A theoretical study is presented herein on the pen- etration of a semi-infinite target by a spherical-headed long rod for Yp 〉 S, where Yp is the penetrator strength and S is the static target resistance. For Yp 〉 S...A theoretical study is presented herein on the pen- etration of a semi-infinite target by a spherical-headed long rod for Yp 〉 S, where Yp is the penetrator strength and S is the static target resistance. For Yp 〉 S, depending upon initial impact velocity, there exist three types of penetration, namely, penetration by a rigid long rod, penetration by a deforming non-erosive long rod and penetration by an erosive long rod. If the impact velocity of the penetrator is higher than the hydrodynamic velocity (VH), it will penetrate the target in an erosive mode; if the impact velocity lies between the hydrodynamic velocity (VH) and the rigid body velocity (VR), it will penetrate the target in a deformable mode; if the impact velocity is less than the rigid body velocity (VR), it will penetrate the target in a rigid mode. The critical conditions for the transition among these three penetration modes are proposed. It is demonstrated that the present model predictions correlate well with the experimental observations in terms of depth of penetration (DOP) and the critical transition conditions.展开更多
Objective To investigate miR-183-5p targeting to forkhead box protein O1(FOXO1)and its corresponding effect on the proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)of non-small cell lung canc...Objective To investigate miR-183-5p targeting to forkhead box protein O1(FOXO1)and its corresponding effect on the proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)of non-small cell lung cancer(NSCLC)cells.Methods NSCLC tissues and adjacent normal tissues from 60 patients with NSCLC adenocarcinoma were obtained via pathological biopsy or intraoperative resection.Several cell lines were cultured in vitro,including the human normal lung epithelial cell line BEAS-2B and human NSCLC cell lines A549,SPCA-1,PC-9,and 95-D.miR-183-5p and FOXO1 mRNA expression in tissues and cells were detected by qRT-PCR;the corresponding correlations in NSCLC tissues were analyzed using the Pearson test,and the relationship between miR-183-5p expression and clinicopathological parameters was analyzed.The miR-183-5p-mediated regulation of FOXO1 was verified by bioinformatics prediction alongside double luciferase,RNA-binding protein immunoprecipitation(RIP)assay,and pull-down experiments.A549 cells were divided into control,anti-miR-NC,anti-miR-183-5p,miR-NC,miR-183-5p,miR-183-5p+pcDNA3.1,and miR-183-5p+pcDNA3.1-FOXO1 groups.Cell proliferation,invasion,migration,apoptosis,and cell cycle distribution were detected using an MTT assay,clone formation assay,Transwell assay,scratch test,and flow cytometry,respectively.The expression of EMT-related proteins in the cells was analyzed by western blotting.The effect of miR-185-3p silencing on the development of transplanted tumors was detected by analyzing tumor formation in nude mice.Results miR-183-5p expression was significantly higher in NSCLC tissues and cells than in adjacent normal tissues,whereas FOXO1 mRNA expression was significantly down-regulated.There was a significant negative correlation between miR-183-5p and FOXO1 mRNA in NSCLC tissues(P<0.05).Additionally,the expression of miR-183-5p was significantly correlated with tumor size,tumor differentiation,and tumor-node-metastasis stage in patients with NSCLC(P<0.05).miR-183-5p targeted and inhibited FOXO1 expression.Compared to the anti-miR-NC group,the cell proliferation,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells were significantly lower in the anti-miR-183-5p group,whereas the protein expression of E-cadherin andα-catenin and the proportion of G0/G1 phase cells were significantly higher;additionally,the frequency of colony formation and invasion were significantly lower in the anti-miR-183-5p group(P<0.05).Compared to the miR-NC group,the cell proliferation,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells in the miR-183-5p group were significantly higher,whereas the E-cadherin andα-catenin protein expression and the proportion of G0/G1 phase cells were significantly lower;furthermore,the frequency of colony formation and invasion were significantly higher in the miR-183-5p group(P<0.05).Compared with the miR-183-5p+pcDNA3.1 group,the OD value,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells were significantly lower in the miR-183-5p+pcDNA3.1-FOXO1 group,whereas E-cadherin andα-catenin protein expression and the proportion of G0/G1 phase cells were significantly higher;additionally,the frequency of colony formation and invasion was significantly lower in the miR-183-5p+pcDNA3.1-FOXO1 group(P<0.05).Overall,silencing miR-185-3p inhibited the growth of transplanted tumors and promoted FOXO1 expression.Conclusion Overexpression of miR-183-5p can inhibit apoptosis and promote the proliferation,migration,invasion,and EMT,of NSCLC cells by down-regulating FOXO1 expression.展开更多
