Artificial Intelligence-Based Multimodal Prediction of Postoperative Adjuvant Immunotherapy Benefit in Urothelial Carcinoma: Results From the Phase III, Multicenter, Randomized, IMvigor010 Trial.

While circulating tumor DNA (ctDNA) testing has demonstrated utility in identifying muscle-invasive urothelial carcinoma (MIUC) patients likely to benefit from adjuvant immunotherapy, the prognostic value of transcriptome data from surgical specimens remains underexplored. Using transcriptomic and ctDNA data from the IMvigor010 trial, we developed an artificial intelligence (AI)-driven biomarker to predict immunotherapy response in urothelial carcinoma, termed UAIscore. Patients with high UAIscore had significantly better outcomes in the atezolizumab arm versus the observation arm.

Immunotyping the Tumor Microenvironment Reveals Molecular Heterogeneity for Personalized Immunotherapy in Cancer.

The tumor microenvironment (TME) significantly influences cancer prognosis and therapeutic outcomes, yet its composition remains highly heterogeneous, and currently, no highly accessible, high-throughput method exists to define it. To address this complexity, the TMEclassifier, a machine-learning tool that classifies cancers into three distinct subtypes: immune Exclusive (IE), immune Suppressive (IS), and immune Activated (IA), is developed. Bulk RNA sequencing categorizes patient samples by TME subtype, and in vivo mouse model validates TME subtype differences and differential responses to immunotherapy.

Inhibiting the Histone Demethylase Kdm4a Restrains Cardiac Fibrosis After Myocardial Infarction by Promoting Autophagy in Premature Senescent Fibroblasts.

Premature senescent fibroblasts (PSFs) play an important role in regulating the fibrotic process after myocardial infarction (MI), but their effect on cardiac fibrosis remains unknown. Here, the investigation is aimed to determine whether PSFs contribute to cardiac fibrosis and the underlying mechanisms involved. It is observed that premature senescence of fibroblasts is strongly activated in the injured myocardium at 7 days after MI and identified that Kdm4a is located in PSFs by the analysis of scRNA-seq data and immunostaining staining.

Safety and efficacy of lesion size index guided 50 W radiofrequency ablation in patients with paroxysmal atrial fibrillation.

Background: Pulmonary vein isolation (PVI) using conventional power (30-35 W) radiofrequency ablation (RFA) has been an effective treatment strategy for paroxysmal atrial fibrillation (PAF), but its longer duration may cause collateral damage to peripheral tissue including esophageal and phrenic nerve. High-power (HP) RFA, due to better transmural performance and shorter duration, may reduce the damage to adjacent tissue and is expected to be a safe and efficient ablation strategy.

Methods: In this retrospective cohort study, we included 259 patients with PAF who underwent lesion size index (LSI)-guided radiofrequency ablation.

A body shape index for visceral fat and its changes predict cardiovascular outcomes of heart failure with preserved ejection fraction.

Aims: This study aimed to investigate the relationship between visceral adipose tissue (VAT), measured using a body shape index (ABSI), and outcomes in patients with heart failure with preserved ejection fraction (HFpEF).

Methods: ABSI data and cardiovascular outcomes were obtained from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. ABSI was calculated using waist circumference (WC), body mass index, and height.

Paddy fields can gain high productivity with low net global warming potential by utilizing green manure.

The use of milk vetch as winter green manure is common in paddy fields across southern China. The greenhouse effect of co-utilizing milk vetch and rice straw has not yet been reported. In this study, we investigated net greenhouse gas emissions and related environmental factors over two years based on a long-term experiment.

Intratumoral and peritumoral PET/CT-based radiomics for non-invasively and dynamically predicting immunotherapy response in NSCLC.

Background: We aimed to develop a machine learning model based on intratumoral and peritumoral F-FDG PET/CT radiomics to non-invasively and dynamically predict the response to immunotherapy in non-small cell lung cancer (NSCLC).

Methods: This retrospective study included 296 NSCLC patients, including a training cohort (N = 183), a testing cohort (N = 78), and a TCIA radiogenomic cohort (N = 35). The extreme gradient boosting algorithm was employed to develop the radiomic models.

A murine model of aortic regurgitation generated by trans-apical wire destruction of the aortic valve.

