The invasive fall armyworm Spodoptera frugiperda(J.E.Smith)invaded Asia in 2018,colonizing the tropical and southern subtropical regions as well as migrating with the monsoons into Northeast Asia during spring and sum...The invasive fall armyworm Spodoptera frugiperda(J.E.Smith)invaded Asia in 2018,colonizing the tropical and southern subtropical regions as well as migrating with the monsoons into Northeast Asia during spring and summer.This has resulted in widespread infestations,with significant impacts on maize production in various Asian countries.Previous studies have shown that the invasion of this pest can alter the species relationships of maize pests,but the actual impact on maize pest management is still unclear.This study investigated the changes in maize pest occurrence and pesticide use in the annual breeding areas of S.frugiperda in Yunnan Province and the Guangxi Zhuang Autonomous Region of China during 2017-2021,based on surveys and interviews with small farmers in maize production.The results showed that S.frugiperda has emerged as the dominant species among maize pests after invasion and colonization,replacing traditional pests such as Ostrinia furnacalis,Spodoptera litura,Agrotis ypsilon,and Rhopalosiphum maidis.The variety of pesticides used for maize pest control has changed from chlorpyrifos,lambda-cyhalothrin,and acetamiprid to emamectin benzoate-based pesticides with high effectiveness against S.frugiperda.Furthermore,the frequency of maize pest chemical applications has increased from an average of 5.88 to 7.21 times per season,with the amounts of pesticides used in summer and autumn maize being significantly higher than in winter and spring maize,thereby increasing application costs by more than 35%.The results of this study clarified the impact of S.frugiperda invasion on maize pest community succession and chemical pesticide use in tropical and south subtropical China,thereby providing a baseline for modifying the regional control strategies for maize pests after the invasion of this relatively new pest.展开更多
Objective:Menage a trois 1(MAT1)is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulat...Objective:Menage a trois 1(MAT1)is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulation is responsible for diseases including cancers.To further explore the role of MAT1 in breast cancer,we investigated the pathways in which MAT1 might be involved,the association between MAT1 and molecular subtypes,and the role of MAT1 in clinical outcomes of breast cancer patients.Methods:We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells.Also,we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis,correlation analysis and prognosis analysis on public databases.Results:MAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling.Furthermore,MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor,and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both m RNA and protein levels.Correlation analysis revealed significant association between MAT1 m RNA amount and epithelial markers,mesenchymal markers,cancer stem cell markers,apoptosis markers,transcription markers and oncogenes.Consistently,the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor,vimentin,sex determining region Y-box 2 and sine oculis homeobox homolog 1.Importantly,Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival.Conclusions:MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.展开更多
Object: To investigate the VOCs from living Prunus persica flowers of different branches and their correlation with floral insects. Special, dominant and 20 VOCs were analysed from living Prunus persica flowers captur...Object: To investigate the VOCs from living Prunus persica flowers of different branches and their correlation with floral insects. Special, dominant and 20 VOCs were analysed from living Prunus persica flowers captured by closely and circularly headspace way in adsorbent tubes and ATD-GC/MS on 29 April in Wanbailin Ecological Garden, China. VOCs from high altitude tree are more than low altitude in sunny site, and floral volatile constituents from upslope branches are less than downslope of the same tree on high altitude. Special floral VOCs were alpha-dimethyl-benzenemethanol, isopropyl palmitate, ethylbenzene, p-xylene, acetophenone, 3-ethyl-2-methyl-Heptane on sunny slope, and propylene glycol, decanal, hexadecane on shady slope. Dominant VOCs founded during 8 temporal quanta were toluene, hexane, 2-ethyl-1-hexanol, dodecane, pentadecane. Floral VOCs’ number from sunny slope was significantly negative correlated with flower-visiting insect community richness, abundance, diversity on sunny or shady slope, which from shady slope was significantly positive correlated with flower-visiting insect community parameters on both slopes tried dividing insects visiting floral branches from Prunus persica in sunny site with n/2 + 1 or n/2 - 1, and shady site with n/2 before sampled volatiles day. On sampled volatiles day, 2-ethyl-1-hexanol from sunny slope was significantly positive correlated with flower-visiting insect community parameters on shady slope (P Prunus persica on sunny slope, and even floral branches kept on shady slope.展开更多
Immunotherapy,particularly with immune checkpoint inhibitors,has significantly transformed cancer treatment.Despite its success,many patients struggle to respond adequately or sustain long-lasting clinical improvement...Immunotherapy,particularly with immune checkpoint inhibitors,has significantly transformed cancer treatment.Despite its success,many patients struggle to respond adequately or sustain long-lasting clinical improvement.A growing consensus has emerged that radiotherapy(RT)enhances the response rate and overall efficacy of immunotherapy.Although combining RT and immunotherapy has been extensively investigated in preclinical models and has shown promising results,establishing itself as a dynamic and thriving area of research,clinical evidence for this combination strategy over the past five years has shown both positive and disappointing results,suggesting the need for a more nuanced understanding.This review provides a balanced and updated analysis of the combination of immunotherapy and RT.We summarized the preclinical mechanisms through which RT boosts antitumor immune responses andmainly focused on the outcomes of recently updated clinical trials,including those that may not have met expectations.We investigated the optimization of the therapeutic potential of this combined strategy,including key challenges,such as fractionation and scheduling,lymph node irradiation,and toxicity.Finally,we offered insights into the prospects and challenges associated with the clinical translation of this combination therapy,providing a realistic perspective on the current state of research and potential future directions.展开更多
