Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system

The present letter to the editor is related to the study titled‘Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells’.Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system.

Cell-free biocatalysis coupled with photo-catalysis and electro-catalysis: Efficient CO_(2)-to-chemical conversion

The increasing atmospheric carbon dioxide (CO_(2)) concentration has exposed a series of crises in the earth's ecological environment.How to effectively fix and convert carbon dioxide into products with added value has attracted the attention of many researchers.Cell-free enzyme catalytic system coupled with electrical and light have been a promising attempt in the field of biological carbon fixation in recent years.In this review,the research progresses of photoenzyme catalysis,electroenzyme catalysis and photo-electroenzyme catalysis for converting carbon dioxide into chemical products in cell-free systems are systematically summarized.We focus on reviewing and comparing various coupling methods and principles of photoenzyme catalysis and electroenzyme catalysis in cell-free systems,especially the materials used in the construction of the coupling system,and analyze and point out the characteristics and possible problems of different coupling methods.Finally,we discuss the major challenges and prospects of coupling physical signals and cell-free enzymatic catalytic systems in the field of CO_(2) fixation,suggesting possible strategies to improve the carbon sequestration capacity of such systems.

In vitro cleavage of hepatitis B virus C mRNA by 10-23 DNA enzyme

BACKGROUND: 10-23 DNA enzyme is one kind of de-oxyribozymes for RNA cleavage. The inhibition effects of 10-23 DNA enzyme on the expression of the HBV C gene in HepG2. 2. 15 cells were demonstrated previously. The aim of this study was to further explore the cleavage activities of 10-23 DNA enzyme targeting at HBV C gene mRNA in vitro. METHODS: 10-23 DNA enzyme named Drz-HBV-C-9 specific to HBV C gene ORF A1816UG was designed and synthesized. HBV C gene mRNA was obtained by the in vitro transcription method. Cleavage activities of Drz-HBV-C-9 were observed in vitro. Values of kinetic parameters including Km,Kcat and Kcat/Km were calculated accordingly. RESULTS: Under the certain cleavage conditions, Drz-HBV-C-9 could efficiently cleave target mRNA at specific sites in vitro. Cleavage products of 109nt plus 191nt were obtained. The kinetic parameters, Km,Kcat and Kcat/ Km for Drz-HBV-C-9, were 1.4 ×10-9 mol, 1.6 min-1 and 1.1 × 109 mol-1 · min-1, respectively. CONCLUSIONS: 10-23 DNA enzyme targeting at HBV C gene mRNA possesses specific cleavage activities in vitro. This would be a potent antiviral strategy with respect to HBV gene therapy.

A new angiotensin-converting enzyme inhibitor from Peperomia pellucida(L.) Kunth

Objective:To isolate,identify,and evaluate a new angiotensin-converting enzyme inhibitor from Peperomia pellucida(L.)Kunth herbs.Methods:A dried sample of Peperomia pellucida herb was successively macerated with n-hexane and ethyl acetate.The ethyl acetate extract solution was evaporated to obtain the crude extract.Vacuum liquid column chromatography and thin layer chromatography were performed to obtain two pure compounds.Then,both compounds were elucidated and identified using the spectroscopic method.Angiotensin-converting enzyme inhibitory activity studies of both compounds were determined using angiotensin-converting enzyme kit WST-1 with spectrophotometer microplate reader 96-well at 450 nm wavelength.Results:Two bioactive compounds were successfully isolated from Peperomia pellucida herb,including a new compound of 2,3,5-trimethoxy-9-(12,14,15-trimethoxybenzyl)-1 H-indene and pellucidin A.Both compounds demonstrated angiotensin-converting enzyme inhibitory activity,with IC50 values of 72 μM(27.95 μg/mL)and 1 1μM(4.4 μg/mL),respectively.Conclusions:In the present study,two active angiotensin-converting enzyme inhibitors were successfully isolated and purified from Peperomia pellucida which is used as an antihypertensive in traditional medicine,and support its use as an angiotensin-converting enzyme-inhibiting drug.

