The rising demand for energy storage solutions,especially in the electric vehicle and renewable energy sectors,highlights the importance of accurately predicting battery health to enhance their longevity and reliabili...The rising demand for energy storage solutions,especially in the electric vehicle and renewable energy sectors,highlights the importance of accurately predicting battery health to enhance their longevity and reliability.This article comprehensively examines various methods used to forecast battery health,including physics-based models,empirical models,and equivalent circuit models,among others.It delves into the promise of data-driven prognostics,utilizing both conventional machine learning and cuttingedge deep neural network techniques.The advantages and limitations of hybrid models are thoroughly analyzed,with a focus on the benefits of integrating diverse data sources to improve prognostic precision.Through practical case studies,the article showcases the effectiveness and flexibility of these approaches.It also critically addresses the challenges encountered in applying battery health prognostics in realworld scenarios,such as issues of scalability,complexity,and data anomalies.Despite these challenges,the article underscores the emerging opportunities brought about by recent technological,academic,and research advancements.These include the development of digital twin models for batteries,the use of data-centric AI and standardized benchmarking,the potential integration of blockchain technology for enhanced data security and transparency,and the synergy between edge and cloud computing to boost data analysis and processing.The primary goal of this article is to enrich the understanding of current battery health prognostic techniques and to inspire further research aimed at overcoming existing hurdles and tapping into new opportunities.It concludes with a visionary perspective on future research directions and potential developments in this evolving field,encouraging both researchers and practitioners to explore innovative solutions.展开更多
Actinobacteria able to produce varieties of bioactive natural products have been long appreciated by the field of drug discovery and development.Recently,a few of CRISPR/Cas9 systems bearing different types of replico...Actinobacteria able to produce varieties of bioactive natural products have been long appreciated by the field of drug discovery and development.Recently,a few of CRISPR/Cas9 systems bearing different types of replicons(pSG5 and pIJ101)were developed to efficiently edit their genomes.Despite wide application in gene editing,their utility in editing challenging DNA regions e.g.high sequence identity has not been compared.In this study,we confirmed that the widely used temperature-sensitive pSG5 replicon is indeed not suitable for editing modular polyketide synthase(PKS)genes due to causing unpredicted gene recombination.This problem can be addressed by replacing the pSG5 with the segregationally unstable pIJ101 replicon.By introducing a counterselection marker CodA,convenient cloning sites in the single guide RNAs(sgRNAs)and homologous template scaffolds,we developed a new CRISPR-Cas9 system pMWCas9.This system was successfully used to delete/replace erythromycin PKS and other biosynthetic genes in Saccharopolyspora erythraea and Streptomyces sp.AL2110.By swapping the promoters of antB and antC with ermE and kasOp,we achieved a deacyl-antimycin hyper producer which produces a 9-fold higher yield than the original Streptomyces sp.AL2110 strain.Our results provide a robust and useful Cas9 tool for genetic studies in Actinobacteria.展开更多
Introduction Liver transplantation(LT)benefits patients with decompensated liver cirrhosis,acute liver failure,or hepatocellular carcinoma.The greatest challenge in LT is the insufficient number of donors for the grow...Introduction Liver transplantation(LT)benefits patients with decompensated liver cirrhosis,acute liver failure,or hepatocellular carcinoma.The greatest challenge in LT is the insufficient number of donors for the growing number of transplantation candidates.Various surgical strategies have been adopted to overcome the increasing donor-recipient disparity,including sequential/“domino”transplantation,split LT,use of marginal livers,and living donor LT(LDLT).To ensure the safety of donors and recipients,dual-graft LT may be considered(1).Herein,we describe the first successful hybrid-dual-graft LT in an obese patient requiring urgent LT,which involved transplantation of an otherwise-wasted resected liver lobe from a patient with a benign hepatic tumor and an inadequate-size living donor graft from the recipient’s father.展开更多
