Enabling as the second phase of the Production-Oriented Approach(POA)instruction(Wen,2015),plays a vital role in determining the quality of productive performance of English language learners.To explore how to apply t...Enabling as the second phase of the Production-Oriented Approach(POA)instruction(Wen,2015),plays a vital role in determining the quality of productive performance of English language learners.To explore how to apply theoretical principles of enabling to practice,this paper interprets theoretical principles and reports the practice of the classroom implementation of enabling.The paper proposes a definition for enabling,clarifies the confusion between enabling and scaffolding,and clears up some misunderstandings about enabling.It explains three criteria for effective enabling,namely,alignment,gradualness,and variety,and elaborates on the relations among them.Based on the teaching material of Unit 7 of iEnglish,the paper demonstrates how to design and implement enabling activities under the guidance of these three criteria and evaluates the actual effectiveness of the enabling implemented in the classroom.展开更多
We analyzed RNA-sequencing(RNA-seq)and clinical data from head and neck squamous cell carcinoma(HNSCC)patients in The Cancer Genome Atlas(TCGA)Genomic Data Commons(GDC)portal to investigate the prognostic value of ano...We analyzed RNA-sequencing(RNA-seq)and clinical data from head and neck squamous cell carcinoma(HNSCC)patients in The Cancer Genome Atlas(TCGA)Genomic Data Commons(GDC)portal to investigate the prognostic value of anoikis-related genes(ARGs)in HNSCC and develop new targeted drugs.Differentially expressed ARGs were screened using bioinformatics methods;subsequently,a prognostic model including three ARGs(CDKN2A,BIRC5,and PLAU)was constructed.Our results showed that the model-based risk score was a good prognostic indicator,and the potential of the three ARGs in HNSCC prognosis was validated by the TISCH database,the model’s accuracy was validated in two independent cohorts of the Gene Expression Omnibus database.Immune correlation analysis and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.Potential small-molecule drugs for HNSCC were subsequently predicted using the L1000FWD database.Finally,in vitro experiments were used to verify the database findings.The relative ARG mRNA expression levels in HNSCC and surrounding normal tissues remained consistent with the model results.BIRC5 knockdown inhibited anoikis resistance in WSU-HN6 and CAL-27 cells.Molecular docking,real-time PCR,cell counting kit-8(CCK-8),plate clone,and flow cytometry analyses showed that small-molecule drugs predicted by the database may target the ARGs in the prognostic model,inhibit HNSCC cells survival rate,and promote anoikis in vitro.Therefore,we constructed a new ARG model for HNSCC patients that can predict prognosis and immune activity and identify a potential small-molecule drug for HNSCC,paving the way for clinically targeting anoikis in HNSCC.展开更多
Based on conventional particle swarm optimization(PSO),this paper presents an efficient and reliable heuristic approach using PSO with an adaptive random inertia weight(ARIW)strategy,referred to as the ARIW-PSO algori...Based on conventional particle swarm optimization(PSO),this paper presents an efficient and reliable heuristic approach using PSO with an adaptive random inertia weight(ARIW)strategy,referred to as the ARIW-PSO algorithm,to build a multi-objective optimization model for reservoir operation.Using the triangular probability density function,the inertia weight is randomly generated,and the probability density function is automatically adjusted to make the inertia weight generally greater in the initial stage of evolution,which is suitable for global searches.In the evolution process,the inertia weight gradually decreases,which is beneficial to local searches.The performance of the ARIWPSO algorithm was investigated with some classical test functions,and the results were compared with those of the genetic algorithm(GA),the conventional PSO,and other improved PSO methods.Then,the ARIW-PSO algorithm was applied to multi-objective optimal dispatch of the Panjiakou Reservoir and multi-objective flood control operation of a reservoir group on the Luanhe River in China,including the Panjiakou Reservoir,Daheiting Reservoir,and Taolinkou Reservoir.The validity of the multi-objective optimization model for multi-reservoir systems based on the ARIW-PSO algorithm was verified.展开更多