Cytokines are critical in regulating immune responses and cellular behavior,playing dual roles in both normal physiology and the pathology of diseases such as cancer.These molecules,including interleukins,interferons,...Cytokines are critical in regulating immune responses and cellular behavior,playing dual roles in both normal physiology and the pathology of diseases such as cancer.These molecules,including interleukins,interferons,tumor necrosis factors,chemokines,and growth factors like TGF-β,VEGF,and EGF,can promote or inhibit tumor growth,influence the tumor microenvironment,and impact the efficacy of cancer treatments.Recent advances in targeting these pathways have shown promising therapeutic potential,offering new strategies to modulate the immune system,inhibit tumor progression,and overcome resistance to conventional therapies.In this review,we summarized the current understanding and therapeutic implications of targeting cytokine and chemokine signaling pathways in cancer.By exploring the roles of these molecules in tumor biology and the immune response,we highlighted the development of novel therapeutic agents aimed at modulating these pathways to combat cancer.The review elaborated on the dual nature of cytokines as both promoters and suppressors of tumorigenesis,depending on the context,and discussed the challenges and opportunities this presents for therapeutic intervention.We also examined the latest advancements in targeted therapies,including monoclonal antibodies,bispecific antibodies,receptor inhibitors,fusion proteins,engineered cytokine variants,and their impact on tumor growth,metastasis,and the tumor microenvironment.Additionally,we evaluated the potential of combining these targeted therapies with other treatment modalities to overcome resistance and improve patient outcomes.Besides,we also focused on the ongoing research and clinical trials that are pivotal in advancing our understanding and application of cytokine-and chemokine-targeted therapies for cancer patients.展开更多
The NOTCH gene was identified approximately 110 years ago.Classical studies have revealed that NOTCH signaling is an evolutionarily conserved pathway.NOTCH receptors undergo three cleavages and translocate into the nu...The NOTCH gene was identified approximately 110 years ago.Classical studies have revealed that NOTCH signaling is an evolutionarily conserved pathway.NOTCH receptors undergo three cleavages and translocate into the nucleus to regulate the transcription of target genes.NOTCH signaling deeply participates in the development and homeostasis of multiple tissues and organs,the aberration of which results in cancerous and noncancerous diseases.However,recent studies indicate that the outcomes of NOTCH signaling are changeable and highly dependent on context.In terms of cancers,NOTCH signaling can both promote and inhibit tumor development in various types of cancer.The overall performance of NOTCH-targeted therapies in clinical trials has failed to meet expectations.Additionally,NOTCH mutation has been proposed as a predictive biomarker for immune checkpoint blockade therapy in many cancers.Collectively,the NOTCH pathway needs to be integrally assessed with new perspectives to inspire discoveries and applications.In this review,we focus on both classical and the latest findings related to NOTCH signaling to illustrate the history,architecture,regulatory mechanisms,contributions to physiological development,related diseases,and therapeutic applications of the NOTCH pathway.The contributions of NOTCH signaling to the tumor immune microenvironment and cancer immunotherapy are also highlighted.We hope this review will help not only beginners but also experts to systematically and thoroughly understand the NOTCH signaling pathway.展开更多
Tumor-associated macrophages have emerged as crucial factors for metastases.Microglia are indispensable components of the brain microenvironment and play vital roles in brain metastasis(BM).However,the underlying mech...Tumor-associated macrophages have emerged as crucial factors for metastases.Microglia are indispensable components of the brain microenvironment and play vital roles in brain metastasis(BM).However,the underlying mechanism of how activated microglia promote brain metastasis of non-small cell lung cancer(NSCLC)remains elusive.展开更多
While CrylAc has been known to bind with larval midgut proteins cad- herin, APN (amino peptidase N), ALP (alkaline phosphatase) and ABCC2 (adenosine triphosphate-binding cassette transporter subfamily C2), littl...While CrylAc has been known to bind with larval midgut proteins cad- herin, APN (amino peptidase N), ALP (alkaline phosphatase) and ABCC2 (adenosine triphosphate-binding cassette transporter subfamily C2), little is known about the recep- tors of Cry2Ab. To provide a clue to the receptors of Cry2Ab, we tested the baseline cytotoxicity of activated Cry 1Ac and Cry2Ab against the midgut and fat body cell lines of Helicoverpa zea and the ovary cell line ofSpodopterafrugiperda (SFg). As expected, the descending order of cytotoxicity of CrylAc against the three cell lines in terms of 50% lethal concetration (LC50) was midgut (31.0μg/mL) 〉 fat body (59.0μg/mL) and SF9 cell (99.6μg/mL). By contrast, the fat body cell line (LC50 = 7.55μg/mL) was about twice more susceptible to Cry2Ab than the midgut cell line (16.0/xg/mL), the susceptibility of which was not significantly greater than that of SF9 cells (27.0μg/mL). Further, ligand blot showed the binding differences between CrylAc and Cry2Ab in the three cell lines. These results indicated that the receptors of Cry2Ab were enriched in fat body cells and thus largely different from the receptors of CrylAc, which were enriched in midgut cells.展开更多