Background:The associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)for hepatocellular carcinoma(HCC)with fibrosis/cirrhosis is often associated with limited growth of future liver remnant...Background:The associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)for hepatocellular carcinoma(HCC)with fibrosis/cirrhosis is often associated with limited growth of future liver remnant(FLR).We introduced a new procedure named transcatheter arterial embolization-salvaged ALPPS(TAE-salvaged ALPPS)which was shown to be especially suitable for HCC patients with cirrhosis or fibrosis who failed adequately to respond to conventional ALPPS.The short-term efficacy and safety for the TAE-salvaged ALPPS on patients with HCC and fibrosis/cirrhosis were studied.Methods:Consecutive HCC patients who underwent TAE-salvaged ALPPS in our hospital between November 2016 and June 2020 were retrospectively studied.The new ALPPS procedure included conventional ALPPS stage-1 using associating liver partition and portal vein ligation.When FLR failed to reach sufficient hypertrophy,TAE was carried out 2 weeks later followed by liver resection 3 weeks after ALPPS stage-1.Results:Nine of 10 patients had a single tumor(median diameter 14.0 cm,range,5.2-17 cm).The remaining patient had multiple tumors(diameter of one tumor 14.0 cm,and two satellite foci 2.0 and 3.0 cm).R0 resection was achieved in all patients(100%)after a median of 21 days.Six patients had cirrhosis,1 had METAVIR grade-3 fibrosis,and 3 had METAVIR grade-2 fibrosis.The median increase in FLR volume after TAE-salvaged ALPPS was 69.7%(34.4-143.9%).The absolute and relative kinetic growth rates(KGRs)were 9.9(7.1-17.3)mL/day and 3.4%(1.9-7.2%)/day,respectively.The median absolute KGRs were 15.7,2.6,and 19.5 mL/day in the first,second,and third postoperative weeks after ALPPS stage-1,respectively.The rapid increase in KGR on the third week was induced by TAE.The overall postoperative morbidity rates were 50,0%(5/10),20.0%(2/10)and 70.0%(7/10)after ALPPS stage-1,TAE and ALPPS stage-2,respectively.The 90-day mortality rate was 10.0%(1/10).The median overall survival was 40 months.Conclusions:The new TAE-salvaged ALPPS induced significant increases in FLR volumes within 3 weeks in patients with HCC and fibrosis/cirrhosis.The procedure is promising in treating patients with HCC and fibrosis/cirrhosis who fail to achieve sufficient FLR hypertrophy after conventional ALPPS stage-1.展开更多
Natural product discovery is pivot for drug development,however,this endeavor is often challenged by the wide inactivation or silence of natural products biosynthetic pathways.We recently developed a highly efficient ...Natural product discovery is pivot for drug development,however,this endeavor is often challenged by the wide inactivation or silence of natural products biosynthetic pathways.We recently developed a highly efficient approach to activate cryptic/silenced biosynthetic pathways through augmentation of the phosphopantetheinylation of carrier proteins.By applying this approach in the Streptomyces alboniger NRRL B-1832,we herein identified three cryptic nucleosides products,including one known puromycin A and two new derivatives(puromycin B and C).The biosynthesis of these products doesn't require the involvement of carrier protein,indicating the phosphopantetheinyl transferase(PPtase)indeed plays a fundamental regulatory role in metabolites biosynthesis.These results demonstrate that the PPtasebased approach have a much broader effective scope than the previously assumed carrier proteininvolving pathways,which will benefit future natural products discovery and biosynthetic studies.展开更多
