Polymorphism

多态性
  • 文章类型: Journal Article
    多晶型物工程涉及通过受控的结构修饰来操纵材料特性,并且是用于创建独特的二维过渡金属二硫属化物(TMDC)纳米器件的候选技术。尽管承诺,磁性TMDC单层的多晶型物工程尚未得到证实。在这里,我们通过分子束外延生长FeSe2单层,并发现它们对磁性多晶型物工程有很大的希望。使用扫描隧道显微镜(STM)和光谱学(STS),我们发现FeSe2单层在5K时主要表现出1T的结构多晶型。从STM尖端施加电压脉冲会导致局部,从1T阶段到1T阶段的可逆过渡。密度泛函理论计算表明,这种单层结构相变伴随着从反铁磁结构到铁磁结构的磁转变。这些结果为通过多晶型物工程创建具有TMDC单层的功能性磁性设备开辟了新的可能性。
    Polymorph engineering involves the manipulation of material properties through controlled structural modification and is a candidate technique for creating unique two-dimensional transition metal dichalcogenide (TMDC) nanodevices. Despite its promise, polymorph engineering of magnetic TMDC monolayers has not yet been demonstrated. Here we grow FeSe2 monolayers via molecular beam epitaxy and find that they have great promise for magnetic polymorph engineering. Using scanning tunneling microscopy (STM) and spectroscopy (STS), we find that FeSe2 monolayers predominantly display a 1T\' structural polymorph at 5 K. Application of voltage pulses from an STM tip causes a local, reversible transition from the 1T\' phase to the 1T phase. Density functional theory calculations suggest that this single-layer structural phase transition is accompanied by a magnetic transition from an antiferromagnetic to a ferromagnetic configuration. These results open new possibilities for creating functional magnetic devices with TMDC monolayers via polymorph engineering.
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  • 文章类型: Journal Article
    标题化合物,3-[(苯并-1,3-二氧代-5-基)氨基]-4-甲氧基环丁-3-烯-1,2-二酮,C12H9NO5(3),是抗分枝杆菌squaramide的前体。单斜晶形的块状晶体(3-I,空间群P21/c,Z=8,Z\'=2)和三斜晶形的针状晶体(3-II,发现空间群P-1,Z=4,Z\'=2)同时结晶。在两种晶体形式中,R22(10)二聚体通过N-H组装。..O=C氢键。这些二聚体由3-I中的晶体学上独特的分子形成,但在3-II中表现出晶体学Ci对称性。在3-II的晶体中遇到了假杂物的孪生。固体形式3-I和3-II中的3的构象彼此不同,但对于每种多晶型物中的独特分子是相似的。对3的游离分子的密度泛函理论(DFT)计算表明,优选接近平面的构象。
    The title compound, 3-[(benzo-1,3-dioxol-5-yl)amino]-4-methoxycyclobut-3-ene-1,2-dione, C12H9NO5 (3), is a precursor to an antimycobacterial squaramide. Block-shaped crystals of a monoclinic form (3-I, space group P21/c, Z = 8, Z\' = 2) and needle-shaped crystals of a triclinic form (3-II, space group P-1, Z = 4, Z\' = 2) were found to crystallize concomitantly. In both crystal forms, R22(10) dimers assemble through N-H...O=C hydrogen bonds. These dimers are formed from crystallographically unique molecules in 3-I, but exhibit crystallographic Ci symmetry in 3-II. Twinning by pseudomerohedry was encountered in the crystals of 3-II. The conformations of 3 in the solid forms 3-I and 3-II are different from one another but are similar for the unique molecules in each polymorph. Density functional theory (DFT) calculations on the free molecule of 3 indicate that a nearly planar conformation is preferred.
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  • 文章类型: Journal Article
    背景:母体免疫系统的异常和妊娠免疫耐受不足可能会导致先兆子痫(PE)的发展。NLR家族pyrin结构域包含3(NLRP3)作为模式识别受体,可识别病原体相关的分子模式。白细胞介素-4(IL-4)是一种有效的抗炎细胞因子,可调节免疫反应。因此,本研究旨在阐明NLRP3和IL-4可变串联重复序列(VNTR)多态性对PE易感性的影响.