To ensure safe use of genetically modified organisms(GMOs),since 1993,China has made great efforts to establish and improve the safety regulatory system for GMOs.Here,we summarize and analyze the regulatory framework ...To ensure safe use of genetically modified organisms(GMOs),since 1993,China has made great efforts to establish and improve the safety regulatory system for GMOs.Here,we summarize and analyze the regulatory framework of agricultural GMOs,and the progress in regulatory approval of GM crops in China.In general,the development of GMO safety regulations underwent four stages:exploration(1993–2000),development(2001–2010),improvement(2011–2020)and current(2021-present)stage.The first formal regulation was promulgated in 1993,which provided a basis for further development of the regulations,during the exploration stage,when insect-resistant GM cotton,expressing genes from Bacillus thuringiensis(Bt),was approved for cultivation.During the development stage,the Chinese government issued a series of administrative measures,which covered almost all the fields relative to GMO safety when the basic regulatory system was established.Along with the controversy over GMO safety,the regulations have been further,and greatly improved,during improvement stage.From 2021,a few additional revisions have been made,and meanwhile,the new regulation on gene-edited crops was introduced with the development of biotechnology,forming a relative complete regulation and law system for China.The well-developed GMO regulations establishes a firm basis for safe use of GM crops in China.Currently,GM cotton and GM papaya have been widely grown on a large scale in China that have brought great economic and ecological benefits.In addition,12 corn events,3 soybean events,and 2 rice events have also obtained biosafety certification,but presently,these lines have yet to enter commercial production.However,several GM soybean and corn events have entered pilot industrialization,and can soon be expected to be commercially grown in China.In addition to planting,six GM crops,including soybean,corn,cotton,canola,papaya and sugar beet,with a total of 64 events,have been approved for import as processing material in China.展开更多
The importance of food security,especially in combating the problem of acute hunger,has been underscored as a key component of sustainable development.Considering the major challenge of rapidly increasing demands for ...The importance of food security,especially in combating the problem of acute hunger,has been underscored as a key component of sustainable development.Considering the major challenge of rapidly increasing demands for both food security and safety,the management and control of major pests is urged to secure supplies of major agricultural products.However,owing to global climate change,biological invasion(e.g.,fall armyworm),decreasing agricultural biodiversity,and other factors,a wide range of crop pest outbreaks are becoming more frequent and serious,making China,one of the world’s largest country in terms of agricultural production,one of the primary victims of crop yield loss and the largest pesticide consumer in the world.Nevertheless,the use of science and technology in monitoring and early warning of major crop pests provides better pest management and acts as a fundamental part of an integrated plant protection strategy to achieve the goal of sustainable development of agriculture.This review summarizes the most fundamental information on pest monitoring and early warning in China by documenting the developmental history of research and application,Chinese laws and regulations related to plant protection,and the National Monitoring and Early Warning System,with the purpose of presenting the Chinese model as an example of how to promote regional management of crop pests,especially of cross border pests such as fall armyworm and locust,by international cooperation across pest-related countries.展开更多
In recent years,accumulating evidence has elucidated the role of lysosomes in dynamically regulating cellular and organismal homeostasis.Lysosomal changes and dysfunction have been correlated with the development of n...In recent years,accumulating evidence has elucidated the role of lysosomes in dynamically regulating cellular and organismal homeostasis.Lysosomal changes and dysfunction have been correlated with the development of numerous diseases.In this review,we interpreted the key biological functions of lysosomes in four areas:cellular metabolism,cell proliferation and differentiation,immunity,and cell death.More importantly,we actively sought to determine the characteristic changes and dysfunction of lysosomes in cells affected by these diseases,the causes of these changes and dysfunction,and their significance to the development and treatment of human disease.Furthermore,we outlined currently available targeting strategies:(1)targeting lysosomal acidification;(2)targeting lysosomal cathepsins;(3)targeting lysosomal membrane permeability and integrity;(4)targeting lysosomal calcium signaling;(5)targeting mTOR signaling;and(6)emerging potential targeting strategies.Moreover,we systematically summarized the corresponding drugs and their application in clinical trials.By integrating basic research with clinical findings,we discussed the current opportunities and challenges of targeting lysosomes in human disease.展开更多
The diamondback moth,Plutella xylostella(L.),is one of the most destructive migratory pest species of cruciferous vegetables worldwide and has developed resistance to most of the insecticides used for its control.The ...The diamondback moth,Plutella xylostella(L.),is one of the most destructive migratory pest species of cruciferous vegetables worldwide and has developed resistance to most of the insecticides used for its control.The migration regularity,migratory behavior,and relationship between flight and reproduction of P.xylostella have been widely reported.However,the effect of migration on insecticide resistance in this pest is still unclear.In this study,the effect of migration on P.xylostella resistance to seven insecticides was investigated using populations across the Bohai Sea that were collected in the early and late seasons during 2017–2019.The bioassay results showed that the early season populations of P.xylostella from south China possessed much higher resistance to insecticides because of intensive insecticide application;alternatively,the late season populations migrated from northeast China,where the insecticides were only used occasionally,showed much lower insecticide resistance.The genome re-sequencing results revealed that,among the eight mutations involved in insecticide resistance,the frequencies of two acetylcholinesterase mutations(A298S and G324A)responsible for organophosphorus insecticide resistance were significantly decreased in the late season populations.The results indicated that P.xylostella migration between tropical and temperate regions significantly delayed the development of insecticide resistance.These findings illustrated the effect of regional migration on the evolution of insecticide resistance in P.xylostella,and provided foundational information for further research on the relationship between migration and insecticide resistance development in other insects.展开更多
