To enhance power flow regulation in scenarios involving large-scale renewable energy transmission via high-voltage direct current(HVDC)links and multi-infeed DC systems in load-center regions,this paper proposes a hyb...To enhance power flow regulation in scenarios involving large-scale renewable energy transmission via high-voltage direct current(HVDC)links and multi-infeed DC systems in load-center regions,this paper proposes a hybrid modular multilevel converter–capacitor-commutated line-commutated converter(MMC-CLCC)HVDC transmission system and its corresponding control strategy.First,the system topology is constructed,and a submodule configuration method for the MMC—combining full-bridge submodules(FBSMs)and half-bridge submodules(HBSMs)—is proposed to enable direct power flow reversal.Second,a hierarchical control strategy is introduced,includingMMCvoltage control,CLCC current control,and a coordinationmechanism,along with the derivation of the hybrid system’s power flow reversal characteristics.Third,leveraging the CLCC’s fast current regulation and theMMC’s negative voltage control capability,a coordinated power flow reversal control strategy is developed.Finally,an 800 kV MMC-CLCC hybrid HVDC system is modeled in PSCAD/EMTDC to validate the power flow reversal performance under a high proportion of full-bridge submodule configuration.Results demonstrate that the proposed control strategy enables rapid(1-s transition)and smooth switching of bidirectional power flow without modifying the structure of primary equipment:the transient fluctuation ofDC voltage from the rated value(UdcN)to themaximumreverse voltage(-kUdcN)is less than 5%;the DC current strictly follows the preset characteristic curve with a deviation of≤3%;the active power reverses continuously,and the system maintains stable operation throughout the reversal process.展开更多
Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and diffe...Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quantitatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fractionated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor accounting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.展开更多
CO_(2),as a greenhouse gas,has excessive emissions that lead to many environmental problems and is a rich and cheap C1 resource.Effective utilization and transformation of CO_(2)has become an important means of achiev...CO_(2),as a greenhouse gas,has excessive emissions that lead to many environmental problems and is a rich and cheap C1 resource.Effective utilization and transformation of CO_(2)has become an important means of achieving carbon neutrality.Oxazolidinones are important intermediates in pharmaceutical chemistry that can be synthesized by carboxylation cyclization of CO_(2)with propargyl amines or cycloaddition of CO_(2)with aziridines.Owing to CO_(2)’s high stability,these reactions typically require harsh conditions,such as high temperatures or pressures.It is desirable,but challenging,to find a catalyst that can catalyze these two types of reactions under relatively mild conditions.Metal-organic frameworks(MOFs)are an emerging class of heterogeneous catalysts that with great potential in the catalytic conversion of CO_(2)to value-added products because of their attractive features,such as abundant metal active sites,inherent porosity,and easy functionalities.Herein,a unique three-dimensional(3D)MOF,{(CH_(3)NH_(2)CH_(3))_(2)[Co_(3)(BCP)_(2)]·6H_(2)O·4DMF}n(1)(H_(4)BCP:5‐(2,6‐bis(4‐carboxyphenyl)pyridin‐4‐yl)isophthalic acid;DMF:N,N'‐dimethylformamide),was synthesized using carboxylic acid ligands and cobalt salts via a solvothermal method.According to structural analysis,[Co_(3)]clusters as secondary building units(SBU)are bridged by BCP4−ligands,forming an anion framework with flu topology,and dimethylamine cations act as counter ions in the pores.The framework has rectangular channels of approximately 0.4 nm×0.9 nm along the a-axis direction,exhibiting its porous property.Infrared spectroscopy(IR)and X-ray photoelectron spectroscopy(XPS)characterizations proved the coordination interaction between the carboxyl groups in the ligands and the metal ions.The powder X-Ray diffraction(PXRD)test further confirmed the phase purity of the synthesized samples.PXRD and thermogravimetry(TG)analyses indicated that 1 possessed good solvent and thermal stabilities.The catalytic experiments revealed that 1 could effectively