α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively dete...α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.展开更多
In this study,we employed a combination of genome mining and heteronuclear single quantum coherence(HSQC)-based small molecule accurate recognition technology(SMART)technology to search for fernane-type triterpenoids....In this study,we employed a combination of genome mining and heteronuclear single quantum coherence(HSQC)-based small molecule accurate recognition technology(SMART)technology to search for fernane-type triterpenoids.Initially,potential endophytic fungi were identified through genome mining.Subsequently,fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction.These triterpenoids were then obtained through targeted isolation and identification.Finally,their antifungal activity was evaluated.As a result,three fernane-type triterpenoids,including two novel compounds,along with two new sesquiterpenes and four known compounds were isolated from one potential strain,Diaporthe discoidispora.Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry(HR-ESI-MS)and nuclear magnetic resonance(NMR)spectroscopic data.The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector(ECD)analysis.Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.展开更多
The combination of ultrasonic and acid fracturing fluid can strengthen the modification effect on the micropore structure of the coal matrix,thereby enhancing the efficiency of the acid fracturing process.In this rese...The combination of ultrasonic and acid fracturing fluid can strengthen the modification effect on the micropore structure of the coal matrix,thereby enhancing the efficiency of the acid fracturing process.In this research,acetic acid was utilized to formulate acid fracturing fluids with varying concentrations,and the evolutionary traits of both the acid fracturing fluids and ultrasonic waves in relation to coal samples were investigated.The functional group structure,mineral composition,micropore structure and surface morphology of coal samples were characterized by FTIR,XRD,N_(2)adsorption at low temperature and SEM-EDS.The results showed that aromatics(I)and branching parameters(CH_(2)/CH_(3))were reduced by 81.58%and 88.67%,respectively,after 9%acetic acid treatment.Acetic acid can dissolve carbonates and clay minerals in coal,create new pores,and increase porosity,pore volume and pore fractal dimension.After modification by 7%acetic acid,the pore volume increased by 5.7 times.SEM observation shows that the diameter of coal surface holes increases,EDS scanning shows that the content of mineral elements in coal decreases,the connectivity of coal holes increases,and the holes expand.The findings of this research offer theoretical direction for optimizing ultrasonic-enhanced acid fracturing fluid modification.展开更多
Chromatin interactions functionally affect genome architecture and gene regulation,but to date,only fresh samples must be used in High-through chromosome conformation capture(Hi-C)to keep natural chromatin conformatio...Chromatin interactions functionally affect genome architecture and gene regulation,but to date,only fresh samples must be used in High-through chromosome conformation capture(Hi-C)to keep natural chromatin conformation intact.This requirement has impeded the advancement of 3 D genome research by limiting sample collection and storage options for researchers and severely limiting the number of samples that can be processed in a short time.Here,we develop a freeze substitution Hi-C(FS-Hi-C)technique that overcomes the need for fresh samples.FS-Hi-C can be used with samples stored in liquid nitrogen(LN2):the water in a vitreous form in the sample cells is replaced with ethanol via automated freeze substitution.After confirming that the FS step preserves the natural chromosome conformation during sample thawing,we tested the performance of FS-Hi-C with Drosophila melanogaster and Gossypium hirsutum.Beyond allowing the use of frozen samples and confirming that FS-Hi-C delivers robust data for generating contact heat maps and delineating A/B compartments and topologically associating domains,we found that FS-HiC outperforms the in situ Hi-C in terms of library quality,reproducibility,and valid interactions.Thus,FS-HiC will probably extend the application of 3D genome structure analysis to the vast number of experimental contexts in biological and medical research for which Hi-C methods have been unfeasible to date.展开更多
In recent years,frequent network attacks have highlighted the importance of efficient detection methods for ensuring cyberspace security.This paper presents a novel intrusion detection system consisting of a data prep...In recent years,frequent network attacks have highlighted the importance of efficient detection methods for ensuring cyberspace security.This paper presents a novel intrusion detection system consisting of a data prepro-cessing stage and a deep learning model for accurately identifying network attacks.We have proposed four deep neural network models,which are constructed using architectures such as Convolutional Neural Networks(CNN),Bi-directional Long Short-Term Memory(BiLSTM),Bidirectional Gate Recurrent Unit(BiGRU),and Attention mechanism.These models have been evaluated for their detection performance on the NSL-KDD dataset.To enhance the compatibility between the data and the models,we apply various preprocessing techniques and employ the particle swarm optimization algorithm to perform feature selection on the NSL-KDD dataset,resulting in an optimized feature subset.Moreover,we address class imbalance in the dataset using focal loss.Finally,we employ the BO-TPE algorithm to optimize the hyperparameters of the four models,maximizing their detection performance.The test results demonstrate that the proposed model is capable of extracting the spatiotemporal features of network traffic data effectively.In binary and multiclass experiments,it achieved accuracy rates of 0.999158 and 0.999091,respectively,surpassing other state-of-the-art methods.展开更多
Mushrooms have been utilized by humans for thousands of years due to their medicinal and nutritional properties.They are a crucial natural source of bioactive secondary metabolites,and recent advancements have led to ...Mushrooms have been utilized by humans for thousands of years due to their medicinal and nutritional properties.They are a crucial natural source of bioactive secondary metabolites,and recent advancements have led to the isolation of several alkynyl-containing compounds with potential medicinal uses.Despite their relatively low abundance,naturally occurring alkynyl compounds have attracted considerable attention due to their high reactivity.Bioactivity studies have shown that alkynyl compounds exhibit significant biological and pharmacological activities,including antitumor,antibacterial,antifungal,insecticidal,phototoxic,HIV-inhibitory,and immunosuppressive properties.This review systematically compiles 213 alkynyl-containing bioactive compounds isolated from mushrooms since 1947 and summarizes their diverse biological activities,focusing mainly on cytotoxicity and anticancer effects.This review serves as a detailed and comprehensive reference for the chemical structures and bioactivity of alkynyl-containing secondary metabolites from mushrooms.Moreover,it provides theoretical support for the development of chemical constituents containing alkynyl compounds in mushrooms based on academic research and theory.展开更多