Novel hexadecyl 3- { 4-[2-hydroxy-3(isopropylamino)propoxy]phenyl }propionate (HPP)was synthesized and its effect on delivery of liposomes into cultured cardiomyocytes was examined. The structure of HPP was charac...Novel hexadecyl 3- { 4-[2-hydroxy-3(isopropylamino)propoxy]phenyl }propionate (HPP)was synthesized and its effect on delivery of liposomes into cultured cardiomyocytes was examined. The structure of HPP was characterized by IH NMR, 1R and MS. The amount of cardiomyocytes uptake of HPP-liposome was 3.9-fold higher than plain-liposome, and the increase was 6.2-fold when hypoxia happens. It indicated that HPP was a potential ligand for liposome targeting to ischemic myocardium.展开更多
Over the past decade, a multitude of molecular targeted agents have been explored in the treatment of advanced metastatic gastric. Recent advances in molecular signaling pathways that are dysregulated in gastric cance...Over the past decade, a multitude of molecular targeted agents have been explored in the treatment of advanced metastatic gastric. Recent advances in molecular signaling pathways that are dysregulated in gastric cancer lead to the development of new targeted therapies for the treatment of advanced and metastatic gastric cancer. The addition of trastuzumab to first-line chemotherapy is now a standard of care for the treatment of Human epidermal growth factor receptor (HER2-) positive advanced or metastatic disease, and other HER2-targeted therapies are in late-stage clinical development. Findings from recent major clinical trials provide important insight into the future of metastatic gastric cancer management, which may include the use of anti-angiogenesis, Mesenchymal epithelial transition factor (MET) and Hedgehog Pathways Inhibitortherapy across multiple treatment lines, in the salvage setting, and as part of novel regimens in combination with other targeted agents.展开更多
BACKGROUND The incidence of colorectal cancer in humans is high,and it is in the top five for cancer-related morbidity and mortality.It is one of the main threats to human health.The function of long noncoding RNAs in...BACKGROUND The incidence of colorectal cancer in humans is high,and it is in the top five for cancer-related morbidity and mortality.It is one of the main threats to human health.The function of long noncoding RNAs in tumor occurrence and development has gradually gained attention in recent years.In increasing numbers of studies,researchers have demonstrated that it plays an important role in the pathogenesis of colorectal cancer.AIM To find out if long noncoding RNA RP5-881L22.5 played a role in the pathogenesis of colorectal cancer in relation to the tumor microenvironment.METHODS We analyzed the transcriptome data and clinical data in The Cancer Genome Atlas-colon adenocarcinoma.The CIRBERSORT algorithm was applied to evaluate these tumor-infiltrating immune cells in The Cancer Genome Atlas-colon adenocarcinoma cancer tissue samples.Using the“estimate”package in R,we assessed the tumor immune microenvironment.The expression level of RP5-881L22.5 in tumor tissue and adjacent normal tissue samples from 4 pairs of colorectal cancer patients was determined by quantitative reverse transcription PCR.Colorectal cancer cells were tested for invasiveness using a transwell invasion assay after RP5-881L22.5 expression was knocked down.RESULTS The expression of lncRNA RP5-881L22.5 was related to the clinical characteristics of the tumors,and it was negatively related to the infiltration level of immune cells in the tumor microenvironment and the expression of T cell inhibitory receptors.A major function of its coexpressed mRNA was to regulate tumor immunity,such as the immune response.When quantitative reverse transcription PCR was performed on tumor tissues from 4 pairs of colorectal cancer patients,the results showed that RP5-881L22.5 was highly expressed.Subsequently,knocking down the expression of RP5-881L22.5,the invasiveness of colorectal cancer cell lines was reduced,and the apoptosis rate was increased.CONCLUSION RP5-881L22.5 plays a crucial role in the microenvironment of tumors as well as in the pathogenesis of colorectal cancer.The relationship between RP5-881L22.5 and the tumor immune microenvironment deserves further study.展开更多
Aiming at the problems of convergence-slow and convergence-free of Discrete Particle Swarm Optimization Algorithm(DPSO) in solving large scale or complicated discrete problem, this article proposes Intuitionistic Fuzz...Aiming at the problems of convergence-slow and convergence-free of Discrete Particle Swarm Optimization Algorithm(DPSO) in solving large scale or complicated discrete problem, this article proposes Intuitionistic Fuzzy Entropy of Discrete Particle Swarm Optimization(IFDPSO) and makes it applied to Dynamic Weapon Target Assignment(WTA). First, the strategy of choosing intuitionistic fuzzy parameters of particle swarm is defined, making intuitionistic fuzzy entropy as a basic parameter for measure and velocity mutation. Second, through analyzing the defects of DPSO, an adjusting parameter for balancing two cognition, velocity mutation mechanism and position mutation strategy are designed, and then two sets of improved and derivative algorithms