16 ADT carboxylate esters were prepared by means of esterification and these compounds were expected to increase the bioavailability of 4-hydroxyanehole trithione.In vivo studies showed that ADT concentration of 3a in...16 ADT carboxylate esters were prepared by means of esterification and these compounds were expected to increase the bioavailability of 4-hydroxyanehole trithione.In vivo studies showed that ADT concentration of 3a in plasma was much higher than that of ATT during 120 min.Compound 3a could reach blood peak values of ADT at 660.6 ng/mL which was about 14 times of that by ATT.Additionally,the acute toxicity assay indicated high safety of compound 3a that the maximum tolerated dose was no less than 3.25 g/kg.展开更多
The composition of fatty acids in triacylglycerides （TAGs） and their position on the glycerol backbone de- termine the nutritional value of vegetable oil. In this study, gas chromatography and high-performance liqui...The composition of fatty acids in triacylglycerides （TAGs） and their position on the glycerol backbone de- termine the nutritional value of vegetable oil. In this study, gas chromatography and high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） were used to analyze the compo- sition and distribution of fatty acids in TAGs of different rapeseed oils. Our results show the content of oleic acid in higb-oleic-acid rapeseed oil to be about 80%. In terms of the number of acyl carbon atoms （CN）, TAGs with CN52-54 were most abundant, with a maximum concentration at CN54 （80%）. The main type of TAG was oleic-oleic-oleic （OOO）, accounting for 71.75%, while oleic-oleic-linoleic （OOL） accounted for ？.56%, oleic-oleic-linolenic （OOLn） accounted for 4.81%, and stearic-oleic-oleic （SO0） accounted for 4.74%. Oleic acid in high-oleic-acid rapeseed oil was distributed in the following order of preference： sn-2 〉 sn-1/3. In high-erucic-acid rapeseed oil, however, oleic acid was enriched at the sn-1/3. These data show that the content of oleic acid can be as high as about 80% in high-oleic-acid material. This finding suggests that high-oleic-acid rapeseed oil has high nutritional value.展开更多
To establish identification and evaluation methods of N(nitrogen)absorption and utilization of rapeseed(Brassica napus L.),difference of N nutrition efficiency(NNE)among rapeseed germplasms and relationship between NN...To establish identification and evaluation methods of N(nitrogen)absorption and utilization of rapeseed(Brassica napus L.),difference of N nutrition efficiency(NNE)among rapeseed germplasms and relationship between NNE and plant traits under various N application rates were analyzed in this research.Pot cultivating experiments were conducted to investigate NNE with 3 N application rates in soil(0.05,0.2 and 0.3 g/kg).A total of 12 rapeseed germplasms were planted,nitrogen absorption efficiency(NAE)and nitrogen utilization efficiency(NUE)in seedling stage,bolting stage,initial flowering stage,final flowering stage,and maturity stage were obtained.Results showed that bolting stage was the best period for NAE identification and evaluation.Low N application rate in soil(0.05 g/kg)was the best for NAE,and the indirect indexes were basal stem diameter,plant root dry weight and above ground plant dry weight.Maturity stage was the best period for NUE identification and evaluation.High N application rate in soil(0.3 g/kg)was the best for NUE,and indirect indexes were above ground plant dry weight and basal stem diameter.N application rates of 0.05 g/kg in soil was the best for nitrogen harvest index at maturity stage,and indirect indexes was number of pods per plant.Plant traits of rapeseed germplasms affected NNE.Higher basal stem diameter,plant root dry weight and above ground plant dry weight at bolting stage under low N application rate were important characteristics of N absorption in rapeseed.Higher above ground plant dry weight and basal stem diameter at maturity stage under high N application rate were important characteristics of N utilization.Higher number of pods per plant at maturity stage under lowe N application rate was an important characteristic of N harvest index.These results provided a reliable index for N management and provided theoretical basis for guiding rapeseed breeding.展开更多
Two chiral building blocks 1 and 2 for anti-and syn-1, 3-diols has been achieved in 8 steps and 7 steps respectively, starting from the readily available and inexpensive D (+)-xylose 3.
