Ginkgo biloba resources in China are enormous. With the demand of the market, the preparation and application of flavonoids have become a current research hotspot. The main active substances in G. biloba leaves, flavo...Ginkgo biloba resources in China are enormous. With the demand of the market, the preparation and application of flavonoids have become a current research hotspot. The main active substances in G. biloba leaves, flavonoids, have various functional activities and are widely used in fields such as food, medicine, cosmetics, feed, etc. In this paper, the introduction, functional activity, extraction methods, and application research of flavonoids from G. biloba leaves are reviewed, and the development prospects of flavonoids from G. biloba leaves are expected.展开更多
Cellulase is a complex enzyme that can decompose cellulose into glucose,and it could effectively treat cellulose waste. In this paper,it aims to explore development status and research progress of cellulase,and introd...Cellulase is a complex enzyme that can decompose cellulose into glucose,and it could effectively treat cellulose waste. In this paper,it aims to explore development status and research progress of cellulase,and introduce concept and action mechanism of cellulase,research situation of cellulase in molecular aspect,application of cellulase,and development of cellulase is also prospected.展开更多
Pectinase is a group of enzymes that can decompose complex pectin into small molecules such as galacturonic acid. It is mainly produced by microorganisms by liquid and solid fermentation and immobilized cell method. I...Pectinase is a group of enzymes that can decompose complex pectin into small molecules such as galacturonic acid. It is mainly produced by microorganisms by liquid and solid fermentation and immobilized cell method. Its representative strain is Aspergillus niger,and yeast and actinomycete are also high-yield strains for screening pectinase. Pectinase can be used in many fields of life and production,such as clarification of fruit juice and wine,pulping of paper making industry,degumming of textile,extracting of traditional Chinese medicine components,animal feed and other industries,which is economic,green,and efficient and pollution-free. Moreover,pectinase is one of the four major enzymes in the world,and its practical application has very important significance,and the prospect of pectinase application is also important.展开更多
The research status of nutrient composition, medicinal value, development and utilization and cultivation techniques of purslane was analyzed to provide reference for further development and utilization of medicinal p...The research status of nutrient composition, medicinal value, development and utilization and cultivation techniques of purslane was analyzed to provide reference for further development and utilization of medicinal plant purslane.展开更多
In the paper, the homoclinic (hateroclinic) breather limit method (HBLM) is applied to seek rogue wave solution of the Benjamin Ono equation. We find that the rational breather wave solution is just a rogue wave solut...In the paper, the homoclinic (hateroclinic) breather limit method (HBLM) is applied to seek rogue wave solution of the Benjamin Ono equation. We find that the rational breather wave solution is just a rogue wave solution. This result shows that rogue wave can come from the extreme behavior of the breather solitary wave for (1+1)-dimensional nonlinear wave fields.展开更多
In the paper, we will discuss the Kadomtsev-Petviashvili Equation which is used to model shallow-water waves with weakly non-linear restoring forces and is also used to model waves in ferromagnetic media by employing ...In the paper, we will discuss the Kadomtsev-Petviashvili Equation which is used to model shallow-water waves with weakly non-linear restoring forces and is also used to model waves in ferromagnetic media by employing the method of variable separation. Abundant exact solutions including global smooth solutions and local blow up solutions are obtained. These solutions would contribute to studying the behavior and blow up properties of the solution of the Kadomtsev-Petviashvili Equation.展开更多
