Cell. 2026 Sep 29:S0092-8674(26)01081-0. doi: 10.1016/j.cell.2026.09.012. Online ahead of print.

ABSTRACT

Cachexia is a major cause of morbidity in pancreatic cancer, but the cellular circuitry linking tumor progression to systemic wasting remains incompletely understood. Integrating single-cell RNA sequencing, Xenium spatial transcriptomics, multiplex immunohistochemistry, bulk transcriptomics, and functional studies across human non-cachexia, pre-cachexia, and cachexia samples, together with mouse models, we define a cachexia-associated microenvironmental niche composed of SEMA4A⁺ tumor cells, AQP9⁺ macrophages, and LOXL2⁺ cancer-associated fibroblasts. Mechanistically, SEMA4A-associated signaling promotes bone morphogenetic protein-2 (BMP2)-dependent acquisition of an AQP9-associated macrophage phenotype, and macrophage-derived CXCL8 activates LOXL2⁺ fibroblasts. LOXL2⁺ fibroblasts reciprocally enhance tumor cell FOSL1/SEMA4A signaling through exosomal N-glycosylated LOXL2. Spatial analyses demonstrate progressive enrichment of this niche with cachexia severity and association with postoperative development of cachexia in previously non-cachectic patients. These findings provide a framework linking local tumor ecosystem dynamics to cachexia progression.

PMID:42810340 | DOI:10.1016/j.cell.2026.09.012

Biology (Basel). 2026 Sep 17;15(18):1646. doi: 10.3390/biology15181646.

ABSTRACT

Salinity, temperature and body weight dominate seawater acclimation in rainbow trout (Oncorhynchus mykiss), yet few studies simultaneously explore their main effects and potential correlative interactive patterns in hepatic responses. A 60-day L₉ (3³) orthogonal trial was performed on triploid rainbow trout with three gradients of body weight, temperature and salinity. Hepatic transcriptomics revealed that salinity drove global transcriptional remodeling and high salinity induced far fewer DEGs than medium salinity. WGCNA screened a salinity-positive blue module (r = 0.408, p = 0.0346), while alternative splicing confirmed extensive salinity-dependent post-transcriptional regulation. Semi-quantitative histology showed that 20 °C was associated with more pronounced salinity-caused hepatocellular vacuolation and karyopyknosis in the orthogonal test. Survival statistics indicated that salinity was the only factor with significant main effects (p < 0.05), and the 500 g-10 °C-10 ppt group obtained the highest survival. This multi-omics and histological dataset reveals a suggestive regulatory hierarchy-like pattern: salinity acts as the primary driver, temperature serves as a synergistic amplifier, and body weight plays a minor modulatory role. These findings provide a theoretical basis for developing size-specific salinity acclimation protocols in commercial triploid rainbow trout farming.

PMID:42792591 | PMC:PMC13604319 | DOI:10.3390/biology15181646