Association analysis of polymorphism in the NR6A1 gene with the lumbar vertebrae number traits in sheep

Xiangyu Zhang,Cunyuan Li,Xiaoyue Li,Zhijin Liu,Wei Ni,Yang Cao,Yang Yao,Esenbay Islamov,Junchang Wei,Xiaoxu Hou,Shengwei Hu 한국유전학회 2019 Genes & Genomics Vol.41 No.10

Introduction The vertebral number is an economically significant trait, which is associated with body length and carcass traits. Nuclear Receptor Subfamily 6, Group A, Member 1 (NR6A1) is a member of the nuclear receptor superfamily and it plays an important role in the early development of embryos. Objectives The NR6A1 gene was considered as an important candidate for influence vertebrae number, while the potential associations between this gene and the number of lumbar vertebrae traits of sheep have not been explored. Methods In this study, we detected the genetic variants of NR6A1 gene and analyzed the associations of the polymorphisms with lumbar number traits in 130 Kazakh sheep. We use single-strand conformation polymorphism (SSCP) technique to detect single nucleotide polymorphism (SNP) of NR6A1 gene, and the association of the genotype and lumbar number variation was analyzed by independent Chi-square test. Results We detect SNP of NR6A1 gene by PCR-SSCP technique, and polymorphisms were only found in the coding region of exon-6 and exon-8 of NR6A1 gene. In order to investigate the connection between the SNP locus and lumbar number traits in sheep, we conducted a Chi-square test for independence for exon-6 and exon-8 of NR6A1 gene, respectively. Association analysis revealed significant associations between the SNP (rs414302710: A >C) in the exon-8 of NR6A1 gene with the number of lumbar vertebrae (P < 0.01). Conclusion Our study indicated that this SNP (rs414302710: A>C) locus of exon-8 of NR6A1 gene in sheep possible influence the number of lumbar vertebrae, which has the potential to be applied in selective breeding of sheep.

Spermine and oxacillin stress response on the cell wall synthesis and the global gene expression analysis in Methicillin-resistance Staphylococcus aureus

Shrikant Pawar,Xiangyu Yao,Chung‑Dar Lu 한국유전학회 2019 Genes & Genomics Vol.41 No.1

Methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly emerging bacteria causing infection, which has developed resistance to most of the beta-lactam antibiotics because of newly acquired low-affinity penicillin-binding protein (PBP2a), which can continue to build the cell wall when beta-lactams block other PBPs. Exogenous spermine exerts a dose-dependent inhibition effect on the growth of Escherichia coli, Salmonella enterica serovar, and S. aureus. Selection of an MRSA Mu50 derivative which harbors mutation on PBP2 gene (named as MuM) showing spermine resistance and which confers a complete abolishment of spermine-beta-lactam synergy was identified. To further investigate the gene expression changes, a transcriptome profiling of MuM against Mu50 (wild-type) without any treatment, MuM and Mu50 in response to high dose spermine and Mu50 in response to spermine-beta-lactam synergy at 15, 30 and 60 min time points was performed. Functional annotation was further performed to delineate the metabolic pathways associated with the significant genes. A significant down-regulation in the iron regulatory system, potassium channel uptake and polyamine transport system with an up-regulation in general stress response sigB dependent operon in MuM strain at 15, 30 and 60 min time points with spermine treatment compared to Mu50 strain was observed. Analysis of spermine-dependent synergy with beta-lactams on cell wall synthesis revealed that it significantly reduces the degree of cross-linkage on cell wall with no change in trypsin digestion pattern of purified PBPs and without affecting PBPs expression or PBPs acylation by Bocillin. A strong relation between PBP2 protein and general stress sigB response, iron, potassium and polyamine transport systems was observed. SigB regulon should be activated on stress, which was not seen in some of our previous studies where it was down-regulated in wild-type Mu50 strain with spermine stress. Here, an intriguing finding is made where there seems to be a correction of this abnormal response of no SigB induction to a significant induction by PBP2 mutation. In MuM strain, a significant downregulation of KdpABC operon genes at 15, 30 and 60 min time points on spermine stress is seen, which seems to be absent without spermine treatment. Since KCL has been found to protect the cell against spermine stress in wild-type strain by induction of KdpABC operon, it fails to do so in MuM strain underlying the importance of PBP2 protein in spermine stress. Analysis of spermine-dependent synergy with beta-lactams on cell wall synthesis revealed that it significantly reduces the degree of cross-linkage on cell wall with no change in trypsin digestion patterns of purified PBPs and without affecting PBPs expression or PBPs acylation by Bocillin. Furthermore, spermine does not help in enhancing the binding of beta-lactams to PBPs and binding of spermine to PBPs does not cause conformational changes to PBPs, as tested with trypsin digestion patterns. Future studies on the molecular mechanism of spermine interactions with these systems hold great potential for the development of new therapeutics for MRSA infections.

