Comparison of biliary protein spectrum in gallstone patients with obesity and those with normal body weight

Background: Obesity is a common public health issue and is currently deemed a disease. Research has shown that the risk of gallstones in individuals with obesity is elevated. This study aimed to explore the bile proteomics differences between cholelithiasis patients with obesity and normal body weight. Methods: Bile samples from 20 patients(10 with obesity and 10 with normal body weight) who underwent laparoscopic cholecystectomy at our center were subjected to tandem mass tag labeling(TMT) and liquid chromatography-tandem mass spectrometry(LC-MS/MS), followed by further bioinformatic analysis. Results: Among the differentially expressed proteins, 23 were upregulated and 67 were downregulated. Bioinformatic analysis indicated that these differentially expressed proteins were mainly involved in cell development, inflammatory responses, glycerolipid metabolic processes, and protein activation cascades. In addition, the activity of the peroxisome proliferator-activated receptor(PPAR, a subfamily of nuclear receptors) signaling pathway was decreased in the Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis. Two downregulated proteins in the PPAR signaling pathway, APO A-Ⅰ and APO A-Ⅱ, were confirmed using enzyme-linked immunosorbent assay. Conclusions: The PPAR signaling pathway may play a crucial role in the development of cholelithiasis among patients with obesity. Furthermore, biliary proteomics profiling of gallstones patients with obesity is revealed, providing a reference for future research.

城市供水管网运行安全监测技术及应用

城市供水管网运行安全监测存在信息不全、手段缺乏的问题。首先通过管损数据分析,研究了供水管网运行安全的影响因素,提出了保护性监测和预防性监测2类监测,建立了供水管网运行状态、管道结构和管网环境等“三类参数”的监测指标;其次针对埋地管网,研究了无线信号在地层中传输的路径损耗规律,研发了无线透传感知网络技术;最后,在上海市供水管网抢修现场部署了监测系统。结果表明:管网交叉路口、交叠管线和交变荷载“三交区域”为管损高发区域,为监测的关键位置;体积含水率是影响无线信号路径损耗的主要因素,在高含水量下,砂性土较黏性土路径损耗小;多跳自组网可有效提升无线网络整体的地层穿透能力;管道下方的回填土密实度对管道后期沉降影响大,应确保回填质量,结构监测系统可先于管网渗漏、压力流量变化进行安全预警。

A new isochroman-4-one derivative from the peel of Musa sapientum L.and its total synthesis

A new isochroman-4-one, 7,8-dihydroxy-3-methylisochroman-4-one was isolated from water soluble fraction of Musa sapientum L. Its structure was determined by spectroscopic evidences and its total synthesis has also been reported. The compound showed potent antihypertensive activity.

3-D Thermo-Stress Field in Laminated Cylindrical Shells

The temperature and the stress distribution in simply-supported laminated cylindrical shells undergo thermal loads on the surface have been investigated.Exact solutions of physical quantities including temperature,heat flux,thermal displacement and stress are developed for the cylindrical laminated shell.Cylindrical shells are partitioned into more thin layers.In cylindrical coordinate,analytical expressions for physical quantities inside each layer are derived.Taking into account the compatibility of physical quantities at the interfaces,the relations between the outer and the inner layer of the laminated shell can be described with a transfer matrix.The undetermined parameters from the solutions of each layer can be obtained with boundary conditions.The convergence of the solutions to the number of Fourier series terms has been checked.The accuracy and feasibility of the present method is verified by comparing theoretical results with numerical outcomes due to Finite Element Method(FEM).Finally,the influences of surface temperature,geometrical size and material properties with respects to temperature,thermal stresses and displacement of layered cylindrical shell are worked out in details in a parameter study.