catalyze CO_(2)with aziridines or propargyl amines to prepare oxazolidinones.In the cycloaddition of CO_(2)with aziridines,1 can facilitate the reaction under relatively mild conditions compared to other reported MOF-based catalysts.It shows excellent universality for substrates with various substitutions on the N atom or benzene ring.Investigation of the mechanism indicated that the coordination interaction of cobalt metal sites with the nitrogen atoms of aziridines can activate the substrates.For the carboxylative cyclization of CO_(2)with propargylic amines,this catalyst also has a broad substrate scope.Control experiments and nuclear magnetic resonance(NMR)tests suggest that Lewis acid metal sites are responsible for the high catalytic efficiency achieved by activating the alkyne groups.Moreover,1 showed good reusability in both reactions.Compound 1 represents a new catalyst that enables“two birds with one stone”in the catalytic synthesis of oxazolidinones using CO_(2).展开更多
Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that...Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that the expression levels of family with sequence similarity 64,member A(FAM64A)were significantly higher in HNSCC tissues and cell lines.In addition,FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC.Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells,and vice versa.Moreover,we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model.Mechanistically,a physical interaction was found between FAM64A and forkhead box protein M1(FOXM1)in HNSCC cells.FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1,but also,more importantly,by modulating FOXM1 expression via the autoregulation loop.Furthermore,a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts.Taken together,our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC,and FAM64A might be a promising molecular therapeutic target for treating HNSCC.展开更多
As an important part of steel bridge deck,the engineering quality and service condition of steel bridge deck pavement(SBDP)directly affects the capacity and operational efficiency of the bridge.This paper reviews the ...As an important part of steel bridge deck,the engineering quality and service condition of steel bridge deck pavement(SBDP)directly affects the capacity and operational efficiency of the bridge.This paper reviews the history of the development of SBDP in China over the past 20 years from the exploration stage,rapid development stage and prosperity stage.The development and application of SBDP at different stages are discussed in terms of materials,structure,design,performance evaluation,maintenance and rehabilitation,respectively.The advantages and disadvantages of different pavement materials and structures,and the application of different research methods are summarized.The review shows that the improvement of pavement materials and structures and the development of new materials should be further studied on the multi-scale to enhance the durability of pavement materials,so as to extend the service life of pavements.The design method of SBDP related to the synergistic effect of vehicle,pavement and bridge should be established,and the design concept and method standard of rigid base pavement structure should be improved and formulate a complete design standard.In addition,multi-disease intelligent identification system and equipment should be studied to track the entire course of disease development in real time.And it is necessary to develop appropriate algorithms to select and classify the complex data of disease and maintenance history.展开更多
Aggregation-induced emission （AIE） luminogen displays bright fluorescence and has photobleaching resistance in its aggregation state. It is an ideal fluorescent contrast agent for bioimaging. Multiphoton microscopy ...Aggregation-induced emission （AIE） luminogen displays bright fluorescence and has photobleaching resistance in its aggregation state. It is an ideal fluorescent contrast agent for bioimaging. Multiphoton microscopy is an important tool for bioimaging since it possesses the ability to penetrate deep into biological tissues. Herein, we used AIE luminogen together with multiphoton microscopy for long-term imaging of zebrafish. A typical AIE luminogen, 2,3-bis（4-（phenyl（4- （1,Z2-triphenylvinyl） phenyl）amino）phenyl） fumaronitrile （TPE-TPA-FN or TTF）, was encapsulated with 