Heat acclimation defense against exertional heat stroke by improving the function of preoptic TRPV1 neurons.

Record-breaking heatwaves caused by greenhouse effects lead to multiple hyperthermia disorders, the most serious of which is exertional heat stroke (EHS) with the mortality reaching 60 %. Repeat exercise with heat exposure, termed heat acclimation (HA), protects against EHS by fine-tuning feedback control of body temperature (Tb), the mechanism of which is opaque. This study aimed to explore the molecular and neural circuit mechanisms of the HA training against EHS.

Catalytic-independent functions of the Integrator-PP2A complex (INTAC) confer sensitivity to BET inhibition.

Chromatin and transcription regulators are critical to defining cell identity through shaping epigenetic and transcriptional landscapes, with their misregulation being closely linked to oncogenesis. Pharmacologically targeting these regulators, particularly the transcription-activating BET proteins, has emerged as a promising approach in cancer therapy, yet intrinsic or acquired resistance frequently occurs, with poorly understood mechanisms. Here, using genome-wide CRISPR screens, we find that BET inhibitor efficacy in mediating transcriptional silencing and growth inhibition depends on the auxiliary/arm/tail module of the Integrator-PP2A complex (INTAC), a global regulator of RNA polymerase II pause-release dynamics.

Establishment and internal validation of a model to predict the efficacy of Adalimumab in Crohn's disease.

Background: Clinically, the ability to distinguish which Crohn's disease patients can benefit from Adalimumab is limited.

Aims: This study aimed to develop a model for predicting clinical remission probability for Crohn's disease patients with Adalimumab at 12 weeks. The model assists clinicians in identifying which Crohn's disease patients are likely to benefit from Adalimumab treatment before starting therapy, thus optimizing individualized treatment strategies.

Chimeric antigen receptor with novel intracellular modules improves antitumor performance of T cells.

The excessive cytokine release and limited persistence represent major challenges for chimeric antigen receptor T (CAR-T) cell therapy in diverse tumors. Conventional CARs employ an intracellular domain (ICD) from the ζ subunit of CD3 as a signaling module, and it is largely unknown how alternative CD3 chains potentially contribute to CAR design. Here, we obtained a series of CAR-T cells against HER2 and mesothelin using a domain comprising a single immunoreceptor tyrosine-based activation motif from different CD3 subunits as the ICD of CARs.

A practical distribution pattern of α-SMA-positive carcinoma associated fibroblasts indicates poor prognosis of patients with pancreatic ductal adenocarcinoma.

Purpose The present study aimed to clarify the distribution pattern of carcinoma associated fibroblasts (CAFs) across pancreatic ductal adenocarcinoma (PDAC) and its prognostic prediction value. Methods Data of two cohorts were retrospectively collected from consecutive patients who underwent primary pancreatic resection from January 2015 to December 2017. We used tumor specimens to screen out the most suitable markers for the spatial distribution analysis for CAFs subpopulations.

Effects of minocycline on patients with acute anterior circulation ischaemic stroke undergoing intravenous thrombectomy (MIST-A): the study protocol for a multicentre, prospective, randomised, open-label, blinded-endpoint trial.

Introduction: Despite the implementation of mechanical thrombectomy, acute ischaemic stroke with large vessel occlusion (AIS-LVO) remains a significant health concern, characterised by substantial morbidity and mortality. Our trial aims to evaluate the efficacy and safety of minocycline in reducing infarct volume and improving functional outcomes in patients undergoing mechanical thrombectomy for anterior circulation AIS-LVO.

Methods And Analysis: The MIST-A trial is a prospective, randomised, open-label, blinded-endpoint trial to be conducted across 12 medical centres.

Autophagy in brain tumors: molecular mechanisms, challenges, and therapeutic opportunities.

Autophagy is responsible for maintaining cellular balance and ensuring survival. Autophagy plays a crucial role in the development of diseases, particularly human cancers, with actions that can either promote survival or induce cell death. However, brain tumors contribute to high levels of both mortality and morbidity globally, with resistance to treatments being acquired due to genetic mutations and dysregulation of molecular mechanisms, among other factors.

Amantadine modulates novel macrophage phenotypes to enhance neural repair following spinal cord injury.

Background: Spinal cord injury (SCI) triggers a complex inflammatory response that impedes neural repair and functional recovery. The modulation of macrophage phenotypes is thus considered a promising therapeutic strategy to mitigate inflammation and promote regeneration.

