To the Editor:According to the latest statistics published by National Cancer Center of China,approximately 4,824,700 cancer cases were newly diagnosed and 2,574,200 patients died from cancer in China in 2022.[1]Uncon...To the Editor:According to the latest statistics published by National Cancer Center of China,approximately 4,824,700 cancer cases were newly diagnosed and 2,574,200 patients died from cancer in China in 2022.[1]Uncontrolled cell proliferation and physiological death resistance,which are the most representative cancer characteristics,complicate the process of restoring health and restrict treatment effectiveness in clinical practice.[2]Regulating multiple cell-death pathways to reprogram cancerous suicide has emerged as a promising approach to achieve valuable drugs discovery.Given the use of Leonurus japonicus as a historical folk medicine,relative hypotoxicity,and malignancy-inhibiting properties,it has shifted scientists’attention to mining its diverse active components and determining its pharmacological activities,thereby paving the way for its administration in clinical cancer treatment.展开更多
Conventional offshore wind integration systems use 33kV or 66kV AC cables to collect wind energy and employ high voltage direct current(HVDC)transmission technology to deliver wind power to onshore grids.This scheme s...Conventional offshore wind integration systems use 33kV or 66kV AC cables to collect wind energy and employ high voltage direct current(HVDC)transmission technology to deliver wind power to onshore grids.This scheme suffers from high costs for collection systems and offshore platforms when the capacity of offshore wind farms increases.This paper proposes a hybrid AC/DC collection and HVDC transmission concept for the large-scale offshore wind integration system.Wind farms near the offshore converter platform are integrated using AC collection cables,while the remaining wind farms are integrated using DC collection cables.The AC and DC collection cables infeed to the offshore converter platform,which features a three-terminal hybrid AC/DC/DC hub.The system layout and operating principle of the hybrid AC/DC collection and HVDC transmission system are introduced in detail.The control strategy and parameter design of the hybrid AC/DC/DC hub are presented.An economic evaluation comparing conventional AC collection and HVDC transmission schemes is conducted.It is indicated that the proposed integration concept can reduce the operating power capacity and power loss of the offshore converter,enhancing the economic efficiency of the overall integration system.Finally,the effectiveness of the proposed integration technology is validated in a 2000MW offshore wind power integration system by PSCAD/EMTDC simulation analysis.展开更多
Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%,mainly including lung adenocarcinoma(LUAD).Tumor microenvironment(TME)has become a new research focus in t...Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%,mainly including lung adenocarcinoma(LUAD).Tumor microenvironment(TME)has become a new research focus in the treatment of lung cancer.The TME is heterogeneous in composition and consists of cellular components,growth factors,proteases,and extracellular matrix.The various cellular components exert a different role in apoptosis,metastasis,or proliferation of lung cancer cells through different pathways,thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods.This review summarizes the research progress on different cellular components with cell–cell interactions in the TME of LUAD,along with their corresponding drug candidates,suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.展开更多
Mitochondria energize the inner ear to maintain the cochlear potential createdbythe striavascularis,assist the motility of outer hair cells,perform synaptic processes,and maintain the spontaneous and sound-driven disc...Mitochondria energize the inner ear to maintain the cochlear potential createdbythe striavascularis,assist the motility of outer hair cells,perform synaptic processes,and maintain the spontaneous and sound-driven discharges of the spiral ganglion neurons(SGNs).Mitophagy deficiencies induce the accumulation of damaged organelles and mitochondria in cells and are a primary cause of drug-induced hearing loss.展开更多