for IFDPSO are put forward, which ensures the IFDPSO possibly search as much as possible sub-optimal positions and its neighborhood and the algorithm ability of searching global optimal value in solving large scale 0-1 knapsack problem is intensified. Third, focusing on the problem of WTA, some parameters including dynamic parameter for shifting firepower and constraints are designed to solve the problems of weapon target assignment. In addition, WTA Optimization Model with time and resource constraints is finally set up, which also intensifies the algorithm ability of searching global and local best value in the solution of WTA problem. Finally, the superiority of IFDPSO is proved by several simulation experiments. Particularly, IFDPSO, IFDPSO1~IFDPSO3 are respectively effective in solving large scale, medium scale or strict constraint problems such as 0-1 knapsack problem and WTA problem.展开更多
We have been developing debris-free laser plasma sources for EUV lithography since 1996. Two types of debris-free sources, such as cryogenic target and gas-puff target laser plasma sources, were designed and built up ...We have been developing debris-free laser plasma sources for EUV lithography since 1996. Two types of debris-free sources, such as cryogenic target and gas-puff target laser plasma sources, were designed and built up in CIOMP. EUV radiation spectra of the sources with a variety of targets have been obtained by different ways.展开更多
Recurrent GBM (RGBM) has a highly unfavorable prognosis with majority of patients dying within 6 months and no standard treatments available. Antineoplaston (ANP) A10 and AS2-1 injections underwent Phase II trials in ...Recurrent GBM (RGBM) has a highly unfavorable prognosis with majority of patients dying within 6 months and no standard treatments available. Antineoplaston (ANP) A10 and AS2-1 injections underwent Phase II trials in RGBM patients, which reported a long-term overall survival (OS) in a small percentage of patients. The additional Phase II studies BT-07, and BT-21 with ANP in GBM also revealed cases of a long-term OS. ANP shares active ingredients with metabolites of sodium phenylbutyrate (PB), which was used in private practice setting in combination of targeted and chemotherapeutic agents for the treatment of RGBM. The treatment contributed to cases of rapid complete response (CR) and significant OS. This paper provides case studies of three patients treated with ANP under Phase II protocols and two patients treated with PB in combination with targeted therapy, who obtained CR and long-term OS. Based on these studies and basic research on the effects of ANP and PB on the genome of GBM and review of results of preclinical and clinical research on targeted agents, the authors suggest a new strategy for successful treatment of RGBM. They propose Phase I/II clinical trials with ANP and PB in combination with targeted agents, bevacizumab (BVZ), pazopanib, dasatinib and everolimus in patients with RGBM after failure of standard surgery, radiation therapy (RT) and chemotherapy including temozolomide (TMZ) to be conducted to evaluate survival, response and toxicity in these patients.展开更多
A computer program MACA was developed for simulating high-dose ion implantation into amorphous solids. The topology of amorphous solids was modelled by adjusting the free flight path distribution between collisions, s...A computer program MACA was developed for simulating high-dose ion implantation into amorphous solids. The topology of amorphous solids was modelled by adjusting the free flight path distribution between collisions, so that the radial distribution function will characterize the short - range order and long - range disorder of amorphous targets. A simulation example is given.展开更多
Objective To investigate the potential therapeutic targets and pharmacological mechanism of(-)-epigallocatechin-3-gallate(EGCG)based on network pharmacology and experimental verification.METHODS The druggability of EG...Objective To investigate the potential therapeutic targets and pharmacological mechanism of(-)-epigallocatechin-3-gallate(EGCG)based on network pharmacology and experimental verification.METHODS The druggability of EGCG was measured by the traditional Chinese medicine systems pharmacology(TCMSP)server,and potential targets of EGCG were identified by Pharm Mapper and Drug Repositioning and Adverse drug Reaction via Chemical-Protein Interactome(DRAR-CPI).The potential targets were imported into GeneMANIA database to obtain the protein-protein direct interaction network,and target physical interaction,co-expression,prediction,genetic interaction,and shared protein domains.The biological process,molecular functions,cellular components and KEGG signaling pathways of potential targets were analyzed using DAVID database.For further study,ethanol was used to establish a model of endothelial injury in vitro.The cell viability was assayed by MTT method,the cellular apoptosis was stained by Annexin V/PI,and the expression levels of Bcl-2,Bax and cleved-caspase-3 were tested by Western blotting.Then,JC-1 and nuclear translocation of NF-κB experiments were used to