Intradomain Allosteric Regulation of Soluble Epoxide Hydrolase by Its Substrates.

Soluble epoxide hydrolase (sEH) is a bifunctional enzyme with epoxide hydrolase activity in the C-terminal domain (C-EH) and lipid phosphate phosphatase activity in the N-terminal domain (N-phos). The C-EH hydrolyzes bioactive epoxy fatty acids such as epoxyeicosatrienoic acid (EET). The N-phos hydrolyzes lipid phosphomonesters, including the signaling molecules of lysophosphatidic acid (LPA).

Computational design of serine hydrolases.

Enzymes that proceed through multistep reaction mechanisms often utilize complex, polar active sites positioned with sub-angstrom precision to mediate distinct chemical steps, which makes their de novo construction extremely challenging. We sought to overcome this challenge using the classic catalytic triad and oxyanion hole of serine hydrolases as a model system. We used RFdiffusion to generate proteins housing catalytic sites of increasing complexity and varying geometry, and a newly developed ensemble generation method called ChemNet to assess active site geometry and preorganization at each step of the reaction.

Treatment of Rectovaginal Fistula.

[This corrects the article DOI: 10.23922/jarc.2023-007.

Treatment of Rectovaginal Fistula.

Rectovaginal fistula (RVF) is a challenging complication with unsatisfactory success and a significant burden for the patients. With insufficient clinical data due to the rare entity, the present state of treatments for RVFs was reviewed especially form the point of factors to determine management, classifications, principle of treatment, conservative and surgical treatments with outcomes. Size, fistula localization and etiology, type of fistula; "simple" or "complex," status of anal sphincter complex and surrounding tissue, presence or absence of inflammation, presence of diverting stoma, previous attempted repair and radiation therapy, patient's condition with co-morbidities, and surgeon's experience are important factors to determine the management of RVF.

Significant Acceleration of Regional Brain Aging and Atrophy After Mild Traumatic Brain Injury.

Brain regions' rates of age-related volumetric change after traumatic brain injury (TBI) are unknown. Here, we quantify these rates cross-sectionally in 113 persons with recent mild TBI (mTBI), whom we compare against 3 418 healthy controls (HCs). Regional gray matter (GM) volumes were extracted from magnetic resonance images.