Background: The mechanisms underlying cardiac remodeling in aortic valvular (AoV) disease remain poorly understood, partially due to the insufficiency of appropriate preclinical animal models. Here, we present a novel murine model of aortic regurgitation (AR) generated by trans-apical wire destruction of the AoV.

Methods: Directed by echocardiography, apical puncture of the left ventricle (LV) was performed in adult male C57BL/6 mice, and a metal guidewire was used to induce AoV destruction.

Deciphering the Significance of Platelet-Derived Chloride Ion Channel Gene (BEST3) Through Platelet-Related Subtypes Mining for Non-Small Cell Lung Cancer.

This study investigates platelet-related subtypes in non-small cell lung cancer (NSCLC) and seeks to identify genes associated with prognosis, focusing on the clinical significance of the chloride ion channel gene BEST3. We utilised sequencing and clinical data from GEO, TCGA and the Xena platform, building a risk model based on genetic features. TCGA and GSE37745 served as training cohorts, while GSE50081, GSE13213, GSE30129 and GSE42127 were validation cohorts.

Tumor microenvironment assessment-based signatures for predicting response to immunotherapy in non-small cell lung cancer.

Immunotherapy has significantly altered the treatment paradigm of non-small cell lung cancer (NSCLC), but not all patients experience durable benefits. Predictive biomarkers are needed to identify patients who may benefit from immunotherapy. We retrospectively collected tumor tissues from 65 patients with advanced NSCLC before treatment, and performed transcriptomic and genomic analysis.

Hypoxia Microenvironment Preconditioning Attenuated Myocardial Ischemia-Reperfusion Injury via Stc1-Mediating Cardiomyocyte Self-Protection and Neutrophil Polarization.

Ischemic preconditioning (IPC) therapy application to attenuate myocardial ischemia-reperfusion (MI/R) injury in clinical practice remains challenging. The secretome, derived from hypoxia-preconditioned cardiomyocytes (SHPC), potentially mimics the IPC microenvironment and facilitates IPC clinical translation. This study aims to determine whether SHPC can be a feasible alternative to IPC for attenuating MI/R injury, and to identify the functional factor of SHPC.

CircRNA-RBAC induces cardiac repair by promoting ribosome biogenesis and cell cycle progression in cardiomyocytes.

Ribosome biogenesis (RiBi) is an essential process that controls the protein synthesis rate, but its function in regulating endogenous cardiac regeneration remains unknown. Herein, we investigated the function and underlying mechanism of RiBi-associated circRNAs in cardiomyocyte (CM) proliferation and cardiac regeneration. We used high-throughput sequencing, quantitative PCR and in situ hybridization techniques to identify an adult downregulated circRNA, RiBi-associated circRNA (RBAC), in CMs.

Canagliflozin reverses doxorubicin-induced cardiotoxicity via restoration of autophagic homeostasis.

Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been reported as successful for preventing doxorubicin (DOX) -induced cardiotoxicity (DIC), but the underlying mechanisms are elusive. This study aimed to determine whether canagliflozin, an SGLT2i, protects against DIC by regulation of autophagic flux in cardiomyocytes through a mechanism independent of SGLT2. The differentially expressed autophagy-related genes (ARGs) in DIC were analyzed.

CircHipk3 serves a dual role in macrophage pyroptosis by promoting NLRP3 transcription and inhibition of autophagy to induce abdominal aortic aneurysm formation.

Aims: CircRNAs could regulate macrophage pyroptosis, which has the potential in promoting the synergistic effect of inflammation and matrix metalloproteinase (MMP) activity in abdominal aortic aneurysm (AAA). But the roles of circRNAs in modulating macrophage pyroptosis in the AAA remain unknown. This study explored the contribution to AAA of circHipk3, which was macrophage pyroptosis promoter, and the underlying mechanism.

RNA-Binding Protein Hnrnpa1 Triggers Daughter Cardiomyocyte Formation by Promoting Cardiomyocyte Dedifferentiation and Cell Cycle Activity in a Post-Transcriptional Manner.

Stimulating cardiomyocyte (CM) dedifferentiation and cell cycle activity (DACCA) is essential for triggering daughter CM formation. In addition to transcriptional processes, RNA-binding proteins (RBPs) are emerging as crucial post-transcriptional players in regulating CM DACCA. However, whether post-transcriptional regulation of CM DACCA by RBPs could effectively trigger daughter CM formation remains unknown.

