EFR is a plasma-membrane resident receptor responsible for recognition of microbial elongation factorTu （EF-Tu） and thus triggering plant innate immunity to fend off phytopathogens. Functional EFR must be subject to...EFR is a plasma-membrane resident receptor responsible for recognition of microbial elongation factorTu （EF-Tu） and thus triggering plant innate immunity to fend off phytopathogens. Functional EFR must be subject to the endoplasmic reticulum quality control （ERQC） machinery for the correct folding and proper assembly in order to reach its final destination. Genetic studies have demonstrated that ERD2b, a counterpart of the yeast or mammalian HDEL receptor ERD2 for retaining proteins in the endoplasmic reticulum （ER） lumen, is required for EFR function in plants （Li et al., 2009）. In this study, we characterized the Arabidopsis glucosidase Ⅱ β--subunit via the H DEL motif against the non-redundant protein database. Data mining also revealed that the glucosidase Ⅱ β--subunit gene has a highly similar expression pattern to ERD2b and the other known ERQC components involved in EFR biogenesis. Importantly, the T-DNA insertion lines of the glucosidase Ⅱ β-subunit gene showed that EFR-controlled responses were substantially reduced or completely blocked in these mutants. The responses include seedling growth inhibition, induction of marker genes, MAP kinase activation, and callose deposition, trigged by peptide elf18, a full mimic of E F-Tu. Taken together, ourdata indicate a requirement of the glucosidase Ⅱ β-subunitfor EFR function.展开更多
Background： Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene （GAA）. A wide clinical and genetic variability exists between patients from different ethnic populat...Background： Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene （GAA）. A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease （LOPD） who carried novel GAA gene mutations. Methods： Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted. Results： Of the five patients included in the study, the median disease onset age was 13 years, with a median 5 years delay in diagnosis. The patients mainly manifested as progressive weakness in the proximal and axial muscles, while one patient developed respiratory insufficiency that required artificial ventilation. In muscle biopsies, vacuoles with variable sizes and shapes appeared inside muscle fibers, and they stained positive for both periodic acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including seven novel ones （c.796C〉A, c. 1057C〉T, c. 1201C〉A, c. 1780C〉T, c. 1799G〉C, c.2051C〉A, c.2235dupG）, were identified by genetic tests. Conclusions： The seven novel GAA gene mutations revealed in this study broaden the genetic spectrum of LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.展开更多
In this study,a novel class of histidine Schiff base silver（Ⅰ） complexes derived from salicylaldehyde,1a-9a,was found to be an effective inhibitor of α-glucosidase.The results of this study showed that the newly s...In this study,a novel class of histidine Schiff base silver（Ⅰ） complexes derived from salicylaldehyde,1a-9a,was found to be an effective inhibitor of α-glucosidase.The results of this study showed that the newly synthesized complexes inhibited α-glucosidase through noncompetitive mechanisms;the IC50values were ranging from 0.00431 μmol L ~1 to 0.492 μmol L ~1.The structure-activity relationship was established as well.These results demonstrated that compound 7a,5-nitro salicylaldehyde Schiff base silver complex,is the most promising α-glucosidase inhibitor with the lowest IC50 value,which could be exploited as a drug candidate to alleviate postprandial hyperglycemia in the treatment of type II diabetes mellitus.This research provided a catalyst-free,simple,and environmentally benign reaction to synthesize compounds using mechanochemistry.展开更多
文摘EFR is a plasma-membrane resident receptor responsible for recognition of microbial elongation factorTu （EF-Tu） and thus triggering plant innate immunity to fend off phytopathogens. Functional EFR must be subject to the endoplasmic reticulum quality control （ERQC） machinery for the correct folding and proper assembly in order to reach its final destination. Genetic studies have demonstrated that ERD2b, a counterpart of the yeast or mammalian HDEL receptor ERD2 for retaining proteins in the endoplasmic reticulum （ER） lumen, is required for EFR function in plants （Li et al., 2009）. In this study, we characterized the Arabidopsis glucosidase Ⅱ β--subunit via the H DEL motif against the non-redundant protein database. Data mining also revealed that the glucosidase Ⅱ β--subunit gene has a highly similar expression pattern to ERD2b and the other known ERQC components involved in EFR biogenesis. Importantly, the T-DNA insertion lines of the glucosidase Ⅱ β-subunit gene showed that EFR-controlled responses were substantially reduced or completely blocked in these mutants. The responses include seedling growth inhibition, induction of marker genes, MAP kinase activation, and callose deposition, trigged by peptide elf18, a full mimic of E F-Tu. Taken together, ourdata indicate a requirement of the glucosidase Ⅱ β-subunitfor EFR function.
基金This work was supported by grants of National Natural Science Foundation of China （No. 81501083 and 81671236）.
文摘Background： Pompe disease is a rare lysosomal glycogen storage disorder linked to the acid alpha-glucosidase gene （GAA）. A wide clinical and genetic variability exists between patients from different ethnic populations, and the genotype-phenotype correlations are still not well understood. The aim of this study was to report the clinicopathological and genetic characteristics of five Chinese patients with late-onset Pompe disease （LOPD） who carried novel GAA gene mutations. Methods： Clinical and pathological data of patients diagnosed with glycogen storage disease at our institution from April 1986 to August 2017 were collected, and next-generation sequencing of frozen muscle specimens was conducted. Results： Of the five patients included in the study, the median disease onset age was 13 years, with a median 5 years delay in diagnosis. The patients mainly manifested as progressive weakness in the proximal and axial muscles, while one patient developed respiratory insufficiency that required artificial ventilation. In muscle biopsies, vacuoles with variable sizes and shapes appeared inside muscle fibers, and they stained positive for both periodic acid-Schiff and acid phosphatase staining. Ten GAA gene mutations, including seven novel ones （c.796C〉A, c. 1057C〉T, c. 1201C〉A, c. 1780C〉T, c. 1799G〉C, c.2051C〉A, c.2235dupG）, were identified by genetic tests. Conclusions： The seven novel GAA gene mutations revealed in this study broaden the genetic spectrum of LOPD and highlight the genetic heterogeneity in Chinese LOPD patients.
文摘In this study,a novel class of histidine Schiff base silver（Ⅰ） complexes derived from salicylaldehyde,1a-9a,was found to be an effective inhibitor of α-glucosidase.The results of this study showed that the newly synthesized complexes inhibited α-glucosidase through noncompetitive mechanisms;the IC50values were ranging from 0.00431 μmol L ~1 to 0.492 μmol L ~1.The structure-activity relationship was established as well.These results demonstrated that compound 7a,5-nitro salicylaldehyde Schiff base silver complex,is the most promising α-glucosidase inhibitor with the lowest IC50 value,which could be exploited as a drug candidate to alleviate postprandial hyperglycemia in the treatment of type II diabetes mellitus.This research provided a catalyst-free,simple,and environmentally benign reaction to synthesize compounds using mechanochemistry.