目的探究闽产食用菌的氨基酸组成特征及其营养价值。方法采用氨基酸自动分析仪分析食用菌氨基酸含量,利用鸡蛋蛋白模式和联合国粮食及农业组织(Food and Agriculture Organization,FAO)/世界卫生组织(World Health Organization,WHO)推...目的探究闽产食用菌的氨基酸组成特征及其营养价值。方法采用氨基酸自动分析仪分析食用菌氨基酸含量,利用鸡蛋蛋白模式和联合国粮食及农业组织(Food and Agriculture Organization,FAO)/世界卫生组织(World Health Organization,WHO)推荐的理想蛋白模式系统评价各食用菌的氨基酸营养价值。结果食用菌至少包含18种氨基酸,包括8种成人必需氨基酸、2种儿童必需氨基酸。成人必需氨基酸、非必需氨基酸、酸味类氨基酸、甜味类氨基酸、苦味类氨基酸、儿童必需氨基酸、药用氨基酸、支链氨基酸、增香与着色氨基酸、伯胺基氨基酸含量等特殊功效氨基酸含量分别为3.19%-10.90%、4.51%-16.24%、1.73%-7.77%、2.09%-7.39%、3.03%-9.73%、0.55%-2.30%、4.84%-17.16%、1.30%-4.86%、2.90%-12.06%、3.94%-14.89%,品种间含量差异明显。必需氨基酸与氨基酸总量的百分比、必需氨基酸与非必需氨基酸含量的百分比、氨基酸比值系数分、必需氨基酸指数和营养指数依次为40.86%-48.72%、69.10%-95.00%、46.19-88.18、58.37-83.43、7.12-24.53,品种间营养价值差异明显。蛋氨酸+胱氨酸均相对过剩,缬草氨酸、异亮氨酸、亮氨酸、赖氨酸表现严重不足,而苯丙氨酸+酪氨酸、苏氨酸、色氨酸各品种表现不一。通过聚类分析,样品可分为3大类:高、中、低品质蛋白组。结论 18种食用菌氨基酸组成及营养价值存在一定的差异,具有不同的开发应用前景。展开更多
3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole(YC-1),the hypoxia-inducible factor-1 alpha(HIF-1α) inhibitor,suppresses tumor proliferation and metastasis by down-regulating HIF-1α expression under hypoxic c...3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole(YC-1),the hypoxia-inducible factor-1 alpha(HIF-1α) inhibitor,suppresses tumor proliferation and metastasis by down-regulating HIF-1α expression under hypoxic conditions.Our previous studies demonstrated that YC-1 inhibited breast cancer cell proliferation under normoxic conditions.In the current study,we investigated the targets of YC-1 and mechanism of its action in MDA-MB-468 breast cancer cells.In the in vitro experiments,we found that YC-1 significantly inhibited MDA-MB-468 cell proliferation in normoxia and hypoxia.Under normoxic conditions,YC-1 induced apoptosis of MDA-MB-468 cells and blocked cell cycle in the G1 phase,and these effects were possibly related to caspase 8,p21,and p27 expression.RT-PCR and Western blotting results showed that YC-1 primarily inhibited HIF-1α at the mRNA and protein levels under hypoxic conditions,but suppressed the expression of epidermal growth factor receptor(EGFR) at the mRNA and protein levels under normoxic conditions.In vivo,YC-1 prolonged survival,increased survival rate,decreased tumor size and metastasis rate,and inhibited tissue EGFR and HIF-1α expression.However,YC-1 exerted no obvious effect on body weight.These results indicate that YC-1 inhibits the proliferation of MDA-MB-468 cells by acting on multiple targets with minimal side effects.Thus,YC-1 is a promising target drug for breast cancer.展开更多
Background: The mitogen-activated extracellular signal-regulated kinase 1/2(MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer(CRC) is limited. Synt...Background: The mitogen-activated extracellular signal-regulated kinase 1/2(MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer(CRC) is limited. Synthetic lethality arises with a combination of two or more separate gene mutations that causes cell death, whereas individual mutations keep cells alive. This study aimed to identify the genes responsible for resistance to trametinib in CRC cells,using a synthetic lethal short hairpin RNA(shRNA) screening approach.Methods: We infected HT29 cells with a pooled lentiviral shRNA library and applied next-generation sequencing to identify shRNAs with reduced abundance after 8-day treatment of 20 nmol/L trametinib. HCT116 and HT29 cells were used in validation studies. Stable ring finger protein 183(RNF183)-overexpressing cell lines were generated by pcDNA4-myc/his-RNF183 transfection. Stable RNF 183-knockdown cell lines were generated by infection of lentiviruses that express RNF183 shRNA, and small interference RNA(siRNA) was