The NASICON-structured Na_(2)VTi(PO_(4))_(3)(NVTPO)has attracted significant attention due to its exceptional structural stability and rapid Na~+mobility.However,the development of this material has been hindered by p...The NASICON-structured Na_(2)VTi(PO_(4))_(3)(NVTPO)has attracted significant attention due to its exceptional structural stability and rapid Na~+mobility.However,the development of this material has been hindered by poor electronic conductivity and inadequate low-temperature performance.Herein,a feasible strategy of lattice regulation integrated with surface modification for NVTPO by nitrogen(N)deep doping is proposed.Systematic characterizations and theoretical calculations confirm that N is doped into both the inner crystal structure of NVTPO and the outer carbon layer.The blueshift of the P—O bonds and charge redistribution induced by the V/Ti—N bonds strengthen the local environment and narrow the bandgap,thereby enabling reversible structural evolution and improving electronic conductivity.As expected,the optimized NVTPO/N@CN material achieves an ultra-high capacity of 188.48 mA h g^(-1)at 10 mA g^(-1)and a long-term lifespan of 2000 cycles at 1 A g^(-1).More importantly,it exhibits competitive low-temperature performance(92.15%retention after 1000 cycles at 300 mA g^(-1)and-15℃)due to reduced charge transfer impedance and activation energy.This deep doping strategy modification is expected to broaden the applications of NASICON-type cathodes.展开更多
The depolymerization and upgrading of lignin from raw biomass,while keeping cellulose intact is important in biorefinery and various metal-based catalysts have been used in reductive catalytic fractionation,a key meth...The depolymerization and upgrading of lignin from raw biomass,while keeping cellulose intact is important in biorefinery and various metal-based catalysts have been used in reductive catalytic fractionation,a key method in"lignin-first"strategy,Recently,we found that a core-shell structured Co@CoO catalyst with CoO shell as the real active site had excellent performance in the hydrogenolysis of 5-hydromethylfurfural to 2,5-dimethylfuran due to its unique ability to dissociate H_(2)and yield active H^(δ-)species(Xiang et al.,2022).In this work,we report a one-pot depolymerization and upgrading of lignocellulose to alkylcyclohexanols,a flavour precursor,with intact cellulose over this unique core-shell structured catalyst,Co@CoO.Lignin model compounds(β-O-4,4-O-5,α-O-4)were first used to clarify the activity of Co@CoO catalyst.Then,the one-pot conversion of various organosolv lignin(birch,pine and poplar)to alkylcyclohexanols was realized with the mass yield of alkylcyclohexanols up to25.8 wt%from birch lignin under the reaction condition of 210℃,1 MPa H_(2),16 h.Finally,the corresponding woody sawdusts were used as feedstocks and found that the Co@CoO catalyst indeed preferentially depolymerized and upgraded the lignin part and obtained the same alkylcyclohexanols products with the retention of cellulose-rich pulp.The collected alkylcyclohexanols were further esterified to obtain valueadded esters,which can be used as flavors.This work will inspire the design of new efficient metal oxide catalysts in lignin fractionation and depolymerization to high-value-added chemicals with intact cellulose.展开更多
The mangrove Kandelia obovata(Rhizophoraceae)is an important coastal shelterbelt and landscape tree distributed in tropical and subtropical areas across East Asia and Southeast Asia.Herein,a chromosome-level reference...The mangrove Kandelia obovata(Rhizophoraceae)is an important coastal shelterbelt and landscape tree distributed in tropical and subtropical areas across East Asia and Southeast Asia.Herein,a chromosome-level reference genome of K.obovata based on PacBio,Illumina,and Hi-C data is reported.The high-quality assembled genome size is 177.99 Mb,with a contig N50 value of 5.74 Mb.A large number of contracted gene families and a small number of expanded gene families,as well as a small number of repeated sequences,may account for the small K.obovata genome.We found that K.obovata experienced two whole-genome polyploidization events:one whole-genome duplication shared with other Rhizophoreae and one shared with most eudicots(γevent).We confidently annotated 19,138 protein-coding genes in K.obovata and identified the MADS-box gene class and the RPW8 gene class,which might be related to flowering and resistance to powdery mildew in K.obovata and Rhizophora apiculata,respectively.The reference K.obovata genome described here will be very useful for further molecular elucidation of various traits,the breeding of this coastal shelterbelt species,and evolutionary studies with related taxa.展开更多
