Biomedical subjects

Shaohua Zhang

Publications and source records attributed to Shaohua Zhang.

6 recordsLinked to original sources

PubMed2026

Multiomics profiling of plasma reveals lipid-immune dysregulation and exosome remodeling in mpox and mpox-HIV co-infection.

BACKGROUND: Monkeypox virus (MPXV) infects diverse human cell types, and human immunodeficiency virus (HIV) co-infection is common. The immunometabolic consequences of MPXV infection, and how it may be altered by HIV, remain poorly defined. METHODS: We performed quantitative plasma lipidomics and precise metabolomics in a discovery cohort (n = 81) comprising MPXV-monoinfected (MPLWOH), MPXV-HIV-coinfected (MPLWH), and HIV-monoinfected (PLWH) patients and healthy controls, integrating exosome proteomics, cytokine profiling, and transcriptomics of exosome-treated HepG2 and A549 cells for functional interpretation. An independent validation cohort (n = 65) was used to assess cross-cohort reproducibility. FINDINGS: MPXV infection induced broad lipid remodeling, with elevations in phosphatidylserine (PS) and phosphatidylethanolamine (PE) and reductions in phosphatidylcholine (PC), lysophospholipids, cholesteryl ester (CE), and exosomal lecithin-cholesterol acyltransferase (LCAT) and lipoprotein lipase (LPL). These lipid alterations were correlated with tissue injury markers and inflammatory cytokines. The MPLWH group exhibited more severe metabolic disruption, including marked sulfatide (SL) depletion, lower cholesterol and high-density lipoprotein cholesterol (HDL-c), and extensive rewiring of lipid-cytokine associations. SL depletion in MPLWH correlated with abundances of COPI-mediated retrograde trafficking proteins in exosomes. Transcriptomic profiling of exosome-treated cells provided functional validation: MPLWOH exosomes induced lipid metabolism and repair-associated epithelial programs, while MPLWH exosomes drove phospholipid remodeling and acute inflammatory and mucosal barrier-stress responses. CONCLUSIONS: MPXV infection reprograms host lipid metabolism and exosome composition, with HIV co-infection amplifying inflammatory, metabolic, and trafficking disruptions. These convergent multi-omics signatures link systemic lipid dysregulation to exosome-mediated immunomodulation and identify potential targets for host-directed interventions. FUNDING: This study was funded by the Major Project of Guangzhou National Laboratory.

Adult↗

PubMed2025

Deep learning-based assessment of missense variants in the COG4 gene presented with bilateral congenital cataract.

OBJECTIVE: We compared the protein structure and pathogenicity of clinically relevant variants of the COG4 gene with AlphaFold2 (AF2), Alpha Missense (AM), and ThermoMPNN for the first time. METHODS AND ANALYSIS: The sequences of clinically relevant Cog4 missense variants (one novel identified p.Y714F and three pre-existing p.G512R, p.R729W and p.L769R from Uniprot Q9H9E3) were imported into AF2 for protein structural prediction, and the pathogenicity was estimated using AM and ThermoMPNN. Different pathogenicity metrics were aggregated with principal component analysis (PCA) and further analysed at three levels (amino acid position, substitution and post-translation) based on all possible Cog4 missense variants (n=14 915). RESULTS: Localised protein structural impact including change of conformation and amino acid polarity, breakage of hydrogen bond and salt-bridge, and formation of alpha-helix were identified among clinically relevant Cog4 variants. The global structural comparison with multidimensional scaling demonstrated variants with similar protein structures (AF2) tended to exhibit similar clinical and biological phenotypes. The Cog4 p.Y714F variant exhibited greater protein structural similarity to mutated Cog4 found in Saul‒Wilson syndrome (p.G512R) and shared similar clinical phenotype (congenital cataract and psychomotor retardation). PCA of included pathogenic metrics demonstrated p.Y714F occurred at a critical position in Cog4 amino acid sequence with disrupted post-translational phosphorylation. CONCLUSION: Deep learning algorithms, including AF2, AM and ThermoMPNN, can be useful for evaluating variant of uncertain significance (VUS) by structural and pathogenicity prediction. Despite classified as VUS (American College of Medical Genetics and Genomics criteria: PM1, PP4), the pathogenicity in this Cog4 variant cannot be ruled out and warrants further investigation.

Mutation, Missense↗

PubMed2006

Inclusion complexes of beta-cyclodextrin with ionic liquid surfactants.