study the mitochondrial membrane potential and nuclear translocation.RESULTS The oral availability of EGCG was 55.09%(≥30%)and drug-like index was 0.77(≥0.18),which were considered pharmacokinetically active.17 potential targetable proteins of EGCG were predicted by Pharm Mapper and DRAR-CPI.Further research showed that 68.13%displayed similar co-expression characteristics,26.11%physical interactions,and 2.74%shared the same protein domain.The depth network analysis results showed that the biofunctions of EGCG were mainly by regulating glutathione derivative biosynthetic process,glutathione metabolic process,nitrogen compound metabolic process etc..via drug binding,catalytic activity,glutathione transferase activity,anion binding etc..in sarcoplasmic reticulum,spindle pole,microtubule cytoskeleton and cytoplasm.KEGG enrichment analysis showed that Glutathione metabolism,IL^(-1)7 signaling pathway,EGFR tyrosine kinase inhibitor resistance,PI3K-Akt signaling pathway and other pathways were involves in the biofunction of EGCG.The above analyses indicated that EGCG exerts its biofunction through antioxidant and anti-inflammatory mechanisms.The experimental results showed that ethanol 20.0 mmol·L^(-1) decreased cell viability,Bcl-2 expression,and increased cell apoptosis,the intracellular ROS,as well as the expression of Bax and cleaved-caspase-3 of human endothelial cells.However,treatment of the cells with EGCG can significantly alleviate ethanol induced endothelial cells injury.Further study showed that EGCG significantly alleviates ethanol induced mitochondrial depolarization and nuclear translocation of NF-κB.CONCLUSIONS EGCG exerts pharmacological efficacies on ethanol induced endothelial cell injury through multi-target,multi-function and multi-pathway mode.Protective effect of EGCG on ethanol induced cell injury was mainly through alteration of mitochondrial function and NF-κB translocation.Therefore,EGCG have great potential in protecting against endothelial dysfunction of the persons who are chronically abuse of ethanol.This study also provides a new understanding of EGCG in clinical application on cardiovascular and cerebrovascular diseases.展开更多
This paper clarifies the steady-state properties and performance of an α-β filter for moving target tracking using both position and velocity measurements. We call this filter velocity measured α-β (VM-α-β) filt...This paper clarifies the steady-state properties and performance of an α-β filter for moving target tracking using both position and velocity measurements. We call this filter velocity measured α-β (VM-α-β) filter. We first derive the stability condition and steady-state predicted errors as fundamental properties of the VM-α-β filter. The optimal gains for representative motion models are then derived from the Kalman filter equations. Theoretical and numerical analyses verify that VM-α-β filters with these optimal gains realize more accurate tracking than conventional α-β filters when the filter gains are relatively large. Our study reveals the conditions under which the predicted errors of the VM-α-β filters are less than those of conventional α-β filters. Moreover, numerical simulations clarify that the variance of the tracking error of the VM-α-β filters is approximately 3/4 of that of the conventional α-β filters in realistic situations, even when the accuracy of the position/velocity measurements is the same.展开更多
<strong>Introduction</strong> In Central-African Republic, according to UNAIDS in 2019, out of approximately 100,000 people living with HIV, 70% (72,000) knew their HIV status and 47,000 (46%) were on ARV ...<strong>Introduction</strong> In Central-African Republic, according to UNAIDS in 2019, out of approximately 100,000 people living with HIV, 70% (72,000) knew their HIV status and 47,000 (46%) were on ARV therapy;however, there is a paucity of data on viral load suppression in people on ARV therapy. The objective of this study was to assess the third 90 of the UNAIDS strategy for the years 2019 and 2020 in the CAR. <strong>Methods</strong> We analyzed the available viral load data extracted from the data base of the medical analysis laboratory (SYSLAM) of the Institut Pasteur of Bangui for the years 2019 and 2020. The viral loads were determined based on plasma collected in an EDTA tube with Cepheid’s GeneXpert<sup><span style="white-space:nowrap;">®</span></sup> 16-module controllers. Viral load data were extracted from SYSLAM, converted to Excel format, and analyzed with STATA version 14 software. The significance threshold for the statistical tests was set at 5%. <strong>Results</strong> This study included 22,895 patients, of who 72% were female. The average age was 40.82 years, and the majority of the patients (80%) came from the city of Bangui. Regarding the virological parameters associated with this study, 66% of the patients had significant viral load suppression according to the WHO recommendations and 34% were in virological failure. Patients over 50 years of age (71.85%) and age group 40 - 49 years (69.25%) recorded significant levels of viral load suppression. On the other hand, 63.45% of patients under 18 years of age had virological failure. All of these results were statistically significant (p < 0.005). <strong>Conclusion</strong> There should be a concerted effort, to make viral load accessible and available to all patients receiving ARV treatment in the CAR and the management of HIV/AIDS infection of children and adolescents should be given special attention.展开更多