Updated Bayesian Network Meta-Analysis of Adjuvant Targeted Treatment Regimens for Early Human Epidermal Growth Factor Receptor-2 Positive Breast Cancer

Xinyan Li,Litong Yao,Mozhi Wang,Mengshen Wang,Xiang Li,Xueting Yu,Jingyi Guo,Haoran Dong,Xiangyu Sun,Yingying Xu 한국유방암학회 2020 Journal of breast cancer Vol.23 No.4

Purpose: Combining targeted agents with adjuvant chemotherapy prolongs survival in human epidermal growth factor receptor 2 (HER2)-positive breast cancer patients, but also increases the risk of adverse effects. The updated results of 3 randomized controlled trials (RCTs) were reported in 2019. Given the lack of adequate head-to-head pairwise assessment for anti-HER2 agents, network meta-analysis facilitates obtaining more precise inference for evidence-based therapy. Methods: RCTs comparing at least 2 anti-HER2 regimens in an adjuvant setting for HER2- positive early-stage breast cancer (EBC) were included. Hazard ratios for overall survival (OS) and disease free survival (DFS), with respective 95% confidence intervals were pooled for assessment of efficacy. A Bayesian statistical model was used, and odds ratios (ORs) for adverse events (AEs) were used to pool effect sizes. Results: We demonstrated that 1-year trastuzumab plus chemotherapy had increased efficacy compared to shorter or longer treatment duration. The OR of cardiac events gradually increased from 6 months to 1 and 2-year trastuzumab arms, relative to chemotherapy only. Compared to trastuzumab plus chemotherapy, dual HER2-targeting therapies increased DFS, especially for hormone receptor negative patients. Dual anti-HER2 blockade regimens revealed an increased probability of gastrointestinal reactions. As a second agent, pertuzumab showed significantly higher DFS and OS. Conclusion: We conclude that 1-year adjuvant trastuzumab should remain as the standard treatment for HER2-positive EBC patients, as it has greater efficacy and a manageable proportion of AEs. Clinical efficacy can be increased for hormone receptor-negative tumors by including a second HER2-targeted agent to the treatment regimen. For hormone receptor-positive cases with basal disease, it is acceptable to reduce the risk of cardiotoxicity by shortening the duration of trastuzumab.

Mechanical and antibacterial properties of resin co-filled with mesoporous silica and graphene quantum dots

Lu Shuxin,Zhang Hongyu,Chai Maozhou,Yao Xiaohong,Zhang Xiangyu,Yang Yongqiang 한국탄소학회 2023 Carbon Letters Vol.33 No.2

Poor mechanical properties and bacterial infection are the main problems faced by dental restorative resins in clinical use. In this study, graphene quantum dots (GQDs) grafted with imidazole groups and mesoporous silica (MSN) are co-filled in a dental resin to impart excellent antimicrobial activity and mechanical properties to the dental resin. The higher specific surface area of GQDs and MSN results in an increased contact area with the resin matrix, which enhances the strength of the dental composite resin. The introduction of GQDs significantly improves the antimicrobial activity of the resin. The inhibition efficiency of the composite resin against Streptococcus mutans reached 99.9% with the addition of GQDs at only 0.2 wt.%. When MSN and GQDs are co-filled, MSN interferes with the release of GQDs, thus reducing the antimicrobial activity of the dental resin but improving the cyto-compatibility. By reasonably adjusting the amount of GQDs and MSN, the dental composite resin can exhibit excellent antimicrobial properties, mechanical properties and cyto-compatibility at the same time.