Nor-1α, 25-dihydroxy-22-oxo-vitamin D3 4 was synthesized by the coupling of known compound 5 and the A-ring phosphine oxide 6 followed by deprotection of the hydroxy functions.
High oleic acid rapeseed oil offers superior nutritional and health benefits,but its mass production is limited due to poor resistance and slightly lower yield.Photosynthesis serves as the foundation of biological sur...High oleic acid rapeseed oil offers superior nutritional and health benefits,but its mass production is limited due to poor resistance and slightly lower yield.Photosynthesis serves as the foundation of biological survival and closely correlates with crop resistance to stresses,yield,and quality.To identify photosynthesis-related genes,transcriptome sequencing was conducted on high oleic acid rapeseed Gaoyousuan No.1 and low oleic acid rapeseed Xiangyou 15 resulting in the identification of a total of 9396 differentially expressed genes(4669 upregulated and 4727 down-regulated).From these genes nine candidate genes were screened using GO and KEGG analysis with BnGLO4 being selected for cloning purposes.The BnGLO4 gene fragment has a length of 1161 bp with an ORF sequence of 1092 bp encoding a theoretical isoelectric point of pI 7.60;it encodes an unstable lipid-soluble protein localized in peroxisomes without transmembrane structural domains or signal peptides.Its amino acid sequence homology was highest with that of BnaA01G0355200ZS,BnaA01G0355600ZS,BnaA05G0410400ZS,BnaC01G0441800ZS,and Brassica rapa(XP_009117145.1),Brassica napus(CDY39100.1),Brassica cretica(KAF3533604.1)and Brassica oleracea var.oleracea(XP_013610644.1)belonging to the same cruciferous family.The BnGLO4 gene may be associated with responses to abiotic stresses such as salt,drought,and temperature extremes along with photosynthesis and growth in rapeseed plants.The expression levels of the GLO4 gene(BnaA01G0355200 ZS)were highest in filaments while being higher at each stage in seeds and siliques with the highest expression level at day 14 in seeds.Expression was significantly upregulated after 3 h of salt stress treatment,reaching a maximum at 12 h before slightly decreasing at 24 h.The findings of this study lay a foundation for further investigation on photosynthesis and stress response in high oleic rapeseed.展开更多
Flower color,an important rapeseed character,has great practical value and research significance.It has become an area of intensive research in recent years.This paper summarizes the latest research progress on rape f...Flower color,an important rapeseed character,has great practical value and research significance.It has become an area of intensive research in recent years.This paper summarizes the latest research progress on rape flower color in terms of variety,source,pigment composition,formation mechanism,and omics.Moreover,it provides an overview of rape flower color breeding and omics.展开更多
Fatty acid(FA)desaturases,as the key enzymes in lipid metabolism,are responsible for biosynthesis of the unsaturated fatty FAs,which play important roles in maintaining cell membrane integrity and multiple stress resp...Fatty acid(FA)desaturases,as the key enzymes in lipid metabolism,are responsible for biosynthesis of the unsaturated fatty FAs,which play important roles in maintaining cell membrane integrity and multiple stress responses.Although attention has been drawn to some plant FA desaturase genes,their global landscape in oil crops is still lacking.Here,we performed systematic characterization and phylogenomic synteny network analyses of the FA desaturase gene family in polyploid oil crop B.napus and other 54 species covering major streptophyte lineages.A total of 1653 FA desaturase genes were identified from these plant genomes.Based on the broad-scale family phylogeny and functional domains,we proposed a unified eight-group classification system for angiosperm FA desaturases,and found that the origin of genes responsible for FA desaturation evolved early and some genes were absent in different species.Phylogenomic analyses revealed deeply conserved syntenic relationships within each of the eight FA desaturase groups.B.napus contains up to 93 FA desaturase genes from the eight groups.Recurrent duplication events in Brassicaceae contributed to the expansion of FA desaturase genes in B.napus,leading to further functional diversification.These FA desaturase genes exhibited spatio-temporal specific expression patterns in different tissues of B.napus,and a set of FA desaturase genes seem to be orchestrated by key transcriptional factors during seed development,such as zf-HD,B3,GATA3,PEI1,NFYA7,YAB1 and YAB2.Altogether,our data have inferred the evolutionary trajectory of this important gene family across distinct plant lineages,providing theoretical basis for future manipulation of FA desaturase genes to improve the seed oil quality of B.napus.展开更多