Evolution of resistance to Cry proteins in multiple pest insects has been threatening the sustainable use of Bacillus thuringiensis(Bt)-transgenic crops.Better understanding about the mechanism of resistance to Cry pr...Evolution of resistance to Cry proteins in multiple pest insects has been threatening the sustainable use of Bacillus thuringiensis(Bt)-transgenic crops.Better understanding about the mechanism of resistance to Cry proteins in insects is needed.Our preliminary study reported that the transcription of HaABCC3 was significantly decreased in a near-isogenic line(LFC2)of a Cry1Ac-resistant strain(LF60)of the global pest Helicoverpa armigera.However,the causality between HaABCC3 downregulation and resistance to Cry1Ac remains to be verified,and the regulatory mechanism underlying the HaABCC3 downregulation is still unclear.In this study,our data showed that both HaABCC3 and HaABCC3 downregulation were genetically linked to resistance to Cry1Ac in LF60.However,no InDels were observed in the coding sequence of HaABCC3 from LF60.Furthermore,F_(1) offspring from the cross of LF60 and a HaABCC2/3-knockout mutant exhibited moderate resistance to Cry1Ac toxin;this indicated that the high resistance to CrylAc toxin in LF60 may have resulted from multiple genetic factors,including HaABCC2 missplicing and HaABCC3 downregulation.Results from luciferase reporter assays showed that promoter activity of HaABCC3 in LF60 was significantly lower than that in the susceptible strain,which indicated that HaABCC3 downregulation was likely mediated by promoter variation.Consistently,multiple variations of the GATA-or FoxA-binding sites in the promoter region of HaABCC3 were identified.Collectively,all results in this study suggested that the downregulation of HaABCC3 observed in the H.armigera LF60 strain,which is resistant to CrylAc,may be mediated by a cis-regulatory mechanism.展开更多
The cotton bollworm,Helicoverpa armigera,is set to become the most economically devastating crop pest in the world,threatening food security and biosafety as its range expands across the globe.Key to understanding the...The cotton bollworm,Helicoverpa armigera,is set to become the most economically devastating crop pest in the world,threatening food security and biosafety as its range expands across the globe.Key to understanding the eco-evolutionary dynamics of H.armigera,and thus its management,is an understanding of population connectivity and the adaptations that allow the pest to establish in unique environments.We assembled a chromosome-scale reference genome and re-sequenced 503 individuals spanning the species range to delineate global patterns of connectivity,uncovering a previously cryptic population structure.展开更多
China is the largest agricultural producer in the world.Reducing yield losses caused by pests is an important issue and major challenge for China,especially when confronting global climate change,biological invasions ...China is the largest agricultural producer in the world.Reducing yield losses caused by pests is an important issue and major challenge for China,especially when confronting global climate change,biological invasions and declining agricultural biodiversity of recent decades.Wang et al.(this issue)summarized the impacts of changing climate on two staple crops in China,wheat and rice(https://doi.org/FASE-2021432).展开更多
It has been well established that the gut microbiota has a substantial influence on the host immune system.By crosstalk between specific microorganism-associated molecular patterns and the immune system,in addition to...It has been well established that the gut microbiota has a substantial influence on the host immune system.By crosstalk between specific microorganism-associated molecular patterns and the immune system,in addition to bacterial metabolic activity,gut microbiota regulates local or systemic inflammation(1).Recently,the composition of gut microbiota has been presumed to be one of the factors affecting the cancer-immune set point of cancer patients,which subsequently determines the efficacy of immune checkpoint inhibitor(ICI)treatment(2).展开更多
基金supported by the Lingnan Modern Agriculture Project China(NT2021003)the earmarked fund for China Agricultural Research System(CARS-02)。
文摘The invasive fall armyworm Spodoptera frugiperda(J.E.Smith)invaded Asia in 2018,colonizing the tropical and southern subtropical regions as well as migrating with the monsoons into Northeast Asia during spring and summer.This has resulted in widespread infestations,with significant impacts on maize production in various Asian countries.Previous studies have shown that the invasion of this pest can alter the species relationships of maize pests,but the actual impact on maize pest management is still unclear.This study investigated the changes in maize pest occurrence and pesticide use in the annual breeding areas of S.frugiperda in Yunnan Province and the Guangxi Zhuang Autonomous Region of China during 2017-2021,based on surveys and interviews with small farmers in maize production.The results showed that S.frugiperda has emerged as the dominant species among maize pests after invasion and colonization,replacing traditional pests such as Ostrinia furnacalis,Spodoptera litura,Agrotis ypsilon,and Rhopalosiphum maidis.The variety of pesticides used for maize pest control has changed from chlorpyrifos,lambda-cyhalothrin,and acetamiprid to emamectin benzoate-based pesticides with high effectiveness against S.frugiperda.Furthermore,the frequency of maize pest chemical applications has increased from an average of 5.88 to 7.21 times per season,with the amounts of pesticides used in summer and autumn maize being significantly higher than in winter and spring maize,thereby increasing application costs by more than 35%.The results of this study clarified the impact of S.frugiperda invasion on maize pest community succession and chemical pesticide use in tropical and south subtropical China,thereby providing a baseline for modifying the regional control strategies for maize pests after the invasion of this relatively new pest.
