and Zn.