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Biomedical subjects

Hao Zheng

Publications and source records attributed to Hao Zheng.

3 recordsLinked to original sources

Standardization Challenges in Glycated Albumin Measurement: Methodological Heterogeneity and Quantification Discrepancies.

BACKGROUND: Glycated albumin (GA) is a valuable biomarker for monitoring glycemic status. However, measurement standardization is challenged by methodological heterogeneity, where different analytical principles and target measurands cause quantification discrepancies. This study systematically compared prevailing methodologies to identify a robust reference measurement procedure for widespread standardization. METHODS: We compared a targeted bottom-up proteomics method (ID-LC-MS/MS) with an enzymatic assay and the Japan Society of Clinical Chemistry (JSCC) reference method. A cohort of 129 donor serum specimens and certified reference materials (JCCRM-611) were analyzed to assess methodological comparability. Furthermore, GA concentration-dependent glycation kinetics at the Lys-525 site of albumin was examined. RESULTS: The optimized targeted bottom-up proteomics method showed a strong correlation (r = 0.986) with both the enzymatic assay and JSCC reference method. However, a progressively increasing negative systematic bias was observed at higher GA levels, confirming that Lys-525 underestimates GA at higher levels. In addition, with increasing overall GA concentration, the glycation ratio at the Lys-525 site consistently declined compared to the total glycated lysine residues. CONCLUSIONS: The standardization of GA measurements requires a precise, universally accepted definition to address analytical discrepancies. The present results indicate that quantification targeting all glycated lysine residues (as in the JSCC method) aligns more closely with biologically relevant GA values than site-specific measurement at Lys-525, which shows greater bias at higher concentrations. Therefore, further GA standardization would focus on adopting total glycated lysine residues on albumin as the preferred measurand definition, to improve detection accuracy and clinical comparability.

Serum Albumin

A novel frameshift variant leads to familial osteopetrosis with variable phenotypes in a Chinese Han consanguineous family.

Osteopetrosis, a group of highly heterogeneous genetic bone disorders, is characterized by deafness, increased bone density, hepatosplenomegaly, pancytopenia and intellectual disability. Osteopetrosis can be divided into three subtypes: autosomal recessive osteopetrosis (ARO), intermediate autosomal recessive osteopetrosis (IARO), and autosomal dominant osteopetrosis (ADO). CLCN7 has been reported to be the most common gene responsible for the ADO-II subtype. In this study, a novel variant, c.175dupA (p.Met59Asnfs*8), of CLCN7 was identified in a Chinese Han consanguineous family with suspected ADO-II. The proband was homozygous for the p.Met59Asnfs*8 variant and exhibited multiple severe phenotypes, including deafness, short stature, brittle bones, optic atrophy, hepatosplenomegaly, intellectual disability, cleft palate and recurrent infection. However, except for the mother of the proband, who presented a series of clinical phenotypes caused by bone marrow failure, all the other family members who were heterozygous had no obvious abnormal phenotypes. Our study suggested that the novel variant p.Met59Asnfs*8 in CLCN7 was very likely pathogenic factor in our suspected ADO-II family. The phenotypes of heterozygous carriers may be affected by incomplete penetrance. Loss of function of CLCN7 caused by nonsense-mediated mRNA decay (NMD) due to the frameshift variant was likely the underlying pathogenic mechanism. This study broadened the mutation spectrum of CLCN7, provided a foundation for timely and effective clinical intervention for related diseases, and demonstrates the importance of genetic counselling.

Adult

The SlWRKY39-SlZF61 module synergistically regulates SlGSTU42 to enhance low-temperature tolerance in tomato.

Low-temperature stress affects plant growth, and WRKY transcription factors alleviate such damage by regulating downstream genes. This study found that tomato SlWRKY39 significantly responds to low temperatures: its overexpression enhances seedling low-temperature tolerance by promoting ROS scavenging, while knockout exacerbates ROS accumulation and increases sensitivity to low temperatures. Transcriptome analysis indicated induction of glutathione metabolic pathway genes in slwrky39 plants under low-temperature stress. Y1H, EMSA, and Dual-LUC experiments confirmed that SlWRKY39 specifically binds to and activates the SlGSTU42 promoter; silencing SlGSTU42 attenuated the low-temperature tolerance conferred by SlWRKY39 overexpression, verifying that SlWRKY39 improves low-temperature tolerance via direct regulation of SlGSTU42. Additionally, SlZF61 interacts with SlWRKY39, enhancing its regulatory effect on SlGSTU42. SlZF61 overexpression strengthens low-temperature tolerance, while knockout increases sensitivity to low temperatures. In summary, under low-temperature stress, SlWRKY39 and SlZF61 are upregulated expression in tomato; SlWRKY39 binds to the SlGSTU42 promoter, and SlZF61 interacts with SlWRKY39 to form a protein complex, enhancing this binding. They synergistically activate SlGSTU42 transcription, thereby improving seedling low-temperature tolerance by scavenging ROS. This coordinated regulatory mechanism provides a new theoretical basis and practical insights for enhancing tomato low-temperature tolerance and ensuring stable production under low-temperature stress conditions.

Solanum lycopersicum