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Biomedical subjects

Yanhong Zhou

Publications and source records attributed to Yanhong Zhou.

11 recordsLinked to original sources

Uncovering the mechanism of female restitution in sugarcane hybrids.

Variations of meiosis, which normally halve genetic complements prior to fertilization, can have profound consequences. For example, whole-genome duplications (polyploidy) have shaped the evolution and diversification of most angiosperm lineages. The century-long success of sugarcane interspecific hybrids has been attributed to unusual female restitution-an unreduced maternal gamete fusing with a normal haploid paternal gamete1,2. Here we generated haplotype-resolved genomes of octoploid Saccharum officinarum LA Purple and decaploid Saccharum spontaneum US56-14-4. Eight F1 hybrids between these species exhibited 2:1 maternal to paternal genomic ratios, with 2 assemblies revealing canonical haploid sets of approximately 40 paternal and approximately 80 maternal chromosomes. The maternal chromosomes comprise 40 pairs of duplicated, partially recombined sister chromatids that retain around 62.5% of maternal genetic diversity, characteristic of second division restitution. Using single-molecule long-read sequencing and a novel algorithm that is broadly applicable to polyploid genomes, we identified two classes of recombination breakpoints, including a previously unrecognized configuration supported by both recombinant and non-recombinant reads, across all hybrids and diagnostic of second division restitution. These findings resolve a century-old cytological debate, add new insights into meiotic variations, and offer a genomic approach to accelerate genetic gain in this globally critical sugar and bioenergy crop.

Chimera↗

Genetic Variants at the NAT2 and HLA-DOA are Associated With Anti-Tuberculosis Drug-Induced Liver Injury Susceptibility and Clinical Manifestations in Western Chinese Populations.

BACKGROUND: Anti-tuberculosis drug-induced liver injury (ATDILI) is one of the most prevalent and serious adverse reactions during anti-tuberculosis treatment and can potentially lead to liver failure or mortality. This study aims to investigate whether genetic variants in the N-acetyltransferase 2 gene (NAT2) and the HLA-DOA gene (HLA-DOA) are associated with ATDILI susceptibility and clinical manifestations in a Western Chinese population. METHODS: A total of 1358 participants with active tuberculosis were enrolled and genotyped for four NAT2 polymorphisms and five HLA-DOA loci. Associations between candidate genetic variants and ATDILI were evaluated using logistic regression analyses, with multiple comparisons adjusted by Bonferroni correction. RESULTS: The overall incidence of ATDILI was 28.4% (385/1358) in this cohort. Under a recessive model, NAT2 rs1799930 was found to increase the risk of ATDILI (odds ratio [OR] = 1.88, 95% confidence interval [CI]: 1.20-2.95, p = 0.006), which remained significant after Bonferroni correction (adjusted p = 0.048). Meanwhile, while HLA-DOA rs1367731 (OR = 0.41, 95% CI: 0.18-0.93, p = 0.033), rs6913008 (OR = 0.39, 95% CI: 0.17-0.89, p = 0.024), and rs9276975 (OR = 0.47, 95% CI: 0.23-0.98, p = 0.045) demonstrated a promising protective genomic characteristic that may mitigate the development of ATDILI. However, none of the reported HLA-DOA associations remained statistically significant after applying Bonferroni corrections. Regarding clinical manifestations, NAT2 rs1799930 and rs1799931 have been linked to poor ATDILI clinical presentations, whereas certain HLA-DOA variants (rs1367731, rs6913008, and rs9276975) were possibly linked to milder ATDILI severity. CONCLUSION: Our findings preliminarily suggest that the NAT2 and HLA-DOA genetic variants may play a role in ATDILI susceptibility and clinical outcomes. NAT2 rs1799930 represents a potential genetic risk marker, while HLA-DOA variants may serve as protective factors warranting further validation. These findings may contribute to the precision management of ATDILI and the prevention of anti-TB drug-associated liver injury.

Adult↗

Analysis of gene expression identifies candidate molecular markers in nasopharyngeal carcinoma using microdissection and cDNA microarray.

PURPOSE: Microarray analysis was used to bring a comprehensive insight into underlying molecular mechanisms and obtain a whole assessment of aberrant gene expression in nasopharyngeal carcinoma (NPC). METHODS: Combined with microdissection, gene expression profiles in 23 NPCs and 10 nontumor nasopharyngeal epithelial tissue samples were analyzed. RESULTS: Gene expression patterns suggested the dysregulation of the GTP/GDP-bound Ras cycle and an abnormal hyperactivity of cell cycle in NPC. Alterations in the WNT pathway suggest that this pathway may be activated in NPC. A 6-feature weighted-voting model was chosen because it represented the main characteristics of NPCs and predicted NPCs most accurately from the nontumor tissues (33 of 34 correct calls; 97.1% accuracy, Fisher's exact test, P value = 8.389 x 10(-8)). CONCLUSIONS: The data generated in this study represent a comprehensive list of genes aberrantly regulated in NPC. The 6-feature weighted-voting model may provide an extensive list of potential molecular markers for early diagnosis.