Magnoliids represent the third largest branch of the most diverse and species-rich angiosperms,and their phylogenetic position relative to monocots and eudicots remains uncertain(Dong et al.,2021).Here,we describe the...Magnoliids represent the third largest branch of the most diverse and species-rich angiosperms,and their phylogenetic position relative to monocots and eudicots remains uncertain(Dong et al.,2021).Here,we describe the assembly of a high-quality chromosome-level genome sequence for Cinnamomum camphora(camphor),an evergreen tree belonging to Lauraceae.Genomebased phylogenetic analysis indicated possible incomplete lineage sorting(ILS)during the rapid diversification of the early diverging branches of angiosperms,which may have led to the unstable phylogenetic position of magnoliids.展开更多
Objective:Tumor-derived exosomes(TDEs)play crucial roles in intercellular communication.Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis.Jiedu recipe(JR),a traditional ...Objective:Tumor-derived exosomes(TDEs)play crucial roles in intercellular communication.Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis.Jiedu recipe(JR),a traditional Chinese medicinal formula,has demonstrated efficacy in preventing the metastasis of hepatocellular carcinoma(HCC).However,the underlying mechanism remains largely unknown.Methods:Animal experiments were performed to investigate the metastasis-preventing effects of JR.Bioinformatics analysis and in vitro assays were conducted to explore the potential targets and active components of JR.TDEs were assessed using nanoparticle tracking analysis(NTA)and Western blotting(WB).Exosomes derived from normoxic or hypoxic HCC cells(H-TDEs)were collected to establish premetastatic mouse models.JR was intragastrically administered to evaluate its metastasis-preventive effects.WB and lysosomal staining were performed to investigate the effects of JR on lysosomal function and autophagy.Bioinformatics analysis,WB,NTA,and immunofluorescence staining were used to identify the active components and potential targets of JR.Results:JR effectively inhibited subcutaneous-tumor-promoted lung premetastatic niche development and tumor metastasis.It inhibited the release of exosomes from tumor cells under hypoxic condition.JR treatment promoted both lysosomal acidification and suppressed secretory autophagy,which were dysregulated in hypoxic tumor cells.Quercetin was identified as the active component in JR,and the epidermal growth factor receptor(EGFR)was identified as a potential target.Quercetin inhibited EGFR phosphorylation and promoted the nuclear translocation of transcription factor EB(TFEB).Hypoxia-impaired lysosomal function was restored,and secretory autophagy was alleviated by quercetin treatment.Conclusion:JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release,restoring lysosomal function,and suppressing secretory autophagy.Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling.Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion.展开更多
There is an urgent need to develop innovative electrochemical energy storage devices that can offer high energy density,long lifespan,excellent rate capability,and improved security.For the electrochemical system,the ...There is an urgent need to develop innovative electrochemical energy storage devices that can offer high energy density,long lifespan,excellent rate capability,and improved security.For the electrochemical system,the electrode interphase,namely the cathode electrolyte interphase(CEI)and solid electrolyte interphase(SEI)play crucial roles in the operating mechanism,kinetics,and overall performance of the battery.However,the in-depth investigation of the unstable and complex electrode interphase is limited by the unavoidable air and moisture contact during the material transfer process and probable high-energy radiation damage in the characterization procedure.Recently,cryogenic techniques and in situ techniques have been developed and applied in the electrode interphase research to settle the radiation damage and air erosion,respectively.However,there has not been a special review that summarizes the relevant methods,so a systematic review is very important to accelerate the development.In this review,we summarize these two state-of-the-art methods,including their working principle,characterization process,advantages,and applications in electrode interphase analysis.And the integrative techniques,which are considered as the future development perspectives,are also discussed.This review can provide important directions for next-generation characterization techniques and strategies to effectively analyze the electrode interphase for advanced batteries.展开更多
