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,hea...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.展开更多
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...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.展开更多
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 ...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.展开更多
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 prote...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.展开更多
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 ...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.展开更多
文摘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.
基金supported by the Natural ScienceFoundation of Jiangsu Province (Grant No. BK20160519)the Research Foundation forAdvanced Talents of Jiangsu University (Grant No. 16JDG053)+2 种基金the National NaturalScience Foundation of China (Grant No. 51641804)the Natural Science Foundation ofJiangsu Province of China (Grant No. BK20160536)the Advanced Talents ScientificResearch Foundation of Jiangsu University (Grant No. 15JDG170).
文摘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.
基金the National Science Foundation of China(Nos.81872733,82173674,and 81872734)the Research&Development Project in Key Areas of Guangdong Province(No.2019B020203003)for supporting this study。
文摘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.
基金Public Welfare Re-search Fund of Huzhou City(2018GYB60).
文摘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.
基金supported by the National Natural Science Fundation of China(No.30772647)the special major science and technology project of"Creation of Major New Drugs"(No.2009ZX09102-033)
基金supported by grants from the National Natural Science Foundation of China(No.81872733)the Natural Science Foundation of Jiangsu Province of China(No.15KJB310004)
文摘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.