In order to study the underwater trajectory of the non-powered vehicle discharged from the broadside of the underwater platform,the simulation on the ascent process of non-powered vehicle was realized based on the mat...In order to study the underwater trajectory of the non-powered vehicle discharged from the broadside of the underwater platform,the simulation on the ascent process of non-powered vehicle was realized based on the mathematical model including the movement of the vehicle on the slope plate and in the seawater,the air chamber underwater working process etc. The simulation results show that the outlet speed and attitude of the vehicle meet the requirements of missile launching,the non-powered vehicle discharged from the broadside of the underwater platform is feasible. The simulation results with varying parameters show that the negative buoyancy of the vehicle imposes great impacts on the security of its discharge and the floating process,and the vehicle discharge depth is proportional to the floating time. The models and simulation result can be used in further research on the broadside discharging technology of the underwater platform.展开更多
Fungal bifunctional terpene synthases(BFTSs)catalyze the formation of numerous di-/sester-/tri-terpenes skeletons.However,the mechanism in controlling the cyclization pattern of terpene scaffolds is rarely deciphered ...Fungal bifunctional terpene synthases(BFTSs)catalyze the formation of numerous di-/sester-/tri-terpenes skeletons.However,the mechanism in controlling the cyclization pattern of terpene scaffolds is rarely deciphered for further application of tuning the catalytic promiscuity of terpene synthases for expanding the chemical space.In this study,we expanded the catalytic promiscuity of Fusarium oxysporum fusoxypene synthase(FoFS)by a single mutation at L89,leading to the production of three new sesterterpenes.Further computational analysis revealed that the reconstitution of the hydrogen-bond(H-bond)network of second-shell residues around the active site of FoFS influences the orientation of the aromatic residue W69 within the first-shell catalytic pocket.Thus,the dynamic orientation of W69 alters the carbocation transport,leading to the production of diverse ring system skeletons.These findings enhance our knowledge on understanding the molecular mechanisms,which could be applied on protein engineering terpene synthases on regulating the terpene skeletons.展开更多
Coal is widely utilized as an important energy source,but coal-fired power plant was considered to be an important anthropogenic lead emission source.In the present study,the distribution characteristics of lead in co...Coal is widely utilized as an important energy source,but coal-fired power plant was considered to be an important anthropogenic lead emission source.In the present study,the distribution characteristics of lead in coal and combustion by-products are reviewed.Specifically,lead is mainly transferred to ash particles and the formation and migration mechanisms of particulate lead are summarized.Also,targeted measures are proposed to control the formation of fine particulate lead as well as to increase the removal efficiency during the low-temperature flue gas clean process.In detail,interactions between gaseous lead and some coal-bearing minerals or added adsorbents could obviously suppress the formation of fine particulate lead.On the other hand,some efforts(including promoting capture of fine particles,reducing resistivity of particles and strengthening the gas-liquid contact)could be made to improve the fine particulate lead removal capacity.Notably,the formation mechanism of fine particulate lead is still unclear due to the limitations of research methods.Some differences in the removal principles of fine particles and particulate lead make the lead emission precisely control a great challenge.Finally,the environmental potential risk of lead emission from flue gas and ash residues is addressed and further discussed.展开更多
