Insects represent a diverse group of organisms on earth that carry a vast array of symbiotic microorganisms in their intestines.These microorganisms have established a complex and intimate symbiotic relationship with ...Insects represent a diverse group of organisms on earth that carry a vast array of symbiotic microorganisms in their intestines.These microorganisms have established a complex and intimate symbiotic relationship with their host insects over an extended period of evolutionary adaptation.The population structure of intestinal symbiotic microorganisms in insects exhibits a high degree of diversity,with notable differences among insect species.Conversely,within the same insect species,the population structure of symbiotic microorganisms in specific intestinal sites demonstrates a certain degree of stability and specificity.These symbiotic microorganisms perform various physiological functions in the host insect.Their biological functions encompass nutrient and material metabolism and immune and protective mechanisms,which have significant effects on host insect longevity,development,and reproductive capacity.These microorganisms have diverse applications,including pest control,bioenergy production,the development of insect resources,etc.Recent advancements in high-throughput sequencing technology have revealed a growing diversity and biological properties of these microorganisms.The application of these techniques has significantly contributed to the advancement of research in the field of insect intestinal microbial research,providing researchers with powerful tools for a deeper understanding and utilization of these symbiotic microorganisms.This study reviewed the research progress of insect intestinal microorganisms in three aspects:diversity,biological functions,and applications.The objective was to provide useful references and insights for further research and applications of insect intestinal microorganisms.展开更多
Kenaf is considered to have great potential for remediation of heavy metals in ecosystems.However,studies on molecular mechanisms of root Cd accumulation and tolerance are still inadequate.In this study,two differentl...Kenaf is considered to have great potential for remediation of heavy metals in ecosystems.However,studies on molecular mechanisms of root Cd accumulation and tolerance are still inadequate.In this study,two differently tolerant kenaf cultivars were selected as materials and the physiological and transcriptomic effects were evaluated under Cd stress.This study showed that 200μmol/L CdCl_(2) treatment triggered the reactive oxygen species(ROS)explosion and membrane lipid peroxidation.Compared with the Cd-sensitive cultivar‘Z',the Cd-tolerant cultivar‘F'was able to resist oxidative stress in cells by producing higher antioxidant enzyme activities and increasing the contents of ascorbic acid(AsA)and glutathione(GSH).The root cell wall of‘F'exhibited higher polysaccharide contents under Cd treatment,providing more Cd-binding sites.There were 3,439 differentially expressed genes(DEGs)that were co-regulated by Cd treatment in two cultivars.Phenylpropanoid biosynthesis and plant hormone signal transduction pathways were significantly enriched by functional annotation analysis.DEGs associated with pectin,cellulose,and hemi-cellulose metabolism were involved in Cd chelation of root cell wall;V-ATPases,ABCC3 and Narmp3 could participated in vacuolar compartmentalization of Cd;PDR1 was responsible for Cd effux;the organic acid transporters contributed to the absorption of Cd in soil.These genes might have played key roles in kenaf Cd tolerance and Cd accumulation.Moreover,HcZIP2 was identified to be involved in Cd uptake and transport in kenaf.Our findings provide a deeper understanding of the molecular pathways underlying Cd accumulation and detoxification mechanisms in kenaf.展开更多
Background:Trastuzumab is a first-line targeted therapy for human epidermal growth factor receptor-2(HER2)-positive gastric cancer.However,the inevitable occurrence of acquired trastuzumab resistance limits the drug b...Background:Trastuzumab is a first-line targeted therapy for human epidermal growth factor receptor-2(HER2)-positive gastric cancer.However,the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit,and there is currently no effective reversal measure.Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves,while the understanding of the mechanisms of environment-mediated drug resistance is relatively lacking.This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients.Methods:Trastuzumab-sensitive and trastuzumab-resistant HER2-positive tumor tissues and cells were collected for transcriptome sequencing.Bioinformatics were used to analyze cell subtypes,metabolic pathways,and molecular signaling pathways.Changes in microenvironmental indicators(such as macrophage,angiogenesis,and metabolism)were verified by immunofluorescence(IF)and immunohistochemical(IHC)analyses.Finally,a multi-scale agent-based model(ABM)was constructed.The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM.Results:Based on transcriptome sequencing,molecular biology,and in vivo experiments,we found that the level of glutamine metabolism in trastuzumabresistant HER2-positive cells was increased,and glutaminase 1(GLS1)was significantly overexpressed.Meanwhile,tumor-derived GLS1 microvesicles drove M2macrophage polarization.Furthermore,angiogenesis promoted trastuzumab resistance.IHC showed high glutamine metabolism,M2 macrophage polarization,and angiogenesis in trastuzumab-resistant HER2-positive tumor tissues from patients and nudemice.Mechanistically,the cell division cycle 42(CDC42)promoted GLS1 expression in tumor cells by activating nuclear factor kappa-B(NF-κB)p65 and drove GLS1microvesicle secretion through IQmotif-containing GTPase-activating protein 1(IQGAP1).Based on the ABM and in vivo experiments,we confirmed that the combination of anti-glutamine metabolism,anti-angiogenesis,and pro-M1 polarization therapy had the best effect in reversing trastuzumab resistance in HER2-positive gastric cancer.Conclusions:This study revealed that tumor cells secrete GLS1 microvesicles via CDC42 to promote glutamine metabolism,M2 macrophage polarization,and pro-angiogenic function of macrophages,leading to acquired trastuzumab resistance in HER2-positive gastric cancer.A combination of anti-glutamine metabolism,anti-angiogenesis,and pro-M1 polarization therapy may provide a new insight into reversing trastuzumab resistance.展开更多
基金Supported by Science and Technology Innovation Guidance Project of Zhaoqing in 2023(2023040308006)Undergraduate Innovation and Entrepreneurship Training Program of Guangdong Province(S202310580041)Innovation Platform Construction Project of Zhaoqing University(202413004).