Indole diterpenoids(IDTs)are an essential class of structurally diverse fungal secondary metabolites,that generally appear to be restricted to a limited number of fungi,such as Penicillium,Aspergillus,Claviceps,and Ep...Indole diterpenoids(IDTs)are an essential class of structurally diverse fungal secondary metabolites,that generally appear to be restricted to a limited number of fungi,such as Penicillium,Aspergillus,Claviceps,and Epichloe species,etc.These compounds share a typical core structure consisting of a cyclic diterpene skeleton of geranylgeranyl diphos-phate(GGPP)and an indole ring moiety derived from indole-3-glycerol phosphate(IGP).3-geranylgeranylindole(3-GGI)is the common precursor of all IDTs.On this basis,it is modified by cyclization,oxidation,and prenylation to generate a large class of compounds with complex structures.These compounds exhibit antibacterial,anti-insect,and ion channel inhibitory activities.We summarized 204 compounds of IDTs discovered from various fungi over the past 50 years,these compounds were reclassified,and their biological activities were summarized.This review will help to understand the structural diversity of IDTs and provide help for their physiological activities.展开更多
Pre-cooling the inlet air of a dry cooling tower by means of a spray can improve the tower performance during periods of high temperature.To study the spray effect on the thermal performance of natural draft dry cooli...Pre-cooling the inlet air of a dry cooling tower by means of a spray can improve the tower performance during periods of high temperature.To study the spray effect on the thermal performance of natural draft dry cooling towers(NDDCTs),in this study 3-D numerical simulations of such a process have been conducted using Fluent 16.2(a two-way coupled Eulerian-Lagrangian approach).The considered NDDCT is 120 m high and only half system is simulated due to its structural symmetry.Three different spray strategies have been investigated at a typical crosswind speed of 4 m/s,which is the most frequent wind speed.The results have shown that:(1)The three implemented spray strategies can improve the thermal performance of the studied NDDCT with a vary-ing degree of success.In one case,the heat rejection rate can be increased by 35.2%,and the tower outlet water temperature can be decreased by 2.1℃ when compared with the no spray case;(2)To improve the thermal per-formance of the NDDCT using a small amount of water,the design of the spray pre-cooling system must include more nozzles on the windward and fewer or even no nozzles on the leeward sides of the NDDCT.展开更多
Glycosylation is a prevalent post-modification found in natural products and has a significant impact on the structural diversity and activity variation of natural products.Glucosylation is the most common type of gly...Glycosylation is a prevalent post-modification found in natural products and has a significant impact on the structural diversity and activity variation of natural products.Glucosylation is the most common type of glycosylation,whereas xylosylation is relatively rare.Despite their unique chemical structures and beneficial activities,xylosylated natural products from microorganisms have received little attention.This review provides,for the first time,a comprehensive summary of 126 microbial-derived xylosylated natural products,including xylosyl-cyathane diterpenes,xylosylated triterpenes,xylosyl aromatic compounds,and others.Among these compounds,xylosyl-cyathane diterpenes represent the highest number of derivatives,followed by xylosylated triterpenes.Xylosyl compounds from bacterial sources have less defined structural profiles compared to those from fungi.The characterization of xylosyltransferase EriJ from Basidiomycota extended the structural diversity of xylosyl cyathane diterpenes.This work provides a valuable reference for the research and use of xylosyltransferase for drug discovery and synthetic chemistry.Further work is needed to explore the potential applications of microbial derived xylosyl compounds and to develop novel xylosyl transferases.With the deepening of genomic sequencing of medicinal fungi,more biosynthesis of bioactive xylosyl compounds is expected to be elucidated in the future.展开更多
This paper proposes a method for creating a three-dimensional(above-ground and underground)fracture network in deep coalbed methane(CBM)reservoirs,which is the directional fracturing by slotted hydraulic blasting in u...This paper proposes a method for creating a three-dimensional(above-ground and underground)fracture network in deep coalbed methane(CBM)reservoirs,which is the directional fracturing by slotted hydraulic blasting in underground drilling.First,theoretical analysis was conducted to explain the mechanism by which the slotted borehole enables the separation and incidence of explosive shock wave at the slot tip,resulting in the superposition of two sub-stress waves to cause directional fracture and damage to the rock.Then,LS-DYNA was used to simulate the process of directional fracturing by slotted hydraulic blasting to verify the theoretical mechanism.Finally,similar simulation experiments were performed on traditional blasting and slotted hydraulic blasting to confirm the directional fracturing effect of the proposed method.The results indicate that the slotted hydraulic blasting method can predominate the fracture orientation under formation stress,creating extensive directional fractures in rocks in the slot direction.This study is supplemental to the efforts on directional fracturing of rocks and provides a new approach for efficient exploitation of CBM.展开更多
Meroterpenoids are secondary metabolites partially derived from the terpenoid biosynthetic pathway,and are widely distributed in plants,animals,and fungi.These natural products possess complex backbone structures and ...Meroterpenoids are secondary metabolites partially derived from the terpenoid biosynthetic pathway,and are widely distributed in plants,animals,and fungi.These natural products possess complex backbone structures and diverse bioactivities.Ganoderma meroterpenoids(GMs)form a distinct group of meroterpenoids were characterized by the presence of 1,2,4-trisubstituted phenyl and polyunsaturated terpene moieties.Various Ganoderma species have been extensively studied,leading to the discovery of several structurally unique meroterpenoids with significant pharmacological activities.After the first isolation and identification of GMs in 2000,over 300 compounds from 14 species have been characterized for their structures and biological activities.The structures and activities of some GMs from different Ganoderma species vary greatly,probably due to significant differences in the genome and transcriptome of different Ganoderma species.We predicted the related enzymes based on the reported Ganoderma genome and proposed the biosynthetic pathway related to GMs.The results presented in this review provide a scientific foundation for the comprehensive exploration and utilization of diverse Ganoderma resources.展开更多