Gene editing technology provides important technical basics for the research in plant functional genes and crop genetic improvement.CRISPR/Cas9-mediated gene editing is an effective experimental tool for crop genome d...Gene editing technology provides important technical basics for the research in plant functional genes and crop genetic improvement.CRISPR/Cas9-mediated gene editing is an effective experimental tool for crop genome directed editing in recent years,which has been widely used in many crops as rice,wheat and other crops.CRISPR/Cas9 system was expected to be a powerful experimental tool in genetic improvement and molecular design breeding of rapeseed.This paper,which based on the development history and the latest research of CRISPR/Cas9-mediated gene editing technology in rapeseed,summarized the progress of CRISPR/Cas9 including plant type improvement,yield traits,quality improvement,disease and stress resistance improvement,yellow seed creation and other utilizes at present.The application scope,development direction and target analysis method of this technology in rape were focused.The problems of CRISPR/cas9 system in rapeseed breeding were analyzed and the improvement strategies were discussed.Finally,views on direction of rapeseed breeding by gene editing were emphasized.展开更多
The gene-expression profiles between the Sclerotinia-resistant and its nearisogenic susceptible rapeseed lines (Brassica napus) infected with Sclerotinia sclerotiorum were examined by microarray analysis. 102 differen...The gene-expression profiles between the Sclerotinia-resistant and its nearisogenic susceptible rapeseed lines (Brassica napus) infected with Sclerotinia sclerotiorum were examined by microarray analysis. 102 differentially expressed genes (DEGs)were successfully identified, including genes highly related to pathogen resistance. Among these DEGs, 46 were up-regulated and 56 were down-regulated. To verify the reliability of microarray, 2 up-regulated genes (NM_130355 and NM_126666) and 1 down-regulated gene (NM_100191) were chosen and their expression level were detected by real-time fluorescence-based quantitative PCR analysis (RT-PCR). Subsequently, the 102 DEGs were GO (gene ontology) annotated, and to be classified into 22 categories, including enzymes,binding proteins, transcription factors, and proteins with unknown functions. Further subcellular localization prediction demonstrated that these DEGs might be located in/on intracellular region, cell wall, cell membrane, cytoplasm, nucleus, endoplasmic reticulum, chloroplasts and mitochondria. The analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that 10 DEGs were participated in several known biological pathways, including lysine biosynthesis, sulfur assimilation, cysteine metabolism, carotenoid biosynthesis, glyoxylic acid and oxalic acid metabolism etc. Taken together, the preliminary results would provide important information for exploring the molecular basis of Sclerotinia-resistance in Brassica napus.展开更多
Malignant insulinomas are rare neuroendocrine tumors that require management for both symptomatic control and tumor reduction.It is clinically challenging to optimize treatment strategies for refractory malignant insu...Malignant insulinomas are rare neuroendocrine tumors that require management for both symptomatic control and tumor reduction.It is clinically challenging to optimize treatment strategies for refractory malignant insulinoma.We report a case of metastatic grade 3 insulinoma presented with recurrent hypoglycemia in a 23-year-old female with RAD51D p.Q192 germline mutation.During the disease course of 5 years,the tumor has continuously progressed despite locoregional therapy and multiple lines of systemic treatment.However,oxaliplatin-based chemotherapy achieved a partial response,which was maintained for 2 years.The hypoglycemic symptoms were controlled after the treatment response and did not recur.The platinum-based regimen could be a feasible therapeutic strategy for malignant insulinoma.The relationship between germline mutation in the DNA damage repair pathway and treatment response to platinum-based regimens in neuroendocrine tumors warrants further investigation.展开更多
