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工程（英文）

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2095-8099

工程（英文）/Journal EngineeringCSTPCDCSCD北大核心SCI
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    Decreased Amino Acid Transporter LAT2 Is the Main Determinant of Impaired Protein Utilization During Aging

    Rui SongGuang LiLiang ZhaoLili Qiu...
    88-98页
    查看更多>>摘要：As the global demographic shifts toward an aging population,understanding the efficiency of protein uti-lization in older adults becomes crucial.Our study explores the intricate relationship between protein intake and aging,with a focus on precision nutrition for older people.Through a meta-analysis,we con-firm a decline in protein-utilization capacity in older individuals and examine the different contributions of plant and animal protein.In experiments involving mice of different ages,older mice exhibited decreases in the biological utilization of four proteins(casein,beef protein,soy protein,and gluten),par-ticularly casein.In subsequent research,casein was studied as a key protein.A decline in gastric digestion function was observed through peptidomics and the examination of pepsin levels using casein.Nevertheless,this decline did not significantly affect the overall protein digestion during the aging pro-cess.The combined application of targeted amino acid metabolomics identified abnormal absorption of amino acids as the underlying cause of decreased protein utilization during aging,particularly emphasiz-ing a reduction in branched-chain amino acids(BCAAs)in older mice.Delving deeper into the proteomics of the intestinal protein digestion and absorption pathway,a reduction of over 60％in large neutral amino acid transporter 2(LAT2)protein expression was observed in both older humans and aged mice.The reduction in LAT2 protein was found to be a key factor influencing the diminished BCAA availability.Overall,our study establishes the significance of amino acid absorption through LAT2 in protein utiliza-tion during aging and offers a new theoretical foundation for improving protein utilization in the older adults.
      原文链接:
    • 万方数据
    • 维普

    Modifiers of the Effects of Vitamin D Supplementation on Cardiometabolic Risk Factors:A Systematic Review and Meta-Analysis

    Peng AnSitong WanLangrun WangTiancheng Xu...
    99-107页
    查看更多>>摘要：The inconsistent findings concerning the effects of vitamin D supplementation on cardiometabolic risk fac-tors and the large heterogeneity in the published literature call for further research to identify sources of heterogeneity and potential effect modifiers.We performed a meta-analysis of randomized controlled tri-als(RCTs)published until March 2024 that reported estimates for the effects of vitamin D supplementation on cardiometabolic factors and relevant baseline covariates of RCT participants.A total of 17 656 partici-pants from 99 RCTs were analyzed,and weighted mean differences(95％confidence intervals(CI))for the intervention status were derived using random-effects modeling.Overall,compared with the placebo,vitamin D supplementation(median dose:3320 international unit(IU)·day-1;range 40-120 000 IU·day-1)had favorable effects on systolic blood pressure(SBP;-2.04(95％CI,-3.50,-0.59)mmHg;1 mmHg=0.133 kPa),diastolic blood pressure(DBP;-3.00(95％CI,-3.61,-2.39)mmHg),total cholesterol(TC;-0.12(95％CI,-0.21,-0.03)mmol·L-1),fasting blood glucose(FBG;-0.13(95％CI,-0.20,-0.05)mmol·L-1),hemoglobin A1C(A1C;-0.09％(95％CI,-0.13％,-0.05％)),and fasting blood insulin(FBI:-7.61(95％CI,-11.93,-3.30)pmol·L-1).The benefits of vitamin D were most evident in trials performed in non-Westerners,participants with baseline 25-hydroxyvitamin D(25[OH]D)lower than 15.0 ng·mL-1,non-obese(body mass index(BMI)＜30 kg·m-2),and older(age ≥ 50 years).The findings of this study underscore the need for personalized vitamin D intervention strategies that comprehensively account for individual patient characteristics(such as ethnocultural background,age,BMI,and circulating 25[OH]D level),intervention dosage,and intervention duration to optimize cardiometabolic health outcomes.
      原文链接:
    • 万方数据
    • 维普

    Procyanidin C1 Modulates the Microbiome to Increase FOXO1 Signaling and Valeric Acid Levels to Protect the Mucosal Barrier in Inflammatory Bowel Disease

