A New Activation Method for Electroless Metal Plating：Palladium Laden via Bonding with Self—Assembly Monolayers

A new activation method has been developed for electroless copper plating on silicon wafer based on palladium chemisorption on SAMs of APTS without SnCl2 sensitization and roughening condition.A closely packed electroless copper film with strong adhesion is successfully formed by AFM observation.XPS study indicates that palladium chemisorption occurred via palladium chloride bonding to the pendant amino group of the SAMs.     

全自动固相萃取技术同时测定动物产品中9种磺胺药物残留

针对目前动物产品中兽药残留检测样品前处理繁琐的问题,应用全自动固相萃取技术对动物产品中9种磺胺类药物残留检测的样品前处理方法进行了系统的研究,对提取溶剂、固相萃取柱、淋洗液、洗脱溶剂及仪器分析条件进行了优化选择,建立了新型磺胺药物残留检测的全自动固相萃取净化方法.经不同检测单位验证,该方法的加标回收率为78.4%～107.8%,精密度为3.9%～11.0%检出限为0.010～0.020mg/kg,满足出口检测要求.     

An Fc variant with two mutations confers prolonged serum half-life and enhanced effector functions on IgG antibodies

The pH-selective interaction between the immunoglobulin G (IgG) fragment crystallizable region (Fc region) and the neonatal Fc receptor (FcRn) is critical for prolonging the circulating half-lives of IgG molecules through intracellular trafficking and recycling. By using directed evolution, we successfully identified Fc mutations that improve the pH-dependent binding of human FcRn and prolong the serum persistence of a model IgG antibody and an Fc-fusion protein. Strikingly, trastuzumab-PFc29 and aflibercept-PFc29, a model therapeutic IgG antibody and an Fc-fusion protein, respectively, when combined with our engineered Fc (Q311R/M428L), both exhibited significantly higher serum half-lives in human FcRn transgenic mice than their counterparts with wild-type Fc. Moreover, in a cynomolgus monkey model, trastuzumab-PFc29 displayed a superior pharmacokinetic profile to that of both trastuzumab-YTE and trastuzumab-LS, which contain the well-validated serum half-life extension Fcs YTE (M252Y/S254T/T256E) and LS (M428L/N434S), respectively. Furthermore, the introduction of two identified mutations of PFc29 (Q311R/M428L) into the model antibodies enhanced both complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity activity, which are triggered by the association between IgG Fc and Fc binding ligands and are critical for clearing cancer cells. In addition, the effector functions could be turned off by combining the two mutations of PFc29 with effector function-silencing mutations, but the antibodies maintained their excellent pH-dependent human FcRn binding profile. We expect our Fc variants to be an excellent tool for enhancing the pharmacokinetic profiles and potencies of various therapeutic antibodies and Fc-fusion proteins.Subject terms: Antibody therapy, Molecularly targeted therapy, Drug development     

Synthesis of Phenylboronic Acid-Functionalized Magnetic Nanoparticles for Sensitive Soil Enzyme Assays

Soil enzymes, such as invertase, urease, acidic phosphatase and catalase, play critical roles in soil biochemical reactions and are involved in soil fertility. However, it remains a great challenge to efficiently concentrate soil enzymes and sensitively assess enzyme activity. In this study, we synthesized phenylboronic acid-functionalized magnetic nanoparticles to rapidly capture soil enzymes for sensitive soil enzyme assays. The iron oxide magnetic nanoparticles (MNPs) were firstly prepared by the co-precipitation method and then functionalized by (3-aminopropyl)triethoxysilane, polyethyleneimine and phenylboric acid in turn, obtaining the final nanoparticles (MNPPBA). Protein-capturing assays showed that the functionalized MNPs had a much higher protein-capturing capacity than the naked MNPs (56% versus 6%). Moreover, MNPPBA almost thoroughly captured the tested enzymes, i.e., urease, invertase, and alkaline phosphatase, from enzyme solutions. Based on MNPPBA, a soil enzyme assay method was developed by integration of enzyme capture, magnetic separation and trace enzyme analysis. The method was successfully applied in determining trace enzyme activity in rhizosphere soil. This study provides a strategy to sensitively determine soil enzyme activity for mechanistic investigation of soil fertility and plant–microbiome interaction.     

