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We report an 8-year-old male from a consanguineous union presenting with global developmental delay, microcephaly, failure to thrive, and distinctive dysmorphic features (dolichocephaly, triangular face, malar flattening). His elder brother shared similar clinical and dysmorphic findings. The pattern of inheritance within the family (affected male siblings, subtle dysmorphism in mother and consanguinity) prompted consideration of both autosomal recessive and X-linked modes of inheritance. Whole exome sequencing (WES) identified a novel hemizygous STAG2 frameshift variant (NM_001042750.2: c.3688_3689del; p.(Thr1230Hisfs*20)) in both brothers, inherited maternally. The variant is predicted to escape nonsense-mediated decay (NMD), potentially explaining survival, as complete STAG2 loss of function mutations in hemizygous males are most often embryonic lethal. This represents the first report of NMD-escaping STAG2 truncation in living males, expanding the mutational spectrum of STAG2-related disorders. The findings underscore the importance of considering hypomorphic STAG2 variants in males with syndromic neurodevelopmental delay and dysmorphism.

Fungal metabolites represent a valuable but underexplored source of anticancer agents, in part due to poorly defined mechanisms of action. Kojic acid (KA) is a fungal secondary metabolite with reported anti-melanoma activity, but its mechanism of action remains unclear. Here, we show that KA inhibits melanoma progression by disrupting MYC-driven transcriptional programs. KA treatment reduced proliferation and induced apoptosis in melanoma cells in vitro, and suppressed tumor growth in xenograft models. Transcriptomic profiling revealed a dose-dependent repression of MYC target genes, with CCNA2 and KPNA2 identified as key effectors. Both genes were validated as direct MYC targets and were associated with poor prognosis in the melanoma cohort (TCGA-SKCM). KA did not alter MYC expression but impaired its promoter binding and transcriptional activation of CCNA2 and KPNA2. Single-cell analysis further localized this axis to a proliferative mitotic subpopulation, promoting melanoma progression. These findings uncover a previously unrecognized mechanism by which KA inhibits melanoma growth and suggest that targeting the MYC-CCNA2/KPNA2 pathway may provide a therapeutic strategy for melanoma.

Type 2 diabetes mellitus (T2DM), a chronic hyperglycemic disorder, adversely affects multiple organs, including the kidneys, retina, and cardiovascular system. Despite significant advancements, the understanding of early screening, diagnosis, prognosis, biomarkers, and the molecular pathways involved in T2DM and its complications remains limited. Metabolomics has emerged as a powerful tool for exploring complex metabolic networks, allowing rapid investigation of disease-specific metabolic processes and offering deeper insights into pathophysiological mechanisms. This review evaluates the application of metabolomics in T2DM research, with a particular emphasis on its role in risk prediction and elucidating disease mechanisms. By summarising current literature, the review highlights metabolomics' contributions to the discovery of T2DM biomarkers, the understanding of metabolic mechanisms, and the study of T2DM complications. Additionally, it examines its potential in personalised diagnosis, prognosis, and treatment. Metabolomics plays a pivotal role in T2DM research, as the analysis of metabolites in biological fluids facilitates the identification of biomarkers for early diagnosis and risk prediction, provides insights into disease mechanisms, supports precision medicine, and enables early detection of diabetic complications. However, challenges remain, and future efforts should focus on multi-omics cohort studies to advance its clinical applications.

Cleft Lip and Palate (CL/P) is the most common congenital craniofacial malformation. However, a central challenge remains in understanding how this multi-layered, dynamically interactive gene network is precisely modulated across specific cell lineages and developmental time windows, and how environmental factors integrate with genetic susceptibilities to drive phenotypic outcomes. Its etiology originates from an imbalance in a multi-layered, dynamically interactive gene network composed of core transcription factors (the p63-IRF6-GRHL3 axis), key signaling pathways (Wnt, BMP/TGF-β, FGF, Shh), and epigenetic regulation. This network precisely controls epithelial integrity, mesenchymal patterning, and epithelial-mesenchymal crosstalk. Variations at its key nodes (such as IRF6, SATB2, MSX1, PAX9, etc.) disrupt the developmental program, leading to the malformation. Single-cell and multi-omics technologies have revealed the cell-type specificity and spatiotemporal dynamics of disease-causing genes. Animal models (mice, zebrafish) provide essential tools for functional validation and mechanistic studies. These advances are driving CL/P research towards molecular subtype-based precise risk assessment, targeted intervention, and personalized treatment.

This study presents a comprehensive transcriptomic atlas of Picea purpurea, an endemic Qinghai-Tibet Plateau conifer, integrating full-length and short-read transcriptome datasets. We identified 39,156 non-redundant transcripts across four tissues (roots, stems, needles, cones), with 61.52% showing broad expression and 6.15% exhibiting tissue specificity. Tissue-specific transcripts were markedly enriched in secondary metabolism, particularly terpenoid biosynthesis. Phylogenomic analysis of 1642 terpene synthase (TPS) genes from 25 gymnosperms (covering 75% of extant orders) yielded an updated classification of three gymnosperm-specific subfamilies: TPS-d1 (monoterpene synthases), TPS-d2 (sesquiterpene synthases), and TPS-d3 (diterpene synthases). Pan-genome comparisons across six Picea species identified 74 TPS orthogroups, including 6 core conserved families and 38 lineage-specific expansions. These findings elucidate the molecular basis of terpenoid diversification in this ecologically pivotal genus.

Testicular germ cell tumors (TGCTs) are the most common cancer among young men of European ancestry. TGCT incidence is rising worldwide while risk factors remain elusive. Genomically, TGCTs have high aneuploidy, low somatic mutational burden, and are globally hypomethylated. TGCT genetics is polygenic, with 78 susceptibility loci identified from large genome-wide association studies. It is highly curable when utilizing multimodal therapy with cisplatin chemotherapy and surgical interventions. However, since patients can live many decades after cure, the long-term health consequences and psychosocial impacts caused by treatment must be considered. Recently, the microRNA cluster miR-371-3 and ctDNA have emerged as TGCT biomarkers with promising clinical utility. We review recent efforts on elucidating TGCT biology, identifying factors associated with risk, disease progression and recurrence, and treatment de-escalation to limit impacts on disease survivorship.