Discovery of HZS60 as a Novel Brain Penetrant NMDAR/TRPM4 Interaction Interface Inhibitor with Improved Activity and Pharmacokinetic Properties for the Treatment of Cerebral Ischemia.

The death signaling complex comprising extrasynaptic NMDAR and TRPM4 plays a pivotal role in the pathogenesis of ischemic stroke. Targeting the protein-protein interactions between NMDAR and TRPM4 represents a promising therapeutic strategy for ischemic stroke. Herein, we describe the discovery of a novel series of NMDAR/TRPM4 interaction interface inhibitors aimed at enhancing neuroprotective efficacy and optimizing pharmacokinetic profiles.

Integrated transcriptomic and metabolomic analyses uncover the key pathways of Limonium bicolor in response to salt stress.

Salinity significantly inhibits plant growth and development. While the recretohalophyte Limonium bicolor can reduce its ion content by secreting salt, the metabolic pathways it employs to adapt to high salt stress remain unclear. This study aims to unravel this enigma through integrated transcriptomic and metabolomic analyses of L.

Screen Time and Autism Spectrum Disorder: A Comprehensive Systematic Review of Risk, Usage, and Addiction.

The relationship between autism spectrum disorder (ASD) and screen time (ST) has been extensively studied; but the evidence remains inconsistent, and a comprehensive quantitative synthesis of this association is lacking. This study aims to provide a robust quantitative assessment of the relationship between ASD and ST by consolidating and analyzing available evidence to offer a more precise understanding of this complex association. This systematic review followed PRISMA 2020 statement, and applied a quality assessment tool for quantitative studies to identity best available evidence.

Isoscopoletin inhibits hepatocellular carcinoma cell proliferation via regulating glycolysis-related proteins.

Objective: Isoscopoletin is one of the primary metabolites of natural product scoparone, which was reported to against tumor proliferation. The aim of this study was to explore the mechanism of isoscopoletin against hepatocellular carcinoma (HCC).

Methods: Transcriptomics was used to reveal the possible pathways of isoscopoletin against HCC in vitro.

Dynamic change and risk factors of intense thirst in patients admitted to neuro-intensive care unit: An observational study.

Background: Thirst is a clinical discomfort symptom reported by most patients admitted to intensive care unit (ICU). Little is known about the dynamic change and risk factors of intense thirst in neuro-intensive care unit (Neuro-ICU).

Aim: The objective of this study was to explore the dynamic change and determine the risk factors of intense thirst in patients admitted to Neuro-ICU, providing reference for personalized interventions of intense thirst.

Personalized Prediction of Long-Term Renal Function Prognosis Following Nephrectomy Using Interpretable Machine Learning Algorithms: Case-Control Study.

Background: Acute kidney injury (AKI) is a common adverse outcome following nephrectomy. The progression from AKI to acute kidney disease (AKD) and subsequently to chronic kidney disease (CKD) remains a concern; yet, the predictive mechanisms for these transitions are not fully understood. Interpretable machine learning (ML) models offer insights into how clinical features influence long-term renal function outcomes after nephrectomy, providing a more precise framework for identifying patients at risk and supporting improved clinical decision-making processes.

Natural Product-Inspired Discovery of Naphthoquinone-Furo-Piperidine Derivatives as Novel STAT3 Inhibitors for the Treatment of Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer, and STAT3 has emerged as an effective drug target for TNBC treatment. Herein, we employed a scaffold-hopping strategy of natural products to develop a series of naphthoquinone-furopiperidine derivatives as novel STAT3 inhibitors. The assay showed that compound possessed higher antiproliferative activity than Cryptotanshinone and Napabucasin against TNBC cell lines, along with lower toxicity and potent antitumor activity in a TNBC xenograft model.

Transcriptomics analysis reveals potential regulatory role of nSMase2 (Smpd3) in nervous system development and function of middle-aged mouse brains.

Neutral sphingomyelinase-2 (nSMase2), gene name sphingomyelin phosphodiesterase-3 (Smpd3), is a key regulatory enzyme responsible for generating the sphingolipid ceramide. The function of nSMase2 in the brain is still controversial. To better understand the functional roles of nSMase2 in the aging mouse brain, we applied RNA-seq analysis, which identified a total of 1462 differentially abundant mRNAs between +/fro and fro/fro, of which 891 were increased and 571 were decreased in nSMase2-deficient mouse brains.

Genome-wide identification of the AP2/ERF gene family from Limonium bicolor and functional characterization of LbAP2/ERF32 under salt stress.

AP2/ERF transcription factors (TFs) play important roles in plant growth and development, plant morphogenesis and response to environmental stresses. However, their biological roles in recretohalophytes are still not fully revealed. Limonium bicolor L.

Multifunctional Nanosystem Based on Ultrasmall Carbon Dots for the Treatment of Acute Kidney Injury.

Acute kidney injury (AKI) is a critical medical condition characterized by high morbidity and mortality rates. The pathogenesis of AKI potentially involves bursts of reactive oxygen species (ROS) bursts and elevated levels of inflammatory mediators. Developing nanoparticles (NPs) that downregulate ROS and inflammatory mediators is a promising approach to treat AKI.

Ceramide-mediated orchestration of oxidative stress response through filopodia-derived small extracellular vesicles.