Tert promotes cardiac regenerative repair after MI through alleviating ROS-induced DNA damage response in cardiomyocyte.

Telomerase reverse transcriptase (Tert) has been found to have a protective effect on telomeric DNA, but whether it could improve the repair of reactive oxygen species (ROS)-induced DNA damage and promote myocardial regenerative repair after myocardial infarction (MI) by protecting telomeric DNA is unclear. The immunofluorescence staining with TEL-CY3 and the TeloTAGGG Telomerase PCR ELISA kit were used to show the telomere length and telomerase activity. The heart-specific Tert-deletion homozygotes were generated by using commercial Cre tool mice and flox heterozygous mice for mating.

Association of Oral Microbiome Diversity and All-Cause Mortality in the General US Population and in Individuals With Chronic Diseases: A Prospective Cohort Study.

Aim: To investigate whether oral microbiome diversity is associated with all-cause mortality in the general US population and in individuals with chronic diseases.

Materials And Methods: We included 8224 individuals with oral microbiome diversity data from the National Health and Nutrition Examination Survey (2009-2012), representing 164,000,205 US adults, using a survey-weighted analysis method. Cox regression analyses were performed to identify the association between oral microbiome diversity and all-cause mortality.

Sympathetic hyperinnervation drives abdominal aortic aneurysm development by promoting vascular smooth muscle cell phenotypic switching.

Introduction: Sympathetic hyperinnervation plays an important role in modulating the vascular smooth muscle cell (VSMC) phenotype and vascular diseases, but its role in abdominal aortic aneurysm (AAA) is still unknown.

Objectives: This study aimed to investigate the role of sympathetic hyperinnervation in promoting AAA development and the underlying mechanism involved.

Methods: Western blotting and immunochemical staining were used to detect sympathetic hyperinnervation.

Enhancing phosphorus transformation in typical reddish paddy soil from China: Insights on long-term straw return and pig manure application via microbial mechanisms.

Effective utilization of organic resources to activate residual phosphorus (P) in soil and enhance its availability is crucial for mitigating P resource scarcity and assessing the sustainable use of P in agricultural practices. However, the mechanisms through which organic resources affect soil P conversion via microorganisms and functional genes remain unknown, particularly in long-term organic-inorganic agricultural systems. In this study, we examined the impact of combined organic-inorganic fertilizer application on P availability, carbon (C) and P cycling genes, and microbial communities (bacterial and fungal) in reddish paddy soil based on a 42-year field experiment.

Soil Cd bioavailability response characteristics to microbes in paddy fields with co-incorporation of milk vetch, rice straw and amendments.

Excessive heavy metals in soils can threaten food security and soil health. New practical technology is urgently needed to remediate cadmium (Cd) contaminated paddies in many parts of the world. Chinese milk vetch (M), rice straw (R), and soil amendments can reduce Cd activity in soil; however, the mechanism underlying this reduction is not well understood.

Titration of Sedentary Behavior With Varying Physical Activity Levels Reduces Mortality in Patients With Type 2 Diabetes.

Context: Both physical activity (PA) and sedentary behavior (SB) exert an important impact on type 2 diabetes, but it remains unclear regarding how the maximum impact on improving mortality by an optimized proportion of the two lifestyles can be achieved.

Objective: To explore the impacts of PA/SB combinations on mortality in patients with diabetes.

Methods: Patients with type 2 diabetes samplings were collected from the National Health and Nutrition Examination Survey dataset.

A combined model of serum neutrophil extracellular traps, CD8 T cells, and tumor proportion score provides better prediction of PD-1 inhibitor efficacy in patients with NSCLC.

Immune checkpoint inhibitors provide a definite survival benefit for patients with driver-negative advanced non-small cell lung cancer (NSCLC), but predictors of efficacy are still lacking. There may be a relationship between immune inflammatory state and tumor immune response. We explored the relationship of serum neutrophil extracellular traps (NETs) with infiltrating cells in the tumor tissues of patients with NSCLC as well as their relationship with the therapeutic efficacy of programmed cell death protein 1 (PD-1) inhibitors.