Cytidine triphosphate(CTP),as a substance involved in the metabolism of phospholipids,proteins and nucleic acids,has precise drug effects and is a direct precursor for the synthesis of drugs such as citicoline.In this...Cytidine triphosphate(CTP),as a substance involved in the metabolism of phospholipids,proteins and nucleic acids,has precise drug effects and is a direct precursor for the synthesis of drugs such as citicoline.In this study,we established an in vitro six-enzyme cascade system to generate CTP.To avoid thermodynamic bottlenecks,we employed a circuitous and two-stage reaction strategy.Using cytidine as the key substrate,the final product CTP is obtained via the deamination and uridine phosphorylation pathways,relying on the irreversible reaction of cytidine triphosphate synthase to catalyze the amination of uridine triphosphate.Several extremophilic microbial-derived deaminases were screened and characterized,and a suitable cytidine deaminase was selected to match the first-stage reaction conditions.In addition,directed evolution modification of the rate-limiting enzyme CTP synthetase in the pathway yielded a variant that successfully relieved the product feedback inhibition,along with a 1.7-fold increase in activity over the wild type.After optimizing the reaction conditions,we finally carried out the catalytic reaction at an initial cytidine concentration of 20 mM,and the yield of CTP exceeded 82%within 10.0 h.展开更多
Polyelectrolyte-doped microcapsules(PDM)was fabricated by coaxial electrospray of a mixture of glycerol and water containing 10 mg/mL cationic polyelectrolyte poly(allylamine hydrochloride)(PAH)fed as the core phase s...Polyelectrolyte-doped microcapsules(PDM)was fabricated by coaxial electrospray of a mixture of glycerol and water containing 10 mg/mL cationic polyelectrolyte poly(allylamine hydrochloride)(PAH)fed as the core phase solution,and a N,N-dimethylacetylamide solution of 10 wt%polyurethane fed as the shell phase solution.Multienzyme system involving Candida Antarctica lipase B(CALB),glucose oxidase(GOD),and horseradish peroxidase(HRP)for cascade reaction was assembled in the PDM at three different places,namely,surface,shell,and lumen.Placing of enzyme inside aqueous lumen of the PDM was realized by in situ encapsulation through adding the enzyme in the core-phase solution for coaxial electrospray.By ion-pairing of enzyme with cationic surfactant CTAB,an organic soluble enzyme-CTAB complex was prepared,so that in situ embedding of enzyme in the shell of the PDM was realized by adding it into the shell phase solution.Surface attachment of enzymes was achieved by layer-by-layer(LbL)technology,which is based on the ion-exchange interactions between oppositely charged enzymes and PAH that was doped in PDM.The enzyme-decorated microcapsule was then studied as a microbioreactor,in which 1-Oxododecyla-α-glucopyranoside was converted by CALB to glucose,which was oxidised by GOD to gluconolactone in a second step.The hydrogen peroxide produced was then used by HRP to oxidize ABTS to form coloured radical cation ABTS•+for activity analysis.The successful fabrication of the PDM and precise localization of enzymes in the PDM by different strategies were fully characterized.By varying the immobilization strategy,totally six PDM bioreactors with three enzymes precisely positional assembled in different strategies were constructed and their activities for the cascade reaction were investigated and compared.The PDM micro-bioreactor prepared by novel electrospray technologies provide a smart platform for positional assembly of multi-enzyme cascade reaction in a precise and well-controlled manner.展开更多
Multi-enzyme complexes are the results of natural evolution to facilitate cascade biocatalysis.Through enzyme colocalization within a complex,the transfer efficiency of reaction intermediates between adjacent cascade ...Multi-enzyme complexes are the results of natural evolution to facilitate cascade biocatalysis.Through enzyme colocalization within a complex,the transfer efficiency of reaction intermediates between adjacent cascade enzymes can be promoted,resulting in enhanced overall reaction efficiency.Inspired by nature,a variety of approaches have been developed for the assembly of artificial multi-enzyme complexes with different spatial organizations,aiming at improving the catalytic efficiency of enzyme cascade.A recent trend of this research area is the creation of enzyme complexes with a controllable spatial organization which helps with the mechanistic studies and bears the potential to further increase metabolic productivity.In this review,we summarize versatile strategies for the assembly of artificial multi-enzyme complexes,followed by an inspection of the mechanistic studies of artificial multi-enzyme complexes for their enhancement of catalytic efficiency.Furthermore,we provide some highlighted in vivo,ex vivo,and in vitro examples that demonstrate the ability of artificial multi-enzyme complexes for enhancing the overall production efficiency of value-added compounds.Recent research progress has revealed the great biotechnological potential of artificial multi-enzyme complexes as a powerful tool for biomanufacturing.展开更多
l-Threonine transaldolase could catalyze the transaldolation of l-threonine and aldehyde to generateβ-hydroxy-α-amino acids with high diastereoselectivity.A novel l-threonine transaldolase(PmLTTA)was identified from...l-Threonine transaldolase could catalyze the transaldolation of l-threonine and aldehyde to generateβ-hydroxy-α-amino acids with high diastereoselectivity.A novel l-threonine transaldolase(PmLTTA)was identified from Pseudomonas sp.through genome mining.PmLTTA exhibited high activity in the synthesis of l-threo-phenylserine from l-threonine and benzaldehyde,with specific activity of 5.48 U mg-1.However,the application of PmLTTA was impeded by the low conversion ratio and variable diastereoselectivity,which were caused by the toxicity of aldehydes and kinetic/thermodynamic controls in the transaldolation reaction.To solve these issues,alcohol dehydrogenase was used to remove the by-product acetaldehyde,and then carboxylic acid reductase was introduced to alleviate the inhibition of benzaldehyde and toxicity of DMSO.Finally,a multi-enzyme cascade reaction,comprising of PmLTTA,carboxylic acid reductase,alcohol dehydrogenase and glucose dehydrogenase,was constructed to prepare l-threo-phenylserine from cheap benzoic acid,in which alleviated inhibition of aldehydes and desirable diastereoselectivity were achieved.Under the optimized conditions,the conversion ratio of 57.1%and de value of 95.3%were reached.This study provides an efficient and green approach for the synthesis of chiral l-threo-phenylserine from industrial byproduct,and provides guidance for the development of cascade reactions influenced by the toxic intermediates and complicated kinetic/thermodynamic controls.展开更多
Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation ...Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa,in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis(Phase I)to gastric precancerous lesions(Phase II)and finally to GC(Phase III).Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa.Intervening in early gastric mucosal lesions,i.e.,Phases I and II,will be the key strategy to prevent and treat GC.Natural products(NPs)have been an important source for drug development due to abundant sources,tremendous safety,and multiple pharmacodynamic mechanisms.This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis.In Phase I,NPs modulate Helicobacter pylori urease activity,motility,adhesion,virulence factors,and drug resistance,thereby inhibiting H.pylori-induced gastric mucosal inflammation and oxidative stress,and facilitating ulcer healing.In Phase II,NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle,apoptosis,autophagy,and angiogenesis to reverse gastric precancerous lesions.In Phase III,NPs suppress cell proliferation,migration,invasion,angiogenesis,and cancer stem cells,induce apoptosis and autophagy,and enhance chemotherapeutic drug sensitivity for the treatment of GC.In contrast to existing work,we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development,providing new ideas for gastric cancer prevention,treatment,and drug development.展开更多
Broad area quantum cascade lasers(BA QCLs)have significant applications in many areas,but suffer from demanding pulse operating conditions and poor beam quality due to heat accumulation and generation of high order mo...Broad area quantum cascade lasers(BA QCLs)have significant applications in many areas,but suffer from demanding pulse operating conditions and poor beam quality due to heat accumulation and generation of high order modes.A structure of mini-array is adopted to improve the heat dissipation capacity and beam quality of BA QCLs.The active region is etched to form a multi-emitter and the channels are filled with In P:Fe,which acts as a lateral heat dissipation channel to improve the lateral heat dissipation efficiency.A device withλ~4.8μm,a peak output power of 122 W at 1.2%duty cycle with a pulse of 1.5μs is obtained in room temperature,with far-field single-lobed distribution.This result allows BA QCLs to obtain high peak power at wider pump pulse widths and higher duty cycle conditions,promotes the application of the mid-infrared laser operating in pulsed mode in th e field of standoff photoacoustic chemical detection,space optical communication,and so on.展开更多
In the process of power scaling large-area Quantum Cascade Lasers(QCLs),challenges such as degradation of beam quality and emission of multilobed far-field modes are frequently encountered.These issues become particul...In the process of power scaling large-area Quantum Cascade Lasers(QCLs),challenges such as degradation of beam quality and emission of multilobed far-field modes are frequently encountered.These issues become particularly pronounced with an increase in ridge width,resulting in multimode problems.To tackle this,an innovative multi ridge waveguide structure based on the principle of supersymmetry(SUSY)was proposed.This structure comprises a wider main waveguide in the center and two narrower auxiliary waveguides on either side.The high-order modes of the main waveguide are coupled with the modes of the auxiliary waveguides through mode-matching design,and the optical loss of the auxiliary waveguides suppresses these modes,thereby achieving fundamental mode lasing of the wider main waveguide.This paper employs the finite difference eigenmode(FDE)method to perform detailed structural modeling and simulation optimization of the 4.6μm wavelength quantum cascade laser,successfully achieving a single transverse mode QCL with a ridge width of 10μm.In comparison to the traditional single-mode QCL(with a ridge width of about 5μm),the MRW structure has the potential to increase the gain area of the laser by 100%.This offers a novel design concept and methodology for enhancing the single-mode luminous power of mid-infrared quantum cascade lasers,which is of considerable significance.展开更多
[Objective]The construction of weirs changes the hydraulic characteristics of rivers and affects the structure of phytoplankton communities and the health of aquatic ecosystems in the river.This study aims to explore ...[Objective]The construction of weirs changes the hydraulic characteristics of rivers and affects the structure of phytoplankton communities and the health of aquatic ecosystems in the river.This study aims to explore the nonlinear response relationship between phytoplankton community structure and its driving factors in spring and autumn in Furong Creek under the construction of cascade weirs.[Methods]The structure of phytoplankton communities and related environmental factors were investigated in Furong Creek from 2023 to 2024.This study focused on the analysis of the changes of nutrient concentrations and biomass of phytoplankton in autumn and spring within the same dry season in Furong Creek.Redundancy analysis was used to identify the key factors influencing the structure of phytoplankton communities.The MIKE 11 model was employed to simulate the hydrodynamic changes in the river.Combined with total nitrogen and permanganate index,a GAM model of phytoplankton diversity index and hydrodynamic factors was developed,and the change of phytoplankton diversity after the optimized layout of the cascade weirs was fitted.