INTRODUCTIONProgramed cell death plays an important role in thegenesis of cancer.Certain cancer genes canregulate apoptosis.Recently,several proteins thatare structurally related to Bcl-2,an inhibitor ofapoptosis,have...INTRODUCTIONProgramed cell death plays an important role in thegenesis of cancer.Certain cancer genes canregulate apoptosis.Recently,several proteins thatare structurally related to Bcl-2,an inhibitor ofapoptosis,have been identified.Therefore,novel strategies and agents that target specificmolecular pathways,as well as triggering a展开更多
Steel production involves the transfer and transformation of material and energy at different levels, structures, and scales, and this process incurs substantial information in the material and energy dimensions. Give...Steel production involves the transfer and transformation of material and energy at different levels, structures, and scales, and this process incurs substantial information in the material and energy dimensions. Given the black-box feature of iron and steel production processes, process visualization plays an important role and inevitably benefits parameter correction, technical support decision-making, personnel training, and other aspects of the steel metallurgy industry. The technological characteristics of the entire process in the steel industry were analyzed in this study, a visualization technology route based on virtual reality(VR) was built, and the important components of visual simulation system for steel industry and the important technical points needed to realize the system were proposed. On the foundation, a visual simulation model for the process scheduling of the iron and steel enterprise raw materials' field, slab, and hot rolling processes was built, and a visualization simulation platform of the iron and steel metallurgy plant-wide process, including ironmaking, steelmaking, hot rolling, and cold rolling, was developed. Lastly, the effectiveness of platform was illustrated by practical application.展开更多
Starting the cracking gas compressor and precooling the refrigeration system are keys to start-up of an ethylene plant and accounts for up to 50% of the total start-up time and plant flare emissions. Premature feeding...Starting the cracking gas compressor and precooling the refrigeration system are keys to start-up of an ethylene plant and accounts for up to 50% of the total start-up time and plant flare emissions. Premature feeding of cracking furnaces can be avoided if the cracking gas compressor is started and the refrigeration system is precooled in advance using mixed gas as the start-up working medium(SWM). Start-up scenario with mixed gas as SWM could significantly reduce the emission loss and shorten the precooling time. Research shows that making appropriate start-up scheme is important not only to ensure operational safety and feasibility, but also to reduce energy consumption. In this paper, a method is proposed to select suitable start-up operational parameters of compression and refrigeration system with sufficient safe operating ranges and short precooling time. The complex interrelation among key parameters of start-up is analyzed. It is found that higher energy consumption, especially for super high-pressure steam(SS), can promote operational safety and shorten the precooling time during start-up.Based on steady-state and dynamic simulation, appropriate operating parameter ranges are determined with reasonable SS consumption. A real case study demonstrates that an appropriate start-up scheme will optimize the operation.展开更多
Objective: To study the correlation between mi R-21 and Treg/Th17 ratio in the microenvironment of rats with hepatocellular carcinoma. Methods: Diethylnitrosamine was used to build the hepatocel ular carcinoma model o...Objective: To study the correlation between mi R-21 and Treg/Th17 ratio in the microenvironment of rats with hepatocellular carcinoma. Methods: Diethylnitrosamine was used to build the hepatocel ular carcinoma model of rats; the content of Treg cells and Th17 cells and the expression of mi R-21 in the peripheral blood of rats with hepatocellular carcinoma were detected. The statistical analysis was performed on the correlation between mi R-21 expression and Treg/Th17 ratio. Results: Hepatocellular carcinoma model of rats was successfully constructed. The proportion of Th17 cells among all CD4+T cells in the peripheral blood of rats with hepatocellular carcinoma was 5.319%, which was higher than the control group; while the proportion of Treg cells was 9.472%, which was higher than the control group. Treg/Th17 ratio in the model group was 1.781, compared with 1.478 in the control group. The expression of mi R-21 was increased in the peripheral blood of rats with hepatocellular carcinoma and it showed a positive correlation with the ratio of Treg/Th17. Conclusions: There is a positive correlation between the expression level of miR-21 and the ratio of Treg/Th17.展开更多
