Genome-wide identification of the SAM-dependent methyltransferase members and functional analysis of GmSAMMt30 in soybean (Glycine max) under salt-alkali stress.

Saline-alkali soil poses a severe threat to the cultivation and yield of soybean, which is an important oilseed and staple crop. As a key metabolic intermediate, S-adenosyl-L-methionine (SAM) and its associated methyltransferases (SAMMTs) play crucial but poorly understood roles in plant stress responses. This study investigated the expression of SAM-depend methyltransferase (SAMMt) family in soybean.

Oxidative stress in cancer: from tumor and microenvironment remodeling to therapeutic frontiers.

Oxidative stress is a pathological condition of redox signaling dysregulation and macromolecular oxidative damage arising from elevated ROS levels. Oxidative stress interacts with tumor cell growth regulation and tumor microenvironment remodeling, and has been a critical hallmark of cancer. Targeting oxidative stress has garnered great attention in cancer therapy development.

Protein Spatial Structure Meets Artificial Intelligence: Revolutionizing Drug Synergy-Antagonism in Precision Medicine.

Targeted drug design and development, as a core area of modern pharmaceutical research, critically depends on the assessment of protein site druggability as a fundamental component. This review systematically examines the latest research progress and application prospects of drug synergy and antagonism prediction methods that integrate protein three-dimensional spatial structure with artificial intelligence (AI) technologies. This review showcases the molecular biological mechanisms of drug synergism vs antagonism mediated by transcription factors, signal pathway regulation, and membrane transport proteins, and subsequently delves into the molecular structural basis of protein-drug interactions, including precise identification methods for drug binding sites, optimization strategies for molecular docking techniques, and the mechanisms and structural characteristics of multi-target drugs.

Metabolic checkpoints in immune cell reprogramming: rewiring immunometabolism for cancer therapy.

Immune cell metabolism plays a pivotal role in regulating cellular proliferation, differentiation, and functional responses, collectively shaping immune responses within the tumor microenvironment (TME). Recent advancements increasingly highlight diverse metabolic phenotypes of immune cells and their complex interplay with tumor dynamics. Immune cell metabolism exhibits remarkable plasticity, enabling metabolic networks to finely tune immune cell behaviors in response to external stimuli.

AMPs inhibit the proliferation, migration, and invasion of lung cancer via the CHRM3/PI3K/AKT and CHRM3/MAPK pathways.

Aims: Our previous studies indicated that the overexpression of M3 muscarinic receptor (M3R/CHRM3) is related to a poor prognosis in patients with lung cancer and that polysaccharides (AMPs) can exhibit strong anticancer activity via apoptosis-related mechanisms in lung cancer cells. This study investigated whether AMPs exert anticancer activity through the CHRM3 signaling pathway.

Materials And Methods: Lung cancer cell lines (A549, NCI-H1299, and NCI-H520) with stable overexpression or knockdown of CHRM3 were established by infection with recombinant lentivirus and selected under puromycin for one month.

Relationship between sleep characteristics and aortic aneurysm/dissection: a two-sample Mendelian randomisation study.

Objective: The causal relationship between sleep characteristics and aortic aneurysm and dissection (AAD) is little known.

Methods: In this two-sample Mendelian randomisation (MR) study, we selected seven sleep-related traits (sleep duration, getting up in the morning, chronotype, nap during day, insomnia, snoring, and narcolepsy) from published genome-wide association study (GWAS)-related genetic variants as instrumental variables. Causality was assessed by two-sample MR analysis using inverse-variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple model.

Terrestrial temperature history reveals Late Miocene rapid uplift of the northern Tibetan Plateau.

Paleoaltimetry data are essential for deciphering the growth trajectory of orogenic plateaus and underlying forcing mechanisms. However, paleoaltitude reconstructions using conventional paleotemperature analysis often have low resolution or large calibration uncertainties. Here, we use Group III alkenones, a marine paleothermometer normally not present in terrestrial basins, to reconstruct paleolake temperatures and refine the paleoelevation history of the Qaidam Basin, northern Tibetan Plateau, during the Late Miocene.