Hericium mushrooms are a group of rare medicinal mushrooms that have attracted considerable attention worldwide.in order to gain insight into the current trends and frontiers of Hericium research,we conducted a compre...Hericium mushrooms are a group of rare medicinal mushrooms that have attracted considerable attention worldwide.in order to gain insight into the current trends and frontiers of Hericium research,we conducted a comprehensive search of the Web of science(Wos)database to identify relevant literature on Hericium research.Following an optimised search strategy and careful removal of duplicate entries,a total of 839 documents were selected from the core Wos database for bibliometric analysis.We used Vosviewer to visualize the co-occurrence network between publishing organizations,while Citespace allowed us to visualize and analyse the national co-occurrence network,author co-occurrence network,keyword co-linearity,keyword clustering and co-citation mapping.our analysis revealed a significant and continuous increase in the number of publications related to Hericium mushrooms,with a peak observed in 2021.Examination of publication statistics by country(region)and institution identified China and Universiti Malaysia as the leading contributors in their respective fields,with active collaboration with other countries and institutions.the analysis of author co-occurrence suggests that inter-author communications and collaborations may be geographically limited by the research institutions to which they belong.Various keyword-based analyses highlighted the structural diversity and bioactivities of small molecule compounds derived from Hericium mushrooms,underscoring their potential health-protective effects as rare food and medicinal mushrooms.through co-citation analysis,we identified J.agr.Food Chem.as the most cited journal for Hericium mushroom research results,while Yoko Kawagishi of shizuoka University(Japan)emerged as the most cited researcher in the field.overall,our findings suggest that research into the potential anti-neurodegenerative properties of Hericium mushrooms is a promising area of investigation,with a focus on elucidating the underlying mechanisms of action.展开更多
ABSTRACT Introduction:Mushroom poisoning was the leading cause of foodborne disease outbreaks and outbreak-associated deaths in China.Mushroom poisoning outbreak surveillance can provide insight into the epidemiologic...ABSTRACT Introduction:Mushroom poisoning was the leading cause of foodborne disease outbreaks and outbreak-associated deaths in China.Mushroom poisoning outbreak surveillance can provide insight into the epidemiological characteristics of mushroom poisonings and guide policymaking and health education to reduce illnesses and deaths.Methods:Foodborne Disease Outbreak Surveillance System was upgraded in 2011 to collect foodborne disease outbreaks in China.Mushroom poisoning outbreaks during 2010–2020 were selected to analyze geographical distribution,seasonal distribution,and setting of food preparation.Results:A total of 10,036 outbreaks,which resulted in 38,676 illnesses and 788 deaths,were reported in this period.Mushroom poisonings occurred all over the country,but with highest incidence in the southwest and central China.展开更多
Introduction:Adverse reactions to food(ARF)are a major worldwide public health and food safety problem.Among the various causes of ARF,food allergies(FA)are particularly serious as the immune response that is triggere...Introduction:Adverse reactions to food(ARF)are a major worldwide public health and food safety problem.Among the various causes of ARF,food allergies(FA)are particularly serious as the immune response that is triggered can be fatal even at very low doses.However,the prevalence of ARF and FA in the general population in China is presently unclear.This study aims to determine the epidemiological characteristics and risk factors for ARF and FA,which can be a basis for estimating thresholds for major food allergens.Methods:This is a multicenter,cross-sectional,epidemiologic survey with a case-control study nested among a selected population in China.Random individuals were recruited using stratified cluster random sampling;ARF and FA were comprehensively assessed using modified EuroPrevall FA Project questionnaires as well as structured interviews,sensitization testing,and double-blind placebocontrolled food challenges(DBPCFC).Results:This method of epidemiologic study on ARF and FA was a pilot application in Jiangxi Province from January 2020;among the total 21,273 children and adults that completed the questionnaire,5.8%reported ARF and 4.3%reported FA.ARF were determined to be associated with age,gender,and region.Animal-derived foods were the dominant offending foods,especially shrimp,and skin symptoms were the most commonly reported ARF.Discussion:This is the first multi-center,largescale,epidemiologic study on ARF and FA using standardized methods,including DBPCFC,in the Chinese general population.This study presents an important approach to assessing ARF and FA,provides significant insights about the prevalence of ARF and FA,and facilitates support for updating the list of allergenic food labels:which will be essential for improving ARF prevention and management in China.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
Salmonella is widely known as one of the most common foodborne pathogens,and antibiotics remain effective in clinical therapies against its infections.To guide better clinical antibiotic treatment,we analyzed the anti...Salmonella is widely known as one of the most common foodborne pathogens,and antibiotics remain effective in clinical therapies against its infections.To guide better clinical antibiotic treatment,we analyzed the antimicrobial resistance(AMR)profiles of a nation-wide collection of 36,822 Salmonella isolates derived from sporadic diarrhea cases in China from 2014 to 2021.A panel of 15 antibiotics,including 10 critically important and 5 highly important antimicrobial agents for human medicine based on the WHO CIA List,was selected for AMR surveillance.Salmonella enterica serovar Typhimurium,Enteritidis,I 4,[5],12:i:-,London,and Stanley were turns to be the top five serotypes from human diarrhea cases in China.Antimicrobial susceptibility testing revealed that the majority of the isolates(87.2%)were resistant to at least one antimicrobial agent,and 66.5%were multidrug resistant(MDR).Salmonella isolates were found to be highly resistant to ampicillin(73.4%)while sensitive to imipenem(98.73%).Over the eight years,the isolates were demonstrated generally an increase in resistance to ampicillin,chloramphenicol,trimethoprim-sulfameth-oxazole,and azithromycin,but displayed varied resistance profiles in terms of serotypes.Stanley(0.66-27.18%)and Agona(0.78-45.30%)had lower resistance rates compared to Typhimurium(1.11-85.6%),Enteritidis(1.55-91.29%),and I 4,[5],12:i:-(1.02-94.28%).In conclusion,our results provide systematic data on the resistance characteristics of Salmonella isolates from human diarrhea cases in China.Furthermore,this data identifies priorities for the clinical treatments of antibiotics.展开更多