Continuous-flow synthesis of polysubstituted γ-butyrolactones via enzymatic cascade catalysis

Polysubstituted chiral γ-butyrolactones are the core structural units of many natural products and high value-added flavors and fragrances used in the food and cosmetic industry. Current enzymatic cascade synthesis of these molecules faces the problems of low enzyme activity and phase separation in batch reaction, resulting in low productivity. Herein, we report a new continuous-flow process to synthesize the optically pure Nicotiana tabacum lactone(3S,4S)-4a and whisky lactone(3R,4S)-4b from α,β-unsaturatedγ-ketoesters. A new ene reductase(ER) from Swingsia samuiensi(Ss ER) and a carbonyl reductase(Ss CR)were engineered by directed evolution to improve their activity and thermostability. The continuous-flow preparative reactions were performed in two 3D microfluidic reactors, generating(3S,4S)-4a(99% ee and87% de) and(3R,4S)-4b(99% ee and 98% de) with space-time yields 3 and 7.4 times higher than those of the batch reactions. The significant enhancement in the productivity of enzyme cascade catalysis brought by cutting-edge continuous microfluidic technology will benefit the general multi-enzyme catalytic systems in the future.

DICP Symposium (I) on Catalysis: Future Directions of Catalysis Science and Technology October 16-18, 2003, Dalian, China

Introduction and Invitation DICP Symposium is a special series of interna-tional conference named after the Dalian Instituteof Chemical Physics (DICP). The DICP Symposiumwas founded with the purpose to promote the interna-tional communication and collaboration between theDICP and the international scientific community, to

Exosomes derived from microglia overexpressing miR-124-3p alleviate neuronal endoplasmic reticulum stress damage after repetitive mild traumatic brain injury

We previously reported that miR-124-3p is markedly upregulated in microglia-derived exosomes following repetitive mild traumatic brain injury.However,its impact on neuronal endoplasmic reticulum stress following repetitive mild traumatic brain injury remains unclear.In this study,we first used an HT22 scratch injury model to mimic traumatic brain injury,then co-cultured the HT22 cells with BV2 microglia expressing high levels of miR-124-3p.We found that exosomes containing high levels of miR-124-3p attenuated apoptosis and endoplasmic reticulum stress.Furthermore,luciferase reporter assay analysis confirmed that miR-124-3p bound specifically to the endoplasmic reticulum stress-related protein IRE1α,while an IRE1αfunctional salvage experiment confirmed that miR-124-3p targeted IRE1αand reduced its expression,thereby inhibiting endoplasmic reticulum stress in injured neurons.Finally,we delivered microglia-derived exosomes containing miR-124-3p intranasally to a mouse model of repetitive mild traumatic brain injury and found that endoplasmic reticulum stress and apoptosis levels in hippocampal neurons were significantly reduced.These findings suggest that,after repetitive mild traumatic brain injury,miR-124-3 can be transferred from microglia-derived exosomes to injured neurons,where it exerts a neuroprotective effect by inhibiting endoplasmic reticulum stress.Therefore,microglia-derived exosomes containing miR-124-3p may represent a novel therapeutic strategy for repetitive mild traumatic brain injury.

Electrochemical Enzyme Immunoassay of Tumor Marker CA15-3 with Capillary Electrophoresis

Tumor marker CA15-3 was determined by using capillary electrophoretic enzyme immunoassay with electrochemical detection (CE-EIA-ED). The method can be used to detect CA15-3 with a limit of 0.024 U/mL.

Effects of tachykinin neuropeptide NKB and A<i>β</i>(25-35) on antioxidant enzymes status in 17<i>β</i>estradiol treated aging female rats

Aging is the leading risk factor for neurodegenerative diseases and oxidative stress involved in the pathophysiology of these diseases. These changes increase during menopausal condition in females when the level of estradiol is decreased. The aim of the present study was to determine the effect of tachykinin neuropeptide, Neurokinin B (NKB) and Amyloid beta fragment Aβ (25 -?35) on 17β estradiol (E2) treated aging female rat synaptosomes of different age groups. Aging brain functions were assayed by measuring the activities of antioxidant enzymes—superoxide dismutase (SOD) and monoamine oxidase (MAO) with neuropeptides. An in-vitro incubation of Aβ (25 -?35) in E2 treated brain synaptosomes showed toxic effects on all the parameters. However, NKB and NKB combined with Aβ (25 35) showed stimulating effects in E2 treated rat brain synaptosomes. In the present study, an increase in activity of SOD and decrease in the level of MAO, in the presence of NKB and combined NKB and Aβ in E2 treated brain synaptosomes of aging rats. This study elucidates that treatment of NKB and Aβ with E2 incombination exerts more protective influence than their individual application, against excitotoxicity in age related changes.

