The authors first propose the GAFEE(Goal-Oriented Engagement,Autonomous Exploration,Feedback-Enhanced Explanation,Challenge-Driven Elaboration,Collaborative Evaluation,Iterative Design,and Technological Synergy)instru...The authors first propose the GAFEE(Goal-Oriented Engagement,Autonomous Exploration,Feedback-Enhanced Explanation,Challenge-Driven Elaboration,Collaborative Evaluation,Iterative Design,and Technological Synergy)instructional design model,which is based on the integration of gamified teaching and the 5E teaching model.It aims to address the issue of gamification not being systematically incorporated into the curriculum,while also enhancing engagement in the educational setting,stimulating interest in learning,and achieving better learning outcomes.The theoretical application of the GAFEE model is demonstrated through a hypothetical case involving a fourth-grade English class,highlighting its potential to improve students'vocabulary acquisition,grammar comprehension,and speaking proficiency.The study argues that the GAFEE model offers a novel approach to enhancing instructional practices by leveraging gamification strategies.It also emphasizes the need for empirical research to validate the model's effectiveness and broader applicability in gamified educational settings.展开更多
The identification of tumor-related microRNAs(miRNAs)exhibits excellent promise for the early diagnosis of cancer and other bioanalytical applications.Therefore,we developed a sensitive and efficient biosensor using p...The identification of tumor-related microRNAs(miRNAs)exhibits excellent promise for the early diagnosis of cancer and other bioanalytical applications.Therefore,we developed a sensitive and efficient biosensor using polyadenine(polyA)-mediated fluorescent spherical nucleic acid(FSNA)for miRNA analysis based on strand displacement reactions on gold nanoparticle(AuNP)surfaces and electrokinetic signal amplification(ESA)on a microfluidic chip.In this FSNA,polyA-DNA biosensor was anchored on AuNP surfaces via intrinsic affinity between adenine and Au.The upright conformational polyA-DNA recognition block hybridized with 6-carboxyfluorescein-labeled reporter-DNA,resulting in fluorescence quenching of FSNA probes induced by AuNP-based resonance energy transfer.Reporter DNA was replaced in the presence of target miRNA,leading to the recovery of reporter-DNA fluorescence.Subsequently,reporter-DNAs were accumulated and detected in the front of with Nafion membrane in the microchannel by ESA.Our method showed high selectivity and sensitivity with a limit of detection of 1.3 pM.This method could also be used to detect miRNA-21 in human serum and urine samples,with recoveries of 104.0%-113.3% and 104.9%-108.0%,respectively.Furthermore,we constructed a chip with three parallel channels for the simultaneous detection of multiple tumor-related miRNAs(miRNA-21,miRNA-141,and miRNA-375),which increased the detection efficiency.Our universal method can be applied to other DNA/RNA analyses by altering recognition sequences.展开更多
Standing-wave supermode microresonators that are created through the strong coupling between counter-propagating modes have emerged as versatile platforms for sensing and nonlinear optics.For example,these microresona...Standing-wave supermode microresonators that are created through the strong coupling between counter-propagating modes have emerged as versatile platforms for sensing and nonlinear optics.For example,these microresonators have shown potential in nanoparticle sizing and counting,as well as enhancing the single-photon optomechanical coupling rate of stimulated Brillouin scattering.However,it has been observed that the relation between the mode linewidth and on-resonance transmission of the split supermodes differs obviously from that of the non-split modes.This behavior is typically quantified by the coupling ideality(I),which remains inadequately explored for the standing-wave supermodes.In this study,we theoretically and experimentally investigate the coupling ideality of standing-wave supermodes in a commonly employed configuration involving a Si O2microresonator side-coupled to a tapered fiber.Our findings demonstrate that,even with a single-mode tapered fiber,the coupling ideality of the standing-wave supermodes is limited to 0.5,due to the strong backscattering-induced energy loss into the counter-propagating direction,resulting in an additional equivalent parasitic loss.While achieving a coupling ideality of 0.5 presents challenges for reaching over-coupled regimes,it offers a convenient approach for adjusting the total linewidth of the modes while maintaining critically-coupled conditions.展开更多