基金supported by the National Natural Science Foundation of China (Grant No.81572608 and 81172422)the Wuhan Science and Technology Bureau (Grant No.2017060201010170)
文摘Objective:Menage a trois 1(MAT1)is a targeting subunit of cyclin-dependent kinase-activating kinase and general transcription factor IIH kinase,which modulates cell cycle,transcription and DNA repair.Its dysregulation is responsible for diseases including cancers.To further explore the role of MAT1 in breast cancer,we investigated the pathways in which MAT1 might be involved,the association between MAT1 and molecular subtypes,and the role of MAT1 in clinical outcomes of breast cancer patients.Methods:We conducted immunohistochemistry staining on tissue microarray and immunofluorescence staining on sections of MAT1 stable breast cancer cells.Also,we performed Kyoto Encyclopedia of Genes and Genomes pathway analysis,correlation analysis and prognosis analysis on public databases.Results:MAT1 was involved in multiple pathways including normal physiology signaling and disease-related signaling.Furthermore,MAT1 positively correlated with the protein status of estrogen receptor and progesterone receptor,and was enriched in luminal-type and human epidermal growth factor receptor 2-enriched breast cancer in comparison with basal-like subtype at both m RNA and protein levels.Correlation analysis revealed significant association between MAT1 m RNA amount and epithelial markers,mesenchymal markers,cancer stem cell markers,apoptosis markers,transcription markers and oncogenes.Consistently,the results of immunofluorescence stain indicated that MAT1 overexpression enhanced the protein abundance of epidermal growth factor receptor,vimentin,sex determining region Y-box 2 and sine oculis homeobox homolog 1.Importantly,Kaplan-Meier Plotter analysis reflected that MAT1 could serve as a prognostic biomarker predicting worse relapse-free survival and metastasis-free survival.Conclusions:MAT1 is correlated with molecular subtypes and is associated with unfavorable prognosis for breast cancer patients.
文摘Object: To investigate the VOCs from living Prunus persica flowers of different branches and their correlation with floral insects. Special, dominant and 20 VOCs were analysed from living Prunus persica flowers captured by closely and circularly headspace way in adsorbent tubes and ATD-GC/MS on 29 April in Wanbailin Ecological Garden, China. VOCs from high altitude tree are more than low altitude in sunny site, and floral volatile constituents from upslope branches are less than downslope of the same tree on high altitude. Special floral VOCs were alpha-dimethyl-benzenemethanol, isopropyl palmitate, ethylbenzene, p-xylene, acetophenone, 3-ethyl-2-methyl-Heptane on sunny slope, and propylene glycol, decanal, hexadecane on shady slope. Dominant VOCs founded during 8 temporal quanta were toluene, hexane, 2-ethyl-1-hexanol, dodecane, pentadecane. Floral VOCs’ number from sunny slope was significantly negative correlated with flower-visiting insect community richness, abundance, diversity on sunny or shady slope, which from shady slope was significantly positive correlated with flower-visiting insect community parameters on both slopes tried dividing insects visiting floral branches from Prunus persica in sunny site with n/2 + 1 or n/2 - 1, and shady site with n/2 before sampled volatiles day. On sampled volatiles day, 2-ethyl-1-hexanol from sunny slope was significantly positive correlated with flower-visiting insect community parameters on shady slope (P Prunus persica on sunny slope, and even floral branches kept on shady slope.