Correlation of serum Aβ1-42 content with inflammatory factors and receptors as well as antioxidant enzymes in patients with Parkinson's Disease

Objective: To investigate the correlation of serum β-amyloid 1-42 (Aβ1-42) content with inflammatory factors and receptors as well as antioxidant enzymes in patients with Parkinson's Disease. Methods: A total of 48 patients with Parkinson's disease who were treated in this hospital between December 2014 and October 2017 were selected as Parkinson's disease group, and 50 healthy volunteers who received physical examination in this hospital during the same period were selected as normal control group. The differences in serum contents of Aβ1-42, inflammatory factors and receptors as well as antioxidant enzymes were compared between the two groups, and Pearson test was used to assess the correlation between serum Aβ1-42 content and illness in patients with Parkinson's disease. Results: Serum Aβ1-42 content of Parkinson's disease group was lower than that of normal control group;serum inflammatory factors and receptors IL-2, sIL-2R, IL-6 and sIL-6R contents were higher than those of normal control group;serum antioxidant enzymes SOD, GSH-Px, CAT and TPX contents were lower than those of control group. Pearson test showed that serum Aβ1-42 content of patients with Parkinson's disease was directly correlated with the contents of inflammatory factors and receptors as well as antioxidant enzymes. Conclusions: Serum Aβ1-42 content decreases in patient with Parkinson's disease, and the specific content is directly correlated with the condition of Parkinson's disease, and can be used as an important auxiliary indicator for diagnosis and judgment of Parkinson's disease.

(3R,4R)-N,4-二甲基-1-(苯基甲基)-3-哌啶胺盐酸盐的制备

以a-乙酰-γ-丁内酯为起始原料与碘甲烷反应合成化合物II;化合物II与氢溴酸反应水解溴代化合物III;化合物III再与溴素反应得到二溴代产物IV;化合物IV与苄胺关环得到化合物V;化合物V在转氨酶作用下,甲胺作为氨源,得到ee值99.5%以上的化合物I。考察催化剂、酶催化剂、物质的量比、反应温度对反应的影响,考察氢溴酸、溴素的回收利用情况。结果表明:化合物II的最佳工艺条件为碳酸钠为催化剂,碘甲烷为甲基化试剂,化合物III的最佳工艺条件氢溴酸既做反应试剂同时也作为溶剂;化合物IV最佳工艺条件酸性条件下溴素溴代得到二溴产物;化合物V的最佳工艺条件是与苄胺直接反应得到产物;化合物I的最佳工艺条件是常温下酶转化得到手性产品。

Role of Microstructure and Spectrum Features on the Catalysis Effect of Ce1-x(Nd0.5Eu0.5)xO2-δSolid Solutions

Nanosized Ce^1-x）（Nd^0.5）Eu^0.5））xO^2-δ） solid solutions（x = 0.00-0.20） were synthesized by means of hydrothermal method.Then the solid solutions were ball milled with Mg2Ni and Ni powders for 20 h to get the Mg2Ni–Ni–5 mol% Ce^1-x）（Nd^0.5）Eu^0.5））xO^2-δ） composites.The structures and spectrum characteristics of the Ce^1-x）（Nd^0.5）Eu^0.5））xO^2-δ） solid solutions catalysts were analyzed systemically.XRD results showed that the doped samples exhibited single phase of CeO2 fluorite structure.The cell parameters and cell volumes were increased with increasing the doped content.Raman spectrum revealed that the peak position of F^2g mode shift to higher wavenumbers and the peak corresponding to oxygen vacancies were observed distinctly for the doped samples.UV-Vis technique indicated that the absorption peaks of Eu^3＋ and Nd^3＋ ions appeared; the bandgap energy was decreased linearly.The electrochemical and kinetic properties of the Mg2Ni–Ni–5 mol% Ce1-x（Nd0.5Eu0.5xO2-δ composites were measured.The maximum discharge capacity was increased from 722.3 mA h/g for x = 0.00 to 819.7 mA h/g for x = 0.16,and the cycle stability S20 increased from 25.0%（x = 0.00） to 42.2%（x = 0.20）.The kinetic measurement proved that the catalytic activity of composite surfaces and the hydrogen diffusion rate were improved for the composites with doped catalysts,especially for the composites with x = 0.16 and x = 0.20.The catalysis mechanism was analyzed from the point of microstructure and spectrum features of the Ce1-x（Nd0.5Eu0.5）xO2-δ solid solutions.