The chemical diversity of terpenoids is typically established by terpene synthase-catalyzed cyclization and diversified by post-tailoring modifications.Fungal bifunctional terpene synthase(BFTS)associated P450 enzymes...The chemical diversity of terpenoids is typically established by terpene synthase-catalyzed cyclization and diversified by post-tailoring modifications.Fungal bifunctional terpene synthase(BFTS)associated P450 enzymes have shown significant catalytic potentials through the development of various new terpenoids with different biological activities.This study discovered the BFTS and its related gene cluster from the plant endophytic fungus Didymosphaeria variabile 17020.Heterologous expression of the BFTS in Saccharomyces cerevisiae resulted in the characterization of a major product diterpene variediene(1),along with two new minor products neovariediene and neoflexibilene.Further heterologous expression of the BFTS and one cytochrome P450 enzyme VndE(CYP6138B1)in Aspergillus oryzae NSAR1 led to the identification of seven norditerpenoids(19 carbons)with a structurally unique 5/5 bicyclic ring system.Interestingly,in vivo experiments suggested that the cyclized terpene variediene(1)was modified by VndE along with the endogenous enzymes from the host cell A.oryzae through serial chemical conversions,followed by multi-site hydroxylation via A.oryzae endogenous enzymes.Our work revealed that the two-enzymes biosynthetic system and host cell machinery could produce structurally unique terpenoids.展开更多
R-2-Bromobutyric acid is a very important intermediate for the synthesis of agrochemicals and pharmaceuticals.Bioresolution of rac-2-bromobutyric acid(rac-2-BBA)provides a promising process for R-2-bromobutyric acid(R...R-2-Bromobutyric acid is a very important intermediate for the synthesis of agrochemicals and pharmaceuticals.Bioresolution of rac-2-bromobutyric acid(rac-2-BBA)provides a promising process for R-2-bromobutyric acid(R-2-BBA)production.The fluoroacetate dehalogenase(FAcD)has been always studied in the defluorination process.We found that FAcD RPA1163 showed detectable activity but no enantioselectivity towards rac-2-BBA.The iterative saturation mutagenesis(ISM)of FAcD RPA1163 resulted in a mutant H155V/W156R/Y219M,which catalyzed the kinetic resolution of rac-2-BBA to produce R-2-BBA with enhanced activity and enantioselectivity(99.3%ee).The high preference for S-2-bromobutyric acid(S-2-BBA)is of synthetic value.Molecular docking analysis indicated that the H155V/W156R/Y219M mutation reduced steric hindrance and broadened the halide pocket.It is not only the steric hindrance but also the electrostatic environment that has an effect on the activity and enantioselectivity.展开更多
基金funded by the Independent Innovation Projects of the Hubei Longzhong Laboratory(2022ZZ-24)the Central Government to Guide Local Science and Technology Development fund Projects of Hubei Province(2022BGE267).
文摘The rising demand for energy storage solutions,especially in the electric vehicle and renewable energy sectors,highlights the importance of accurately predicting battery health to enhance their longevity and reliability.This article comprehensively examines various methods used to forecast battery health,including physics-based models,empirical models,and equivalent circuit models,among others.It delves into the promise of data-driven prognostics,utilizing both conventional machine learning and cuttingedge deep neural network techniques.The advantages and limitations of hybrid models are thoroughly analyzed,with a focus on the benefits of integrating diverse data sources to improve prognostic precision.Through practical case studies,the article showcases the effectiveness and flexibility of these approaches.It also critically addresses the challenges encountered in applying battery health prognostics in realworld scenarios,such as issues of scalability,complexity,and data anomalies.Despite these challenges,the article underscores the emerging opportunities brought about by recent technological,academic,and research advancements.These include the development of digital twin models for batteries,the use of data-centric AI and standardized benchmarking,the potential integration of blockchain technology for enhanced data security and transparency,and the synergy between edge and cloud computing to boost data analysis and processing.The primary goal of this article is to enrich the understanding of current battery health prognostic techniques and to inspire further research aimed at overcoming existing hurdles and tapping into new opportunities.It concludes with a visionary perspective on future research directions and potential developments in this evolving field,encouraging both researchers and practitioners to explore innovative solutions.
基金This work was supported by the National Nature Science Foundation of China Grants(Nos.31570057,31430002,31320103911 and 31770063)Taishan Scholarship and“the Fundamental Research Funds for the Central Universities 22221818014.
