Hypoxia-induced HIF1A impairs sorafenib sensitivity in hepatocellular carcinoma through NSUN2-mediated stabilization of GDF15.

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. Although sorafenib is a first-line systemic therapy for advanced HCC, resistance to treatment remains a major challenge. Hypoxia is a hallmark of the tumor microenvironment and is known to promote tumor growth and progression; however, its role in modulating sorafenib response in HCC remains poorly understood.

KLF5 Regulation of Exosome-Derived miR-152-3p From Bone Marrow Stem Cells Improves Ventricular Arrhythmia After Myocardial Infarction.

Cardiac fibroblasts (CFs) are activated into cardiac myofibroblasts (CMFs) in myocardial infarction (MI) and promote fibrosis, playing a crucial role in deteriorating cardiac function and inducing fatal arrhythmias. Transplantation of bone marrow mesenchymal stem cells (BMSCs) has emerged as a promising therapeutic approach for ischemic heart diseases, including MI. Recent studies have indicated that BMSCs can modulate the survival, differentiation, and antifibrotic activity of CFs.

Meta_B cells: a computationally identified candidate immunosuppressive driver of gastric cancer metastasis revealed by single-cell analysis and machine learning.

Background: Gastric cancer (GC) metastasis remains a major clinical challenge due to insufficient understanding of tumor microenvironment (TME) dynamics. While B cells are implicated in GC progression, their subset-specific roles in metastatic niches are poorly defined.

Methods: We analyzed gastric cancer (GC) single-cell RNA-seq data from the GEO database (GSE163558), complemented by bulk RNA-seq analysis of TCGA-STAD cohorts.

Advanced strategy for cancer detection based on volatile organic compounds in breath.

The analysis of volatile organic compounds (VOCs) in exhaled breath has emerged as a promising non-invasive approach for cancer diagnosis, offering advantages in speed, safety, cost-effectiveness, and real-time monitoring. Two primary methodologies are employed for VOCs detection: mass spectrometry (MS)-based techniques, which provide high-precision identification and quantification of individual compounds, and sensor-based pattern recognition methods, which detect disease-specific VOC signatures. Despite their diagnostic potential, inconsistencies in accuracy highlight the need for a comprehensive evaluation of these techniques.

Membrane-initiated estrogen receptor-α signaling in osteoblasts is crucial for normal regulation of the cortical bone in female mice.

Membrane-initiated estrogen receptor α (mERα) signaling has been shown to affect bone mass in murine models. However, it remains unknown which cell types mediate the mERα-dependent effects on bone. In this study, we generated a novel mouse model with a conditional C451A mutation in Esr1, which enables selective knockout of the palmitoylation site essential for the membrane localization of ERα (C451A).

Adipose-derived stem cell exosomes alleviate TGF-β1-induced urethral stricture fibrosis by suppressing the TGF-β/Smad pathway and downstream PDGFR-β/RAS/ERK signaling.

This study aimed to investigate the therapeutic effects and underlying mechanisms of adipose-derived stem cell exosomes (ADSCs-exo) in ameliorating fibrosis in a rat model. ADSCs were isolated and cultured from rat adipose tissue, and ADSCs-exo were extracted via ultracentrifugation. Urethral fibrosis was induced by local injection of TGF-β1 (10 μg), followed by ADSCs-exo treatment.

Effect of Telemedicine-Supported Structured Exercise Program in Patients with Chronic Low Back Pain: Study Protocol for a Randomized Controlled Trial.

Purpose: Telemedicine-based structured exercise programs have the potential to benefit patients with chronic low back pain (CLBP). However, evidence-practice gaps persist, including low exercise adherence and insufficient focus on mental health. Consequently, further research is warranted to clarify the impact of telemedicine-supported structured exercise programs on patients with CLBP.

Accelerating IND-enabling toxicology studies using protein products from stable pools or pools of clones in Chinese hamster ovary cells.

In recent years, accelerating Chemistry, Manufacturing, and Controls (CMC) workflows for clinical entry has become a critical focus in biologics development. Advances in the development of cell lines, cell culture processes, and analytical technologies have enabled the generation of more homogeneous stable pool populations with increased productivity. Leveraging the experience gained from the COVID-19 product development, the strategic use of stable cell pools or a pool of clones for early-stage non-GMP material generation and process development has proven transformative in significantly reducing the CMC timeline to investigational new drug (IND).

Systematic Review and Meta-Analysis of the Association Between Clinical Severity and Co-Infection of Human Adenovirus With Other Respiratory Pathogens in Children.

The correlation between the co-infection of human respiratory adenovirus (HAdV) and clinical severity has not been firmly established yet. We carried out a systematic review and meta-analysis. We scoured six databases for studies published up to 16 May 2024.

Arterial-venous differences of brain-derived neurotrophic factor isoforms across the brain and muscle after exercise at different intensities.

Brain-derived neurotrophic factor (BDNF) is essential for neuroplasticity. Exercise can induce increases in forearm venous plasma and serum BDNF, often assumed to be indicative of release from the brain. We investigated the effects of exercise on circulating levels of mature BDNF (mBDNF) and its precursor proBDNF.

Pirfenidone Ameliorates Hypertrophic Scar Through Inhibiting Proliferation and Migration of Fibroblasts by Regulating the Wnt/GSK-3β/β-Catenin Signaling Pathway.

Hypertrophic scar (HS) is a prevalent complication that arises from burn injuries. While Pirfenidone (PFD) is known to be an effective antifibrotic agent, its precise effects on HS caused by burn injuries are still unclear. This study was to assess the influence of PFD on HS fibroblasts and investigate the underlying mechanism.