Background:A therapeutic strategy involving combined treatment with lenvatinib plus pembrolizumab(LEP)has demonstrated a relatively high antitumor response in several solid tumors;however,the efficacy and safety of LE...Background:A therapeutic strategy involving combined treatment with lenvatinib plus pembrolizumab(LEP)has demonstrated a relatively high antitumor response in several solid tumors;however,the efficacy and safety of LEP in patients with refractory bile tract carcinoma(BTC)remains unknown.Methods:This is a single-arm study for a preliminary assessment of the efficacy and tolerability of LEP in patients who experienced progression from prior systemic treatments.Pre-treatment tumor tissues were collected to retrospectively evaluate the expression status of PDL1.Results:Thirty-two patients received second-line and above treatment with LEP.Overall,the objective response rate(ORR)was 25%,the disease control rate(DCR)was 78.1%,and the clinical benefit rate(CBR)was 40.5%.The median progression-free survival(PFS)was 4.9 months(95%CI:4.7–5.2 months),and the median overall survival(OS)was 11.0 months(95%CI:9.6–12.3 months).For tolerability,no grade 5 serious adverse events(AEs)were reported.All patients had any-grade AEs,and 59.3%of the patients experienced grade 3 AEs,while only 1 patient experienced a grade 4 AE of stomach bleeding.Fatigue was the most common AE,followed by hypertension and elevated aminotransferase levels.Retrospective analysis for PDL1 expression revealed that PDL1 positive tumor cells were associated with improved clinical benefits and survival outcomes.Conclusions:LEP is a promising alternative as a non-first-line therapeutic regimen for patients with refractory BTC.Furthermore,well-designed prospective clinical trials with a control arm are still needed to obtain more evidences to confirm the efficacy and safety of this particular regimen as well as the role of PDL1 expression.展开更多
A high oleic acid rapeseed material MI5 （derived from Xiangyou 15 variety） has been received more attention for its significant effect for human health. And it has almost the same physiological characteristic with X...A high oleic acid rapeseed material MI5 （derived from Xiangyou 15 variety） has been received more attention for its significant effect for human health. And it has almost the same physiological characteristic with Xiangyou 15 variety. To find out the difference between high oleic acid rapeseed material and Xiangyou 15 seedling, a comparative proteomic approach based on 2-DE and mass spectrometry was adopted. A total of 277 protein spots showed a significant change in intensity by more than 2.0-fold from M15 compared with Xiangyou 15 variety. Among them, 48 spots that changed at least 3.0-fold were excised from gels and successfully identified by MALDI-TOF/TOF MS. The identified proteins involved in metabolism of carbohydrate and energy （75%）, stress and defense （8.3%）, photosynthesis （6.3%）, protein metabolism （2.1%） and other functions （8.3%）. Then real-time quantitative PCR （qPCR） analysis was used to verify the expression levels of differentially expressed proteins, but the results did well agree with the proteomic results. In this work, most of the proteins involved in metabolism of carbohydrate and energy have higher expression in M15, which may reveal M15 has higher metabolism ability. These results provided much information to understand the differences between high oleic acid rapeseed material and Xiangyou 15 variety, which will be useful to screen high oleic rapeseed materials in seedling period.展开更多
The synthesis of two isomers of Aprepitant （APT） and three isomers of Fosaprepitant （FPT）, crucial components for quality control in manufacturing, is described. Herein, three chiral centers in the isomers of Apre...The synthesis of two isomers of Aprepitant （APT） and three isomers of Fosaprepitant （FPT）, crucial components for quality control in manufacturing, is described. Herein, three chiral centers in the isomers of Aprepitant are established in high yield by induced crystallization and chiral reduction. Additionally, the isomers of Aprepitant are utilized to synthesize the isomers of Fosaprepitant with the same stereochemistry. All the target compounds were confirmed by elemental analyses, 1R, NMR and MS data analysis.展开更多
文摘16 ADT carboxylate esters were prepared by means of esterification and these compounds were expected to increase the bioavailability of 4-hydroxyanehole trithione.In vivo studies showed that ADT concentration of 3a in plasma was much higher than that of ATT during 120 min.Compound 3a could reach blood peak values of ADT at 660.6 ng/mL which was about 14 times of that by ATT.Additionally,the acute toxicity assay indicated high safety of compound 3a that the maximum tolerated dose was no less than 3.25 g/kg.