文摘Actinobacteria able to produce varieties of bioactive natural products have been long appreciated by the field of drug discovery and development.Recently,a few of CRISPR/Cas9 systems bearing different types of replicons(pSG5 and pIJ101)were developed to efficiently edit their genomes.Despite wide application in gene editing,their utility in editing challenging DNA regions e.g.high sequence identity has not been compared.In this study,we confirmed that the widely used temperature-sensitive pSG5 replicon is indeed not suitable for editing modular polyketide synthase(PKS)genes due to causing unpredicted gene recombination.This problem can be addressed by replacing the pSG5 with the segregationally unstable pIJ101 replicon.By introducing a counterselection marker CodA,convenient cloning sites in the single guide RNAs(sgRNAs)and homologous template scaffolds,we developed a new CRISPR-Cas9 system pMWCas9.This system was successfully used to delete/replace erythromycin PKS and other biosynthetic genes in Saccharopolyspora erythraea and Streptomyces sp.AL2110.By swapping the promoters of antB and antC with ermE and kasOp,we achieved a deacyl-antimycin hyper producer which produces a 9-fold higher yield than the original Streptomyces sp.AL2110 strain.Our results provide a robust and useful Cas9 tool for genetic studies in Actinobacteria.
基金supported by the National Natural Science Foundation of China(Nos.82150004,81830102),and Shanghai Municipal Key Clinical Specialty.
文摘Introduction Liver transplantation(LT)benefits patients with decompensated liver cirrhosis,acute liver failure,or hepatocellular carcinoma.The greatest challenge in LT is the insufficient number of donors for the growing number of transplantation candidates.Various surgical strategies have been adopted to overcome the increasing donor-recipient disparity,including sequential/“domino”transplantation,split LT,use of marginal livers,and living donor LT(LDLT).To ensure the safety of donors and recipients,dual-graft LT may be considered(1).Herein,we describe the first successful hybrid-dual-graft LT in an obese patient requiring urgent LT,which involved transplantation of an otherwise-wasted resected liver lobe from a patient with a benign hepatic tumor and an inadequate-size living donor graft from the recipient’s father.
基金This work was supported by grants from the National Natural Science Foundation of China(No.82150004).
文摘Background:The associating liver partition and portal vein ligation for staged hepatectomy(ALPPS)for hepatocellular carcinoma(HCC)with fibrosis/cirrhosis is often associated with limited growth of future liver remnant(FLR).We introduced a new procedure named transcatheter arterial embolization-salvaged ALPPS(TAE-salvaged ALPPS)which was shown to be especially suitable for HCC patients with cirrhosis or fibrosis who failed adequately to respond to conventional ALPPS.The short-term efficacy and safety for the TAE-salvaged ALPPS on patients with HCC and fibrosis/cirrhosis were studied.Methods:Consecutive HCC patients who underwent TAE-salvaged ALPPS in our hospital between November 2016 and June 2020 were retrospectively studied.The new ALPPS procedure included conventional ALPPS stage-1 using associating liver partition and portal vein ligation.When FLR failed to reach sufficient hypertrophy,TAE was carried out 2 weeks later followed by liver resection 3 weeks after ALPPS stage-1.Results:Nine of 10 patients had a single tumor(median diameter 14.0 cm,range,5.2-17 cm).The remaining patient had multiple tumors(diameter of one tumor 14.0 cm,and two satellite foci 2.0 and 3.0 cm).R0 resection was achieved in all patients(100%)after a median of 21 days.Six patients had cirrhosis,1 had METAVIR grade-3 fibrosis,and 3 had METAVIR grade-2 fibrosis.The median increase in FLR volume after TAE-salvaged ALPPS was 69.7%(34.4-143.9%).The absolute and relative kinetic growth rates(KGRs)were 9.9(7.1-17.3)mL/day and 3.4%(1.9-7.2%)/day,respectively.The median absolute KGRs were 15.7,2.6,and 19.5 mL/day in the first,second,and third postoperative weeks after ALPPS stage-1,respectively.The rapid increase in KGR on the third week was induced by TAE.The overall postoperative morbidity rates were 50,0%(5/10),20.0%(2/10)and 70.0%(7/10)after ALPPS stage-1,TAE and ALPPS stage-2,respectively.The 90-day mortality rate was 10.0%(1/10).The median overall survival was 40 months.Conclusions:The new TAE-salvaged ALPPS induced significant increases in FLR volumes within 3 weeks in patients with HCC and fibrosis/cirrhosis.The procedure is promising in treating patients with HCC and fibrosis/cirrhosis who fail to achieve sufficient FLR hypertrophy after conventional ALPPS stage-1.