文摘Insects represent a diverse group of organisms on earth that carry a vast array of symbiotic microorganisms in their intestines.These microorganisms have established a complex and intimate symbiotic relationship with their host insects over an extended period of evolutionary adaptation.The population structure of intestinal symbiotic microorganisms in insects exhibits a high degree of diversity,with notable differences among insect species.Conversely,within the same insect species,the population structure of symbiotic microorganisms in specific intestinal sites demonstrates a certain degree of stability and specificity.These symbiotic microorganisms perform various physiological functions in the host insect.Their biological functions encompass nutrient and material metabolism and immune and protective mechanisms,which have significant effects on host insect longevity,development,and reproductive capacity.These microorganisms have diverse applications,including pest control,bioenergy production,the development of insect resources,etc.Recent advancements in high-throughput sequencing technology have revealed a growing diversity and biological properties of these microorganisms.The application of these techniques has significantly contributed to the advancement of research in the field of insect intestinal microbial research,providing researchers with powerful tools for a deeper understanding and utilization of these symbiotic microorganisms.This study reviewed the research progress of insect intestinal microorganisms in three aspects:diversity,biological functions,and applications.The objective was to provide useful references and insights for further research and applications of insect intestinal microorganisms.
基金supported by the China Agriculture Research System of MOF and MARA (No.CARS-16-E14)。
文摘Kenaf is considered to have great potential for remediation of heavy metals in ecosystems.However,studies on molecular mechanisms of root Cd accumulation and tolerance are still inadequate.In this study,two differently tolerant kenaf cultivars were selected as materials and the physiological and transcriptomic effects were evaluated under Cd stress.This study showed that 200μmol/L CdCl_(2) treatment triggered the reactive oxygen species(ROS)explosion and membrane lipid peroxidation.Compared with the Cd-sensitive cultivar‘Z',the Cd-tolerant cultivar‘F'was able to resist oxidative stress in cells by producing higher antioxidant enzyme activities and increasing the contents of ascorbic acid(AsA)and glutathione(GSH).The root cell wall of‘F'exhibited higher polysaccharide contents under Cd treatment,providing more Cd-binding sites.There were 3,439 differentially expressed genes(DEGs)that were co-regulated by Cd treatment in two cultivars.Phenylpropanoid biosynthesis and plant hormone signal transduction pathways were significantly enriched by functional annotation analysis.DEGs associated with pectin,cellulose,and hemi-cellulose metabolism were involved in Cd chelation of root cell wall;V-ATPases,ABCC3 and Narmp3 could participated in vacuolar compartmentalization of Cd;PDR1 was responsible for Cd effux;the organic acid transporters contributed to the absorption of Cd in soil.These genes might have played key roles in kenaf Cd tolerance and Cd accumulation.Moreover,HcZIP2 was identified to be involved in Cd uptake and transport in kenaf.Our findings provide a deeper understanding of the molecular pathways underlying Cd accumulation and detoxification mechanisms in kenaf.
基金National Natural Science Foundation of China,Grant/Award Number:82073325。
文摘Background:Trastuzumab is a first-line targeted therapy for human epidermal growth factor receptor-2(HER2)-positive gastric cancer.However,the inevitable occurrence of acquired trastuzumab resistance limits the drug benefit,and there is currently no effective reversal measure.Existing researches on the mechanism of trastuzumab resistance mainly focused on tumor cells themselves,while the understanding of the mechanisms of environment-mediated drug resistance is relatively lacking.This study aimed to further explore the mechanisms of trastuzumab resistance to identify strategies to promote survival in these patients.Methods:Trastuzumab-sensitive and trastuzumab-resistant HER2-positive tumor tissues and cells were collected for transcriptome sequencing.Bioinformatics were used to analyze cell subtypes,metabolic pathways,and molecular signaling pathways.Changes in microenvironmental indicators(such as macrophage,angiogenesis,and metabolism)were verified by immunofluorescence(IF)and immunohistochemical(IHC)analyses.Finally,a multi-scale agent-based model(ABM)was constructed.The effects of combination treatment were further validated in nude mice to verify these effects predicted by the ABM.Results:Based on transcriptome sequencing,molecular biology,and in vivo experiments,we found that the level of glutamine metabolism in trastuzumabresistant HER2-positive cells was increased,and glutaminase 1(GLS1)was significantly overexpressed.Meanwhile,tumor-derived GLS1 microvesicles drove M2macrophage polarization.Furthermore,angiogenesis promoted trastuzumab resistance.IHC showed high glutamine metabolism,M2 macrophage polarization,and angiogenesis in trastuzumab-resistant HER2-positive tumor tissues from patients and nudemice.Mechanistically,the cell division cycle 42(CDC42)promoted GLS1 expression in tumor cells by activating nuclear factor kappa-B(NF-κB)p65 and drove GLS1microvesicle secretion through IQmotif-containing GTPase-activating protein 1(IQGAP1).Based on the ABM and in vivo experiments,we confirmed that the combination of anti-glutamine metabolism,anti-angiogenesis,and pro-M1 polarization therapy had the best effect in reversing trastuzumab resistance in HER2-positive gastric cancer.Conclusions:This study revealed that tumor cells secrete GLS1 microvesicles via CDC42 to promote glutamine metabolism,M2 macrophage polarization,and pro-angiogenic function of macrophages,leading to acquired trastuzumab resistance in HER2-positive gastric cancer.A combination of anti-glutamine metabolism,anti-angiogenesis,and pro-M1 polarization therapy may provide a new insight into reversing trastuzumab resistance.