Extracellular vesicles (EVs) are shed from the plasma membrane, but the regulation and function of these EVs remain unclear. We found that oxidative stress induced by HO in Hela cells stimulated filopodia formation and the secretion of EVs. EVs were small (150 nm) and labeled for CD44, indicating that they were derived from filopodia.

Analysis of the roles of MAD proteins in the wing dimorphism of Nilaparvata lugens.

Wing dimorphism in Nilaparvata lugens is controlled by the insulin-like growth factor 1 (IGF-1) signaling - Forkhead transcription factors (IIS-FoxO) pathway. However, the role of this signal in the wing development program remains largely unclear. Here, we identified 2 R-SMAD proteins, NlMAD1 and NlMAD2, in the brown planthopper (BPH) transcriptome, derived from the intrinsic transforming growth factor-β pathway of insect wing development.

Blocking the utilization of carbon sources via two pathways to induce tumor starvation for cancer treatment.

Glucose oxidase (GOx) is often used to starvation therapy. However, only consuming glucose cannot completely block the energy metabolism of tumor cells. Lactate can support tumor cell survival in the absence of glucose.

The WRKY gene family in the halophyte Limonium bicolor: identification, expression analysis, and regulation of salt stress tolerance.

63 L. bicolor WRKY genes were identified and their informatics was analyzed. The results suggested that the LbWRKY genes involved in the development and salt secretion of salt glands in L.

Effectiveness of eHealth interventions for HIV prevention, testing and management: An umbrella review.

Background: Human immunodeficiency virus (HIV) infection has become a major contributor to the global burden of disease. Globally, the number of cases of HIV continues to increase. Electronic health (eHealth) interventions have emerged as promising tools to support disease self-management among people living with HIV.

Nondestructive testing of runny salted egg yolk based on improved ConvNeXt-T.

Salted egg yolks from salted duck eggs are widely utilized in the domestic and international food industry as both raw materials and ingredients. When salted egg yolks are not fully cured and matured, they exist in a fluid state, with a mixture of solid and liquid internally. Due to this composition, they are susceptible to deterioration during storage and usage, necessitating their detection and classification.

Novel Withanolides from Suppress Triple-Negative Breast Cancer by Triggering Apoptosis and p53-ASCT2-SLC7A11-Mediated Ferroptosis.

Triple-negative breast cancer (TNBC) is a malignant breast cancer. There is an urgent need for effective drugs to be developed for TNBC. () has been reported to have an anti-tumor effect, and six novel withanolides were isolated from it and designated as TAMEWs.

Decompression-first or direct enucleation: The choice of treatment for medium-sized odontogenic jaw cysts.

Background: The treatment of medium-sized odontogenic jaw cysts is inconsistent at present. Two main treatments, namely decompression and enucleation, are used overlappingly. This retrospective analysis aims to provide useful references for technique selection for future management of medium-sized odontogenic jaw cysts.

Innovative surgical approach for trigeminal trophic syndrome: Successful healing of facial ulcers through cross-face nerve grafts.

Background: Trigeminal trophic syndrome (TTS) is a rare condition caused by damage to the trigeminal nervous system, resulting in sensory disturbances and ulcers on the face. Treating TTS is complex and often requires medical or surgical intervention like flap reconstruction. However, there is limited research on surgical treatments for TTS ulcers.

Association between baseline office blood pressure level and the incidence and development of long-term frailty in the community-dwelling very elderly with hypertension.

Frailty is the most important risk factor causing disability in the elderly. Hypertension is one of the most common chronic diseases in the elderly and is closely related to frailty, but there is still controversy about the association between blood pressure and frailty. To explore the association between baseline blood pressure level and the incident and development of long-term frailty in the community-dwelling very elderly (i.

Feasibility of a Mobile Health Intervention for Providing a Continuum of HIV Services for MSM: Pilot Study of the WeTest Program in 3 Cities in China.

Background: Men who have sex with men (MSM) in China have a high risk for HIV infection but experience suboptimal rates of HIV testing and service engagement due to various social and structural barriers. We developed a mobile health (mHealth) intervention entitled "WeTest-Plus" (WeTest+) as a user-centered "one-stop service" approach for delivering access to comprehensive information about HIV risk, HIV self-testing, behavioral and biomedical prevention, confirmatory testing, treatment, and care.

Objective: The goal of the current study was to investigate the feasibility of WeTest+ to provide continuous HIV services to high-risk MSM.

Effects of aerobic exercise or Tai Chi Chuan interventions on problematic mobile phone use and the potential role of intestinal flora: A multi-arm randomized controlled trial.

Background: Problematic use of mobile phones (PMPU) has been described as a serious public health issue.

Methods: This study was a parallel three-arm randomized controlled trial and has completed registration (ClinicalTrials.gov Identifier: NCT05843591).

Association between mobile phone addiction, sleep disorder and the gut microbiota: a short-term prospective observational study.

Bidirectional communication between the gut microbiota and the brain has sparked interest in exploring the link between mobile phone addiction (MPA) and sleep disorders (SD) in microbiome research. However, investigating the role of gut microbiota in this relationship using animal models presents challenges due to the unique nature of MPA, and human research in this area is scarce. We recruited 99 healthy college students to evaluate the gut microbiome using 16S rRNA gene amplicon sequencing and assess MPA and SD at baseline and after a two-month follow-up.