At present,the grape and cherry industries in Shandong are in the leading position in China and have driven the development of related high-end manufacturing industries such as wine,brandy,preserved fruit processing,f...At present,the grape and cherry industries in Shandong are in the leading position in China and have driven the development of related high-end manufacturing industries such as wine,brandy,preserved fruit processing,fruit juice processing and health products. Therefore,vigorously developing the grape and cherry industries in Shandong Province and carrying out development and innovation are important parts of Shandong Province in responding to the strategy of national new and old kinetic energy conversion. However,currently the germplasm resources preserved in the fruit tree resources banks in China are only 45% of those in the US and 27. 2% of those in the EU. Moreover,the development of fruit trees resources banks in Shandong is relatively backward in China,and there is still no banks related with grape and cherry germplasm resources in Shandong. Therefore,importance can be attached to the agriculture,forestry,and animal husbandry to build germplasm resources banks for grape and cherry industries in Shandong Province. Building the national-level grape and cherry germplasm resources bank in Shandong Province can also promote the utilization of wild and farm germplasm resources in the future; advance the research on the genes related to disease resistance,stress resistance and quality of grapes and cherries; push forward the construction and development of cherry and grape mutants banks. It is conducive to the research on the agronomic traits of grapes and cherries,and can provide the parents resources for planting innovation and improving the quality of grapes and cherries,as well as promote the development and application of molecular markers of grapes and cherries,including the identification of lines and crossbreeding. Thereby,it cannot only promote the industry development,but also achieve the development of cultivation,breeding and basic research in an all-round way and the development of " production,study and research" going side by side.展开更多
Shrimp(Penaeus vannamei)proteins have been shown an allergenic potential;however,little information is available on the sensitizing and eliciting capacity of shrimp protein digestion products.In this study,a BALB/c mi...Shrimp(Penaeus vannamei)proteins have been shown an allergenic potential;however,little information is available on the sensitizing and eliciting capacity of shrimp protein digestion products.In this study,a BALB/c mice model was used to explore the allergenicity of shrimp protein sample(SPS)and their gastric and gastrointestinal digestion products(GDS/GIDS).As compared with the SPS groups,the GDS/GIDS groups caused lower specific immunoglobulins(Ig E/Ig G1)levels(P<0.05),but higher than the control groups,indicating that the digestion products sensitized the mice.Meanwhile,spleen index,mouse mast cell protease-1(m MCP-1)concentration and proportion of degranulated mast cells were significantly reduced in the GDS/GIDS groups(P<0.05);simultaneously,allergic symptoms,vascular permeability and histopathological changes of tissues were alleviated.Nevertheless,the allergenicity of digestion products cannot be eliminated and still cause systemic allergic reactions in mice.The study showed that the digestion products of shrimp still had high sensitizing and eliciting capacity.展开更多
There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a prom...There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury.In this study,we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1(3D-CC-INEXOS) to improve traumatic brain injury repair and functional recove ry after traumatic brain injury in rats.Composite scaffolds comprising collagen,chitosan,and exosomes derived from neural stem cells pretreated with insulin-like growth fa ctor-1(INEXOS) continuously released exosomes for 2weeks.Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model,as assessed by the Morris water maze test and modified neurological seve rity scores.In addition,immunofluorescence staining and transmission electron microscopy showed that3D-CC-INExos implantation significantly improved the recove ry of damaged nerve tissue in the injured area.In conclusion,this study suggests that transplanted3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.展开更多
