Biomedical subjects

Qian Zhu

Publications and source records attributed to Qian Zhu.

10 recordsLinked to original sources

PubMed2025

WDFY2 promotes MRN complex formation required for homologous recombination-mediated DNA repair.

The MRE11-RAD50-NBS1 (MRN) complex is fundamental for detecting and repairing DNA double-strand breaks (DSBs), thereby safeguarding genome integrity. However, the precise mechanism governing MRN complex recruitment to DSBs remains largely unexplored. Here, we identify WD40- and FYVE domain-containing protein 2 (WDFY2) as an important regulator of MRN complex formation at DNA damage sites, facilitating homologous recombination (HR) repair. Mechanistically, WDFY2 is phosphorylated at serine 84 by the ATM-CHK2 axis, priming it for recruitment to DSBs. Through direct interactions with MRE11 and NBS1, WDFY2 bridges the MRE11-RAD50 subcomplex with NBS1, thereby promoting MRN complex formation at DSBs and DNA end resection. WDFY2 deficiency, as well as the non-phosphorylatable S84A mutant, results in impaired HR repair and reduced cell survival following DNA damage. Collectively, our findings establish WDFY2 as a key platform for MRN complex loading at DSBs and HR repair, highlighting it as a potential therapeutic target for cancer treatment.

Humans↗

PubMed2025

HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury.

Hepatocytes can reprogram into biliary epithelial cells (BECs) during liver injury, but the underlying epigenetic mechanisms remain poorly understood. Here, we define the chromatin dynamics of this process using single-cell ATAC-seq and identify YAP/TEAD activation as a key driver of chromatin remodeling. An in vivo CRISPR screen highlights the histone acetyltransferase HBO1 as a critical barrier to reprogramming. HBO1 is recruited by YAP to target loci, where it promotes histone H3 lysine 14 acetylation (H3K14ac) and engages the chromatin reader zinc-finger MYND-type containing 8 (ZMYND8) to suppress YAP/TEAD-driven transcription. Loss of HBO1 accelerates chromatin remodeling, enhances YAP binding, and enables a more complete hepatocyte-to-BEC transition. Our findings position HBO1 as an epigenetic brake that restrains YAP-mediated reprogramming, suggesting that targeting HBO1 may enhance hepatocyte plasticity for liver regeneration.

Hepatocytes↗

PubMed2005

A Kir2.1 gain-of-function mutation underlies familial atrial fibrillation.

The inward rectifier K(+) channel Kir2.1 mediates the potassium I(K1) current in the heart. It is encoded by KCNJ2 gene that has been linked to Andersen's syndrome. Recently, strong evidences showed that Kir2.1 channels were associated with mouse atrial fibrillation (AF), therefore we hypothesized that KCNJ2 was associated with familial AF. Thirty Chinese AF kindreds were evaluated for mutations in KCNJ2 gene. A valine-to-isoleucine mutation at position 93 (V93I) of Kir2.1 was found in all affected members in one kindred. This valine and its flanking sequence is highly conserved in Kir2.1 proteins among different species. Functional analysis of the V93I mutant demonstrated a gain-of-function consequence on the Kir2.1 current. This effect is opposed to the loss-of-function effect of previously reported mutations in Andersen's syndrome. Kir2.1 V93I mutation may play a role in initiating and/or maintaining AF by increasing the activity of the inward rectifier K(+) channel.

Adult↗

PubMed2004

The prevalence of the metabolic syndrome among arab americans.

