Binding Ensembles of p53-MDM2 Peptide Inhibitors by Combining Bayesian Inference and Atomistic Simulations

Designing peptide inhibitors of the p53-MDM2 interaction against cancer is of wide interest. Computational modeling and virtual screening are a well established step in the rational design of small molecules. But they face challenges for binding flexible peptide molecules that fold upon binding. We look at the ability of five different peptides, three of which are intrinsically disordered, to bind to MDM2 with a new Bayesian inference approach (MELD × MD). The method is able to capture the folding upon binding mechanism and differentiate binding preferences between the five peptides. Processing the ensembles with statistical mechanics tools depicts the most likely bound conformations and hints at differences in the binding mechanism. Finally, the study shows the importance of capturing two driving forces to binding in this system: the ability of peptides to adopt bound conformations (ΔGconformation) and the interaction between interface residues (ΔGinteraction).     

基于正态分布概率模型的渗滤液回灌影响分析

渗滤液回灌能有效加速填埋场的稳定并处理多余的渗滤液, 而预测回灌过程中渗滤液的运移规律对于合理设置回灌井的间距和数量具有重要的意义. 考虑了垃圾体的非均质性, 建立了垃圾体的渗透系数随空间正态分布变化的概率模型. 利用 COMSOL Multiphysics^® 软件, 首先对单孔隙度的横纵向均质模型和正态分布模型的 渗透系数以及压力水头进行了比较, 其次研究了在横纵向渗透系数比值、回灌速率和回灌时间等不同 影响因素下, 均质模型和正态分布模型的含水率以及横向影响范围的变化规律. 结果表明, 随着横纵向渗透系数比值的增加, 最终在 100 d 时: 均质模型的含水率由 0.609 增加到 0.68, 横向影响范围从4.842 m 增加到 6.79 m; 正态分布模型的含水率由 0.573 增加到 0.610, 横向影响范围从4.097 m 变为 4.04 m. 这说明横纵向渗透系数比值对正态分布模型的含水 率和渗滤液横向影响范围的影响明显高于均质模型. 而当回灌速率和回灌时间相同时, 正态分布模型渗滤液的渗流速度更快, 易于优先达到饱和含水率, 并在短暂的峰值后迅速下降, 且随着回灌速率和回灌时间的增加, 达到饱和含水率和峰值的时间也逐渐增加.     

Practical Synthesis of 2-Iodosobenzoic Acid (IBA) without Contamination by Hazardous 2-Iodoxybenzoic Acid (IBX) under Mild Conditions

We report a convenient and practical method for the preparation of nonexplosive cyclic hypervalent iodine(III) oxidants as efficient organocatalysts and reagents for various reactions using Oxone^® in aqueous solution under mild conditions at room temperature. The thus obtained 2-iodosobenzoic acids (IBAs) could be used as precursors of other cyclic organoiodine(III) derivatives by the solvolytic derivatization of the hydroxy group under mild conditions of 80 °C or lower temperature. These sequential procedures are highly reliable to selectively afford cyclic hypervalent iodine compounds in excellent yields without contamination by hazardous pentavalent iodine(III) compound.     

Terroir Effect on the Phenolic Composition and Chromatic Characteristics of Mencía/Jaen Monovarietal Wines: Bierzo D.O. (Spain) and Dão D.O. (Portugal)