Objective:To discuss the abnormal expression of Wnt inhibitory factor(WIFI) in hepatocellular carcinoma cells and its regulating effect on the hepatocellular carcinoma invasion and metastasis factors of tissue inhibit...Objective:To discuss the abnormal expression of Wnt inhibitory factor(WIFI) in hepatocellular carcinoma cells and its regulating effect on the hepatocellular carcinoma invasion and metastasis factors of tissue inhibitor of matrix metalloproteinases-3(TIMP-3)and caveolin-1.Methods:RT-PCR and Western blot were employed to detect the expression of WIF1 in six hepatocellular carcinoma eell lines of HepG2,Hep3 B,Huh7,PLC/PRF/5.SMMC-7721 and MHCC97 and the immortalized human liver cell line THLE-3.Besides,Lipofectamine 2000 was employed to transfect the eukaryotic expression vector pcDNA3.lWIF1 and blank plasmid pcDNA3.1 into hepatocellular carcinoma cell lines.Transwell assay was used to detect the effect of WIF1 on the invasion ability of hepatocellular carcinoma cells;Western blot was used to detect the effect of WIF1 on the expression of TIMP-3 and caveolin-1in hepatocellular carcinoma cells,it also discussed the effect on the expression of β-catenin.Results:The expression of WIF1 in hepatocellular carcinoma cell lines was lower than that in the normal liver cell lines(P<0.01);while there was basically no expression of WIF1 in the human highly metastatic cell line MHCC-97 and moderate expression in HepG2 and SMMC-7721.Therefore,HepG2 and SMMC-7721 were chosen as the further experimental cell lines.After transfecting the eukaryotic expression vector peDNA3.1-WEFl and blank plasmid pcDNA3.1 into hepatocellular carcinoma eell lines,compared with(he blank plasmid group,the cell viability and invasion ability in the WIF1 group were all reduced(P<0.01),the expression of TIMP-3,caveolin-1 and mRNA were all down-regulated(P<0.01),and the expression of β-catenin was decreased(P<0.01).Conclusions:Because of down-regulation or missing of expression of WIFI in hepatocellular carcinoma cell lines,the up-regulation of WIFI expression can significantly inhibit the invasion and metastasis of HepG2 and SMMC-7721 of hepatocellular carcinoma cell lines,which are related to the up-regulated expression of TIMP-3 and down-regulated expression of caveolin-1 and may be realized through the Wnt/β-catenin signaling pathway.展开更多
BACKGROUND Helicobacter pylori(H. pylori) is a Gram-negative bacterium found in the upper digestive tract. Although H. pylori infection is an identified risk factor for gastric cancer, its role in esophageal squamous ...BACKGROUND Helicobacter pylori(H. pylori) is a Gram-negative bacterium found in the upper digestive tract. Although H. pylori infection is an identified risk factor for gastric cancer, its role in esophageal squamous cell carcinoma(ESCC) remains a topic of much debate.AIM To evaluate the association between H. pylori infection and the risk of precancerous lesions of ESCC, and further explore the association between dietary factors and the risk of H. pylori infection.METHODS Two hundred patients with esophageal precancerous lesions(EPL) aged 63.01 ± 6.08 years and 200 healthy controls aged 62.85 ± 6.03 years were included in this case-control study. Epidemiological data and qualitative food frequency data were investigated. Enzyme-linked immunosorbent assay measuring serum immunoglobulin G antibodies was used to determine H. pylori seropositivity. An unconditional logistic regression model was used to assess the association between H. pylori infection and EPL risk dichotomized by gender, age, and the use of tobacco and alcohol, as well as the association between dietary factors and the risk of H. pylori infection.RESULTS A total of 47(23.5%) EPL cases and 58(29.0%) healthy controls had positive H. pylori infection. An inverse relation between H. pylori infection and the risk of EPL was found in the group of drinkers after adjustment for covariates [odds ratio(OR) = 0.32, 95% confidence interval(95%CI): 0.11-0.95]. Additionally, peanut intake was significantly associated with a decreased risk of H. pylori infection(OR = 0.39, 95%CI: 0.20-0.74).CONCLUSION Our study suggested that H. pylori infection may decrease the risk of EPL for drinkers in a rural adult Chinese population, and the consumption of peanut may reduce the risk of H. pylori infection. These findings should be framed as preliminary evidence, and further studies are required to address whether the mechanisms are related to the localization of lesions and alcohol consumption.展开更多
Cardioplegia has been widely used to reduce myocardial injury during pediatric cardiac surgery;however,which cardioplegia solution has the best protective effect has not been established.Thus,we compared the myocardia...Cardioplegia has been widely used to reduce myocardial injury during pediatric cardiac surgery;however,which cardioplegia solution has the best protective effect has not been established.Thus,we compared the myocardial protective effects of different cardioplegia solutions used in pediatric cardiac surgery.Seven databases were searched to identify the relevant randomized controlled trials.A network meta-analysis with a Bayesian framework was conducted.The outcomes included the following biochemical and clinical outcomes:serum concentrations of the creatine kinase-myocardial band at 6 h postoperatively;cardiac troponin I(cTnI)at 4,12,and 24 h postoperatively;spontaneous beating after declamping;postoperative arrhythmias;inotropic support percentage and duration;mechanical ventilation hours;intensive care unit stay in days;hospital stay in days;and mortality.The group treated with cold crystalloid cardioplegia(cCCP)was chosen as the control group.The 22 studies involved 1529 patients.Six types of cardioplegia solutions were described in these studies,including cold blood cardioplegia,cCCP,del Nido,histidine-tryptophan-ketoglutarate(HTK),terminal warm blood cardioplegia,and warm blood cardioplegia(wBCP).The serum concentrations of the 24-h cTnI with wBCP(MD=−2.52,95%CI:−4.74 to−0.27)was significantly lower than cCCP.The serum concentrations of the 24-h cTnI with HTK(MD=4.91,95%CI:2.84–7.24)was significantly higher than cCCP.There was no significant difference in other biochemical and clinical outcomes when compared to cCCP.In conclusion,wBCP may have a superior myocardial protective effect with lower 24-h cTnI levels postoperatively and similar clinical outcomes after pediatric cardiac surgery.展开更多
