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Zhenfeng Zhang

Publications and source records attributed to Zhenfeng Zhang.

5 recordsLinked to original sources

Structural insights into histone mimicry by the small hepatitis delta antigen.

Hepatitis delta virus (HDV) is a satellite RNA virus that requires hepatitis B virus (HBV) for propagation but replicates its genome independently in the nucleus. The small form of the hepatitis delta antigen (S-HDAg) is essential for replication and is regulated by post-translational modifications. Acetylation at lysine 72 (K72ac) enables S-HDAg to interact with the bromodomain (BRD) of the host chromatin remodeler bromodomain adjacent to zinc finger domain protein 2B (BAZ2B) to promote viral replication. However, the structural basis for this interaction has remained elusive. Here, we provide structural and biophysical insights into this interaction through quantitative binding assays and X-ray crystallography. Isothermal titration calorimetry revealed that BRDs of BAZ2B and its close homolog BAZ2A bind to the viral peptide weakly, with BAZ2A-BRD exhibiting a modestly higher affinity. The crystal structure of BAZ2A-BRD in complex with the S-HDAg-K72ac peptide demonstrates an inverted binding orientation relative to canonical histone ligands, rationalizing the weak interaction. Mutagenesis studies confirmed the critical binding interface both in vitro and in cells. These findings elucidate the molecular mechanism by which HDV co-opts host BAZ2 bromodomains via a unique, weak-affinity interaction, providing a structural framework for understanding viral replication.

Hepatitis delta Antigens↗

Association between 1400 blood metabolites and the risk of ankylosing spondylitis: A 2-stage, 2-sample Mendelian randomization study.

Human blood metabolites have been closely linked to ankylosing spondylitis (AS) in observational studies, yet direct causal evidence remains limited. This study aims to use Mendelian randomization (MR) to pinpoint causal metabolites associated with AS and to predict potential side effects of metabolite interventions. Genetic instruments for exposure were sourced from a genome-wide association study of 1400 blood metabolites, while genome-wide association study data for AS outcomes were derived from the FinnGen cohort. The primary MR analysis was conducted using the inverse variance weighted method. Supplemental analyses were conducted using weighted median, MR-Egger, simple mode, and weighted mode methods, while sensitivity analyses were performed to evaluate heterogeneity and pleiotropy. A replication analysis using an additional the UK Biobank cohort was also performed to determine metabolites associated with AS. The Steiger test and linkage disequilibrium score regression were used to further strengthen causal inference. Lastly, a phenome-wide Mendelian randomization analysis was performed to investigate the potential on-target side effects of metabolite interventions. After comprehensive analyses, 3 metabolites (the 2'-deoxyuridine levels, the hate to mannose ratio, and the Uridine to 2'-deoxyuridine ratio) were identified as being genetically associated with AS. The phenome-wide Mendelian randomization analysis revealed that the hate to mannose ratio might have deleterious effects on 4 other diseases, while no significant associations were found for the 2'-deoxyuridine levels or the uridine to 2'-deoxyuridine ratio with other diseases. This systematic MR analysis unveiled the potential role of the 2'-deoxyuridine levels, hate to mannose ratio and uridine to 2'-deoxyuridine ratio as the causal mediator in the development of AS. Considering the advantages and disadvantages, 2'-deoxyuridine appears as the most promising prospective therapeutic target for the prevention of AS.

Humans↗

Attenuated partial internal reflection infrared spectroscopy.

A new method for the spectroscopic study of absorbing films is proposed. In contrast to the well-established methods that take advantage of the attenuation of total internal reflection (ATR) to obtain spectra, we intentionally arrange the optics to permit partial internal reflection from the sampling prism face. Attenuated partial internal reflection (APR) spectroscopy is introduced through theoretical calculations and experimental demonstrations. The calculated APR spectra in the infrared region were generated from the Fresnel and Airy equations. Experimentally, APR spectra of water films on a NaCl prism were obtained. APR is more sensitive than ATR, and can easily distinguish water films at the monolayer level (310 pm). The determination of film thickness from interference fringes in APR spectra is also illustrated. It is shown that APR can be used for film thickness measurements that can span 6 orders of magnitude. The limitations of APR are also discussed.

Journal Article↗

Infrared spectroscopy of SO2 aqueous solutions.

The chemistry of SO2 solutions was studied with infrared transmission and total internal reflection (ATR) spectroscopy. The cross-sections of the SO2 stretching vibrations v1, v3 and the combination band of v1 + v3 were obtained and found to be slightly different from their gas phase values. Six features we associate with sulfur-containing ions were observed. We present the first infrared evidence for the bisulfite ion HOSO2- through detection of its OH stretching vibration. Other features may be associated with HSO3-, another isomer of the bisulfite ion, and a new compound we propose to be H2S2O6(2-). We found no evidence for sulfurous acid H2SO3.

Molecular Conformation↗

[Comparison of enhanced thin CT sections with pathologic findings in pulmonary carcinoma, inflammatory, pseudo-tumor and pulmonary tuberculoma].

OBJECTIVE: To compare quantitatively the enhanced thin CT section with pathologic findings in pulmonary carcinoma, pulmonary inflammatory pseudotumor (IPT) and pulmonary tuberculoma so as to demonstrate the relation of degree of enhancement and the vascular structure within the lesion with special emphasis on pulmonary carcinoma. METHODS: Enhanced thin CT sections were obtained in 35 cases with nodular or patchy lesions in the peripheral lung field which are difficult to differentiate clinically. There were pulmonary carcinoma 21, inflammatory pseudotumor 7 and tuberculoma 7. The number of small vessels (inner diameter 0.02 approximately 0.1 mm), relatively large vessels (inner diameter > 0.1 mm) and their vascular bed areas were analyzed by computed image analyzing system. The relation between CT average attenuation and the number of vessels or the vascular bed areas were statistically evaluated. RESULTS: 1. The differences of average attenuation in carcinoma, inflammatory pseudotumor and tuberculoma were statistically significant (P < 0.05). 2. The differences in number of small vessels, relatively large vessels and vascular bed areas among these three types of lesion were also significant (P < 0.05). 3. A positive correlation was found in the average CT affenuation of lung carcinoma and its number of small vessels and relatively large vessels and 4. A positive correlation was found between the average CT attenuation in these three lesions and the relatively large vessels, total vascular amount and vascular bed areas. CONCLUSIONS: 1. The average degree of attenuation, being divided into four degrees, is of practical value in the differentiation of lung carcinoma, inflammatory pseudotumor and tuberculoma. 2. The average CT attenuation of lung carcinoma, inflammatory pseudotumor and tuberculoma is in direct proportion to the number of vessels and vessel bed areas and 3. The characteristic CT enhancement in lung carcinoma reflexes the condition of vessels and blood supply within the tumor.

Adult↗