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工程（英文）
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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    Natural Products Improve Organ Microcirculation Dysfunction Following Ischemia/Reperfusion-and Lipopolysaccharide-Induced Disturbances:Mechanistic and Therapeutic Views

    Jingyan HanQuan LiKai SunChunshui Pan...
    77-99页
    查看更多>>摘要：Microcirculatory disturbances are complex processes caused by many factors,including abnormal vaso-motor responses,decreased blood flow velocity,vascular endothelial cell injury,altered leukocyte and endothelial cell interactions,plasma albumin leakage,microvascular hemorrhage,and thrombosis.These disturbances involve multiple mechanisms and interactions among mechanisms that can include energy metabolism,the mitochondrial respiratory chain,oxidative stress,inflammatory factors,adhesion molecules,the cytoskeleton,vascular endothelial cells,caveolae,cell junctions,the vascular basement membrane,neutrophils,monocytes,and platelets.In clinical practice,aside from drugs that target abnor-mal vasomotor responses and platelet adhesion,there continues to be a lack of multi-target drugs that can regulate the complex mechanistic links and interactions underlying microcirculatory disturbances.Natural products have demonstrated obvious positive therapeutic effects in treating ischemia/reperfu-sion(I/R)-and lipopolysaccharide(LPS)-induced microcirculatory disturbances.In recent years,numer-ous research papers on the improvement of microcirculatory function by natural products have been published in international journals.In 2008 and 2017,the first listed author of this review was invited to publish reviews in the journal of Pharmacology & Therapeutics on the improvement of microcirculatory disturbances and organ injury induced by I/R using Salvia miltiorrhiza ingredients and other natural com-ponents of compounded Chinese medicine,respectively.This review systematically summarizes the effects,targets of action,and mechanisms of natural products regarding improving I/R-and LPS-induced microcirculatory disturbances and tissue injury.Based on this summary,scientific proposals are suggested for the discovery of new drugs to improve microcirculatory disturbances in disease.
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    Artificial Bear Bile:A Novel Approach to Balancing Medical Requirements and Animal Welfare

    Yong LiYuhong HuangNan FengHeping Zhang...
    100-112页
    查看更多>>摘要：Bear bile has been a valuable and effective medicinal material in traditional Chinese medicine(TCM)for over 13 centuries.However,the current practice of obtaining it through bear farming is under scrutiny for its adverse impact on bear welfare.Here,we present a new approach for creating artificial bear bile(ABB)as a high-quality and sustainable alternative to natural bear bile.This study addresses the scientific chal-lenges of creating bear bile alternatives through interdisciplinary collaborations across various fields,including resources,chemistry,biology,medicine,pharmacology,and TCM.A comprehensive efficacy assessment system that bridges the gap between TCM and modern medical terminology has been estab-lished,allowing for the systematic screening of therapeutic constituents.Through the utilization of chemical synthesis and enzyme engineering technologies,our research has achieved the environmentally friendly,large-scale production of bear bile therapeutic compounds,as well as the optimization and recomposition of ABB formulations.The resulting ABB not only closely resembles natural bear bile in its composition but also offers advantages such as consistent product quality,availability of raw materi-als,and independence from threatened or wild resources.Comprehensive preclinical efficacy evaluations have demonstrated the equivalence of the therapeutic effects from ABB and those from commercially available drained bear bile(DBB).Furthermore,preclinical toxicological assessment and phase Ⅰ clinical trials show that the safety of ABB is on par with that of the currently used DBB.This innovative strategy can serve as a new research paradigm for developing alternatives for other endangered TCMs,thereby strengthening the integrity and sustainability of TCM.
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    Rational Engineering of Secondary Metabolic Pathways in a Heterologous Host to Enable the Biosynthesis of Hibarimicin Derivatives with Enhanced Anti-Melanomic Activity