What is already known about this topic?The prevalence of food allergy(FA)among the general population has been increasing in recent decades,and seriously affects the physical and mental health and the quality of life ...What is already known about this topic?The prevalence of food allergy(FA)among the general population has been increasing in recent decades,and seriously affects the physical and mental health and the quality of life of many people—especially children.What is added by this report?The survey estimated self-reported FA prevalence using a standardized FA questionnaire among school children in Nanchang City,Jiangxi Province,China in 2021.What are the implications for public health practice?Based on the local,epidemiological characteristics of food allergy,public policies on the prevention and management of FA should be developed and preventive practices should be promoted to decrease the overall prevalence of FA.展开更多
A series of bimetallic lanthanide bis(amido) complexes stabilized by bridged bis(guanidinate) ligands {[(Me3Si)2N]2Ln[(RN)2-CN(CH2)2]}2 [R=iPr, Ln=Sm(1), Yb(2), Y(3); R=cyclohexyl(Cy), Ln=Sm(4), and Yb(5)] were synthe...A series of bimetallic lanthanide bis(amido) complexes stabilized by bridged bis(guanidinate) ligands {[(Me3Si)2N]2Ln[(RN)2-CN(CH2)2]}2 [R=iPr, Ln=Sm(1), Yb(2), Y(3); R=cyclohexyl(Cy), Ln=Sm(4), and Yb(5)] were synthesized through the metathesis reactions of {Ln(μ-Cl)[N(Si Me3)2]2(THF)}2(Ln=Sm, Yb, Y) with lithium guanidinate {Li[(RN)2CN(CH2)2]}2(R=iPr, Cy), the latter of which was generated in situ by the reaction of carbodiimides with lithium amides. Complexes 1–5 were well characterized by elemental analyses, IR spectra, and(for Complex 3) NMR spectroscopy. The solid-state molecular structures of all of the complexes were determined by single-crystal X-ray analyses with the exception of Complex 3, which showed similar unsolvated centrosymmetric dinuclear structures. Each of the lanthanide centers is four-coordinated with two nitrogen atoms from a guanidinate ligand and two nitrogen atoms from two amido groups. The piperazidine rings adopt chair conformations in all cases. These organolanthanide complexes were found to be efficient catalysts for the hydrophosphonylation reaction of various aldehydes and unactivated ketones and to afford ?-hydroxyphosphonates in high yields under low catalyst loading(0.1 mol%) in a short reaction time.展开更多
L-phenylglycine(L-phg)is a valuable non-proteinogenic amino acid used as a precursor to β-lactam antibiotics,antitumor agent taxol and many other pharmaceuticals.L-phg synthesis through microbial bioconversion allows...L-phenylglycine(L-phg)is a valuable non-proteinogenic amino acid used as a precursor to β-lactam antibiotics,antitumor agent taxol and many other pharmaceuticals.L-phg synthesis through microbial bioconversion allows for high enantioselectivity and sustainable production,which will be of great commercial and environmental value compared with organic synthesis methods.In this work,an L-phg synthesis pathway was built in Escher-ichia coli resulting in 0.23 mM L-phg production from 10 mM L-phenylalanine.Then,new hydroxymandelate synthases and hydroxymandelate oxidases were applied in the L-phg synthesis leading to a 5-fold increase in L-phg production.To address 2-oxoglutarate,NH_(4)^(+),and NADH shortage,a cofactor self-sufficient system was introduced,which converted by-product L-glutamate and NAD^(+)to these three cofactors simultaneously.In this way,L-phg increased 2.5-fold to 2.82 mM.Additionally,in order to reduce the loss of these three cofactors,a protein scaffold between synthesis pathway and cofactor regeneration modular was built,which further improved the L-phg production to 3.72 mM with a yield of 0.34 g/g L-phe.This work illustrated a strategy applying for whole-cell biocatalyst converting amino acid to its value-added chiral amine in a cofactor self-sufficient manner.展开更多
基金supported by the Natural Science Foundation of Guangxi Zhuang Automomous Region,Nos.2019GXNSFDA245015(to MC),2022GXNSFBA035654(to HL)the National Natural Science Foundation of China,Nos.82360241(to MC),82304876(to HL)+1 种基金Scientific Research and Technology Development Project of Guilin City,Nos.20220139-3(to MC),20210218-5(to HL)Guangxi Medical and Health Key Discipline Construction Project(to QL)。
文摘α-Synuclein accumulation and transmission are vital to the pathogenesis of Parkinson's disease,although the mechanisms underlying misfoldedα-synuclein accumulation and propagation have not been conclusively determined.The expression of low-density lipoprotein receptor–related protein 1,which is abundantly expressed in neurons and considered to be a multifunctional endocytic receptor,is elevated in the neurons of patients with Parkinson's disease.However,whether there is a direct link between low-density lipoprotein receptor–related protein 1 andα-synuclein aggregation and propagation in Parkinson's disease remains unclear.Here,we established animal models of Parkinson's disease by inoculating monkeys and mice withα-synuclein pre-formed fibrils and observed elevated low-density lipoprotein receptor–related protein 1 levels in the striatum and substantia nigra,accompanied by dopaminergic neuron loss and increasedα-synuclein levels.However,low-density lipoprotein receptor–related protein 1 knockdown efficiently rescued dopaminergic neurodegeneration and inhibited the increase inα-synuclein levels in the nigrostriatal system.In HEK293A cells overexpressingα-synuclein fragments,low-density lipoprotein receptor–related protein 1 levels were upregulated only when the N-terminus ofα-synuclein was present,whereas anα-synuclein fragment lacking the N-terminus did not lead to low-density lipoprotein receptor–related protein 1 upregulation.Furthermore,the N-terminus ofα-synuclein was found to be rich in lysine residues,and blocking lysine residues in PC12 cells treated withα-synuclein pre-formed fibrils effectively reduced the elevated low-density lipoprotein receptor–related protein 1 andα-synuclein levels.These findings indicate that low-density lipoprotein receptor–related protein 1 regulates pathological transmission ofα-synuclein from the striatum to the substantia nigra in the nigrostriatal system via lysine residues in theα-synuclein N-terminus.
