Regulates -Mediated Autophagy in High Glucose-Induced Vascular Smooth Muscle Cells.

Background: Vascular smooth muscle cells(VSMCs) phenotypic switching under hyperglycemic conditions accelerates atherosclerotic progression. Notch receptor 3(NOTCH3), a critical stabilizer of VSMC homeostasis implicated in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) pathogenesis, ensures vascular integrity; however, its interplay with RAN Binding Protein 1() during pathological hyperglycemia remains uncharacterized. We hypothesize that hyperglycemia-induced autophagic dysregulation is mechanistically governed by theNotch receptor 3 ()/ axis, proliferative capacity, and apoptotic signaling in high glucose (HG)-stimulated VSMCs.

High and low dose radiotherapy combined with ICIs for MSS colorectal cancer patients with liver metastases: a phase I study (HaRyPOT).

Introduction: Microsatellite stable (MSS) colorectal cancer with liver metastases (CLRM) responds poorly to immunotherapy, and various approaches to break immune tolerance have been tried. Radiotherapy in combination with immune checkpoint inhibitors is one of promising therapies, and the choice of radiotherapy and immunotherapy modalities is also a hot issue.

Methods: Here, we report on a Phase I trial treating nine patients with MSS CLRM using a combination of high and low dose radiotherapy and immune checkpoint inhibitors (ICIs).

Difference between estimated glomerular filtration rate based on cystatin C versus creatinine and cardiovascular-kidney-metabolic health.

Background: The difference between the estimated glomerular filtration rate (eGFR) calculated from cystatin C and creatinine (eGFRdiff) serves as a biomarker of kidney function impairment. However, the role of eGFRdiff in cardiovascular-kidney-metabolic (CKM) health and its impact on mortality in CKM syndrome patients has not yet been studied.

Methods: This study included 3,622 participants from the National Health and Nutrition Examination Survey (NHANES) conducted between 1999 and 2004.

c-di-GMP inhibits rRNA methylation and impairs ribosome assembly in the presence of kanamycin.

Cyclic diguanosine monophosphate (c-di-GMP) is a ubiquitous bacterial secondary messenger with diverse functions. A previous Escherichia coli proteome microarray identified that c-di-GMP binds to the 23S rRNA methyltransferases RlmI and RlmE. Here we show that c-di-GMP inhibits RlmI activity in rRNA methylation assays, and that it modulates ribosome assembly in the presence of kanamycin.

Dietary limonin alleviates Typhimurium-induced colitis dual targeting virulence SopB and SopE2 and inhibiting RAC1/CDC42/Arp2/3 pathway and regulating gut microbiota.

serovar Typhimurium (STM) causes severe colitis, necessitating the development of effective drugs. Here, the dockings of limonin with the STM T3SS-1 virulence factor SopB or SopE2 showed strong binding activity and was verified by CETSA and DARTS assays . Limonin inhibited the enzyme activities and expression of SopB and SopE2 .

Structure-Based Design of 2-Aminopyrazolpyrimidopyridone Derivatives as New Rearranged During Transfection (RET) Kinase Inhibitors.

RET (Rearranged during transfection) kinase is a validated target for non-small cell lung cancer (NSCLC). In 2020, two selective RET inhibitors, selpercatinib and pralsetinib were approved by the US FDA. However, high treatment costs and clinically acquired resistance (e.

Association between "Life's Essential 8" cardiovascular health and apparent treatment-resistant hypertension among US adults from the NHANES, 2005 to 2018.

Background: The association between healthy lifestyle and American Heart Association (AHA) Life's Essential 8 (LE8) score and apparent treatment-resistant hypertension(aTRH)remains uncertain. We aimed to explore the association between healthy lifestyle and higher LE8 score and apparent treatment-resistant hypertension in the general population.

Methods: Using NHANES data from 2005 to 2018, we included and analyzed information on 7,474 participants eligible for this study.

Ginsenoside Ro improves Salmonella Typhimurium-induced colitis through inhibition of the virulence factors SopB and SopE2 via the RAC1/CDC42/ARP2/3 pathway.

Salmonella enterica serovar Typhimurium (S. Typhimurium) poses a serious threat to human and animal health, and there is an urgent need to develop new therapeutic agents. In our in vivo study, ginsenoside Ro (Ro) reduced the mortality rate of S.

Association of artificial intelligence-based immunoscore with the efficacy of chemoimmunotherapy in patients with advanced non-squamous non-small cell lung cancer: a multicentre retrospective study.

Purpose: Currently, chemoimmunotherapy is effective only in a subset of patients with advanced non-squamous non-small cell lung cancer. Robust biomarkers for predicting the efficacy of chemoimmunotherapy would be useful to identify patients who would benefit from chemoimmunotherapy. The primary objective of our study was to develop an artificial intelligence-based immunoscore and to evaluate the value of patho-immunoscore in predicting clinical outcomes in patients with advanced non-squamous non-small cell lung cancer (NSCLC).