Aim:Glioma accounts for 81%of all cancers of the nervous system cancers and presents one of the most drug-resistant malignancies,resulting in a relatively high mortality rate.Despite extensive efforts,the complete tre...Aim:Glioma accounts for 81%of all cancers of the nervous system cancers and presents one of the most drug-resistant malignancies,resulting in a relatively high mortality rate.Despite extensive efforts,the complete treatment options for glioma remain elusive.The effect of isocucurbitacin B(isocuB),a natural compound extracted from melon pedicels,on glioma has not been investigated.This study aims to investigate the inhibitory effect of isocuB on glioma and elucidate its underlying mechanisms,with the objective of developing it as a potential therapeutic agent for glioma.Methods:We used network pharmacology and bioinformatics analysis to predict potential targets and associated pathways of isocuB in glioma.Subsequently,the inhibitory effect of isocuB on glioma and its related mechanisms were assessed through Counting Kit-8(CCK-8),wound healing,transwell,Western blot(WB),reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and other in vitro experiments,alongside tumor formation experiments in nude mice.Results:Based on this investigation,it suggested that isocuB might inhibit the growth of gliomas through the PI3K-AKT and MAPK pathways.Additionally,we proposed that isocuB may enhance glioma drug sensitivity to temozolomide(TMZ)via modulation of hsa-mir-1286a.The CCK-8 assay revealed that isocuB exhibited inhibitory effects on U251 and U87 proliferation and outperformed TMZ.Wound healing and transwell experiments showed that isocuB inhibited the invasion and migration of U251 cells by suppressing the activity of MMP-2/9,N-cadherin,and Vimentin.The TdT-mediated dUTP-biotin nick end labeling(TUNEL)and flow cytometry(FCM)assays revealed that isocuB induced cell apoptosis through inhibition of BCL-2.Subsequently,we conducted RT-qPCR and WB experiments,which revealedthat PI3K/AKT and MAPK pathways might be involved in the mechanism of the inhibition isocuB on glioma.Additionally,isocuB promoted the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a.Furthermore,weconstructed TMZ-resistant U251 strains and demonstrated effective inhibition by isocuB against these resistantstrains.Finally,we confirmed that isocuB can inhibit tumor growth in vivo through experiments on tumors in nudemice.Conclusion:IsocuB may protect against glioma by acting on the PI3K/AKT and MAPK pathways and promote the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a.展开更多
Brassinosteroid is an important hormone that interacts with auxin and gibberellin to regulate plant growth and development. However,there is currently a relative lack of information regarding brassinosteroid in apple....Brassinosteroid is an important hormone that interacts with auxin and gibberellin to regulate plant growth and development. However,there is currently a relative lack of information regarding brassinosteroid in apple. Previous study confirmed that exogenous brassinosteroid treatments increased growth and endogenous brassinosteroid, auxin, as well as gibberellin levels of apple nursery trees. Here we succeeded to find that exogenous brassinosteroid treatments upregulated the transcript expression of auxin biosynthesis, transport, and positive signal transduction genes as well as gibberellin biosynthesis genes. In contrast, the application of exogenous brassinosteroid downregulated the expression of genes encoding negative regulators of auxin and gibberellin signal transductions. Rapid responses of several brassinosteroid-,auxin-, and gibberellin-related genes to the brassinosteroid and brassinazole treatments inferred the crosstalk of BR and IAA or GA. Furthermore,the expression levels of cell growth-related genes were also enhanced by exogenous brassinosteroid. Auxin and gibberellin treatments also influenced growth of apple tree and enhanced the expression of brassinosteroid-and cell growth-related genes. These results indicate that the growth of apple tree is regulated by the interaction between brassinosteroid, auxin, and gibberellin. Our work opened new avenues for deep portfolio of apple tree growth and laid the foundation for future studies aimed at elucidating the mechanisms regulating hormone interactionsmediated growth in apple trees.展开更多
文摘To the Editor:According to the latest statistics published by National Cancer Center of China,approximately 4,824,700 cancer cases were newly diagnosed and 2,574,200 patients died from cancer in China in 2022.[1]Uncontrolled cell proliferation and physiological death resistance,which are the most representative cancer characteristics,complicate the process of restoring health and restrict treatment effectiveness in clinical practice.[2]Regulating multiple cell-death pathways to reprogram cancerous suicide has emerged as a promising approach to achieve valuable drugs discovery.Given the use of Leonurus japonicus as a historical folk medicine,relative hypotoxicity,and malignancy-inhibiting properties,it has shifted scientists’attention to mining its diverse active components and determining its pharmacological activities,thereby paving the way for its administration in clinical cancer treatment.