基金supported by the National Natural Science Foundation of China (10872195)
文摘A theoretical study is presented herein on the pen- etration of a semi-infinite target by a spherical-headed long rod for Yp 〉 S, where Yp is the penetrator strength and S is the static target resistance. For Yp 〉 S, depending upon initial impact velocity, there exist three types of penetration, namely, penetration by a rigid long rod, penetration by a deforming non-erosive long rod and penetration by an erosive long rod. If the impact velocity of the penetrator is higher than the hydrodynamic velocity (VH), it will penetrate the target in an erosive mode; if the impact velocity lies between the hydrodynamic velocity (VH) and the rigid body velocity (VR), it will penetrate the target in a deformable mode; if the impact velocity is less than the rigid body velocity (VR), it will penetrate the target in a rigid mode. The critical conditions for the transition among these three penetration modes are proposed. It is demonstrated that the present model predictions correlate well with the experimental observations in terms of depth of penetration (DOP) and the critical transition conditions.
文摘Objective To investigate miR-183-5p targeting to forkhead box protein O1(FOXO1)and its corresponding effect on the proliferation,migration,invasion,and epithelial-mesenchymal transition(EMT)of non-small cell lung cancer(NSCLC)cells.Methods NSCLC tissues and adjacent normal tissues from 60 patients with NSCLC adenocarcinoma were obtained via pathological biopsy or intraoperative resection.Several cell lines were cultured in vitro,including the human normal lung epithelial cell line BEAS-2B and human NSCLC cell lines A549,SPCA-1,PC-9,and 95-D.miR-183-5p and FOXO1 mRNA expression in tissues and cells were detected by qRT-PCR;the corresponding correlations in NSCLC tissues were analyzed using the Pearson test,and the relationship between miR-183-5p expression and clinicopathological parameters was analyzed.The miR-183-5p-mediated regulation of FOXO1 was verified by bioinformatics prediction alongside double luciferase,RNA-binding protein immunoprecipitation(RIP)assay,and pull-down experiments.A549 cells were divided into control,anti-miR-NC,anti-miR-183-5p,miR-NC,miR-183-5p,miR-183-5p+pcDNA3.1,and miR-183-5p+pcDNA3.1-FOXO1 groups.Cell proliferation,invasion,migration,apoptosis,and cell cycle distribution were detected using an MTT assay,clone formation assay,Transwell assay,scratch test,and flow cytometry,respectively.The expression of EMT-related proteins in the cells was analyzed by western blotting.The effect of miR-185-3p silencing on the development of transplanted tumors was detected by analyzing tumor formation in nude mice.Results miR-183-5p expression was significantly higher in NSCLC tissues and cells than in adjacent normal tissues,whereas FOXO1 mRNA expression was significantly down-regulated.There was a significant negative correlation between miR-183-5p and FOXO1 mRNA in NSCLC tissues(P<0.05).Additionally,the expression of miR-183-5p was significantly correlated with tumor size,tumor differentiation,and tumor-node-metastasis stage in patients with NSCLC(P<0.05).miR-183-5p targeted and inhibited FOXO1 expression.Compared to the anti-miR-NC group,the cell proliferation,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells were significantly lower in the anti-miR-183-5p group,whereas the protein expression of E-cadherin andα-catenin and the proportion of G0/G1 phase cells were significantly higher;additionally,the frequency of colony formation and invasion were significantly lower in the anti-miR-183-5p group(P<0.05).Compared to the miR-NC group,the cell proliferation,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells in the miR-183-5p group were significantly higher,whereas the E-cadherin andα-catenin protein expression and the proportion of G0/G1 phase cells were significantly lower;furthermore,the frequency of colony formation and invasion were significantly higher in the miR-183-5p group(P<0.05).Compared with the miR-183-5p+pcDNA3.1 group,the OD value,scratch healing rate,N-cadherin and vimentin protein expression,and the proportion of S phase cells were significantly lower in the miR-183-5p+pcDNA3.1-FOXO1 group,whereas E-cadherin andα-catenin protein expression and the proportion of G0/G1 phase cells were significantly higher;additionally,the frequency of colony formation and invasion was significantly lower in the miR-183-5p+pcDNA3.1-FOXO1 group(P<0.05).Overall,silencing miR-185-3p inhibited the growth of transplanted tumors and promoted FOXO1 expression.Conclusion Overexpression of miR-183-5p can inhibit apoptosis and promote the proliferation,migration,invasion,and EMT,of NSCLC cells by down-regulating FOXO1 expression.