Biomarkers, Tumor↗

LRRC4, a putative tumor suppressor gene, requires a functional leucine-rich repeat cassette domain to inhibit proliferation of glioma cells in vitro by modulating the extracellular signal-regulated kinase/protein kinase B/nuclear factor-kappaB pathway.

We have previously reported that the LRRC4 gene, which contains a conserved leucine-rich repeat (LRR) cassette and an immunoglobulin (Ig) IgC2 domain, is associated with glioma suppression both in vitro and in vivo. The present study provides evidence that the conspicuous absence of LRRC4 in high-grade gliomas directly contributes to the increasing tumor grade. The loss of LRRC4 in U251 cells is caused by the loss of homozygosity at chromosome 7q32-ter. It was also found that LRRC4 requires a functional LRR cassette domain to suppress U251 cell proliferation. In the LRR cassette domain, the third LRR motif of the core LRR is found to be indispensable for the function of LRRC4. The inhibitory effect of LRRC4 is accompanied by a decrease in the expression of pERK, pAkt, pNF-kappaBp65, signal transducer and activator of transcription protein-3 (STAT3), and mutant p53, and an increase in the expression of c-Jun NH2-terminal kinase (JNK)2 and p-c-Jun, suggesting that LRRC4 plays a major role in suppressing U251 cell proliferation by regulating the extracellular signal-regulated kinase (ERK)/Akt/NF-kappaBp65, STAT3, and JNK2/c-Jun pathways. In conclusion, LRRC4 may act as a novel candidate of tumor suppressor gene. Therefore, the loss of LRRC4 function may be an important event in the progression of gliomas.

Apoptosis↗

Family-based association analysis validates chromosome 3p21 as a putative nasopharyngeal carcinoma susceptibility locus.

PURPOSE: Nasopharyngeal carcinoma (NPC) poses one of the serious health problems in southern Chinese, with an incidence rate ranging from 15 to 50/100,000. In our previously linkage analysis, a locus on 3p21 was identified to link to NPC. In this study, family-based association analysis was performed to test the transmission disequilibrium of chromosome 3p in 18 high-risk nasopharyngeal carcinoma families of Hunan province in southern China. METHODS: Single locus and multi-point of transmission disequilibrium test was performed by Genehunter program package with 15 microsatellite markers on chromosome 3p in 18 nasopharyngeal carcinoma pedigrees. RESULTS: A major transmission disequilibrium peak was observed near D3S1568, which possessed 20 alleles or haplotypes of 6 loci, spanning a 12.4 cM region from D3S1298 to D3S1289 on chromosome 3p21.31-3p21.2, and 3 alleles or haplotypes reached high significantly difference (P < 0.01). CONCLUSION: These results reflected a link disequilibrium between this chromosome region and a nasopharyngeal carcinoma susceptibility locus, and provided further evidence that a novel nasopharyngeal carcinoma susceptibility gene may be located in this chromosome region. These alleles or haplotypes transmitting disequilibrium in nasopharyngeal carcinoma pedigrees may act as the highly risk molecular markers after verified in large population.

Alleles↗

Using silico methods predicting ligands for orphan GPCRs.

The G-protein coupled receptor (GPCR) superfamily is one of the most important drug target classes for the pharmaceutical industry. The completion of the human genome project has revealed that there are more than 300 potential GPCR targets of interest. The identification of their natural ligands can gain significant insights into regulatory mechanisms of cellular signaling networks and provide unprecedented opportunities for drug discovery. Much effort has been directed towards the GPCR ligand discovery study by both academic institutions and pharmaceutical industries. However, the endogenous ligands still remain unknown for about 150 GPCRs in the human genome. It is necessary to develop new strategies to predict candidate ligands for these so-called orphan receptors. Computational techniques are playing an increasingly important role in finding and validating novel ligands for orphan GPCRs (oGPCRs). In this paper, we focus on recent development in applying bioinformatics approaches for the discovery of GPCR ligands. In addition, some of the data resources for ligand identification are also provided.

Animals↗

Poly-L-lysine-modified silica nanoparticles: a potential oral gene delivery system.