1,2-distearoyl-sn-glycero-3-phosphoethanola-mine-N- [methoxy（polyethylene glycol）-2000] （DSPE-mPEG2000） to form nanodots that exhibited bright three-photon fluorescence under 1,560 nm-femtosecond （fs） laser excitation. The TTF-nanodots were chemically stable in a wide range of pH values and showed no in vivo toxicity in zebrafish according to a series of biological tests. The TTF-nanodots were microinjected into zebrafish embryos, and the different growth stages of the labeled embryos were monitored with a three-photon fluorescence microscope. TTF-nanodots could be traced inside the zebrafish body for as long as 120 hours. In addition, the TTF-nanodots were utilized to target the blood vessel of zebrafish, and three-photon fluorescence angiogram was performed. More importantly, these nanodots were highly resistant to photobleaching under 1,560 nm-fs excitation, allowing long-term imaging of zebrafish.展开更多
Background:Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis,high lymph node metastasis and early recurrence.However,the molec...Background:Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis,high lymph node metastasis and early recurrence.However,the molecular events regulating HNSCC tumorigenesis remain poorly understood.Therefore,uncovering the underlying mechanisms is urgently needed to identify novel and promising therapeutic targets for HNSCC.In this study,we aimed to explore the role of pleckstrin-2(PLEK2)in regulating HNSCC tumorigenesis.Methods:The expression pattern of PLEK2 and its clinical significance in HNSCC were determined by analyzing publicly assessable datasets and our own independent HNSCC cohort.In vitro and in vivo experiments,including cell proliferation,colony formation,Matrigel invasion,tumor sphere formation,ALDEFLUOR,Western blotting assays and xenograft mouse models,were used to investigate the role of PLEK2 in regulating the malignant behaviors of HNSCC cells.The underlying molecular mechanisms for the tumor-promoting role of PLEK2 were elucidated using co-immunoprecipitation,cycloheximide chase analysis,ubiquitination assays,chromatin immunoprecipitation-quantitative polymerase chain reaction,luciferase reporter assays and rescue experiments.Results:The expression levels of PLEK2 mRNA and protein were significantly increased in HNSCC tissues,and PLEK2 overexpression was strongly associated with poor overall survival and therapeutic resistance.Additionally,PLEK2 was important for maintaining the proliferation,invasion,epithelial-mesenchymal transition,cancer stemness and tumorigenesis of HNSCC cells and could alter the cellular metabolism of the cancer cells.Mechanistically,PLEK2 interacted with c-Myc and reduced the association of F-box and WD repeat domain containing 7(FBXW7)with c-Myc,thereby avoiding ubiquitination and subsequent proteasome-mediated degradation of c-Myc.Moreover,the c-Myc signaling activated by PLEK2 was important for sustaining the aggressive malignant phenotypes and tumorigenesis of HNSCC cells.c-Myc also directly bounded to the PLEK2 promoter and activated its transcription,forming a positive feedback loop.Conclusions:Collectively,these findings uncover a previously unknown molecular basis of PLEK2-enhanced c-Myc signaling in HNSCC,suggesting that PLEK2 may represent a promising therapeutic target for treating HNSCC.展开更多
The gut microbiome of plant-eaters is affected by the food they eat,but it is currently unclear how the plant metabolome and microbiome are influenced by the substrate the plant grows in and how this subsequently impa...The gut microbiome of plant-eaters is affected by the food they eat,but it is currently unclear how the plant metabolome and microbiome are influenced by the substrate the plant grows in and how this subsequently impacts the feeding behavior and gut microbiomes of insect herbivores.Here,we use Plutella xylostella caterpillars and show that the larvae prefer leaves of cabbage plants growing in a vermiculite substrate to those from plants growing in conventional soil systems.From a plant metabolomics analysis,we identified 20 plant metabolites that were related to caterpillar feeding performance.In a bioassay,the effects of these plant metabolites on insects'feeding were tested.Nitrate and compounds enriched with leaves of soilless cultivation promoted the feeding of insects,while compounds enriched with leaves of plants growing in natural soil decreased feeding.Several microbial groups(e.g.,Sporolactobacillus,Haliangium)detected inside the plant correlated with caterpillar feeding performance and other microbial groups,such as Ramlibacter and Methylophilus,correlated with the gut microbiome.Our results highlight the role of growth substrates on the food metabolome and microbiome and on the feeding performance and the gut microbiome of plant feeders.It illustrates how belowground factors can influence the aboveground properties of plant-animal systems,which has important implications for plant growth and pest control.展开更多