Methods: We employed microarray and single-cell RNA sequencing (scRNA-seq) to investigate gene expression changes and immune cell dynamics in mice following crush injury at 3 and 7 days post-injury (dpi).

Constructing the Well Regenerated Decellularized Adipose Tissue Using External Volume Expansion Device.

Background: External volume expansion (EVE) devices has been demonstrated to enhance the survival of fat grafts. Decellularized adipose tissue (DAT) serves as a promising scaffold for adipose regeneration; however, the effectiveness of adipose regeneration in DAT remains limited, and the underlying mechanisms of its regeneration require further investigation.

Objective: This study explores the potential of EVE technology to enhance DAT-mediated adipogenesis by facilitating cellular recruitment and establishing a microenvironment conducive to adipose tissue regeneration.

Modulating the gut microbiota: A novel perspective in colorectal cancer treatment.

Colorectal cancer (CRC), the second leading cause of cancer-related deaths worldwide, is intricately linked to the dysregulation of the gut microbiota. Manipulating the gut microbiota has emerged as a novel strategy for the prevention and treatment of CRC. Natural products, a pivotal source in new drug discovery, have shown promise in recent research as regulators of the gut microbiota, offering potential applications in the prevention and treatment of CRC.

The immune-related gene CD5 is a prognostic biomarker associated with the tumor microenvironment of breast cancer.

The occurrence and progression of breast cancer (BCa) are complex processes involving multiple factors and multiple steps. The tumor microenvironment (TME) plays an important role in this process, but the functions of immune components and stromal components in the TME require further elucidation. In this study, we obtained the RNA-seq data of 1086 patients from The Cancer Genome Atlas (TCGA) database.

Assessing the clinical utility of tumor invasion proportion of lymph nodes for enhanced risk stratification in N1 colorectal cancer.

N staging systems are paramount clinical features for colorectal cancer (CRC). In N1 stage (N1) CRC, patients present with a limited number of metastatic lymph nodes, yet their prognoses vary widely. The tumor invasion proportion of lymph nodes (TIPLN) has gained attention, but its prognostic value in N1 CRC remains unclear.

Chinese guidelines for the diagnosis and treatment of rheumatoid arthritis: 2024 update.

Rheumatoid arthritis (RA) is an autoimmune disease with destructive arthritis as its main clinical manifestation, which is a major cause of disability. It is very important to formulate and update a guideline for the diagnosis and treatment of RA that adhere to international guideline development standards and can be applied to clinical practice in China. This guideline is endorsed and developed by the National Clinical Research Center for Dermatologic and Immunologic Diseases, collaborated with Rheumatologists Branch of Chinese Medical Doctor Association, Rheumatology Rehabilitation Branch of Chinese Association of Rehabilitation Medicine, Rheumatology Branch of Chinese Research Hospital Association, and Rheumatology Branch of Beijing Association of Holistic Integrative Medicine, based on grading of recommendations assessment, development and evaluation (GRADE) and reporting items for practice guidelines in healthcare (RIGHT).

Suppressing the progression of bladder cancer using cyclovirobuxine D based on network pharmacology and bioinformatics approaches.

Limited treatment options are available for bladder cancer (BCa) resulting in extremely high mortality rates. Cyclovirobuxine D (CVB-D), a naturally alkaloid, reportedly exhibits notable antitumor activity against diverse tumor types. However, its impact on CVB-D on BCa and its precise molecular targets remain unexplored.

Brain with coexistent acoustic schwannoma and ependymoma.

Background: This particular case is a world-first with no previous literature reports on patients presenting with both benign acoustic schwannoma and malignant ependymoma.

Case Presentation: A 60-year-old woman with unexplained right-sided hearing loss that had worsened progressively over 4 years, along with intermittent dizziness that had begun 3 years prior. Our preliminary diagnosis included: (1) Right acoustic neuroma; (2) Ependymoma of the fourth ventricle; and (3) Hydrocephalus.

Lower respiratory tract microbiome dysbiosis impairs clinical responses to immune checkpoint blockade in advanced non-small-cell lung cancer.

Background: Gut microbiome on predicting clinical responses to immune checkpoint inhibitors (ICIs) has been discussed in detail for decades, while microecological features of the lower respiratory tract within advanced non-small-cell lung cancer (NSCLC) are still relatively vague.