The revegetation protection system(VPS)on the edge of the Tengger Desert can be referred to as a successful model of sand control technology in China and even the world,and there has been a substantial amount of resea...The revegetation protection system(VPS)on the edge of the Tengger Desert can be referred to as a successful model of sand control technology in China and even the world,and there has been a substantial amount of research on revegetation stability.However,it is unclear how meso-and micro-scale revegetation activity has responded to climatic change over the past decades.To evaluate the relative influence of climatic variables on revegetation activities in a restored desert ecosystem,we analysed the trend of revegetation change from 2002 to 2015 using a satellite-derived normalized difference vegetation index(NDVI)dataset.The time series of the NDVI data were decomposed into trend,seasonal,and random components using a segmented regression method.The results of the segmented regression model indicate a changing trend in the NDVI in the VPS,changing from a decrease(−7×10−3/month)before 2005 to an increase(0.3×10−3/month)after 2005.We found that precipitation was the most important climatic factor influencing the growing season NDVI(P<0.05),while vegetation growth sensitivity to water and heat varied significantly in different seasons.In the case of precipitation reduction and warming in the study area,the NDVI of the VPS could still maintain an overall slow upward trend(0.04×10−3/month),indicating that the ecosystem is sustainable.Our findings suggest that the VPS has been successful in maintaining stability and sustainability under current climate change conditions and that it is possible to introduce the VPS in similar areas as a template for resistance to sand and drought hazards.展开更多
We theoretically investigate the thermoelectric properties of a three-terminal double-dot interferometer with Rashba spin-orbit interaction. It is found that with some temperature distributions a thermal spin current ...We theoretically investigate the thermoelectric properties of a three-terminal double-dot interferometer with Rashba spin-orbit interaction. It is found that with some temperature distributions a thermal spin current can even be produced without the help of magnetic flux and by tuning the spin interference effect in the system, a pure spin or fully spin-polarized current can be driven by temperature differences. For the cases that two of the terminals are held at the same temperature, the charge (spin) thermopower and the charge (spin) figure of merit are defined and calculated in the linear response regime. With some choices of the system parameters the calculated spin and charge thermopowers are of the same order of magnitude and the charge figure of merit can exceed 1.展开更多
The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reve...The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis.Here we employed three independent systems biology approaches toward this goal.First,protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and20,240 human proteins revealed multiple conserved cellular pathways and protein complexes,including proteasome complexes.Second,an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process.Third,high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds,including six proteasome inhibitors that suppress both ZIKV and DENV replication.Integrative analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV replication.Our study provides multi-omics datasets for further studies of flavivirus–host interactions,disease pathogenesis,and new drug targets.展开更多
文摘INTRODUCTIONProgramed cell death plays an important role in thegenesis of cancer.Certain cancer genes canregulate apoptosis.Recently,several proteins thatare structurally related to Bcl-2,an inhibitor ofapoptosis,have been identified.Therefore,novel strategies and agents that target specificmolecular pathways,as well as triggering a
基金financially supported by the Major International Joint Research Project of the National Natural Science Foundation of China (No.71520107004)the Major Program of National Natural Science Foundation of China (No.71790614)the 111 Project (No.B16009)。
文摘Steel production involves the transfer and transformation of material and energy at different levels, structures, and scales, and this process incurs substantial information in the material and energy dimensions. Given the black-box feature of iron and steel production processes, process visualization plays an important role and inevitably benefits parameter correction, technical support decision-making, personnel training, and other aspects of the steel metallurgy industry. The technological characteristics of the entire process in the steel industry were analyzed in this study, a visualization technology route based on virtual reality(VR) was built, and the important components of visual simulation system for steel industry and the important technical points needed to realize the system were proposed. On the foundation, a visual simulation model for the process scheduling of the iron and steel enterprise raw materials' field, slab, and hot rolling processes was built, and a visualization simulation platform of the iron and steel metallurgy plant-wide process, including ironmaking, steelmaking, hot rolling, and cold rolling, was developed. Lastly, the effectiveness of platform was illustrated by practical application.