In this paper,we accomplish the unified convergence analysis of a second-order method of multipliers(i.e.,a second-order augmented Lagrangian method)for solving the conventional nonlinear conic optimization problems.S...In this paper,we accomplish the unified convergence analysis of a second-order method of multipliers(i.e.,a second-order augmented Lagrangian method)for solving the conventional nonlinear conic optimization problems.Specifically,the algorithm that we investigate incorporates a specially designed nonsmooth(generalized)Newton step to furnish a second-order update rule for the multipliers.We first show in a unified fashion that under a few abstract assumptions,the proposed method is locally convergent and possesses a(nonasymptotic)superlinear convergence rate,even though the penalty parameter is fixed and/or the strict complementarity fails.Subsequently,we demonstrate that for the three typical scenarios,i.e.,the classic nonlinear programming,the nonlinear second-order cone programming and the nonlinear semidefinite programming,these abstract assumptions are nothing but exactly the implications of the iconic sufficient conditions that are assumed for establishing the Q-linear convergence rates of the method of multipliers without assuming the strict complementarity.展开更多
In a recent Cancer Discovery publication,Bianchi et al.unveil a crucial mechanism driving therapeutic resistance in pancreatic ductal adenocarcinoma(PDAC),orchestrated by cell-autonomous Cxcl1 and TNF from polymorphon...In a recent Cancer Discovery publication,Bianchi et al.unveil a crucial mechanism driving therapeutic resistance in pancreatic ductal adenocarcinoma(PDAC),orchestrated by cell-autonomous Cxcl1 and TNF from polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs).This insight provides fresh perspectives for surmounting such resistance in PDAC.1 PDAC represents a highly aggressive malignancy exhibiting substantial therapeutic resistance,attributable to factors such as intractable genomic aberrations,immunosuppression mediated by myeloid cells,and pro-inflammatory activation of cancerassociated fibroblasts.展开更多
基金supported by Science and Technology Project of the headquarters of the State Grid Corporation of China(No.5500-202324492A-3-2-ZN).
文摘To enhance power flow regulation in scenarios involving large-scale renewable energy transmission via high-voltage direct current(HVDC)links and multi-infeed DC systems in load-center regions,this paper proposes a hybrid modular multilevel converter–capacitor-commutated line-commutated converter(MMC-CLCC)HVDC transmission system and its corresponding control strategy.First,the system topology is constructed,and a submodule configuration method for the MMC—combining full-bridge submodules(FBSMs)and half-bridge submodules(HBSMs)—is proposed to enable direct power flow reversal.Second,a hierarchical control strategy is introduced,includingMMCvoltage control,CLCC current control,and a coordinationmechanism,along with the derivation of the hybrid system’s power flow reversal characteristics.Third,leveraging the CLCC’s fast current regulation and theMMC’s negative voltage control capability,a coordinated power flow reversal control strategy is developed.Finally,an 800 kV MMC-CLCC hybrid HVDC system is modeled in PSCAD/EMTDC to validate the power flow reversal performance under a high proportion of full-bridge submodule configuration.Results demonstrate that the proposed control strategy enables rapid(1-s transition)and smooth switching of bidirectional power flow without modifying the structure of primary equipment:the transient fluctuation ofDC voltage from the rated value(UdcN)to themaximumreverse voltage(-kUdcN)is less than 5%;the DC current strictly follows the preset characteristic curve with a deviation of≤3%;the active power reverses continuously,and the system maintains stable operation throughout the reversal process.