[Results]The result showed that the annual average value of Shannon-Wiener diversity index of phytoplankton in Furong Creek was 2.79,which was in a state of mild pollution.A total of 239 species from 95 genera in 8 phyla were identified.Among the phytoplankton,Chlorophyta was the dominant group throughout the year in Furong Creek,followed by Bacillariophyta and Cyanophyta.The cell abundance of phytoplankton ranged from 3.11 to 20.64 mg/L and from 0.23 to 6.31 mg/L in spring and autumn,which indicated a clear seasonal succession of phytoplankton community structure.Compared with autumn,the relative abundance of Cyanophyta significantly decreased in spring across the whole river section,while Chrysophyta and Dinophyta showed significant increase at some monitoring sites,leading to water bloom phenomenon and a noticeable decline in the diversity of phytoplankton.The dominant species in the water bodies throughout the year were Cyclotella catenata,Chlorella vulgaris,Scenedesmus bijuga,Scenedesmus quadricauda,Chroomonas acuta,Cryptomonas ovata,and Cryptomonas erosa.Redundancy analysis(RDA)showed that hydrodynamic factors(v,h)and water environmental factors(TN,COD_(Mn))were the main influencing factors of phytoplankton community structure.[Conclusion]The result show that the nutrient concentration,phytoplankton biomass,and density in Furong Creek in spring are significantly higher than in autumn.The GAM model,constructed by combining hydrodynamic and environmental factors,can effectively reflect the nonlinear relationship between phytoplankton diversity index and its driving factors.In spring,with an increase in nutrient concentration,the habitat conditions of low flow speed and high water depths formed by overflow weirs will lead to a decrease in the Shannon-Wiener index of phytoplankton and an intensified risk of eutrophication.However,a reasonable layout scheme of cascade weirs will improve the diversity of phytoplankton and reduce the risk of eutrophication in the river.The findings of this study can help deepen the understanding of the ecological and environmental effects of cascade weir construction in the river.展开更多
A novel synthesis of C2-spiroindoline derivatives based on the cascade reaction of 2-aryl-3H-indoles with cyclo- propanols is presented. The formation of product involves Rh(III)-catalyzed aryl C(sp2)—H bond alkylati...A novel synthesis of C2-spiroindoline derivatives based on the cascade reaction of 2-aryl-3H-indoles with cyclo- propanols is presented. The formation of product involves Rh(III)-catalyzed aryl C(sp2)—H bond alkylation of 2-aryl- 3H-indole, which is followed by intramolecular spiroannulation. In this tandem process, cyclopropanol acts as not only an alkylating agent but also a masked nucleophile to take part in the construction of the spirocyclic scaffold. Meanwhile, air acts as an economical and sustainable oxidant to promote the regeneration of the active catalyst. By using this method, hybrid compounds containing the central scaffolds of some clinical drugs were prepared effectively. In general, this newly developed method has advantages such as easily obtainable substrates, concise synthetic procedure, excellent atom-economy, good compatibility with diverse functional groups and ready scalability.展开更多
Aberration-corrected focus scanning is crucial for high-precision optics,but the conventional optical systems rely on bulky and complicated dynamic correctors.Recently,Shiyi Xiao's group proposed a method using tw...Aberration-corrected focus scanning is crucial for high-precision optics,but the conventional optical systems rely on bulky and complicated dynamic correctors.Recently,Shiyi Xiao's group proposed a method using two rotating cascaded transmissive metasurfaces for adaptive aberration correction in focus scanning.The optimized phase profiles enable precise control of the focal position for scanning custom-curved surfaces.This concept was experimentally validated by two allsilicon meta-devices in the terahertz regime,paving the way for high-precision and compact optical devices in various applications.展开更多
Using molecular dynamics methods,simulations of collision cascades in polycrystalline tungsten(W)have been conducted in this study,including different primary-knock-on atom(PKA)directions,grain sizes,and PKA energies ...Using molecular dynamics methods,simulations of collision cascades in polycrystalline tungsten(W)have been conducted in this study,including different primary-knock-on atom(PKA)directions,grain sizes,and PKA energies between 1 keV and 150 keV.The results indicate that a smaller grain size leads to more defects forming in grain boundary regions during cascade processes.The impact of high-energy PKA may cause a certain degree of distortion of the grain boundaries,which has a higher probability in systems with smaller grain sizes and becomes more pronounced as the PKA energy increases.The direction of PKA can affect the formation and diffusion pathways of defects.When the PKA direction is perpendicular to the grain boundary,defects preferentially form near the grain boundary regions;by contrast,defects are more inclined to form in the interior of the grains.These results are of great significance for comprehending the changes in the performance of polycrystalline W under the high-energy fusion environments and can provide theoretical guidance for further optimization and application of W-based plasma materials.展开更多
This paper focuses on the problem of leaderfollowing consensus for nonlinear cascaded multi-agent systems.The control strategies for these systems are transformed into successive control problem schemes for lower-orde...This paper focuses on the problem of leaderfollowing consensus for nonlinear cascaded multi-agent systems.The control strategies for these systems are transformed into successive control problem schemes for lower-order error subsystems.A distributed consensus analysis for the corresponding error systems is conducted by employing recursive methods and virtual controllers,accompanied by a series of Lyapunov functions devised throughout the iterative process,which solves the leaderfollowing consensus problem of a class of nonlinear cascaded multi-agent systems.Specific simulation examples illustrate the effectiveness of the proposed control algorithm.展开更多