电-酶偶联催化转化CO_(2) 的研究进展

实现对CO_(2)的高效资源化利用不仅可保障经济高质量发展,而且能助力实现“双碳”目标。生物催化转化CO_(2)是利用活细胞或酶作为催化剂,以CO_(2)为原料合成复杂有机分子的过程。生物酶催化剂具有选择性高、操作条件绿色温和以及易实现碳碳偶联等优点,有助于将CO_(2)转化为高附加值产品。但由于CO_(2)的高化学惰性,使得CO_(2)的活化和C O断键成为一个难题。受天然光合作用启发,研究人员提出了电酶偶联催化转化CO_(2)策略,即利用电化学体系,结合非固定化或固定化酶,利用电能驱动酶催化C O断键,并将CO_(2)转化为高附加值化合物。本文从NAD(P)H非依赖型和NAD(P)H依赖型氧化还原酶与电极之间的电子传递机制出发,重点阐述了酶与电极间的相互作用、电极的修饰方法和新型电酶耦合体系的研究进展,概述了电酶偶联用于CO_(2)催化转化所面临的主要挑战和未来发展前景。

Dendrimer-induced synthesis of porous organosilica capsules for enzyme encapsulation

Organic matter-induced mineralization is a green and versatile method for synthesizing hybrid nanostructured materials,where the material properties are mainly influenced by the species of natural biomolecules,linear synthetic polymer,or small molecules,limiting their diversity.Herein,we adopted dendrimer poly(amidoamine)(PAMAM)as the inducer to synthesize organosilica-PAMAM network(OSPN)capsules for mannose isomerase(MIase)encapsulation based on a hard-templating method.The structure of OSPN capsules can be precisely regulated by adjusting the molecular weight and concentration of PAMAM,thereby demonstrating a substantial impact on the kinetic behavior of the MIase@OSPN system.The MIase@OSPN system was used for catalytic production of mannose from Dfructose.A mannose yield of 22.24% was obtained,which is higher than that of MIase in organosilica network capsules and similar to that of the free enzyme.The overall catalytic efficiency(kcat/Km)of the MIase@OSPN system for the substrate D-fructose was up to 0.556 s^(-1)·mmol^(-1)·L.Meanwhile,the MIase@OSPN system showed excellent stability and recyclability,maintaining more than 50% of the yield even after 12 cycles.

D-band center coordination modulated enzyme-like activity in Fe-Cu dual-metal single-atom nanozymes

After explorations in a diversity of single-atom nanozymes(SAzymes),developing dual-centered SAzymes becomes a promising approach for superior catalytic performance.But confusing mechanisms including atomic coordination,spatial configuration,and metal–metal atom interaction hinder the development and design of SAzymes.Herein,a dual-centered Fe-Cu-N_(x)SAzyme exhibits excellent peroxidase(POD)-and catalase(CAT)-like activities with d-band center(ε_(d))coordination of Fe and Cu in multiple reaction stages,which plays a critical role in the adsorption of H_(2)O_(2)molecule and H_(2)O and O_(2)release.Therefore,the dband center coordination,which can be represented byε_(d)(Fe)–ε_(d)(Cu)shifts,leads to the competition between one-side and bilateral adsorption,which determines the favorable reaction path with lower energy barriers.Based on experimental statistics,simulated formation energies,and reaction barriers,3 configurations,Fe-Cu-N6-I,Fe-Cu-N_(8)-II,and Fe-Cu-N_(8)-III,are modeled and validated.Impressively,configuration-dependent catalytic selectivity and the competition between one-side and bilateral adsorption can be unveiled by d-band center coordination paradigm analysis.Theoretical simulations suggest that the unsymmetrical charge distribution over the three Fe-Cu configurations could tune the adsorption strength compared with the counterparts FeN_(4)and CuN_(4).The present work provides a potential route for optimizing enzyme-like catalysis by designing the dual-or even triple-metal SAzymes,which demonstrates the large space to modulate the metal atomic configuration and interaction.