基金Supported by the National Basic Research Program of China(2012CB720500)the National Natural Science Foundation of China(U1462206)
文摘Starting the cracking gas compressor and precooling the refrigeration system are keys to start-up of an ethylene plant and accounts for up to 50% of the total start-up time and plant flare emissions. Premature feeding of cracking furnaces can be avoided if the cracking gas compressor is started and the refrigeration system is precooled in advance using mixed gas as the start-up working medium(SWM). Start-up scenario with mixed gas as SWM could significantly reduce the emission loss and shorten the precooling time. Research shows that making appropriate start-up scheme is important not only to ensure operational safety and feasibility, but also to reduce energy consumption. In this paper, a method is proposed to select suitable start-up operational parameters of compression and refrigeration system with sufficient safe operating ranges and short precooling time. The complex interrelation among key parameters of start-up is analyzed. It is found that higher energy consumption, especially for super high-pressure steam(SS), can promote operational safety and shorten the precooling time during start-up.Based on steady-state and dynamic simulation, appropriate operating parameter ranges are determined with reasonable SS consumption. A real case study demonstrates that an appropriate start-up scheme will optimize the operation.
文摘Objective: To study the correlation between mi R-21 and Treg/Th17 ratio in the microenvironment of rats with hepatocellular carcinoma. Methods: Diethylnitrosamine was used to build the hepatocel ular carcinoma model of rats; the content of Treg cells and Th17 cells and the expression of mi R-21 in the peripheral blood of rats with hepatocellular carcinoma were detected. The statistical analysis was performed on the correlation between mi R-21 expression and Treg/Th17 ratio. Results: Hepatocellular carcinoma model of rats was successfully constructed. The proportion of Th17 cells among all CD4+T cells in the peripheral blood of rats with hepatocellular carcinoma was 5.319%, which was higher than the control group; while the proportion of Treg cells was 9.472%, which was higher than the control group. Treg/Th17 ratio in the model group was 1.781, compared with 1.478 in the control group. The expression of mi R-21 was increased in the peripheral blood of rats with hepatocellular carcinoma and it showed a positive correlation with the ratio of Treg/Th17. Conclusions: There is a positive correlation between the expression level of miR-21 and the ratio of Treg/Th17.