High-voltage LiCoO_(2)(LCO)offers a prelude to breaking the bottleneck of the energy density of lithium-ion batteries,however,LiCoO_(2)is subject to serious structural and interfacial degradation above voltages>4.5...High-voltage LiCoO_(2)(LCO)offers a prelude to breaking the bottleneck of the energy density of lithium-ion batteries,however,LiCoO_(2)is subject to serious structural and interfacial degradation above voltages>4.55 V(vs.Li/Li^(+)).Herein,an in-situ Li_(6.25)La_(3)Zr_(2)A_(l0.25)O_(12)(LLZAO)layer is constructed on the LCO surface to achieve operating voltage at 4.6 V.The detailed characterizations(ex-situ XRD,ex-situ Raman,DFT,etc.)reveal that the LLZAO layer greatly enhances Li+conductivity attributed to the ionconducting layer on the surface/interface,and closely combines with LiCoO_(2)particle to ensure stable cathode/electrolyte interface,thus suppressing the highly reactive Co^(4+)and O^(-)triggered surface side reactions at high-voltage.Moreover,the introduction of La^(3+)/Zr^(4+)/Al^(3+)with a larger ionic radius(La^(3+)/Zr^(4+)are larger than Co^(3+))and weaker electronegativity(La/Zr/Al are weaker than Co)into Co^(3+)sites readjusts the electron cloud density between Co–O–Li,which reinforces the Co–O bond and widens the band-center gap of Co 3d and O 2p,thus restraining the detrimental phase transition(from H3 to H1-3 phase)and the formation of Co_(3)O_(4)spinel phase(attributed to lattice oxygen release),subsequently alleviating the particle cracking and structural collapse during repeated Li^(+)de/intercalation.Therefore,after 100 cycles at 3.0–4.6 V,LCO@1.0LLZAO exhibits a superior discharge capacity of 188.5 m A h g^(-1),with a capacity retention of 85.1%.The above research has brought about meaningful guidance for the evolution of cathode materials with high voltage.展开更多
Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferropto...Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferroptosis is a recently discovered form of iron-dependent cell death that may have excellent prospect as chemosensitizer.The utilization of ferropotosis inducer Erastin could significantly mediate chemotherapy sensitization of Temozolomide and exert anti-tumor effects in glioblastoma.In this study,a combination of hydrogel-liposome nanoplatform encapsulatedwith Temozolomide and ferroptosis inducer Erastin was constructed.Theαvβ3 integrin-binding peptide cyclic RGD was utilized to modify codelivery system to achieve glioblastoma targeting strategy.As biocompatible drug reservoirs,cross-linked GelMA(gelatin methacrylamide)hydrogel and cRGD-coated liposome realized the sustained release of internal contents.In the modified intracranial tumor resection model,GelMA-liposome system achieved slow release of Temozolomide and Erastin in situ for more than 14 d.The results indicated that nanoplatform(T+E@LPs-cRGD+GelMA)improved glioblastoma sensitivity to chemotherapeutic temozolomide and exerted satisfactory anti-tumor effects.It was demonstrated that the induction of ferroptosis could be utilized as a therapeutic strategy to overcome drug resistance.Furthermore,transcriptome sequencing was conducted to reveal the underlying mechanism that the nanoplatform(T+E@LPs-cRGD+GelMA)implicated in.It is suggested that GelMA-liposome system participated in the immune response and immunomodulation of glioblastoma via interferon/PD-L1 pathway.Collectively,this study proposed a potential combinatory therapeutic strategy for glioblastoma treatment.展开更多
Because plant mechanical strength influences plant growth and development,the regulatory mechanisms underlying cell-wall synthesis deserve investigation.Rice mutants are useful for such research.We have identified a n...Because plant mechanical strength influences plant growth and development,the regulatory mechanisms underlying cell-wall synthesis deserve investigation.Rice mutants are useful for such research.We have identified a novel brittle culm 25(bc25)mutant with reduced growth and partial sterility.BC25 encodes an UDP-glucuronic acid decarboxylase involved in cellulose synthesis and belongs to the UXS family.A single-nucleotide mutation in BC25 accounts for its altered cell morphology and cellwall composition.Transmission electron microscopy analysis showed that the thickness of the secondary cell wall was reduced in bc25.Monosaccharide analysis revealed significant increases in content of rhamnose and arabinose but not of other monosaccharides,indicating that BC25 was involved in xylose synthesis with some level of functional redundancy.Enzymatic assays suggested that BC25 functions with high activity to interconvert UDP-glucuronic acid(UDP-Glc A)and UDP-xylose.GUS staining showed that BC25 was ubiquitously expressed with higher expression in culm,root and sheath,in agreement with that shown by quantitative real-time(q RT)-PCR.RNA-seq further suggested that BC25 is involved in sugar metabolism.We conclude that BC25 strongly influences rice cell wall formation.展开更多
