Elevated protein lactylation promotes immunosuppressive microenvironment and therapeutic resistance in pancreatic ductal adenocarcinoma.

Metabolic reprogramming shapes tumor microenvironment (TME) and may lead to immunotherapy resistance in pancreatic ductal adenocarcinoma (PDAC). Elucidating the impact of pancreatic cancer cell metabolism in the TME is essential to therapeutic interventions. "Immune cold" PDAC is characterized by elevated lactate levels resulting from tumor cell metabolism, abundance of pro-tumor macrophages, and reduced cytotoxic T cell in the TME.

Multi-omics sequencing of gastroesophageal junction adenocarcinoma reveals prognosis-relevant key factors and a novel immunogenomic classification.

Background: Gastroesophageal junction adenocarcinoma (GEJAC) exhibits distinct molecular characteristics due to its unique anatomical location. We sought to investigate effective and reliable molecular classification of GEJAC to guide personalized treatment.

Methods: We analyzed the whole genomic, transcriptomic, T-cell receptor repertoires, and immunohistochemical data in 92 GEJAC patients and delineated the landscape of genetic and immune alterations.

Anti-PD-L1 envafolimab combined with anti-VEGF suvemcitug in pretreated solid tumors and hepatocellular carcinoma: an open-label phase II study with safety run-in stage.

Background: Immune checkpoint inhibitors (ICIs) combined with anti-vascular endothelial growth factor (VEGF) have been the standard first-line treatment of hepatocellular carcinoma (HCC). However, the efficacy of this combination in post-line treatment is still unknown. This study aimed to evaluate the efficacy and safety of the combination of anti-PD-L1 envafolimab and novel humanized anti-VEGF suvemcitug as second-line treatment for patients with HCC.

Principles, challenges, and advances in ribosome profiling: from bulk to low-input and single-cell analysis.

Ribosome profiling has revolutionized our understanding of gene expression regulation by providing a snapshot of global translation in vivo. This powerful technique enables the investigation of the dynamics of translation initiation, elongation, and termination, and has provided insights into the regulation of protein synthesis under various conditions. Despite its widespread adoption, challenges persist in obtaining high-quality ribosome profiling data.

Real-world Plasma Exposure of Nirmatrelvir/Ritonavir in Chinese Hospitalized Patients With COVID-19: A Multicenter Retrospective Study.

Background: Nirmatrelvir/ritonavir is licensed for the treatment of mild-to-moderate coronavirus disease (COVID-19) in patients at an increased risk of progression to severe disease. However, data on the real-world plasma exposure to nirmatrelvir/ritonavir remain limited, particularly in Chinese patients. This study aimed to assess the nirmatrelvir/ritonavir trough concentration (Ctrough) and identify its critical factors in hospitalized Chinese patients treated with nirmatrelvir/ritonavir 300 mg/100 mg twice daily over a 5-day course.

alleviates ischemia-reperfusion injury in steatotic donor liver by inhibiting ferroptosis via the Foxo3-Alox15 signaling pathway.

Ischemia-reperfusion injury (IRI) is a major obstacle in liver transplantation, especially with steatotic donor livers. Dysbiosis of the gut microbiota has been implicated in modulating IRI, and plays a pivotal role in regulating host inflammatory and immune responses, but its specific role in liver transplantation IRI remains unclear. This study explores whether can mitigate IRI and its underlying mechanisms.

Aging-enhanced autophagy activity promotes fibrotic progression via the TGF-β2/Smad signaling pathway in trabecular meshwork cells-a new insight from POAG.

Introduction: Glaucoma, a leading cause of irreversible blindness, is characterized by optic neuropathy and retinopathy, with primary open-angle glaucoma (POAG) being the most prevalent form. The primary pathogenic mechanism of POAG involves elevated intraocular pressure caused by chronic fibrosis of the trabecular meshwork (TM). Autophagy, a critical process for maintaining cellular homeostasis, has been implicated in fibrosis across various organs.

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.