基金supported by National Science&Technology Pillar Program during the 12th Five-year Plan Period under the research and development of new trisacryl gelatin microspheres(No.2012BAH5B06)
文摘Objective:To discuss the abnormal expression of Wnt inhibitory factor(WIFI) in hepatocellular carcinoma cells and its regulating effect on the hepatocellular carcinoma invasion and metastasis factors of tissue inhibitor of matrix metalloproteinases-3(TIMP-3)and caveolin-1.Methods:RT-PCR and Western blot were employed to detect the expression of WIF1 in six hepatocellular carcinoma eell lines of HepG2,Hep3 B,Huh7,PLC/PRF/5.SMMC-7721 and MHCC97 and the immortalized human liver cell line THLE-3.Besides,Lipofectamine 2000 was employed to transfect the eukaryotic expression vector pcDNA3.lWIF1 and blank plasmid pcDNA3.1 into hepatocellular carcinoma cell lines.Transwell assay was used to detect the effect of WIF1 on the invasion ability of hepatocellular carcinoma cells;Western blot was used to detect the effect of WIF1 on the expression of TIMP-3 and caveolin-1in hepatocellular carcinoma cells,it also discussed the effect on the expression of β-catenin.Results:The expression of WIF1 in hepatocellular carcinoma cell lines was lower than that in the normal liver cell lines(P<0.01);while there was basically no expression of WIF1 in the human highly metastatic cell line MHCC-97 and moderate expression in HepG2 and SMMC-7721.Therefore,HepG2 and SMMC-7721 were chosen as the further experimental cell lines.After transfecting the eukaryotic expression vector peDNA3.1-WEFl and blank plasmid pcDNA3.1 into hepatocellular carcinoma eell lines,compared with(he blank plasmid group,the cell viability and invasion ability in the WIF1 group were all reduced(P<0.01),the expression of TIMP-3,caveolin-1 and mRNA were all down-regulated(P<0.01),and the expression of β-catenin was decreased(P<0.01).Conclusions:Because of down-regulation or missing of expression of WIFI in hepatocellular carcinoma cell lines,the up-regulation of WIFI expression can significantly inhibit the invasion and metastasis of HepG2 and SMMC-7721 of hepatocellular carcinoma cell lines,which are related to the up-regulated expression of TIMP-3 and down-regulated expression of caveolin-1 and may be realized through the Wnt/β-catenin signaling pathway.
基金Supported by the Fellowship of China Postdoctoral Science Foundation,No. 2022M710675the National Natural Science Foundation of China,No. 81673147the Danone Dietary Nutrition Research and Education Foundation,No. DIC2020-08。
文摘BACKGROUND Helicobacter pylori(H. pylori) is a Gram-negative bacterium found in the upper digestive tract. Although H. pylori infection is an identified risk factor for gastric cancer, its role in esophageal squamous cell carcinoma(ESCC) remains a topic of much debate.AIM To evaluate the association between H. pylori infection and the risk of precancerous lesions of ESCC, and further explore the association between dietary factors and the risk of H. pylori infection.METHODS Two hundred patients with esophageal precancerous lesions(EPL) aged 63.01 ± 6.08 years and 200 healthy controls aged 62.85 ± 6.03 years were included in this case-control study. Epidemiological data and qualitative food frequency data were investigated. Enzyme-linked immunosorbent assay measuring serum immunoglobulin G antibodies was used to determine H. pylori seropositivity. An unconditional logistic regression model was used to assess the association between H. pylori infection and EPL risk dichotomized by gender, age, and the use of tobacco and alcohol, as well as the association between dietary factors and the risk of H. pylori infection.RESULTS A total of 47(23.5%) EPL cases and 58(29.0%) healthy controls had positive H. pylori infection. An inverse relation between H. pylori infection and the risk of EPL was found in the group of drinkers after adjustment for covariates [odds ratio(OR) = 0.32, 95% confidence interval(95%CI): 0.11-0.95]. Additionally, peanut intake was significantly associated with a decreased risk of H. pylori infection(OR = 0.39, 95%CI: 0.20-0.74).CONCLUSION Our study suggested that H. pylori infection may decrease the risk of EPL for drinkers in a rural adult Chinese population, and the consumption of peanut may reduce the risk of H. pylori infection. These findings should be framed as preliminary evidence, and further studies are required to address whether the mechanisms are related to the localization of lesions and alcohol consumption.
文摘Cardioplegia has been widely used to reduce myocardial injury during pediatric cardiac surgery;however,which cardioplegia solution has the best protective effect has not been established.Thus,we compared the myocardial protective effects of different cardioplegia solutions used in pediatric cardiac surgery.Seven databases were searched to identify the relevant randomized controlled trials.A network meta-analysis with a Bayesian framework was conducted.The outcomes included the following biochemical and clinical outcomes:serum concentrations of the creatine kinase-myocardial band at 6 h postoperatively;cardiac troponin I(cTnI)at 4,12,and 24 h postoperatively;spontaneous beating after declamping;postoperative arrhythmias;inotropic support percentage and duration;mechanical ventilation hours;intensive care unit stay in days;hospital stay in days;and mortality.The group treated with cold crystalloid cardioplegia(cCCP)was chosen as the control group.The 22 studies involved 1529 patients.Six types of cardioplegia solutions were described in these studies,including cold blood cardioplegia,cCCP,del Nido,histidine-tryptophan-ketoglutarate(HTK),terminal warm blood cardioplegia,and warm blood cardioplegia(wBCP).The serum concentrations of the 24-h cTnI with wBCP(MD=−2.52,95%CI:−4.74 to−0.27)was significantly lower than cCCP.The serum concentrations of the 24-h cTnI with HTK(MD=4.91,95%CI:2.84–7.24)was significantly higher than cCCP.There was no significant difference in other biochemical and clinical outcomes when compared to cCCP.In conclusion,wBCP may have a superior myocardial protective effect with lower 24-h cTnI levels postoperatively and similar clinical outcomes after pediatric cardiac surgery.