This paper presents a comprehensive experimental study on the effect of extreme waves on a LNG carrier.The LNG carrier model was equipped with a variety of sensors to measure motions,green water height on deck as well...This paper presents a comprehensive experimental study on the effect of extreme waves on a LNG carrier.The LNG carrier model was equipped with a variety of sensors to measure motions,green water height on deck as well as local and global loads.Experiments in transient wave packets provided the general performance in waves in terms of response amplitude operators and were accompanied by tests in regular waves with two different wave steepness.These tests allowed detailed insights into the nonlinear behavior of the vertical wave bending moment in steep waves showing that green water on deck can contribute to a decrease of vertical wave bending moment.Afterwards,systematic model tests in irregular waves were performed to provide the basis for statistical analysis.It is shown that the generalized extreme value distribution model is suitable for the estimation of the extreme peak values of motions and loads.Finally,model tests in tailored extreme wave sequences were conducted comparing the results with the statistical analysis.For this purpose,analytical breather solutions of the nonlinear Schrödinger equation were applied to generate tailored extreme waves of certain critical wave lengths in terms of ship response.Besides these design extreme waves,the LGN carrier was also investigated in the model scale reproduction of the real-world Draupner wave.By comparing the motions,vertical wave bending moment,green water column and slamming pressures it is concluded that the breather solutions are a powerful and efficient tool for the generation of design extreme waves of certain critical wave lengths for wave/structure investigations on different subjects.展开更多
Colorectal cancer(CRC)has become a major threat to human health.Recent years,improvements have been seen in the treatment of advanced CRC with immune checkpoint inhibitors(ICIs).Nonetheless,sensitivity to ICIs notably...Colorectal cancer(CRC)has become a major threat to human health.Recent years,improvements have been seen in the treatment of advanced CRC with immune checkpoint inhibitors(ICIs).Nonetheless,sensitivity to ICIs notably varies among patients,thus greatly limiting clinical applications of ICIs in CRC.Hence,the identification of biomarkers that can accurately distinguish between ICI-sensitive and drug-resistant patients is of utmost importance.Such biomarkers are essential for selecting appropriate treatment regimens and achieving precision therapy(Figure 1).The biomarkers discussed below provide insights into the advancements made in this field(Table 1).展开更多
The existing Maximum Power Point Tracking(MPPT)method has low tracking efficiency and poor stability.It is easy to fall into the Local Maximum Power Point(LMPP)in Partial Shading Condition(PSC),resulting in the degrad...The existing Maximum Power Point Tracking(MPPT)method has low tracking efficiency and poor stability.It is easy to fall into the Local Maximum Power Point(LMPP)in Partial Shading Condition(PSC),resulting in the degradation of output power quality and efficiency.It was found that various bio-inspired MPPT based optimization algorithms employ different mechanisms,and their performance in tracking the Global Maximum Power Point(GMPP)varies.Thus,a Cuckoo search algorithm(CSA)combined with the Incremental conductance Algorithm(INC)is proposed(CSA-INC)is put forward for the MPPT method of photovoltaic power generation.The method can improve the tracking speed by more than 52%compared with the traditional Cuckoo Search Algorithm(CSA),and the results of the study using this algorithm are compared with the popular Particle Swarm Optimization(PSO)and the Gravitational Search Algorithm(GSA).CSA-INC has an average tracking efficiency of 99.99%and an average tracking time of 0.19 s when tracking the GMPP,which improves PV power generation’s efficiency and power quality.展开更多
MOOC (Massive Open Online Course)即“大规模在线开放课程”,采用在线的方式来实现基于互联网的课程学习、互动、共享和测试,它被认为是对传统高等教育模式和产业的颠覆性创新,近年来受到了教育界的高度关注。深入分析和研究MOOC模式...MOOC (Massive Open Online Course)即“大规模在线开放课程”,采用在线的方式来实现基于互联网的课程学习、互动、共享和测试,它被认为是对传统高等教育模式和产业的颠覆性创新,近年来受到了教育界的高度关注。深入分析和研究MOOC模式对高等教育带来的影响,既有利于高等教育的健康全面发展,也是MOOC本身可持续发展的需求。对MOOC课程对高等教育带来的改变、高等教育者应采取的态度和应对措施进行了分析,总结了在辅导学生选修MOOC课程和建设MOOC课程实践过程的一些体会,并对未来MOOC的发展进行了展望,旨在推动大规模在线开放课程实践的建设及运用。展开更多
Intestinal dysbiosis is now known to be a complication in a myriad of diseases.Fecal microbiota transplantation(FMT),as a microbiota-target therapy,is arguably very effective for curing Clostridium difficile infection...Intestinal dysbiosis is now known to be a complication in a myriad of diseases.Fecal microbiota transplantation(FMT),as a microbiota-target therapy,is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases.New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota.This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas,including metabolic diseases,neuropsychiatric disorders,autoimmune diseases,allergic disorders,and tumors.A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces,with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity,along with increased levels of butyrate-producing intestinal microbiota.Case reports of FMT have also shown favorable outcomes in Parkinson's disease,multiple sclerosis,myoclonus dystonia,chronic fatigue syndrome,and idiopathic thrombocytopenic purpura.FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.展开更多