    Xifan WangPengjie WangYixuan LiHuiyuan Guo...
    108-120页
    查看更多>>摘要：Inflammatory bowel disease(IBD)refers to a pair of prevalent conditions(Crohn's disease and ulcerative colitis)distinguished by persistent inflammation of the large intestine.Procyanidin C1(PCC1)is a natu-rally occurring substance derived from grape seeds that has demonstrated notable anti-inflammatory properties.This study examines the potential utility of PCC1 as a treatment for IBD and subsequently examines the host-cell-and microbiome-related mechanisms underlying the detected therapeutic bene-fits.Working with a classic dextran sodium sulfate(DSS)-induced mouse IBD model,we show that PCC1 protects the mucosal barrier and thereby confers strong protective effects against IBD.PCC1 pretreatment resulted in anti-inflammatory effects and protection against multiple pathological phenotypes in the IBD model mice,including reduced weight loss,lower disease activity index(DAI)totals,and enhanced colon size,as well as obviously beneficial effects on the mucosal barrier(e.g.,barrier thickness and activity of mucus-degrading enzymes).We also analyzed the autophagy marker microtubule-associated protein1 light chain 3(LC3)and found that the level of LC3 was significantly elevated in the intestinal epithelial cell samples of the PCC1-pretreatment group as compared with the non-model mice samples.PCC1 altered the fecal microbiome composition,which included elevating the abundance of Akkermansia muci-niphila and Christensenella minuta.Fecal microbiome transplant(FMT)experiments showed that deliver-ing a microbiome from PCC1-treated animals into PCC1-naïve animals conferred protection.Metabolic profiling revealed that both the PCC1-pretreatment and PCC1 FMT groups had elevated levels of the microbiota-derived metabolite valeric acid,and supplementation with this short-chain fatty acid(SCFA)also conferred strong protection against IBD.Finally,inhibitor experiments confirmed that the beneficial effects of valeric acid on the mucus layer are mediated by FOXO1 signaling in the goblet cells of the intestinal epithelium.Beyond showing that PCC1 confers anti-inflammatory effects and protection against IBD by altering the microbiome,our study demonstrates proof of principle for multiple straight-forward interventions(PCC1,FMT,and valeric acid supplementation)for ameliorating mucosal barrier damage to treat IBD.
      原文链接:
    • 万方数据
    • 维普

    Progress in Organ Bioprinting for Regenerative Medicine

    Xiang WangDi ZhangYogendra Pratap SinghMiji Yeo...
    121-142页
    查看更多>>摘要：Organ damage or failure arising from injury,disease,and aging poses challenges due to the body's limited regenerative capabilities.Organ transplantation presents the issues of donor shortages and immune rejection risks,necessitating innovative solutions.The three-dimensional(3D)bioprinting of organs on demand offers promise in tissue engineering and regenerative medicine.In this review,we explore the state-of-the-art bioprinting technologies,with a focus on bioink and cell type selections.We follow with discussions on advances in the bioprinting of solid organs,such as the heart,liver,kidney,and pancreas,highlighting the importance of vascularization and cell integration.Finally,we provide insights into key challenges and future directions in the context of the clinical translation of bioprinted organs and their large-scale production.
      原文链接:
    • 万方数据
    • 维普

    Activation of the Macrophage-Associated Inflammasome Exacerbates Myocardial Fibrosis Through the 15-HETE-Mediated Pathway in Acute Myocardial Infarction

    Xu ChenZhiyong DuDongqing GuoJincheng Guo...
    143-156页
    查看更多>>摘要：This investigation elucidates the spatiotemporal dynamics of NOD-like receptor family pyrin domain con-taining 3(NLRP3)inflammasome activation following myocardial infarction(MI),a process that has not been fully characterized.We revealed early activation of the NLRP3 inflammasome in mice with MI and characterized its dynamic temporal expression.Notably,the knockout and inhibition of Nlrp3 expression were found to significantly mitigate infarct size and enhance cardiac function.Furthermore,our analysis of the spatial characteristics of inflammasome activation revealed predominant activation in macro-phages and subsequent activation in fibroblasts on the third day post-MI.To elucidate the nexus between macrophage-associated NLRP3 inflammasome activation and myocardial fibrosis,we employed targeted metabolomics analyses of inflammatory oxylipins,small interfering RNA(siRNA)interference experi-ments,and various molecular assays.These findings revealed that macrophage-associated inflammasome activation facilitates the conversion of fibroblasts into myofibroblasts via the 15-hydroxy-5,8,11,13-eicosatetraenoic acid(15-HETE)-mediated small mother against decapentaplegic(Smad)pathway.Additionally,both mass spectrometry imaging(MSI)and targeted metabolomics analyses confirmed the significant increase in 15-HETE levels in mice with MI and in patients with MI and acute coronary syndrome(ACS).Our comprehensive dataset suggests that NLRP3 inflammasome activation in MI is char-acterized by distinct temporal and spatial patterns.These insights mark a significant advancement toward precise MI prevention and treatment strategies,particularly early myocardial fibrosis intervention.
      原文链接:
    • 万方数据
    • 维普