Feedforward inhibition of stress by brainstem neuropeptide Y neurons.

Resistance to stress is a key determinant for mammalian functioning. While many studies have revealed neural circuits and substrates responsible for initiating and mediating stress responses, little is known about how the brain resists to stress and prevents overreactions. Here, we identified a previously uncharacterized neuropeptide Y (NPY) neuronal population in the dorsal raphe nucleus and ventrolateral periaqueductal gray region (DRN/vlPAG) with anxiolytic effects in male mice.

Initial treatment for surgery-naïve desmoid tumors by high intensity focused ultrasound.

Introduction: Desmoid tumor (DT) is a rare proliferative disease occurring in connective tissues, characterized by high infiltration and recurrence rates. While surgery remains the primary treatment, its recurrence risk is high, and some extra-abdominal desmoid tumors are inoperable due to their locations. Despite attempts with radiotherapy and systemic therapy, the efficacy remains limited.

Value of the triglyceride-glucose index and related parameters in heart failure patients.

The triglyceride-glucose (TyG) index, proven to be a crucial insulin resistance biomarker (better than the Homeostasis Model Assessment for Insulin Resistance), is simple and non-invasive. Recently, indisputable evidence has shown that the TyG index is strongly associated with cardiovascular disease [CVD, including atherosclerosis, heart failure (HF), and hypertension] prognosis and mortality. Nevertheless, the value of the TyG index in HF patients treated with sodium-glucose cotransporter 2 inhibitors (SGLT2is) has not been systematically evaluated.

Ligand-enabled ruthenium-catalyzed meta-C-H alkylation of (hetero)aromatic carboxylic acids.

Carboxylates are ideal directing groups because they are widely available, readily cleavable and excellent linchpins for diverse follow-up reactions. However, their use in meta-selective C-H functionalizations remains a substantial unmet catalytic challenge. Herein, we report the ruthenium-catalyzed meta-C-H alkylation of aromatic carboxylic acids with various functionalized alkyl halides.

Scutellarin Protects against Myocardial Ischemia-reperfusion Injury by Enhancing Aerobic Glycolysis through miR-34c-5p/ALDOA Axis.

Background: Aerobic glycolysis has recently demonstrated promising potential in mitigating the effects of ischemia-reperfusion (IR) injury. Scutellarin (Scu) possesses various cardioprotective properties that warrant investigation. To mimic IR injury , this study employed hypoxia/reoxygenation (H/R) injury.

Hierarchical joint analysis of marginal summary statistics-Part II: High-dimensional instrumental analysis of omics data.

Instrumental variable (IV) analysis has been widely applied in epidemiology to infer causal relationships using observational data. Genetic variants can also be viewed as valid IVs in Mendelian randomization and transcriptome-wide association studies. However, most multivariate IV approaches cannot scale to high-throughput experimental data.

Targeting Super-Enhancer-Driven Transcriptional Dependencies Suppresses Aberrant Hedgehog Pathway Activation and Overcomes Smoothened Inhibitor Resistance.

Aberrant activation of the Hedgehog (Hh) signaling pathway plays important roles in oncogenesis and therapeutic resistance in several types of cancer. The clinical application of FDA-approved Hh-targeted smoothened inhibitors (SMOi) is hindered by the emergence of primary or acquired drug resistance. Epigenetic and transcriptional-targeted therapies represent a promising direction for developing improved anti-Hh therapies.

EGFR degraders in non-small-cell lung cancer: Breakthrough and unresolved issue.

The epidermal growth factor receptor (EGFR) has been well validated as a therapeutic target for anticancer drug discovery. Osimertinib has become the first globally accessible third-generation EGFR inhibitor, representing one of the most advanced developments in non-small-cell lung cancer (NSCLC) therapy. However, a tertiary Cys797 to Ser797 (C797S) point mutation has hampered osimertinib treatment in patients with advanced EGFR-mutated NSCLC.

Hierarchical joint analysis of marginal summary statistics-Part I: Multipopulation fine mapping and credible set construction.

Recent advancement in genome-wide association studies (GWAS) comes from not only increasingly larger sample sizes but also the shift in focus towards underrepresented populations. Multipopulation GWAS increase power to detect novel risk variants and improve fine-mapping resolution by leveraging evidence and differences in linkage disequilibrium (LD) from diverse populations. Here, we expand upon our previous approach for single-population fine-mapping through Joint Analysis of Marginal SNP Effects (JAM) to a multipopulation analysis (mJAM).

The Treatment of Refractory Vitiligo With Autologous Cultured Epithelium Grafting: A Real-World Retrospective Cohort Study.

Background: Surgical intervention is the main therapy for refractory vitiligo. We developed a modified autologous cultured epithelial grafting (ACEG) technique for vitiligo treatment. Between January 2015 and June 2019, a total of 726 patients with vitiligo underwent ACEG in China, with patient characteristics and clinical factors being meticulously documented.