基金supported by the Outstanding Youth Foundation of Heilongjiang Province(No.YQ2021H009).
文摘In this study,we employed a combination of genome mining and heteronuclear single quantum coherence(HSQC)-based small molecule accurate recognition technology(SMART)technology to search for fernane-type triterpenoids.Initially,potential endophytic fungi were identified through genome mining.Subsequently,fine fractions containing various fernane-type triterpenoids were selected using HSQC data collection and SMART prediction.These triterpenoids were then obtained through targeted isolation and identification.Finally,their antifungal activity was evaluated.As a result,three fernane-type triterpenoids,including two novel compounds,along with two new sesquiterpenes and four known compounds were isolated from one potential strain,Diaporthe discoidispora.Their structures were elucidated through analysis of high-resolution electrospray ionization mass spectrometry(HR-ESI-MS)and nuclear magnetic resonance(NMR)spectroscopic data.The absolute configurations were determined using single-crystal X-ray diffraction analysis and electron capture detector(ECD)analysis.Compound 3 exhibited moderate antifungal activity against Candida albicans CMCC 98001 and Aspergillus niger.
基金financially supported by the National Natural Science Foundation of China(Nos.52304129 and 52274130)Natural Science Foundation of Sichuan Province(No.2024NSFSC0971)+1 种基金Guizhou Provincial Basic Research Program(Natural Science)(No.ZK[2023]general 070)Shandong Key Laboratory of Mining Disaster Prevention and Control,Shandong University of Science and Technology(No.SMDPC202403)。
文摘The combination of ultrasonic and acid fracturing fluid can strengthen the modification effect on the micropore structure of the coal matrix,thereby enhancing the efficiency of the acid fracturing process.In this research,acetic acid was utilized to formulate acid fracturing fluids with varying concentrations,and the evolutionary traits of both the acid fracturing fluids and ultrasonic waves in relation to coal samples were investigated.The functional group structure,mineral composition,micropore structure and surface morphology of coal samples were characterized by FTIR,XRD,N_(2)adsorption at low temperature and SEM-EDS.The results showed that aromatics(I)and branching parameters(CH_(2)/CH_(3))were reduced by 81.58%and 88.67%,respectively,after 9%acetic acid treatment.Acetic acid can dissolve carbonates and clay minerals in coal,create new pores,and increase porosity,pore volume and pore fractal dimension.After modification by 7%acetic acid,the pore volume increased by 5.7 times.SEM observation shows that the diameter of coal surface holes increases,EDS scanning shows that the content of mineral elements in coal decreases,the connectivity of coal holes increases,and the holes expand.The findings of this research offer theoretical direction for optimizing ultrasonic-enhanced acid fracturing fluid modification.
基金supported by funding from the National Natural Science Foundation of China,China(grants 31621005 and 31600093 to F.G.L.)the Young Elite Scientists Sponsorship Program by CAST(2019zx08010033-002-012 to Z.E.Y.)Central Public-interest Scientific Institution Basal Research Fund(Y2020PT13)。
文摘Chromatin interactions functionally affect genome architecture and gene regulation,but to date,only fresh samples must be used in High-through chromosome conformation capture(Hi-C)to keep natural chromatin conformation intact.This requirement has impeded the advancement of 3 D genome research by limiting sample collection and storage options for researchers and severely limiting the number of samples that can be processed in a short time.Here,we develop a freeze substitution Hi-C(FS-Hi-C)technique that overcomes the need for fresh samples.FS-Hi-C can be used with samples stored in liquid nitrogen(LN2):the water in a vitreous form in the sample cells is replaced with ethanol via automated freeze substitution.After confirming that the FS step preserves the natural chromosome conformation during sample thawing,we tested the performance of FS-Hi-C with Drosophila melanogaster and Gossypium hirsutum.Beyond allowing the use of frozen samples and confirming that FS-Hi-C delivers robust data for generating contact heat maps and delineating A/B compartments and topologically associating domains,we found that FS-HiC outperforms the in situ Hi-C in terms of library quality,reproducibility,and valid interactions.Thus,FS-HiC will probably extend the application of 3D genome structure analysis to the vast number of experimental contexts in biological and medical research for which Hi-C methods have been unfeasible to date.
文摘In recent years,frequent network attacks have highlighted the importance of efficient detection methods for ensuring cyberspace security.This paper presents a novel intrusion detection system consisting of a data prepro-cessing stage and a deep learning model for accurately identifying network attacks.We have proposed four deep neural network models,which are constructed using architectures such as Convolutional Neural Networks(CNN),Bi-directional Long Short-Term Memory(BiLSTM),Bidirectional Gate Recurrent Unit(BiGRU),and Attention mechanism.These models have been evaluated for their detection performance on the NSL-KDD dataset.To enhance the compatibility between the data and the models,we apply various preprocessing techniques and employ the particle swarm optimization algorithm to perform feature selection on the NSL-KDD dataset,resulting in an optimized feature subset.Moreover,we address class imbalance in the dataset using focal loss.Finally,we employ the BO-TPE algorithm to optimize the hyperparameters of the four models,maximizing their detection performance.The test results demonstrate that the proposed model is capable of extracting the spatiotemporal features of network traffic data effectively.In binary and multiclass experiments,it achieved accuracy rates of 0.999158 and 0.999091,respectively,surpassing other state-of-the-art methods.
