Ultrasound mediated efficient synthesis of new 4-oxoquinazolin-3(4H)-yl)furan-2-carboxamides as potent tyrosinase inhibitors: Mechanistic approach through chemoinformatics and molecular docking studies

We have carried out the synthesis of new 4-oxoquinazolin-3(4H)-yl)furan-2-carboxamide derivatives by the reaction between isatoic anhydride, 2-furoic hydrazide and substituted salicylaldehydes in ethanol: water (5:5 v/v) solvent system using p-TSA as a catalyst under ultrasound irradiation at room temperature. The structures of newly synthesized compounds were confirmed through spectral techniques such as IR, ¹H NMR, ¹³C NMR, and LCMS. The important features of this protocol include simple and easy workup procedure, reaction carried out at ambient temperature, use of ultrasound and high yield of oxoquinazolin-3(4H)-yl)furan-2-carboxamides in short reaction time. The synthesized compounds 4a–4j were screened against tyrosinase enzyme and all these compounds found to be potent inhibitors with much lower IC₅₀ value of 0.028 ± 0.016 to 1.775 ± 0.947 µM than the standard kojic acid (16.832 ± 1.162 µM). The kinetics mechanism for compound 4e was analyzed by Lineweaver-Burk plots which revealed that compound inhibited tyrosinase non-competitively by forming an enzyme-inhibitor complex. Along with this all the synthesized compounds (4a–4j) were scanned for their DPPH free radical scavenging ability. The outputs received through in vitro and in silico analysis are coherent to the each other with good binding energy values (kcal/mol) posed by synthesized ligands.     

基于间隔二肽组分和递归特征消除法的DNA结合蛋白的鉴定

DNA结合蛋白(DNA-binding proteins,DBPs)的鉴定在原核和真核生物的基因和蛋白质功能注释研究中具有十分重要的意义.本研究首次运用间隔二肽组分(gapped-dipeptide composition,Gap DPC)结合递归特征消除法(recursive feature elimination,RFE)鉴定DBPs.首先获得待测蛋白质氨基酸序列的位置特异性得分矩阵(position specific scoring matrix,PSSM),在此基础上提取蛋白质的Gap DPC特征,通过RFE法选择最优特征,然后利用支持向量机(support vector machine,SVM)作为分类器,在蛋白质序列数据集PDB396和LB1068中进行夹克刀交叉验证(jackknife cross validation test).研究结果显示,基于PDB396和LB1068数据集,DBPs预测的准确率、Matthews相关系数、敏感性和特异性分别达到93.43%、0.86、89.04%和96.00%,以及86.33%、0.73、86.49%和86.18%,明显优于文献报道中的相关方法,为DBPs的鉴定提供了新的模型.     

黄伞菌丝蛋白质营养价值评价

本文测定了黄伞Pholiotaadiposa菌丝粗蛋白含量和氨基酸组成,采用国际上通用的营养价值评价方法,对其蛋白质的营养价值进行全面评价,并与营养价值较高的白灵侧耳Pleurotusnebrodensis、刺芹侧耳Pleurotuseryngii和金顶侧耳Pleurotrscitrinopileatus进行比较。分析结果表明,黄伞菌丝的必需氨基酸含量最高,占其氨基酸总量的43.9%,蛋白质的氨基酸评分(AAS)、化学评分(CS)、必需氨基酸指数(EAAI)、生物价(BV)、营养指数(NI)和氨基酸比值系数分(SRCAA)分别为92.0、71.3、88.5、84.8、40.4和78.8,六项指标均比参比食用菌高。结果说明黄伞菌丝具有很高的营养价值。     

Convergence to Normality of the Asymptotic Quasi‐Score Function on a Linear Model

The asymptotic quasi‐likelihood method is considered for the model y_t = f_t(θ) + M_t, t = 0,1, …,T where f_tθ) is a linear predictable process of the parameter of interest θ, M_t is a martingale difference, and the nature of E(M_t² | ℱ_t–1) is unknown. This paper is concerned with the limiting distribution of the asymptotic quasi‐score function of such a model. Confidence intervals and hypothesis testing of θ is derived from the limiting distribution. Comparison is made between the estimates obtained through this method and those obtained through the least squares method.     

