Symbiotic microorganisms improve nutrient uptake by plants.To initiate mutualistic symbiosis with arbus-cular mycorrhizal(AM)fungi,plants perceive Myc factors,including lipochitooligosaccharides(LCOs)and short-chain c...Symbiotic microorganisms improve nutrient uptake by plants.To initiate mutualistic symbiosis with arbus-cular mycorrhizal(AM)fungi,plants perceive Myc factors,including lipochitooligosaccharides(LCOs)and short-chain chitooligosaccharides(CO4/CO5),secreted by AM fungi.However,the molecular mechanism of Myc factor perception remains elusive.In this study,we identified a heteromer of LysM receptor-like kinases consisting of OsMYR1/OsLYK2 and OsCERK1 that mediates the perception of AM fungi in rice.CO4 directly binds to OsMYR1,promoting the dimerization and phosphorylation of this receptor complex.Compared with control plants,Osmyr1 and Oscerk1 mutant rice plants are less sensitive to Myc factors and show decreased AM colonization.We engineered transgenic rice by expressing chimeric receptors that respectively replaced the ectodomains of OsMYR1 and OsCERK1 with those from the homologous Nod factor receptors MtNFP and MtL YK3 of Medicago truncatula.Transgenic plants displayed increased cal-cium oscillations in response to Nod factors compared with control rice.Our study provides significant mechanistic insights into AM symbiotic signal perception in rice.Expression of chimeric Nod/Myc recep-tors achieves a potentially important step toward generating cereals that host nitrogen-fixing bacteria.展开更多
Lymph node status is considered a key prognostic and predictive factor in patients with gastric cancer(GC).Although there is a practical approach to the intraoperative detection of sentinel lymph nodes(SLNs),such a pr...Lymph node status is considered a key prognostic and predictive factor in patients with gastric cancer(GC).Although there is a practical approach to the intraoperative detection of sentinel lymph nodes(SLNs),such a procedure is not included in the European surgical protocol.In this report,we present a practical approach to SLN mapping in a representative case with early gastric cancer(EGC).A 74-year-old female was hospitalized with an endoscopically observed,superficially ulcerated tumor located in the antral region.Subtotal gastrectomy with D2 lymphadenectomy and SLN mapping was performed by injecting methylene blue dye into the peritumoral submucosal layer.An incidentally detected blue-stained lymph node located along the middle colic artery was also removed.This was detected 40 min after injection of the methylene blue.Histopathologic examination showed a p T1b-staged well-differentiated HER-2-negative adenocarcinoma.All of the 41 LNs located at the first,third,and fifth station of the regional LN compartments were found to be free of tumor cells.The only lymph node with metastasis was located along the middle colicartery and was considered a non-regional lymph node.This incidentally identified skip metastasis indicated stage Ⅳ GC.A classic chemotherapy regimen was given,and no recurrences were observed six months after surgery.In this representative case,low-cost SLN mapping,with a longer intraoperative waiting time,totally changed the stage of the tumor in a patient with EGC.展开更多
