We propose a tractable SOFR-swaption pricing framework that integrates Jamshidian's decomposition with the one-factor Hull-White model in the extended forward-measure/ extended-bond setting and derives closed-form formulae consistent with SOFR's compounded-in-arrears convention. Model calibration generates a trader-ready 6-surface that supports interpolation across the expiry-tenor grid and facilitates pricing and mark-to-market valuation of less-liquid or bespoke contracts. Empirical results show good fit for short-and intermediate-maturity swaptions but significant errors for long-dated options, highlighting both the model's practical value and its structural limitations.
OBJECTIVE:Autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD), cerebral palsy (CP), and developmental delay are major childhood neurodevelopmental disorders. Sibling status and birth order may influence neurodevelopmental outcomes, yet population-based evidence remains limited. This study examined their associations with childhood neurodevelopmental disorder risks in a nationwide birth cohort. METHODS:We analyzed 2,045,178 live births from Taiwan's Birth Registration Database (2004-2014), linked to National Health Insurance and Death Registry records through 2020. CP, developmental delay, ASD, and ADHD were identified using ICD codes. Children were classified by sibling status and birth order using maternal identifiers. Kaplan-Meier and Cox models estimated adjusted hazard ratios (aHRs), controlling for maternal age, birth period, perinatal factors, socioeconomic status, and urbanization. RESULTS:Compared with single children, those with siblings generally showed lower risks of CP and ASD, whereas associations with ADHD and developmental delay varied according to birth order. Later birth order was associated with lower recorded risks of ASD and ADHD. Similar patterns were observed after excluding multiple births and in analyses restricted to diagnoses before 6 years of age. CONCLUSIONS:Family structure, including single-child status and birth order, was associated with childhood neurodevelopmental disorder risks. Compared with children who had siblings, single children generally had higher risks across multiple neurodevelopmental outcomes. These findings suggest that family structure may represent an important early-life context for neurodevelopment and may help inform developmental surveillance in societies experiencing declining fertility rates and delayed childbearing.
The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has driven the global COVID-19 pandemic, imposing a tremendous burden on public health. As the virus continually evolves through rapid mutations, the pandemic has transitioned into a prolonged endemic phase. Despite the development of novel drugs and vaccines, clinical outcomes remain suboptimal for vulnerable populations, including the elderly and those with comorbidities or compromised immunity. Tea polyphenols, a class of structurally diverse and bioactive nutraceuticals, may modulate viral entry, replication, and host inflammatory pathways implicated in disease progression through pleiotropic effects on viral attachment, membrane fusion, intracellular replication, and proteolytic processing. Here, we provide an updated chemo-biological perspective on the antiviral and immunomodulatory mechanisms of tea polyphenols against SARS-CoV-2. Current evidence highlights their potential to serve as promising candidates for further mechanistic and translational investigation as adjunctive strategies and nutraceuticals for COVID-19 management. Importantly, no large-scale randomized controlled trials have yet demonstrated clinical benefit of tea polyphenols in COVID-19.
BACKGROUND/AIM:Cabozantinib is a multi-target tyrosine kinase inhibitor used in renal cell carcinoma (RCC), yet the exposure-dependent remodeling of phosphorylation networks under short-term versus chronic treatment remains insufficiently defined. This study applied quantitative phosphoproteomics to delineate remodeling programs induced by acute and chronic cabozantinib exposure and to examine cellular features within the same signaling background. MATERIALS AND METHODS:RCC cells were subjected to acute (48 h) or chronic (>4-month) cabozantinib exposure. Dimethyl-labeling-based phosphoproteomics was used to quantify phosphosites and derive pathway- and kinase-substrate-level modules, integrated with functional enrichment, 2D-annotation and PTM-signature analyses, immunoblotting, migration, and Matrigel invasion assays. RESULTS:A total of 6,305 phosphosites were quantified. Acute cabozantinib exposure predominantly downregulated cell-cycle and CDK-associated phosphorylation, consistent with a broad cytostatic remodeling pattern, whereas chronic cabozantinib exposure produced a more selective redistribution enriched for adhesion- and stress-associated modules, including MAPK/AP-1/MAPKAPK2/HSPB1-linked signatures. Activation-loop MET phosphorylation (Y1234/1235) remained suppressed under both exposure conditions, while phosphorylation of MET at T977 increased under chronic cabozantinib treatment and was interpreted as site-specific regulation within the remodeled phosphorylation context rather than restoration of MET signaling activity. Motility features examined in the same cellular background showed pattern-specific differences: migration exhibited modest but significant increases with a larger effect size in chronically cabozantinib-exposed cells under drug treatment, whereas invasion was consistently higher in chronically cabozantinib-exposed cells than in parental cells across conditions without a marked treatment-specific change. CONCLUSION:Chronic cabozantinib exposure is characterized by sustained suppression of MET phosphorylation and a selective adhesion- and MAPK/AP-1-associated phosphorylation program, accompanied by modest, pattern-specific motility differences observed within the same signaling context. These findings provide a systems level framework for future mechanistic and in vivo evaluation.
Diabetic retinopathy (DR) represents one of the most common microvascular complications of diabetes, and proliferative diabetic retinopathy (PDR) is the most vision-threatening form. Carbonic anhydrase IX (CA9), a hypoxia-inducible enzyme, has been implicated in several pathological processes, but its involvement in DR has not been clarified. In this study, three CA9 single nucleotide polymorphisms (rs3829078, rs2071676, and rs1048638) were genotyped in diabetic patients with and without DR. Clinical characteristics were compared between groups, and expression analyses were conducted using public databases and ARPE-19 cells under hyperglycemic and hypoxic conditions. No significant association was observed between CA9 variants and DR susceptibility in the overall cohort. However, among patients aged ≤60 years, carriers of the rs1048638 C/A and C/A + A/A genotypes exhibited a significantly increased risk of PDR. Expression quantitative trait locus (eQTL) data from the GTEx database revealed higher CA9 mRNA expression in tissues harboring the rs1048638 A allele. Moreover, both transcriptomic data and in vitro experiments demonstrated upregulation of CA9 in ARPE-19 cells exposed to high glucose and hypoxia. These findings suggest that the rs1048638 polymorphism may modulate CA9 expression and contribute to PDR development in younger diabetic patients through hypoxia- and glucose-related mechanisms. Collectively, our findings suggest that CA9 may serve as a potential risk biomarker associated with the progression of DR, particularly in younger patients.
