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Biomedical subjects

Yi Tang

Publications and source records attributed to Yi Tang.

2 recordsLinked to original sources

Ultra-high-field 7T MRI reveals neural abnormalities of attention networks in relation to cognitive impairment in hypertension.

Hypertension is a significant risk factor for cognitive impairment (CI), yet the corresponding neural network abnormalities remain underexplored. In this study, we examined the associations among global and domain-specific cognitive dysfunction, neuroimaging measures, and blood pressure in a subgroup of hypertensive patients with CI (N = 41) from a randomized controlled trial who underwent ultra-high-field 7 T MRI. Structural atrophy related to CI was localized to regions overlapping the attention networks. Both whole-brain and within-network dysfunction of the attention networks were associated with worse global cognitive performance. Notably, hyperconnectivity within key attention network hubs, including the right anterior insula and posterior intraparietal sulcus, was associated with declined processing speed in hypertensive patients, mediating the association between pulse pressure and processing speed. These findings provide new insights into the neural pathophysiology of hypertension-related CI and suggest potential network-based targets for intervention.

Magnetic Resonance Imaging

Biosynthesis of the 5-Isoxazolidinone-Containing Hexacyclic Structure of Parnafungin.

Parnafungins A-D (1-4) are fungal natural products that inhibit eukaryotic poly(A)-polymerase and were first discovered by Merck & Co., Inc., through a Candida albicans Fitness Test (CaFT) screening program. The biological activity of parnafungins is a result of the unique fused hexacyclic structure highlighted by a 5-isoxazolidinone (5ILD) N-heterocycle. In this work, we characterize the complete biosynthetic pathway of parnafungins through heterologous reconstitution and enzymatic assays. Nearly half of the 26-gene biosynthetic gene cluster of parnafungin is responsible for the production of a known polyketide natural product, blennolide C. Starting from the blennolide C fragment, a three-enzyme cascade involving CoA-ligase ParJ, P450 ParO, and DUF829 ParD catalyzes the formal biaryl cross-coupling between blennolide C and anthranilate. Subsequent oxidative cyclization generates a phenanthridine product that is then reduced by atypical short-chain reductase ParT. N-Hydroxylation by flavin-dependent monooxygenase ParB and subsequent lactonization catalyzed by a homologue of dienenolactone hydrolase ParF form the 5ILD ring and complete the biosynthesis of 1 and 2. Methylation of 1 forms parnafungin C (3), and lastly epoxidation forms parnafungin D (4). Together, our work revealed the chemical logic and enzymology in extending the biosynthetic pathway of a well-characterized natural product, blennolide C, to introduce considerable additional structural diversity that affords parnafungins with unique biological activity.

Molecular Structure