This paper studied and compared the effects of three preservation methods( normal temperature 20℃,fresh-keeping box cold storage 4℃,and fresh-keeping box + fresh-keeping film cold storage 4℃) on six kinds of vegeta...This paper studied and compared the effects of three preservation methods( normal temperature 20℃,fresh-keeping box cold storage 4℃,and fresh-keeping box + fresh-keeping film cold storage 4℃) on six kinds of vegetables. The results showed that the content of vitamin C in the six vegetables was higher in cold storage than in normal temperature storage; the nitrate content was lower in cold storage than in normal temperature storage. In both the normal temperature storage and cold storage,the vitamin C in vegetables declined with the increase of the storage time,while the nitrate content increased with the increase of the storage time. Thus,cold storage has better fresh-keeping effect for vegetables. In cold storage conditions,the vitamin C content was higher in vegetables packaged by fresh-keeping box,and the nitrate content was lower,followed by the fresh-keeping film + fresh-keeping box cold storage. In conclusion,the best preservation method for vegetable is fresh-keeping box cold storage.展开更多
[Objectives] Taking Polygala tenuifolia Willd. seeds as experimental material, the changes of physiological and biochemical characteristics of seeds under different storage temperatures and seed moisture contents were...[Objectives] Taking Polygala tenuifolia Willd. seeds as experimental material, the changes of physiological and biochemical characteristics of seeds under different storage temperatures and seed moisture contents were studied. [Methods] The seeds of P. tenuifolia Willd. with moisture contents of 3%, 5% and 15% were stored at-10 ℃, 0 ℃, 20 ℃ and 36 ℃, respectively, and the storage time was one year. The physiological and biochemical characteristics of the seeds, such as conductivity, SOD activity, POD activity, and soluble sugar content were studied.[Results] After one-year storage, as the storage temperature and seed moisture content increased, the relative conductivity, MDA content and soluble sugar content of P. tenuifolia Willd. seeds increased, while the SOD activity, POD activity, and protein content declined. This phenomenon was most obvious in the P. tenuifolia Willd. seeds with moisture content of 15%. [Conclusions] This study will provide reference for seed storage of medicinal plants.展开更多
Objective:To establish a new genomic signature for the prognosis of survival in relation to the tumor microenvironment in esophageal adenocarcinoma.Methods:Data from The Cancer Genome Atlas(TCGA)were applied,and the s...Objective:To establish a new genomic signature for the prognosis of survival in relation to the tumor microenvironment in esophageal adenocarcinoma.Methods:Data from The Cancer Genome Atlas(TCGA)were applied,and the stromal and immune scores of patients with esophageal adenocarcinoma(EAC)were generated through the ESTIMATE algorithm.Differentially expressed genes were obtained,and genes concerning immune prognosis were identified on the basis of these scores.Functional analysis showed that these genes were primarily involved in immunobiological processes.Additionally,CIBERSORT was used to analyze 22 subgroups of tumor-infiltrating immune cells in the tumor microenvironment.Results:The results of the genomic assessment shown on the Kaplan-Meier curve revealed that EAC patients with high-risk scores have the worst survival.The risk score is valid as an independent prognostic factor for the overall survival in EAC patients.The tumor microenvironment was systematically analyzed,and the immune-related prognostic biomarkers of EAC have been proposed.Conclusion:The expression of tumor-infiltrating immune cells and immune-related genes in EAC have been identified.Some previously overlooked genes may be used as additional biomarkers for EAC in the future.展开更多
Rapid analysis of metal ions and organic compounds in strong acidic solutions is of sustainable interest in multiple disciplines.However,complicated and time-consuming pretreatments are always required for MS analysis...Rapid analysis of metal ions and organic compounds in strong acidic solutions is of sustainable interest in multiple disciplines.However,complicated and time-consuming pretreatments are always required for MS analysis of the compounds in strong acidic solutions.Otherwise,it will result in a weak signal and cause serious damage to the mass spectrometer.Herein,a simple method inherited from nano-ESI MS was developed for rapid analysis of strong acidic solutions.Nanoliter(nL)strong acidic solution was first loaded in the nano-ESI emitter,followed by evaporation to remove the H+and leave the analytes on the wall of the nano-ESI emitter.The evaporation process can be completed within 1 min because of the extremely tiny volume(≤1 nL)of the loaded solution.Then,the dried analytes on the wall of the nano-ESI emitter were redissolved by loading a new solvent,followed by nano-ESI MS analysis.By using this method,metal ions and organic compounds in the strong acidic solution can be detected with low sample consumption(1 nL),high speed(<2 min/sample),high sensitivity(limit of detection=0.2µg/L),and high accuracy(>90%).Proof-of-concept applications of the present method have been successfully achieved for the analysis of gastric juice(pH of the sample=1),monitoring reaction catalyzed by strong acid(pH of the system=0),and micro-area analysis of ores(pH of the extraction solvent=0),showing great application potential in multiple fields.展开更多
