Mendelian randomization leverages genetic variants to mitigate confounding bias in causal inference. This paper systematically reviews the methodological evolution of Mendelian randomization, elaborates on its expanding applications in epidemiology and drug target validation, and identifies future research directions to address existing biases via dynamic analysis, multi-omics integration, and trans-ethnic data harmonization.

Researchers at Pennington Biomedical Research Center have identified a key brain mechanism that connects environmental temperature with appetite and energy balance, offering new insight into how external conditions can shape body weight over time.

The findings, published in the journal Communications Biology, highlight a group of neurons that act as a critical integration point between thermoregulation – the body’s ability to maintain its internal temperature – and the systems that control hunger and metabolism.

GAnnoViz a cloud-integrated framework for chromosome-level feature annotation and visualization in biomedical multi-omics. Encompassing 30+ analytical and visualization modules across five key areas: acquisition of species genomic annotations, extraction of genomic features, drawing of gene structures, sliding window annotation, and chromosome-scale visualization of multi-omics. It supports genomic annotation retrieval for 349 species from Ensembl, newly assembled genome with GFF3 or GTF format, and an interactive interface deployed on the HiPlot cloud platform.

Building on recent advances in skull marrow–meningeal channel research, this article summarizes the developmental remodeling of skull bone channels, RANKL/TRPV4-associated osteoclast regulation, and their effects on meningeal immune-cell trafficking during neuroinflammation. It further proposes a putative craniomaxillary–brain interface to explore how oral and craniofacial tissues may influence CNS-border immunity through local osseous/vascular, trigeminal neuroimmune, and systemic inflammatory routes. The article also discusses relevant imaging and tracing approaches, translational potential, and current limitations, while emphasizing that direct functional connectivity between craniomaxillary bone and the meninges remains unproven and requires validation through anatomical tracing, source-to-destination cell tracking, and disease models.

Gastric cancer remains one of the most common causes of cancer-related death worldwide, causing an estimated 660,000 deaths in 2022, and more than 70% of patients are diagnosed at an advanced stage. Although immune checkpoint blockade has transformed cancer immunotherapy, its efficacy in gastric cancer remains limited, with response rates below 20% in unselected cohorts. Tumor progression necessitates the metabolic reprogramming of cancer cells, and metabolic alterations together with immune dysfunction critically drive gastric cancer progression and therapeutic resistance. However, the metabolic landscapes of tumor cells and their interplay with immune components remain underexplored.

Glucagon-like peptide-1 (GLP-1) is secreted by intestinal L cells in response to postprandial glucose, yet how glucose triggers this secretion has remained unclear. Here, the authors show that glucose itself acts as a ligand for glucokinase (GK), independent of its metabolism. Glucose-bound GK directly interacts with and inhibits K_ATP channels, leading to membrane depolarization and GLP-1 release without any increase in intracellular ATP. This mechanism is distinct from the classical ATP-dependent model and is validated by GK mutations found in MODY2 patients. The study also reveals that SGLT1 mediates basal GLP-1 secretion at low glucose, while the GK-K_ATP axis drives the postprandial response at high glucose. These findings redefine glucose as a signaling molecule and GK as its receptor, offering new therapeutic avenues for diabetes and obesity.