    方法:选取1,018例PE患者和1,007例正常孕妇作为病例组和对照组,分别。提取外周血DNA,使用聚合酶链反应和凝胶电泳对NLRP3和IL-4VNTR多态性进行基因分型。在两个队列中评估了孕妇的基因型和等位基因频率。
    结果:PE组NLRP3VNTR9-7基因型明显低于对照组,但是9和14等位基因频率在PE患者中明显更高。与对照组相比,IL-4VNTR基因型1-2的个体发生PE的风险较低,IL-4VNTR2等位基因频率在PE患者中明显降低。
    结论:这项研究,这是文献中的第一个,评估NLRP3VNTR和IL-4VNTR多态性对PE的影响,揭示了与PE易感性的显著相关性。这项研究有助于了解PE的发病机理,并为将来制定预防和治疗该疾病的策略提供参考。
    BACKGROUND: Abnormalities in the maternal immune system and insufficient gestational immune tolerance may significantly contribute to the development of preeclampsia (PE). The NLR family pyrin domain containing 3 (NLRP3) functions as a pattern recognition receptor that identifies pathogen-associated molecular patterns. Interleukin-4 (IL-4) is a potent anti-inflammatory cytokine that modulates the immune response. Therefore, this study aims to elucidate the impact of NLRP3 and IL-4 variable number of tandem repeats (VNTR) polymorphisms on susceptibility to PE.
    METHODS: A total of 1,018 patients with PE and 1,007 normal pregnant women were recruited as the case group and the control group, respectively. Peripheral blood DNA was extracted, and NLRP3 and IL-4 VNTR polymorphisms were genotyped using polymerase chain reaction and gel electrophoresis. Genotypes and allele frequencies of pregnant women were assessed in both cohorts.
    RESULTS: The NLRP3 VNTR 9-7 genotype in the PE group was significantly lower than that in the control group, but 9 and 14 allele frequencies were significantly higher in patients with PE. Individuals with IL-4 VNTR genotypes 1-2 had a lower risk of PE than controls, and the IL-4 VNTR 2 allele frequency was significantly lower in patients with PE.
    CONCLUSIONS: This study, the first of its kind in the literature, evaluates the impact of NLRP3 VNTR and IL-4 VNTR polymorphisms on PE, revealing a significant correlation with PE susceptibility. This investigation contributes to understanding the pathogenesis of PE and provides a reference point for developing strategies to prevent and treat the disease in the future.
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  • 文章类型: Journal Article
    从它的概念来看,X射线晶体学提供了对结构的独特理解,材料的键合和电子状态,which,反过来,解锁检查晶体系统的性质和功能的手段。使用最先进的单晶X射线衍射,随着紫外-可见光谱和DFT计算,Zwolenik等人。[(2024)。IUCrJ,11,519-527]提供了对1,3-二乙酰基芘的结构-光学性质关系的全面研究,其方法越来越多地为非专业实验室所用。
    From its conception, X-ray crystallography has provided a unique understanding of the structure, bonding and electronic state of materials, which, in turn, unlocks a means of examining the properties and function of crystalline systems. Using state-of-the-art single-crystal X-ray diffraction, along with UV-Vis spectroscopy and DFT calculations, Zwolenik et al. [(2024). IUCrJ, 11, 519-527] have provided a comprehensive study of the structure-optical property relationship of 1,3-diacetylpyrene with methodologies that are increasingly accessible to non-specialist laboratories.