Prevalence of chronic kidney disease among Chinese adults with diabetes: a nationwide population-based cross-sectional study.

Background: To date, comprehensive data on the distribution of chronic kidney disease (CKD), the most prevalent comorbidity in diabetes, among Chinese adults with diabetes is lacking. Additionally, research gaps exist in understanding the association between CKD and cardiovascular health (CVH), an integrated indicator of lifestyle and metabolic control, within a nationwide sample of Chinese adults with diabetes.

Methods: A nationally community-based cross-sectional survey was conducted in 2018-2020.

Increased cardiac macrophages in -deficient hearts: revealing a potential role for macrophage in responding to embryonic myocardial abnormalities.

Macrophages are known to support cardiac development and homeostasis, contributing to tissue remodeling and repair in the adult heart. However, it remains unclear whether embryonic macrophages also respond to abnormalities in the developing heart. Previously, we reported that the structural protein Sorbs2 promotes the development of the second heart field, with its deficiency resulting in atrial septal defects (ASD).

Association between controlling nutritional status score and the prognosis of patients with acute myocardial infarction: a systematic review and meta-analysis.

Background: Recent studies have reported growing evidence supporting applying the controlling nutritional status (CONUT) score in acute myocardial infarction (AMI) patients. This investigation intended to ascertain the link between CONUT scores and the prognosis in the AMI population.

Methods: Multiple electronic databases, encompassing PubMed, Web of Science, Embase, and the Cochrane Library, were retrieved from the inception of the databases until July 20, 2024, to explore the link between CONUT scores and adverse clinical outcomes in individuals with AMI.

Cardiac resynchronization therapy via left bundle branch pacing in heart failure with complete left bundle branch block: is the defibrillator needed?

Aims: This retrospective cohort study aimed to investigate the efficacy of dual-chamber left Bundle branch pacing (LBBP) as an alternative therapy for heart failure patients with complete left bundle branch block (CLBBB) and indications for defibrillator with cardiac resynchronization therapy (CRT-D).

Methods: 34 patients met inclusion criteria were enrolled in the study. These criteria included a left ventricular ejection fraction (LVEF) of lower than 35%, a New York Heart Association functional class of II-IV, CLBBB meeting Strauss's criteria, intraventricular dyssynchrony, and confirmed correction of CLBBB during LBBP.

Apelin/APJ system: a novel promising target for anti-oxidative stress in stroke.

The apelin/APJ system has garnered increasing attention in recent years. In this review, we comprehensively discuss the physiological and pathological mechanisms of the apelin/APJ system in stroke. The apelin/APJ system is widely expressed in the central nervous system (CNS).

Discovery of Novel Na1.7-Selective Inhibitors with the 1-Indole-3-Propionamide Scaffold for Effective Pain Relief.

Na1.7 is considered a promising target for developing next-generation analgesic drugs, given its critical role in human pain pathologies. Although most reported inhibitors with strong in vitro activity and high selectivity share the aryl sulfonamide scaffold, they failed to demonstrate marked clinical efficacy.

Long COVID facts and findings: a large-scale online survey in 74,075 Chinese participants.

Background: Research on long COVID in China is limited, particularly in terms of large-sample epidemiological data and the effects of recent SARS-CoV-2 sub-variants. China provides an ideal study environment owing to its large infection base, high vaccine coverage, and stringent pre-pandemic measures.

Methods: This retrospective study used an online questionnaire to investigate SARS-CoV-2 infection status and long COVID symptoms among 74,075 Chinese residents over one year.

EZH2 inhibition induces pyroptosis via RHA-mediated S100A9 overexpression in myelodysplastic syndromes.

Myelodysplastic Syndromes (MDS) represent a group of heterogeneous myeloid clonal diseases derived from aberrant hematopoietic stem/progenitor cells. Enhancer of zeste homolog 2 (EZH2) is an important regulator in gene expression through methyltransferase-dependent or methyltransferase-independent mechanisms. Herein, we found EZH2 inhibition led to MDS cell pyroptosis through RNA Helicase A (RHA) down-regulation induced overexpression of S100A9, a key regulator of inflammasome activation and pyroptosis.

