Discovery of a selective alpha-kinase 1 inhibitor for the rare genetic disease ROSAH syndrome.

ROSAH (retinal dystrophy, optic nerve edema, splenomegaly, anhidrosis, and headache) syndrome is a rare genetic disease caused by variants in alpha-kinase 1 (ALPK1) resulting in downstream pro-inflammatory signaling mediated by the TIFA/TRAF6/NF-κB pathway. Here, we report the design of an ALPK1 inhibitor, DF-003, with pharmacokinetic properties suitable for daily oral dosing. In biochemical assays, DF-003 potently inhibits human ALPK1 (IC = 1.

P,N Hemilabile Ligand-Enabled Palladium-Catalyzed Dearomative Allylation of α-(Trialkylsilyl) Benzyl Chlorides.

The first dearomative allylation of -(trialkylsilyl) benzyl chlorides with allyltributylstannane via RSi-Pd-π-benzyl intermediates is described. The reactions proceeded smoothly in the presence of a specific P,N hemilabile ligand to generate vinylsilanes bearing an allyl group in satisfactory to good yields. Systematic evaluation of phosphine ligands identified ESPmin and % Vbur (min) as key parameters correlating ligand structure with catalytic activity.

Socioeconomic disparity and risk of irritable bowel syndrome: a cohort study with mediation analysis.

Background & Aims: To investigate association between socioeconomic status (SES) and risk of incident irritable bowel syndrome (IBS), and mediating role of lifestyle factors.

Methods: Participants free of IBS at recruitment were included in this retrospective analysis of a prospectively collected cohort (N=353,790). SES was assessed through household income, education and employment status, with different patterns identified through latent class analysis.

Delayed administration of Jiuwei Qianghuo Decoction combined with Zhuye Shigao Decoction mitigates the severity of influenza A virus infection by inhibiting cell death and alleviating the subsequent cytokine storm response.

Ethnopharmacological Relevance: The high mortality rate associated with severe influenza partly results from delayed initiation of antiviral therapy and subsequent cytokine storms. Jiuwei Qianghuo Decoction combined with Zhuye Shigao Decoction (JZF) has been clinically prescribed to prevent the progression to a more severe illness in influenza treatment. However, the precise mode of action and active components have not yet been elucidated.