基金This project was supported by the National Natural Science Foundation of China(No.30271548).
文摘Novel hexadecyl 3- { 4-[2-hydroxy-3(isopropylamino)propoxy]phenyl }propionate (HPP)was synthesized and its effect on delivery of liposomes into cultured cardiomyocytes was examined. The structure of HPP was characterized by IH NMR, 1R and MS. The amount of cardiomyocytes uptake of HPP-liposome was 3.9-fold higher than plain-liposome, and the increase was 6.2-fold when hypoxia happens. It indicated that HPP was a potential ligand for liposome targeting to ischemic myocardium.
文摘Over the past decade, a multitude of molecular targeted agents have been explored in the treatment of advanced metastatic gastric. Recent advances in molecular signaling pathways that are dysregulated in gastric cancer lead to the development of new targeted therapies for the treatment of advanced and metastatic gastric cancer. The addition of trastuzumab to first-line chemotherapy is now a standard of care for the treatment of Human epidermal growth factor receptor (HER2-) positive advanced or metastatic disease, and other HER2-targeted therapies are in late-stage clinical development. Findings from recent major clinical trials provide important insight into the future of metastatic gastric cancer management, which may include the use of anti-angiogenesis, Mesenchymal epithelial transition factor (MET) and Hedgehog Pathways Inhibitortherapy across multiple treatment lines, in the salvage setting, and as part of novel regimens in combination with other targeted agents.
基金Supported by the Shenzhen Third People’s Hospital,No.G2022117.
文摘BACKGROUND The incidence of colorectal cancer in humans is high,and it is in the top five for cancer-related morbidity and mortality.It is one of the main threats to human health.The function of long noncoding RNAs in tumor occurrence and development has gradually gained attention in recent years.In increasing numbers of studies,researchers have demonstrated that it plays an important role in the pathogenesis of colorectal cancer.AIM To find out if long noncoding RNA RP5-881L22.5 played a role in the pathogenesis of colorectal cancer in relation to the tumor microenvironment.METHODS We analyzed the transcriptome data and clinical data in The Cancer Genome Atlas-colon adenocarcinoma.The CIRBERSORT algorithm was applied to evaluate these tumor-infiltrating immune cells in The Cancer Genome Atlas-colon adenocarcinoma cancer tissue samples.Using the“estimate”package in R,we assessed the tumor immune microenvironment.The expression level of RP5-881L22.5 in tumor tissue and adjacent normal tissue samples from 4 pairs of colorectal cancer patients was determined by quantitative reverse transcription PCR.Colorectal cancer cells were tested for invasiveness using a transwell invasion assay after RP5-881L22.5 expression was knocked down.RESULTS The expression of lncRNA RP5-881L22.5 was related to the clinical characteristics of the tumors,and it was negatively related to the infiltration level of immune cells in the tumor microenvironment and the expression of T cell inhibitory receptors.A major function of its coexpressed mRNA was to regulate tumor immunity,such as the immune response.When quantitative reverse transcription PCR was performed on tumor tissues from 4 pairs of colorectal cancer patients,the results showed that RP5-881L22.5 was highly expressed.Subsequently,knocking down the expression of RP5-881L22.5,the invasiveness of colorectal cancer cell lines was reduced,and the apoptosis rate was increased.CONCLUSION RP5-881L22.5 plays a crucial role in the microenvironment of tumors as well as in the pathogenesis of colorectal cancer.The relationship between RP5-881L22.5 and the tumor immune microenvironment deserves further study.