This study presents the design of an erbium-doped fiber laser(EDFL) featuring switchable wavelength intervals achieved through the implementation of cascaded and parallel Lyot filters. The proposed laser system utiliz...This study presents the design of an erbium-doped fiber laser(EDFL) featuring switchable wavelength intervals achieved through the implementation of cascaded and parallel Lyot filters. The proposed laser system utilizes a cascaded and parallel configuration of three Lyot filters, facilitated by a polarization beam splitter(PBS) for branch switching. The transmission properties of the filter are analyzed through theoretical modeling and experimental validation using the transmission matrix method. The experimental results are found to be consistent with the theoretical predictions, demonstrating the effectiveness of the proposed design. By adjusting the polarization controllers(PCs), the proposed laser can switch between wavelength spacings of 0.46 nm, 0.27 nm, and 0.76 nm, with a maximum optical signal-to-noise ratio(OSNR) of 38 d B. However, the stability of the laser with a 0.27 nm spacing is not high due to wavelength competition. Power fluctuation for 0.46 nm and 0.76 nm intervals is less than 0.93 d B and 0.78 d B in 1 h, with wavelength fluctuation less than 0.068 nm and 0.19 nm, respectively. This EDFL has the advantages of simple structure, great flexibility, and switchability, which can be applied to fiber optic sensing, wavelength division multiplexing(WDM) networks, and other fields that require a very flexible light source.展开更多
Chiral cyclic amino alcohols with contiguous stereocenters are key building blocks in the synthesis of bioactive molecules and pharmaceuticals.Artificial cascade biocatalysis represents an attractive method for the sy...Chiral cyclic amino alcohols with contiguous stereocenters are key building blocks in the synthesis of bioactive molecules and pharmaceuticals.Artificial cascade biocatalysis represents an attractive method for the synthesis of chiral molecules bearing multiple stereocenters from readily available materials.Here we reported an artificial cascade biocatalysis comprising an epoxide hydrolase,an alcohol dehydrogenase,and a reductive aminase or an amine dehydrogenase.It can be utilized to access all four stereoisomers of 2-aminocyclohexanol with two contiguous stereocenters in high yields(up to 95%)and excellent stereoselectivity(up to 98%de)starting from readily available cyclohexene oxide without isolation of the intermediates.Additionally,the biocatalytic cascade has been successfully extended to the production of structurally diverse 2-(alkylamino)cyclohexanols by replacing ammonia with different organic amines.展开更多
Herein,anthracene-pyridinium derivative(A1)is synthesized to assemble with amphiphilic sulfonatocalix[4]arene(SC4AD)with a porous cavity through electrostatic interaction,exhibiting enhanced fluorescence emission and ...Herein,anthracene-pyridinium derivative(A1)is synthesized to assemble with amphiphilic sulfonatocalix[4]arene(SC4AD)with a porous cavity through electrostatic interaction,exhibiting enhanced fluorescence emission and multipath fluorescence resonance energy transfer(FRET)with organic dyes(EY,Ni R or Cy5.5).In this nanoassembly,A1/SC4AD first transfers the energy to dye EY(first acceptor),and then delivers it to Ni R(second acceptor),which further transfers the energy to Cy5.5(third acceptor),accompanying with an emission ranging from 535 nm to 570 nm,then to 638 nm,and finally to near-infrared emission at 717 nm.Compared to one-step FRET(43.0%),the three-step FRET system shows higher energy transfer efficiency(FRET Ⅰ:84.9%,FRET Ⅱ:81.4%,FRET Ⅲ:66.9%).The donor/acceptor ratio is 3000(A1):20(EY):8(Ni R):5(Cy5.5),together with an antenna effect of 2.3.Additionally,diverse two-step cascade light-harvesting systems are successfully fabricated via tuning combination of dye acceptors.We believe that this multipath light-harvesting assembly will provide a direction for designing multiple sequential FRET and artificial light-harvesting systems.展开更多
Deprivation of glucose and lactate provides an effective pathway to terminate the nutrients supplement for tumor growth.In this work,biomimetic nanozymes called m@BGLC are constructed for catalytic tumor inhibition th...Deprivation of glucose and lactate provides an effective pathway to terminate the nutrients supplement for tumor growth.In this work,biomimetic nanozymes called m@BGLC are constructed for catalytic tumor inhibition through nutrients deprivation and oxidative damage induction.Concretely,the catalytic enzymes of glucose oxidase(GOx),lactate oxidase(LOx)and chloroperoxidase(CPO)are precrosslinked with bovine serum albumin(BSA)to construct nanozymes,which are then biomimetic functionalized with cancer cell membrane to prepare m@BGLC.Benefiting from the biomimetic camouflage with homologous cell membrane,m@BGLC inherit homotypic binding and immune escape abilities,facilitating the tumor targeting accumulation and preferable cell internalization for improved drug delivery efficiency.Subsequently,under the cascade catalysis of nanozymes,m@BGLC consume glucose and lactate for tumor starvation therapy through nutrients deprivation,and meanwhile,the resulting hyprochloric acid(HClO)causes an oxidative damage of cells to synergistically inhibit tumor growth.In vitro and in vivo findings demonstrate a robust tumor eradication effect of m@BGLC without obvious adverse reactions via the targeted combination therapy.Such cascade catalytic nanomedicine may inspire the development of sophisticated strategies for tumor combination therapy under unfavorable tumor microenvironments.展开更多
基金supported by the National Key Research and Development Program of China(2022YFC3401700)the National Natural Science Foundation of China(Grant No.32171478)the Tianjin Synthetic Biotechnology Innovation Capacity Improvement Project(Grant No.TSBICIP-KJGG-009).