血清IgE水平与冠心病的相关性分析

目的:探讨血清IgE水平与冠心病的相关性。方法:将我院收治的135例患者根据冠脉造影结果分为冠心病组(CHD)和非冠心病组(non-CHD),冠心病组根据临床症状分为稳定型心绞痛组(SAP)、不稳定型心绞痛组(UAP)和急性心肌梗死组(AMI),动脉堵塞程度用Gensini评分量化,采用SIMENS BNII全自动免疫散射比浊仪测定总IgE水平。比较CHD和non-CHD组患者及SAP、UAP和AMI组患者血清IgE水平的差异,并进一步分析血清IgE等级与冠心病Gensini积分的相关性。结果:non-CHD患者血清IgE水平(32.3(13.5,61)KU/L)明显低于CHD患者(69(26.4,169)KU/L)(P=0.001),UAP和AMI患者血清IgE水平(78.6(37.0,191.0)KU/L、118.5(75.3,148.1)KU/L)均显著高于SAP组(36.7(20.7,96.7)KU/L)(P=0.034和P=0.001),且多支血病变组患者血清IgE水平(67.2(30.9,249.0)KU/L)显著高于单支血管病变患者(34.6(18.1,59.0)KU/L)(P=0.039)。IgE水平根据四分位间距分为四个等级,随着IgE分级水平增加冠心病Gensini积分增加。结论:冠心病患者血清IgE水平升高,且与冠心病类型和血管堵塞程度都存在显著相关性,可能辅助冠心病的诊断及病情监测。     

布地奈德福莫特罗治疗支气管哮喘患者的临床疗效及对患者血清炎性因子水平的影响

目的:探讨布地奈德福莫特罗吸入治疗对慢性支气管哮喘患者的临床疗效及其对患者血清炎性因子水平、肺功能和生活质量的影响。方法:选择2014年2月至2016年2月于我院呼吸内科就诊并确诊为慢性支气管哮喘患者123例,根据随机数字表法分为观察组65例和对照组58例。比较两组患者治疗前后血清白介素17(IL-17)、白介素33(IL-33)、基质金属蛋白酶9(MMP-9)、肺功能、生活质量评分的变化、临床疗效有效率及不良反应的发生情况。结果:观察组的总有效率为92.3%(60/65),显著高于对照组(81.03%,P0.05)。治疗后,两组患者的血清IL-17、IL-33水平与治疗前相比均显著降低(P0.05),且观察组显著低于对照组(P0.05);两组血清MMP-9水平与治疗前相比差异均无统计学意义(P0.05);观察组患者的第一秒用力呼吸容积(FEV1)、峰值呼气流速(PEF)与第一秒用力呼气容积与用力肺活量比值(FEV1/FVC)水平均明显增加,且观察组上述指标明显高于对照组(P0.05);圣.乔治呼吸问卷(SGRQ)评分结果显示观察组患者的生活质量显著高于对照组患者。结论:布地奈德福莫特罗吸入治疗对慢性支气管哮喘临床效果显著,可显著控制炎症反应,改善肺功能,显著提升患者生活质量。     

甲状腺功能减退症患者心理健康状况及影响因素分析

目的:研究甲状腺功能减退症患者的心理健康状况及其影响因素,为预防、改善甲减患者心理健康状况提供参考依据。方法:选取2014年1月-2016年1月来我院治疗的226例甲减患者作为甲减组,另从杨浦区多个社区随机抽取同期254例健康者作为健康组,采用SCL-90症状自评量表、社会支持评定量表(SSRS)及一般情况调查问卷对两组研究对象进行调查,采用Logistic回归分析甲减患者的影响因素。结果:两组性别、年龄及职业之间的差异无统计学意义(P0.05),而文化程度、经济收入的差异具有统计学意义(P0.05);甲减组患者强迫症状、抑郁、焦虑、精神病性评分及总分均高于健康组(P0.05);甲减组患者中焦虑、抑郁、人际关系敏感所占比重较高,分别为30.97%,26.11%,26.11%;与健康组相比,甲减组患者SSRS评分中主观支持、客观支持、支持利用度评分及总分均明显降低(P0.05);多因素Logistic回归分析显示社会支持、文化程度为小学、经济收入30000元/年是甲减患者心理健康的影响因素(P0.05)。结论:甲减患者心理状况较差,存在较严重的焦虑和抑郁情况,在治疗同时应注意健康教育和心理关怀,尤其是对收入低、文化程度低或社会支持程度低的患者,应给予及时的心理治疗,可提高患者的生活质量。