基金The authors gratefully acknowledge the editor and two anonymous reviewers for valuable comments on the manuscript.We also acknowledge DingHai Zhang for their help in the data analysis.This work was supported by the Funds for Creative Research Groups of China(Grant No.41621001)the National Natural Science Foundation of China(Grant Nos.41530746+1 种基金41901064)the Foundation for Excellent Youth Scholars of NIEER,CAS.
文摘The revegetation protection system(VPS)on the edge of the Tengger Desert can be referred to as a successful model of sand control technology in China and even the world,and there has been a substantial amount of research on revegetation stability.However,it is unclear how meso-and micro-scale revegetation activity has responded to climatic change over the past decades.To evaluate the relative influence of climatic variables on revegetation activities in a restored desert ecosystem,we analysed the trend of revegetation change from 2002 to 2015 using a satellite-derived normalized difference vegetation index(NDVI)dataset.The time series of the NDVI data were decomposed into trend,seasonal,and random components using a segmented regression method.The results of the segmented regression model indicate a changing trend in the NDVI in the VPS,changing from a decrease(−7×10−3/month)before 2005 to an increase(0.3×10−3/month)after 2005.We found that precipitation was the most important climatic factor influencing the growing season NDVI(P<0.05),while vegetation growth sensitivity to water and heat varied significantly in different seasons.In the case of precipitation reduction and warming in the study area,the NDVI of the VPS could still maintain an overall slow upward trend(0.04×10−3/month),indicating that the ecosystem is sustainable.Our findings suggest that the VPS has been successful in maintaining stability and sustainability under current climate change conditions and that it is possible to introduce the VPS in similar areas as a template for resistance to sand and drought hazards.
基金Supported by the National Natural Science Foundation of China under Grant No.11604113the Natural Science Foundation of the Jiangsu Higher Education Institutions of China under Grant No.17KJB140004
文摘We theoretically investigate the thermoelectric properties of a three-terminal double-dot interferometer with Rashba spin-orbit interaction. It is found that with some temperature distributions a thermal spin current can even be produced without the help of magnetic flux and by tuning the spin interference effect in the system, a pure spin or fully spin-polarized current can be driven by temperature differences. For the cases that two of the terminals are held at the same temperature, the charge (spin) thermopower and the charge (spin) figure of merit are defined and calculated in the linear response regime. With some choices of the system parameters the calculated spin and charge thermopowers are of the same order of magnitude and the charge figure of merit can exceed 1.
基金supported by the National Institutes of Health(NIH),USA(Grant Nos.U19AI131130,R01GM111514,R21AI131706,R35NS097370,and R37NS047344)the Intramural Research Program of the NCATS/NIH,USA
文摘The Zika virus(ZIKV)and dengue virus(DENV)flaviviruses exhibit similar replicative processes but have distinct clinical outcomes.A systematic understanding of virus–host protein–protein interaction networks can reveal cellular pathways critical to viral replication and disease pathogenesis.Here we employed three independent systems biology approaches toward this goal.First,protein array analysis of direct interactions between individual ZIKV/DENV viral proteins and20,240 human proteins revealed multiple conserved cellular pathways and protein complexes,including proteasome complexes.Second,an RNAi screen of 10,415 druggable genes identified the host proteins required for ZIKV infection and uncovered that proteasome proteins were crucial in this process.Third,high-throughput screening of 6016 bioactive compounds for ZIKV inhibition yielded 134 effective compounds,including six proteasome inhibitors that suppress both ZIKV and DENV replication.Integrative analyses of these orthogonal datasets pinpoint proteasomes as critical host machinery for ZIKV/DENV replication.Our study provides multi-omics datasets for further studies of flavivirus–host interactions,disease pathogenesis,and new drug targets.