Theoretical Study on the Conformational Conversion of 1,3-Dioxane Inside a Capsular Host

The mechanism for the conformational conversion of 1,3-dioxane guest encapsulated inside a capsular host was theoretically investigated using semiempirical PM3 method and DFT methods. The free-state process of the conformational conversion of 1,3-dioxane was also investigated to make a comparison between the two different states using the same theory. The influences of the inner phase of the capsule on the conformational conversion of guest molecule were discussed via analyzing the comparative results. It was found that the capsular host could accommodate 1,3-dioxane within its cavity by the weak attractive interactions between host and guest, and it responds to the conformational conversion of guest by the deformation of hydrogen-bonding seam at the middle of the capsule. When entrapped in the capsule, the guest molecule undergoes the conformational conversion from chair form to twist-boat form slower than that under the free condition. The deformation of the capsule is favorable to maximize the attractive interactions between host and guest.     

O-GlcNAcylation mapping of single living cells by in situ quantitative SERS imaging

O-GlcNAcylation is involved in many biological processes including cancerization. Nevertheless, its in situ quantification in single living cells is still a bottleneck. Here we develop a quantitative SERS imaging strategy for mapping the O-GlcNAcylation distribution of single living cells. O-GlcNAcylated compounds (OGCs) can be quantified through their in situ azide labeling and then a click reaction competing with azide and Raman reporter labeled 15 nm-gold nanoparticles (AuNPs) for linking to dibenzocyclooctyne labeled 40 nm-AuNPs to produce OGC-negatively correlated SERS signals. The calibration curve obtained in vitro can be conveniently used for detecting OGCs in different areas of single living cells due to the negligible effect of cell medium on the click linkage and Raman signal. This method has been successfully applied in mapping O-GlcNAcylation distribution in different cell lines and monitoring O-GlcNAcylation variation during cell cycling, which demonstrate its great practicability and expansibility in glycosylation related analysis.

A quantitative SERS imaging strategy is developed for O-GlcNAcylation mapping of single living cells through a competitive click reaction.     

气溶胶及能见度变化对标准大气中远红外传输的影响分析

红外制导系统发现、识别和跟踪目标主要依据背景、目标物辐射特性和对比特性信息。气溶胶及其能见度变化是大气环境中影响红外辐射传输的主要因素之一。以标准大气为例,开展了气溶胶及其能见度变化对中、远红外光谱区间（3～5mm,8～12mm）大气透过率和目标背景对比度的影响分析,重点分析了标准大气中相同能见度不同气溶胶类型及同气溶胶类型不同能见度对中远红外传输特性的影响。结果显示：大气透过率对目标背景对比度的理论计算值有重要影响。在其他大气条件既定情况下,气溶胶及其能见度变化对两波段的透过特性和目标识别效果影响明显,且以8～12mm波段的好于3～5mm的。同能见度不同气溶胶类型下的透过率和目标背景对比度差异较大,需要考虑气溶胶的影响。在中远红外区间,3.4～4.2mm和9.5～12mm波段内的透过率和目标背景对比度平均值相对较大,变化振幅小,可作为武器使用理想波段加以选择应用。     

Insights into the Allosteric Effect of SENP1 Q597A Mutation on the Hydrolytic Reaction of SUMO1 via an Integrated Computational Study

Small ubiquitin-related modifier (SUMO)-specific protease 1 (SENP1) is a cysteine protease that catalyzes the cleavage of the C-terminus of SUMO1 for the processing of SUMO precursors and deSUMOylation of target proteins. SENP1 is considered to be a promising target for the treatment of hepatocellular carcinoma (HCC) and prostate cancer. SENP1 Gln597 is located at the unstructured loop connecting the helices α4 to α5. The Q597A mutation of SENP1 allosterically disrupts the hydrolytic reaction of SUMO1 through an unknown mechanism. Here, extensive multiple replicates of microsecond molecular dynamics (MD) simulations, coupled with principal component analysis, dynamic cross-correlation analysis, community network analysis, and binding free energy calculations, were performed to elucidate the detailed mechanism. Our MD simulations showed that the Q597A mutation induced marked dynamic conformational changes in SENP1, especially in the unstructured loop connecting the helices α4 to α5 which the mutation site occupies. Moreover, the Q597A mutation caused conformational changes to catalytic Cys603 and His533 at the active site, which might impair the catalytic activity of SENP1 in processing SUMO1. Moreover, binding free energy calculations revealed that the Q597A mutation had a minor effect on the binding affinity of SUMO1 to SENP1. Together, these results may broaden our understanding of the allosteric modulation of the SENP1−SUMO1 complex.