基金supported by The National Natural Science Foundation of China under Grant Nos.61402517, 61573375The Foundation of State Key Laboratory of Astronautic Dynamics of China under Grant No. 2016ADL-DW0302+2 种基金The Postdoctoral Science Foundation of China under Grant Nos. 2013M542331, 2015M572778The Natural Science Foundation of Shaanxi Province of China under Grant No. 2013JQ8035The Aviation Science Foundation of China under Grant No. 20151996015
文摘Aiming at the problems of convergence-slow and convergence-free of Discrete Particle Swarm Optimization Algorithm(DPSO) in solving large scale or complicated discrete problem, this article proposes Intuitionistic Fuzzy Entropy of Discrete Particle Swarm Optimization(IFDPSO) and makes it applied to Dynamic Weapon Target Assignment(WTA). First, the strategy of choosing intuitionistic fuzzy parameters of particle swarm is defined, making intuitionistic fuzzy entropy as a basic parameter for measure and velocity mutation. Second, through analyzing the defects of DPSO, an adjusting parameter for balancing two cognition, velocity mutation mechanism and position mutation strategy are designed, and then two sets of improved and derivative algorithms for IFDPSO are put forward, which ensures the IFDPSO possibly search as much as possible sub-optimal positions and its neighborhood and the algorithm ability of searching global optimal value in solving large scale 0-1 knapsack problem is intensified. Third, focusing on the problem of WTA, some parameters including dynamic parameter for shifting firepower and constraints are designed to solve the problems of weapon target assignment. In addition, WTA Optimization Model with time and resource constraints is finally set up, which also intensifies the algorithm ability of searching global and local best value in the solution of WTA problem. Finally, the superiority of IFDPSO is proved by several simulation experiments. Particularly, IFDPSO, IFDPSO1~IFDPSO3 are respectively effective in solving large scale, medium scale or strict constraint problems such as 0-1 knapsack problem and WTA problem.
文摘We have been developing debris-free laser plasma sources for EUV lithography since 1996. Two types of debris-free sources, such as cryogenic target and gas-puff target laser plasma sources, were designed and built up in CIOMP. EUV radiation spectra of the sources with a variety of targets have been obtained by different ways.
文摘Recurrent GBM (RGBM) has a highly unfavorable prognosis with majority of patients dying within 6 months and no standard treatments available. Antineoplaston (ANP) A10 and AS2-1 injections underwent Phase II trials in RGBM patients, which reported a long-term overall survival (OS) in a small percentage of patients. The additional Phase II studies BT-07, and BT-21 with ANP in GBM also revealed cases of a long-term OS. ANP shares active ingredients with metabolites of sodium phenylbutyrate (PB), which was used in private practice setting in combination of targeted and chemotherapeutic agents for the treatment of RGBM. The treatment contributed to cases of rapid complete response (CR) and significant OS. This paper provides case studies of three patients treated with ANP under Phase II protocols and two patients treated with PB in combination with targeted therapy, who obtained CR and long-term OS. Based on these studies and basic research on the effects of ANP and PB on the genome of GBM and review of results of preclinical and clinical research on targeted agents, the authors suggest a new strategy for successful treatment of RGBM. They propose Phase I/II clinical trials with ANP and PB in combination with targeted agents, bevacizumab (BVZ), pazopanib, dasatinib and everolimus in patients with RGBM after failure of standard surgery, radiation therapy (RT) and chemotherapy including temozolomide (TMZ) to be conducted to evaluate survival, response and toxicity in these patients.
文摘A computer program MACA was developed for simulating high-dose ion implantation into amorphous solids. The topology of amorphous solids was modelled by adjusting the free flight path distribution between collisions, so that the radial distribution function will characterize the short - range order and long - range disorder of amorphous targets. A simulation example is given.
