蛋白质柔性复合物的结构预测

将自洽系综最优化方法（ＳＣＥＯ）推广到主链可变的分子体系,并以此来实现蛋白质复合物结合界面的柔性优化。据此,提出了一种模拟蛋白质“诱导契合”过程的计算方法,来实现蛋白质柔性复合物的结构预测。经过三个蛋白质柔性复合物结构预测的检验,表明这种方法是可行的,并且达到了计算精度和计算速度上的兼顾     

输尿管软镜术后肾结石患者的临床特征及结石残留的影响因素分析

摘要 目的：探究输尿管软镜术后肾结石患者的临床特征及结石残留的影响因素。方法：选择2019年1月~2022年1月本院收治的200例肾结石患者，所有患者予以输尿管软镜术治疗，术后一周，开展泌尿系CT及尿路平片复查，根据术后结石残留情况，将其分为无残石组（n=155）及残石组（n=45）。并依据两组患者术后是否伴随并发症，将其分为并发症组（n=41）及无并发症组（n=159）。比较术后并发症组与无并发症组的基线资料、术后结石残留率、影响肾结石患者术后结石残留的单因素及肾结石患者术后结石残留的Logistic回归分析。结果：既往输尿管疾病史、鹿角形结石、操作时间及住院时间，均会在不同程度上增加术后并发症风险（P＜0.05），年龄、术前合并慢性病、性别、体质量指数、结石位置未明显增加术后并发症风险（P＞0.05）；200例肾结石患者，输尿管软镜术后，结石残留率为22.50 %（45/200），结石清除率为77.50 %（155/200），残石组及无残石组性别、年龄及平均病程比较，无较大差异（P＞0.05）；肾功能不全、结石直径、结石数量、结石脓苔包裹、肾盂肾下盏夹角、结石成分、手术时间、术中出血量是影响肾结石术后结石残留的单因素（P＜0.05），糖尿病、高血压、肾积水、结石位置等因素未对术后结石残留产生显著影响（P＞0.05）；Logistic回归分析提示，肾功能不全、结石直径≥2 cm、结石脓苔包裹、肾盂肾下盏夹角＜30°及结石成分是影响肾结石患者术后结石残留的独立危险因素（P＜0.05）。结论：肾结石患者输尿管软镜术后，可依据影响术后并发症的临床特征，对不良风险事件予以预警，此外研究结果提示，肾功能不全、结石直径≥2 cm、结石脓苔包裹、肾盂肾下盏夹角＜30°及结石成分是影响结石残留的独立危险因素，术前可基于危险因素开展相应预防，以提高结石清除率。     

多齿蛇鲻鳞片表面结构的扫描电镜观察

本文对多齿蛇鲻鳞片表面结构进行扫描电镜观祭,描述了鳞纹、年轮形式、齿状粒突、辐射沟、伸缩缝、后区隆突和小棘。鳞纹嵴顶上的齿状粒突,其形态特征和排列方式可作为辅助鉴别疑难种类的依据。鳞纹和后区隆突上的伸缩缝,作者认为对鳞片的伸缩起着柔软缓冲作用。     

侧卧体位下经皮肾穿刺取石术联合经尿道输尿管镜取石术治疗复杂上尿路结石的临床应用价值

目的：探讨侧卧体位下经皮肾穿刺取石术联合经尿道输尿管镜取石术治疗复杂上尿路结石的可行性及临床应用价值。方法：回顾性分析2009年8月至2011年9月我院采用侧卧体住下经皮肾穿刺取石术联合经尿道输尿管镜取石术治疗复杂上尿路结石患者52例的临床资料：患者同时存在肾脏铸型结石或多发结石和或输尿管上段结石,单个结石最大径8-30mm。结果：平均手术时间60分钟（50—120分钟）;术前血红蛋白116±30g／L,术后第一天复查105±26g／L,无大出血需要输血病例;一次结石取净率为86．5％（45／52）,总取净率为92．3％（48／52）。结论：侧卧体位下经皮肾穿刺取石术及经尿道输尿管镜取石术两种术式联合应用具有可行性及互补性,在预防及减少术中出血、获得清晰的手术视野、减少灌注液外渗、增加结石清除速度及碎石成功率、缩短手术时间、减少术后发热等方面疗效显著,为治疗复杂上尿路结石提供了一个可行的新方法。     