Methods: During this study, 26 bronchoalveolar lavage fluids (BALF) from advanced NSCLC participants who received immune checkpoint inhibitor monotherapy were performed 16S rRNA sequencing and untargeted metabolome sequencing to identify differentially abundant microbes and metabolic characteristics. Additionally, inflammatory cytokines and chemokines were also launched in paired BALF and serum samples by immunoassays to uncover their underlying correlations.

Genetic variants in PD-1 and its ligands, gene-gene and gene-environment interactions in allergic rhinitis.

Background: The etiology of allergic rhinitis (AR), in which genetic and environmental factors are closely intertwined, has not yet been completely clarified. Programmed cell death 1 (PD-1) and its ligands (PD-L1 and PD-L2) regulate the immune and inflammatory responses during the development of immune-related and atopic diseases. To clarify the associations of genetic variants in PD-1, PD-L1 and PD-L2 with susceptibility to AR, gene-gene and gene-environment interactions were investigated.

Advancement of 3D biofabrication in repairing and regeneration of cartilage defects.

Three-dimensional (3D) bioprinting, an additive manufacturing technology, fabricates biomimetic tissues that possess natural structure and function. It involves precise deposition of bioinks, including cells, and bioactive factors, on basis of computer-aided 3D models. Articular cartilage injurie, a common orthopedic issue.

Long-term glucosamine supplementation aggravates atrial fibrillation susceptibility by impairing AMPK signaling.

Aims: Glucosamine, a widely used dietary supplement, has been linked to potential cardiovascular risks, including atrial fibrillation (AF). This study aimed to investigate the effects of long-term glucosamine supplementation on AF susceptibility and the underlying mechanisms.

Materials And Methods: C57BL/6 J mice were treated with low-dose (15 mg/kg/day) or high-dose (250 mg/kg/day) glucosamine via drinking water for 6 weeks.

Early identification of potentially reversible cancer cachexia using explainable machine learning driven by body weight dynamics: a multicenter cohort study.

Background: Cachexia is associated with multiple adverse outcomes in cancer. However, clinical decision-making for oncology patients at the cachexia stage presents significant challenges.

Objectives: This study aims to develop a machine learning (ML) model to identify potentially reversible cancer cachexia (PRCC).

Importance of clinical trials and contributions to contemporary medicine: commentary.

Clinical trials are crucial to contemporary medicine, offering valuable insights into the safety, efficacy, and appropriate use of new treatments. They contribute to public health improvements, reduce healthcare costs, uncover new understandings of disease biology, and facilitate the development of therapies for rare conditions. Investing in clinical trials is therefore essential for advancing medical science and enhancing patient outcomes globally.

A Novel Prognostic Risk Model Based on Oxidative Stress to Predict Survival and Improve Treatment Strategies in Stomach Adenocarcinoma.

Background: Stomach adenocarcinoma (STAD) is the fifth most common tumor worldwide, imposing a significant disease burden on populations, particularly in Asia. Oxidative stress is well-known to play an essential role in the occurrence and progression of malignancies. Our study aimed to construct a prediction model by exploring the correlation between oxidative stress-related genes and the prognosis of patients with STAD.

Mangiferin Attenuates Myocardial Ischemia Reperfusion Injury by Regulating the GAS6/Axl Signaling Pathway.

Ischemia reperfusion-induced myocardial injury is a prominent pathological feature in patients with coronary artery disease, contributing to significant mortality and morbidity rates. Mangiferin (MGF), the main active ingredient extracted from Anemarrhena asphodeloides Bge, has anti-inflammatory, anti-oxidation, anti-diabetes, and anti-tumor effects. The present study confirmed that the GAS6/Axl pathway was identified as a promising novel target for the treatment of myocardial ischemia reperfusion (IR) injury.

Genetically engineered biomimetic ATP-responsive nanozyme for the treatment of cardiac fibrosis.

Background: Cardiac fibrosis plays a critical role in the progression of various forms of heart disease, significantly increasing the risk of sudden cardiac death. However, currently, there are no therapeutic strategies available to prevent the onset of cardiac fibrosis.

Methods And Results: Here, biomimetic ATP-responsive nanozymes based on genetically engineered cell membranes are adapted to specifically recognize activated cardiac fibroblasts (CFs) for the treatment of cardiac fibrosis.