Water diversion is a common strategy to enhance water quality in eutrophic lakes by increasing available water resources and accelerating nutrient circulation.Its effectiveness depends on changes in the source water a...Water diversion is a common strategy to enhance water quality in eutrophic lakes by increasing available water resources and accelerating nutrient circulation.Its effectiveness depends on changes in the source water and lake conditions.However,the challenge of optimizing water diversion remains because it is difficult to simultaneously improve lake water quality and minimize the amount of diverted water.Here,we propose a new approach called dynamic water diversion optimization(DWDO),which combines a comprehensive water quality model with a deep reinforcement learning algorithm.We applied DWDO to a region of Lake Dianchi,the largest eutrophic freshwater lake in China and validated it.Our results demonstrate that DWDO significantly reduced total nitrogen and total phosphorus concentrations in the lake by 7%and 6%,respectively,compared to previous operations.Additionally,annual water diversion decreased by an impressive 75%.Through interpretable machine learning,we identified the impact of meteorological indicators and the water quality of both the source water and the lake on optimal water diversion.We found that a single input variable could either increase or decrease water diversion,depending on its specific value,while multiple factors collectively influenced real-time adjustment of water diversion.Moreover,using well-designed hyperparameters,DWDO proved robust under different uncertainties in model parameters.The training time of the model is theoretically shorter than traditional simulation-optimization algorithms,highlighting its potential to support more effective decisionmaking in water quality management.展开更多
Hypoxia-inducible factor(HIF)is a main heterodimeric transcription factor that regulates the cellular adaptive response to hypoxia by stimulating the transcription of a series of hypoxia-inducible genes.HIF is frequen...Hypoxia-inducible factor(HIF)is a main heterodimeric transcription factor that regulates the cellular adaptive response to hypoxia by stimulating the transcription of a series of hypoxia-inducible genes.HIF is frequently upregulated in solid tumors,and the overexpression of HIF can promote tumor progression or aggressiveness by blood vessel architecture and altering cellular metabolism.In this review,we focused on the pivotal role of HIF in tumor angiogenesis and energy metabolism.Furthermore,we also emphasized the possibility of HIF pathway as a potential therapeutic target in cancer.展开更多
Degradation prediction of proton exchange membrane fuel cell(PEMFC)stack is of great significance for improving the rest useful life.In this study,a PEMFC system including a stack of 300 cells and subsystems has been ...Degradation prediction of proton exchange membrane fuel cell(PEMFC)stack is of great significance for improving the rest useful life.In this study,a PEMFC system including a stack of 300 cells and subsystems has been tested under semi-steady operations for about 931 h.Then,two different models are respectively established based on semi-empirical method and data-driven method to investigate the degradation of stack performance.It is found that the root mean square error(RMSE)of the semi-empirical model in predicting the stack voltage is around 1.0 V,while the predicted voltage has no local dynamic characteristics,which can only reflect the overall degradation trend of stack performance.The RMSE of short-term voltage degradation predicted by the DDM can be less than 1.0 V,and the predicted voltage has accurate local variation characteristics.However,for the long-term prediction,the error will accumulate with the iterations and the deviation of the predicted voltage begins to fluctuate gradually,and the RMSE for the long-term predictions can increase to 1.63 V.Based on the above characteristics of the two models,a hybrid prediction model is further developed.The prediction results of the semi-empirical model are used to modify the input of the data-driven model,which can effectively improve the oscillation of prediction results of the data-driven model during the long-term degradation.It is found that the hybrid model has good error distribution(RSEM=0.8144 V,R2=0.8258)and local performance dynamic characteristics which can be used to predict the process of long-term stack performance degradation.展开更多
Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acti...Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.展开更多
The purpose of this study is to measure the expression of microRNA-4463 and microRNA-6087 between normal persons and patients with hepatocellular carcinoma(HCC),and to clarify the meaning of them in the prognosis eval...The purpose of this study is to measure the expression of microRNA-4463 and microRNA-6087 between normal persons and patients with hepatocellular carcinoma(HCC),and to clarify the meaning of them in the prognosis evaluation in HCC.Forty-five samples from healthy people and patients,who had been diagnosed with hepatocellular carcinoma before any treatment,were collected to study respectively.Real-time PCR was used to detect the expression of miRNA-4463 and miRNA-6087 in the serum of control group and hepatocellular carcinoma patients.The expression of miR-4463 in the serum of HCC patients was significantly higher than that in control group(P<0.05),and the expression level was independent of gender,tumor size,cell types,stages,alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)and HBsAg status(P>0.05).But there was a significant difference of different level of AFP in HCC(P<0.05),and the difference between the group of AFP lower than 400 ug/l and the control group is statistically significant(P<0.05).Besides,the survival time had showed a significant difference at the high and low expression levels(P<0.05).But the expression level of miRNA-6087 was no difference in HCC and control group.The disorder of miRNA-4463 occurred in HCC,even the AFP level doesn’t rises.What’s more,patients who get the high level of miRNA-4463 seem to have a shorter survival time.And it contributes great to the prognostic evaluation.This is the first study to illustrate the potential significance of miRNA-4463 in the prognosis in HCC.展开更多