文摘The composition of fatty acids in triacylglycerides （TAGs） and their position on the glycerol backbone de- termine the nutritional value of vegetable oil. In this study, gas chromatography and high-performance liquid chromatography-tandem mass spectrometry （HPLC-MS/MS） were used to analyze the compo- sition and distribution of fatty acids in TAGs of different rapeseed oils. Our results show the content of oleic acid in higb-oleic-acid rapeseed oil to be about 80%. In terms of the number of acyl carbon atoms （CN）, TAGs with CN52-54 were most abundant, with a maximum concentration at CN54 （80%）. The main type of TAG was oleic-oleic-oleic （OOO）, accounting for 71.75%, while oleic-oleic-linoleic （OOL） accounted for ？.56%, oleic-oleic-linolenic （OOLn） accounted for 4.81%, and stearic-oleic-oleic （SO0） accounted for 4.74%. Oleic acid in high-oleic-acid rapeseed oil was distributed in the following order of preference： sn-2 〉 sn-1/3. In high-erucic-acid rapeseed oil, however, oleic acid was enriched at the sn-1/3. These data show that the content of oleic acid can be as high as about 80% in high-oleic-acid material. This finding suggests that high-oleic-acid rapeseed oil has high nutritional value.
基金This research was partially granted by the National Science Foundation of China(31760393)the Double Thousand Talent Plan of Jiangxi Province,and the Doctoral Program of Jiangxi Academy of Agricultural Sciences(20162CBS009).
文摘To establish identification and evaluation methods of N(nitrogen)absorption and utilization of rapeseed(Brassica napus L.),difference of N nutrition efficiency(NNE)among rapeseed germplasms and relationship between NNE and plant traits under various N application rates were analyzed in this research.Pot cultivating experiments were conducted to investigate NNE with 3 N application rates in soil(0.05,0.2 and 0.3 g/kg).A total of 12 rapeseed germplasms were planted,nitrogen absorption efficiency(NAE)and nitrogen utilization efficiency(NUE)in seedling stage,bolting stage,initial flowering stage,final flowering stage,and maturity stage were obtained.Results showed that bolting stage was the best period for NAE identification and evaluation.Low N application rate in soil(0.05 g/kg)was the best for NAE,and the indirect indexes were basal stem diameter,plant root dry weight and above ground plant dry weight.Maturity stage was the best period for NUE identification and evaluation.High N application rate in soil(0.3 g/kg)was the best for NUE,and indirect indexes were above ground plant dry weight and basal stem diameter.N application rates of 0.05 g/kg in soil was the best for nitrogen harvest index at maturity stage,and indirect indexes was number of pods per plant.Plant traits of rapeseed germplasms affected NNE.Higher basal stem diameter,plant root dry weight and above ground plant dry weight at bolting stage under low N application rate were important characteristics of N absorption in rapeseed.Higher above ground plant dry weight and basal stem diameter at maturity stage under high N application rate were important characteristics of N utilization.Higher number of pods per plant at maturity stage under lowe N application rate was an important characteristic of N harvest index.These results provided a reliable index for N management and provided theoretical basis for guiding rapeseed breeding.
文摘Two chiral building blocks 1 and 2 for anti-and syn-1, 3-diols has been achieved in 8 steps and 7 steps respectively, starting from the readily available and inexpensive D (+)-xylose 3.