基金the National Natural Science Foundation of China(No.32370069 and U22A20369)the Fundamental Research Funds for the Central Universities(2572023AW40)+1 种基金the Natural Science Foundation of Heilongjiang Province of China(No.LH2023C035)the Key R&D Projects in Shaanxi Province of China(No.2023-YBSF-164).
文摘Mushrooms have been utilized by humans for thousands of years due to their medicinal and nutritional properties.They are a crucial natural source of bioactive secondary metabolites,and recent advancements have led to the isolation of several alkynyl-containing compounds with potential medicinal uses.Despite their relatively low abundance,naturally occurring alkynyl compounds have attracted considerable attention due to their high reactivity.Bioactivity studies have shown that alkynyl compounds exhibit significant biological and pharmacological activities,including antitumor,antibacterial,antifungal,insecticidal,phototoxic,HIV-inhibitory,and immunosuppressive properties.This review systematically compiles 213 alkynyl-containing bioactive compounds isolated from mushrooms since 1947 and summarizes their diverse biological activities,focusing mainly on cytotoxicity and anticancer effects.This review serves as a detailed and comprehensive reference for the chemical structures and bioactivity of alkynyl-containing secondary metabolites from mushrooms.Moreover,it provides theoretical support for the development of chemical constituents containing alkynyl compounds in mushrooms based on academic research and theory.
基金the National Natural Science Foundation of China(Project No.22077102 and 21877089)the Shaanxi Key Laboratory of Natural Product&Chemical Biology Open Foundation(Project No.SXNPCB 2021001).
文摘Indole diterpenoids(IDTs)are an essential class of structurally diverse fungal secondary metabolites,that generally appear to be restricted to a limited number of fungi,such as Penicillium,Aspergillus,Claviceps,and Epichloe species,etc.These compounds share a typical core structure consisting of a cyclic diterpene skeleton of geranylgeranyl diphos-phate(GGPP)and an indole ring moiety derived from indole-3-glycerol phosphate(IGP).3-geranylgeranylindole(3-GGI)is the common precursor of all IDTs.On this basis,it is modified by cyclization,oxidation,and prenylation to generate a large class of compounds with complex structures.These compounds exhibit antibacterial,anti-insect,and ion channel inhibitory activities.We summarized 204 compounds of IDTs discovered from various fungi over the past 50 years,these compounds were reclassified,and their biological activities were summarized.This review will help to understand the structural diversity of IDTs and provide help for their physiological activities.
基金supported by the Shandong Provincial Science and Technology SMEs Innovation Capacity Improvement Project(2022TSGC2018)the Shandong Natural Science Foundation(Grant No.ZR2022ME008)+3 种基金the Shenzhen Science and Technology Program(KCXFZ20201221173409026)the“Young Scholars Program of Shandong University”(YSPSDU,No.2018WLJH73)the Open Project of State Key Laboratory of Clean Energy Utilization,Zhejiang University(Program Number ZJUCEU2020011)the Shandong Natural Science Foundation(Grant No.ZR2021ME118).
文摘Pre-cooling the inlet air of a dry cooling tower by means of a spray can improve the tower performance during periods of high temperature.To study the spray effect on the thermal performance of natural draft dry cooling towers(NDDCTs),in this study 3-D numerical simulations of such a process have been conducted using Fluent 16.2(a two-way coupled Eulerian-Lagrangian approach).The considered NDDCT is 120 m high and only half system is simulated due to its structural symmetry.Three different spray strategies have been investigated at a typical crosswind speed of 4 m/s,which is the most frequent wind speed.The results have shown that:(1)The three implemented spray strategies can improve the thermal performance of the studied NDDCT with a vary-ing degree of success.In one case,the heat rejection rate can be increased by 35.2%,and the tower outlet water temperature can be decreased by 2.1℃ when compared with the no spray case;(2)To improve the thermal per-formance of the NDDCT using a small amount of water,the design of the spray pre-cooling system must include more nozzles on the windward and fewer or even no nozzles on the leeward sides of the NDDCT.
基金supported by the Key R&D Projects in Shaanxi Province of China(No.2023-YBSF-164)the National Natural Science Foundation of China(No.31800031 and No.32370069)+1 种基金the Fundamental Research Funds for the Central Universities(2572023AW40)the Natural Science Foundation of Heilongjiang Province of China(No.LH2023C035).
文摘Glycosylation is a prevalent post-modification found in natural products and has a significant impact on the structural diversity and activity variation of natural products.Glucosylation is the most common type of glycosylation,whereas xylosylation is relatively rare.Despite their unique chemical structures and beneficial activities,xylosylated natural products from microorganisms have received little attention.This review provides,for the first time,a comprehensive summary of 126 microbial-derived xylosylated natural products,including xylosyl-cyathane diterpenes,xylosylated triterpenes,xylosyl aromatic compounds,and others.Among these compounds,xylosyl-cyathane diterpenes represent the highest number of derivatives,followed by xylosylated triterpenes.Xylosyl compounds from bacterial sources have less defined structural profiles compared to those from fungi.The characterization of xylosyltransferase EriJ from Basidiomycota extended the structural diversity of xylosyl cyathane diterpenes.This work provides a valuable reference for the research and use of xylosyltransferase for drug discovery and synthetic chemistry.Further work is needed to explore the potential applications of microbial derived xylosyl compounds and to develop novel xylosyl transferases.With the deepening of genomic sequencing of medicinal fungi,more biosynthesis of bioactive xylosyl compounds is expected to be elucidated in the future.
基金supported by the Science and Technology Department of Guizhou Province Fund(Qiankehe Basic-ZK[2023]Normal-446 and Qiankehe Basic-ZK[2023]Normal-445)Liupanshui Science and Technology Bureau Fund(52020-2022-PT-15)the Education Department of Guizhou Province Fund(Youth Science and Technology Talent Development Project Qianjiaoji[2024]150).