Under nutrient-limiting conditions, plants will enter into symbiosis with arbuscular mycorrhizal （AM） fungi for the enhancement of mineral nutrient acquisition from the surrounding soil. AM fungi live in close, intr...Under nutrient-limiting conditions, plants will enter into symbiosis with arbuscular mycorrhizal （AM） fungi for the enhancement of mineral nutrient acquisition from the surrounding soil. AM fungi live in close, intracellular association with plant roots where they transfer phosphate and nitrogen to the plant in exchange for carbon. They are obligate fungi, relying on their host as their only carbon source. Much has been discovered in the last decade concerning the signaling events during initiation of the AM symbiosis, including the identification of signaling molecules generated by both partners. This signaling occurs through symbiosis-specific gene products in the host plant, which are indispensable for normal AM development. At the same time, plants have adapted complex mechanisms for avoiding infection by pathogenic fungi, including an innate immune response to general microbial molecules, such as chitin present in fungal cell walls. How it is that AM fungal colonization is maintained without eliciting a defensive response from the host is still uncertain. In this review, we present a summary of the molecular signals and their elicited responses during initiation of the AM symbiosis, including plant immune responses and their suppression.展开更多
目的观察麦冬地芍汤对干燥综合征模型(nonobese diabetic mouse,NOD)小鼠颌下腺的保护作用。方法取雌性NOD小鼠33只,随机分为模型组、羟氯喹组、麦冬地芍汤组,另取ICR(Institute of Cancer Research)小鼠8只作为空白组。适应性喂养一周...目的观察麦冬地芍汤对干燥综合征模型(nonobese diabetic mouse,NOD)小鼠颌下腺的保护作用。方法取雌性NOD小鼠33只,随机分为模型组、羟氯喹组、麦冬地芍汤组,另取ICR(Institute of Cancer Research)小鼠8只作为空白组。适应性喂养一周后,羟氯喹组、麦冬地芍汤组分别灌服羟氯喹溶液(0.1 g/kg,20 ml/kg)及麦冬地芍汤(10 g/kg,20 ml/kg),空白及模型组生理盐水灌胃。观察小鼠10、13、16周龄唾液流率的变化,18周龄时取颌下腺,对颌下腺进行HE染色,免疫组化法测AQP5的表达。结果与模型组相比,麦冬地芍汤组小鼠16周龄时唾液流率明显改善(P<0.01),18周龄时,麦冬地芍汤组组织学评分低于模型组(P<0.05),AQP5的表达较模型组明显上调(P<0.05)。结论麦冬地芍汤对NOD小鼠颌下腺有保护作用,其机制可能与其上调AQP5的表达相关。展开更多
目的探讨3~8岁人鼻病毒(HRV)感染喘息急性发作儿童外周血NOD样受体蛋白(NLRP)3和Toll样受体(TLR)4水平及临床意义。方法选择2023年9月至2024年3月在青岛大学附属妇女儿童医院急诊科就诊因HRV感染所致首次喘息急性发作的126例3~8岁患儿...目的探讨3~8岁人鼻病毒(HRV)感染喘息急性发作儿童外周血NOD样受体蛋白(NLRP)3和Toll样受体(TLR)4水平及临床意义。方法选择2023年9月至2024年3月在青岛大学附属妇女儿童医院急诊科就诊因HRV感染所致首次喘息急性发作的126例3~8岁患儿为研究对象。根据病情程度,将其分为轻、中度组(n=80)和重度组(n=46)。采用独立样本t检验,对2组患儿年龄、体重、人体质量指数(BMI),外周血白细胞计数(WBC)、中性粒细胞计数(NEUT)、淋巴细胞计数(LY)、C反应蛋白(CRP)及白细胞介素(IL)-6、TLR4水平和NLRP3 m RNA相对表达水平等比较。采用χ2检验,对2组患儿性别构成比,湿疹史、父母变态反应史占比等进行比较。再采用Pearson相关性分析外周血IL-6、TLR4水平和NLRP3 m RNA相对表达水平与儿童喘息急性发作严重程度的相关性。本研究遵循的伦理学原则获得医院伦理委员会的批准(审批文号:QFELL-KY-2020-23)。结果①2组患儿性别构成比、年龄、体重、BMI与湿疹史及父母变态反应史占比等一般临床资料比较,差异均无统计学意义(P>0.05)。②轻、中度组患儿外周血IL-6、TLR4水平和NLRP3 m RNA相对表达水平,均低于重度组,并且差异有统计学意义(P<0.05)。③HRV感染喘息急性发作儿童喘息严重程度与外周血IL-6、TLR4水平和NLRP3 m RNA相对表达水平分别呈正相关关系(r=0.772、0.792、0.897,P<0.001)。④外周血TLR4与NLRP3 m RNA亦呈正相关关系(r=0.820,P<0.001)。结论HRV感染致喘息急性发作儿童外周血NLRP3及TLR4水平,与其喘息严重程度密切相关。NLRP3可能通过诱导外周血IL-6分泌,上调TLR4介导HRV感染患儿气道高反应性(AHR),诱导喘息急性发作。展开更多
A 66-year-old female presented with the main complaint of defecation trouble and abdominal distention. With diagnosis of rectal cancer, c SS, c N0, c H0, c P0, c M0 c Stage Ⅱ, Hartmann's operation with D3 lymph n...A 66-year-old female presented with the main complaint of defecation trouble and abdominal distention. With diagnosis of rectal cancer, c SS, c N0, c H0, c P0, c M0 c Stage Ⅱ, Hartmann's operation with D3 lymph node dissection was performed and a para-aortic lymph node and a disseminated node near the primary tumor were resected. Histological examination showed moderately differentiated adenocarcinoma, p SS, p N3, p H0, p P1, p M1(para-aortic lymph node, dissemination) f Stage Ⅳ. After the operation, the patient received chemotherapy with FOLFIRI regimen. After 12 cycles of FOLFIRI regimen, computed tomography(CT) detected an 11 mm of liver metastasis in the posteroinferior segment of right hepatic lobe. With diagnosis of liver metastatic recurrence, we performed partial hepatectomy. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer with cut end microscopically positive. After the second operation, the patient received chemotherapy with TS1 alone for 2 years. Ten months after the break, CT detected a 20 mm of paraaortic lymph node metastasis and a 10 mm of lymph node metastasis at the hepato-duodenal ligament. With diagnosis of lymph node metastatic recurrences, we performed lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as metastatic rectal cancer in paraaortic and hepato-duodenal ligament areas. After the third operation, we started chemotherapy with modified FOLFOX6 regimen. After 2 cycles of modified FOLFOX6 regimen, due to the onset of neutropenia and liver dysfunction, we switched to capecitabine aloneand continued it for 6 mo and then stopped. Eleven months after the break, CT detected two swelling 12 mm of lymph nodes at the left supraclavicular region. With diagnosis of Virchow lymph node metastatic recurrence, we started chemotherapy with capecitabine plus bevacizumab regimen. Due to the onset of neutropenia and hand foot syndrome(Grade 3), we managed to continue capecitabine administration with展开更多
Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with ...Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.展开更多
基金This work is supported by the NSFC(31730103,31825003,31522007)the National Key Basic Research Programme in China(2015CB158300)+2 种基金the Strategic Priority Research Program of the Chinese Academy of Sciences(XDB27040207)the International Partnership Program of Chinese Academy of Sciences(153D31KYSB20160074)the National Key Laboratory of Plant Molecular Genetics to E.W.
文摘Symbiotic microorganisms improve nutrient uptake by plants.To initiate mutualistic symbiosis with arbus-cular mycorrhizal(AM)fungi,plants perceive Myc factors,including lipochitooligosaccharides(LCOs)and short-chain chitooligosaccharides(CO4/CO5),secreted by AM fungi.However,the molecular mechanism of Myc factor perception remains elusive.In this study,we identified a heteromer of LysM receptor-like kinases consisting of OsMYR1/OsLYK2 and OsCERK1 that mediates the perception of AM fungi in rice.CO4 directly binds to OsMYR1,promoting the dimerization and phosphorylation of this receptor complex.Compared with control plants,Osmyr1 and Oscerk1 mutant rice plants are less sensitive to Myc factors and show decreased AM colonization.We engineered transgenic rice by expressing chimeric receptors that respectively replaced the ectodomains of OsMYR1 and OsCERK1 with those from the homologous Nod factor receptors MtNFP and MtL YK3 of Medicago truncatula.Transgenic plants displayed increased cal-cium oscillations in response to Nod factors compared with control rice.Our study provides significant mechanistic insights into AM symbiotic signal perception in rice.Expression of chimeric Nod/Myc recep-tors achieves a potentially important step toward generating cereals that host nitrogen-fixing bacteria.