used to knock down RNF183 transiently.Quantitative real-time PCR was used to determine the mRNA expression. Western blotting, immunohistochemical analysis, and enzyme-linked immunosorbent assay(ELISA) were used to evaluate the protein abundance. MTT assay,colony formation assay, and subcutaneous xenograft tumor growth model were used to evaluate cell proliferation.Results: In the primary screening, we found that the abundance of RNF183 shRNA was markedly reduced after treatment with trametinib. Trametinib induced the expression of RNF183, which conferred resistance to drug-induced cell growth repression and apoptotic and non-apoptotic cell deaths. Moreover, interleukin-8(IL-8) was a downstream gene of RNF183 and was required for the function of RNF183 in facilitating cell growth. Additionally, elevated RNF183 expression partly reduced the inhibitory effect of trametinib on IL-8 expression. Finally, xenograft tumor model showed the synergism of RNF183 knockdown and trametinib in repressing the growth of CRC cells in vivo.Conclusion: The RNF183-IL-8 axis is responsible for the resistance of CRC cells to the MEK1/2 inhibitor trametinib and may serve as a candidate target for combined therapy for CRC.展开更多
文摘Enabling as the second phase of the Production-Oriented Approach(POA)instruction(Wen,2015),plays a vital role in determining the quality of productive performance of English language learners.To explore how to apply theoretical principles of enabling to practice,this paper interprets theoretical principles and reports the practice of the classroom implementation of enabling.The paper proposes a definition for enabling,clarifies the confusion between enabling and scaffolding,and clears up some misunderstandings about enabling.It explains three criteria for effective enabling,namely,alignment,gradualness,and variety,and elaborates on the relations among them.Based on the teaching material of Unit 7 of iEnglish,the paper demonstrates how to design and implement enabling activities under the guidance of these three criteria and evaluates the actual effectiveness of the enabling implemented in the classroom.
基金supported by the National Nature Science Foundation of China(Grant Numbers 81072214,30371547)the National Key R&D Program of China(Grant Number 2016YFC1102603).
文摘We analyzed RNA-sequencing(RNA-seq)and clinical data from head and neck squamous cell carcinoma(HNSCC)patients in The Cancer Genome Atlas(TCGA)Genomic Data Commons(GDC)portal to investigate the prognostic value of anoikis-related genes(ARGs)in HNSCC and develop new targeted drugs.Differentially expressed ARGs were screened using bioinformatics methods;subsequently,a prognostic model including three ARGs(CDKN2A,BIRC5,and PLAU)was constructed.Our results showed that the model-based risk score was a good prognostic indicator,and the potential of the three ARGs in HNSCC prognosis was validated by the TISCH database,the model’s accuracy was validated in two independent cohorts of the Gene Expression Omnibus database.Immune correlation analysis and half-maximal inhibitory concentration were also performed to reveal the different landscapes of TIME between risk groups and to predict immuno-and chemo-therapeutic responses.Potential small-molecule drugs for HNSCC were subsequently predicted using the L1000FWD database.Finally,in vitro experiments were used to verify the database findings.The relative ARG mRNA expression levels in HNSCC and surrounding normal tissues remained consistent with the model results.BIRC5 knockdown inhibited anoikis resistance in WSU-HN6 and CAL-27 cells.Molecular docking,real-time PCR,cell counting kit-8(CCK-8),plate clone,and flow cytometry analyses showed that small-molecule drugs predicted by the database may target the ARGs in the prognostic model,inhibit HNSCC cells survival rate,and promote anoikis in vitro.Therefore,we constructed a new ARG model for HNSCC patients that can predict prognosis and immune activity and identify a potential small-molecule drug for HNSCC,paving the way for clinically targeting anoikis in HNSCC.