基金This work was financially supported by NSFC(Nos.31322002,31500049 and 31270119,81760633)the State Key Laboratory of Microbial Metabolism(MMLKF17-08).
文摘Natural product discovery is pivot for drug development,however,this endeavor is often challenged by the wide inactivation or silence of natural products biosynthetic pathways.We recently developed a highly efficient approach to activate cryptic/silenced biosynthetic pathways through augmentation of the phosphopantetheinylation of carrier proteins.By applying this approach in the Streptomyces alboniger NRRL B-1832,we herein identified three cryptic nucleosides products,including one known puromycin A and two new derivatives(puromycin B and C).The biosynthesis of these products doesn't require the involvement of carrier protein,indicating the phosphopantetheinyl transferase(PPtase)indeed plays a fundamental regulatory role in metabolites biosynthesis.These results demonstrate that the PPtasebased approach have a much broader effective scope than the previously assumed carrier proteininvolving pathways,which will benefit future natural products discovery and biosynthetic studies.
基金the financial support from the National Key Research and Development Program of China(2020YFA0907800 and 2019YFA0906200)the National Natural Science Foundation of China(21907031,81903529,21977029,31720103901,21877124)+2 种基金the Open Project Funding of the State Key Laboratory of Bioreactor Engineeringthe 111 Project(B18022)Genome sequencing and assembly of strain DV17020 were supported by funding from the Natural Science and Engineering Research Council of Canada to Prof.T.Hsiang.
文摘The chemical diversity of terpenoids is typically established by terpene synthase-catalyzed cyclization and diversified by post-tailoring modifications.Fungal bifunctional terpene synthase(BFTS)associated P450 enzymes have shown significant catalytic potentials through the development of various new terpenoids with different biological activities.This study discovered the BFTS and its related gene cluster from the plant endophytic fungus Didymosphaeria variabile 17020.Heterologous expression of the BFTS in Saccharomyces cerevisiae resulted in the characterization of a major product diterpene variediene(1),along with two new minor products neovariediene and neoflexibilene.Further heterologous expression of the BFTS and one cytochrome P450 enzyme VndE(CYP6138B1)in Aspergillus oryzae NSAR1 led to the identification of seven norditerpenoids(19 carbons)with a structurally unique 5/5 bicyclic ring system.Interestingly,in vivo experiments suggested that the cyclized terpene variediene(1)was modified by VndE along with the endogenous enzymes from the host cell A.oryzae through serial chemical conversions,followed by multi-site hydroxylation via A.oryzae endogenous enzymes.Our work revealed that the two-enzymes biosynthetic system and host cell machinery could produce structurally unique terpenoids.
文摘R-2-Bromobutyric acid is a very important intermediate for the synthesis of agrochemicals and pharmaceuticals.Bioresolution of rac-2-bromobutyric acid(rac-2-BBA)provides a promising process for R-2-bromobutyric acid(R-2-BBA)production.The fluoroacetate dehalogenase(FAcD)has been always studied in the defluorination process.We found that FAcD RPA1163 showed detectable activity but no enantioselectivity towards rac-2-BBA.The iterative saturation mutagenesis(ISM)of FAcD RPA1163 resulted in a mutant H155V/W156R/Y219M,which catalyzed the kinetic resolution of rac-2-BBA to produce R-2-BBA with enhanced activity and enantioselectivity(99.3%ee).The high preference for S-2-bromobutyric acid(S-2-BBA)is of synthetic value.Molecular docking analysis indicated that the H155V/W156R/Y219M mutation reduced steric hindrance and broadened the halide pocket.It is not only the steric hindrance but also the electrostatic environment that has an effect on the activity and enantioselectivity.