Objective:Angiogenesis is a critical target for hepatocellular carcinoma(HCC)treatment The previous studies indicated that Jiedu Fang(JDF)could inhibit hypoxia-induced angiogenesis through interleukin-8(IL-8).Therefor...Objective:Angiogenesis is a critical target for hepatocellular carcinoma(HCC)treatment The previous studies indicated that Jiedu Fang(JDF)could inhibit hypoxia-induced angiogenesis through interleukin-8(IL-8).Therefore,the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis.Methods:Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo.A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform.Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels,respectively.The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells.The orthotopic tumor xenograft model was established,and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression,while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels.Results:In vitro and in vivo assays showed that IL-8 promoted angiogenesis,and JDF could antagonize this effect.Bioinformatics analysis indicated that aurora kinase A(Aurora A)was an important candidate,which can promote IL-8 expression through activation of signal transducer and activator of transcription3(STAT3).The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration,invasion,and angiogenesis,which was partly inhibited by JDF.Such effects were validated by in vivo assays.Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A.Conclusion:JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway.Therefore,JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis.展开更多
Neurotrophic receptor kinase(NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors,and tropomyosin receptor kinase(TRK) has been considered as an attractive therapeutic target for...Neurotrophic receptor kinase(NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors,and tropomyosin receptor kinase(TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these fusions.Currently,two generations TRK inhibitors have been developed.The representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target mutations.However,xDFG(TRKAG667C/A/S,homologous TRKCG696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib,and overcoming these resistances represents a major unmet clinical need.In this review,we summarize the acquired resistance mechanism of the first-and second-generation TRK inhibitors,and firstly put forward the emerging selective type Ⅱ TRK inhibitors to overcome xDFG mutations mediated resistance.Additionally,we concluded our perspectives on new challenges and future directions in this field.展开更多
Infrastructure as a Service(laaS)has brought advantages to users because virtualization technology hides the details of the physical resources,but this leads to the problem of users being unable to perceive their secu...Infrastructure as a Service(laaS)has brought advantages to users because virtualization technology hides the details of the physical resources,but this leads to the problem of users being unable to perceive their security.This defect has obstructed cloud computing from wide-spread popularity and development.To solve this problem,a dynamic measurement protocol in laaS is presented in this paper.The protocol makes it possible for the user to get the real-time security status of the resources,thereby solving the problem of guaranteeing dynamic credibility.This changes the cloud service security provider from the operator to the users themselves.This study has verified the security of the protocol by means of Burrow-Abadi-Needham(BAN)logic,and the result shows that it can satisfy requirements for innovation,privacy,and integrity.Finally,based on different laaS platforms,this study has conducted a performance analysis to demonstrate that this protocol is reliable,secure,and efficient.展开更多
Phosphorus plays a vital role in the growth and development of rice in the cold northern regions,affecting the yield and quality of rice.The phosphorus content of leaves can indicate the nutritional status of rice.Rap...Phosphorus plays a vital role in the growth and development of rice in the cold northern regions,affecting the yield and quality of rice.The phosphorus content of leaves can indicate the nutritional status of rice.Rapid and accurate acquisition of the phosphorus content in leaves is the basis for ensuring healthy rice growth and maintaining stable and high rice yield.Hyperspectral technology can reflect the shape of rice leaves and then evaluate the phosphorus content in the leaves,so hyperspectral technology has the potential to estimate the phosphorus content in plant leaves quickly and accurately.The hyperspectral data of the rice leaves were pretreated using the SG smoothing method.The spectral characteristics of pretreated spectral data were extracted using principal component analysis(PCA)and linear discriminant analysis(LDA).Extreme learning machine(ELM)and Bat algorithm optimized extreme learning machine(BA-ELM)were constructed to retrieve the phosphorus content in rice leaves.The results show that there are seven feature vectors produced by the two methods,and the feature vectors selected by the two methods are used as inputs,respectively.The