‘Mencía’/‘Jaen’ it’s an important red grape variety, exclusive of the Iberian Peninsula, used in wine production namely in Bierzo D.O. and Dão D.O., respectively. This work evaluates the effect of the two different “terroirs” on the phenolic composition and chromatic characteristics of ‘Mencía’/‘Jaen’ monovarietal wines produced at an industrial scale in the same vintage. Using Principal Component Analysis (PCA), Partial Least Squares-Discrimination Analysis (PLS-DA), and Orthogonal PLS-DA (OPLS-DA) it was found that peonidin-3-coumaroylglucoside, petunidin-3-glucoside, malvidin-3-coumaroylglucoside, peonidin-3-glucoside, malvidin-3-acetylglucoside, malvidin-3-glucoside, and ferulic acid were the phenolic compounds with the highest differences between the two regions. PLS regression allowed to correlate the differences in lightness (L*) and redness (a*) of wines from ‘Jaen’ and ‘Mencía’ to differences in colored anthocyanins, polymeric pigments, total pigments, total anthocyanins, cyanidin-3-acetylglucoside, delphinidin-3-acetylglucoside, delphinidin-3-glucoside, peonidin-3-coumaroylglucoside, petunidin-3-glucoside and malvidin-3-glucoside in wines, and the colorless ferulic, caffeic, and coutaric acids, and ethyl caffeate. The wines a* values were more affected by colored anthocyanins, ferulic acid, total anthocyanins, delphinidin-3-acetylglucoside, delphinidin-3-glucoside and petunidin-3-acetylglucoside, and catechin. The positive influence of ferulic acid in the a* values and ferulic, caffeic, coutaric acids, and ethyl caffeate on the L* values can be due to the co-pigmentation phenomena. The higher dryness and lower temperatures during the September nights in this vintage might explain the differences observed in the anthocyanin content and chromatic characteristics of the wines.     

Phytochemical and Biological Activity Studies on Nasturtium officinale (Watercress) Microshoot Cultures Grown in RITA® Temporary Immersion Systems

The main compounds in both extracts were gluconasturtiin, 4-methoxyglucobrassicin and rutoside, the amounts of which were, respectively, determined as 182.93, 58.86 and 23.24 mg/100 g dry weight (DW) in biomass extracts and 640.94, 23.47 and 7.20 mg/100 g DW in plant herb extracts. The antioxidant potential of all the studied extracts evaluated using CUPRAC (CUPric Reducing Antioxidant Activity), FRAP (Ferric Reducing Ability of Plasma), and DPPH (1,1-diphenyl-2-picrylhydrazyl) assays was comparable. The anti-inflammatory activity of the extracts was tested based on the inhibition of 15-lipoxygenase, cyclooxygenase-1, cyclooxygenase-2 (COX-2), and phospholipase A₂. The results demonstrate significantly higher inhibition of COX-2 for in vitro cultured biomass compared with the herb extracts (75.4 and 41.1%, respectively). Moreover, all the studied extracts showed almost similar antibacterial and antifungal potential. Based on these findings, and due to the fact that the growth of in vitro microshoots is independent of environmental conditions and unaffected by environmental pollution, we propose that biomass that can be rapidly grown in RITA^® bioreactors can serve as an alternative source of bioactive compounds with valuable biological properties.     

模拟酸雨对小黑杨幼苗生长和光合特性的影响

目的 研究小黑杨(Populus simonii × P. nigra)幼苗生长、生理特性和叶片光系统Ⅱ(PSⅡ)活性对酸雨胁迫的响应情况,为其在酸雨沉降日趋频发的北方地区栽植提供参考。方法 以小黑杨为研究材料,对其连续喷施不同酸度[pH为2.5、4.5和7.0(CK)]的模拟酸雨,待小黑杨叶片出现明显病症时,测定其生长、叶片超微结构、抗氧化酶和光系统Ⅱ活性指标。结果 与对照相比,pH 4.5的模拟酸雨处理下小黑杨株高、茎粗、叶片数和叶面积显著增加;叶片颜色变浅绿色,但叶绿体结构紧凑,类囊体排列规则,未见淀粉粒,嗜锇滴数量略增多。而pH 2.5模拟酸雨处理的小黑杨幼苗茎粗和叶面积显著降低;叶片颜色变黄、叶尖和叶脉出现明显斑点,且细胞膜局部破损,叶绿体体积增大,类囊体间隙增大,可见少量淀粉粒,嗜锇滴数量和体积明显增加。模拟酸雨处理的小黑杨叶片中超氧阴离子 000b7; -产生速率、过氧化氢(H₂O₂)含量和过氧化氢酶活性较CK显著增加,且酸度越大,增幅越大;而过氧化物酶活性和超氧化物歧化酶活性随酸度的增大表现为先升后降。其中,pH 2.5模拟酸雨处理杨树叶片的可变荧光强度(V_L、V_K、V_J、V_I)和诱导曲线初始斜率(M_O)显著高于CK,但叶绿素荧光曲线面积(Fix Area)和质体醌库的大小(S_m)显著低于CK。pH 4.5模拟酸雨处理中,仅V_L和V_K显著高于CK,而其他荧光参数与CK差异不显著。结论 酸雨对小黑杨生长的影响主要取决于其pH,pH 2.5模拟酸雨处理抑制小黑杨生长,并且叶片出现坏死斑点症状时,叶绿体结构异常,类囊体排列不规整,光系统Ⅱ电子传递受到抑制;而pH 4.5模拟酸雨处理促进小黑杨生长、叶片超微结构表现正常,小黑杨幼苗对pH 4.5酸雨沉降具有一定抗性。     