Poly-L-lysine-modified silica nanoparticles (PMS-NP) is a novel nonviral vector for gene delivery, which can efficiently deliver plasmid DNA and antisense oligonucleotides into cultured cells in vitro in the presence of serum-free medium. However, little is known about whether PMS-NP is a suitable carrier for gene delivery by oral administration. To this end, oral gene delivery assays were performed, and glucose transporting tests showed that PMS-NP had no obvious toxicity to intestine of BALB/C mice. Efficient reporter gene expression was detected in stomach and intestine where expression was mainly observed in mucous membrane cells. These results indicated that PMS-NP was a low-toxicity carrier, hence demonstrating its potential for fundamental research and gene therapy, especially for oral gene therapy.

Administration, Oral↗

Using bioinformatics for drug target identification from the genome.

Genomics and proteomics technologies have created a paradigm shift in the drug discovery process, with bioinformatics having a key role in the exploitation of genomic, transcriptomic, and proteomic data to gain insights into the molecular mechanisms that underlie disease and to identify potential drug targets. We discuss the current state of the art for some of the bioinformatic approaches to identifying drug targets, including identifying new members of successful target classes and their functions, predicting disease relevant genes, and constructing gene networks and protein interaction networks. In addition, we introduce drug target discovery using the strategy of systems biology, and discuss some of the data resources for the identification of drug targets. Although bioinformatics tools and resources can be used to identify putative drug targets, validating targets is still a process that requires an understanding of the role of the gene or protein in the disease process and is heavily dependent on laboratory-based work.

Alzheimer Disease↗

Non-linear viscoelastic models predict fingertip pulp force-displacement characteristics during voluntary tapping.

We evaluated whether lumped-parameter non-linear viscoelastic models of human fingertip tissue can describe fingertip force-displacement characteristics during a range of rapid, dynamic tapping tasks. Eight human subjects tapped with their index finger on the surface of a rigid load cell while an optical system tracked fingertip position using an infra-red LED attached to the fingernail. Four different tapping conditions were tested: normal and high-speed taps with a relaxed hand, and normal and high-speed taps with the other fingers co-contracted. A non-linear viscoelastic model comprised of an instantaneous stiffness function and viscous relaxation function was capable of predicting fingertip tissue force response due to measured pulp compression under these four different loading conditions. The model could successfully reconstruct very rapid (less than 5 ms) force transients, and forces occurring over time periods greater than 100 ms, with errors of 10%. Model parameters varied by less than 20% over the four conditions, despite almost 3-fold differences in average forces and 38% differences in fingertip velocities. Energy dissipation by the fingertip averaged 81%, and varied little (<3%) across conditions, despite a 1. 5-fold range of energy input. The ability of a lumped-parameter model to describe fingertip force-displacement characteristics during a range of conditions contributes both to understanding the transmission of force through the fingertip to the musculoskeletal system and to predicting the stimulation of mechano-receptors located within the fingertip.

Adult↗

[Effects of chilling and low light on cucumber seedlings growth and their antioxidative enzyme activities].

Studies on the growth and antioxidative enzyme activities of cucumber seedlings grown under low light and low temperature indicated that exposure of cucumber plants to low light at normal temperature and chilling under low light resulted in a retardation and a complete inhibition of plant growth, respectively, and their root vigor was also decreased. Chilling under low light increased the activities of SOD and GPOD, showing more significant effects at 7 degrees C than at 12 degrees C. The activities of these enzymes returned to normal after 5 days of recovery under normal conditions. Low light at normal temperature didn't affect SOD activity, which was increased when the plants were returned to normal growth conditions. GPOD activities increased markedly after 5 days of low light treatment and decreased during recovery. In addition, the content of MDA was increased during chilling and low light treatment.

Cold Temperature↗

[Distribution characteristics of types of stroke in three urban area in China].

OBJECTIVE: To analyze the distribution characteristics of types of stroke in china. METHODS: A prospective study and comprehensive prevention were conducted in urban communities with 300 000 people in Changsha, Beijing and Shanghai, and 2 570 case of stroke at their first occurance were selected with established typing diagnosis (r). RESULTS: Hemmorrhagic, ischemic, and unclassified stroke accounted for 37.1%, 62.3%, and 0.6% respectively. The proportion of hemmorrhagic stroke was more than 50 percent among persons under 50. The average yearly incidence of stroke was 142.3/100 thousand in the intervention areas and was 187.0/100 thousand in the control areas. CONCLUSION: Prevention should be focused on hemorrhagic stroke for those aged over 50 and on ischemic stroke for those aged less than 50. The average incidence rates of hemmorrhagic and of ischemic stroke were lower in the intervention area than in the control area.

Adolescent↗