Viruses often manipulate ubiquitination pathways to facilitate their replication and pathogenesis.CUL2ZYG11B known as the substrate receptor of cullin-2 RING E3 ligase,is bound by SARS-CoV-2 ORF10 to increase its E3 l...Viruses often manipulate ubiquitination pathways to facilitate their replication and pathogenesis.CUL2ZYG11B known as the substrate receptor of cullin-2 RING E3 ligase,is bound by SARS-CoV-2 ORF10 to increase its E3 ligase activity,leading to degradation of IFT46,a protein component of the intraflagellar transport(IFT)complex B.This results in dysfunctional cilia,which explains certain symptoms that are specific to COVID-19.However,the precise molecular mechanism of how ORF10 recognizes CUL2ZYG11B remains unknown.Here,we determined the crystal structure of CUL2ZYG11B complexed with the N-terminal extension(NTE)of SARS-CoV-2 ORF10(2.9 A°).The structure reveals that the ORF10 N-terminal heptapeptide(NTH)mimics the Gly/N-degron to bind CUL2ZYG11B.Mutagenesis studies identified key residues within ORF10 that are key players in its interaction with CUL2ZYG11B both in ITC assay and in vivo cells.In addition,we prove that enhancement of CUL2ZYG11B activity for IFT46 degradation by which ORF10-mediated correlates with the binding affinity between ORF10 and CUL2ZYG11B.Finally,we used a Global Protein Stability system to show that the NTH of ORF10 mimics the Gly/N-degron motif,thereby binding competitively to CUL2ZYG11B and inhibiting the degradation of target substrates bearing the Gly/N-degron motif.Overall,this study sheds light on how SARS-CoV-2 ORF10 exploits the ubiquitination machinery for proteasomal degradation,and offers valuable insights for optimizing PROTAC-based drug design based on NTH CUL2ZYG11B interaction,while pinpointing a promising target for the development of treatments for COVID-19.展开更多
Dear Editor,The safety and modernization of traditional Chinese medicine (TCM) are significant concerns for users’ lives and health. Recently, the adverse effects caused by TCM and traditional nontoxic TCM have been ...Dear Editor,The safety and modernization of traditional Chinese medicine (TCM) are significant concerns for users’ lives and health. Recently, the adverse effects caused by TCM and traditional nontoxic TCM have been frequently reported (Joo et al., 2020;Liu et al., 2021). As the safety of TCM continues to attract widespread attention, many researchers have been investigating the toxicity of TCM in regard to the toxic ingredients, effects, mechanisms, and detoxification strategies in TCM (Figure S1 in Supporting Information). Although some TCMs cause toxic reactions, they also play key roles in treating certain unignorable diseases (Fang et al., 2022).Therefore, toxicity research is crucial and urgently needed to develop and safely use TCM.展开更多
Tumor relapse is the major cause of treatment failure in childhood acute lymphoblastic leukemia(ALL),yet the underlying mechanisms are still elusive.Here,we demonstrate that phosphoribosyl pyrophosphate synthetase 2(P...Tumor relapse is the major cause of treatment failure in childhood acute lymphoblastic leukemia(ALL),yet the underlying mechanisms are still elusive.Here,we demonstrate that phosphoribosyl pyrophosphate synthetase 2(PRPS2)mutations drive ALL relapse through influencing PRPS1/2 hexamer stability.Ultra-deep sequencing was performed to identify PRPS2 mutations in ALL samples.The effects of PRPS2 mutations on cell survival,cell apoptosis,and drug resistance were evaluated.In vitro PRPS2 enzyme activity and ADP/GDP feedback inhibition of PRPS enzyme activity were assessed.Purine metabolites were analyzed by ultra-performance liquid-chromatography tandem mass spectrometry(UPLC–MS/MS).Integrating sequencing data with clinical information,we identified PRPS2 mutations only in relapsed childhood ALL with thiopurine therapy.Functional PRPS2 mutations mediated purine metabolism specifically on thiopurine treatment by influencing PRPS1/2 hexamer stability,leading to reduced nucleotide feedback inhibition of PRPS activity and enhanced thiopurine resistance.The 3-amino acid V103-G104-E105,the key difference between PRPS1 and PRPS2,insertion in PRPS2 caused severe steric clash to the interface of PRPS hexamer,leading to its low enzyme activity.In addition,we demonstrated that PRPS2 P173R increased thiopurine resistance in xenograft models.Our work describes a novel mechanism by which PRPS2 mutants drive childhood ALL relapse and highlights PRPS2 mutations as biomarkers for relapsed childhood ALL.展开更多