OBJECTIVE: To estimate the prevalence of the metabolic syndrome in Arab Americans by age, sex, and BMI and to examine the association between insulin resistance and each of the components of the metabolic syndrome. RESEARCH DESIGN AND METHODS: We studied a representative, cross-sectional, population-based sample of 542 Arab Americans aged 20-75 years. The metabolic syndrome was defined by Adult Treatment Panel III (ATP III) and World Health Organization (WHO) diagnostic criteria. Insulin resistance was estimated by homeostasis model assessment (HOMA-IR). RESULTS: The age-adjusted prevalence of the metabolic syndrome was 23% (95% CI 19-26%) by the ATP III definition and 28% (24-32%) by the WHO definition. Although the prevalence increased significantly with age and BMI in both sexes by both definitions, differences in estimates were noted. With ATP III, the age-specific rates were similar for men and women aged 20-49 years but were significantly higher for women aged >/=50 years. With WHO, rates were higher for men than women aged 20-49 years and similar for those aged >/=50 years. The most common component of the metabolic syndrome in men and women was low HDL cholesterol with the ATP III and the presence of glucose intolerance and HOMA-IR with the WHO. Strong associations between HOMA-IR and individual components of the metabolic syndrome were observed. After fitting a model with HOMA-IR as the outcome, waist circumference, triglyceride level, and fasting plasma glucose level were significantly associated with HOMA-IR. CONCLUSIONS: The metabolic syndrome is common among Arab Americans and is related to modifiable risk factors.

Adult↗

PubMed2003

Epidemiology of diabetes among Arab Americans.

OBJECTIVE: To examine the prevalence of diabetes and glucose intolerance by age and sex in the Arab-American community of Dearborn, Michigan. RESEARCH DESIGN AND METHODS: Participants were randomly selected adult Arab Americans, 20-75 years of age, from randomly selected households in Dearborn, Michigan. Demographic and anthropometric data were recorded. Glucose tolerance was assessed with 2-h 75-g oral glucose tolerance tests and classified according to 1997 American Diabetes Association and 1998 World Health Organization criteria. RESULTS: A total of 626 eligible adults were selected, and 542 participated (87% response rate). Because prevalence increases with age and the overall response rate for women (328/352; 93%) was higher than that for men (214/274; 78%), prevalence rates were adjusted for age and sex. The overall prevalence of diabetes was 15.5% (95% CI 12.2-18.7%) in women and 20.1% (15.0-25.2%) in men (P = 0.13). The prevalence of previously diagnosed diabetes was similar to that of undiagnosed diabetes. Impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) were present in 16.8% (12.8-20.8%) of women and 29.7% (23.4-35.9%) of men (P = 0.0007). The combined rates of glucose intolerance (diabetes, IGT, and IFG) were 32.3% (27.8-36.7%) for women and 49.8% (43.1-56.4%) for men (P < 0.0001). Among younger adults, the prevalence in men was higher than that in women. As expected, subjects with diabetes or IGT/IFG were older and had greater BMI and waist-to-hip ratios than subjects with normal glucose tolerance. CONCLUSIONS: The prevalence of diabetes and glucose intolerance is extremely high among adult Arab Americans in Michigan and represents a major clinical and public health problem. Community-based intervention programs to prevent and treat diabetes are urgently needed.

Adult↗

PubMed2003

Lack of acculturation is a risk factor for diabetes in arab immigrants in the US.

OBJECTIVE: To examine the relationship between dysglycemia (impaired fasting glucose, impaired glucose tolerance, and diabetes) and acculturation, physical activity, and perceived stress in Arab immigrants in the U.S. RESEARCH DESIGN AND METHODS: In a cross-sectional population-based study, we examined 520 Arab Americans, aged 20-75 years, who were born in the Middle East and immigrated to southeastern Michigan. Dysglycemia was assessed by history and with a 2-h 75-g oral glucose tolerance test. Acculturation, physical activity, and perceived stress were measured with standardized questionnaires. RESULTS: Associations were found between dysglycemia in men and older age at immigration, unemployment, speaking Arabic with friends, being less active in Arabic organizations, more frequent consumption of Arabic food, and less integration into American society. Dysglycemia in women was associated with being raised in rural areas of the Middle East, older age at immigration, longer length of stay in the U.S., not being employed outside the home, less than high school education, not attending Arabic or American schools, and not being able to read Arabic. Among men, older age at immigration, shorter length of stay in the U.S., less activity in Arab organizations, and eating Arabic food were associated with dysglycemia independent of age and BMI. Among women, acculturation was very low and was confounded with age and BMI as powerful risk factors for dysglycemia. No association was found between physical activity, perceived stress, and the risk of dysglycemia in either sex. CONCLUSIONS: Lack of acculturation is an important risk factor for dysglycemia in immigrant Arab Americans. Intervention programs aimed at diabetes prevention should consider the acculturation process.