基金Financial support from the National Natural Science foundation of China (No: 29972013) is gratefully acknowledged.
文摘Nor-1α, 25-dihydroxy-22-oxo-vitamin D3 4 was synthesized by the coupling of known compound 5 and the A-ring phosphine oxide 6 followed by deprotection of the hydroxy functions.
基金This work was financially supported by China Agriculture Research System of MOF and MARA(CARS-13)Hunan Agriculture Research System of DARA.
文摘High oleic acid rapeseed oil offers superior nutritional and health benefits,but its mass production is limited due to poor resistance and slightly lower yield.Photosynthesis serves as the foundation of biological survival and closely correlates with crop resistance to stresses,yield,and quality.To identify photosynthesis-related genes,transcriptome sequencing was conducted on high oleic acid rapeseed Gaoyousuan No.1 and low oleic acid rapeseed Xiangyou 15 resulting in the identification of a total of 9396 differentially expressed genes(4669 upregulated and 4727 down-regulated).From these genes nine candidate genes were screened using GO and KEGG analysis with BnGLO4 being selected for cloning purposes.The BnGLO4 gene fragment has a length of 1161 bp with an ORF sequence of 1092 bp encoding a theoretical isoelectric point of pI 7.60;it encodes an unstable lipid-soluble protein localized in peroxisomes without transmembrane structural domains or signal peptides.Its amino acid sequence homology was highest with that of BnaA01G0355200ZS,BnaA01G0355600ZS,BnaA05G0410400ZS,BnaC01G0441800ZS,and Brassica rapa(XP_009117145.1),Brassica napus(CDY39100.1),Brassica cretica(KAF3533604.1)and Brassica oleracea var.oleracea(XP_013610644.1)belonging to the same cruciferous family.The BnGLO4 gene may be associated with responses to abiotic stresses such as salt,drought,and temperature extremes along with photosynthesis and growth in rapeseed plants.The expression levels of the GLO4 gene(BnaA01G0355200 ZS)were highest in filaments while being higher at each stage in seeds and siliques with the highest expression level at day 14 in seeds.Expression was significantly upregulated after 3 h of salt stress treatment,reaching a maximum at 12 h before slightly decreasing at 24 h.The findings of this study lay a foundation for further investigation on photosynthesis and stress response in high oleic rapeseed.
基金funded by the China Agriculture Research System of MOF and MARA (CARS-13),Hunan Agriculture Research System of DARA (Xiangnongfa)。
文摘Flower color,an important rapeseed character,has great practical value and research significance.It has become an area of intensive research in recent years.This paper summarizes the latest research progress on rape flower color in terms of variety,source,pigment composition,formation mechanism,and omics.Moreover,it provides an overview of rape flower color breeding and omics.
基金funded by the Agricultural Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences(CAAS-ASTIP-OCRI),the National Natural Science Foundation of China(grant number 31801399)the Research Foundation of Education Bureau of Hunan Province,China(grant number 21A0135)。
文摘Fatty acid(FA)desaturases,as the key enzymes in lipid metabolism,are responsible for biosynthesis of the unsaturated fatty FAs,which play important roles in maintaining cell membrane integrity and multiple stress responses.Although attention has been drawn to some plant FA desaturase genes,their global landscape in oil crops is still lacking.Here,we performed systematic characterization and phylogenomic synteny network analyses of the FA desaturase gene family in polyploid oil crop B.napus and other 54 species covering major streptophyte lineages.A total of 1653 FA desaturase genes were identified from these plant genomes.Based on the broad-scale family phylogeny and functional domains,we proposed a unified eight-group classification system for angiosperm FA desaturases,and found that the origin of genes responsible for FA desaturation evolved early and some genes were absent in different species.Phylogenomic analyses revealed deeply conserved syntenic relationships within each of the eight FA desaturase groups.B.napus contains up to 93 FA desaturase genes from the eight groups.Recurrent duplication events in Brassicaceae contributed to the expansion of FA desaturase genes in B.napus,leading to further functional diversification.These FA desaturase genes exhibited spatio-temporal specific expression patterns in different tissues of B.napus,and a set of FA desaturase genes seem to be orchestrated by key transcriptional factors during seed development,such as zf-HD,B3,GATA3,PEI1,NFYA7,YAB1 and YAB2.Altogether,our data have inferred the evolutionary trajectory of this important gene family across distinct plant lineages,providing theoretical basis for future manipulation of FA desaturase genes to improve the seed oil quality of B.napus.