文摘Cytidine triphosphate(CTP),as a substance involved in the metabolism of phospholipids,proteins and nucleic acids,has precise drug effects and is a direct precursor for the synthesis of drugs such as citicoline.In this study,we established an in vitro six-enzyme cascade system to generate CTP.To avoid thermodynamic bottlenecks,we employed a circuitous and two-stage reaction strategy.Using cytidine as the key substrate,the final product CTP is obtained via the deamination and uridine phosphorylation pathways,relying on the irreversible reaction of cytidine triphosphate synthase to catalyze the amination of uridine triphosphate.Several extremophilic microbial-derived deaminases were screened and characterized,and a suitable cytidine deaminase was selected to match the first-stage reaction conditions.In addition,directed evolution modification of the rate-limiting enzyme CTP synthetase in the pathway yielded a variant that successfully relieved the product feedback inhibition,along with a 1.7-fold increase in activity over the wild type.After optimizing the reaction conditions,we finally carried out the catalytic reaction at an initial cytidine concentration of 20 mM,and the yield of CTP exceeded 82%within 10.0 h.
基金The authors thank the support from the National Natural Science Foundation of China(Grant No.21676276).
文摘Polyelectrolyte-doped microcapsules(PDM)was fabricated by coaxial electrospray of a mixture of glycerol and water containing 10 mg/mL cationic polyelectrolyte poly(allylamine hydrochloride)(PAH)fed as the core phase solution,and a N,N-dimethylacetylamide solution of 10 wt%polyurethane fed as the shell phase solution.Multienzyme system involving Candida Antarctica lipase B(CALB),glucose oxidase(GOD),and horseradish peroxidase(HRP)for cascade reaction was assembled in the PDM at three different places,namely,surface,shell,and lumen.Placing of enzyme inside aqueous lumen of the PDM was realized by in situ encapsulation through adding the enzyme in the core-phase solution for coaxial electrospray.By ion-pairing of enzyme with cationic surfactant CTAB,an organic soluble enzyme-CTAB complex was prepared,so that in situ embedding of enzyme in the shell of the PDM was realized by adding it into the shell phase solution.Surface attachment of enzymes was achieved by layer-by-layer(LbL)technology,which is based on the ion-exchange interactions between oppositely charged enzymes and PAH that was doped in PDM.The enzyme-decorated microcapsule was then studied as a microbioreactor,in which 1-Oxododecyla-α-glucopyranoside was converted by CALB to glucose,which was oxidised by GOD to gluconolactone in a second step.The hydrogen peroxide produced was then used by HRP to oxidize ABTS to form coloured radical cation ABTS•+for activity analysis.The successful fabrication of the PDM and precise localization of enzymes in the PDM by different strategies were fully characterized.By varying the immobilization strategy,totally six PDM bioreactors with three enzymes precisely positional assembled in different strategies were constructed and their activities for the cascade reaction were investigated and compared.The PDM micro-bioreactor prepared by novel electrospray technologies provide a smart platform for positional assembly of multi-enzyme cascade reaction in a precise and well-controlled manner.
基金supported by the National Natural Science Foundation of China(21778073)。
文摘Multi-enzyme complexes are the results of natural evolution to facilitate cascade biocatalysis.Through enzyme colocalization within a complex,the transfer efficiency of reaction intermediates between adjacent cascade enzymes can be promoted,resulting in enhanced overall reaction efficiency.Inspired by nature,a variety of approaches have been developed for the assembly of artificial multi-enzyme complexes with different spatial organizations,aiming at improving the catalytic efficiency of enzyme cascade.A recent trend of this research area is the creation of enzyme complexes with a controllable spatial organization which helps with the mechanistic studies and bears the potential to further increase metabolic productivity.In this review,we summarize versatile strategies for the assembly of artificial multi-enzyme complexes,followed by an inspection of the mechanistic studies of artificial multi-enzyme complexes for their enhancement of catalytic efficiency.Furthermore,we provide some highlighted in vivo,ex vivo,and in vitro examples that demonstrate the ability of artificial multi-enzyme complexes for enhancing the overall production efficiency of value-added compounds.Recent research progress has revealed the great biotechnological potential of artificial multi-enzyme complexes as a powerful tool for biomanufacturing.
基金We are grateful to the National Key Research and Development Program(2021YFC2102700)the National Natural Science Foundation of China(22077054,22078127)+1 种基金the National First-Class Discipline Program of Light Industry Technology and Engineering(LITE2018-07)Program of Introducing Talents of Discipline to Universities(111-2-06)for the financial support of this research.