Rapid and sensitive detection of various analytes is in high demand.Apart from its application in genome editing,CRISPR-Cas also shows promises in nucleic acid detection applications.To further exploit the potential o...Rapid and sensitive detection of various analytes is in high demand.Apart from its application in genome editing,CRISPR-Cas also shows promises in nucleic acid detection applications.To further exploit the potential of CRISPR-Cas for detection of diverse analytes,we present a versatile biosensing platform that couples the excellent affinity of aptamers for broad-range analytes with the collateral single-strand DNA cleavage activity of CRISPR-Cas12 a.We demonstrated that the biosensors developed by this platform can be used to detect protein and small molecule in human serum with a complicated background,i.e.,the tumor marker alpha fetoprotein and cocaine with the detection limits of 0.07 fmol/L and 0.34 lmol/L,respectively,highlighting the advantages of simplicity,sensitivity,short detection time,and low cost compared with the state-of-the-art biosensing approaches.Altogether,this biosensing platform with plug-and-play design show great potential in the detection of diverse analytes.展开更多
Clinical use of antimicrobials faces great challenges from the emergence of multidrug-resistant pathogens. The overexpression of drug efflux pumps is one of the major contributors to multidrug resistance(MDR). Reversi...Clinical use of antimicrobials faces great challenges from the emergence of multidrug-resistant pathogens. The overexpression of drug efflux pumps is one of the major contributors to multidrug resistance(MDR). Reversing the function of drug efflux pumps is a promising approach to overcome MDR. In the life-threatening fungal pathogen Candida albicans, the major facilitator superfamily(MFS) transporter Mdr1p can excrete many structurally unrelated antifungals, leading to MDR. Here we report a counterintuitive case of reversing MDR in C. albicans by using a natural product berberine to hijack the overexpressed Mdr1p for its own importation. Moreover, we illustrate that the imported berberine accumulates in mitochondria and compromises the mitochondrial function by impairing mitochondrial membrane potential and mitochondrial Complex I. This results in the selective elimination of Mdr1 p overexpressed C. albicans cells. Furthermore, we show that berberine treatment can prolong the mean survival time of mice with blood-borne dissemination of Mdr1p overexpressed multidrug-resistant candidiasis. This study provides a potential direction of novel anti-MDR drug discovery by screening for multidrug efflux pump converters.展开更多
文摘In order to study the underwater trajectory of the non-powered vehicle discharged from the broadside of the underwater platform,the simulation on the ascent process of non-powered vehicle was realized based on the mathematical model including the movement of the vehicle on the slope plate and in the seawater,the air chamber underwater working process etc. The simulation results show that the outlet speed and attitude of the vehicle meet the requirements of missile launching,the non-powered vehicle discharged from the broadside of the underwater platform is feasible. The simulation results with varying parameters show that the negative buoyancy of the vehicle imposes great impacts on the security of its discharge and the floating process,and the vehicle discharge depth is proportional to the floating time. The models and simulation result can be used in further research on the broadside discharging technology of the underwater platform.
基金We gratefully acknowledge the financial support from the National Key Research and Development Program of China(2019YFA0906201,2020YFA090032,2022YFC2105400)the National Natural Science Foundation of China(22307037,21907031,81903529,21977029,31720103901,21877124)the Open Project Funding of the State Key Laboratory of Bioreactor Engineering,the 111 Project(B18022).
文摘Fungal bifunctional terpene synthases(BFTSs)catalyze the formation of numerous di-/sester-/tri-terpenes skeletons.However,the mechanism in controlling the cyclization pattern of terpene scaffolds is rarely deciphered for further application of tuning the catalytic promiscuity of terpene synthases for expanding the chemical space.In this study,we expanded the catalytic promiscuity of Fusarium oxysporum fusoxypene synthase(FoFS)by a single mutation at L89,leading to the production of three new sesterterpenes.Further computational analysis revealed that the reconstitution of the hydrogen-bond(H-bond)network of second-shell residues around the active site of FoFS influences the orientation of the aromatic residue W69 within the first-shell catalytic pocket.Thus,the dynamic orientation of W69 alters the carbocation transport,leading to the production of diverse ring system skeletons.These findings enhance our knowledge on understanding the molecular mechanisms,which could be applied on protein engineering terpene synthases on regulating the terpene skeletons.