verification sets R2 and RMSE of the two models constructed using the feature reflectivity chosen by the LDA algorithm as input were between 0.603 and 0.604,and 0.025 and 0.032,respectively.Under the condition of the same inversion model,the model constructed by using the reflectivity of the features selected by the PCA algorithm as input has a better prediction effect,and the verification set R2 of the two models was between 0.685-0.765,and RMSE was between 0.022-0.038.In addition,when using the features selected by these two algorithms to model,comparing the prediction results of the two models,it was found that the accuracy of the BA-ELM was higher than that of ELM.Its determination coefficient R2 and RMSE of the verification set were 0.765 and 0.022,respectively.Because of this,the ELM optimized by principal component analysis and BA has certain advantages in the hyperspectral inversion of phosphorus content in rice leaves in cold regions,and can provide some reference for rapid and accurate detection of phosphorus content in rice leaves.展开更多
基金supported by the National Natural Science Foundation of China(22272205 and 22178094)the Hunan Provincial Nature Science Foundation of China(2022JJ30685,2023JJ20059 and 2024JJ5292)+2 种基金the Hunan Provincial Science and Technology Plan Projects of China(2022RC3050 and 2017TP1001)the financial support from the Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Provincesupport from the Young Elite Scientists Sponsorship Program by CAST(YESS20220432)。
文摘The NASICON-structured Na_(2)VTi(PO_(4))_(3)(NVTPO)has attracted significant attention due to its exceptional structural stability and rapid Na~+mobility.However,the development of this material has been hindered by poor electronic conductivity and inadequate low-temperature performance.Herein,a feasible strategy of lattice regulation integrated with surface modification for NVTPO by nitrogen(N)deep doping is proposed.Systematic characterizations and theoretical calculations confirm that N is doped into both the inner crystal structure of NVTPO and the outer carbon layer.The blueshift of the P—O bonds and charge redistribution induced by the V/Ti—N bonds strengthen the local environment and narrow the bandgap,thereby enabling reversible structural evolution and improving electronic conductivity.As expected,the optimized NVTPO/N@CN material achieves an ultra-high capacity of 188.48 mA h g^(-1)at 10 mA g^(-1)and a long-term lifespan of 2000 cycles at 1 A g^(-1).More importantly,it exhibits competitive low-temperature performance(92.15%retention after 1000 cycles at 300 mA g^(-1)and-15℃)due to reduced charge transfer impedance and activation energy.This deep doping strategy modification is expected to broaden the applications of NASICON-type cathodes.
基金supported financially by the National Natural Science Foundation of China(Nos.21832002,21808063,22002043,21872050)。
文摘The depolymerization and upgrading of lignin from raw biomass,while keeping cellulose intact is important in biorefinery and various metal-based catalysts have been used in reductive catalytic fractionation,a key method in"lignin-first"strategy,Recently,we found that a core-shell structured Co@CoO catalyst with CoO shell as the real active site had excellent performance in the hydrogenolysis of 5-hydromethylfurfural to 2,5-dimethylfuran due to its unique ability to dissociate H_(2)and yield active H^(δ-)species(Xiang et al.,2022).In this work,we report a one-pot depolymerization and upgrading of lignocellulose to alkylcyclohexanols,a flavour precursor,with intact cellulose over this unique core-shell structured catalyst,Co@CoO.Lignin model compounds(β-O-4,4-O-5,α-O-4)were first used to clarify the activity of Co@CoO catalyst.Then,the one-pot conversion of various organosolv lignin(birch,pine and poplar)to alkylcyclohexanols was realized with the mass yield of alkylcyclohexanols up to25.8 wt%from birch lignin under the reaction condition of 210℃,1 MPa H_(2),16 h.Finally,the corresponding woody sawdusts were used as feedstocks and found that the Co@CoO catalyst indeed preferentially depolymerized and upgraded the lignin part and obtained the same alkylcyclohexanols products with the retention of cellulose-rich pulp.The collected alkylcyclohexanols were further esterified to obtain valueadded esters,which can be used as flavors.This work will inspire the design of new efficient metal oxide catalysts in lignin fractionation and depolymerization to high-value-added chemicals with intact cellulose.
基金funded by the National Science Foundation of China(41801062)the Special Project for the Cultivation of Major Achievements in the Peak Discipline of Forestry Science(118/71201800709)+1 种基金the Special Subsidy for Leading Talents of Scientific and Technological Innovation in Fujian Province(118/KRC16006A)the Fujian Forestry Science and Technology Research Project(Min[2019]6).