基金the financial support from the National Key Program for Basic Research of China(Grant Nos.:2018YFC0910302 and 2017YFF0205400)the National Natural Science Foundation of China(Grant No.:81530021)Innovation Foundation of Medicine(Grant Nos.:BWS14J052 and 16CXZ027)
文摘Posttranslational modifications of antibody products affect their stability,charge distribution,and drug activity and are thus a critical quality attribute.The comprehensive mapping of antibody modifications and different charge isomers(CIs)is of utmost importance,but is challenging.We intended to quantitatively characterize the posttranslational modification status of CIs of antibody drugs and explore the impact of posttranslational modifications on charge heterogeneity.The CIs of antibodies were fractionated by strong cation exchange chromatography and verified by capillary isoelectric focusing-whole column imaging detection,followed by stepwise structural characterization at three levels.First,the differences between CIs were explored at the intact protein level using a top-down mass spectrometry approach;this showed differences in glycoforms and deamidation status.Second,at the peptide level,common modifications of oxidation,deamidation,and glycosylation were identified.Peptide mapping showed nonuniform deamidation and glycoform distribution among CIs.In total,10 N-glycoforms were detected by peptide mapping.Finally,an in-depth analysis of glycan variants of CIs was performed through the detection of enriched glycopeptides.Qualitative and quantitative analyses demonstrated the dynamics of 24 N-glycoforms.The results revealed that sialic acid modification is a critical factor accounting for charge heterogeneity,which is otherwise missed in peptide mapping and intact molecular weight analyses.This study demonstrated the importance of the comprehensive analyses of antibody CIs and provides a reference method for the quality control of biopharmaceutical analysis.
文摘CO_(2),as a greenhouse gas,has excessive emissions that lead to many environmental problems and is a rich and cheap C1 resource.Effective utilization and transformation of CO_(2)has become an important means of achieving carbon neutrality.Oxazolidinones are important intermediates in pharmaceutical chemistry that can be synthesized by carboxylation cyclization of CO_(2)with propargyl amines or cycloaddition of CO_(2)with aziridines.Owing to CO_(2)’s high stability,these reactions typically require harsh conditions,such as high temperatures or pressures.It is desirable,but challenging,to find a catalyst that can catalyze these two types of reactions under relatively mild conditions.Metal-organic frameworks(MOFs)are an emerging class of heterogeneous catalysts that with great potential in the catalytic conversion of CO_(2)to value-added products because of their attractive features,such as abundant metal active sites,inherent porosity,and easy functionalities.Herein,a unique three-dimensional(3D)MOF,{(CH_(3)NH_(2)CH_(3))_(2)[Co_(3)(BCP)_(2)]·6H_(2)O·4DMF}n(1)(H_(4)BCP:5‐(2,6‐bis(4‐carboxyphenyl)pyridin‐4‐yl)isophthalic acid;DMF:N,N'‐dimethylformamide),was synthesized using carboxylic acid ligands and cobalt salts via a solvothermal method.According to structural analysis,[Co_(3)]clusters as secondary building units(SBU)are bridged by BCP4−ligands,forming an anion framework with flu topology,and dimethylamine cations act as counter ions in the pores.The framework has rectangular channels of approximately 0.4 nm×0.9 nm along the a-axis direction,exhibiting its porous property.Infrared spectroscopy(IR)and X-ray photoelectron spectroscopy(XPS)characterizations proved the coordination interaction between the carboxyl groups in the ligands and the metal ions.The powder X-Ray diffraction(PXRD)test further confirmed the phase purity of the synthesized samples.PXRD and thermogravimetry(TG)analyses indicated that 1 possessed good solvent and thermal stabilities.The catalytic experiments revealed that 1 could effectively catalyze CO_(2)with aziridines or propargyl amines to prepare oxazolidinones.In the cycloaddition of CO_(2)with aziridines,1 can facilitate the reaction under relatively mild conditions compared to other reported MOF-based catalysts.It shows excellent universality for substrates with various substitutions on the N atom or benzene ring.Investigation of the mechanism indicated that the coordination interaction of cobalt metal sites with the nitrogen atoms of aziridines can activate the substrates.For the carboxylative cyclization of CO_(2)with propargylic amines,this catalyst also has a broad substrate scope.Control experiments and nuclear magnetic resonance(NMR)tests suggest that Lewis acid metal sites are responsible for the high catalytic efficiency achieved by activating the alkyne groups.Moreover,1 showed good reusability in both reactions.Compound 1 represents a new catalyst that enables“two birds with one stone”in the catalytic synthesis of oxazolidinones using CO_(2).