基金National Natural Science Foundation of China,Grant/Award Numbers:82073370,82272794。
文摘Immunotherapy,particularly with immune checkpoint inhibitors,has significantly transformed cancer treatment.Despite its success,many patients struggle to respond adequately or sustain long-lasting clinical improvement.A growing consensus has emerged that radiotherapy(RT)enhances the response rate and overall efficacy of immunotherapy.Although combining RT and immunotherapy has been extensively investigated in preclinical models and has shown promising results,establishing itself as a dynamic and thriving area of research,clinical evidence for this combination strategy over the past five years has shown both positive and disappointing results,suggesting the need for a more nuanced understanding.This review provides a balanced and updated analysis of the combination of immunotherapy and RT.We summarized the preclinical mechanisms through which RT boosts antitumor immune responses andmainly focused on the outcomes of recently updated clinical trials,including those that may not have met expectations.We investigated the optimization of the therapeutic potential of this combined strategy,including key challenges,such as fractionation and scheduling,lymph node irradiation,and toxicity.Finally,we offered insights into the prospects and challenges associated with the clinical translation of this combination therapy,providing a realistic perspective on the current state of research and potential future directions.
基金This work was supported by the National Natural Science Foundation of China(Nos.82373281 and 82272794)Natural Science Foundation of Zhejiang Province(Nos.LQ24H160007 and LZ22H160005)China Postdoctoral Science Foundation(Nos.GZB20230642,2022M722766,and 2023M743016).
文摘Cytokines are critical in regulating immune responses and cellular behavior,playing dual roles in both normal physiology and the pathology of diseases such as cancer.These molecules,including interleukins,interferons,tumor necrosis factors,chemokines,and growth factors like TGF-β,VEGF,and EGF,can promote or inhibit tumor growth,influence the tumor microenvironment,and impact the efficacy of cancer treatments.Recent advances in targeting these pathways have shown promising therapeutic potential,offering new strategies to modulate the immune system,inhibit tumor progression,and overcome resistance to conventional therapies.In this review,we summarized the current understanding and therapeutic implications of targeting cytokine and chemokine signaling pathways in cancer.By exploring the roles of these molecules in tumor biology and the immune response,we highlighted the development of novel therapeutic agents aimed at modulating these pathways to combat cancer.The review elaborated on the dual nature of cytokines as both promoters and suppressors of tumorigenesis,depending on the context,and discussed the challenges and opportunities this presents for therapeutic intervention.We also examined the latest advancements in targeted therapies,including monoclonal antibodies,bispecific antibodies,receptor inhibitors,fusion proteins,engineered cytokine variants,and their impact on tumor growth,metastasis,and the tumor microenvironment.Additionally,we evaluated the potential of combining these targeted therapies with other treatment modalities to overcome resistance and improve patient outcomes.Besides,we also focused on the ongoing research and clinical trials that are pivotal in advancing our understanding and application of cytokine-and chemokine-targeted therapies for cancer patients.
基金the National Natural Science Foundation of China(No.62131009,82072597,81874120,and 82073370).
文摘The NOTCH gene was identified approximately 110 years ago.Classical studies have revealed that NOTCH signaling is an evolutionarily conserved pathway.NOTCH receptors undergo three cleavages and translocate into the nucleus to regulate the transcription of target genes.NOTCH signaling deeply participates in the development and homeostasis of multiple tissues and organs,the aberration of which results in cancerous and noncancerous diseases.However,recent studies indicate that the outcomes of NOTCH signaling are changeable and highly dependent on context.In terms of cancers,NOTCH signaling can both promote and inhibit tumor development in various types of cancer.The overall performance of NOTCH-targeted therapies in clinical trials has failed to meet expectations.Additionally,NOTCH mutation has been proposed as a predictive biomarker for immune checkpoint blockade therapy in many cancers.Collectively,the NOTCH pathway needs to be integrally assessed with new perspectives to inspire discoveries and applications.In this review,we focus on both classical and the latest findings related to NOTCH signaling to illustrate the history,architecture,regulatory mechanisms,contributions to physiological development,related diseases,and therapeutic applications of the NOTCH pathway.The contributions of NOTCH signaling to the tumor immune microenvironment and cancer immunotherapy are also highlighted.We hope this review will help not only beginners but also experts to systematically and thoroughly understand the NOTCH signaling pathway.
基金This work was supported by the National Natural Science Foundation of China(Grant no.81773360)the Engineering Research Center Innovation Capacity Building Project of Hubei(Grant no.2018-420114-35-03-071705)the National Independent Innovation Fund(Grant no.5003540112).
文摘Tumor-associated macrophages have emerged as crucial factors for metastases.Microglia are indispensable components of the brain microenvironment and play vital roles in brain metastasis(BM).However,the underlying mechanism of how activated microglia promote brain metastasis of non-small cell lung cancer(NSCLC)remains elusive.