Objective: Recent studies have shown that tumor-associated macrophages(TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis o...Objective: Recent studies have shown that tumor-associated macrophages(TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer(GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be clarified.Methods: THP-1 monocytes were induced by PMA/interleukin(IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation(Ch IP) assay were used to investigate the mechanism of transforming growth factor β2(TGFβ2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in vivo.Results: We found that Kindlin-2 expression was upregulated at both m RNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGFβ2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-кB. TAMs thus participated in the progression of GC through the TGFβ2/NF-κB/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in vivo.Conclusions: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGFβ2/NF-κB/Kindlin-2 axis, providing a possibility for new treatment options and approaches.展开更多
基金supported by the Agricultural scientific and technological innovation project of Shandong Academy of Agricultural Sciences(CXGC2016D01)Agricultural scientific and technological innovation project of Shandong Academy of Agricultural Sciences-cultivating project for National Natural Science Foundation of China in 2018"identification and function research of Vitis vinifera and Vitis amurensis cold stress response-related micro RNAs"+2 种基金Major Agricultural Application Technology Innovation Project of Shandong Province"Research and Application of Precision Control of Maturation and Product Innovation of Featured Brewing Grape"Major Agricultural Application Technology Innovation Project of Shandong Province"Development of Landmark Wines and Integrated Application of Key Technologies in Shandong Province"Fruit innovation team of modern agricultural industry technology system in Shandong Province-Jinan comprehensive test station(SDAIT-06-21)
文摘At present,the grape and cherry industries in Shandong are in the leading position in China and have driven the development of related high-end manufacturing industries such as wine,brandy,preserved fruit processing,fruit juice processing and health products. Therefore,vigorously developing the grape and cherry industries in Shandong Province and carrying out development and innovation are important parts of Shandong Province in responding to the strategy of national new and old kinetic energy conversion. However,currently the germplasm resources preserved in the fruit tree resources banks in China are only 45% of those in the US and 27. 2% of those in the EU. Moreover,the development of fruit trees resources banks in Shandong is relatively backward in China,and there is still no banks related with grape and cherry germplasm resources in Shandong. Therefore,importance can be attached to the agriculture,forestry,and animal husbandry to build germplasm resources banks for grape and cherry industries in Shandong Province. Building the national-level grape and cherry germplasm resources bank in Shandong Province can also promote the utilization of wild and farm germplasm resources in the future; advance the research on the genes related to disease resistance,stress resistance and quality of grapes and cherries; push forward the construction and development of cherry and grape mutants banks. It is conducive to the research on the agronomic traits of grapes and cherries,and can provide the parents resources for planting innovation and improving the quality of grapes and cherries,as well as promote the development and application of molecular markers of grapes and cherries,including the identification of lines and crossbreeding. Thereby,it cannot only promote the industry development,but also achieve the development of cultivation,breeding and basic research in an all-round way and the development of " production,study and research" going side by side.
基金financially supported by the National Natural Science Foundation of China(32022067)the Dalian Sci-Tech Talent Innovation Support Program(2022RY04)。
文摘Shrimp(Penaeus vannamei)proteins have been shown an allergenic potential;however,little information is available on the sensitizing and eliciting capacity of shrimp protein digestion products.In this study,a BALB/c mice model was used to explore the allergenicity of shrimp protein sample(SPS)and their gastric and gastrointestinal digestion products(GDS/GIDS).As compared with the SPS groups,the GDS/GIDS groups caused lower specific immunoglobulins(Ig E/Ig G1)levels(P<0.05),but higher than the control groups,indicating that the digestion products sensitized the mice.Meanwhile,spleen index,mouse mast cell protease-1(m MCP-1)concentration and proportion of degranulated mast cells were significantly reduced in the GDS/GIDS groups(P<0.05);simultaneously,allergic symptoms,vascular permeability and histopathological changes of tissues were alleviated.Nevertheless,the allergenicity of digestion products cannot be eliminated and still cause systemic allergic reactions in mice.The study showed that the digestion products of shrimp still had high sensitizing and eliciting capacity.