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  • 文章类型: Journal Article
    牛皮癣是一种慢性炎症性皮肤病,影响世界各地的人们。它与HLA-Cw6等位基因有关,这在高加索人比在亚洲人更常见,并且因种族而异。我们调查了越南牛皮癣患者的疾病严重程度与HLA-Cw6患病率发病年龄之间的关系。在121名银屑病患者和30名健康对照者中,我们研究了HLA-Cw6与临床特征之间的关系.我们发现牛皮癣患者的HLA-Cw6水平(64.5%)明显高于对照组(26.7%)(p=0.0001),赔率比为4.98(2.04-12.15)。HLA-Cw6阳性患者的银屑病发病平均年龄明显低于HLA-Cw6阴性患者。轻度银屑病患者(100%)更可能有AA基因型,而中重度银屑病患者(47.2%和59.0%,分别)和PASI得分高的人(55.1%和54.1%,分别)更有可能具有TA基因型。因此,HLA-Cw6是越南患者银屑病的主要遗传危险因素,尤其是早发性病例。HLA-Cw6基因型的变异也影响疾病的严重程度。
    Psoriasis is a chronic inflammatory skin disease that affects people all over the world. It is linked to the HLA-Cw6 allele, which is more common in Caucasians than in Asians and varies across ethnic groups. We investigated the association between the disease severity and the onset age of HLA-Cw6 prevalence in Vietnamese psoriasis patients. In 121 psoriasis patients and 30 healthy controls, we looked at the relationship between HLA-Cw6 and clinical features. We found that patients with psoriasis had significantly higher levels of HLA-Cw6 (64.5%) than controls (26.7%) (p=0.0001), with an odds ratio of 4.98 (2.04-12.15). Positive HLA-Cw6 patients had a significantly lower mean age of psoriasis onset than negative HLA-Cw6 patients. Patients with mild psoriasis (100%) were more likely to have the AA genotype, while patients with moderate to severe psoriasis (47.2% and 59.0%, respectively) and those with high PASI scores (55.1% and 54.1%, respectively) were more likely to have the TA genotype. Thus, HLA-Cw6 is a major genetic risk factor for psoriasis in Vietnamese patients, especially early-onset cases. Variations in HLA-Cw6 genotypes also affect disease severity.
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  • 文章类型: Journal Article
    分析SNPs(rs1801131和rs1801133)中MTHFR基因的遗传变异与伊拉克类风湿关节炎(RA)患者的治疗结果之间的关系。该研究是对95名伊拉克RA患者进行的。根据他们的治疗反应,该队列分为两组:应答者(47例患者)和无应答者(48例患者),在甲氨蝶呤(MTX)治疗至少三个月后鉴定。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术分析MTHFR变异,特别是在rs1801133和rs1801131。总的来说,rs1801131遵循共同主导和主导模式,在共支配模型中,与TT基因型相比,GG[OR(95%CI)0.11(0.022-0.553)]和TG[OR(95%CI)0.106(0.021-0.528)]预测反应者;同时,对于主导模型,与TT基因型相比,GG和TG基因型[OR(95%CI)0.108(0.023-0.507)]的存在共同预测应答者.Ars1801133Grs1801131单倍型与应答者显著相关[OR(95%CI):0.388(0.208-0.723)],而Grs1801133Trs1801131单倍型与无反应者略有相关[OR(95%CI)1.980(0.965-4.064)].在最后的多变量分析中,GG/TGrs1801131基因型在调整患者后与应答者独立相关,疾病,和治疗特点,而TTrs1801131基因型与无反应者相关。伊拉克RA患者显示MTHFR基因rs1801131的遗传多态性,T携带者等位基因与MTX治疗无反应者相关。rs1801131遵循共显性和显性模型。rs1801131的G携带等位基因在调整患者后显示出与MTX治疗应答者的独立关联,疾病,和治疗特点。
    Analyze the relationship between genetic variations in the MTHFR gene at SNPs (rs1801131 and rs1801133) and the therapy outcomes for Iraqi patients with rheumatoid arthritis (RA). The study was conducted on a cohort of 95 RA Iraqi patients. Based on their treatment response, the cohort was divided into two groups: the responder (47 patients) and the nonresponder (48 patients), identified after at least three months of methotrexate (MTX) treatment. A polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) technique was employed to analyze the MTHFR variations, specifically at rs1801133 and rs1801131. Overall, rs1801131 followed both codominant and dominate models, in which in the codominant model, GG [OR (95% CI) 0.11 (0.022-0.553)] and TG [OR (95% CI) 0.106 (0.021-0.528)] predict responders compared to the TT genotype; meanwhile, for the dominate model, the presence of both GG and TG genotypes [OR (95% CI) 0.108 (0.023-0.507)] together predict responders compared to the TT genotype. The Ars1801133Grs1801131 haplotype was significantly associated with responders [OR (95% CI): 0.388 (0.208-0.723)], while the Grs1801133Trs1801131 haplotype was associated marginally with nonresponders [OR (95% CI) 1.980 (0.965-4.064)]. In the final multivariate analysis, GG/TGrs1801131 genotypes were independently related to responders after adjustment for patients, disease, and treatment characteristics, while TTrs1801131 genotypes were associated with nonresponders. The Iraqi RA patients showed genetic polymorphism in MTHFR gene rs1801131 with T carrier allele associated with nonresponders to MTX therapy. The rs1801131 followed both codominant and dominant models. The G-carried allele for rs1801131 showed an independent association with responder to MTX therapy after adjustment for patients, disease, and treatment characteristics.