基金Supported by Romanian government,the research project frame POSDRU/159/1.5/S/136893University of Medicine and Pharmacy of Tirgu-Mures,Romania,the team research project POS-UMFTGM-CC-13-01-V01,No.15/16189/2013+1 种基金In Japan,funds were obtained by grants from the Ministry of Health,Labour and Welfare(19-19,10103838)Ministry of Education,Culture,Sports,Science and Technology(MEXT)(S-001)
文摘Lymph node status is considered a key prognostic and predictive factor in patients with gastric cancer(GC).Although there is a practical approach to the intraoperative detection of sentinel lymph nodes(SLNs),such a procedure is not included in the European surgical protocol.In this report,we present a practical approach to SLN mapping in a representative case with early gastric cancer(EGC).A 74-year-old female was hospitalized with an endoscopically observed,superficially ulcerated tumor located in the antral region.Subtotal gastrectomy with D2 lymphadenectomy and SLN mapping was performed by injecting methylene blue dye into the peritumoral submucosal layer.An incidentally detected blue-stained lymph node located along the middle colic artery was also removed.This was detected 40 min after injection of the methylene blue.Histopathologic examination showed a p T1b-staged well-differentiated HER-2-negative adenocarcinoma.All of the 41 LNs located at the first,third,and fifth station of the regional LN compartments were found to be free of tumor cells.The only lymph node with metastasis was located along the middle colicartery and was considered a non-regional lymph node.This incidentally identified skip metastasis indicated stage Ⅳ GC.A classic chemotherapy regimen was given,and no recurrences were observed six months after surgery.In this representative case,low-cost SLN mapping,with a longer intraoperative waiting time,totally changed the stage of the tumor in a patient with EGC.
基金Financial support for this research program was provided by the US National Science Foundation (IOS‐0842720)an award from the US National Science Foundation Graduate Research Fellowship (DGE‐1144153)
文摘Under nutrient-limiting conditions, plants will enter into symbiosis with arbuscular mycorrhizal （AM） fungi for the enhancement of mineral nutrient acquisition from the surrounding soil. AM fungi live in close, intracellular association with plant roots where they transfer phosphate and nitrogen to the plant in exchange for carbon. They are obligate fungi, relying on their host as their only carbon source. Much has been discovered in the last decade concerning the signaling events during initiation of the AM symbiosis, including the identification of signaling molecules generated by both partners. This signaling occurs through symbiosis-specific gene products in the host plant, which are indispensable for normal AM development. At the same time, plants have adapted complex mechanisms for avoiding infection by pathogenic fungi, including an innate immune response to general microbial molecules, such as chitin present in fungal cell walls. How it is that AM fungal colonization is maintained without eliciting a defensive response from the host is still uncertain. In this review, we present a summary of the molecular signals and their elicited responses during initiation of the AM symbiosis, including plant immune responses and their suppression.