Synthesis and crystal structures of dimeric W(Mo)/Cu/S and polymeric W/Cu/S neutral clusters with flexible 1,4-bis(3,5-dimethylpyrazol-1-yl)butane as a linker ligand

Reactions of [MES₃]²⁻ (M = W, Mo; E = S, O) with CuCl and bbd [1,4-bis(3,5-dimethylpyrazol-1-yl)butane] in DMF affords two new double nest-shape clusters, [WOS₃Cu₃Cl(μ-bbd)]₂ (1) and [MoOS₃Cu₃Cl(μ-bbd)]₂ (2) and a novel one-dimensional polymeric complex [WS₄Cu₂(μ-bbd)]_n (4). The complexes have been characterized by elemental analysis, IR and UV-Vis spectroscopy, and single-crystal X-ray diffraction. In the core structure of the isostructural dimeric [MOS₃Cu₃Cl(μ-bbd)]₂ clusters, the copper atoms have a distorted trigonal planar geometry, with CuS₂N and CuS₂Cl core environments. The [MOS₃Cu₃] fragments are interconnected by a pair of flexible μ-bbd ligands via their nitrogen donor atoms to form a centrosymmetric macrocyclic twin-nest-shaped cluster in which the two fragments are also linked by direct secondary Cu…Cl interactions. Complex 4 represents the first example of a polymeric heterothiometallic cluster, interconnected by bbd ligands, to be structurally characterized by X-ray crystallography. In the repeat unit of 4, the skeleton of the cluster core [CuS₂WS₂Cu] has an essentially linear Cu…W…Cu arrangement. The W atom retains the tetrahedral geometry of the parent [WS₄]²⁻ anion. These cluster cores are linked by bbd bridges having alternately two different conformations to construct a zigzag structure. Complexes [MoS₄Cu₃Cl(bbd)_0.5]₂ (3) and [WS₄Cu₄(NCS)₂(bbd)₂]_n (5) have been synthesized and characterized by elemental analysis, IR and UV-Vis spectroscopy, but we have been unable to grow suitable crystals of 3 and 5 for X-ray analysis.     

Co(II), Zn(II) and Cu(II) compounds with 1,4; 1,3 or 1,2-bis-(benzimidazole-1-yl-methylene)-benzene as a flexible spacer ligand: Synthesis, characterization and X-ray structures of some polynuclear species

New dinuclear and polynuclear Co(II), Zn(II) and Cu(II) compounds with the ligands 1,4-bis-(benzimidazole-1-yl-methylene)-benzene (bbpx), 1,3-bis-(benzimidazole-1-yl-methylene)-benzene (bbmx) and 1,2-bis-(benzimidazole-1-yl-methylene)-benzene (bbox) are reported. With Co(II) and Zn(II) and the ligands bbpx, bbmx and bbox six new dinuclear and polynuclear compounds are described, i.e. [CoCl₂(bbpx)]_n(DMF)_2n (1), [CoCl₂(bbmx)]₂(DMF)₂ (2), [ZnCl₂(bbmx)]₂(DMF)₂ (3), [CoCl₂(bbmx)]_n(DMF)_n/2(CH₃OH)_n/4 (4), [CoCl₂(bbox)]_n(DMF)_3n/2 (5) and [ZnCl₂(bbox)]_n(DMF)_3n/2 (6). Also one polynuclear Cu(II) compound is reported, i.e. [Cu(bbpx)₂(C₂N₃)_1.5(OH)_0.5]₂(DMF)_4.15(CH₃OH)_1.75(H₂O)_3.5. The X-ray structures, physical and electronic properties are discussed.     