基金supported by the National Major Scientific and Technological Special Project for Significant New Drugs Development,No.2019ZX09301-147 (to LXZ)。
文摘There are various clinical treatments for traumatic brain injury,including surgery,drug therapy,and rehabilitation therapy;howeve r,the therapeutic effects are limited.Scaffolds combined with exosomes represent a promising but challenging method for improving the repair of traumatic brain injury.In this study,we determined the ability of a novel 3D-printed collagen/chitosan scaffold loaded with exosomes derived from neural stem cells pretreated with insulin-like growth factor-1(3D-CC-INEXOS) to improve traumatic brain injury repair and functional recove ry after traumatic brain injury in rats.Composite scaffolds comprising collagen,chitosan,and exosomes derived from neural stem cells pretreated with insulin-like growth fa ctor-1(INEXOS) continuously released exosomes for 2weeks.Transplantation of 3D-CC-INExos scaffolds significantly improved motor and cognitive functions in a rat traumatic brain injury model,as assessed by the Morris water maze test and modified neurological seve rity scores.In addition,immunofluorescence staining and transmission electron microscopy showed that3D-CC-INExos implantation significantly improved the recove ry of damaged nerve tissue in the injured area.In conclusion,this study suggests that transplanted3D-CC-INExos scaffolds might provide a potential strategy for the treatment of traumatic brain injury and lay a solid foundation for clinical translation.
基金supported by the Chongzuo Science and Technology Program Project Fund(No.FA20210713)。
文摘High-voltage LiCoO_(2)(LCO)offers a prelude to breaking the bottleneck of the energy density of lithium-ion batteries,however,LiCoO_(2)is subject to serious structural and interfacial degradation above voltages>4.55 V(vs.Li/Li^(+)).Herein,an in-situ Li_(6.25)La_(3)Zr_(2)A_(l0.25)O_(12)(LLZAO)layer is constructed on the LCO surface to achieve operating voltage at 4.6 V.The detailed characterizations(ex-situ XRD,ex-situ Raman,DFT,etc.)reveal that the LLZAO layer greatly enhances Li+conductivity attributed to the ionconducting layer on the surface/interface,and closely combines with LiCoO_(2)particle to ensure stable cathode/electrolyte interface,thus suppressing the highly reactive Co^(4+)and O^(-)triggered surface side reactions at high-voltage.Moreover,the introduction of La^(3+)/Zr^(4+)/Al^(3+)with a larger ionic radius(La^(3+)/Zr^(4+)are larger than Co^(3+))and weaker electronegativity(La/Zr/Al are weaker than Co)into Co^(3+)sites readjusts the electron cloud density between Co–O–Li,which reinforces the Co–O bond and widens the band-center gap of Co 3d and O 2p,thus restraining the detrimental phase transition(from H3 to H1-3 phase)and the formation of Co_(3)O_(4)spinel phase(attributed to lattice oxygen release),subsequently alleviating the particle cracking and structural collapse during repeated Li^(+)de/intercalation.Therefore,after 100 cycles at 3.0–4.6 V,LCO@1.0LLZAO exhibits a superior discharge capacity of 188.5 m A h g^(-1),with a capacity retention of 85.1%.The above research has brought about meaningful guidance for the evolution of cathode materials with high voltage.