基金supported by the Foundation of the Scientific and Technological Innovation Team of Colleges and Universities in Henan Province(Grant No.181RTSTHN009)the Foundation of the Key Laboratory of Water Environment Simulation and Treatment in Henan Province(Grant No.2017016).
文摘Based on conventional particle swarm optimization(PSO),this paper presents an efficient and reliable heuristic approach using PSO with an adaptive random inertia weight(ARIW)strategy,referred to as the ARIW-PSO algorithm,to build a multi-objective optimization model for reservoir operation.Using the triangular probability density function,the inertia weight is randomly generated,and the probability density function is automatically adjusted to make the inertia weight generally greater in the initial stage of evolution,which is suitable for global searches.In the evolution process,the inertia weight gradually decreases,which is beneficial to local searches.The performance of the ARIWPSO algorithm was investigated with some classical test functions,and the results were compared with those of the genetic algorithm(GA),the conventional PSO,and other improved PSO methods.Then,the ARIW-PSO algorithm was applied to multi-objective optimal dispatch of the Panjiakou Reservoir and multi-objective flood control operation of a reservoir group on the Luanhe River in China,including the Panjiakou Reservoir,Daheiting Reservoir,and Taolinkou Reservoir.The validity of the multi-objective optimization model for multi-reservoir systems based on the ARIW-PSO algorithm was verified.
文摘目的探究闽产食用菌的氨基酸组成特征及其营养价值。方法采用氨基酸自动分析仪分析食用菌氨基酸含量,利用鸡蛋蛋白模式和联合国粮食及农业组织(Food and Agriculture Organization,FAO)/世界卫生组织(World Health Organization,WHO)推荐的理想蛋白模式系统评价各食用菌的氨基酸营养价值。结果食用菌至少包含18种氨基酸,包括8种成人必需氨基酸、2种儿童必需氨基酸。成人必需氨基酸、非必需氨基酸、酸味类氨基酸、甜味类氨基酸、苦味类氨基酸、儿童必需氨基酸、药用氨基酸、支链氨基酸、增香与着色氨基酸、伯胺基氨基酸含量等特殊功效氨基酸含量分别为3.19%-10.90%、4.51%-16.24%、1.73%-7.77%、2.09%-7.39%、3.03%-9.73%、0.55%-2.30%、4.84%-17.16%、1.30%-4.86%、2.90%-12.06%、3.94%-14.89%,品种间含量差异明显。必需氨基酸与氨基酸总量的百分比、必需氨基酸与非必需氨基酸含量的百分比、氨基酸比值系数分、必需氨基酸指数和营养指数依次为40.86%-48.72%、69.10%-95.00%、46.19-88.18、58.37-83.43、7.12-24.53,品种间营养价值差异明显。蛋氨酸+胱氨酸均相对过剩,缬草氨酸、异亮氨酸、亮氨酸、赖氨酸表现严重不足,而苯丙氨酸+酪氨酸、苏氨酸、色氨酸各品种表现不一。通过聚类分析,样品可分为3大类:高、中、低品质蛋白组。结论 18种食用菌氨基酸组成及营养价值存在一定的差异,具有不同的开发应用前景。
基金supported by a grant from Jilin Province Science and Technology Development Project(No.200905198)
文摘3-(5'-hydroxymethyl-2'-furyl)-1-benzyl indazole(YC-1),the hypoxia-inducible factor-1 alpha(HIF-1α) inhibitor,suppresses tumor proliferation and metastasis by down-regulating HIF-1α expression under hypoxic conditions.Our previous studies demonstrated that YC-1 inhibited breast cancer cell proliferation under normoxic conditions.In the current study,we investigated the targets of YC-1 and mechanism of its action in MDA-MB-468 breast cancer cells.In the in vitro experiments,we found that YC-1 significantly inhibited MDA-MB-468 cell proliferation in normoxia and hypoxia.Under normoxic conditions,YC-1 induced apoptosis of MDA-MB-468 cells and blocked cell cycle in the G1 phase,and these effects were possibly related to caspase 8,p21,and p27 expression.RT-PCR and