Single-cell transcriptomics reveals BMP4-BMPR2 signaling promotes radiation resistance in hematopoietic stem cells following injury.

High doses of ionizing radiation (IR) cause severe damage to the hematopoietic system. However, the heterogeneity of hematopoietic stem and progenitor cells (HSPCs) in response to IR stress remains largely uncharacterized. Here, we present a dynamic single cell transcriptomic landscape and elucidate the complex crosstalk between HSPCs and the bone marrow (BM) microenvironment during IR-induced regeneration process.

Decoding the hepatic fibrosis-hepatocellular carcinoma axis: from mechanisms to therapeutic opportunities.

Background: Hepatocellular carcinoma (HCC) ranks as the sixth most prevalent malignant neoplasm globally and represents the third-leading cause of cancer-associated mortality worldwide. Epidemiological data indicate that 80-90% of HCC cases demonstrate documented progression from hepatic fibrosis or cirrhosis. This fibrotic-carcinogenic continuum represents a complex multistep pathological cascade, with mechanistic insights being progressively revealed through contemporary investigations.

Curvature-tuning membrane mimetics as novel sensing interface to probe affinity fluctuation of bridging integrator 1 protein by SPR.

Curvature-sensitive proteins play important roles in cellular physiology. To study their interaction properties, reliable platforms of curved membrane mimics are key but current systems are limited by the requirement for fluorescent labels, which can modify membrane conformation and activity, leading to obscured description of interaction behavior as compared to native conditions. We report here the construction and application of a robust and tunable curved membrane interface for label-free surface plasmon resonance (SPR) based probing of the interactions with bridging integrator 1 (BIN1), a BAR-domain containing protein that has been linked to cancer and autoimmune diseases.

FLASH Irradiation Modulates Immune Responses and Accelerates Lung Recovery: A Single-Cell Perspective.

Radiation therapy (RT) is essential for treating thoracic malignancies but often causes significant lung damage. FLASH-RT, an ultra-high dose rate irradiation technique, shows potential in reducing radiation-induced lung injury (RILI) while maintaining tumor control. However, the underlying immune mechanisms remain poorly understood.

Identification of potential drug targets for erectile dysfunction with single-cell RNA sequencing: A Mendelian randomization study.

Background: A subset of patients with erectile dysfunction (ED) responds poorly to current pharmacological treatments, largely due to the limited availability of well-defined therapeutic targets beyond phosphodiesterase 5 inhibitors (PDE5i).

Methods: This study used Mendelian randomization (MR) to identify potential therapeutic targets for ED. Cis-expression quantitative trait loci (cis-eQTL) were sourced from the eQTLGen Consortium (31,684 individuals).

Performance analysis of large language models in multi-disease detection from chest computed tomography reports: a comparative study.

Background: Computed tomography (CT) is widely acknowledged as the gold standard for diagnosing thoracic diseases. However, the accuracy of interpretation significantly depends on radiologists' expertise. Large language models (LLMs) have shown considerable promise in various medical applications, particularly in radiology.

Microbiota boost immunotherapy? A meta-analysis dives into fecal microbiota transplantation and immune checkpoint inhibitors.

Background: Immune checkpoint inhibitors (ICIs) are a cornerstone of modern cancer treatment, but their effectiveness is limited. Fecal microbiota transplantation (FMT), which alters the gut microbiome, has shown promise in enhancing ICIs' therapeutic effects.

Methods: We conducted a comprehensive search of relevant studies available up to September 30, 2024, to analyze the clinical efficacy and safety of combining FMT with ICIs in cancer treatment.

Immunotherapy-induced cholestasis in cancer: insights from the two real-world pharmacovigilance databases of FAERS and VigiBase.