基金supported by National Natural Science Foundation of China(81901006)Guangdong Basic and Applied Basic Research Foundation(2020A1515110051)+1 种基金Scientific Research Talent Cultivation Project of Stomatological Hospital,Southern Medical University(RC202005)Science Research Cultivation Program of Stomatological Hospital,Southern Medical University(PY2020002)。
文摘Head and neck squamous cell carcinoma(HNSCC)still lacks effective targeted treatment.Therefore,exploring novel and robust molecular targets is critical for improving the clinical outcome of HNSCC.Here,we reported that the expression levels of family with sequence similarity 64,member A(FAM64A)were significantly higher in HNSCC tissues and cell lines.In addition,FAM64A overexpression was found to be strongly associated with an unfavorable prognosis of HNSCC.Both in vitro and in vivo evidence showed that FAM64A depletion suppressed the malignant activities of HNSCC cells,and vice versa.Moreover,we found that the FAM64A level was progressively increased from normal to dysplastic to cancerous tissues in a carcinogenic 4-nitroquinoline-1-oxide mouse model.Mechanistically,a physical interaction was found between FAM64A and forkhead box protein M1(FOXM1)in HNSCC cells.FAM64A promoted HNSCC tumorigenesis not only by enhancing the transcriptional activity of FOXM1,but also,more importantly,by modulating FOXM1 expression via the autoregulation loop.Furthermore,a positive correlation between FAM64A and FOXM1 was found in multiple independent cohorts.Taken together,our findings reveal a previously unknown mechanism behind the activation of FOXM1 in HNSCC,and FAM64A might be a promising molecular therapeutic target for treating HNSCC.
基金The authors appreciate the financial support from the National Natural Science Foundation of China(No.51878167)Qing Lan Project of Jiangsu Province。
文摘As an important part of steel bridge deck,the engineering quality and service condition of steel bridge deck pavement(SBDP)directly affects the capacity and operational efficiency of the bridge.This paper reviews the history of the development of SBDP in China over the past 20 years from the exploration stage,rapid development stage and prosperity stage.The development and application of SBDP at different stages are discussed in terms of materials,structure,design,performance evaluation,maintenance and rehabilitation,respectively.The advantages and disadvantages of different pavement materials and structures,and the application of different research methods are summarized.The review shows that the improvement of pavement materials and structures and the development of new materials should be further studied on the multi-scale to enhance the durability of pavement materials,so as to extend the service life of pavements.The design method of SBDP related to the synergistic effect of vehicle,pavement and bridge should be established,and the design concept and method standard of rigid base pavement structure should be improved and formulate a complete design standard.In addition,multi-disease intelligent identification system and equipment should be studied to track the entire course of disease development in real time.And it is necessary to develop appropriate algorithms to select and classify the complex data of disease and maintenance history.
基金This work was supported by the National Basic Research Program of China （973 Program） （No. 2013CB834704）, the National Natural Science Foundation of China （No. 61275190）, the Program of Zhejiang Leading Team of Science and Technology Innovation （No. 2010R50007）, the Fundamental Research Funds for the Central Universities, the Open Fund of the State Key Laboratory of Luminescent Materials and Devices （South China University of Technology）, and the Research Grants Council of Hong Kong （No. HKUST2/CRF/10）.