    Xiangyang LiuFei-Peng ZhaoTian TianWei-Chen Wang...
    113-123页
    查看更多>>摘要：A 61-kb biosynthetic gene cluster(BGC),which is accountable for the biosynthesis of hibarimicin(HBM)B from Microbispora rosea subsp.hibaria TP-A0121,was heterologously expressed in Streptomyces coeli-color M1 154,which generated a trace of the target products but accumulated a large amount of shunt products.Based on rational analysis of the relevant secondary metabolism,directed engineering of the biosynthetic pathways resulted in the high production of HBM B,as well as new HBM derivates with improved antitumor activity.These results not only establish a biosynthetic system to effectively synthe-size HBMs-a class of the largest and most complex Type-Ⅱ polyketides,with a unique pseudo-dimeric structure-but also set the stage for further engineering and deep investigation of this complex biosyn-thetic pathway toward potent anticancer drugs.
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    The Triple Combination of Meropenem,Avibactam,and a Metallo-β-Lactamase Inhibitor Optimizes Antibacterial Coverage Against Different β-Lactamase Producers

    Zhuoren LingAlistair James Macdonald FarleyAditya LankapalliYanfang Zhang...
    124-132页
    查看更多>>摘要：This work explores the potential of a triple combination of meropenem(MEM),a novel metallo-β-lactamase(MBL)inhibitor(indole-2-carboxylate 58(InC58)),and a serine-β-lactamase(SBL)inhibitor(avibactam(AVI))for broad-spectrum activity against carbapenemase-producing bacteria.A diverse panel comprising MBL-and SBL-producing strains was used for susceptibility testing of the triple combi-nation using the agar dilution method.The frequency of resistance(FoR)to MEM combined with InC58 was investigated.Mutants were sequenced and tested for cross resistance,fitness,and the stability of the resistance phenotype.Compared with the double combinations of MEM plus an SBL or MBL inhibitor,the triple combination extended the spectrum of activity to most of the isolates bearing SBLs(oxacillinase-48(OXA-48)and Klebsiella pneumoniae carbapenemase-2(KPC-2))and MBLs(New Delhi metallo-β-lactamases(NDMs)),although it was not effective against Verona integron-encoded metallo-β-lactamase(VIM)-carrying Pseudomonas aeruginosa(P.aeruginosa)and OXA-23-carrying Acinetobacter baumannii(A.baumannii).The FoR to MEM plus InC58 ranged from 2.22×10-7 to 1.13×10-6.The resis-tance correlated with mutations to ompC and comR,affecting porin C and copper permeability,respec-tively.The mutants manifested a fitness cost,a decreased level of resistance during passage without antibiotic pressure,and cross resistance to another carbapenem(imipenem)and a β-lactamase inhibitor(taniborbactam).In conclusion,compared with the dual combinations,the triple combination of MEM with InC58 and AVI showed a much wider spectrum of activity against different carbapenemase-producing bacteria,revealing a new strategy to combat β-lactamase-mediated antimicrobial resistance.
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    Buxu Tongyu Granule Alleviates Myocardial Ischemia by Activating Vascular Smooth Muscle Cell Soluble Guanylate Cyclase to Inhibit Abnormal Vasomotion

    Shuang YangYixiu ZhaoXiaoling ChengTingting Zhan...
    133-143页
    查看更多>>摘要：Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ische-mia.However,the underlying mechanism of BXTY is still unclear.In this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-3',5'-cyclic gua-nosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the arteries.BXTY was given by gavage for ten consecutive days before establish-ing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin.The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma enzymes.In addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner.These effects were eliminated by pre-incubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT 5823.Moreover,BXTY increased the protein expression of sGC-β1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of BXTY.The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY.NS 2028,ODQ,or KT 5823 also reversed this effect of BXTY.In conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.
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    Highly Aromatic Norditerpenoid Heterodimers and Monomers from Trigonostemon fragilis