It is necessary to evaluate the interactions between the different functional layers in optoelectronic devices to optimize device performance.Recently,the I-rich allinorganic perovskite CsPbI2 Br has attracted tremend...It is necessary to evaluate the interactions between the different functional layers in optoelectronic devices to optimize device performance.Recently,the I-rich allinorganic perovskite CsPbI2 Br has attracted tremendous attention for use in solar cell applications because of its suitable band gap and favorable photo and thermal stabilities.It has been reported that the undesirable phase degradation of the photoactiveαphase CsPbI2 Br to the non-perovskiteδphase could be triggered by high humidity.To obtain stable devices,it is thus important to protect CsPbI2 Br from moisture.In this paper,CuI,a non-hygroscopic p-type hole-transporting material,is found to induce the phase degradation ofα-CsPbI2 Br to theδ-CsPbI2 Br.The rate and extent of phase degradation of CsPbI2 Br are closely associated with the heating temperature and coverage of a Cu I granular capping layer.This discovery is different from the widely reported water-induced phase degradation of CsPbI2 Br.Our work highlights the importance of careful selection of hole-transporting materials during the processing of I-rich all-inorganic CsPbX3(X=Br,I)perovskites to realize high-performance optoelectronic devices.展开更多
文摘The authors first propose the GAFEE(Goal-Oriented Engagement,Autonomous Exploration,Feedback-Enhanced Explanation,Challenge-Driven Elaboration,Collaborative Evaluation,Iterative Design,and Technological Synergy)instructional design model,which is based on the integration of gamified teaching and the 5E teaching model.It aims to address the issue of gamification not being systematically incorporated into the curriculum,while also enhancing engagement in the educational setting,stimulating interest in learning,and achieving better learning outcomes.The theoretical application of the GAFEE model is demonstrated through a hypothetical case involving a fourth-grade English class,highlighting its potential to improve students'vocabulary acquisition,grammar comprehension,and speaking proficiency.The study argues that the GAFEE model offers a novel approach to enhancing instructional practices by leveraging gamification strategies.It also emphasizes the need for empirical research to validate the model's effectiveness and broader applicability in gamified educational settings.
基金supported financially by the National Natural Science Foundation of China(Grant No.:81973282)Guangdong Basic and Applied Basic Research Foundation(Grant Nos.:2018A030313843 and 2021A1515011493)+3 种基金National College Students Innovation and Entrepreneurship Training Program(Grant No.:202012121024)Science and Technology Innovation Strategic Special Project of Guangdong Province("Climbing Program"Special ProjectGrantNo.:pdjh2022b0106)Guangdong College Students Innovation and Entrepreneurship Training Program(Grant No.:S202112121154).
文摘The identification of tumor-related microRNAs(miRNAs)exhibits excellent promise for the early diagnosis of cancer and other bioanalytical applications.Therefore,we developed a sensitive and efficient biosensor using polyadenine(polyA)-mediated fluorescent spherical nucleic acid(FSNA)for miRNA analysis based on strand displacement reactions on gold nanoparticle(AuNP)surfaces and electrokinetic signal amplification(ESA)on a microfluidic chip.In this FSNA,polyA-DNA biosensor was anchored on AuNP surfaces via intrinsic affinity between adenine and Au.The upright conformational polyA-DNA recognition block hybridized with 6-carboxyfluorescein-labeled reporter-DNA,resulting in fluorescence quenching of FSNA probes induced by AuNP-based resonance energy transfer.Reporter DNA was replaced in the presence of target miRNA,leading to the recovery of reporter-DNA fluorescence.Subsequently,reporter-DNAs were accumulated and detected in the front of with Nafion membrane in the microchannel by ESA.Our method showed high selectivity and sensitivity with a limit of detection of 1.3 pM.This method could also be used to detect miRNA-21 in human serum and urine samples,with recoveries of 104.0%-113.3% and 104.9%-108.0%,respectively.Furthermore,we constructed a chip with three parallel channels for the simultaneous detection of multiple tumor-related miRNAs(miRNA-21,miRNA-141,and miRNA-375),which increased the detection efficiency.Our universal method can be applied to other DNA/RNA analyses by altering recognition sequences.
