Objective:To explore the diagnostic value of endoscopic ultrasound(EUS)in the staging of rectal cancer.Methods:Fifty patients with rectal cancer,treated at the Department of Endoscopy,Cancer Hospital Affiliated to Fud...Objective:To explore the diagnostic value of endoscopic ultrasound(EUS)in the staging of rectal cancer.Methods:Fifty patients with rectal cancer,treated at the Department of Endoscopy,Cancer Hospital Affiliated to Fudan University,from March 2023 to June 2024,were selected.All patients underwent EUS and computed tomography(CT)examination within two weeks before surgery.The postoperative pathological staging was used as the standard to compare the accuracy of tumor TN staging using EUS and/or CT.Results:The accuracy rates of T and N staging by abdominal spiral CT were 72.00%and 76.00%,respectively,while those by EUS were 88.00%and 74%,respectively.There was a significant difference in the accuracy of T staging between the two methods(both P<0.05).Conclusion:EUS has high diagnostic value in the staging of rectal cancer,providing important reference information for clinicians,aiding in the development of personalized treatment plans,and assessing patient prognosis.展开更多
Vitamin B6 plays a crucial role in cellular metabolism and stress response,making it an essential component for growth in all known organisms.However,achieving efficient biosynthesis of vitamin B6 faces the challenge ...Vitamin B6 plays a crucial role in cellular metabolism and stress response,making it an essential component for growth in all known organisms.However,achieving efficient biosynthesis of vitamin B6 faces the challenge of maintaining a balanced distribution of metabolic flux between growth and production.In this study,our focus is on addressing this challenge through the engineering of phosphoserine aminotransferase(SerC)to resolve its redundancy and promiscuity.The enzyme SerC was semi-designed and screened based on sequences and predicted kcat values,respectively.Mutants and heterologous proteins showing potential were then fine-tuned to optimize the production of vitamin B6.The resulting strain enhances the production of vitamin B6,indicating that different fluxes are distributed to the biosynthesis pathway of serine and vitamin B6.This study presents a promising strategy to address the challenge posed by multifunctional enzymes,with significant implications for enhancing biochemical production through engineering processes.展开更多
Optimizing the supply of biosynthetic precursors and cofactors is usually an effective metabolic strategy to improve the production of target compounds.Here,the combination of optimizing precursor synthesis and balanc...Optimizing the supply of biosynthetic precursors and cofactors is usually an effective metabolic strategy to improve the production of target compounds.Here,the combination of optimizing precursor synthesis and balancing cofactor metabolism was adopted to improve tryptophan production in Escherichia coli.First,glutamine synthesis was improved by expressing heterologous glutamine synthetase from Bacillus subtilis and Bacillus megaterium in the engineered Escherichia coli strain KW001,resulting in the best candidate strain TS-1.Then icd and gdhA were overexpressed in TS-1,which led to the accumulation of 1.060 g/L tryptophan.Subsequently,one more copy of prs was introduced on the chromosome to increase the flux of 5-phospho-α-D-ribose 1-diphosphate followed by the expression of mutated serA and thrA to increase the precursor supply of serine,resulting in the accumulation of 1.380 g/L tryptophan.Finally,to maintain cofactor balance,sthA and pntAB,encoding transhydrogenase,were overexpressed.With sufficient amounts of precursors and balanced cofactors,the engineered strain could produce 1.710 g/L tryptophan after 48 h of shake-flask fermentation,which was 2.76-times higher than the titer of the parent strain.Taken together,our results demonstrate that the combination of optimizing precursor supply and regulating cofactor metabolism is an effective approach for high-level production of tryptophan.Similar strategies could be applied to the production of other amino acids or related derivatives.展开更多
Cell cycle is a fundamental process underlying growth and development in evolutionarily diverse organisms, including fungi. In human fungal pathogens, cell cycle control generally determines their life cycles, either ...Cell cycle is a fundamental process underlying growth and development in evolutionarily diverse organisms, including fungi. In human fungal pathogens, cell cycle control generally determines their life cycles, either in the environment or during infections.Thus, cell cycle components can potentially serve as important targets for the development of antifungal strategy against fungal infections. Here, in Cryptococcus neoformans, the most common cause of fatal fungal meningitis, we show that a previously uncharacterized B-type cyclin named Cbc1 is essential for both its infectious and sexual cycles. We reveal that Cbc1 coordinates various sexual differentiation and molecular processes, including meiosis. Especially, the absence of Cbc1 abolishes formation of sexual spores in C. neoformans, which are presumed infectious particles. Cbc1 is also required for the major Cryptococcus pathogenic attributes. Virulence assessment using the murine model of cryptococcosis revealed that the cbc1 mutant is avirulent.Together, our results provide an important insight into how C. neoformans employs shared cell cycle regulation to coordinate its infectious and sexual cycles, which are considered crucial for virulence evolution and the production of infectious spores.展开更多
Newton’s law of gravity is a theory of instantaneous action at a distance.However,Einstein’s general relativity states that the speed of gravity equals the speed of light,which is finite.Therefore,it is a worthy pro...Newton’s law of gravity is a theory of instantaneous action at a distance.However,Einstein’s general relativity states that the speed of gravity equals the speed of light,which is finite.Therefore,it is a worthy problem to discuss if Newton’s law of gravity needs modification,when studying and observing the gravitational tidal.In this paper,it is shown that the Newton’s law of gravity is fully applicable in the framework of general relativity.Based on the post-Newtonian approximation,we find that the observable effect for the speed of gravity is irrelevant to the velocity of a moving source,but it is dependent on its acceleration.In general,the effect of the speed of gravity is so weak that today’s any astronomical observations,including the sun tidal observations,can not confirm that the gravitational field travels at the speed of light.展开更多
文摘Objective:To explore the diagnostic value of endoscopic ultrasound(EUS)in the staging of rectal cancer.Methods:Fifty patients with rectal cancer,treated at the Department of Endoscopy,Cancer Hospital Affiliated to Fudan University,from March 2023 to June 2024,were selected.All patients underwent EUS and computed tomography(CT)examination within two weeks before surgery.The postoperative pathological staging was used as the standard to compare the accuracy of tumor TN staging using EUS and/or CT.Results:The accuracy rates of T and N staging by abdominal spiral CT were 72.00%and 76.00%,respectively,while those by EUS were 88.00%and 74%,respectively.There was a significant difference in the accuracy of T staging between the two methods(both P<0.05).Conclusion:EUS has high diagnostic value in the staging of rectal cancer,providing important reference information for clinicians,aiding in the development of personalized treatment plans,and assessing patient prognosis.
