Energetic coupling between native-state prolyl isomerization and conformational protein folding

In folded proteins, prolyl peptide bonds are usually thought to be either trans or cis because only one of the isomers can be accommodated in the native folded protein. For the N-terminal domain of the gene-3 protein of the filamentous phage fd (N2 domain), Pro161 resides at the tip of a beta hairpin and was found to be cis in the crystal structure of this protein. Here we show that Pro161 exists in both the cis and the trans conformations in the folded form of the N2 domain. We investigated how conformational folding and prolyl isomerization are coupled in the unfolding and refolding of N2 domain. A combination of single-mixing and double-mixing unfolding and refolding experiments showed that, in unfolded N2 domain, 7% of the molecules contain a cis-Pro161 and 93% of the molecules contain a trans-Pro161. During refolding, the fraction of molecules with a cis-Pro161 increases to 85%. This implies that 10.3 kJ mol(-1) of the folding free energy was used to drive this 75-fold change in the Pro161 cis/trans equilibrium constant during folding. The stabilities of the forms with the cis and the trans isomers of Pro161 and their folding kinetics could be determined separately because their conformational folding is much faster than the prolyl isomerization reactions in the native and the unfolded proteins. The energetic coupling between conformational folding and Pro161 isomerization is already fully established in the transition state of folding, and the two isomeric forms are thus truly native forms. The folding kinetics are well described by a four-species box model, in which the N2 molecules with either isomer of Pro161 can fold to the native state and in which cis/trans isomerization occurs in both the unfolded and the folded proteins.     

汽车尾气污染对四种北方阔叶树苗木膜脂过氧化和保护酶活性的影响

采用相同浓度(25μgNO2·m^-3)不同处理时间(1、3、5、7d)和相同处理时间(2h)不同浓度(40、60、80、100μgNO2·m^-3)两种方法进行熏气处理,研究了汽车尾气对五角槭、山荆子、山梨和茶条槭苗木叶液pH值、相对电导率、MDA含量、叶绿素含量、SOD和POD活性及ASA含量的影响．结果表明．随着熏气时间的延长和熏气浓度的增加,4个树种苗木的叶液pH值、叶绿素含量和ASA含量均逐渐降低,相对电导率、MDA含量、SOD和POD活性逐渐上升,不同树种苗木叶片组织的各项指标间存在较大差异,相同浓度处理7d后．山梨苗木叶片组织的pH降幅最大,山荆子次之,茶条槭最小;叶绿素含量的下降顺序为山梨>山荆子>茶条槭>五角槭;ASA含量的下降幅度以五角槭和茶条槭较小,山荆子和山梨较大,随着处理时间的延长．五角槭苗木叶片组织的相对电导率和MDA含量上升幅度最大．分别比对照升高了68．1％和52．50％,山荆子次之,茶条槭最小．随着处理浓度的增加,山荆子苗木的相对电导率和MDA上升幅度最大,分别比对照升高99．8％和52．5％,山梨次之,五角槭和茶条槭较小．4个树种苗木的自由基清除系统受到明显影响．SOD、POD活性呈上升趋势,茶条槭除ASA变幅稍高于五角槭外．各项生理指标的变化明显低于其它3个树种,表现出相对较强的抗性,山荆子的各项生理指标变化幅度相对较大,且其SOD和POD在最高浓度处理时开始遭到破坏．表现出相对较弱的抗性。     

耦合风险与服务的市域生态安全格局构建——以陕西省咸阳市为例

生态安全格局如何结合地域生态风险和地方生态需求进行构建,是该领域服务于国土空间治理并且能否有效应用的主要议题之一。本研究以咸阳市为对象,结合市域地貌形态、地域生态安全影响因素和景观特征,基于“源地”空间可达性和空间质量,融合形态学空间格局分析和生态抗性、生态连通性、生态系统服务价值综合评价结果,叠加生态梯度分析,以源地-廊道-节点的方式构建生态安全格局。结果表明: 咸阳市生态源地66个,总面积2506.65 km²,约占全市总面积的24.6%,主要分布于东北、西侧、中部山区;生态廊道106条,总长823.5 km,包括潜在廊道、水系、灌渠遗址、秦直道等自然与人文系统,沿生态源地向西北、南部渭河延伸;提升生态连通性的生态节点20处,主要分布于二道塬与旱腰带之间。     