基金supported by the National Key Research and Development Program of China(2022YFB2405400)in part by the National Natural Science Foundation of China(52237004).
文摘Conventional offshore wind integration systems use 33kV or 66kV AC cables to collect wind energy and employ high voltage direct current(HVDC)transmission technology to deliver wind power to onshore grids.This scheme suffers from high costs for collection systems and offshore platforms when the capacity of offshore wind farms increases.This paper proposes a hybrid AC/DC collection and HVDC transmission concept for the large-scale offshore wind integration system.Wind farms near the offshore converter platform are integrated using AC collection cables,while the remaining wind farms are integrated using DC collection cables.The AC and DC collection cables infeed to the offshore converter platform,which features a three-terminal hybrid AC/DC/DC hub.The system layout and operating principle of the hybrid AC/DC collection and HVDC transmission system are introduced in detail.The control strategy and parameter design of the hybrid AC/DC/DC hub are presented.An economic evaluation comparing conventional AC collection and HVDC transmission schemes is conducted.It is indicated that the proposed integration concept can reduce the operating power capacity and power loss of the offshore converter,enhancing the economic efficiency of the overall integration system.Finally,the effectiveness of the proposed integration technology is validated in a 2000MW offshore wind power integration system by PSCAD/EMTDC simulation analysis.
基金supported by National Natural Science Foundation of China(Nos.82003879 and U19A2010)National Natural Science Foundation of Science and Technology Department of Sichuan Province(Nos.2023NSFSC1928 and 2023NSFSC1992)+2 种基金Young Elite Scientists Sponsorship Program by China Association for Science and Technology(No.CACM-2020-QNRC1-01)Project of State Administration of Traditional Chinese Medicine of China(No.ZYYCXTD-D-202209),Project of Sichuan Provincial Administration of Traditional Chinese Medicine(No.2022C001)the Open Research Fund of State Key Laboratory of Southwestern Chinese Medicine Resources(No.SKLTCM202205).
文摘Lung cancer is one of the most lethal tumors in the world with a 5-year overall survival rate of less than 20%,mainly including lung adenocarcinoma(LUAD).Tumor microenvironment(TME)has become a new research focus in the treatment of lung cancer.The TME is heterogeneous in composition and consists of cellular components,growth factors,proteases,and extracellular matrix.The various cellular components exert a different role in apoptosis,metastasis,or proliferation of lung cancer cells through different pathways,thus contributing to the treatment of adenocarcinoma and potentially facilitating novel therapeutic methods.This review summarizes the research progress on different cellular components with cell–cell interactions in the TME of LUAD,along with their corresponding drug candidates,suggesting that targeting cellular components in the TME of LUAD holds great promise for future theraputic development.
基金supported by grants from the National Natural Science Foundation of China(No.82171158,82271177,82271185,82171155)the National Key Research and Development,Project of China(No.2020YFC2008500).
文摘Mitochondria energize the inner ear to maintain the cochlear potential createdbythe striavascularis,assist the motility of outer hair cells,perform synaptic processes,and maintain the spontaneous and sound-driven discharges of the spiral ganglion neurons(SGNs).Mitophagy deficiencies induce the accumulation of damaged organelles and mitochondria in cells and are a primary cause of drug-induced hearing loss.
基金supported by National Natural Science Foundation of China(No.82003879)Project of Science and Technology Department of Sichuan Province(No.2023NSFSC1928+2 种基金2023NSFSC1992)Young Elite Scientists Sponsorship Program by China Association for Science and Technology(No.CACM-2020-QNRC1-01)the Fundamental Research Funds for the central Universities.