    Jun-Su ZhouLong ChengYuan GaoZhan-Peng Ge...
    144-154页
    查看更多>>摘要：Four new norditerpenoid heterodimers with different dimerization patterns-namely,trigofragiloids A-C(denoted as compounds 1-3)and(+)-and(-)-trigofragiloid D(compound 4)-and three new phenan-threnone norditerpenoids-namely,trigofragiloids E-G(compounds 5-7)-were isolated from Trigonostemon fragilis.Compounds 1 and 2 feature a novel heterodimeric carbon skeleton formed by the conjugation of a tetra-norditerpenoid and an ennea-norditerpenoid;they have been identified as class 2 atropisomers by means of quantum chemical calculations.Compound 3 is an unprecedented phenylpropanoid-norditerpenoid adduct with a new dimerization pattern.Compounds(+)-and(-)-4 are the first example of S-shaped 1,4-dioxane-fused norditerpenoid dimers.Inspired by the structure elu-cidation of compound 4,two co-occurring analogues,actephilol A and epiactephilol A,were structurally revised as a pair of geometrical isomers and were identified as two pairs of enantiomers,(+)-and(-)-8 and(+)-and(-)-9,respectively.Their structures were characterized using a combined method.Notably,compound 7 exhibits remarkable adenosine triphosphate-citrate lyase(ACLY)inhibition with a half-maximal inhibition concentration(IC50)value of(0.46±0.11)μmol·L-1,as active as the positive control BMS-303141,and a molecular docking study offers deep insight into the interaction between compound 7 and ACLY.
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    Dewatering of Scenedesmus obliquus Cultivation Substrate with Microfiltration:Potential and Challenges for Water Reuse and Effective Harvesting

    Marco MalagutiLorenzo CraveriFrancesco RicceriVincenzo Riggio...
    155-163页
    查看更多>>摘要：In the microalgae harvesting process,which includes a step for dewatering the algal suspension,directly reusing extracted water in situ would decrease the freshwater footprint of cultivation systems.Among various algae harvesting techniques,membrane-based filtration has shown numerous advantages.This study evaluated the reuse of permeate streams derived from Scenedesmus obliquus(S.obliquus)biomass filtration under bench-scale and pilot-scale conditions.In particular,this study identified a series of chal-lenges and mechanisms that influence the water reuse potential and the robustness of the membrane harvesting system.In a preliminary phase of this investigation,the health status of the initial biomass was found to have important implications for the harvesting performance and quality of the permeate stream to be reused;healthy biomass ensured better dewatering performance(i.e.,higher water fluxes)and higher quality of the permeate water streams.A series of bench-scale filtration experiments with dif-ferent combinations of cross-flow velocity and pressure values were performed to identify the operative conditions that would maximize water productivity.The selected conditions,2.4 m·s-1 and 1.4 bar(1 bar=105 Pa),respectively,were then applied to drive pilot-scale microfiltration tests to reuse the col-lected permeate as a new cultivation medium for S.obliquus growth in a pilot-scale photobioreactor.The investigation revealed key differences between the behavior of the membrane systems at the two scales(bench and pilot).It indicated the potential for beneficial reuse of the permeate stream as the pilot-scale experiments ensured high harvesting performance and growth rates of biomass in permeate water that were highly similar to those recorded in the ideal cultivation medium.Finally,different nutrient reinte-gration protocols were investigated,revealing that both macro-and micro-nutrient levels are critical for the success of the reuse approach.
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    A Deep-Learning and Transfer-Learning Hybrid Aerosol Retrieval Algorithm for FY4-AGRI:Development and Verification over Asia

