The tumor immune microenvironment (TIME) is closely associated with tumor formation, particularly linked to the human papillomavirus (HPV), and regulates tumor initiation, proliferation, infiltration, and metastasis. With the rise of immunotherapy, an increasing amount of sample data used for TIME exploration is available in databases. However, no currently available web tool enables a comprehensive exploration of the TIME of HPV‐associated cancers by leveraging these data. We have developed a web tool called HPV‐associated Tumor Immune MicroEnvironment ExploreR (HPVTIMER), which provides a comprehensive analysis platform that integrates over 10,000 genes and 2290 tumor samples from 65 transcriptome data sets across 8 cancer types sourced from the Gene Expression Omnibus (GEO) database. The tool features four built‐in analysis modules, namely, the differential expression analysis module, correlation analysis module, immune infiltration analysis module, and pathway analysis module. These modules enable users to perform systematic and vertical analyses. We used several analytical modules in HPVTIMER to briefly explore the role of CDKN2A in head and neck squamous cell carcinomas. We expect that HPVTIMER will help users explore the immune microenvironment of HPV‐associated cancers and uncover potential immune regulatory mechanisms and immunotherapeutic targets. HPVTIMER is available at http://www.hpvtimer.com/.

Environmental chemicals are rarely considered stressors in the way that psychological or physical stressors are. Yet many endocrine-disrupting chemicals (EDCs) interact with the body’s core stress response system. This review examines how EDCs alter hypothalamic–pituitary–adrenal (HPA) regulation and how biological sex influences those responses. Drawing on human epidemiological data and experimental models, we describe how EDC exposure affects cortisol dynamics, feedback sensitivity, and adrenal signaling, with a particular focus on sex-dependent outcomes. We propose the concept of endocrine noise to describe how low-dose, often mixed EDC exposures introduce persistent interference into hormone signaling without necessarily causing overt endocrine deficiency or excess. In this framework, EDCs act as chronic, low-grade stressors that reset the timing, feedback precision, and rhythmic organization of the HPA axis rather than as isolated reproductive toxicants. We argue that EDCs should be understood as chronic, context-dependent stress modifiers that reshape sex-specific “risk architectures” for affective, metabolic, and immune disorders. Recognizing sex-specific HPA architecture and endocrine noise has immediate implications for study design and regulation, including the need for sex-stratified analyses, circadian-sensitive sampling of cortisol, and risk assessments that consider how the same exposure can push female and male stress systems in divergent directions.

This study challenges prior findings by demonstrating that CCN5 knockout mice maintain normal body weight and glucose tolerance on a chow diet but exhibit impaired β-cell expansion. Strikingly, under a high-fat diet, male knockout mice display enhanced glucose tolerance without compromising β-cell compensation. These results suggest that CCN5’s influence on metabolism is context-dependent, shaped by both diet and sex, and may critically modulate metabolic outcomes through its regulatory effects on β-cells.

Click on the article title to read more.