基金This work was supported by the National Major Project for Developing New GM Crops(2018ZX08020001).
文摘Gene editing technology provides important technical basics for the research in plant functional genes and crop genetic improvement.CRISPR/Cas9-mediated gene editing is an effective experimental tool for crop genome directed editing in recent years,which has been widely used in many crops as rice,wheat and other crops.CRISPR/Cas9 system was expected to be a powerful experimental tool in genetic improvement and molecular design breeding of rapeseed.This paper,which based on the development history and the latest research of CRISPR/Cas9-mediated gene editing technology in rapeseed,summarized the progress of CRISPR/Cas9 including plant type improvement,yield traits,quality improvement,disease and stress resistance improvement,yellow seed creation and other utilizes at present.The application scope,development direction and target analysis method of this technology in rape were focused.The problems of CRISPR/cas9 system in rapeseed breeding were analyzed and the improvement strategies were discussed.Finally,views on direction of rapeseed breeding by gene editing were emphasized.
文摘The gene-expression profiles between the Sclerotinia-resistant and its nearisogenic susceptible rapeseed lines (Brassica napus) infected with Sclerotinia sclerotiorum were examined by microarray analysis. 102 differentially expressed genes (DEGs)were successfully identified, including genes highly related to pathogen resistance. Among these DEGs, 46 were up-regulated and 56 were down-regulated. To verify the reliability of microarray, 2 up-regulated genes (NM_130355 and NM_126666) and 1 down-regulated gene (NM_100191) were chosen and their expression level were detected by real-time fluorescence-based quantitative PCR analysis (RT-PCR). Subsequently, the 102 DEGs were GO (gene ontology) annotated, and to be classified into 22 categories, including enzymes,binding proteins, transcription factors, and proteins with unknown functions. Further subcellular localization prediction demonstrated that these DEGs might be located in/on intracellular region, cell wall, cell membrane, cytoplasm, nucleus, endoplasmic reticulum, chloroplasts and mitochondria. The analysis of Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways revealed that 10 DEGs were participated in several known biological pathways, including lysine biosynthesis, sulfur assimilation, cysteine metabolism, carotenoid biosynthesis, glyoxylic acid and oxalic acid metabolism etc. Taken together, the preliminary results would provide important information for exploring the molecular basis of Sclerotinia-resistance in Brassica napus.
文摘Malignant insulinomas are rare neuroendocrine tumors that require management for both symptomatic control and tumor reduction.It is clinically challenging to optimize treatment strategies for refractory malignant insulinoma.We report a case of metastatic grade 3 insulinoma presented with recurrent hypoglycemia in a 23-year-old female with RAD51D p.Q192 germline mutation.During the disease course of 5 years,the tumor has continuously progressed despite locoregional therapy and multiple lines of systemic treatment.However,oxaliplatin-based chemotherapy achieved a partial response,which was maintained for 2 years.The hypoglycemic symptoms were controlled after the treatment response and did not recur.The platinum-based regimen could be a feasible therapeutic strategy for malignant insulinoma.The relationship between germline mutation in the DNA damage repair pathway and treatment response to platinum-based regimens in neuroendocrine tumors warrants further investigation.