文摘This paper proposes a method for creating a three-dimensional(above-ground and underground)fracture network in deep coalbed methane(CBM)reservoirs,which is the directional fracturing by slotted hydraulic blasting in underground drilling.First,theoretical analysis was conducted to explain the mechanism by which the slotted borehole enables the separation and incidence of explosive shock wave at the slot tip,resulting in the superposition of two sub-stress waves to cause directional fracture and damage to the rock.Then,LS-DYNA was used to simulate the process of directional fracturing by slotted hydraulic blasting to verify the theoretical mechanism.Finally,similar simulation experiments were performed on traditional blasting and slotted hydraulic blasting to confirm the directional fracturing effect of the proposed method.The results indicate that the slotted hydraulic blasting method can predominate the fracture orientation under formation stress,creating extensive directional fractures in rocks in the slot direction.This study is supplemental to the efforts on directional fracturing of rocks and provides a new approach for efficient exploitation of CBM.
基金funded by the National Natural Science Foundation of China(No.U22A20369,32370069 and 31800031)the Natural Science Foundation of Heilongjiang Province of China(No.LH2023C035).
文摘Meroterpenoids are secondary metabolites partially derived from the terpenoid biosynthetic pathway,and are widely distributed in plants,animals,and fungi.These natural products possess complex backbone structures and diverse bioactivities.Ganoderma meroterpenoids(GMs)form a distinct group of meroterpenoids were characterized by the presence of 1,2,4-trisubstituted phenyl and polyunsaturated terpene moieties.Various Ganoderma species have been extensively studied,leading to the discovery of several structurally unique meroterpenoids with significant pharmacological activities.After the first isolation and identification of GMs in 2000,over 300 compounds from 14 species have been characterized for their structures and biological activities.The structures and activities of some GMs from different Ganoderma species vary greatly,probably due to significant differences in the genome and transcriptome of different Ganoderma species.We predicted the related enzymes based on the reported Ganoderma genome and proposed the biosynthetic pathway related to GMs.The results presented in this review provide a scientific foundation for the comprehensive exploration and utilization of diverse Ganoderma resources.
基金funded by the National Natural science Foundation of China(31800031 and 32370069)the Key r&D Projects in shaanxi Province of China(2023-YBsF-164).
文摘Hericium mushrooms are a group of rare medicinal mushrooms that have attracted considerable attention worldwide.in order to gain insight into the current trends and frontiers of Hericium research,we conducted a comprehensive search of the Web of science(Wos)database to identify relevant literature on Hericium research.Following an optimised search strategy and careful removal of duplicate entries,a total of 839 documents were selected from the core Wos database for bibliometric analysis.We used Vosviewer to visualize the co-occurrence network between publishing organizations,while Citespace allowed us to visualize and analyse the national co-occurrence network,author co-occurrence network,keyword co-linearity,keyword clustering and co-citation mapping.our analysis revealed a significant and continuous increase in the number of publications related to Hericium mushrooms,with a peak observed in 2021.Examination of publication statistics by country(region)and institution identified China and Universiti Malaysia as the leading contributors in their respective fields,with active collaboration with other countries and institutions.the analysis of author co-occurrence suggests that inter-author communications and collaborations may be geographically limited by the research institutions to which they belong.Various keyword-based analyses highlighted the structural diversity and bioactivities of small molecule compounds derived from Hericium mushrooms,underscoring their potential health-protective effects as rare food and medicinal mushrooms.through co-citation analysis,we identified J.agr.Food Chem.as the most cited journal for Hericium mushroom research results,while Yoko Kawagishi of shizuoka University(Japan)emerged as the most cited researcher in the field.overall,our findings suggest that research into the potential anti-neurodegenerative properties of Hericium mushrooms is a promising area of investigation,with a focus on elucidating the underlying mechanisms of action.
基金The National Key Research and Development Program of China(Grant number 2017YFC1601503).
文摘ABSTRACT Introduction:Mushroom poisoning was the leading cause of foodborne disease outbreaks and outbreak-associated deaths in China.Mushroom poisoning outbreak surveillance can provide insight into the epidemiological characteristics of mushroom poisonings and guide policymaking and health education to reduce illnesses and deaths.Methods:Foodborne Disease Outbreak Surveillance System was upgraded in 2011 to collect foodborne disease outbreaks in China.Mushroom poisoning outbreaks during 2010–2020 were selected to analyze geographical distribution,seasonal distribution,and setting of food preparation.Results:A total of 10,036 outbreaks,which resulted in 38,676 illnesses and 788 deaths,were reported in this period.Mushroom poisonings occurred all over the country,but with highest incidence in the southwest and central China.
基金supported by CAMS Innovation Fund for Medical Science(CIFMS 2019-I2M-5-024).
文摘Introduction:Adverse reactions to food(ARF)are a major worldwide public health and food safety problem.Among the various causes of ARF,food allergies(FA)are particularly serious as the immune response that is triggered can be fatal even at very low doses.However,the prevalence of ARF and FA in the general population in China is presently unclear.This study aims to determine the epidemiological characteristics and risk factors for ARF and FA,which can be a basis for estimating thresholds for major food allergens.Methods:This is a multicenter,cross-sectional,epidemiologic survey with a case-control study nested among a selected population in China.Random individuals were recruited using stratified cluster random sampling;ARF and FA were comprehensively assessed using modified EuroPrevall FA Project questionnaires as well as structured interviews,sensitization testing,and double-blind placebocontrolled food challenges(DBPCFC).Results:This method of epidemiologic study on ARF and FA was a pilot application in Jiangxi Province from January 2020;among the total 21,273 children and adults that completed the questionnaire,5.8%reported ARF and 4.3%reported FA.ARF were determined to be associated with age,gender,and region.Animal-derived foods were the dominant offending foods,especially shrimp,and skin symptoms were the most commonly reported ARF.Discussion:This is the first multi-center,largescale,epidemiologic study on ARF and FA using standardized methods,including DBPCFC,in the Chinese general population.This study presents an important approach to assessing ARF and FA,provides significant insights about the prevalence of ARF and FA,and facilitates support for updating the list of allergenic food labels:which will be essential for improving ARF prevention and management in China.