Western blotting results showed that YC-1 primarily inhibited HIF-1α at the mRNA and protein levels under hypoxic conditions,but suppressed the expression of epidermal growth factor receptor(EGFR) at the mRNA and protein levels under normoxic conditions.In vivo,YC-1 prolonged survival,increased survival rate,decreased tumor size and metastasis rate,and inhibited tissue EGFR and HIF-1α expression.However,YC-1 exerted no obvious effect on body weight.These results indicate that YC-1 inhibits the proliferation of MDA-MB-468 cells by acting on multiple targets with minimal side effects.Thus,YC-1 is a promising target drug for breast cancer.
基金supported by the National Natural Science Foundation of China(Nos.81672744,81472252)Science and Technology Project of Guangdong Province(No.2016A020217007)Guangdong Esophageal Cancer Institute(No.M201606)
文摘Background: The mitogen-activated extracellular signal-regulated kinase 1/2(MEK1/2) inhibitor trametinib has shown promising therapeutic effects on melanoma, but its efficacy on colorectal cancer(CRC) is limited. Synthetic lethality arises with a combination of two or more separate gene mutations that causes cell death, whereas individual mutations keep cells alive. This study aimed to identify the genes responsible for resistance to trametinib in CRC cells,using a synthetic lethal short hairpin RNA(shRNA) screening approach.Methods: We infected HT29 cells with a pooled lentiviral shRNA library and applied next-generation sequencing to identify shRNAs with reduced abundance after 8-day treatment of 20 nmol/L trametinib. HCT116 and HT29 cells were used in validation studies. Stable ring finger protein 183(RNF183)-overexpressing cell lines were generated by pcDNA4-myc/his-RNF183 transfection. Stable RNF 183-knockdown cell lines were generated by infection of lentiviruses that express RNF183 shRNA, and small interference RNA(siRNA) was used to knock down RNF183 transiently.Quantitative real-time PCR was used to determine the mRNA expression. Western blotting, immunohistochemical analysis, and enzyme-linked immunosorbent assay(ELISA) were used to evaluate the protein abundance. MTT assay,colony formation assay, and subcutaneous xenograft tumor growth model were used to evaluate cell proliferation.Results: In the primary screening, we found that the abundance of RNF183 shRNA was markedly reduced after treatment with trametinib. Trametinib induced the expression of RNF183, which conferred resistance to drug-induced cell growth repression and apoptotic and non-apoptotic cell deaths. Moreover, interleukin-8(IL-8) was a downstream gene of RNF183 and was required for the function of RNF183 in facilitating cell growth. Additionally, elevated RNF183 expression partly reduced the inhibitory effect of trametinib on IL-8 expression. Finally, xenograft tumor model showed the synergism of RNF183 knockdown and trametinib in repressing the growth of CRC cells in vivo.Conclusion: The RNF183-IL-8 axis is responsible for the resistance of CRC cells to the MEK1/2 inhibitor trametinib and may serve as a candidate target for combined therapy for CRC.