The CRISPR/Cas system has been extensively applied to make precise genetic modifications in various organisms. Despite its importance and widespread use, large-scale mutation screening remains time-consuming, labour-i...The CRISPR/Cas system has been extensively applied to make precise genetic modifications in various organisms. Despite its importance and widespread use, large-scale mutation screening remains time-consuming, labour-intensive and costly. Here, we developed Hi-TOM(available at http://www.hi-tom.net/hi-tom/), an online tool to track the mutations with precise percentage for multiple samples and multiple target sites. We also described a corresponding next-generation sequencing(NGS) library construction strategy by fixing the bridge sequences and barcoding primers. Analysis of the samples from rice, hexaploid wheat and human cells reveals that the Hi-TOM tool has high reliability and sensitivity in tracking various mutations, especially complex chimeric mutations frequently induced by genome editing. Hi-TOM does not require special design of barcode primers,cumbersome parameter configuration or additional data analysis. Thus, the streamlined NGS library construction and comprehensive result output make Hi-TOM particularly suitable for high-throughput identification of all types of mutations induced by CRISPR/Cas systems.展开更多
Transition metal sulfides are of great relevance in pho-toelectrochemical catalytic reactions[1-3],due to their unique electronic structure,tunable composition and morphology,and the possibility of large scale synthes...Transition metal sulfides are of great relevance in pho-toelectrochemical catalytic reactions[1-3],due to their unique electronic structure,tunable composition and morphology,and the possibility of large scale synthesis.We have been looking for low-cost,high-efficiency,and durable catalysts.展开更多
Background and purpose As studies vary in defining the prognostic significance of smoking in acute ischaemic stroke(AIS),we aimed to determine the relation of smoking and key outcomes in patient participants who had t...Background and purpose As studies vary in defining the prognostic significance of smoking in acute ischaemic stroke(AIS),we aimed to determine the relation of smoking and key outcomes in patient participants who had thrombolysed AIS of the international quasi-factorial randomised Enhanced Control of Hypertension and Thrombolysis Stroke Study(ENCHANTED).Methods Post-hoc analyses of ENCHANTED,an international quasi-factorial randomised evaluation of intravenous alteplase-dose comparison and levels of blood pressure control in patients who had thrombolysed AIS.Multivariable logistic regression models with inverse probability of treatment weighting(IPTW)propensity scores were used to determine associations of self-reported smoking status and clinical outcomes,according to 90-day modified Rankin Scale(mRS)scores and symptomatic intracerebral haemorrhage(sICH).Results Of 4540 patients who had an AIS,there were 1008(22.2%)current smokers who were younger and predominantly male,with more comorbidities of hypertension,coronary artery disease,atrial fibrillation and diabetes mellitus,and greater baseline neurological impairment,compared with non-smokers.In univariate analysis,current smokers had a higher likelihood of a favourable shift in mRS scores(OR 0.88,95%CI 0.77 to 0.99;p=0.038)but this association reversed in a fully adjusted model with IPTW(adjusted OR 1.15,95%CI 1.04 to 1.28;p=0.009).A similar trend was also apparent for dichotomised poor outcome(mRS scores 2–6:OR 1.18,95%CI 1.05 to 1.33;p=0.007),but not with the risk of sICH across standard criteria.Conclusion Smoking predicts poor functional recovery in patients who had thrombolysed AIS.Trial registration number NCT01422616.展开更多
基金Supported by Science and Technology Research Project of Hebei Provincial Department of Education (ZC2021206)。
文摘Ginkgo biloba resources in China are enormous. With the demand of the market, the preparation and application of flavonoids have become a current research hotspot. The main active substances in G. biloba leaves, flavonoids, have various functional activities and are widely used in fields such as food, medicine, cosmetics, feed, etc. In this paper, the introduction, functional activity, extraction methods, and application research of flavonoids from G. biloba leaves are reviewed, and the development prospects of flavonoids from G. biloba leaves are expected.