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  • 文章类型: Journal Article
    在兔子中没有报道过朊病毒病的自然病例,并且先前鉴定朊病毒转化剂的尝试都没有成功。然而,朊病毒种子扩增实验技术的最新应用引起了人们对兔对朊病毒病感染的潜在易感性的新兴趣。在与朊病毒疾病相关的几个因素中,朊病毒样蛋白基因(PRND)内的多态性,病毒蛋白家族的一员,据报道,在各种物种中与疾病易感性显着相关。因此,本研究旨在调查家兔PRND基因的多态性并分析其遗传特征。
    从207个兔样本中提取基因组DNA以研究草孔素PRND多态性。随后,进行靶向leporinePRND基因编码区的扩增子测序。此外,连锁不平衡(LD)分析用于评估基因座内部和基因座之间的连接。使用PolyPhen-2评估了非同义单核苷酸多态性(SNP)对Doppel蛋白的影响。
    我们在leporinePRND基因中发现了9个新的SNP:c.18a>G,c.76G>C,c.128C>T,c.146C>T,c.315A>G,c.488G>A,c.525G>C,c.544G>A,和c.579A>G值得注意的是,其中七个PRNDSNP,不包括c.525G>C和c.579A>G,表现出超过0.3的强LD值。此外,LD分析证实了PRNPSNPc.234C>T和PRNDSNP在c.525G>C和c.579A>G之间的牢固联系。此外,根据PolyPhen-2和SIFT分析,预测四个非同义SNP对Doppel蛋白的功能或结构具有有害影响。然而,PANTHER和Missense3D没有显示这种影响。
    在本文中,我们在兔PRND基因中发现了新的SNP,并通过4个非同义SNP预测了它们对蛋白质功能或结构的潜在有害影响.此外,我们观察到PRND和PRNP基因中SNP之间的遗传连锁。这些发现可能为了解兔子作为部分抗性物种的特征提供了见解。据我们所知,这项研究是首次在家兔中对PRNDSNP进行遗传表征。
    UNASSIGNED: Natural cases of prion disease have not been reported in rabbits, and prior attempts to identify a prion conversion agent have been unsuccessful. However, recent applications of prion seed amplifying experimental techniques have sparked renewed interest in the potential susceptibility of rabbits to prion disease infections. Among several factors related to prion disease, polymorphisms within the prion-like protein gene (PRND), a member of the prion protein family, have been reported as significantly associated with disease susceptibility in various species. Therefore, our study aimed to investigate polymorphisms in the PRND gene of rabbits and analyze their genetic characteristics.
    UNASSIGNED: Genomic DNA was extracted from 207 rabbit samples to investigate leporine PRND polymorphisms. Subsequently, amplicon sequencing targeting the coding region of the leporine PRND gene was conducted. Additionally, linkage disequilibrium (LD) analysis was employed to assess the connection within and between loci. The impact of non-synonymous single nucleotide polymorphisms (SNPs) on the Doppel protein was evaluated using PolyPhen-2.