基金National Key Research and Development Program of China(2021YFA1400700)National Natural Science Foundation of China(62222515,12174438,11934019,91950118)+1 种基金Basic Frontier Science Research Program of Chinese Academy of Sciences(ZDBS-LYJSC003)CAS Project for Young Scientists in Basic Research(YSBR-100)。
文摘Standing-wave supermode microresonators that are created through the strong coupling between counter-propagating modes have emerged as versatile platforms for sensing and nonlinear optics.For example,these microresonators have shown potential in nanoparticle sizing and counting,as well as enhancing the single-photon optomechanical coupling rate of stimulated Brillouin scattering.However,it has been observed that the relation between the mode linewidth and on-resonance transmission of the split supermodes differs obviously from that of the non-split modes.This behavior is typically quantified by the coupling ideality(I),which remains inadequately explored for the standing-wave supermodes.In this study,we theoretically and experimentally investigate the coupling ideality of standing-wave supermodes in a commonly employed configuration involving a Si O2microresonator side-coupled to a tapered fiber.Our findings demonstrate that,even with a single-mode tapered fiber,the coupling ideality of the standing-wave supermodes is limited to 0.5,due to the strong backscattering-induced energy loss into the counter-propagating direction,resulting in an additional equivalent parasitic loss.While achieving a coupling ideality of 0.5 presents challenges for reaching over-coupled regimes,it offers a convenient approach for adjusting the total linewidth of the modes while maintaining critically-coupled conditions.
基金supported by the National Social Science Foundation of China(21AZD060),Chinathe National Natural Science Foundation of China(51721006),Chinathe High-Performance Computing Platform of Peking University,China.
文摘Water diversion is a common strategy to enhance water quality in eutrophic lakes by increasing available water resources and accelerating nutrient circulation.Its effectiveness depends on changes in the source water and lake conditions.However,the challenge of optimizing water diversion remains because it is difficult to simultaneously improve lake water quality and minimize the amount of diverted water.Here,we propose a new approach called dynamic water diversion optimization(DWDO),which combines a comprehensive water quality model with a deep reinforcement learning algorithm.We applied DWDO to a region of Lake Dianchi,the largest eutrophic freshwater lake in China and validated it.Our results demonstrate that DWDO significantly reduced total nitrogen and total phosphorus concentrations in the lake by 7%and 6%,respectively,compared to previous operations.Additionally,annual water diversion decreased by an impressive 75%.Through interpretable machine learning,we identified the impact of meteorological indicators and the water quality of both the source water and the lake on optimal water diversion.We found that a single input variable could either increase or decrease water diversion,depending on its specific value,while multiple factors collectively influenced real-time adjustment of water diversion.Moreover,using well-designed hyperparameters,DWDO proved robust under different uncertainties in model parameters.The training time of the model is theoretically shorter than traditional simulation-optimization algorithms,highlighting its potential to support more effective decisionmaking in water quality management.
基金Grant sponsor:National Nature Science Foundation of China,Grant number:81272960Key Research Program from Science and Technology Department of Hunan Province China,Grant number:2013WK2010 and 2014SK2015+3 种基金The fund of Tianqing liver disease researchThis work was supported by National Nature Science Foundation of China(81272960)Key Research Program from Science and Technology Department of Hunan Province,China(2013WK2010 and 2014SK2015)Key Research Program from Ministry of human Resources and Social Security of the People’s Republic of China(2016)176.
文摘Hypoxia-inducible factor(HIF)is a main heterodimeric transcription factor that regulates the cellular adaptive response to hypoxia by stimulating the transcription of a series of hypoxia-inducible genes.HIF is frequently upregulated in solid tumors,and the overexpression of HIF can promote tumor progression or aggressiveness by blood vessel architecture and altering cellular metabolism.In this review,we focused on the pivotal role of HIF in tumor angiogenesis and energy metabolism.Furthermore,we also emphasized the possibility of HIF pathway as a potential therapeutic target in cancer.
基金supported by the National Key Research and Development Program of China(Grant No.SQ2021YFE011145)the Science and Technology Development Program of Jilin Province(Grant No.20200501010GX).
文摘Degradation prediction of proton exchange membrane fuel cell(PEMFC)stack is of great significance for improving the rest useful life.In this study,a PEMFC system including a stack of 300 cells and subsystems has been tested under semi-steady operations for about 931 h.Then,two different models are respectively established based on semi-empirical method and data-driven method to investigate the degradation of stack performance.It is found that the root mean square error(RMSE)of the semi-empirical model in predicting the stack voltage is around 1.0 V,while the predicted voltage has no local dynamic characteristics,which can only reflect the overall degradation trend of stack performance.The RMSE of short-term voltage degradation predicted by the DDM can be less than 1.0 V,and the predicted voltage has accurate local variation characteristics.However,for the long-term prediction,the error will accumulate with the iterations and the deviation of the predicted voltage begins to fluctuate gradually,and the RMSE for the long-term predictions can increase to 1.63 V.Based on the above characteristics of the two models,a hybrid prediction model is further developed.The prediction results of the semi-empirical model are used to modify the input of the data-driven model,which can effectively improve the oscillation of prediction results of the data-driven model during the long-term degradation.It is found that the hybrid model has good error distribution(RSEM=0.8144 V,R2=0.8258)and local performance dynamic characteristics which can be used to predict the process of long-term stack performance degradation.