基金This work was supported by the National Key R&D Program of China(2022YFC2106100)National Natural Science Foundation of China(22178372,32200049)+2 种基金National Science Fund for Distinguished Young Scholars(22325807)Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(TSBICIP-KJGG-011,TSBICIP-CXRC-055)Yellow River Delta Industry Leading Talents(DYRC20190212).
文摘Vitamin B6 plays a crucial role in cellular metabolism and stress response,making it an essential component for growth in all known organisms.However,achieving efficient biosynthesis of vitamin B6 faces the challenge of maintaining a balanced distribution of metabolic flux between growth and production.In this study,our focus is on addressing this challenge through the engineering of phosphoserine aminotransferase(SerC)to resolve its redundancy and promiscuity.The enzyme SerC was semi-designed and screened based on sequences and predicted kcat values,respectively.Mutants and heterologous proteins showing potential were then fine-tuned to optimize the production of vitamin B6.The resulting strain enhances the production of vitamin B6,indicating that different fluxes are distributed to the biosynthesis pathway of serine and vitamin B6.This study presents a promising strategy to address the challenge posed by multifunctional enzymes,with significant implications for enhancing biochemical production through engineering processes.
基金This work was supported by the National Key R&D Program of China(2018YFA0900300)the Tianjin Science Fund for Distinguished Young Scholars(17JCJQJC45300)the Science and Technology Service Network(STS)Initiative of the Chinese Academy of Sciences(CAS)(KFJ-STS-ZDTP-065).
文摘Optimizing the supply of biosynthetic precursors and cofactors is usually an effective metabolic strategy to improve the production of target compounds.Here,the combination of optimizing precursor synthesis and balancing cofactor metabolism was adopted to improve tryptophan production in Escherichia coli.First,glutamine synthesis was improved by expressing heterologous glutamine synthetase from Bacillus subtilis and Bacillus megaterium in the engineered Escherichia coli strain KW001,resulting in the best candidate strain TS-1.Then icd and gdhA were overexpressed in TS-1,which led to the accumulation of 1.060 g/L tryptophan.Subsequently,one more copy of prs was introduced on the chromosome to increase the flux of 5-phospho-α-D-ribose 1-diphosphate followed by the expression of mutated serA and thrA to increase the precursor supply of serine,resulting in the accumulation of 1.380 g/L tryptophan.Finally,to maintain cofactor balance,sthA and pntAB,encoding transhydrogenase,were overexpressed.With sufficient amounts of precursors and balanced cofactors,the engineered strain could produce 1.710 g/L tryptophan after 48 h of shake-flask fermentation,which was 2.76-times higher than the titer of the parent strain.Taken together,our results demonstrate that the combination of optimizing precursor supply and regulating cofactor metabolism is an effective approach for high-level production of tryptophan.Similar strategies could be applied to the production of other amino acids or related derivatives.
基金financially supported by the National Science and Technology Major Project (2018ZX10101004)the Key Research Program of the Chinese Academy of Sciences (QYZDB-SSWSSMC040)the National Natural Science Foundation of China (31770163)
文摘Cell cycle is a fundamental process underlying growth and development in evolutionarily diverse organisms, including fungi. In human fungal pathogens, cell cycle control generally determines their life cycles, either in the environment or during infections.Thus, cell cycle components can potentially serve as important targets for the development of antifungal strategy against fungal infections. Here, in Cryptococcus neoformans, the most common cause of fatal fungal meningitis, we show that a previously uncharacterized B-type cyclin named Cbc1 is essential for both its infectious and sexual cycles. We reveal that Cbc1 coordinates various sexual differentiation and molecular processes, including meiosis. Especially, the absence of Cbc1 abolishes formation of sexual spores in C. neoformans, which are presumed infectious particles. Cbc1 is also required for the major Cryptococcus pathogenic attributes. Virulence assessment using the murine model of cryptococcosis revealed that the cbc1 mutant is avirulent.Together, our results provide an important insight into how C. neoformans employs shared cell cycle regulation to coordinate its infectious and sexual cycles, which are considered crucial for virulence evolution and the production of infectious spores.
基金supported by the National Natural Science Foundation of China(11275057)
文摘Newton’s law of gravity is a theory of instantaneous action at a distance.However,Einstein’s general relativity states that the speed of gravity equals the speed of light,which is finite.Therefore,it is a worthy problem to discuss if Newton’s law of gravity needs modification,when studying and observing the gravitational tidal.In this paper,it is shown that the Newton’s law of gravity is fully applicable in the framework of general relativity.Based on the post-Newtonian approximation,we find that the observable effect for the speed of gravity is irrelevant to the velocity of a moving source,but it is dependent on its acceleration.In general,the effect of the speed of gravity is so weak that today’s any astronomical observations,including the sun tidal observations,can not confirm that the gravitational field travels at the speed of light.