GDP vs. LDP: A Survey from the Perspective of Information-Theoretic Channel

The existing work has conducted in-depth research and analysis on global differential privacy (GDP) and local differential privacy (LDP) based on information theory. However, the data privacy preserving community does not systematically review and analyze GDP and LDP based on the information-theoretic channel model. To this end, we systematically reviewed GDP and LDP from the perspective of the information-theoretic channel in this survey. First, we presented the privacy threat model under information-theoretic channel. Second, we described and compared the information-theoretic channel models of GDP and LDP. Third, we summarized and analyzed definitions, privacy-utility metrics, properties, and mechanisms of GDP and LDP under their channel models. Finally, we discussed the open problems of GDP and LDP based on different types of information-theoretic channel models according to the above systematic review. Our main contribution provides a systematic survey of channel models, definitions, privacy-utility metrics, properties, and mechanisms for GDP and LDP from the perspective of information-theoretic channel and surveys the differential privacy synthetic data generation application using generative adversarial network and federated learning, respectively. Our work is helpful for systematically understanding the privacy threat model, definitions, privacy-utility metrics, properties, and mechanisms of GDP and LDP from the perspective of information-theoretic channel and promotes in-depth research and analysis of GDP and LDP based on different types of information-theoretic channel models.     

Quality Related Safety Evaluation of a South African Traditional Formulation (PHELA®) as Novel Anti-Biofilm Candidate

A South African traditional formulation, PHELA^®, is consumed by the traditional people for severe chest problems with coughing, diarrhea, oral ulcers etc. The present study focused on establishing the anti-infective properties of a safe and standardized poly-herbal formulation through a series of criteria and specifications.     

The Bifurcated σ-Hole···σ-Hole Stacking Interactions

The bifurcated σ-hole···σ-hole stacking interactions between organosulfur molecules, which are key components of organic optical and electronic materials, were investigated by using a combined method of the Cambridge Structural Database search and quantum chemical calculation. Due to the geometric constraints, the binding energy of one bifurcated σ-hole···σ-hole stacking interaction is in general smaller than the sum of the binding energies of two free monofurcated σ-hole···σ-hole stacking interactions. The bifurcated σ-hole···σ-hole stacking interactions are still of the dispersion-dominated noncovalent interactions. However, in contrast to the linear monofurcated σ-hole···σ-hole stacking interaction, the contribution of the electrostatic energy to the total attractive interaction energy increases significantly and the dispersion component of the total attractive interaction energy decreases significantly for the bifurcated σ-hole···σ-hole stacking interaction. Another important finding of this study is that the low-cost spin-component scaled zeroth-order symmetry-adapted perturbation theory performs perfectly in the study of the bifurcated σ-hole···σ-hole stacking interactions. This work will provide valuable information for the design and synthesis of novel organic optical and electronic materials.