    Disong FuHongrong ShiChristian A.GueymardDazhi Yang...
    164-174页
    查看更多>>摘要：The Advanced Geosynchronous Radiation Imager(AGRI)is a mission-critical instrument for the Fengyun series of satellites.AGRI acquires full-disk images every 15 min and views East Asia every 5 min through 14 spectral bands,enabling the detection of highly variable aerosol optical depth(AOD).Quantitative retrieval of AOD has hitherto been challenging,especially over land.In this study,an AOD retrieval algo-rithm is proposed that combines deep learning and transfer learning.The algorithm uses core concepts from both the Dark Target(DT)and Deep Blue(DB)algorithms to select features for the machine-learning(ML)algorithm,allowing for AOD retrieval at 550 nm over both dark and bright surfaces.The algorithm consists of two steps:① A baseline deep neural network(DNN)with skip connections is devel-oped using 10 min Advanced Himawari Imager(AHI)AODs as the target variable,and ② sunphotometer AODs from 89 ground-based stations are used to fine-tune the DNN parameters.Out-of-station validation shows that the retrieved AOD attains high accuracy,characterized by a coefficient of determination(R2)of 0.70,a mean bias error(MBE)of 0.03,and a percentage of data within the expected error(EE)of 70.7％.A sensitivity study reveals that the top-of-atmosphere reflectance at 650 and 470 nm,as well as the sur-face reflectance at 650 nm,are the two largest sources of uncertainty impacting the retrieval.In a case study of monitoring an extreme aerosol event,the AGRI AOD is found to be able to capture the detailed temporal evolution of the event.This work demonstrates the superiority of the transfer-learning tech-nique in satellite AOD retrievals and the applicability of the retrieved AGRI AOD in monitoring extreme pollution events.
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    Planetary Homeostasis of Reactive Nitrogen Through Anaerobic Ammonium Oxidation

    Guibing ZhuBangrui LanShuci LiuCameron M.Callbeck...
    175-183页
    查看更多>>摘要：The availability of nitrogen(N)is crucial for both the productivity of terrestrial and aquatic ecosystems globally.However,the overuse of artificial fertilizers and the energy required to fix nitrogen have pushed the global nitrogen cycle(N-cycle)past its safe operating limits,leading to severe nitrogen pollution and the production of significant amounts of greenhouse gas nitrous oxide(N2O).The anaerobic ammonium oxidation(anammox)mechanism can counteract the release of ammonium and N2O in many oxygen-limited situations,assisting in the restoration of the homeostasis of the Earth's N biogeochemistry.In this work,we looked into the characteristics of the anammox hotspots'distribution across various types of ecosystems worldwide.Anammox hotspots are present at diverse oxic-anoxic interfaces in terrestrial systems,and they are most prevalent at the oxic-anoxic transition zone in aquatic ecosystems.Based on the discovery of an anammox hotspot capable of oxidizing ammonium anoxically into N2 without N2O by-product,we then designed an innovative concept and technical routes of nature-based anammox hotspot geoengineering for climate change,biodiversity loss,and efficient utilization of water resources.After 15 years of actual use,anammox hotspot geoengineering has proven to be effective in ensuring clean drinking water,regulating the climate,fostering plant and animal diversity,and enhancing long-term environmental quality.The sustainable biogeoengineering of anammox could be a workable natural remedy to resolve the conflicts between environmental pollution and food security connected to N management.
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    Efficient Metal Recovery from Industrial Wastewater:Potential Oscillation and Turbulence Mode for Electrochemical System

    Li ChenGong ZhangHuijuan LiuShiyu Miao...
    184-193页
    查看更多>>摘要：Efficient metal recovery from industrial wastewater facilitates addressing of the environmental hazards and resource requirements of heavy metals.The conventional electrodeposition recovery method is ham-pered by the limitations of interfacial ion transport in charge-transfer reactions,creating challenges for simultaneous rapid and high-quality metal recovery.Therefore,we proposed integrating a transient elec-tric field(TE)and swirling flow(SF)to synchronously enhance bulk mass transfer and promote interfacial ion transport.We investigated the effects of the operation mode,transient frequency,and flow rate on metal recovery,enabling determination of the optimal operating conditions for rapid and efficient sequential recovery of Cu in TE&SF mode.These conditions included low and high electric levels of 0 and 4 V,a 50％duty cycle,1 kHz frequency,and 400 L·h-1 flow rate.The kinetic coefficients of TE&SF elec-trodeposition were 3.5-4.3 and 1.37-1.97 times that of single TE and SF electrodeposition,respectively.Simulating the deposition process under TE and SF conditions confirmed the efficient concurrence of interfacial ion transport and charge transfer under TE and SF synergy,which achieved rapid and high-quality metal recovery.Therefore,the combined deposition strategy is considered an effective technique for reducing metal pollution and promoting resource recycling.
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