    Stock Volatility Increases the Mortality Risk of Major Adverse Cardiovascular Events and Suicide:A Case-Crossover Study of 12 Million Deaths

    Ya GaoPeng YinHaidong KanRenjie Chen...
    157-165页
    查看更多>>摘要：Stock volatility constitutes an adverse psychological stressor,but few large-scale studies have focused on its impact on major adverse cardiovascular events(MACEs)and suicide.Here,we conducted an individual-level time-stratified case-crossover study to explore the association of daily stock volatility(daily returns and intra-daily oscillations for three kinds of stock indices)with MACEs and suicide among more than 12 million individual decedents from all counties in the mainland of China between 2013 and 2019.For daily stock returns,both stock increases and decreases were associated with increased mortal-ity risks of all MACEs and suicide.There were consistent and positive associations between intra-daily stock oscillations and mortality due to MACEs and suicide.The excess mortality risks occurred at the cur-rent day(lag 0 d),persisted for two days,and were greatest for suicide and hemorrhagic stroke.Taking the present-day Shanghai and Shenzhen 300 Index as an example,a 1％decrease in daily returns was associated with 0.74％-1.04％and 1.77％increases in mortality risks of MACEs and suicide,respectively;the corresponding risk increments were 0.57％-0.85％and 0.92％for a 1％increase in daily returns and 0.67％-0.77％and 1.09％for a 1％increase in intra-daily stock oscillations.The excess risks were more pro-nounced among individuals aged 65-74 years,males,and those with lower education levels.Our findings revealed considerable health risks linked to sociopsychological stressors,which are helpful for the gov-ernment and general public to mitigate the immediate cardiovascular and mental health risks associated with stock market volatility.
      原文链接:
    • 万方数据
    • 维普

    Controllable Histotomy Based on Hierarchical Magnetic Microneedle Array Robots

    Xiaoxuan ZhangHanxu ChenTaiyu SongJinglin Wang...
    166-174页
    查看更多>>摘要：Investigation of patient-derived primary tissues is of great importance in the biomedical field,but recent tissue slicing and cultivation techniques still have difficulties in satisfying clinical requirements.Here,we propose a controllable histotomy strategy that utilizes hierarchical magnetic microneedle array robots to tailor primary tissues and establish the desired high-throughput tissue-on-a-chip.This histotomy is performed using a three-dimensional printed,mortise-tenon-structured slicing device coupled with a magnetic-particle-loaded and pagoda-shaped microneedle array scaffold.Due to the multilayered struc-ture of these microneedles,tissue specimens can be fixed onto the microneedle scaffold via mechanical interlocking,thereby effectively avoiding tissue slipping during the slicing process.Owing to the encapsu-lation of magnetic microneedle fragments,these tissue pieces can act as magnetically responsive biohybrid microrobots and can be easily manipulated by magnetic fields,facilitating their separation,transportation,and dynamic culture.Using this strategy,we demonstrate that primary pancreatic cancer tissues can be tailored into tiny pieces and cultured in multilayered microfluidic chips for efficient high-throughput drug screening,indicating the promising future of this technique's application in clinical settings.
      原文链接:
    • 万方数据
    • 维普

    Standard Framework Construction of Technology and Equipment for Big Data in Crop Phenomics

    Weiliang WenShenghao GuYing ZhangWanneng Yang...
    175-184页
    查看更多>>摘要：Crop phenomics has rapidly progressed in recent years due to the growing need for crop functional geno-mics,digital breeding,and smart cultivation.Despite this advancement,the lack of standards for the cre-ation and usage of crop phenomics technology and equipment has become a bottleneck,limiting the industry's high-quality development.This paper begins with an overview of the crop phenotyping indus-try and presents an industrial mapping of technology and equipment for big data in crop phenomics.It analyzes the necessity and current state of constructing a standard framework for crop phenotyping.Furthermore,this paper proposes the intended organizational structure and goals of the standard frame-work.It details the essentials of the standard framework in the research and development of hardware and equipment,data acquisition,and the storage and management of crop phenotyping data.Finally,it discusses promoting the construction and evaluation of the standard framework,aiming to provide ideas for developing a high-quality standard framework for crop phenotyping.
      原文链接:
    • 万方数据
    • 维普