文摘Aggregation-induced emission （AIE） luminogen displays bright fluorescence and has photobleaching resistance in its aggregation state. It is an ideal fluorescent contrast agent for bioimaging. Multiphoton microscopy is an important tool for bioimaging since it possesses the ability to penetrate deep into biological tissues. Herein, we used AIE luminogen together with multiphoton microscopy for long-term imaging of zebrafish. A typical AIE luminogen, 2,3-bis（4-（phenyl（4- （1,Z2-triphenylvinyl） phenyl）amino）phenyl） fumaronitrile （TPE-TPA-FN or TTF）, was encapsulated with 1,2-distearoyl-sn-glycero-3-phosphoethanola-mine-N- [methoxy（polyethylene glycol）-2000] （DSPE-mPEG2000） to form nanodots that exhibited bright three-photon fluorescence under 1,560 nm-femtosecond （fs） laser excitation. The TTF-nanodots were chemically stable in a wide range of pH values and showed no in vivo toxicity in zebrafish according to a series of biological tests. The TTF-nanodots were microinjected into zebrafish embryos, and the different growth stages of the labeled embryos were monitored with a three-photon fluorescence microscope. TTF-nanodots could be traced inside the zebrafish body for as long as 120 hours. In addition, the TTF-nanodots were utilized to target the blood vessel of zebrafish, and three-photon fluorescence angiogram was performed. More importantly, these nanodots were highly resistant to photobleaching under 1,560 nm-fs excitation, allowing long-term imaging of zebrafish.
基金National Natural Science Foundation of China,Grant/Award Number:81901006Guangdong Basic and Applied Basic Research Foundation,Grant/Award Number:2020A1515110051+1 种基金Scientific Research Talent Cultivation Project of Stomatological Hospital,Southern Medical University,Grant/Award Number:RC202005Science Research Cultivation Program of Stomatological Hospital,Southern Medical University,Grant/Award Number:PY2020002。
文摘Background:Head and neck squamous cell carcinoma(HNSCC)is one of the most frequent malignancies worldwide and is characterized by unfavorable prognosis,high lymph node metastasis and early recurrence.However,the molecular events regulating HNSCC tumorigenesis remain poorly understood.Therefore,uncovering the underlying mechanisms is urgently needed to identify novel and promising therapeutic targets for HNSCC.In this study,we aimed to explore the role of pleckstrin-2(PLEK2)in regulating HNSCC tumorigenesis.Methods:The expression pattern of PLEK2 and its clinical significance in HNSCC were determined by analyzing publicly assessable datasets and our own independent HNSCC cohort.In vitro and in vivo experiments,including cell proliferation,colony formation,Matrigel invasion,tumor sphere formation,ALDEFLUOR,Western blotting assays and xenograft mouse models,were used to investigate the role of PLEK2 in regulating the malignant behaviors of HNSCC cells.The underlying molecular mechanisms for the tumor-promoting role of PLEK2 were elucidated using co-immunoprecipitation,cycloheximide chase analysis,ubiquitination assays,chromatin immunoprecipitation-quantitative polymerase chain reaction,luciferase reporter assays and rescue experiments.Results:The expression levels of PLEK2 mRNA and protein were significantly increased in HNSCC tissues,and PLEK2 overexpression was strongly associated with poor overall survival and therapeutic resistance.Additionally,PLEK2 was important for maintaining the proliferation,invasion,epithelial-mesenchymal transition,cancer stemness and tumorigenesis of HNSCC cells and could alter the cellular metabolism of the cancer cells.Mechanistically,PLEK2 interacted with c-Myc and reduced the association of F-box and WD repeat domain containing 7(FBXW7)with c-Myc,thereby avoiding ubiquitination and subsequent proteasome-mediated degradation of c-Myc.Moreover,the c-Myc signaling activated by PLEK2 was important for sustaining the aggressive malignant phenotypes and tumorigenesis of HNSCC cells.c-Myc also directly bounded to the PLEK2 promoter and activated its transcription,forming a positive feedback loop.Conclusions:Collectively,these findings uncover a previously unknown molecular basis of PLEK2-enhanced c-Myc signaling in HNSCC,suggesting that PLEK2 may represent a promising therapeutic target for treating HNSCC.
