Virus taxonomy and the Baltimore system organise viruses by evolution and genome expression. We propose hierarchical therapeutic virotyping based on the materials produced during infection. First level assigns a composition virotype (nucleic-acid-only replicators; non-enveloped; enveloped). Second level maps these to three therapeutic material layers: N (nucleic-acid processes), P (protein processes) and L (lipid/membrane processes). Third level resolves the layers into a core scaffold (N1–N8, P1–P8, L1–L8) plus context-dependent extensions. Modifier enzymes are assigned by therapeutic endpoint; host responses remain an optional annotation. The resulting N/P/L dependency fingerprint supplies a structured feature space for combination prioritisation. Candidate combinations advance through claim-specific evidence gates from molecule to clinical evaluation. Therapeutic virotyping therefore links composition, functional dependency and experimentally testable combination design.
Setd7 mediates crosstalk between epigenetic and metabolic signaling to regulate lineage-specific and site-specific bone homeostasis. Osteoporosis stems from impaired osteogenic activity and skeletal compartmental imbalance, and the mechanisms that coordinately regulate craniofacial and appendicular bone remain elusive. Here, we demonstrate that Setd7 epigenetically promotes mitochondrial fusion to drive osteogenic commitment of bone marrow mesenchymal stem cells for appendicular bone development, while enhancing the osteogenic capacity of osteoprogenitors to support craniofacial bone formation. Conditional knockout of Setd7 in mesenchymal stem cells significantly reduced femoral bone mineral density, along with impaired somatic growth and body weight. In contrast, Setd7 deletion in osteoprogenitors specifically impaired craniofacial bone mass, revealing that Setd7 exerts distinct cell type-dependent regulatory effects on skeletal compartmentalization. Mechanistically, Setd7 epigenetically orchestrates mitochondrial fusion in both bone marrow mesenchymal stem cells and osteoprogenitors, as evidenced by increased mitochondrial membrane potential, decreased reactive oxygen species production, and elevated ATP generation. This mitochondrial reprogramming enhances cellular bioenergetics and redox homeostasis, which in turn amplifies osteogenic differentiation and bone matrix mineralization. Together, these findings define the Setd7-mitochondrial fusion cascade as an epigenetic-metabolic signaling module that controls site-specific osteogenic homeostasis, thereby identifying Setd7 as a target to alleviate osteoporotic bone loss by balancing mitochondrial dynamics and histone methylation.
Primary cilia are evolutionarily conserved, microtubule-based organelles that serve as sensory hubs, integrating extracellular signals with intracellular responses. In the eye, they are broadly distributed across the cornea, lens, trabecular meshwork, Schlemm’s canal, neural retina, and retinal pigment epithelium (RPE), where they contribute to development, homeostasis, and, in some tissues, responses to injury. Photoreceptor outer segments are highly specialized ciliary compartments critical for phototransduction, while cilia in other ocular cells regulate signaling pathways, mechanosensation, and tissue polarity. Disruption of ocular ciliogenesis or ciliary signaling causes a spectrum of disorders in which ciliary dysfunction is a primary pathogenic mechanism, collectively termed ciliopathies. These include nonsyndromic diseases such as ciliary gene-associated forms of retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA), as well as syndromic conditions like Lowe syndrome (oculocerebrorenal syndrome of Lowe), Bardet-Biedl syndrome (BBS), Usher syndrome (USH), Joubert syndrome (JBTS), Meckel syndrome (MKS), Senior-Løken syndrome, and Alström syndrome (ALMS). In addition, accumulating evidence implicates ciliary dysfunction in corneal disorders and glaucoma, although direct causal relationships remain incompletely established in many cases. Genetic advances have identified over 100 ciliary genes linked to ocular disease, revealing extensive heterogeneity and conserved pathogenic mechanisms. Recent progress in translational research has opened new therapeutic avenues, including adeno-associated virus (AAV)-mediated gene augmentation, CRISPR-based genome editing, antisense oligonucleotide (AON) therapy, stem cell-based regeneration, and pharmacological modulation of ciliary signaling. This review summarizes the current understanding of ciliary dynamics in ocular development and disease, highlights emerging therapeutic strategies, and discusses key questions to guide future research on ocular ciliopathies.
Defective decidualization in endometriosis is linked to impaired endometrial receptivity, recurrent implantation failure, and adverse pregnancy outcomes, but how endometriosis-related inflammatory cytokines perturb endometrial stromal cells remains unclear. Here, we show that transforming growth factor‑β1 (TGF‑β1) disrupts CEP131‑dependent primary cilia assembly and thereby attenuates decidualization in human endometrial stromal cells. In vitro decidualization induced by medroxyprogesterone acetate (MPA) and cAMP promoted primary cilium formation, and selectively upregulated the centriolar satellite protein CEP131. Structurally, CEP131 accumulated at the basal body and along the ciliary axoneme. Depletion of CEP131 markedly reduced the proportion and length of primary cilia and diminished expression of decidual markers, indicating that CEP131 is required for efficient ciliogenesis and decidualization. Notably, CEP131 expression was downregulated in women with endometriosis. TGF‑β1, but not interleukin‑6, abrogated CEP131 expression, suppressed decidualization, and reduced cilia frequency and length. Disruption of centriolar satellite dynamics by PCM1 depletion, microtubule depolymerization, or dynactin disruption similarly prevented CEP131 aggregation, shortened cilia, and impaired decidualization, supporting a critical role for satellite‑mediated CEP131 assembly in primary ciliogenesis and decidualization. Mechanistically, cAMP–PKA signaling and a CDK2–PLK4 axis promoted CEP131 aggregation at primary cilia, whereas pharmacologic or genetic inhibition of CDK2 or PLK4 reduced CEP131 assembly, ciliary length, and decidual marker expression. Collectively, these findings identify CEP131‑dependent primary cilia as essential organizers of decidual signaling and reveal TGF‑β1 as a cytokine that compromises endometrial stromal cell decidualization by targeting this ciliogenic machinery.
Abnormal senescence of decidual stromal cells (DSCs) is tightly linked to spontaneous abortion, yet the underlying mechanisms remain poorly defined. In this study, we found that DSC senescence was significantly increased in the decidual tissues of patients with recurrent spontaneous abortion (RSA) during the first trimester. Using both in vitro and in vivo models, we show that abnormally elevated branched-chain amino acids (BCAAs) reduce autophagic flux, leading to excessive DSC senescence, which mechanistically involves aberrant heat shock protein A6 (HSPA6) upregulation and subsequent downregulation of the transcription factor forkhead box O1 (FOXO1), thereby predisposing to adverse pregnancy outcomes. In vivo studies, intervention with leucine, a key BCAA, promoted uterine senescence and induced adverse pregnancy outcomes in mice. Conversely, restoring autophagy with rapamycin effectively suppressed excessive senescence at the maternal-fetal interface and significantly improved pregnancy outcomes under high-leucine conditions. Therefore, this study demonstrates that excessive senescence at the maternal-fetal interface resulting from impaired autophagic flux disrupts pregnancy maintenance via the HSPA6-FOXO1 signaling pathway. These findings highlight the roles of metabolic dysregulation and autophagy imbalance in miscarriage and provide a potential mechanistic basis for therapeutic strategies to prevent spontaneous abortion.