The three kinds of ionic liquid (IL) surfactants, 1-dodecyl-3-methylimidazolium hexafluorophosphate (C(12)mimPF(6)), 1-tetradecyl-3-methylimidazolium hexafluorophosphate (C(14)mimPF(6)), and 1-hexadecyl-3-methylimidazolium hexafluorophosphate (C(16)mimPF(6)), were used to form the inclusion complexes (ICs) with beta-cyclodextrin (beta-CD). The surface tension measurements revealed that there were two kinds of inclusion formations, 1:1 and 1:2 (beta-CD/IL) stoichiometry for beta-CD-C(12)mimPF(6) and beta-CD-C(14)mimPF(6) ICs, and only 1:1 stoichiometry for beta-CD-C(16)mimPF(6) ICs. These inclusion compounds were further characterized by XRD, (13)C CP/MAS NMR, (1)H NMR, rotating frame nuclear Overhauser effect spectroscopy (ROESY), and thermogravimetry (TGA). The results showed that these ICs were fine crystalline powder. The host-guest system presented a channel-type structure, and each glucose unit of beta-CD was in a similar environment. It was suggested that hydrophobicity played a crucial role in supporting the formation of ICs. The decomposition temperature of these ICs was lower than those of their precursors. Furthermore, the possible inclusion structures were also speculated. These inclusion behaviors are likely to be used to recover ILs in the process of their preparation.

Imidazoles↗

PubMed2005

Negative regulation of natural killer cell function by EAT-2, a SAP-related adaptor.

EAT-2 is an adaptor expressed in innate immune cells, including natural killer (NK) cells. It is closely related to the adaptor SAP, which regulates signaling lymphocyte activation molecule (SLAM)-related receptors by recruiting the kinase FynT to the receptors. Here we have studied the function of EAT-2 in NK cells by creating mice lacking or overexpressing EAT-2. Like SAP, EAT-2 was associated with the SLAM-related receptor 2B4 in NK cells. However, unlike SAP, EAT-2 was an inhibitor of NK cell function. EAT-2 repressed natural cytotoxicity and interferon-gamma secretion by a mechanism involving tyrosine phosphorylation of its C terminus. We have demonstrated a similar function for the adaptor ERT, a newly identified SAP family member expressed in mouse NK cells. These data identify a previously unknown mechanism of NK cell inhibition. Moreover, they indicate that EAT-2 and SAP have distinct and at times opposing functions in natural immunity.

Adaptor Proteins, Signal Transducing↗

PubMed2004

Genetic evidence linking SAP, the X-linked lymphoproliferative gene product, to Src-related kinase FynT in T(H)2 cytokine regulation.

SAP is an adaptor mutated in X-linked lymphoproliferative disease. It plays a critical role in T helper 2 (T(H)2) cytokine production. This function was suggested to reflect the capacity of SAP to associate with SLAM family receptors and enable tyrosine phosphorylation signaling by these receptors through SAP-mediated recruitment of Src-related kinase FynT. Here, we addressed by genetic means the importance of the SAP-FynT interaction in normal T cell functions. By creating a mouse in which the FynT binding site of SAP was inactivated in the germ line (sap(R78A) mouse) and by analyzing mice lacking SAP, FynT or SLAM, evidence was obtained that the SAP-FynT cascade is indeed crucial for normal T(H)2 functions in vitro and in vivo. These data imply that SAP is necessary for T(H)2 cytokine regulation primarily as a result of its capacity to recruit FynT. They also establish a previously unappreciated role for FynT in SAP-dependent T(H)2 cytokine regulation.

Animals↗

PubMed2002

[Antidotal effects of vitamin B(6) and sodium dimercaptopropane sulfonate on acute poisoning with tetramethylene disulphotetramine in animals].

OBJECTIVE: The study was designed to examine the antidotal effects of vitamin B(6) (Vit B(6)) with sodium dimercaptopropane sulfonate (Na-DMPS) on acute poisoning with tetramethylene disulphotetramine (TETS) in animals. METHODS: Through the acute toxicity experiments, the antidotal effects of Vit B(6) with Na-DMPS on mice immediately and 10 minutes after poisoning were observed. RESULTS: Used of Vit B(6) with Na-DMPS in early stage showed excellent inhibition of tetanic convulsion in acute poisoning with TETS in mice and can reduce very significantly the death rate (P < 0.001). Vit B(6) with Na-DMPS used 10 minutes after poisoning also significantly elongate the death time (68.8 +/- 15.2) and reduce significantly the death rate (60%) then control group's death time (31.6 +/- 7.8) and the death rate (100%) on acute poisoning in mice (P < 0.01). CONCLUSION: Antidotal effects of Vit B(6) with Na-DMPS were significant on acute TETS poisoning in animals. Vit B(6) with Na-DMPS is an excellent antidote for acute TETS poisoning. It is suggested that Vit B(6) with Na-DMPS may be clinically used to rescue patients poisoned by TETS.

Acute Disease↗