基金supported by the National Natural Science Foundation of China(42090060,42277297)Natural Science Foundation of Jiangsu Province(BK20211577)+1 种基金Innovative Research Team Development Plan of the Ministry of Education of China(IRT_17R56)supported by the Qing Lan Project of Jiangsu Province。
文摘The gut microbiome of plant-eaters is affected by the food they eat,but it is currently unclear how the plant metabolome and microbiome are influenced by the substrate the plant grows in and how this subsequently impacts the feeding behavior and gut microbiomes of insect herbivores.Here,we use Plutella xylostella caterpillars and show that the larvae prefer leaves of cabbage plants growing in a vermiculite substrate to those from plants growing in conventional soil systems.From a plant metabolomics analysis,we identified 20 plant metabolites that were related to caterpillar feeding performance.In a bioassay,the effects of these plant metabolites on insects'feeding were tested.Nitrate and compounds enriched with leaves of soilless cultivation promoted the feeding of insects,while compounds enriched with leaves of plants growing in natural soil decreased feeding.Several microbial groups(e.g.,Sporolactobacillus,Haliangium)detected inside the plant correlated with caterpillar feeding performance and other microbial groups,such as Ramlibacter and Methylophilus,correlated with the gut microbiome.Our results highlight the role of growth substrates on the food metabolome and microbiome and on the feeding performance and the gut microbiome of plant feeders.It illustrates how belowground factors can influence the aboveground properties of plant-animal systems,which has important implications for plant growth and pest control.
基金supported by National Natural Science Foundation of China (Grant No. 11801158)the Hunan Provincial Natural Science Foundation of China (Grant No. 2019JJ50040)+2 种基金the Fundamental Research Funds for the Central Universities in Chinasupported by National Natural Science Foundation of China (Grant No. 11871002)the General Program of Science and Technology of Beijing Municipal Education Commission (Grant No. KM201810005004)
文摘In this paper,we accomplish the unified convergence analysis of a second-order method of multipliers(i.e.,a second-order augmented Lagrangian method)for solving the conventional nonlinear conic optimization problems.Specifically,the algorithm that we investigate incorporates a specially designed nonsmooth(generalized)Newton step to furnish a second-order update rule for the multipliers.We first show in a unified fashion that under a few abstract assumptions,the proposed method is locally convergent and possesses a(nonasymptotic)superlinear convergence rate,even though the penalty parameter is fixed and/or the strict complementarity fails.Subsequently,we demonstrate that for the three typical scenarios,i.e.,the classic nonlinear programming,the nonlinear second-order cone programming and the nonlinear semidefinite programming,these abstract assumptions are nothing but exactly the implications of the iconic sufficient conditions that are assumed for establishing the Q-linear convergence rates of the method of multipliers without assuming the strict complementarity.
基金This work was supported by National Natural Science Foundation of China(81901006)Science and Technology Planning Project of Guangdong Province(2022A0505050038)+1 种基金Scientific Research Talent Cultivation Project of Stomatological Hospital,Southern Medical University(RC202005)Science Research Cultivation Program of Stomatological Hospital,Southern Medical University(PY2020002)。
文摘In a recent Cancer Discovery publication,Bianchi et al.unveil a crucial mechanism driving therapeutic resistance in pancreatic ductal adenocarcinoma(PDAC),orchestrated by cell-autonomous Cxcl1 and TNF from polymorphonuclear myeloid-derived suppressor cells(PMN-MDSCs).This insight provides fresh perspectives for surmounting such resistance in PDAC.1 PDAC represents a highly aggressive malignancy exhibiting substantial therapeutic resistance,attributable to factors such as intractable genomic aberrations,immunosuppression mediated by myeloid cells,and pro-inflammatory activation of cancerassociated fibroblasts.