Acculturation↗

PubMed2002

Overexpression of dominant-negative mutant hepatocyte nuclear fctor-1 alpha in pancreatic beta-cells causes abnormal islet architecture with decreased expression of E-cadherin, reduced beta-cell proliferation, and diabetes.

One subtype of maturity-onset diabetes of the young (MODY)-3 results from mutations in the gene encoding hepatocyte nuclear factor (HNF)-1 alpha. We generated transgenic mice expressing a naturally occurring dominant-negative form of human HNF-1 alpha (P291fsinsC) in pancreatic beta-cells. A progressive hyperglycemia with age was seen in these transgenic mice, and the mice developed diabetes with impaired glucose-stimulated insulin secretion. The pancreatic islets exhibited abnormal architecture with reduced expression of glucose transporter (GLUT2) and E-cadherin. Blockade of E-cadherin-mediated cell adhesion in pancreatic islets abolished the glucose-stimulated increases in intracellular Ca(2+) levels and insulin secretion, suggesting that loss of E-cadherin in beta-cells is associated with impaired insulin secretion. There was also a reduction in beta-cell number (50%), proliferation rate (15%), and pancreatic insulin content (45%) in 2-day-old transgenic mice and a further reduction in 4-week-old animals. Our findings suggest various roles for HNF-1 alpha in normal glucose metabolism, including the regulation of glucose transport, beta-cell growth, and beta-cell-to-beta-cell communication.

Animals↗

PubMed2002

Thyroid hormone receptor interacting protein 3 (trip3) is a novel coactivator of hepatocyte nuclear factor-4alpha.

Mutations of the hepatocyte nuclear factor-4alpha (HNF-4alpha) gene are associated with a subtype of maturity-onset diabetes of the young (MODY1) that is characterized by impaired insulin secretion in response to a glucose load. HNF-4alpha, which is a transcription factor expressed in pancreatic beta-cells, plays an important role in regulating the expression of genes involved in glucose metabolism. Thus, cofactors that interact with HNF-4alpha and modify its transcriptional activity might also play an important role in regulating the metabolic pathways in pancreatic beta-cells, and the genes of such cofactors are plausible candidate genes for MODY. In the present study, we showed, using a yeast two-hybrid screening assay, that thyroid hormone receptor interacting protein 3 (Trip3) interacted with HNF-4alpha, and their interaction was confirmed by the glutathione S-transferase pull-down assay. Human Trip3 cDNA contained an open reading frame for a protein of 155 amino acids, and the gene was expressed in both pancreatic islets and MIN6 cells. Cotransfection experiments indicated that Trip3 could enhance (two- to threefold) the transcription activity of HNF-4alpha in COS-7 cells and MIN6 cells. These results suggest that Trip3 is a coactivator of HNF-4alpha. Mutation screening revealed that variation of the Trip3 gene is not a common cause of MODY/early-onset type 2 diabetes in Japanese individuals. Trip3 may play an important role in glucose metabolism by regulating the transcription activity of HNF-4alpha.

Animals↗

PubMed2002

[Determination of indium in smelting waste by flame-AES].

The contents of Indium in smelting waste for extract Indium has been determined by the method of flame-emitting. The requirement of determination, factors of influence have been studied. The result by this method has been contrasted to FAAS. The method is sensitive and has good precision and accuracy. The detection limit was 0.016 microgram.mL-1, the relative standard deviation was 1.1%.

Indium↗

PubMedDate not supplied

Superstructure searching algorithm for generic reaction retrieval.

Chemical reaction knowledge is usually summarized and retrieved by chemists from references, journals, and reaction databases. To rigorously extract chemical reaction knowledge from large data sets, computer algorithms become much more important. This paper presents a new approach, superstructure searching (SSS) algorithm, for generic reaction retrieval. The algorithm considers all known reaction patterns from the targeted structure and assigns synthetic routes for new chemical compounds. This algorithm consists of screening, atom-by-atom comparison, and computation of R-groups' similarity.

Journal Article↗