Background: The US Food and Drug Administration (FDA) recently issued a safety alert regarding cholestasis as a potential adverse reaction to immune checkpoint inhibitor (ICI) therapy. However, the underlying mechanisms of ICI-induced cholestasis remain poorly elucidated.

Methods: This study analyzed adverse event reports of cancer patients treated with ICIs, extracted from the FAERS (2013-2023) and VigiBase (1968-2023) databases.

RBM15 promotes m6A methylation and stability of KLF6 mRNA to accelerate pyroptosis of retinal ganglion cells in early-stage diabetic retinopathy.

Neurodegeneration in early-stage diabetes retinopathy (DR) is mainly caused by the loss of retinal ganglion cells (RGCs), and high glucose-treated cell pyroptosis contributes to an important cause. However, the detailed molecular regulatory mechanism has not yet been thoroughly examined. In this study, primary mouse RGCs were stimulated with different concentrations of glucose, and mouse was intraperitoneally injected with streptozotocin (STZ) to construct DR model in vitro and in vivo.

Natural Killer Cell Immune Checkpoints and Their Therapeutic Targeting in Cancer Treatment.

Natural killer (NK) cells, serving as pivotal mediators of innate immunity, play an important role in antitumor immunity. Immune checkpoint can be expressed on the surface of NK cells and meticulously regulates their activation states and effector functions through complex signaling networks. In recent years, tumor immunotherapy strategies focusing on NK cell immune checkpoints have demonstrated remarkable advancements.

Total and regional fat-to-muscle mass ratio and risks of pan-cancer: a prospective cohort study.

Background: The fat-to-muscle mass ratio (FMR) has served as a marker for various diseases. This study aimed to explore sex-specific associations between FMR in different body regions (whole body, trunk, arm, and leg) and cancer incidence.

Methods: We included 435,986 cancer-free participants (203,133 men and 232,853 women) from the UK Biobank at baseline.

Evaluating generative AI models for explainable pathological feature extraction in lung adenocarcinoma: grading assessment and prognostic model construction.

Background: Given the increasing prevalence of generative AI (GenAI) models, a systematically evaluation of their performance in lung adenocarcinoma histopathological assessment is crucial. This study aimed to evaluate and compare three visual-capable GenAI models (GPT-4o, Claude-3.5-Sonnet, and Gemini-1.

Cancer-associated fibroblast-derived SEMA3C facilitates colorectal cancer liver metastasis via NRP2-mediated MAPK activation.

Liver metastasis remains the predominant cause of mortality in patients with colorectal cancer (CRC). Nevertheless, the mechanisms underlying the initiation of colorectal cancer liver metastasis remain poorly elucidated. During the metastatic process of CRC cells from the primary site to the liver, we performed time-resolved analyses and identified a subset of tumor cells spatially located in the primary tumor and temporally distributed in the early stages of liver metastasis.

Prolonged exposure to leisure screen time notably accelerates biological aging: Evidence from observational studies and genetic associations.

LST is steadily increasing and is associated with various health issues. However, its impact on aging remains unclear. A total of 7212 participants from NHANES 1999-2002 were included.

An extremely rare case of Rosai-Dorfman-Destombes disease in the spleen with secondary thrombocytopenia: a case report.

Background: Rosai-Dorfman-Destombes disease (RDD), also known as sinus histiocytosis with massive lymphadenopathy, is a rare, multisystemic histiocytic disorder. It can affect multiple organs, including bones, the brain, nasal cavities, and breasts. But, RDD in the spleen with secondary thrombocytopenia is extremely rare.

Macrophage-derived exosomes in cancer: a double-edged sword with therapeutic potential.

Solid cancer contains a complicated communication network between cancer cells and components in the tumor microenvironment (TME), significantly influencing the progression of cancer. Exosomes function as key carriers of signaling molecules in these communications, including the intricate signalings of tumor-associated macrophages (TAMs) on cancer cells and the TME. With their natural lipid bilayer structures and biological activity that relates to their original cell, exosomes have emerged as efficient carriers in studies on cancer therapy.