    Development of an Engineered Sugar Aminotransferase with Simultaneously Improved Stability and Non-Natural Substrate Activity to Synthesize the Glucosidase Inhibitor Valienamine

    Runxi WangLu QiaoMufei LiuYanpeng Ran...
    185-195页
    查看更多>>摘要：Sugar aminotransferases(SATs)catalyze the installation of chiral amines onto specific keto sugars,pro-ducing bioactive amino sugars.Their activity has been utilized in artificial reactions,such as using the SAT WecE to transform valienone into the valuable α-glucosidase inhibitor valienamine.However,the low thermostability and limited activity on non-natural substrates have hindered their applications.Simultaneously improving stability and enzyme activity is particularly challenging owing to the acknowledged inherent trade-off between stability and activity.A customized combinatorial active-site saturation test-iterative saturation mutagenesis(CAST-ISM)strategy was used to simultaneously enhance the stability and activity of WecE toward valienone.Fourteen hotspots related to improving the stability-\activity trade-off were identified based on evolutionary conservation and the average mutation folding energy assessment of 57 residues in the active site of WecE.Positive mutagenesis and combinatorial mutations of these specific residues were accomplished via site-directed saturation mutagenesis(SSM)and iterative evolution cycles.Compared with those of the wild-type(WT)WecE,the quadruple mutant M4(Y321F/K209F/V318R/F319V)displayed a 641.49-fold increase in half-life(t1/2)at 40 ℃ and a 31.37-fold increase in activity toward the non-natural substrate valienone.The tri-ple mutant M3(Y321F/K209F/V318R)demonstrated an 83.04-fold increase in(t1/2)at 40 ℃ and a 37.77-fold increase in activity toward valienone.The underlying mechanism was dependent on the strengthened interface interactions and shortened transamination reaction catalytic distance,compared with those of the WT,which improved the stability and activity of the obtained mutants.Thus,we accomplished a general target-oriented strategy for obtaining stable and highly active SATs for artificial amino-sugar biosynthesis applications.
      原文链接:
    • 万方数据
    • 维普

    Revealing High-Efficiency Natural Mycotoxin Antidotes in Zebrafish Model Screening Against Zearalenone-Induced Toxicity

    Hong-Yun ZhangWei-Dan JiangPei WuYang Liu...
    196-212页
    查看更多>>摘要：Zearalenone(ZEA),a mycotoxin,poses a significant global hazard to human and animal health.Natural products(NPs)have shown promise for mitigating the adverse effects of ZEA owing to their diverse func-tional activities.However,the current challenge lies in the absence of an efficient strategy for systematic screening and identification of NPs that can effectively protect against ZEA-induced toxicity.This study describes a phenotype-based screening strategy for screening NP libraries and discovering more effective compounds to mitigate or counteract the adverse consequences of ZEA exposure in animals.Using this strategy,we initially identified 96 NPs and evaluated the potency and efficacy of two effective candidate compounds,fraxetin,and hydroxytyrosol,based on embryonic phenotype and locomotor activity using a scoring system and the TCMacro method.Furthermore,we performed transcriptome and protein-protein interaction(PPI)network analyses to extract two mRNA signatures to query the Connectivity Map(CMap)database and predict NPs.The predicted NPs showed the potential to reverse the gene expression profiles associated with ZEA toxicity.Consequently,we further screened these compounds using our model,which indicated that hispidin,daphnetin,and riboflavin exhibit promising in vivo effi-cacy in zebrafish.Notably,throughout the process,fraxetin consistently stood out as the most promising NP.Biological pathway analysis and functional verification revealed that fraxetin completely reversed the toxic effects of ZEA at very low doses.This was achieved by repairing damaged cell apoptosis,modifying the cell cycle pathway,and preventing senescence induction,indicating good application potential.Overall,we demonstrated that this integration strategy can be successfully applied to effectively discover potential antidotes.
      原文链接:
    • 万方数据
    • 维普