磁共振弥散加权成像及ADC值对鼻咽癌颅底放疗疗效的评价价值

目的:探讨磁共振弥散加权成像(DWI)及表观扩散系数(ADC)值在鼻咽癌颅底放疗中的临床价值。方法:收集我院于2013年6月~2014年6月复查的40例鼻咽癌患者,分别于放疗前及放疗结束12个月以后对所有患者行常规核磁共振成像(MRI)及DWI检查,测量放疗前、后ADC值,根据影像学检查以及临床诊断结果分为复发组(n=5)及未复发组(n=35)。结果:复发组放疗前ADC值为(0.797±0.031)×10~(-3)mm~2/s,与未复发组放疗前ADC值(0.805±0.028)×10~(-3)mm~2/s比较,差异无统计学意义(P0.05)。复发组放疗结束12个月以后ADC值为(1.097±0.091)×10~(-3)mm~2/s,与未复发组放疗结束12个月以后ADC值(1.705±0.128)×10~(-3)mm~2/s比较,差异有统计学意义(P0.05)。结论:DWI作为一种新兴的磁共振成像技术,对于鼻咽癌颅底放疗疗效的评价具有重要价值,通过DWI对ADC值的测量,可有效的预测患者预后是否良好。     

血清ghrelin、NLRP3对老年抑郁症患者认知功能损害的诊断价值分析

摘要 目的：分析血清胃促生长素（ghrelin）、Nod样受体热蛋白结构域相关蛋白3（NLRP3）对老年抑郁症患者认知功能损害的诊断价值。方法：选择2020年1月至2021年10月在我院接受诊治的老年抑郁症患者90例作为抑郁症组,另选取同期精神健康老年志愿者50例作为对照组。根据抑郁症病情严重程度将老年抑郁症患者分为轻度组（n=32）、中度组（n=30）、重度组（n=28）,比较不同分组研究对象血清ghrelin、NLRP3水平变化。另根据老年抑郁症患者是否发生认知功能损害分为认知功能损害组和认知功能未损害组,收集患者一般人口学及临床资料,分析影响老年抑郁症患者认知功能发生损害的危险因素。采用受试者工作特征（ROC）曲线分析血清ghrelin、NLRP3对老年抑郁症患者认知功能损害的诊断价值。结果：重度组血清NLRP3炎症小体水平明显高于中度组,中度组血清NLRP3炎症小体水平明显高于轻度组,轻度组血清NLRP3炎症小体水平明显高于对照组（P<0.05）;重度组血清ghrelin水平明显低于中度组,中度组血清ghrelin水平明显低于轻度组,轻度组血清ghrelin水平明显低于对照组（P<0.05）。多因素Logistic回归分析结果显示,重大生活事件（意外事故、破产、至亲去世等）、合并糖尿病、血清ghrelin水平、独居、血清NLRP3炎症小体水平以及社会支持是老年抑郁症患者认知功能损害的影响因素（P<0.05）。血清NLRP3炎症小体、ghrelin单独以及联合诊断老年抑郁症患者认知功能损害的曲线下面积AUC（0.95CI）分别为0.723（0.506～0.922）、0.782（0.619～0.917）、0.863（0.721～0.981）。结论：血清NLRP3炎症小体水平在老年抑郁症患者中呈高表达、ghrelin水平呈现低表达,二者均是老年抑郁症患者认知功能损害的影响因素,且联合检测二者水平可辅助诊断老年抑郁症患者认知功能损害。     