文摘Cellulase is a complex enzyme that can decompose cellulose into glucose,and it could effectively treat cellulose waste. In this paper,it aims to explore development status and research progress of cellulase,and introduce concept and action mechanism of cellulase,research situation of cellulase in molecular aspect,application of cellulase,and development of cellulase is also prospected.
文摘Pectinase is a group of enzymes that can decompose complex pectin into small molecules such as galacturonic acid. It is mainly produced by microorganisms by liquid and solid fermentation and immobilized cell method. Its representative strain is Aspergillus niger,and yeast and actinomycete are also high-yield strains for screening pectinase. Pectinase can be used in many fields of life and production,such as clarification of fruit juice and wine,pulping of paper making industry,degumming of textile,extracting of traditional Chinese medicine components,animal feed and other industries,which is economic,green,and efficient and pollution-free. Moreover,pectinase is one of the four major enzymes in the world,and its practical application has very important significance,and the prospect of pectinase application is also important.
文摘The research status of nutrient composition, medicinal value, development and utilization and cultivation techniques of purslane was analyzed to provide reference for further development and utilization of medicinal plant purslane.
文摘In the paper, the homoclinic (hateroclinic) breather limit method (HBLM) is applied to seek rogue wave solution of the Benjamin Ono equation. We find that the rational breather wave solution is just a rogue wave solution. This result shows that rogue wave can come from the extreme behavior of the breather solitary wave for (1+1)-dimensional nonlinear wave fields.
文摘In the paper, we will discuss the Kadomtsev-Petviashvili Equation which is used to model shallow-water waves with weakly non-linear restoring forces and is also used to model waves in ferromagnetic media by employing the method of variable separation. Abundant exact solutions including global smooth solutions and local blow up solutions are obtained. These solutions would contribute to studying the behavior and blow up properties of the solution of the Kadomtsev-Petviashvili Equation.
文摘This paper studied and compared the effects of three preservation methods( normal temperature 20℃,fresh-keeping box cold storage 4℃,and fresh-keeping box + fresh-keeping film cold storage 4℃) on six kinds of vegetables. The results showed that the content of vitamin C in the six vegetables was higher in cold storage than in normal temperature storage; the nitrate content was lower in cold storage than in normal temperature storage. In both the normal temperature storage and cold storage,the vitamin C in vegetables declined with the increase of the storage time,while the nitrate content increased with the increase of the storage time. Thus,cold storage has better fresh-keeping effect for vegetables. In cold storage conditions,the vitamin C content was higher in vegetables packaged by fresh-keeping box,and the nitrate content was lower,followed by the fresh-keeping film + fresh-keeping box cold storage. In conclusion,the best preservation method for vegetable is fresh-keeping box cold storage.