文摘The mangrove Kandelia obovata(Rhizophoraceae)is an important coastal shelterbelt and landscape tree distributed in tropical and subtropical areas across East Asia and Southeast Asia.Herein,a chromosome-level reference genome of K.obovata based on PacBio,Illumina,and Hi-C data is reported.The high-quality assembled genome size is 177.99 Mb,with a contig N50 value of 5.74 Mb.A large number of contracted gene families and a small number of expanded gene families,as well as a small number of repeated sequences,may account for the small K.obovata genome.We found that K.obovata experienced two whole-genome polyploidization events:one whole-genome duplication shared with other Rhizophoreae and one shared with most eudicots(γevent).We confidently annotated 19,138 protein-coding genes in K.obovata and identified the MADS-box gene class and the RPW8 gene class,which might be related to flowering and resistance to powdery mildew in K.obovata and Rhizophora apiculata,respectively.The reference K.obovata genome described here will be very useful for further molecular elucidation of various traits,the breeding of this coastal shelterbelt species,and evolutionary studies with related taxa.
基金support received through the Special Funds for Leading Scientific and Technological Innovation Talents of Fujian Province,China(KRC16006A)awarded to S.-Q.Z.Fujian Forestry Science and Technology Project—Genome Sequencing and Application of High-quality Resources Screening of Camphor tree,China(2021FKJ19)awarded to G.-R.C.Fujian Forestry Science and Technology Extension Project—Cultivation Demonstration of a New Camphor Variety Nan’an No.1,China(2021TG10)awarded to X.-H.W.
文摘Magnoliids represent the third largest branch of the most diverse and species-rich angiosperms,and their phylogenetic position relative to monocots and eudicots remains uncertain(Dong et al.,2021).Here,we describe the assembly of a high-quality chromosome-level genome sequence for Cinnamomum camphora(camphor),an evergreen tree belonging to Lauraceae.Genomebased phylogenetic analysis indicated possible incomplete lineage sorting(ILS)during the rapid diversification of the early diverging branches of angiosperms,which may have led to the unstable phylogenetic position of magnoliids.
基金supported by the grants from National Natural Science Foundation of China(No.82030117,82074203,82170033,and 82374540)Special Fund for Research on Community Medicine and Health Management in Shanghai(No.2023SQ01)+2 种基金Medical Research Project of Health Commission of Shanghai Hongkou District(No.HW2302-43)Special Medical Basic Research Project of the First Affiliated Hospital of Naval Medical University(No.2021JCMS12)Wild Goose Array Project of Zhengzhou Center of Chinese People’s Liberation Army Joint Logistic Support Force。
文摘Objective:Tumor-derived exosomes(TDEs)play crucial roles in intercellular communication.Hypoxia in the tumor microenvironment enhances secretion of TDEs and accelerates tumor metastasis.Jiedu recipe(JR),a traditional Chinese medicinal formula,has demonstrated efficacy in preventing the metastasis of hepatocellular carcinoma(HCC).However,the underlying mechanism remains largely unknown.Methods:Animal experiments were performed to investigate the metastasis-preventing effects of JR.Bioinformatics analysis and in vitro assays were conducted to explore the potential targets and active components of JR.TDEs were assessed using nanoparticle tracking analysis(NTA)and Western blotting(WB).Exosomes derived from normoxic or hypoxic HCC cells(H-TDEs)were collected to establish premetastatic mouse models.JR was intragastrically administered to evaluate its metastasis-preventive effects.WB and lysosomal staining were performed to investigate the effects of JR on lysosomal function and autophagy.Bioinformatics analysis,WB,NTA,and immunofluorescence staining were used to identify the active components and potential targets of JR.Results:JR effectively inhibited subcutaneous-tumor-promoted lung premetastatic niche development and tumor metastasis.It inhibited the release of exosomes from tumor cells under hypoxic condition.JR treatment promoted both lysosomal acidification and suppressed secretory autophagy,which were dysregulated in hypoxic tumor cells.Quercetin was identified as the active component in JR,and the epidermal growth factor receptor(EGFR)was identified as a potential target.Quercetin inhibited EGFR phosphorylation and promoted the nuclear translocation of transcription factor EB(TFEB).Hypoxia-impaired lysosomal function was restored,and secretory autophagy was alleviated by quercetin treatment.Conclusion:JR suppressed HCC metastasis by inhibiting hypoxia-stimulated exosome release,restoring lysosomal function,and suppressing secretory autophagy.Quercetin acted as a key component of JR and regulated TDE release through EGFR-TFEB signaling.Our study provides a potential strategy for retarding tumor metastasis by targeting H-TDE secretion.