基金supported by National Key Research and Development Project of China (No. 2018YFB0605103)Program for Huazhong University of Science and Technology Academic Frontier Youth Team (No. 2018QYTD05)
文摘Coal is widely utilized as an important energy source,but coal-fired power plant was considered to be an important anthropogenic lead emission source.In the present study,the distribution characteristics of lead in coal and combustion by-products are reviewed.Specifically,lead is mainly transferred to ash particles and the formation and migration mechanisms of particulate lead are summarized.Also,targeted measures are proposed to control the formation of fine particulate lead as well as to increase the removal efficiency during the low-temperature flue gas clean process.In detail,interactions between gaseous lead and some coal-bearing minerals or added adsorbents could obviously suppress the formation of fine particulate lead.On the other hand,some efforts(including promoting capture of fine particles,reducing resistivity of particles and strengthening the gas-liquid contact)could be made to improve the fine particulate lead removal capacity.Notably,the formation mechanism of fine particulate lead is still unclear due to the limitations of research methods.Some differences in the removal principles of fine particles and particulate lead make the lead emission precisely control a great challenge.Finally,the environmental potential risk of lead emission from flue gas and ash residues is addressed and further discussed.
基金supported by the National Key Research and Development Program of China(2020YFA0907800,2022YFC3400200,and 2022YFA0912200)the National Natural Science Foundation of China(31900060)+1 种基金the Shanghai Pilot Program for Basic Research-Shanghai Jiao Tong University(21TQ1400204)the Natural Science Foundation of Shanghai(20ZR1414500)。
基金supported by the National Natural Science Foundation of China (31770055, 31922002, 31720103901, and 31772242)the 111 Project (B18022)+4 种基金the Fundamental Research Funds for the Central Universities (22221818014)the Shanghai Science and Technology Commission (18JC1411900)the Young Scientists Innovation Promotion Association of Chinese Academy of Sciences (2016087) to Weishan Wangthe Shandong Taishan Scholar Program of China to Lixin Zhangthe Open Project Funding of the State Key Laboratory of Bioreactor Engineering
文摘Rapid and sensitive detection of various analytes is in high demand.Apart from its application in genome editing,CRISPR-Cas also shows promises in nucleic acid detection applications.To further exploit the potential of CRISPR-Cas for detection of diverse analytes,we present a versatile biosensing platform that couples the excellent affinity of aptamers for broad-range analytes with the collateral single-strand DNA cleavage activity of CRISPR-Cas12 a.We demonstrated that the biosensors developed by this platform can be used to detect protein and small molecule in human serum with a complicated background,i.e.,the tumor marker alpha fetoprotein and cocaine with the detection limits of 0.07 fmol/L and 0.34 lmol/L,respectively,highlighting the advantages of simplicity,sensitivity,short detection time,and low cost compared with the state-of-the-art biosensing approaches.Altogether,this biosensing platform with plug-and-play design show great potential in the detection of diverse analytes.
基金supported by the National Key Research and Development Program of China (2020YFA0907800)the National Natural Science Foundation of China (31720103901)+2 种基金the “111” Project of China (B18022)the Fundamental Research Funds for the Central Universities (22221818014S)the Open Project Funding of the State Key Laboratory of Bioreactor Engineering,the Shandong Taishan Scholar Award,and the Novo Nordisk Foundation (NNF10CC1016517)。
文摘Clinical use of antimicrobials faces great challenges from the emergence of multidrug-resistant pathogens. The overexpression of drug efflux pumps is one of the major contributors to multidrug resistance(MDR). Reversing the function of drug efflux pumps is a promising approach to overcome MDR. In the life-threatening fungal pathogen Candida albicans, the major facilitator superfamily(MFS) transporter Mdr1p can excrete many structurally unrelated antifungals, leading to MDR. Here we report a counterintuitive case of reversing MDR in C. albicans by using a natural product berberine to hijack the overexpressed Mdr1p for its own importation. Moreover, we illustrate that the imported berberine accumulates in mitochondria and compromises the mitochondrial function by impairing mitochondrial membrane potential and mitochondrial Complex I. This results in the selective elimination of Mdr1 p overexpressed C. albicans cells. Furthermore, we show that berberine treatment can prolong the mean survival time of mice with blood-borne dissemination of Mdr1p overexpressed multidrug-resistant candidiasis. This study provides a potential direction of novel anti-MDR drug discovery by screening for multidrug efflux pump converters.