基金supported by the National Natural Science Foundations of China(No.81872335)the National Natural Science Youth Foundation(No.81902486)+2 种基金the Natural Science Foundation of Henan(No.161100510300)the Central Plains Science and Technology Innovation Leading Talents(No.224200510015)the Science and Technology Project of Henan Province(No.212102310187).
文摘Esophageal squamous cell carcinoma (ESCC) is one of the leading causes of cancer death worldwide. It is urgent to develop new drugs to improve the prognosis of ESCC patients. Here, we found benzydamine, a locally acting non-steroidal anti-inflammatory drug, had potent cytotoxic effect on ESCC cells. Benzydamine could suppress ESCC proliferation in vivo and in vitro. In terms of mechanism, CDK2 was identified as a target of benzydamine by molecular docking, pull-down assay and in vitro kinase assay. Specifically, benzydamine inhibited the growth of ESCC cells by inhibiting CDK2 activity and affecting downstream phosphorylation of MCM2, c-Myc and Rb, resulting in cell cycle arrest. Our study illustrates that benzydamine inhibits the growth of ESCC cells by downregulating the CDK2 pathway.
基金National Nature Science Foundation of China,Grant number:81272960Key Research Program from Science and Technology Department of Hunan Province China,Grant number:2013WK2010 and 2014SK2015+1 种基金Key Research Program from Ministry of human Resources and Social Security of the People’s Republic of China,Grant number:(2016)176The fund of Tianqing liver disease research,Grant number:(TQGB20140155).
文摘The purpose of this study is to measure the expression of microRNA-4463 and microRNA-6087 between normal persons and patients with hepatocellular carcinoma(HCC),and to clarify the meaning of them in the prognosis evaluation in HCC.Forty-five samples from healthy people and patients,who had been diagnosed with hepatocellular carcinoma before any treatment,were collected to study respectively.Real-time PCR was used to detect the expression of miRNA-4463 and miRNA-6087 in the serum of control group and hepatocellular carcinoma patients.The expression of miR-4463 in the serum of HCC patients was significantly higher than that in control group(P<0.05),and the expression level was independent of gender,tumor size,cell types,stages,alanine aminotransferase(ALT),aspartate aminotransferase(AST),total bilirubin(TBIL)and HBsAg status(P>0.05).But there was a significant difference of different level of AFP in HCC(P<0.05),and the difference between the group of AFP lower than 400 ug/l and the control group is statistically significant(P<0.05).Besides,the survival time had showed a significant difference at the high and low expression levels(P<0.05).But the expression level of miRNA-6087 was no difference in HCC and control group.The disorder of miRNA-4463 occurred in HCC,even the AFP level doesn’t rises.What’s more,patients who get the high level of miRNA-4463 seem to have a shorter survival time.And it contributes great to the prognostic evaluation.This is the first study to illustrate the potential significance of miRNA-4463 in the prognosis in HCC.
基金supported primarily by the National Key Research and Development Program of China(2018YFA0209303)the National Natural Science Foundation of China(U1663228,51902153,51972165 and 61377051)the Fundamental Research Funds for the Central Universities of China。
文摘It is necessary to evaluate the interactions between the different functional layers in optoelectronic devices to optimize device performance.Recently,the I-rich allinorganic perovskite CsPbI2 Br has attracted tremendous attention for use in solar cell applications because of its suitable band gap and favorable photo and thermal stabilities.It has been reported that the undesirable phase degradation of the photoactiveαphase CsPbI2 Br to the non-perovskiteδphase could be triggered by high humidity.To obtain stable devices,it is thus important to protect CsPbI2 Br from moisture.In this paper,CuI,a non-hygroscopic p-type hole-transporting material,is found to induce the phase degradation ofα-CsPbI2 Br to theδ-CsPbI2 Br.The rate and extent of phase degradation of CsPbI2 Br are closely associated with the heating temperature and coverage of a Cu I granular capping layer.This discovery is different from the widely reported water-induced phase degradation of CsPbI2 Br.Our work highlights the importance of careful selection of hole-transporting materials during the processing of I-rich all-inorganic CsPbX3(X=Br,I)perovskites to realize high-performance optoelectronic devices.