文摘目的观察麦冬地芍汤对干燥综合征模型(nonobese diabetic mouse,NOD)小鼠颌下腺的保护作用。方法取雌性NOD小鼠33只,随机分为模型组、羟氯喹组、麦冬地芍汤组,另取ICR(Institute of Cancer Research)小鼠8只作为空白组。适应性喂养一周后,羟氯喹组、麦冬地芍汤组分别灌服羟氯喹溶液(0.1 g/kg,20 ml/kg)及麦冬地芍汤(10 g/kg,20 ml/kg),空白及模型组生理盐水灌胃。观察小鼠10、13、16周龄唾液流率的变化,18周龄时取颌下腺,对颌下腺进行HE染色,免疫组化法测AQP5的表达。结果与模型组相比,麦冬地芍汤组小鼠16周龄时唾液流率明显改善(P<0.01),18周龄时,麦冬地芍汤组组织学评分低于模型组(P<0.05),AQP5的表达较模型组明显上调(P<0.05)。结论麦冬地芍汤对NOD小鼠颌下腺有保护作用,其机制可能与其上调AQP5的表达相关。
文摘目的探讨3~8岁人鼻病毒(HRV)感染喘息急性发作儿童外周血NOD样受体蛋白(NLRP)3和Toll样受体(TLR)4水平及临床意义。方法选择2023年9月至2024年3月在青岛大学附属妇女儿童医院急诊科就诊因HRV感染所致首次喘息急性发作的126例3~8岁患儿为研究对象。根据病情程度,将其分为轻、中度组(n=80)和重度组(n=46)。采用独立样本t检验,对2组患儿年龄、体重、人体质量指数(BMI),外周血白细胞计数(WBC)、中性粒细胞计数(NEUT)、淋巴细胞计数(LY)、C反应蛋白(CRP)及白细胞介素(IL)-6、TLR4水平和NLRP3 m RNA相对表达水平等比较。采用χ2检验,对2组患儿性别构成比,湿疹史、父母变态反应史占比等进行比较。再采用Pearson相关性分析外周血IL-6、TLR4水平和NLRP3 m RNA相对表达水平与儿童喘息急性发作严重程度的相关性。本研究遵循的伦理学原则获得医院伦理委员会的批准(审批文号:QFELL-KY-2020-23)。结果①2组患儿性别构成比、年龄、体重、BMI与湿疹史及父母变态反应史占比等一般临床资料比较,差异均无统计学意义(P>0.05)。②轻、中度组患儿外周血IL-6、TLR4水平和NLRP3 m RNA相对表达水平,均低于重度组,并且差异有统计学意义(P<0.05)。③HRV感染喘息急性发作儿童喘息严重程度与外周血IL-6、TLR4水平和NLRP3 m RNA相对表达水平分别呈正相关关系(r=0.772、0.792、0.897,P<0.001)。④外周血TLR4与NLRP3 m RNA亦呈正相关关系(r=0.820,P<0.001)。结论HRV感染致喘息急性发作儿童外周血NLRP3及TLR4水平,与其喘息严重程度密切相关。NLRP3可能通过诱导外周血IL-6分泌,上调TLR4介导HRV感染患儿气道高反应性(AHR),诱导喘息急性发作。
文摘A 66-year-old female presented with the main complaint of defecation trouble and abdominal distention. With diagnosis of rectal cancer, c SS, c N0, c H0, c P0, c M0 c Stage Ⅱ, Hartmann's operation with D3 lymph node dissection was performed and a para-aortic lymph node and a disseminated node near the primary tumor were resected. Histological examination showed moderately differentiated adenocarcinoma, p SS, p N3, p H0, p P1, p M1(para-aortic lymph node, dissemination) f Stage Ⅳ. After the operation, the patient received chemotherapy with FOLFIRI regimen. After 12 cycles of FOLFIRI regimen, computed tomography(CT) detected an 11 mm of liver metastasis in the posteroinferior segment of right hepatic lobe. With diagnosis of liver metastatic recurrence, we performed partial hepatectomy. Histological examination revealed moderately differentiated adenocarcinoma as a metastatic rectal cancer with cut end microscopically positive. After the second operation, the patient received chemotherapy with TS1 alone for 2 years. Ten months after the break, CT detected a 20 mm of paraaortic lymph node metastasis and a 10 mm of lymph node metastasis at the hepato-duodenal ligament. With diagnosis of lymph node metastatic recurrences, we performed lymph node dissection. Histological examination revealed moderately differentiated adenocarcinoma as metastatic rectal cancer in paraaortic and hepato-duodenal ligament areas. After the third operation, we started chemotherapy with modified FOLFOX6 regimen. After 2 cycles of modified FOLFOX6 regimen, due to the onset of neutropenia and liver dysfunction, we switched to capecitabine aloneand continued it for 6 mo and then stopped. Eleven months after the break, CT detected two swelling 12 mm of lymph nodes at the left supraclavicular region. With diagnosis of Virchow lymph node metastatic recurrence, we started chemotherapy with capecitabine plus bevacizumab regimen. Due to the onset of neutropenia and hand foot syndrome(Grade 3), we managed to continue capecitabine administration with
基金supported by grants from the Spanish Ministry of Health-PNSD(2019-I039 and 2023-I024)(to MP)FEDER/Ministerio de Ciencia e Innovación-Agencia Estatal de Investigación PID2021-1243590B-I100(to VMM)+2 种基金GVA(CIAICO/2021/203)(to MP)the Primary Addiction Care Research Network(RD21/0009/0005)(to MP)a predoctoral fellowship from the Generalitat Valenciana(ACIF/2021/338)(to CPC).
文摘Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.