文摘[Objectives] Taking Polygala tenuifolia Willd. seeds as experimental material, the changes of physiological and biochemical characteristics of seeds under different storage temperatures and seed moisture contents were studied. [Methods] The seeds of P. tenuifolia Willd. with moisture contents of 3%, 5% and 15% were stored at-10 ℃, 0 ℃, 20 ℃ and 36 ℃, respectively, and the storage time was one year. The physiological and biochemical characteristics of the seeds, such as conductivity, SOD activity, POD activity, and soluble sugar content were studied.[Results] After one-year storage, as the storage temperature and seed moisture content increased, the relative conductivity, MDA content and soluble sugar content of P. tenuifolia Willd. seeds increased, while the SOD activity, POD activity, and protein content declined. This phenomenon was most obvious in the P. tenuifolia Willd. seeds with moisture content of 15%. [Conclusions] This study will provide reference for seed storage of medicinal plants.
基金College-Level Youth Fund Project(Project Number:ZZYQ2012).
文摘Objective:To establish a new genomic signature for the prognosis of survival in relation to the tumor microenvironment in esophageal adenocarcinoma.Methods:Data from The Cancer Genome Atlas(TCGA)were applied,and the stromal and immune scores of patients with esophageal adenocarcinoma(EAC)were generated through the ESTIMATE algorithm.Differentially expressed genes were obtained,and genes concerning immune prognosis were identified on the basis of these scores.Functional analysis showed that these genes were primarily involved in immunobiological processes.Additionally,CIBERSORT was used to analyze 22 subgroups of tumor-infiltrating immune cells in the tumor microenvironment.Results:The results of the genomic assessment shown on the Kaplan-Meier curve revealed that EAC patients with high-risk scores have the worst survival.The risk score is valid as an independent prognostic factor for the overall survival in EAC patients.The tumor microenvironment was systematically analyzed,and the immune-related prognostic biomarkers of EAC have been proposed.Conclusion:The expression of tumor-infiltrating immune cells and immune-related genes in EAC have been identified.Some previously overlooked genes may be used as additional biomarkers for EAC in the future.
基金supported by the National Natural Science Foundation of China(Nos.21864001,21727812 and 21765001)the Ph.D.Start-up Foundation of East China University of Technology(No.DHBK2020001).
文摘Rapid analysis of metal ions and organic compounds in strong acidic solutions is of sustainable interest in multiple disciplines.However,complicated and time-consuming pretreatments are always required for MS analysis of the compounds in strong acidic solutions.Otherwise,it will result in a weak signal and cause serious damage to the mass spectrometer.Herein,a simple method inherited from nano-ESI MS was developed for rapid analysis of strong acidic solutions.Nanoliter(nL)strong acidic solution was first loaded in the nano-ESI emitter,followed by evaporation to remove the H+and leave the analytes on the wall of the nano-ESI emitter.The evaporation process can be completed within 1 min because of the extremely tiny volume(≤1 nL)of the loaded solution.Then,the dried analytes on the wall of the nano-ESI emitter were redissolved by loading a new solvent,followed by nano-ESI MS analysis.By using this method,metal ions and organic compounds in the strong acidic solution can be detected with low sample consumption(1 nL),high speed(<2 min/sample),high sensitivity(limit of detection=0.2µg/L),and high accuracy(>90%).Proof-of-concept applications of the present method have been successfully achieved for the analysis of gastric juice(pH of the sample=1),monitoring reaction catalyzed by strong acid(pH of the system=0),and micro-area analysis of ores(pH of the extraction solvent=0),showing great application potential in multiple fields.
基金the following staff members and grant support.BL19U1 beamline of the National Facility for Protein Science in Shanghai(NFPS),BL17U1 beamline,and BL10U2 beamline at the Shanghai Synchrotron Radiation Facility.We thank the staff of PX III beamline at the Swiss Light Source,PaulScherrer Institute(Villigen Switzerland)for assistance in data collection.We thank the staffs from the Core Facility of National Institute of Pathogen Biology,Chinese Academy of Medical Sciences.This work was supported by National Key Research and Development Program of China(2023YFC2307803)Chinese Academy of Medical Sciences(CAMS)Innovation Fund for Medical Sciences(2022-I2M-1-021,China)+2 种基金the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences(2023-PT310-04,China)National Natural Science Foundation of China(82341095,82261160398,82072291,82272308)the Fundamental Research Funds for the Central Universities(3332021092,China).