基金This work was supported by grants from the International Science and Technology Cooperation Projects(2016YFE0107100 and 2015DFA30650)CAMS Innovation Fund for Medical Science(CIFMS)(2017-I2M-4-003)+1 种基金Beijing Natural Science Foundation(L172055)National Ten-thousand Talent Program,Beijing Science and Technology Cooperation Special Award Subsidy Project and CAMS Initiative for Innovative Medicine(CAMS-2018-I2M-3-001)
文摘Background:A therapeutic strategy involving combined treatment with lenvatinib plus pembrolizumab(LEP)has demonstrated a relatively high antitumor response in several solid tumors;however,the efficacy and safety of LEP in patients with refractory bile tract carcinoma(BTC)remains unknown.Methods:This is a single-arm study for a preliminary assessment of the efficacy and tolerability of LEP in patients who experienced progression from prior systemic treatments.Pre-treatment tumor tissues were collected to retrospectively evaluate the expression status of PDL1.Results:Thirty-two patients received second-line and above treatment with LEP.Overall,the objective response rate(ORR)was 25%,the disease control rate(DCR)was 78.1%,and the clinical benefit rate(CBR)was 40.5%.The median progression-free survival(PFS)was 4.9 months(95%CI:4.7–5.2 months),and the median overall survival(OS)was 11.0 months(95%CI:9.6–12.3 months).For tolerability,no grade 5 serious adverse events(AEs)were reported.All patients had any-grade AEs,and 59.3%of the patients experienced grade 3 AEs,while only 1 patient experienced a grade 4 AE of stomach bleeding.Fatigue was the most common AE,followed by hypertension and elevated aminotransferase levels.Retrospective analysis for PDL1 expression revealed that PDL1 positive tumor cells were associated with improved clinical benefits and survival outcomes.Conclusions:LEP is a promising alternative as a non-first-line therapeutic regimen for patients with refractory BTC.Furthermore,well-designed prospective clinical trials with a control arm are still needed to obtain more evidences to confirm the efficacy and safety of this particular regimen as well as the role of PDL1 expression.
基金Acknowledgements This work was financially supported by the Natural Science Foundation of China （31201240, 31000722, 31200522）, National High Technology Research and Development Program of China （2012AA101107-3）, the foundation of Key Laboratory of Biology and Genetic Improvement of Oil Crops （2014008）, and the crop science foundation of Hunan Agricultural University （ZWKF201302）.
文摘A high oleic acid rapeseed material MI5 （derived from Xiangyou 15 variety） has been received more attention for its significant effect for human health. And it has almost the same physiological characteristic with Xiangyou 15 variety. To find out the difference between high oleic acid rapeseed material and Xiangyou 15 seedling, a comparative proteomic approach based on 2-DE and mass spectrometry was adopted. A total of 277 protein spots showed a significant change in intensity by more than 2.0-fold from M15 compared with Xiangyou 15 variety. Among them, 48 spots that changed at least 3.0-fold were excised from gels and successfully identified by MALDI-TOF/TOF MS. The identified proteins involved in metabolism of carbohydrate and energy （75%）, stress and defense （8.3%）, photosynthesis （6.3%）, protein metabolism （2.1%） and other functions （8.3%）. Then real-time quantitative PCR （qPCR） analysis was used to verify the expression levels of differentially expressed proteins, but the results did well agree with the proteomic results. In this work, most of the proteins involved in metabolism of carbohydrate and energy have higher expression in M15, which may reveal M15 has higher metabolism ability. These results provided much information to understand the differences between high oleic acid rapeseed material and Xiangyou 15 variety, which will be useful to screen high oleic rapeseed materials in seedling period.
基金fnancial support from Sichuan provincial science and technology support program (No. 2011SZ0014)
文摘The synthesis of two isomers of Aprepitant （APT） and three isomers of Fosaprepitant （FPT）, crucial components for quality control in manufacturing, is described. Herein, three chiral centers in the isomers of Aprepitant are established in high yield by induced crystallization and chiral reduction. Additionally, the isomers of Aprepitant are utilized to synthesize the isomers of Fosaprepitant with the same stereochemistry. All the target compounds were confirmed by elemental analyses, 1R, NMR and MS data analysis.