文摘l-Threonine transaldolase could catalyze the transaldolation of l-threonine and aldehyde to generateβ-hydroxy-α-amino acids with high diastereoselectivity.A novel l-threonine transaldolase(PmLTTA)was identified from Pseudomonas sp.through genome mining.PmLTTA exhibited high activity in the synthesis of l-threo-phenylserine from l-threonine and benzaldehyde,with specific activity of 5.48 U mg-1.However,the application of PmLTTA was impeded by the low conversion ratio and variable diastereoselectivity,which were caused by the toxicity of aldehydes and kinetic/thermodynamic controls in the transaldolation reaction.To solve these issues,alcohol dehydrogenase was used to remove the by-product acetaldehyde,and then carboxylic acid reductase was introduced to alleviate the inhibition of benzaldehyde and toxicity of DMSO.Finally,a multi-enzyme cascade reaction,comprising of PmLTTA,carboxylic acid reductase,alcohol dehydrogenase and glucose dehydrogenase,was constructed to prepare l-threo-phenylserine from cheap benzoic acid,in which alleviated inhibition of aldehydes and desirable diastereoselectivity were achieved.Under the optimized conditions,the conversion ratio of 57.1%and de value of 95.3%were reached.This study provides an efficient and green approach for the synthesis of chiral l-threo-phenylserine from industrial byproduct,and provides guidance for the development of cascade reactions influenced by the toxic intermediates and complicated kinetic/thermodynamic controls.
基金supported by the Chengdu University of Traditional Chinese Medicine"Xinglin Scholars"Program,China(Grant No.:MPRC2023014).
文摘Gastric carcinoma(GC)is a malignancy with multifactorial involvement,multicellular regulation,and multistage evolution.The classic Correa's cascade of intestinal GC specifies a trilogy of malignant transformation of the gastric mucosa,in which normal gastric mucosa gradually progresses from inactive or chronic active gastritis(Phase I)to gastric precancerous lesions(Phase II)and finally to GC(Phase III).Correa's cascade highlights the evolutionary pattern of GC and the importance of early intervention to prevent malignant transformation of the gastric mucosa.Intervening in early gastric mucosal lesions,i.e.,Phases I and II,will be the key strategy to prevent and treat GC.Natural products(NPs)have been an important source for drug development due to abundant sources,tremendous safety,and multiple pharmacodynamic mechanisms.This review is the first to investigate and summarize the multi-step effects and regulatory mechanisms of NPs on the Correa's cascade in gastric carcinogenesis.In Phase I,NPs modulate Helicobacter pylori urease activity,motility,adhesion,virulence factors,and drug resistance,thereby inhibiting H.pylori-induced gastric mucosal inflammation and oxidative stress,and facilitating ulcer healing.In Phase II,NPs modulate multiple pathways and mediators regulating gastric mucosal cell cycle,apoptosis,autophagy,and angiogenesis to reverse gastric precancerous lesions.In Phase III,NPs suppress cell proliferation,migration,invasion,angiogenesis,and cancer stem cells,induce apoptosis and autophagy,and enhance chemotherapeutic drug sensitivity for the treatment of GC.In contrast to existing work,we hope to uncover NPs with sequential therapeutic effects on multiple phases of GC development,providing new ideas for gastric cancer prevention,treatment,and drug development.
文摘Broad area quantum cascade lasers(BA QCLs)have significant applications in many areas,but suffer from demanding pulse operating conditions and poor beam quality due to heat accumulation and generation of high order modes.A structure of mini-array is adopted to improve the heat dissipation capacity and beam quality of BA QCLs.The active region is etched to form a multi-emitter and the channels are filled with In P:Fe,which acts as a lateral heat dissipation channel to improve the lateral heat dissipation efficiency.A device withλ~4.8μm,a peak output power of 122 W at 1.2%duty cycle with a pulse of 1.5μs is obtained in room temperature,with far-field single-lobed distribution.This result allows BA QCLs to obtain high peak power at wider pump pulse widths and higher duty cycle conditions,promotes the application of the mid-infrared laser operating in pulsed mode in th e field of standoff photoacoustic chemical detection,space optical communication,and so on.
基金Supported by the National Natural Science Foundation of China(62105039)。
文摘In the process of power scaling large-area Quantum Cascade Lasers(QCLs),challenges such as degradation of beam quality and emission of multilobed far-field modes are frequently encountered.These issues become particularly pronounced with an increase in ridge width,resulting in multimode problems.To tackle this,an innovative multi ridge waveguide structure based on the principle of supersymmetry(SUSY)was proposed.This structure comprises a wider main waveguide in the center and two narrower auxiliary waveguides on either side.The high-order modes of the main waveguide are coupled with the modes of the auxiliary waveguides through mode-matching design,and the optical loss of the auxiliary waveguides suppresses these modes,thereby achieving fundamental mode lasing of the wider main waveguide.This paper employs the finite difference eigenmode(FDE)method to perform detailed structural modeling and simulation optimization of the 4.6μm wavelength quantum cascade laser,successfully achieving a single transverse mode QCL with a ridge width of 10μm.In comparison to the traditional single-mode QCL(with a ridge width of about 5μm),the MRW structure has the potential to increase the gain area of the laser by 100%.This offers a novel design concept and methodology for enhancing the single-mode luminous power of mid-infrared quantum cascade lasers,which is of considerable significance.