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.
基金supported by The National Key Research and Development Program of China(Grant number 2022YFC2303900).
文摘Salmonella is widely known as one of the most common foodborne pathogens,and antibiotics remain effective in clinical therapies against its infections.To guide better clinical antibiotic treatment,we analyzed the antimicrobial resistance(AMR)profiles of a nation-wide collection of 36,822 Salmonella isolates derived from sporadic diarrhea cases in China from 2014 to 2021.A panel of 15 antibiotics,including 10 critically important and 5 highly important antimicrobial agents for human medicine based on the WHO CIA List,was selected for AMR surveillance.Salmonella enterica serovar Typhimurium,Enteritidis,I 4,[5],12:i:-,London,and Stanley were turns to be the top five serotypes from human diarrhea cases in China.Antimicrobial susceptibility testing revealed that the majority of the isolates(87.2%)were resistant to at least one antimicrobial agent,and 66.5%were multidrug resistant(MDR).Salmonella isolates were found to be highly resistant to ampicillin(73.4%)while sensitive to imipenem(98.73%).Over the eight years,the isolates were demonstrated generally an increase in resistance to ampicillin,chloramphenicol,trimethoprim-sulfameth-oxazole,and azithromycin,but displayed varied resistance profiles in terms of serotypes.Stanley(0.66-27.18%)and Agona(0.78-45.30%)had lower resistance rates compared to Typhimurium(1.11-85.6%),Enteritidis(1.55-91.29%),and I 4,[5],12:i:-(1.02-94.28%).In conclusion,our results provide systematic data on the resistance characteristics of Salmonella isolates from human diarrhea cases in China.Furthermore,this data identifies priorities for the clinical treatments of antibiotics.
基金Supported by CAMS Innovation Fund for Medical Science(CIFMS 2019-I2M-5-024)TCM Science and Technology Project of Jiangxi Province in 2021(2021B696).
文摘What is already known about this topic?The prevalence of food allergy(FA)among the general population has been increasing in recent decades,and seriously affects the physical and mental health and the quality of life of many people—especially children.What is added by this report?The survey estimated self-reported FA prevalence using a standardized FA questionnaire among school children in Nanchang City,Jiangxi Province,China in 2021.What are the implications for public health practice?Based on the local,epidemiological characteristics of food allergy,public policies on the prevention and management of FA should be developed and preventive practices should be promoted to decrease the overall prevalence of FA.
基金supported by the National Natural Science Foundation of China(21132002,21372172,21402138)the Major Research Project of the Natural Science Foundation of the Jiangsu Higher Education Institutions(14KJA150007)the Qing Lan Project
文摘A series of bimetallic lanthanide bis(amido) complexes stabilized by bridged bis(guanidinate) ligands {[(Me3Si)2N]2Ln[(RN)2-CN(CH2)2]}2 [R=iPr, Ln=Sm(1), Yb(2), Y(3); R=cyclohexyl(Cy), Ln=Sm(4), and Yb(5)] were synthesized through the metathesis reactions of {Ln(μ-Cl)[N(Si Me3)2]2(THF)}2(Ln=Sm, Yb, Y) with lithium guanidinate {Li[(RN)2CN(CH2)2]}2(R=iPr, Cy), the latter of which was generated in situ by the reaction of carbodiimides with lithium amides. Complexes 1–5 were well characterized by elemental analyses, IR spectra, and(for Complex 3) NMR spectroscopy. The solid-state molecular structures of all of the complexes were determined by single-crystal X-ray analyses with the exception of Complex 3, which showed similar unsolvated centrosymmetric dinuclear structures. Each of the lanthanide centers is four-coordinated with two nitrogen atoms from a guanidinate ligand and two nitrogen atoms from two amido groups. The piperazidine rings adopt chair conformations in all cases. These organolanthanide complexes were found to be efficient catalysts for the hydrophosphonylation reaction of various aldehydes and unactivated ketones and to afford ?-hydroxyphosphonates in high yields under low catalyst loading(0.1 mol%) in a short reaction time.
基金the National Natural Science Foundation of China(Project No.31900064)as well as the Natural Science Foundation of Heilongjiang Province of China(Project No.LH2019C012)。
文摘L-phenylglycine(L-phg)is a valuable non-proteinogenic amino acid used as a precursor to β-lactam antibiotics,antitumor agent taxol and many other pharmaceuticals.L-phg synthesis through microbial bioconversion allows for high enantioselectivity and sustainable production,which will be of great commercial and environmental value compared with organic synthesis methods.In this work,an L-phg synthesis pathway was built in Escher-ichia coli resulting in 0.23 mM L-phg production from 10 mM L-phenylalanine.Then,new hydroxymandelate synthases and hydroxymandelate oxidases were applied in the L-phg synthesis leading to a 5-fold increase in L-phg production.To address 2-oxoglutarate,NH_(4)^(+),and NADH shortage,a cofactor self-sufficient system was introduced,which converted by-product L-glutamate and NAD^(+)to these three cofactors simultaneously.In this way,L-phg increased 2.5-fold to 2.82 mM.Additionally,in order to reduce the loss of these three cofactors,a protein scaffold between synthesis pathway and cofactor regeneration modular was built,which further improved the L-phg production to 3.72 mM with a yield of 0.34 g/g L-phe.This work illustrated a strategy applying for whole-cell biocatalyst converting amino acid to its value-added chiral amine in a cofactor self-sufficient manner.