Signal-CF: a subsite-coupled and window-fusing approach for predicting signal peptides

We have developed an automated method for predicting signal peptide sequences and their cleavage sites in eukaryotic and bacterial protein sequences. It is a 2-layer predictor: the 1st-layer prediction engine is to identify a query protein as secretory or non-secretory; if it is secretory, the process will be automatically continued with the 2nd-layer prediction engine to further identify the cleavage site of its signal peptide. The new predictor is called Signal-CF, where C stands for "coupling" and F for "fusion", meaning that Signal-CF is formed by incorporating the subsite coupling effects along a protein sequence and by fusing the results derived from many width-different scaled windows through a voting system. Signal-CF is featured by high success prediction rates with short computational time, and hence is particularly useful for the analysis of large-scale datasets. Signal-CF is freely available as a web-server at http://chou.med.harvard.edu/bioinf/Signal-CF/ or http://202.120.37.186/bioinf/Signal-CF/.     

Exact confidence bounds following adaptive group sequential tests

Summary .  We provide a method for obtaining confidence intervals, point estimates, and p-values for the primary effect size parameter at the end of a two-arm group sequential clinical trial in which adaptive changes have been implemented along the way. The method is based on applying the adaptive hypothesis testing procedure of Müller and Schäfer (2001, Biometrics 57, 886–891) to a sequence of dual tests derived from the stage-wise adjusted confidence interval of Tsiatis, Rosner, and Mehta (1984, Biometrics 40, 797–803). In the nonadaptive setting this confidence interval is known to provide exact coverage. In the adaptive setting exact coverage is guaranteed provided the adaptation takes place at the penultimate stage. In general, however, all that can be claimed theoretically is that the coverage is guaranteed to be conservative. Nevertheless, extensive simulation experiments, supported by an empirical characterization of the conditional error function, demonstrate convincingly that for all practical purposes the coverage is exact and the point estimate is median unbiased. No procedure has previously been available for producing confidence intervals and point estimates with these desirable properties in an adaptive group sequential setting. The methodology is illustrated by an application to a clinical trial of deep brain stimulation for Parkinson's disease.     

Flexible chain conformation of (1 → 3)-β-d-glucan from Poria cocos sclerotium in NaOH/urea aqueous solution

A water-insoluble polysaccharide (PCS3-II) extracted from sclerotium of Poria cocos was identified as a linear (1 → 3)-β-d-glucan by ¹³C NMR and gas chromatography. Aqueous 0.5 M NaOH/0.2 M urea was a good solvent for PCS3-II and the dependence of intrinsic viscosity ([η]) on weight-average molecular weight (M_w) was established in the M_w range from 7.68 × 10⁴ to 5.14 × 10⁵ to be [η] = 3.39 × 10^?2 $M_{\text{W}}^{0.62}{\text{cm}}^3{\text{g}}^{-1}$ at 25 °C by using laser light scattering and viscometry. The chain conformation parameters of PCS3-II in the 0.5 M NaOH/0.2 M urea solution was 2.3 (± 0.3) nm for persistence length (q), 580 g mol^?1 nm^?1 for molar mass per unit contour length (M_L), 0.8 (± 0.2) nm for the diameter of the chain (d) and 3.63 for limited characteristic ratio (C_∞). The results revealed, for the first time, that PCS3-II existed as a flexible chain in 0.5 M NaOH/0.2 M urea aqueous solution.     

Steps towards flexible docking: modeling of three-dimensional structures of the nuclear receptors bound with peptide ligands mimicking co-activators' sequences

We developed a fully flexible docking method that uses a reduced lattice representation of protein molecules, adapted for modeling peptide–protein complexes. The CABS model (Carbon Alpha, Carbon Beta, Side Group) employed here, incorporates three pseudo-atoms per residue—C, Cβ and the center of the side group instead of full-atomic protein representation. Force field used by CABS was derived from statistical analysis of non-redundant database of protein structures. Application of our method included modeling of the complexes between various nuclear receptors (NRs) and peptide co-activators, for which three-dimensional structures are known. We tried to rebuild the native state of the complexes, starting from separated components. Accuracy of the best obtained models, calculated as coordinate root-mean-square deviation (cRMSD) between the target and the modeled structures, was under 1 Å, which is competitive with experimental methods, such as crystallography or NMR. Forthcoming modeling study should lead to better understanding of mechanisms of macromolecular assembly and will explain co-activators’ effects on receptors activity, especially on vitamin D receptor and other nuclear receptors.