文摘Viruses often manipulate ubiquitination pathways to facilitate their replication and pathogenesis.CUL2ZYG11B known as the substrate receptor of cullin-2 RING E3 ligase,is bound by SARS-CoV-2 ORF10 to increase its E3 ligase activity,leading to degradation of IFT46,a protein component of the intraflagellar transport(IFT)complex B.This results in dysfunctional cilia,which explains certain symptoms that are specific to COVID-19.However,the precise molecular mechanism of how ORF10 recognizes CUL2ZYG11B remains unknown.Here,we determined the crystal structure of CUL2ZYG11B complexed with the N-terminal extension(NTE)of SARS-CoV-2 ORF10(2.9 A°).The structure reveals that the ORF10 N-terminal heptapeptide(NTH)mimics the Gly/N-degron to bind CUL2ZYG11B.Mutagenesis studies identified key residues within ORF10 that are key players in its interaction with CUL2ZYG11B both in ITC assay and in vivo cells.In addition,we prove that enhancement of CUL2ZYG11B activity for IFT46 degradation by which ORF10-mediated correlates with the binding affinity between ORF10 and CUL2ZYG11B.Finally,we used a Global Protein Stability system to show that the NTH of ORF10 mimics the Gly/N-degron motif,thereby binding competitively to CUL2ZYG11B and inhibiting the degradation of target substrates bearing the Gly/N-degron motif.Overall,this study sheds light on how SARS-CoV-2 ORF10 exploits the ubiquitination machinery for proteasomal degradation,and offers valuable insights for optimizing PROTAC-based drug design based on NTH CUL2ZYG11B interaction,while pinpointing a promising target for the development of treatments for COVID-19.
基金supported by the National Natural Science Foundation of China (81873194, 81573825, 81273998)the National Talent Project of “Youth Qihuang Scholars”(2020)。
文摘Dear Editor,The safety and modernization of traditional Chinese medicine (TCM) are significant concerns for users’ lives and health. Recently, the adverse effects caused by TCM and traditional nontoxic TCM have been frequently reported (Joo et al., 2020;Liu et al., 2021). As the safety of TCM continues to attract widespread attention, many researchers have been investigating the toxicity of TCM in regard to the toxic ingredients, effects, mechanisms, and detoxification strategies in TCM (Figure S1 in Supporting Information). Although some TCMs cause toxic reactions, they also play key roles in treating certain unignorable diseases (Fang et al., 2022).Therefore, toxicity research is crucial and urgently needed to develop and safely use TCM.
基金National Natural Science Foundation of China(81972341,81900158,81772663,81874078,82072896)Shanghai Municipal Science and Technology Commission(201409002700,19JC1413500,21XD1403100)+1 种基金Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20161310)Pudong New Area Science&Technology Development Fund(PKJ2018-Y47).
文摘Tumor relapse is the major cause of treatment failure in childhood acute lymphoblastic leukemia(ALL),yet the underlying mechanisms are still elusive.Here,we demonstrate that phosphoribosyl pyrophosphate synthetase 2(PRPS2)mutations drive ALL relapse through influencing PRPS1/2 hexamer stability.Ultra-deep sequencing was performed to identify PRPS2 mutations in ALL samples.The effects of PRPS2 mutations on cell survival,cell apoptosis,and drug resistance were evaluated.In vitro PRPS2 enzyme activity and ADP/GDP feedback inhibition of PRPS enzyme activity were assessed.Purine metabolites were analyzed by ultra-performance liquid-chromatography tandem mass spectrometry(UPLC–MS/MS).Integrating sequencing data with clinical information,we identified PRPS2 mutations only in relapsed childhood ALL with thiopurine therapy.Functional PRPS2 mutations mediated purine metabolism specifically on thiopurine treatment by influencing PRPS1/2 hexamer stability,leading to reduced nucleotide feedback inhibition of PRPS activity and enhanced thiopurine resistance.The 3-amino acid V103-G104-E105,the key difference between PRPS1 and PRPS2,insertion in PRPS2 caused severe steric clash to the interface of PRPS hexamer,leading to its low enzyme activity.In addition,we demonstrated that PRPS2 P173R increased thiopurine resistance in xenograft models.Our work describes a novel mechanism by which PRPS2 mutants drive childhood ALL relapse and highlights PRPS2 mutations as biomarkers for relapsed childhood ALL.