3-D Temperature Fields in Laminated Shells Subjected to Thermo-Loads

The temperature fields in the laminated shells were studied, including opencylindrical shells and cylindrical shells, according to the thermal theory. Analyticalsolution of the temperature in the shells with the known temperature on the surfaces waspresent. The thinning layer approach was introduced to simplify the three-dimensionalheat conduction equation. Firstly, the layered shell was divided into N thinner layers. Thegoverning equation was simplified by replacing the variable r by r0 in the center line ofevery thin layer. The general solutions of temperature satisfying the simplified threedimensionalgoverning equation in single-layered shell were deduced in the cylindricalcoordinate system. Then, the temperature and heat flux relationships between the surfacescould be found by transferring matrixes. According to the continuities of temperature andheat flux in the interface of the laminates, the temperature and heat flux relationships ofthe surfaces were derived. With the temperature condition on the surfaces, the unknowncoefficients in the general solution of temperature were obtained. Finally, the effects fromthe thinning layer approach were eliminated by analyzing different numbers of thin layers.The validity and accuracy of the proposal method were proved from the convergence andcomparison studies. And several numerical examples were studied to investigated thetemperature effects from surface temperatures, geometric size of the shells andcomposition of layers.

Emerging Bio-relevant Applications of Polymer Mechanochemistry

Polymer mechanochemistry has rapidly evolved since the mid-20o0s.Recent advancements highlight the development of mechanophore platforms for the controlled release of bioactive payloads and the exploration of biocompatible activation strategies.These platforms,ranging from furan-maleimide Diels-Alder adducts to disulfide motifs withβ-carbonate linkages,demonstrate promising prospects in targeted drug delivery.Additionally,supramolecular assemblies and free radical-generating mechanophores present innovative avenues for potential therapeutic applications.Biocompatible activation methods,notably high-intensity and/or low-intensity focused ultrasound,hold potential for in vivo applications.However,challenges persist in comprehending the fundamental physics of ultrasound and its utilization for activation.

Identification of highly efficacious PROTACs targeting BRD4 against acute myeloid leukemia:Design,synthesis,and biological evaluations

The abnormal activation of BRD4 accelerates the progression of acute myeloid leukemia(AML),developing more precise therapeutics to intervene BRD4 promise to be an excellent opportunity to avoid current limitations of chemotherapy in clinic.Herein,a range of small-molecule PROTACs with the privileged 8-methyl-pyrrolo[1,2-a]pyrazin-1(2H)-one scaffold were rationally designed,which harbored different carbon or ethylenedioxy chains to degrade BRD4 mediated by the E3 ubiquitin ligase CRBN.Among them,the most potential B24 exhibited remarkable BRD4 degradation and excellent anti-proliferative activities in MV4-11 cells,with values of DC_(50)and IC_(50)for 0.75 nmol/L and 0.4 nmol/L,respectively,which were better than the BRD4 inhibitor(+)-JQ-1.Notably,this compound could time-dependently degrade the target protein in the BRD4-,CRBN-,and proteasome-dependent manner.Besides,B24 dramatically decreased the level of proto-oncogene c-Myc,and induced cell apoptosis by arresting the cell cycle in G0/G1 phase,down-regulating Bcl-2 and up-regulating Bax to amplify apoptotic effectors.This proof-of-concept study also highlighted the feasibility of BRD4-based PROTACs as a more powerful strategy against AML.

Synthesis and biological evaluation of andrographolide derivatives as potent anti-HIV agents

A series of Andro derivatives were described and evaluated for their anti-HIV activity in vitro. Compound 10 and 16b, of which TI were 〉 10, had some anti-HIV-1 activity in vitro. Therein, compound 10 which was the best potent compound, could serve as a new lead for further development of anti-AIDS agents.

Histology and antitumor activity study of PTX-loaded micelle,a fluorescent drug delivery system prepared by PEG-TPP

We synthesized PEG-TPP as carrier to encapsulate paclitaxel (PTX) in the form of micelles to overcome its water-solubility problem. PTX-loaded micelles possess a-week stability and appropriate particle size (152.1 ±1.2 nm) which is beneficial for enhanced permeability and retention (EPR) effect. Strong pH dependence of PTX releasing from micelles is verified by in vitro release study. At cellular level, PTX-loaded micelles can target mitochondria effectively which may results a better cytotoxicity of micelles (especially IC50 = 0.123 ± 0.035μmol/L of micelles and 0.298 ± 0.067μmol/L of PTX alone on MCF-7 cells). The fluorescence distributions of both isolated and sliced organs show that the micelles can effectively target tumors. Moreover, we further prove the enhanced therapeutic effects of micelles in tumor-bearing mice comparing with PTX alone. The results show that the biodegradable drug delivery system prepared by PEG-TPP can overcome the poor solubility of paclitaxel and improve its tumor targeting and antitumor activity.