Heterogeneity of microbiome responses to menopausal hormone therapy among perimenopausal women.

November 3, 2026| Source: Nature medicine

Menopausal hormone therapy (MHT) alleviates climacteric symptoms, yet its microbiome-wide effects and efficacy determinants remain unclear. Here we show that oral estradiol/dydrogesterone, given for 6 months to 356 perimenopausal women, improved neuroendocrine, metabolic and symptom outcomes and induced site-specific microbial remodeling. Vaginocervical and urinary niches showed the most pronounced restructuring, with moderate oral and minimal gut changes. MHT increased vaginocervical Lactobacillus crispatus and reduced Gardnerella vaginalis. Higher baseline vaginocervical L. crispatus predicted greater postintervention vaginocervical and urinary colonization and superior Female Sexual Function Index improvement. Baseline vaginocervical community types determined differential outcomes: G. vaginalis-dominated individuals shifted most toward healthier communities, whereas diversified individuals improved least. MHT efficacy also varied according to baseline gut community type: Phocaeicola vulgatus-dominated women exhibited greater hormonal responsiveness, superior clinical outcomes and were more likely to achieve 4-week rapid clinical remission than Prevotella copri-dominated women. These findings support a precision MHT framework integrating gut and vaginocervical community typing for personalized care. Chictr.org.cn ID: ChiCTR2100049768 .

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Spontaneous gas film expansion at an oil-water interface.

Spontaneous interfacial separation of oil and water, by inserting a gas film between the two liquids, is thermodynamically unfavorable because the oil-water interface is replaced by oil-gas and water-gas interfaces with a higher combined interfacial energy. Here, we demonstrate that microstructural confinement enables this transition after bubble introduction through the coupling of wetting, capillarity, and gas transport. Spontaneous oil imbibition into a water-submerged micropillar array, toge

Health & MedicineNovember 10, 2026

Senescent CD8 T effector memory cells are functionally impaired, enriched in aging and disease, and a barrier to immunotherapy.

Senescent cells play important roles in various biological processes that promote fitness and health; however, their timely elimination by immune cells is critical to maintain tissue homeostasis and prevent disease. Despite this, senescent cells accumulate systemically with age, suggesting that certain immune cells also become senescent and dysfunctional during aging. In support of this, we previously demonstrated that CD8 T cells, immune cells capable of targeting senescent cells, increasingly

Health & MedicineNovember 10, 2026

Engineered T cell-agonist chimera for logic-gated STING activation and augmented cancer immunotherapy.

The efficacy of adoptive T cell therapy against solid tumors is markedly hindered by the immunosuppressive microenvironment. Here, we demonstrate that stimulator of interferon genes (STING) activation in tumor-associated macrophages (TAM) enhances the intratumoral infiltration and cytotoxicity of adoptive T cells. We next design a TAM-targeted nanoagonist and engineer a T cell - agonist chimera (SNTC) via covalent surface anchoring, to achieve synchronized biodistribution of STING agonist with a

Health & MedicineNovember 3, 2026

An innervated and vascularized HNSCC-on-a-chip model built on defined and tunable engineered extracellular matrices.

Understanding the tumor microenvironment requires experimental platforms that faithfully recapitulate its key components. Here, we present an innervated and vascularized head and neck squamous cell carcinoma (HNSCC)-on-a-chip platform built with fully defined and tunable engineered extracellular matrices (eECMs). In a stepwise increase of complexity, we first cocultured patient-derived HNSCC cells, cancer-associated fibroblasts, and endothelial cells within tailored eECMs, revealing extracellula

Health & MedicineNovember 3, 2026

Septin binding restricts Shigella growth and triggers intracellular tolerance.

Pathogen survival relies on their ability to adapt to changing environments, yet how intracellular bacteria tolerate cell-autonomous immunity remains unclear. Septins assemble into cage-like structures around cytoplasmic Shigella targeted by autophagy, but their antibacterial activity was unknown. Using advanced microscopy and cell-free reconstitution, we show that septins polymerize into circumferentially oriented filaments that inhibit bacterial growth. RNA-sequencing reveals that septin bindi