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Host environments are complex and highly dynamic for bacterial pathogens, requiring rapid and precise response and adaptation for successful systemic infection. In this study, RNA-Seq was used to investigate the transcriptional response of Vibrio harveyi TS-628 during adaptation to yellow grouper (Epinephelus awoara) blood. A total of 1,273 genes were differentially expressed, accounting for 28.35% of the total gene complement, indicating a highly significant metabolic reprogramming of V. harveyi during host adaptation. Genes encoding two-component systems (TCSs) were prominently enriched among the differentially expressed genes (DEGs). Notably, the pfeS/pfeR TCS was consistently up-regulated during adaptation to host blood, mucus, and muscle, suggesting its core role in the host adaptation. Subsequent knockdown of pfeS or pfeR did not affect bacterial growth but altered the expression of iron uptake-related genes, implying a regulatory role of the TCS in maintaining iron homeostasis. Furthermore, both pfeS₉₇₂-RNAi and pfeR₄₉₂-RNAi strains displayed significantly reduced motility, chemotaxis, and biofilm formation, indicating that the pfeS/pfeR system coordinates multiple adaptive traits essential for host colonization. Blood exposure significantly induced chemotaxis and biofilm formation in the wild-type strain, but this inducibility was lost in the knockdown strains, suggesting that the pfeS/pfeR system may function in environmental signal sensing. In conclusion, we hypothesize that during the early stages of infection, pfeS/pfeR mediates metabolic reprogramming in response to environmental cues, thereby regulating iron homeostasis and virulence-related behaviors to promote bacterial adaptation to the host environment and preparing for further dissemination.

Hepatocellular carcinoma (HCC) is characterized by profound phenotypic plasticity and limited therapeutic durability. Despite the availability of tyrosine kinase inhibitors, chemotherapy, and immune checkpoint inhibitors, most patients eventually develop resistance, often in the absence of clear genetic alterations. This highlights the importance of non-genetic, adaptive mechanisms that enable tumor cells to survive therapeutic and microenvironmental stress. Deubiquitination has emerged as a critical regulatory layer in stress adaptation, yet its role in orchestrating coordinated resistance programs remains underappreciated. Ubiquitin-specific protease 22 (USP22), originally characterized as a component of the SAGA transcriptional complex, is increasingly recognized as a central regulator of adaptive reprogramming in HCC. In this review, we synthesize recent mechanistic and translational studies demonstrating how USP22 integrates hypoxia tolerance, metabolic rewiring, cancer stemness, immune evasion, and drug resistance into a unified adaptive network. We highlight the role of USP22-centered positive feedback loops in converting transient stress signals into stable, drug-tolerant states, thereby driving non-genetic resistance to targeted therapy, chemotherapy, and immunotherapy. Finally, we discuss emerging therapeutic strategies that exploit USP22 dependency through combination and timing-aware interventions, as well as the potential of USP22 as a biomarker for identifying highly adaptive, treatment-refractory HCC. Collectively, these insights position USP22 as a network stabilizer of malignant adaptation and a promising target for overcoming therapeutic resistance in hepatocellular carcinoma.

Background: Autosomal dominant tubulointerstitial kidney disease (ADTKD) is a rare genetic disorder characterized by tubular damage and interstitial fibrosis, with inescapable progression to end-stage renal disease. SEC61A1-related ADTKD has long been neglected and underrecognized because of its rarity, insidious onset and variable clinical manifestations.

Results: A 13-year-old boy was referred to the pediatric nephrology clinic due to renal insufficiency, which had been found unexpectedly while visiting the hospital because of growth retardation. He had normocytic normochromic anemia since early childhood and was recently found to have agranulocytosis. The evaluation suggested elevated serum creatinine, hyperuricemia, bland urinary sediment, the absence of proteinuria, and renal cysts. A novel de novo heterozygous missense variant in SEC61A1, Ser71Pro, was found. So far fifteen patients with SEC61A1-related ADTKD have been reported, most of whom presented with early-onset chronic kidney disease and hyperuricemia. The extrarenal features included growth retardation, hematological abnormalities, cognitive impairment, and immunological abnormalities. There is no specific treatment for the SEC61A1-related ADTKD. Most reported patients survived to adulthood with supportive treatment.

Conclusions: This is the first case of SEC61A1-related ADTKD of Chinese origin, extending its phenotype and mutation spectrum. The diagnosis of SEC61A1-related ADTKD should be considered in patients with early-onset or familial chronic kidney disease, hematological abnormalities and growth retardation, and mutation analysis of SEC61A1 is needed.

Background: Glioma remains a lethal brain malignancy with a dismal prognosis. Syntaphilin (SNPH), a mitochondrial anchoring protein, shows emerging relevance in cancer biology. This study investigates the diagnostic and prognostic potential of SNPH, while elucidatingits functional mechanisms in glioma progression.

Methods: The Cancer Genome Atlas (TCGA), Chinese Glioma Genome Atlas (CGGA), Genotype-Tissue Expression (GTEx) and Human Protein Atlas (HPA) were utilized to systematically analyze SNPH, including its differential transcriptional and translational expression, survival correlation, functional enrichment, and immune microenvironment in glioma. Subsequently, the effects of SNPH on cell migration, invasion, mitochondria distribution, epithelial-mesenchymal transition, focal adhesion (FA) maturation and FA kinase (FAK) signaling were validated via in vitro.

Results: SNPH expression was markedlydownregulatedin glioma (P < 0.001), demonstratinghigh diagnostic potential for glioma detection (area under the curve = 0.819). Clinically, decreasedSNPH levelswere associatedwith aggressive features(WHO grade G4, glioblastoma subtype) (both P < 0.001), unfavorable molecular characteristics[IDH-wildtype (P = 0.005), 1p19q non-codeletion (P < 0.001)], and significantlypredicted worse overall survival (P < 0.001). Functional enrichment analyses revealed SNPH's involvementin immunomodulation and migration-related processes, particularly FA pathway and FAK signaling. Immune profiling indicated an inverse correlation between SNPH expression and the abundance of T helper cells, macrophages and neutrophils. In vitro, SNPH overexpression suppressed invasion and epithelial-mesenchymal transition. Mechanistically, it promoted perinuclear mitochondrial clustering, attenuated FA maturation, FAK phosphorylation and RhoA/Rac1/Cdc42 expression.

Conclusion: These findings establish SNPH as a novel diagnostic/prognostic biomarker and metastasis suppressor in glioma, functioning through mitochondrial repositioning-mediated inhibition of migration pathways.