文摘While CrylAc has been known to bind with larval midgut proteins cad- herin, APN (amino peptidase N), ALP (alkaline phosphatase) and ABCC2 (adenosine triphosphate-binding cassette transporter subfamily C2), little is known about the recep- tors of Cry2Ab. To provide a clue to the receptors of Cry2Ab, we tested the baseline cytotoxicity of activated Cry 1Ac and Cry2Ab against the midgut and fat body cell lines of Helicoverpa zea and the ovary cell line ofSpodopterafrugiperda (SFg). As expected, the descending order of cytotoxicity of CrylAc against the three cell lines in terms of 50% lethal concetration (LC50) was midgut (31.0μg/mL) 〉 fat body (59.0μg/mL) and SF9 cell (99.6μg/mL). By contrast, the fat body cell line (LC50 = 7.55μg/mL) was about twice more susceptible to Cry2Ab than the midgut cell line (16.0/xg/mL), the susceptibility of which was not significantly greater than that of SF9 cells (27.0μg/mL). Further, ligand blot showed the binding differences between CrylAc and Cry2Ab in the three cell lines. These results indicated that the receptors of Cry2Ab were enriched in fat body cells and thus largely different from the receptors of CrylAc, which were enriched in midgut cells.
基金supported by the National Special Biological Breeding Program of the People’s Republic of China.
文摘To ensure safe use of genetically modified organisms(GMOs),since 1993,China has made great efforts to establish and improve the safety regulatory system for GMOs.Here,we summarize and analyze the regulatory framework of agricultural GMOs,and the progress in regulatory approval of GM crops in China.In general,the development of GMO safety regulations underwent four stages:exploration(1993–2000),development(2001–2010),improvement(2011–2020)and current(2021-present)stage.The first formal regulation was promulgated in 1993,which provided a basis for further development of the regulations,during the exploration stage,when insect-resistant GM cotton,expressing genes from Bacillus thuringiensis(Bt),was approved for cultivation.During the development stage,the Chinese government issued a series of administrative measures,which covered almost all the fields relative to GMO safety when the basic regulatory system was established.Along with the controversy over GMO safety,the regulations have been further,and greatly improved,during improvement stage.From 2021,a few additional revisions have been made,and meanwhile,the new regulation on gene-edited crops was introduced with the development of biotechnology,forming a relative complete regulation and law system for China.The well-developed GMO regulations establishes a firm basis for safe use of GM crops in China.Currently,GM cotton and GM papaya have been widely grown on a large scale in China that have brought great economic and ecological benefits.In addition,12 corn events,3 soybean events,and 2 rice events have also obtained biosafety certification,but presently,these lines have yet to enter commercial production.However,several GM soybean and corn events have entered pilot industrialization,and can soon be expected to be commercially grown in China.In addition to planting,six GM crops,including soybean,corn,cotton,canola,papaya and sugar beet,with a total of 64 events,have been approved for import as processing material in China.
基金This study was supported by the National Natural Science Foundation of China(31727901 and 31901873).
文摘The importance of food security,especially in combating the problem of acute hunger,has been underscored as a key component of sustainable development.Considering the major challenge of rapidly increasing demands for both food security and safety,the management and control of major pests is urged to secure supplies of major agricultural products.However,owing to global climate change,biological invasion(e.g.,fall armyworm),decreasing agricultural biodiversity,and other factors,a wide range of crop pest outbreaks are becoming more frequent and serious,making China,one of the world’s largest country in terms of agricultural production,one of the primary victims of crop yield loss and the largest pesticide consumer in the world.Nevertheless,the use of science and technology in monitoring and early warning of major crop pests provides better pest management and acts as a fundamental part of an integrated plant protection strategy to achieve the goal of sustainable development of agriculture.This review summarizes the most fundamental information on pest monitoring and early warning in China by documenting the developmental history of research and application,Chinese laws and regulations related to plant protection,and the National Monitoring and Early Warning System,with the purpose of presenting the Chinese model as an example of how to promote regional management of crop pests,especially of cross border pests such as fall armyworm and locust,by international cooperation across pest-related countries.
基金This research was financially supported by the National Natural Science Foundation of China(No.82073095).
文摘In recent years,accumulating evidence has elucidated the role of lysosomes in dynamically regulating cellular and organismal homeostasis.Lysosomal changes and dysfunction have been correlated with the development of numerous diseases.In this review,we interpreted the key biological functions of lysosomes in four areas:cellular metabolism,cell proliferation and differentiation,immunity,and cell death.More importantly,we actively sought to determine the characteristic changes and dysfunction of lysosomes in cells affected by these diseases,the causes of these changes and dysfunction,and their significance to the development and treatment of human disease.Furthermore,we outlined currently available targeting strategies:(1)targeting lysosomal acidification;(2)targeting lysosomal cathepsins;(3)targeting lysosomal membrane permeability and integrity;(4)targeting lysosomal calcium signaling;(5)targeting mTOR signaling;and(6)emerging potential targeting strategies.Moreover,we systematically summarized the corresponding drugs and their application in clinical trials.By integrating basic research with clinical findings,we discussed the current opportunities and challenges of targeting lysosomes in human disease.
基金supported by Laboratory of Lingnan Modern Agriculture Project(NT2021003).