基金supported by the National Nature Science Foundation of China(No.22272205,No.22279164)Hunan Provincial Nature Science Foundation of China(No.2022JJ30685)+4 种基金Hunan Provincial Science and Technology Plan Project of China(No.2017TP1001)the Science and Technology Innovation Program of Hunan Province(2023RC3058)the Scientific and Technological Research Program of Chongqing Municipal Education Commission(No.KJZD-M202101401)Aid Program for Science and Technology Innovative Research Team in Higher Educational Institutions of Hunan Provincesupport from Science and Technology Innovation Team for Photovoltaic Power and Energy Storage Battery Key Technologies at General University in Hunan Province.D.S.acknowledges support from Young Elite Scientists Sponsorship Program by CAST(No.YESS20220432).
文摘There is an urgent need to develop innovative electrochemical energy storage devices that can offer high energy density,long lifespan,excellent rate capability,and improved security.For the electrochemical system,the electrode interphase,namely the cathode electrolyte interphase(CEI)and solid electrolyte interphase(SEI)play crucial roles in the operating mechanism,kinetics,and overall performance of the battery.However,the in-depth investigation of the unstable and complex electrode interphase is limited by the unavoidable air and moisture contact during the material transfer process and probable high-energy radiation damage in the characterization procedure.Recently,cryogenic techniques and in situ techniques have been developed and applied in the electrode interphase research to settle the radiation damage and air erosion,respectively.However,there has not been a special review that summarizes the relevant methods,so a systematic review is very important to accelerate the development.In this review,we summarize these two state-of-the-art methods,including their working principle,characterization process,advantages,and applications in electrode interphase analysis.And the integrative techniques,which are considered as the future development perspectives,are also discussed.This review can provide important directions for next-generation characterization techniques and strategies to effectively analyze the electrode interphase for advanced batteries.
基金National Natural Science Foundation of China(No.82405512)the University-level Basic Medical Research Project of Naval Medical University(No.2022MS008)Medical Basic Research Program of the First Affiliated Hospital of Naval Medical University(No.2021JCMS12)。
文摘Objective:Angiogenesis is a critical target for hepatocellular carcinoma(HCC)treatment The previous studies indicated that Jiedu Fang(JDF)could inhibit hypoxia-induced angiogenesis through interleukin-8(IL-8).Therefore,the present study further explores the mechanisms behind JDF's inhibition of HCC angiogenesis.Methods:Angiogenesis was assessed with the capillary-like tube formation assay in vitro and the matrigel plug angiogenesis assay in vivo.A liver cancer-related gene set and genes associated with angiogenesis and the hypoxic microenvironment were analyzed using a bioinformatics platform.Real-time reverse transcription-polymerase chain reaction and Western blotting assays were used to assess the targeted mRNA and protein levels,respectively.The Transwell assay was used to assess the migration and invasion potential of EA.hy 926 cells.The orthotopic tumor xenograft model was established,and immunohistochemistry and immunofluorescence assays were used to detect cluster of differentiation 31 and angiopoietin 2 expression,while an enzyme-linked immunosorbent assay was used to detect vascular endothelial growth factor and IL-8 protein levels.Results:In vitro and in vivo assays showed that IL-8 promoted angiogenesis,and JDF could antagonize this effect.Bioinformatics analysis indicated that aurora kinase A(Aurora A)was an important candidate,which can promote IL-8 expression through activation of signal transducer and activator of transcription3(STAT3).The overexpression of Aurora A increased IL-8 secretion and promoted HCC migration,invasion,and angiogenesis,which was partly inhibited by JDF.Such effects were validated by in vivo assays.Further validation using the STAT3 inhibitor S3I-201 demonstrated that STAT3 was regulated by Aurora A.Conclusion:JDF exhibits efficacy in reducing hypoxia-induced angiogenesis in HCC through a mechanism involving the Aurora A/STAT3/IL-8 signaling pathway.Therefore,JDF holds promise as a potential therapeutic approach for targeting HCC angiogenesis.