    UNASSIGNED: We found nine novel SNPs in the leporine PRND gene: c.18A > G, c.76G > C, c.128C > T, c.146C > T, c.315A > G, c.488G > A, c.525G > C, c.544G > A, and c.579A > G. Notably, seven of these PRND SNPs, excluding c.525G > C and c.579A > G, exhibited strong LD values exceeding 0.3. In addition, LD analysis confirmed a robust link between PRNP SNP c.234C > T and PRND SNPs at c.525G > C and c.579A > G. Furthermore, according to PolyPhen-2 and SIFT analyses, the four non-synonymous SNPs were predicted to have deleterious effects on the function or structure of the Doppel protein. However, PANTHER and Missense3D did not indicate such effects.
    UNASSIGNED: In this paper, we have identified novel SNPs in the rabbit PRND gene and predicted their potential detrimental effects on protein function or structure through four non-synonymous SNPs. Additionally, we observed a genetic linkage between SNPs in the PRND and PRNP genes. These findings may provide insights into understanding the characteristics of rabbits as partially resistant species. To the best of our knowledge, this study is the first to genetically characterize PRND SNPs in rabbits.
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  • 文章类型: Journal Article
    确定Gly64Asp(rs77630697)多药和毒素挤出-1(MATE-1)的多态性与2型糖尿病患者二甲双胍治疗反应之间的关系。
    在Riphah国际医院进行了一项纵向研究,2020年6月至2021年12月,伊斯兰堡。纳入符合纳入标准的二甲双胍单药治疗的2型糖尿病患者(n=200),并随访至三个月。基于HbA1c的变化,他们分为响应者和非响应者。提取DNA并通过TETRAARMSPCR进行基因分型。输入数据并通过SPSS22进行关联分析。
    在200名参与者中,104人被归类为响应者,96人被归类为非响应者。rs77630697的基因型和等位基因分布在应答者和非应答者之间显著不同。变异基因型(GG)在研究人群和应答者中最普遍。经过三个月的随访,在三种基因型(GG,GA和AA)。与GA和AA相比,GG基因型的HbA1c下降幅度最大,几乎减少了两倍。等位基因A的携带者与二甲双胍反应受损显著相关。
    应答者和非应答者对二甲双胍的可变治疗反应可能与MATE-1的rs77630697同工型变异有关。
    UNASSIGNED: To determine the relationship between Gly64Asp (rs77630697) polymorphism of multidrug and toxin extrusion-1 (MATE-1) and therapeutic response of metformin in Type-2 diabetic patients.
    UNASSIGNED: A longitudinal study was conducted at Riphah International Hospital, Islamabad from June 2020 to December 2021. Type-2 diabetic patients (n=200) on metformin monotherapy fulfilling the inclusion criteria were enrolled and followed up till three months. Based on change in HbA1c, they were divided into responders and non-responders. DNA was extracted and genotyping was done by TETRA ARMS PCR. Data was entered and association was analyzed by SPSS 22.
    UNASSIGNED: Out of 200 participants, 104 were categorized as responders and 96 as non-responders. The genotype and allelic distribution of rs77630697 was significantly different between responders and non-responders. The variant genotype (GG) was most prevalent among the study population and among responders. After follow up of three months, difference in glycemic response was found to be statistically significant (p < 0.05) among three genotypes (GG, GA and AA). The decline in HbA1c was highest in GG genotype with almost two-fold reduction in comparison with GA and AA. Carriers of allele A were significantly associated with impaired response to metformin.
    UNASSIGNED: The variable therapeutic response to metformin in the responders and non-responders may be contributed to rs77630697 isoform variation of MATE-1.
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  • 文章类型: Journal Article
    目的:使用多组学方法探索核因子E2相关因子2抗氧化反应元件(Nrf2-ARE)信号通路中的基因与绝经后早期激素受体阳性乳腺癌妇女癌因性疲乏(CRF)的相关性。
    从宾夕法尼亚州西部招募绝经后早期激素受体阳性乳腺癌妇女(N=116)。
    研究了来自Nrf2-ARE通路的候选基因与CRF发生和严重程度的关联。使用发生的逻辑回归和严重程度的线性回归评估关联。
    结果:NFE2L2中的rs2706110TT基因型与CRF发生几率增加3.5倍相关。PRDX1中的胞嘧啶-磷酸-鸟嘌呤(CpG)位点cg22820568与CRF的发生和严重程度相关。
    结论:基于Nrf2-ARE基因的生物标志物可能有助于识别患有更严重CRF风险增加的女性,并制定有针对性的干预措施。
    OBJECTIVE: To explore genes in the nuclear factor E2-related factor 2 antioxidative response elements (Nrf2-ARE) signaling pathway using a multiomics approach for associations with variability of cancer-related fatigue (CRF) in postmenopausal women with early-stage hormone receptor-positive breast cancer.