文摘The diamondback moth,Plutella xylostella(L.),is one of the most destructive migratory pest species of cruciferous vegetables worldwide and has developed resistance to most of the insecticides used for its control.The migration regularity,migratory behavior,and relationship between flight and reproduction of P.xylostella have been widely reported.However,the effect of migration on insecticide resistance in this pest is still unclear.In this study,the effect of migration on P.xylostella resistance to seven insecticides was investigated using populations across the Bohai Sea that were collected in the early and late seasons during 2017–2019.The bioassay results showed that the early season populations of P.xylostella from south China possessed much higher resistance to insecticides because of intensive insecticide application;alternatively,the late season populations migrated from northeast China,where the insecticides were only used occasionally,showed much lower insecticide resistance.The genome re-sequencing results revealed that,among the eight mutations involved in insecticide resistance,the frequencies of two acetylcholinesterase mutations(A298S and G324A)responsible for organophosphorus insecticide resistance were significantly decreased in the late season populations.The results indicated that P.xylostella migration between tropical and temperate regions significantly delayed the development of insecticide resistance.These findings illustrated the effect of regional migration on the evolution of insecticide resistance in P.xylostella,and provided foundational information for further research on the relationship between migration and insecticide resistance development in other insects.
基金supported by Shenzhen Natural Science Foundation(grant numberJCYJ20200109150629266)Shenzhen Science and Technology Program(grant number KQTD20180411143628272).
文摘Evolution of resistance to Cry proteins in multiple pest insects has been threatening the sustainable use of Bacillus thuringiensis(Bt)-transgenic crops.Better understanding about the mechanism of resistance to Cry proteins in insects is needed.Our preliminary study reported that the transcription of HaABCC3 was significantly decreased in a near-isogenic line(LFC2)of a Cry1Ac-resistant strain(LF60)of the global pest Helicoverpa armigera.However,the causality between HaABCC3 downregulation and resistance to Cry1Ac remains to be verified,and the regulatory mechanism underlying the HaABCC3 downregulation is still unclear.In this study,our data showed that both HaABCC3 and HaABCC3 downregulation were genetically linked to resistance to Cry1Ac in LF60.However,no InDels were observed in the coding sequence of HaABCC3 from LF60.Furthermore,F_(1) offspring from the cross of LF60 and a HaABCC2/3-knockout mutant exhibited moderate resistance to Cry1Ac toxin;this indicated that the high resistance to CrylAc toxin in LF60 may have resulted from multiple genetic factors,including HaABCC2 missplicing and HaABCC3 downregulation.Results from luciferase reporter assays showed that promoter activity of HaABCC3 in LF60 was significantly lower than that in the susceptible strain,which indicated that HaABCC3 downregulation was likely mediated by promoter variation.Consistently,multiple variations of the GATA-or FoxA-binding sites in the promoter region of HaABCC3 were identified.Collectively,all results in this study suggested that the downregulation of HaABCC3 observed in the H.armigera LF60 strain,which is resistant to CrylAc,may be mediated by a cis-regulatory mechanism.
基金funded by the Agricultural Science and Technology Innovation Programof the Chinese Academy of Agricultural Sciences andMajor Projects of Basic Research of Science,The Sci-Tech Innovation 2030 Agenda(2022ZD04021)the Technology and Innovation Commission of Shenzhen Municipality,the United Kingdom’s Biotechnology and Biological Sciences Research Council(BB/L026821/1)+4 种基金Research Councils UK(BB/P023444/1)(to K.W.)funded by BBSRC(BB/G105364/1)supported by the University of Cambridge Department of Zoologyfunded by EMBO fellowship ATSF-6889 and the CSIRO-Julius Award(R-91040-11)supported by the Lemann Brazil Research Fund from Harvard University.
文摘The cotton bollworm,Helicoverpa armigera,is set to become the most economically devastating crop pest in the world,threatening food security and biosafety as its range expands across the globe.Key to understanding the eco-evolutionary dynamics of H.armigera,and thus its management,is an understanding of population connectivity and the adaptations that allow the pest to establish in unique environments.We assembled a chromosome-scale reference genome and re-sequenced 503 individuals spanning the species range to delineate global patterns of connectivity,uncovering a previously cryptic population structure.
文摘China is the largest agricultural producer in the world.Reducing yield losses caused by pests is an important issue and major challenge for China,especially when confronting global climate change,biological invasions and declining agricultural biodiversity of recent decades.Wang et al.(this issue)summarized the impacts of changing climate on two staple crops in China,wheat and rice(https://doi.org/FASE-2021432).
基金We thank Dr.Tianye Li for the language editing assistance.Funding:This work was supported by the National Natural Science Foundation of China(No.81572608,81874120,81672984)the Wuhan Science and Technology Bureau(No.2017060201010170).
文摘It has been well established that the gut microbiota has a substantial influence on the host immune system.By crosstalk between specific microorganism-associated molecular patterns and the immune system,in addition to bacterial metabolic activity,gut microbiota regulates local or systemic inflammation(1).Recently,the composition of gut microbiota has been presumed to be one of the factors affecting the cancer-immune set point of cancer patients,which subsequently determines the efficacy of immune checkpoint inhibitor(ICI)treatment(2).