基金supported by Natural Science Foundation of China(Grant NO.81972340,82173140,81871196)Shandong Provincial Natural Science Foundation,China(Grant No.ZR202010300086)Academic promotion program of Shandong First Medical University(Grant NO.2019LJ005)。
文摘Glioblastoma is acknowledged as the most aggressive cerebral tumor in adults.However,the efficacy of current standard therapy is seriously undermined by drug resistance and suppressive immune microenvironment.Ferroptosis is a recently discovered form of iron-dependent cell death that may have excellent prospect as chemosensitizer.The utilization of ferropotosis inducer Erastin could significantly mediate chemotherapy sensitization of Temozolomide and exert anti-tumor effects in glioblastoma.In this study,a combination of hydrogel-liposome nanoplatform encapsulatedwith Temozolomide and ferroptosis inducer Erastin was constructed.Theαvβ3 integrin-binding peptide cyclic RGD was utilized to modify codelivery system to achieve glioblastoma targeting strategy.As biocompatible drug reservoirs,cross-linked GelMA(gelatin methacrylamide)hydrogel and cRGD-coated liposome realized the sustained release of internal contents.In the modified intracranial tumor resection model,GelMA-liposome system achieved slow release of Temozolomide and Erastin in situ for more than 14 d.The results indicated that nanoplatform(T+E@LPs-cRGD+GelMA)improved glioblastoma sensitivity to chemotherapeutic temozolomide and exerted satisfactory anti-tumor effects.It was demonstrated that the induction of ferroptosis could be utilized as a therapeutic strategy to overcome drug resistance.Furthermore,transcriptome sequencing was conducted to reveal the underlying mechanism that the nanoplatform(T+E@LPs-cRGD+GelMA)implicated in.It is suggested that GelMA-liposome system participated in the immune response and immunomodulation of glioblastoma via interferon/PD-L1 pathway.Collectively,this study proposed a potential combinatory therapeutic strategy for glioblastoma treatment.
基金supported by the Key Research and Development Program of Zhejiang Province(2021C02056,2021C02063-6)the National Key Research and Development Program of China(2021YFD1200503)+1 种基金the Fundamental Research Funds for Central Public Welfare Research Institutes of China National Rice Research Institute(CPSIBRF-CNRRI-202101)Chinese Academy of Agricultural Sciences(CAAS-ASTIP-201X-CNRRI)。
文摘Because plant mechanical strength influences plant growth and development,the regulatory mechanisms underlying cell-wall synthesis deserve investigation.Rice mutants are useful for such research.We have identified a novel brittle culm 25(bc25)mutant with reduced growth and partial sterility.BC25 encodes an UDP-glucuronic acid decarboxylase involved in cellulose synthesis and belongs to the UXS family.A single-nucleotide mutation in BC25 accounts for its altered cell morphology and cellwall composition.Transmission electron microscopy analysis showed that the thickness of the secondary cell wall was reduced in bc25.Monosaccharide analysis revealed significant increases in content of rhamnose and arabinose but not of other monosaccharides,indicating that BC25 was involved in xylose synthesis with some level of functional redundancy.Enzymatic assays suggested that BC25 functions with high activity to interconvert UDP-glucuronic acid(UDP-Glc A)and UDP-xylose.GUS staining showed that BC25 was ubiquitously expressed with higher expression in culm,root and sheath,in agreement with that shown by quantitative real-time(q RT)-PCR.RNA-seq further suggested that BC25 is involved in sugar metabolism.We conclude that BC25 strongly influences rice cell wall formation.
基金the experimental work performed during the project EXTREME SEASwhich was funded by the European Commissionunder the Grant agreement No. 234175
文摘This paper presents a comprehensive experimental study on the effect of extreme waves on a LNG carrier.The LNG carrier model was equipped with a variety of sensors to measure motions,green water height on deck as well as local and global loads.Experiments in transient wave packets provided the general performance in waves in terms of response amplitude operators and were accompanied by tests in regular waves with two different wave steepness.These tests allowed detailed insights into the nonlinear behavior of the vertical wave bending moment in steep waves showing that green water on deck can contribute to a decrease of vertical wave bending moment.Afterwards,systematic model tests in irregular waves were performed to provide the basis for statistical analysis.It is shown that the generalized extreme value distribution model is suitable for the estimation of the extreme peak values of motions and loads.Finally,model tests in tailored extreme wave sequences were conducted comparing the results with the statistical analysis.For this purpose,analytical breather solutions of the nonlinear Schrödinger equation were applied to generate tailored extreme waves of certain critical wave lengths in terms of ship response.Besides these design extreme waves,the LGN carrier was also investigated in the model scale reproduction of the real-world Draupner wave.By comparing the motions,vertical wave bending moment,green water column and slamming pressures it is concluded that the breather solutions are a powerful and efficient tool for the generation of design extreme waves of certain critical wave lengths for wave/structure investigations on different subjects.