文摘[Objective]The construction of weirs changes the hydraulic characteristics of rivers and affects the structure of phytoplankton communities and the health of aquatic ecosystems in the river.This study aims to explore the nonlinear response relationship between phytoplankton community structure and its driving factors in spring and autumn in Furong Creek under the construction of cascade weirs.[Methods]The structure of phytoplankton communities and related environmental factors were investigated in Furong Creek from 2023 to 2024.This study focused on the analysis of the changes of nutrient concentrations and biomass of phytoplankton in autumn and spring within the same dry season in Furong Creek.Redundancy analysis was used to identify the key factors influencing the structure of phytoplankton communities.The MIKE 11 model was employed to simulate the hydrodynamic changes in the river.Combined with total nitrogen and permanganate index,a GAM model of phytoplankton diversity index and hydrodynamic factors was developed,and the change of phytoplankton diversity after the optimized layout of the cascade weirs was fitted.[Results]The result showed that the annual average value of Shannon-Wiener diversity index of phytoplankton in Furong Creek was 2.79,which was in a state of mild pollution.A total of 239 species from 95 genera in 8 phyla were identified.Among the phytoplankton,Chlorophyta was the dominant group throughout the year in Furong Creek,followed by Bacillariophyta and Cyanophyta.The cell abundance of phytoplankton ranged from 3.11 to 20.64 mg/L and from 0.23 to 6.31 mg/L in spring and autumn,which indicated a clear seasonal succession of phytoplankton community structure.Compared with autumn,the relative abundance of Cyanophyta significantly decreased in spring across the whole river section,while Chrysophyta and Dinophyta showed significant increase at some monitoring sites,leading to water bloom phenomenon and a noticeable decline in the diversity of phytoplankton.The dominant species in the water bodies throughout the year were Cyclotella catenata,Chlorella vulgaris,Scenedesmus bijuga,Scenedesmus quadricauda,Chroomonas acuta,Cryptomonas ovata,and Cryptomonas erosa.Redundancy analysis(RDA)showed that hydrodynamic factors(v,h)and water environmental factors(TN,COD_(Mn))were the main influencing factors of phytoplankton community structure.[Conclusion]The result show that the nutrient concentration,phytoplankton biomass,and density in Furong Creek in spring are significantly higher than in autumn.The GAM model,constructed by combining hydrodynamic and environmental factors,can effectively reflect the nonlinear relationship between phytoplankton diversity index and its driving factors.In spring,with an increase in nutrient concentration,the habitat conditions of low flow speed and high water depths formed by overflow weirs will lead to a decrease in the Shannon-Wiener index of phytoplankton and an intensified risk of eutrophication.However,a reasonable layout scheme of cascade weirs will improve the diversity of phytoplankton and reduce the risk of eutrophication in the river.The findings of this study can help deepen the understanding of the ecological and environmental effects of cascade weir construction in the river.
文摘A novel synthesis of C2-spiroindoline derivatives based on the cascade reaction of 2-aryl-3H-indoles with cyclo- propanols is presented. The formation of product involves Rh(III)-catalyzed aryl C(sp2)—H bond alkylation of 2-aryl- 3H-indole, which is followed by intramolecular spiroannulation. In this tandem process, cyclopropanol acts as not only an alkylating agent but also a masked nucleophile to take part in the construction of the spirocyclic scaffold. Meanwhile, air acts as an economical and sustainable oxidant to promote the regeneration of the active catalyst. By using this method, hybrid compounds containing the central scaffolds of some clinical drugs were prepared effectively. In general, this newly developed method has advantages such as easily obtainable substrates, concise synthetic procedure, excellent atom-economy, good compatibility with diverse functional groups and ready scalability.
文摘Aberration-corrected focus scanning is crucial for high-precision optics,but the conventional optical systems rely on bulky and complicated dynamic correctors.Recently,Shiyi Xiao's group proposed a method using two rotating cascaded transmissive metasurfaces for adaptive aberration correction in focus scanning.The optimized phase profiles enable precise control of the focal position for scanning custom-curved surfaces.This concept was experimentally validated by two allsilicon meta-devices in the terahertz regime,paving the way for high-precision and compact optical devices in various applications.
基金Project supported by the National MCF Energy Research and Development Program of China(Grant No.2018YFE0308101)the National Key Research and Development Program of China(Grant No.2018YFB0704000)+1 种基金the Suqian Science and Technology Program(Grant No.K202337)the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.23KJD490001).
文摘Using molecular dynamics methods,simulations of collision cascades in polycrystalline tungsten(W)have been conducted in this study,including different primary-knock-on atom(PKA)directions,grain sizes,and PKA energies between 1 keV and 150 keV.The results indicate that a smaller grain size leads to more defects forming in grain boundary regions during cascade processes.The impact of high-energy PKA may cause a certain degree of distortion of the grain boundaries,which has a higher probability in systems with smaller grain sizes and becomes more pronounced as the PKA energy increases.The direction of PKA can affect the formation and diffusion pathways of defects.When the PKA direction is perpendicular to the grain boundary,defects preferentially form near the grain boundary regions;by contrast,defects are more inclined to form in the interior of the grains.These results are of great significance for comprehending the changes in the performance of polycrystalline W under the high-energy fusion environments and can provide theoretical guidance for further optimization and application of W-based plasma materials.