基金financial support from the National Natural Science Foundation of China (82273763)the Natural Science Foundation of Guangdong Province (2022A-1515011939, China)+2 种基金the Opening Project of State Key Laboratory of Respiratory Disease (SKLRD-OP-202313, China)the Opening Project of Guangdong Provincial Key Laboratory of New Drug Design and Evaluation (2020B1212060034, China)Wang Kuancheng Young Scholar of Jinan University
文摘Neurotrophic receptor kinase(NTRK) fusions are actionable oncogenic drivers of multiple pediatric and adult solid tumors,and tropomyosin receptor kinase(TRK) has been considered as an attractive therapeutic target for "pan-cancer" harboring these fusions.Currently,two generations TRK inhibitors have been developed.The representative second-generation inhibitors selitrectinib and repotrectinib were designed to overcome clinic acquired resistance of the first-generation inhibitors larotrectinib or entrectinib resulted from solvent-front and gatekeeper on-target mutations.However,xDFG(TRKAG667C/A/S,homologous TRKCG696C/A/S) and some double mutations still confer resistance to selitrectinib and repotrectinib,and overcoming these resistances represents a major unmet clinical need.In this review,we summarize the acquired resistance mechanism of the first-and second-generation TRK inhibitors,and firstly put forward the emerging selective type Ⅱ TRK inhibitors to overcome xDFG mutations mediated resistance.Additionally,we concluded our perspectives on new challenges and future directions in this field.
基金supported by the National Basic Research Program of China(No.2014CB340600)the National Natural Science Foundation of China(Nos.61332019,61173138,6127245,and 91118003)the New Products and Technology Research and Development Projects of Hubei Province(No.2012BAA03004)
文摘Infrastructure as a Service(laaS)has brought advantages to users because virtualization technology hides the details of the physical resources,but this leads to the problem of users being unable to perceive their security.This defect has obstructed cloud computing from wide-spread popularity and development.To solve this problem,a dynamic measurement protocol in laaS is presented in this paper.The protocol makes it possible for the user to get the real-time security status of the resources,thereby solving the problem of guaranteeing dynamic credibility.This changes the cloud service security provider from the operator to the users themselves.This study has verified the security of the protocol by means of Burrow-Abadi-Needham(BAN)logic,and the result shows that it can satisfy requirements for innovation,privacy,and integrity.Finally,based on different laaS platforms,this study has conducted a performance analysis to demonstrate that this protocol is reliable,secure,and efficient.
基金financially supported by the General Program of Natural Science Foundation of Liaoning Province of China(Grant No.2023-MSLH-283)the Platform Program of Education Department of Liaoning Province(Grant No.JYTPT2024002)+1 种基金the Liaoning Province“Xingliao Talent Program”Project(Grant No.XLYC2203005)the Liaoning Provincial Department of Education and the School of Information and Electrical Engineering of Shenyang Agricultural University for their support.
文摘Phosphorus plays a vital role in the growth and development of rice in the cold northern regions,affecting the yield and quality of rice.The phosphorus content of leaves can indicate the nutritional status of rice.Rapid and accurate acquisition of the phosphorus content in leaves is the basis for ensuring healthy rice growth and maintaining stable and high rice yield.Hyperspectral technology can reflect the shape of rice leaves and then evaluate the phosphorus content in the leaves,so hyperspectral technology has the potential to estimate the phosphorus content in plant leaves quickly and accurately.The hyperspectral data of the rice leaves were pretreated using the SG smoothing method.The spectral characteristics of pretreated spectral data were extracted using principal component analysis(PCA)and linear discriminant analysis(LDA).Extreme learning machine(ELM)and Bat algorithm optimized extreme learning machine(BA-ELM)were constructed to retrieve the phosphorus content in rice leaves.The results show that there are seven feature vectors produced by the two methods,and the feature vectors selected by the two methods are used as inputs,respectively.The verification sets R2 and RMSE of the two models constructed using the feature reflectivity chosen by the LDA algorithm as input were between 0.603 and 0.604,and 0.025 and 0.032,respectively.Under the condition of the same inversion model,the model constructed by using the reflectivity of the features selected by the PCA algorithm as input has a better prediction effect,and the verification set R2 of the two models was between 0.685-0.765,and RMSE was between 0.022-0.038.In addition,when using the features selected by these two algorithms to model,comparing the prediction results of the two models,it was found that the accuracy of the BA-ELM was higher than that of ELM.Its determination coefficient R2 and RMSE of the verification set were 0.765 and 0.022,respectively.Because of this,the ELM optimized by principal component analysis and BA has certain advantages in the hyperspectral inversion of phosphorus content in rice leaves in cold regions,and can provide some reference for rapid and accurate detection of phosphorus content in rice leaves.