基金supported by the National Natural Science Foundation of China(Grant No.82272841).
文摘Colorectal cancer(CRC)has become a major threat to human health.Recent years,improvements have been seen in the treatment of advanced CRC with immune checkpoint inhibitors(ICIs).Nonetheless,sensitivity to ICIs notably varies among patients,thus greatly limiting clinical applications of ICIs in CRC.Hence,the identification of biomarkers that can accurately distinguish between ICI-sensitive and drug-resistant patients is of utmost importance.Such biomarkers are essential for selecting appropriate treatment regimens and achieving precision therapy(Figure 1).The biomarkers discussed below provide insights into the advancements made in this field(Table 1).
基金supported by the Natural Science Foundation of Gansu Province(Grant No.21JR7RA321)。
文摘The existing Maximum Power Point Tracking(MPPT)method has low tracking efficiency and poor stability.It is easy to fall into the Local Maximum Power Point(LMPP)in Partial Shading Condition(PSC),resulting in the degradation of output power quality and efficiency.It was found that various bio-inspired MPPT based optimization algorithms employ different mechanisms,and their performance in tracking the Global Maximum Power Point(GMPP)varies.Thus,a Cuckoo search algorithm(CSA)combined with the Incremental conductance Algorithm(INC)is proposed(CSA-INC)is put forward for the MPPT method of photovoltaic power generation.The method can improve the tracking speed by more than 52%compared with the traditional Cuckoo Search Algorithm(CSA),and the results of the study using this algorithm are compared with the popular Particle Swarm Optimization(PSO)and the Gravitational Search Algorithm(GSA).CSA-INC has an average tracking efficiency of 99.99%and an average tracking time of 0.19 s when tracking the GMPP,which improves PV power generation’s efficiency and power quality.
文摘MOOC (Massive Open Online Course)即“大规模在线开放课程”,采用在线的方式来实现基于互联网的课程学习、互动、共享和测试,它被认为是对传统高等教育模式和产业的颠覆性创新,近年来受到了教育界的高度关注。深入分析和研究MOOC模式对高等教育带来的影响,既有利于高等教育的健康全面发展,也是MOOC本身可持续发展的需求。对MOOC课程对高等教育带来的改变、高等教育者应采取的态度和应对措施进行了分析,总结了在辅导学生选修MOOC课程和建设MOOC课程实践过程的一些体会,并对未来MOOC的发展进行了展望,旨在推动大规模在线开放课程实践的建设及运用。
基金Supported by Grants(No.81470796 to Yan F,No.81070283 to Wang BM and No.81300272 to Cao HL)from the National Natural Science Foundation of Chinaa grant(No.20121202110018 to Wang BM)from the Research Fund for the Doctoral Program of Higher Education of Chinaa grant(No.13JCQNJC10600 to Cao HL)from Tianjin Research Program of Application Foundation and Advanced Technology of China
文摘Intestinal dysbiosis is now known to be a complication in a myriad of diseases.Fecal microbiota transplantation(FMT),as a microbiota-target therapy,is arguably very effective for curing Clostridium difficile infection and has good outcomes in other intestinal diseases.New insights have raised an interest in FMT for the management of extra-intestinal disorders associated with gut microbiota.This review shows that it is an exciting time in the burgeoning science of FMT application in previously unexpected areas,including metabolic diseases,neuropsychiatric disorders,autoimmune diseases,allergic disorders,and tumors.A randomized controlled trial was conducted on FMT in metabolic syndrome by infusing microbiota from lean donors or from self-collected feces,with the resultant findings showing that the lean donor feces group displayed increased insulin sensitivity,along with increased levels of butyrate-producing intestinal microbiota.Case reports of FMT have also shown favorable outcomes in Parkinson's disease,multiple sclerosis,myoclonus dystonia,chronic fatigue syndrome,and idiopathic thrombocytopenic purpura.FMT is a promising approach in the manipulation of the intestinal microbiota and has potential applications in a variety of extra-intestinal conditions associated with intestinal dysbiosis.
基金supported by grants from the National Natural Science Foundation of China (No. 81372291).