土地利用变化对昆山生态系统服务价值的影响

参照两种典型的生态系统服务价值系数,根据土地利用变化对比研究了长江三角洲经济快速发展区域昆山的生态系统服务价值变化.结果表明：（1）昆山的生态系统服务价值在1994～2001年呈下降趋势,按两种系数计算分别下降了1.22亿元和0.71亿元,相对下降比例分别为4.93﹪和4.12﹪;（2）昆山的生态系统服务价值在评价年份内随时间的变化趋势可分别用线性函数Y1=-121.25X1＋17342（R2=0.907）和Y2=-199.62X2＋25088（R2=0.906）较好的表示;（3）昆山的生态系统服务价值按两种系数的评价结果均分别与GDP、人口总量和人均GDP指标有较好的线性负相关关系,其中与人均GDP的相关度最高;（4）根据生态系统服务价值与人均GDP之间的线性相关关系式预测表明昆山的生态系统服务价值在未来10a内还将进一步下降,需要采取积极的生态保护措施.采用不同价值系数评价的昆山生态服务价值变化特征相似,但是绝对值相差巨大,由此对生态价值静态评价进行了反思,研究生态系统服务价值变化及其变化的驱动机制更有意义.     

不同放射剂量CT在早期非小细胞肺癌中筛检价值对比

摘要 目的：探讨与对比不同放射剂量计算机断层扫描(Computed Tomography,CT)在早期非小细胞肺癌中筛检价值。方法：2020年1月到2020年12月选择在本院经病理确诊为肺内磨玻璃样结节患者98例作为研究对象,所有患者都给予常规剂量正电子发射计算机断层扫描(Positron emission tomography,PET)/CT检查与低剂量PET/CT检查,记录成像特征、辐射剂量并判定筛检价值。结果：低剂量PET/CT对肺部增厚、边界不规则、钙化、囊变的检出率高于常规剂量PET/CT(P<0.05)。低剂量PET/CT与常规剂量PET/CT的图像质量优良率为98.0 %和96.9 %,对比差异无统计学意义(P>0.05)。低剂量PET/CT的有效放射剂量、剂量长度乘积低于常规剂量PET/CT(P<0.05)。低剂量PET/CT的最大标准摄取值(maximum standardized uptake value,SUVmax)值低于常规剂量PET/CT(P<0.05)。低剂量PET/CT与常规剂量PET/CT分别筛检非小细胞肺癌51例与37例,筛检敏感性分别为98.1 %和69.2 %,特异性分别为100.0 %和97.8 %。结论：低放射剂量PET/CT在肺结节中的应用不会影响图像质量,且能降低辐射剂量,提高对早期非小细胞肺癌患者的筛检效果。     

Calculating phenotypic similarity between genes using hierarchical structure data based on semantic similarity

Phenotypic similarity is correlated with a number of measures of gene function, such as relatedness at the level of direct protein-protein interaction. The phenotypic effect of a deleted or mutated gene, which is one part of gene annotation, has caught broad attention. However, there have been few measures to study phenotypic similarity with the data from Human Phenotype Ontology (HPO) database, therefore more analogous measures should be developed and investigated. We used five semantic similarity-based measures (Jiang and Conrath, Lin, Schlicker, Yu and Wu) to calculate the human phenotypic similarity between genes (PSG) with data from HPO database, and evaluated their accuracy with information of protein-protein interaction, protein complex, protein family, gene function or DNA sequence. Compared with the gene pairs that were random selected, the results of these methods were statistically significant (all P<0.001). Furthermore, we assessed the performance of these five measures by receiver operating characteristic (ROC) curve analysis, and found that most of them performed better than the previous methods. This work had proved that these measures based on semantic similarity for calculation of PSG were effective for hierarchical structure data. Our study contributes to the development and optimization of novel algorithms of PSG calculation and provides more alternative methods to researchers as well as tools and directions for PSG study.