文摘Aim:Glioma accounts for 81%of all cancers of the nervous system cancers and presents one of the most drug-resistant malignancies,resulting in a relatively high mortality rate.Despite extensive efforts,the complete treatment options for glioma remain elusive.The effect of isocucurbitacin B(isocuB),a natural compound extracted from melon pedicels,on glioma has not been investigated.This study aims to investigate the inhibitory effect of isocuB on glioma and elucidate its underlying mechanisms,with the objective of developing it as a potential therapeutic agent for glioma.Methods:We used network pharmacology and bioinformatics analysis to predict potential targets and associated pathways of isocuB in glioma.Subsequently,the inhibitory effect of isocuB on glioma and its related mechanisms were assessed through Counting Kit-8(CCK-8),wound healing,transwell,Western blot(WB),reverse transcription-quantitative polymerase chain reaction(RT-qPCR),and other in vitro experiments,alongside tumor formation experiments in nude mice.Results:Based on this investigation,it suggested that isocuB might inhibit the growth of gliomas through the PI3K-AKT and MAPK pathways.Additionally,we proposed that isocuB may enhance glioma drug sensitivity to temozolomide(TMZ)via modulation of hsa-mir-1286a.The CCK-8 assay revealed that isocuB exhibited inhibitory effects on U251 and U87 proliferation and outperformed TMZ.Wound healing and transwell experiments showed that isocuB inhibited the invasion and migration of U251 cells by suppressing the activity of MMP-2/9,N-cadherin,and Vimentin.The TdT-mediated dUTP-biotin nick end labeling(TUNEL)and flow cytometry(FCM)assays revealed that isocuB induced cell apoptosis through inhibition of BCL-2.Subsequently,we conducted RT-qPCR and WB experiments,which revealedthat PI3K/AKT and MAPK pathways might be involved in the mechanism of the inhibition isocuB on glioma.Additionally,isocuB promoted the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a.Furthermore,weconstructed TMZ-resistant U251 strains and demonstrated effective inhibition by isocuB against these resistantstrains.Finally,we confirmed that isocuB can inhibit tumor growth in vivo through experiments on tumors in nudemice.Conclusion:IsocuB may protect against glioma by acting on the PI3K/AKT and MAPK pathways and promote the sensitivity of glioma U251 to TMZ by inhibiting hsa-mir-1286a.
基金sponsored by the Chinese Postdoctoral Science Foundation (2015K3080215822)the Ecological Adaptability Selection of Apple Superior Stock and Scion Combinations in the Loess Plateau (A2990215082)+5 种基金the Screening and Interaction Molecular Mechanism of Apple Stock and Scion Combinations (K3380217027)the National Apple Industry Technology System of the Agriculture Ministry of China (CARS-27)the National Spark Plan Program (2014GA850002)the Science and Technology Innovative Engineering Project in Shaanxi Province of China (2015NY114)the Innovation Project of Science and Technology of Shaanxi Province (2016TZC-N-11-6)the Key Research Project of Shaanxi Province (2017ZDXM-NY-019)
文摘Brassinosteroid is an important hormone that interacts with auxin and gibberellin to regulate plant growth and development. However,there is currently a relative lack of information regarding brassinosteroid in apple. Previous study confirmed that exogenous brassinosteroid treatments increased growth and endogenous brassinosteroid, auxin, as well as gibberellin levels of apple nursery trees. Here we succeeded to find that exogenous brassinosteroid treatments upregulated the transcript expression of auxin biosynthesis, transport, and positive signal transduction genes as well as gibberellin biosynthesis genes. In contrast, the application of exogenous brassinosteroid downregulated the expression of genes encoding negative regulators of auxin and gibberellin signal transductions. Rapid responses of several brassinosteroid-,auxin-, and gibberellin-related genes to the brassinosteroid and brassinazole treatments inferred the crosstalk of BR and IAA or GA. Furthermore,the expression levels of cell growth-related genes were also enhanced by exogenous brassinosteroid. Auxin and gibberellin treatments also influenced growth of apple tree and enhanced the expression of brassinosteroid-and cell growth-related genes. These results indicate that the growth of apple tree is regulated by the interaction between brassinosteroid, auxin, and gibberellin. Our work opened new avenues for deep portfolio of apple tree growth and laid the foundation for future studies aimed at elucidating the mechanisms regulating hormone interactionsmediated growth in apple trees.
