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

Crit Rev Oncol Hematol. 2026 Mar 27;222:105305. doi: 10.1016/j.critrevonc.2026.105305. Online ahead of print.

ABSTRACT

The management of hepatocellular carcinoma (HCC) faces substantial and evolving challenges, driven by its aggressive biology, drug resistance, and the clinical urgency to detect recurrence. The treatment paradigm has undergone a profound transformation, evolving from surgical interventions and molecular targeted agents to the current era dominated by immunotherapy. Immune checkpoint inhibitors, particularly when used in combination with anti-angiogenic drugs or as part of dual-checkpoint blockade regimens, have established a new first-line standard of treatment for advanced HCC, delivering unprecedented survival improvements. Despite this progress, significant obstacles remain, including primary and acquired resistance, variable patient responses, and notably reduced efficacy in specific etiological subgroups. This comprehensive review synthesizes the emerging modalities such as bispecific antibodies, adoptive cell therapies, and innovative rational combinations that integrate systemic immunotherapy with locoregional treatments or novel targeted agents. Furthermore, we delve into the critical search for predictive biomarkers, encompassing liquid biopsy and multi-omics approaches, and dissect the complex cellular and molecular mechanisms underlying therapeutic resistance within the immunosuppressive tumor microenvironment. Finally, we outline future translational directions, emphasizing the expansion of immunotherapy, the development of tailored strategies for therapy-resistant disease, and the imperative move towards a personalized, biomarker-driven treatment framework. This review provides a cohesive overview of the field and charts a roadmap for future research to overcome the current challenges in HCC immunotherapy.

PMID:41905572 | DOI:10.1016/j.critrevonc.2026.105305