基金National Natural Science Foundation of China(82100488)Key Research and Development Pro⁃gram Project of Shaanxi Province(2021SF-071)and National Training Program of Innovation and Entrepreneurship for Students of China(201910716019,201910716020,202110716027)。
文摘Objective To investigate the potential therapeutic targets and pharmacological mechanism of(-)-epigallocatechin-3-gallate(EGCG)based on network pharmacology and experimental verification.METHODS The druggability of EGCG was measured by the traditional Chinese medicine systems pharmacology(TCMSP)server,and potential targets of EGCG were identified by Pharm Mapper and Drug Repositioning and Adverse drug Reaction via Chemical-Protein Interactome(DRAR-CPI).The potential targets were imported into GeneMANIA database to obtain the protein-protein direct interaction network,and target physical interaction,co-expression,prediction,genetic interaction,and shared protein domains.The biological process,molecular functions,cellular components and KEGG signaling pathways of potential targets were analyzed using DAVID database.For further study,ethanol was used to establish a model of endothelial injury in vitro.The cell viability was assayed by MTT method,the cellular apoptosis was stained by Annexin V/PI,and the expression levels of Bcl-2,Bax and cleved-caspase-3 were tested by Western blotting.Then,JC-1 and nuclear translocation of NF-κB experiments were used to study the mitochondrial membrane potential and nuclear translocation.RESULTS The oral availability of EGCG was 55.09%(≥30%)and drug-like index was 0.77(≥0.18),which were considered pharmacokinetically active.17 potential targetable proteins of EGCG were predicted by Pharm Mapper and DRAR-CPI.Further research showed that 68.13%displayed similar co-expression characteristics,26.11%physical interactions,and 2.74%shared the same protein domain.The depth network analysis results showed that the biofunctions of EGCG were mainly by regulating glutathione derivative biosynthetic process,glutathione metabolic process,nitrogen compound metabolic process etc..via drug binding,catalytic activity,glutathione transferase activity,anion binding etc..in sarcoplasmic reticulum,spindle pole,microtubule cytoskeleton and cytoplasm.KEGG enrichment analysis showed that Glutathione metabolism,IL^(-1)7 signaling pathway,EGFR tyrosine kinase inhibitor resistance,PI3K-Akt signaling pathway and other pathways were involves in the biofunction of EGCG.The above analyses indicated that EGCG exerts its biofunction through antioxidant and anti-inflammatory mechanisms.The experimental results showed that ethanol 20.0 mmol·L^(-1) decreased cell viability,Bcl-2 expression,and increased cell apoptosis,the intracellular ROS,as well as the expression of Bax and cleaved-caspase-3 of human endothelial cells.However,treatment of the cells with EGCG can significantly alleviate ethanol induced endothelial cells injury.Further study showed that EGCG significantly alleviates ethanol induced mitochondrial depolarization and nuclear translocation of NF-κB.CONCLUSIONS EGCG exerts pharmacological efficacies on ethanol induced endothelial cell injury through multi-target,multi-function and multi-pathway mode.Protective effect of EGCG on ethanol induced cell injury was mainly through alteration of mitochondrial function and NF-κB translocation.Therefore,EGCG have great potential in protecting against endothelial dysfunction of the persons who are chronically abuse of ethanol.This study also provides a new understanding of EGCG in clinical application on cardiovascular and cerebrovascular diseases.
文摘This paper clarifies the steady-state properties and performance of an α-β filter for moving target tracking using both position and velocity measurements. We call this filter velocity measured α-β (VM-α-β) filter. We first derive the stability condition and steady-state predicted errors as fundamental properties of the VM-α-β filter. The optimal gains for representative motion models are then derived from the Kalman filter equations. Theoretical and numerical analyses verify that VM-α-β filters with these optimal gains realize more accurate tracking than conventional α-β filters when the filter gains are relatively large. Our study reveals the conditions under which the predicted errors of the VM-α-β filters are less than those of conventional α-β filters. Moreover, numerical simulations clarify that the variance of the tracking error of the VM-α-β filters is approximately 3/4 of that of the conventional α-β filters in realistic situations, even when the accuracy of the position/velocity measurements is the same.
文摘<strong>Introduction</strong> In Central-African Republic, according to UNAIDS in 2019, out of approximately 100,000 people living with HIV, 70% (72,000) knew their HIV status and 47,000 (46%) were on ARV therapy;however, there is a paucity of data on viral load suppression in people on ARV therapy. The objective of this study was to assess the third 90 of the UNAIDS strategy for the years 2019 and 2020 in the CAR. <strong>Methods</strong> We analyzed the available viral load data extracted from the data base of the medical analysis laboratory (SYSLAM) of the Institut Pasteur of Bangui for the years 2019 and 2020. The viral loads were determined based on plasma collected in an EDTA tube with Cepheid’s GeneXpert<sup><span style="white-space:nowrap;">®</span></sup> 16-module controllers. Viral load data were extracted from SYSLAM, converted to Excel format, and analyzed with STATA version 14 software. The significance threshold for the statistical tests was set at 5%. <strong>Results</strong> This study included 22,895 patients, of who 72% were female. The average age was 40.82 years, and the majority of the patients (80%) came from the city of Bangui. Regarding the virological parameters associated with this study, 66% of the patients had significant viral load suppression according to the WHO recommendations and 34% were in virological failure. Patients over 50 years of age (71.85%) and age group 40 - 49 years (69.25%) recorded significant levels of viral load suppression. On the other hand, 63.45% of patients under 18 years of age had virological failure. All of these results were statistically significant (p < 0.005). <strong>Conclusion</strong> There should be a concerted effort, to make viral load accessible and available to all patients receiving ARV treatment in the CAR and the management of HIV/AIDS infection of children and adolescents should be given special attention.