    UNASSIGNED: Postmenopausal women (N = 116) with early-stage hormone receptor-positive breast cancer were recruited from western Pennsylvania.
    UNASSIGNED: Candidate genes from the Nrf2-ARE pathway were investigated for associations with CRF occurrence and severity. Associations were evaluated using logistic regression for occurrence and linear regression for severity.
    RESULTS: The rs2706110 TT genotype in NFE2L2 was associated with a 3.5-fold increase in odds of CRF occurrence. The cytosine-phosphate-guanine (CpG) site cg22820568 in PRDX1 was associated with CRF occurrence and severity.
    CONCLUSIONS: Biomarkers based on Nrf2-ARE genes may help to identify women at increased risk for more severe CRF and to develop targeted interventions.
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  • 文章类型: Journal Article
    神经母细胞瘤是儿童最常见的颅外恶性实体瘤之一。AlkB同源物5(ALKBH5)是一种RNAN6-甲基腺苷(m6A)去甲基酶,在肿瘤发生和发展中起关键作用。我们在一项病例对照研究中评估了ALKBH5中的单核苷酸多态性(SNP)与神经母细胞瘤风险之间的关联,该研究包括402名患者和473名非癌症对照。
    通过TaqMan方法测定基因分型。使用比值比(OR)和95%置信区间(CI)评估ALKBH5多态性(rs1378602和rs8400)与神经母细胞瘤风险之间的关联。
    我们没有发现ALKBH5rs1378602和rs8400与神经母细胞瘤风险的强关联。按年龄进一步分层分析,性别,主站点,和临床分期显示,rs1378602AG/AA基因型与男性(校正OR=0.58,95%CI=0.35-0.97,p=0.036)和腹膜后神经母细胞瘤儿童(校正OR=0.58,95%CI=0.34-0.98,p=0.040)的神经母细胞瘤风险较低。
    ALKBH5SNP似乎与神经母细胞瘤风险无关。需要更多的研究来证实这一阴性结果,并揭示m6A修饰物ALKBH5的基因多态性与神经母细胞瘤之间的关系。
    UNASSIGNED: Neuroblastoma is one of the most common extracranial malignant solid tumors in children. AlkB homolog 5 (ALKBH5) is an RNA N6-methyladenosine (m6A) demethylase that plays a critical role in tumorigenesis and development. We assessed the association between single nucleotide polymorphisms (SNPs) in ALKBH5 and the risk of neuroblastoma in a case-control study including 402 patients and 473 non-cancer controls.
    UNASSIGNED: Genotyping was determined by the TaqMan method. The association between ALKBH5 polymorphisms (rs1378602 and rs8400) and the risk of neuroblastoma was evaluated using the odds ratio (OR) and 95% confidence interval (CI).
    UNASSIGNED: We found no strong association of ALKBH5 rs1378602 and rs8400 with neuroblastoma risk. Further stratification analysis by age, sex, primary site, and clinical stage showed that the rs1378602 AG/AA genotype was associated with a lower risk of neuroblastoma in males (adjusted OR = 0.58, 95% CI = 0.35-0.97, p = 0.036) and children with retroperitoneal neuroblastoma (adjusted OR = 0.58, 95% CI = 0.34-0.98, p = 0.040).
    UNASSIGNED: ALKBH5 SNPs do not seem to be associated with neuroblastoma risk. More studies are required to confirm this negative result and reveal the relationship between gene polymorphisms of the m6A modifier ALKBH5 and neuroblastoma.
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