基金supported by the National Key Research and Development Program of China (2017YFD0102002)the Agricultural Science and Technology Innovation Program of Chinese Academy of Agricultural Sciencesthe National Natural Science Foundation of China (31401363)
文摘The CRISPR/Cas system has been extensively applied to make precise genetic modifications in various organisms. Despite its importance and widespread use, large-scale mutation screening remains time-consuming, labour-intensive and costly. Here, we developed Hi-TOM(available at http://www.hi-tom.net/hi-tom/), an online tool to track the mutations with precise percentage for multiple samples and multiple target sites. We also described a corresponding next-generation sequencing(NGS) library construction strategy by fixing the bridge sequences and barcoding primers. Analysis of the samples from rice, hexaploid wheat and human cells reveals that the Hi-TOM tool has high reliability and sensitivity in tracking various mutations, especially complex chimeric mutations frequently induced by genome editing. Hi-TOM does not require special design of barcode primers,cumbersome parameter configuration or additional data analysis. Thus, the streamlined NGS library construction and comprehensive result output make Hi-TOM particularly suitable for high-throughput identification of all types of mutations induced by CRISPR/Cas systems.
基金the funding support from the National Natural Science Foundation of China(61774033)Guangdong Province Key Area R&D Program(2019B010940001)。
文摘Transition metal sulfides are of great relevance in pho-toelectrochemical catalytic reactions[1-3],due to their unique electronic structure,tunable composition and morphology,and the possibility of large scale synthesis.We have been looking for low-cost,high-efficiency,and durable catalysts.
基金the National Health and Medical Research Council(NHMRC)of Australia(Project Grant 1020462)the Stroke Association of the United Kingdom(Reference TSA 2012/01)the National Council for Scientific and Technological Development of Brazil(CNPq grant number 467322/2014-7).
文摘Background and purpose As studies vary in defining the prognostic significance of smoking in acute ischaemic stroke(AIS),we aimed to determine the relation of smoking and key outcomes in patient participants who had thrombolysed AIS of the international quasi-factorial randomised Enhanced Control of Hypertension and Thrombolysis Stroke Study(ENCHANTED).Methods Post-hoc analyses of ENCHANTED,an international quasi-factorial randomised evaluation of intravenous alteplase-dose comparison and levels of blood pressure control in patients who had thrombolysed AIS.Multivariable logistic regression models with inverse probability of treatment weighting(IPTW)propensity scores were used to determine associations of self-reported smoking status and clinical outcomes,according to 90-day modified Rankin Scale(mRS)scores and symptomatic intracerebral haemorrhage(sICH).Results Of 4540 patients who had an AIS,there were 1008(22.2%)current smokers who were younger and predominantly male,with more comorbidities of hypertension,coronary artery disease,atrial fibrillation and diabetes mellitus,and greater baseline neurological impairment,compared with non-smokers.In univariate analysis,current smokers had a higher likelihood of a favourable shift in mRS scores(OR 0.88,95%CI 0.77 to 0.99;p=0.038)but this association reversed in a fully adjusted model with IPTW(adjusted OR 1.15,95%CI 1.04 to 1.28;p=0.009).A similar trend was also apparent for dichotomised poor outcome(mRS scores 2–6:OR 1.18,95%CI 1.05 to 1.33;p=0.007),but not with the risk of sICH across standard criteria.Conclusion Smoking predicts poor functional recovery in patients who had thrombolysed AIS.Trial registration number NCT01422616.