The triglyceride-glucose index and its obesity-related derivatives as predictors of all-cause and cardiovascular mortality in hypertensive patients: insights from NHANES data with machine learning analysis.

Background: Hypertension (HTN) is a global public health concern and a major risk factor for cardiovascular disease (CVD) and mortality. Insulin resistance (IR) plays a crucial role in HTN-related metabolic dysfunction, but its assessment remains challenging. The triglyceride-glucose (TyG) index and its derivatives (TyG-BMI, TyG-WC, and TyG-WHtR) have emerged as reliable IR markers.

ADSL promotes autophagy and tumor growth through fumarate-mediated Beclin1 dimethylation.

As an enzyme with a critical role in de novo purine synthesis, adenylosuccinate lyase (ADSL) expression is upregulated in various malignancies. However, whether ADSL possesses noncanonical functions that contribute to cancer progression remains poorly understood. Here, we demonstrate that protein kinase R-like endoplasmic reticulum kinase (PERK) activated by lipid deprivation or ER stress phosphorylates ADSL at S140, leading to an enhanced association between ADSL and Beclin1.

Peer Victimization and School Engagement among Chinese Adolescents: Does Classroom-Level Victimization Matter?

Peer victimization has been demonstrated to have a long-lasting negative impact on adolescents' psychological well-being, yet its impact on school engagement is inconclusive, particularly during high school. In addition, research about the role of classroom-level victimization in the association between individual-level peer victimization and adolescents' school engagement remains underexplored. Previous research has relied solely on self-report measures to assess peer victimization, potentially limiting the scope of understanding.

Bat genomes illuminate adaptations to viral tolerance and disease resistance.

Zoonoses are infectious diseases transmitted from animals to humans. Bats have been suggested to harbour more zoonotic viruses than any other mammalian order. Infections in bats are largely asymptomatic, indicating limited tissue-damaging inflammation and immunopathology.

Mouse gut blueprint: regionality and resilience.

Mayassi and colleagues utilized spatial transcriptomics to create a comprehensive blueprint of the mouse gut, exploring its adaptability and resilience under perturbed conditions. Their work highlights the adaptive capabilities of the murine gut's regionalized structure, providing insights into how it functions in a coordinated manner and how it responds to external challenges.

Prognostic Value of Coronary Angiography-Derived Index of Microcirculatory Resistance in Patients With Intermediate Coronary Stenosis.

Background: The association between coronary microcirculation and clinical outcomes in patients with intermediate stenosis remains unclear.

Objectives: The aim of this study was to assess the prognostic significance of angiography-derived index of microcirculatory resistance (angio-IMR) in patients with intermediate coronary stenosis.

Methods: This post hoc analysis included 1,658 patients from the FLAVOUR (Fractional Flow Reserve and Intravascular Ultrasound for Clinical Outcomes in Patients with Intermediate Stenosis) trial, with angio-IMR measured in each vessel exhibiting intermediate stenosis.

Barriers and facilitators to improved sedentary behaviour in coronary heart disease patients: a scoping review.

Introduction: The majority of patients with coronary heart disease (CHD) are at high sedentary levels, which severely affects patient prognosis and outcome. Despite the proven benefits of reducing sedentary behaviour (SB), intervention studies' effectiveness has been limited. Thus, the factors influencing SB change in patients with CHD need to be explored.

Iontophoresis-driven transdermal drug delivery system based on porous microneedles for hyperuricemia treatment.

An iontophoresis-driven porous microneedles (IPMNs) system has been developed for hyperuricemia management, which can be effectively prolong the anti-hyperuricemia effect. Porous microneedles (PMNs) with good biocompatibility, high porous volume, and excellent substance exchange capacity were firstly prepared for drug transdermal delivery and active iontophoresis.In vitro experiments showed that the transdermal delivery efficiency of anti-hyperuricemia drug (Allopurinol, AP) could be controlled using the iontophoresis current of IPMNs system.