文摘Objective: Recent studies have shown that tumor-associated macrophages(TAMs) play an important role in cancer invasion and metastasis. Our previous studies have reported that TAMs promote the invasion and metastasis of gastric cancer(GC) cells through the Kindlin-2 pathway. However, the mechanism needs to be clarified.Methods: THP-1 monocytes were induced by PMA/interleukin(IL)-4/IL-13 to establish an efficient TAM model in vitro and M2 macrophages were isolated via flow cytometry. A dual luciferase reporter system and chromatin immunoprecipitation(Ch IP) assay were used to investigate the mechanism of transforming growth factor β2(TGFβ2) regulating Kindlin-2 expression. Immunohistochemistry was used to study the relationships among TAM infiltration in human GC tissues, Kindlin-2 protein expression, clinicopathological parameters and prognosis in human GC tissues. A nude mouse oncogenesis model was used to verify the invasion and metastasis mechanisms in vivo.Results: We found that Kindlin-2 expression was upregulated at both m RNA and protein levels in GC cells cocultured with TAMs, associated with higher invasion rate. Kindlin-2 knockdown reduced the invasion rate of GC cells under coculture condition. TGFβ2 secreted by TAMs regulated the expression of Kindlin-2 through the transcription factor NF-кB. TAMs thus participated in the progression of GC through the TGFβ2/NF-κB/Kindlin-2 axis. Kindlin-2 expression and TAM infiltration were significantly positively correlated with TNM stage, and patients with high Kindlin-2 expression had significantly poorer overall survival than patients with low Kindlin-2 expression. Furthermore, Kindlin-2 promoted the invasion of GC cells in vivo.Conclusions: This study elucidates the mechanism of TAMs participating in GC cell invasion and metastasis through the TGFβ2/NF-κB/Kindlin-2 axis, providing a possibility for new treatment options and approaches.
基金We thank members of our group for insightful discussion dur- ing the course of this study and Drs Haiming Wei and Zhigang Tian for NK92 cells. This work was supported by grants from National Natural Science Foundation of China （30972681 to XW 90508002 to XY+1 种基金 30872286 to LS）, Guangdong-NSFC Joint Key Program （to XW）, Chinese Academy of Sciences （KSCX1- YW-R65, KSCX2-YWH-10）, National Basic Research Program of China （973 Program） （2007CB512402 to XW 2007CB914503 and 2010CB912103 to XY）, Ministry of Science ＆ Technology of China International Collaboration Program （2009DFA31010 to XD）, China National Key Projects for Infectious Disease （2008ZX 10002-021 to XY）, 2007 National Undergraduate Innova- tive Research Program of China （PX） and KC Wong Education Foundation （ZG）.
文摘细胞毒素的淋巴细胞是在有缺点的房间的有免疫力的反应和消除的组织的关键播放器。我们以前报导了生来的杀手(NK ) 房间进入目标肿瘤房间，导致在肿瘤房间以内的任何一个目标房间死亡或自我毁灭。然而，它留下了至于在成为主观以后的 NK 房间的命运逃犯并且 heterotypic cell-in-cell 过程最近是否与同型的 cell-in-cell 事件的不同，说出 entosis。这里，我们证明 NK 房间在肿瘤房间以内与 apoptosis 的最终的命运经历一个 cell-in-cell 过程并且表明成为主观过程要求肌动朊细胞骨架管理者， ezrin。设想 NK 房间怎么进入肿瘤房间，我们执行了 NK 房间成为主观的即时双颜色成像分析进肿瘤房间。令人惊讶地，大多数 NK 房间在他们的入口以后承诺规划房间死亡进肿瘤房间，它与在同型的 cell-in-cell 过程观察的 entosis 区别地不同。使内在化的 NK 房间的 apoptotic 房间死亡由 caspase 的激活是明显的 3 并且 DNA 破碎。而且，在成为主观以后的 NK 房间死亡被 caspase 禁止者稀释， Z-VAD-FMK，在肿瘤房间以内作为 NK 房间死亡的模式证实 apoptosis。决定为 NK 房间的入口必要的蛋白质因素进肿瘤房间，我们执行了基于 siRNA 的击倒的分析并且在 NK 房间成为主观发现了 ezrin 的一个关键角色。重要地， ezrin 的调停 PKA 的 phosphorylation 支持 NK 房间成为主观过程。我们的调查结果建议 ezrin 由管理 NK 房间成为主观进肿瘤房间的新奇规章的机制。