基金National Natural Science Foundation of China(No.12071370)。
文摘This paper focuses on the problem of leaderfollowing consensus for nonlinear cascaded multi-agent systems.The control strategies for these systems are transformed into successive control problem schemes for lower-order error subsystems.A distributed consensus analysis for the corresponding error systems is conducted by employing recursive methods and virtual controllers,accompanied by a series of Lyapunov functions devised throughout the iterative process,which solves the leaderfollowing consensus problem of a class of nonlinear cascaded multi-agent systems.Specific simulation examples illustrate the effectiveness of the proposed control algorithm.
基金supported by the Primary Research and Development Plan of Zhejiang Province (No.2023C03014)the Key Research and Development Program of Zhejiang Province (No.2022C03037)。
文摘This study presents the design of an erbium-doped fiber laser(EDFL) featuring switchable wavelength intervals achieved through the implementation of cascaded and parallel Lyot filters. The proposed laser system utilizes a cascaded and parallel configuration of three Lyot filters, facilitated by a polarization beam splitter(PBS) for branch switching. The transmission properties of the filter are analyzed through theoretical modeling and experimental validation using the transmission matrix method. The experimental results are found to be consistent with the theoretical predictions, demonstrating the effectiveness of the proposed design. By adjusting the polarization controllers(PCs), the proposed laser can switch between wavelength spacings of 0.46 nm, 0.27 nm, and 0.76 nm, with a maximum optical signal-to-noise ratio(OSNR) of 38 d B. However, the stability of the laser with a 0.27 nm spacing is not high due to wavelength competition. Power fluctuation for 0.46 nm and 0.76 nm intervals is less than 0.93 d B and 0.78 d B in 1 h, with wavelength fluctuation less than 0.068 nm and 0.19 nm, respectively. This EDFL has the advantages of simple structure, great flexibility, and switchability, which can be applied to fiber optic sensing, wavelength division multiplexing(WDM) networks, and other fields that require a very flexible light source.
文摘Chiral cyclic amino alcohols with contiguous stereocenters are key building blocks in the synthesis of bioactive molecules and pharmaceuticals.Artificial cascade biocatalysis represents an attractive method for the synthesis of chiral molecules bearing multiple stereocenters from readily available materials.Here we reported an artificial cascade biocatalysis comprising an epoxide hydrolase,an alcohol dehydrogenase,and a reductive aminase or an amine dehydrogenase.It can be utilized to access all four stereoisomers of 2-aminocyclohexanol with two contiguous stereocenters in high yields(up to 95%)and excellent stereoselectivity(up to 98%de)starting from readily available cyclohexene oxide without isolation of the intermediates.Additionally,the biocatalytic cascade has been successfully extended to the production of structurally diverse 2-(alkylamino)cyclohexanols by replacing ammonia with different organic amines.
基金financially supported by the National Natural Science Foundation of China(No.22131008)。
文摘Herein,anthracene-pyridinium derivative(A1)is synthesized to assemble with amphiphilic sulfonatocalix[4]arene(SC4AD)with a porous cavity through electrostatic interaction,exhibiting enhanced fluorescence emission and multipath fluorescence resonance energy transfer(FRET)with organic dyes(EY,Ni R or Cy5.5).In this nanoassembly,A1/SC4AD first transfers the energy to dye EY(first acceptor),and then delivers it to Ni R(second acceptor),which further transfers the energy to Cy5.5(third acceptor),accompanying with an emission ranging from 535 nm to 570 nm,then to 638 nm,and finally to near-infrared emission at 717 nm.Compared to one-step FRET(43.0%),the three-step FRET system shows higher energy transfer efficiency(FRET Ⅰ:84.9%,FRET Ⅱ:81.4%,FRET Ⅲ:66.9%).The donor/acceptor ratio is 3000(A1):20(EY):8(Ni R):5(Cy5.5),together with an antenna effect of 2.3.Additionally,diverse two-step cascade light-harvesting systems are successfully fabricated via tuning combination of dye acceptors.We believe that this multipath light-harvesting assembly will provide a direction for designing multiple sequential FRET and artificial light-harvesting systems.
基金financial support of Guangdong Basic and Applied Basic Research Foundation(No.2022B1515020095)National Natural Science Foundation of China(No.52073140)。
文摘Deprivation of glucose and lactate provides an effective pathway to terminate the nutrients supplement for tumor growth.In this work,biomimetic nanozymes called m@BGLC are constructed for catalytic tumor inhibition through nutrients deprivation and oxidative damage induction.Concretely,the catalytic enzymes of glucose oxidase(GOx),lactate oxidase(LOx)and chloroperoxidase(CPO)are precrosslinked with bovine serum albumin(BSA)to construct nanozymes,which are then biomimetic functionalized with cancer cell membrane to prepare m@BGLC.Benefiting from the biomimetic camouflage with homologous cell membrane,m@BGLC inherit homotypic binding and immune escape abilities,facilitating the tumor targeting accumulation and preferable cell internalization for improved drug delivery efficiency.Subsequently,under the cascade catalysis of nanozymes,m@BGLC consume glucose and lactate for tumor starvation therapy through nutrients deprivation,and meanwhile,the resulting hyprochloric acid(HClO)causes an oxidative damage of cells to synergistically inhibit tumor growth.In vitro and in vivo findings demonstrate a robust tumor eradication effect of m@BGLC without obvious adverse reactions via the targeted combination therapy.Such cascade catalytic nanomedicine may inspire the development of sophisticated strategies for tumor combination therapy under unfavorable tumor microenvironments.