Neighbor-Guided Unbiased Framework for Generalized Category Discovery in Medical Image Classification.

Generalized category discovery (GCD) utilizes seen category knowledge to automatically discover new semantic categories that are not defined in the training phase. Nevertheless, there has been no research conducted on identifying new classes using medical images and disease categories, which is essential for understanding and diagnosing specific diseases. Moreover, existing methods still produce predictions that are biased towards seen categories since the model is mainly supervised by labeled seen categories, which in turn leads to sub-optimal clustering performance.

Artificial Intelligence in Endoscopy for Predicting Helicobacter pylori Infection: A Systematic Review and Meta-Analysis.

Purpose: This meta-analysis aimed to assess the diagnostic performance of artificial intelligence (AI) based on endoscopy for detecting Helicobacter pylori (H. pylori) infection.

Methods: A comprehensive literature search was conducted across PubMed, Embase, and Web of Science to identify relevant studies published up to January 10, 2025.

Genome sequencing enhances the diagnostic yield and expands the genetic landscape of male breast cancer.

Purpose: To understand the broader genetic landscape of male breast cancer (MBC), focusing on the utility of genome sequencing (GS) beyond (HGNC: 1100, 1101) variants.

Methods: Twenty-four patients with MBC underwent a multistep genetic analysis. Initial screening targeted variants followed by GS to identify pathogenic/likely pathogenic germline variants through a 3-tiered classification.

The beneficial effects of a probiotic mix on bone and lean mass are dependent on the diet in female mice.

Bone mass and lean mass decrease with age and these changes are associated with increased fracture risk and sarcopenia. Previous studies demonstrated that a probiotic mixture of Lacticaseibacillus paracasei DSM13434, Lactiplantibacillus plantarum DSM 15312 and DSM 15313 (L. Mix) prevents bone loss in ovariectomized (ovx) female mice.

Modifiable factors for irritable bowel syndrome: evidence from Mendelian randomisation approach.

Background: The potential modifiable factors influencing irritable bowel syndrome (IBS) have not been thoroughly documented. We aimed to systematically investigate the modifiable factors associated with IBS, while accounting for the impact of unobserved confounders and coexisting disorders.

Methods: Genetic correlation and Mendelian randomisation (MR) analyses were integrated to identify potential modifiable factors and coexisting disorders linked to IBS.

Factors Influencing Preoperative Psychological Resilience in Patients With Traumatic Lower Extremity Fractures.

Background: The psychological resilience of patients with traumatic lower extremity fractures is relevant and has been studied in the postoperative rehabilitation phase; yet, few studies have focused on the early preoperative phase.

Objective: This study aims to explore preoperative psychological resilience in patients with traumatic lower extremity fractures.

Methods: This single-center cross-sectional survey design study was conducted over 5 months from December 2022 to April 2023 in a tertiary hospital in Shanghai, China.

Quercetin Alleviates Cardiac Fibrosis via Regulating the SIRT3 Signaling Pathway.

Purpose: Cardiovascular diseases, exacerbated by cardiac fibrosis, are the leading causes of mortality. We aimed to determine the role of quercetin (QU) in cardiac fibrosis and the underlying mechanism.

Methods: In this study, 8-week-old mice were subjected to either transverse aortic constriction (TAC) or sham surgery, then they were administered QU or saline.

Exosome-loaded biomaterials for tendon/ligament repair.

Exosomes, a specialised type of extracellular vesicle, have attracted significant attention in the realm of tendon/ligament repair as a potential biologic therapeutic tool. While the competence of key substances responsible for the delivery function was gradually elucidated, series of shortcomings exemplified by the limited stability still need to be improved. Therefore, how to take maximum advantage of the biological characteristics of exosomes is of great importance.

Plasma markers of neurodegeneration, latent cognitive abilities and physical activity in healthy aging.

Blood-based biomarkers of neurodegeneration demonstrate great promise for the diagnosis and prognosis of Alzheimer's disease. Ultra-sensitive plasma assays now allow for quantification of the lower concentrations in cognitively unimpaired older adults, making it possible to investigate whether these markers can provide insight also into the early neurodegenerative processes that affect cognitive function and whether the markers are influenced by modifiable risk factors. Adopting an exploratory approach in 93 healthy older adults (65-75 years), we used structural equation modelling to investigate cross-sectional associations between multiple latent cognitive abilities (working memory, episodic memory, spatial and verbal reasoning) and plasma amyloid beta (Aβ42/Aβ40 ratio), phosphorylated-tau 181 (ptau-181), glial fibrillary acidic protein (GFAP), and neurofilament light (NfL), as well as the influence of device-measured habitual physical activity on these associations.

Photoreceptor-targeted extracellular vesicles-mediated delivery of Cul7 siRNA for retinal degeneration therapy.

Photoreceptor loss is a primary pathological feature of retinal degeneration (RD) with limited treatment strategies. RNA interference (RNAi) has emerged as a promising method of gene therapy in regenerative medicine. However, the transfer of RNAi therapeutics to photoreceptors and the deficiency of effective therapeutic targets are still major challenges in the treatment of RD.

The association between urinary sodium and the risk of dementia: Evidence from a population-based cohort study.

Background: Sodium intake reduction is crucial for cardiovascular health, however, its lasting impact on dementia remains unclear.

Methods: We included 458,577 UK Biobank participants without dementia at baseline. We estimated 24-h urinary sodium (E24hUNa) using spot urinary parameters and obtained the incidence of all-cause dementia, Alzheimer's disease, and vascular dementia from multiple sources.