Pd/Zn Dual Catalysis for Site-,Enantio-,and Diastereo-Divergent 2-(Alkoxycarbonyl)allylation ofα-Hydroxyketones with Morita–Baylis–Hillman Adducts

A synergistic Pd/Zn dual chiral catalyst system has been developed for the stereodivergent transformation of Morita–Baylis–Hillman(MBH)carbonates and unprotectedα-hydroxyketones to afford the corresponding allylation products(>50 examples).These products bearing vicinal stereocenters were obtained in high yields with excellent regio-/diastereo-/enantioselectivities.On cyclization in an acidic medium,the allylation products could transform to the corresponding acyl-functionalizedβ,γ-disubstitutedα-methylene-γ-butyrolactones(AMGBLs).All four stereoisomers of AMGBL were readily accessed using the same starting materials with full control of the stereochemistry of the contiguous stereogenic centers,simply by switching the chiral ligand combination for the Pd/Zn system.A nucleophilic site-divergent reactivity was observed for the allylation of primary and secondaryα-hydroxyketones,suggesting that distinct enolate intermediates might have prevailed in these reactions.

酶-光偶联催化系统中分子-电子-质子传递过程与机制

酶-光偶联催化系统(EPCS)集成了半导体的光吸收能力和酶的高活性/特异性,可模拟自然界光合作用实现太阳能驱动的有用化学品合成.作为EPCS中的“能量货币”,辅因子(如NAD(P)+和NAD(P)H)参与了约80%的酶促氧化还原反应,且在酶-光间充当物质/能量交换的枢纽.然而,EPCS涉及光催化和酶催化反应,涉及分子、电子和质子传递过程,属于典型的复杂多相反应,导致其光-化学转化效率与理论值差距较大.本文从微观尺度对EPCS中分子-电子-质子传递过程进行了理解和剖析,系统介绍了自然界光合作用和EPCS中的“新三传”现象.此外,与传统化工领域通过强化宏观尺度上“三传”(即质量传递、热量传递和动量传递)提升单元操作过程效率的方法类似,本文总结并提出了通过协调优化“新三传”(即分子传递、电子传递和质子传递)来强化EPCS中物质-能量耦合关系,进而提升光-化学转化效率的新策略.其中,分子传递主要包括电子供体分子从反应液向催化剂传递以及辅因子分子在光催化模块和酶催化模块间穿梭;电子传递主要包括光生电子从其生成位点到光催化剂表面进而到电子媒介的传递;质子传递主要包括质子从溶液或催化剂表面向电子媒介的传递.期望通过“新三传”强化EPCS效率的理念,打破自然界光合作用的局限,实现温和条件下多种功能分子的高效合成,为人工光合与绿色生物制造领域提供新思路.

Effect of Cl￣ on Behavior of Fertilizer Nitrogen, Nnmberof Microorganisms and Enzyme Activities in Soils

Pot experiments were conducted to study the effect of Cl￣- on transformation of fertilizer N, number ofmicroorganisms and enzyme activities in soils. It is indicated that Cl￣- did not show significant influenceon total number of bacteria, actinomyces and fungi, but significantly reduced the number of nitrosobacteria,which led to decrease of NO content in the soil. Application of Cl￣- to soil could significantly enhance theactivities of phosphatase and urease in the coastal saline soil and orthic aquisols. In hilly red soil, however,the application of Cl￣- at the rate of 500-1000 mg Cl￣- kg￣(-1) soil significantly decreased the activity of thetwo enzymes mentioned above.

Serum levels of angiotensin converting enzyme as a biomarker of liver fibrosis

The renin angiotensin system(RAS) is classically conceived as a circulating hormonal system involved in blood pressure control and hydroelectrolyte balance. The discovery that RAS components are locally expressed in a wide range of organs and tissues,including the liver,pointed to a role for this system in the pathogenesis of several conditions including hepatic fibrosis and cirrhosis. It has been widely reported that the classical RAS axis composed by the angiotensin converting enzyme(ACE)-angiotensin(Ang) Ⅱ-Ang type 1(AT1) receptor mediates pro-inflammatory,pro-thrombotic,and pro-fibrotic processes. On the other hand,the alternative axis comprising ACE2-Ang-(1-7)-Mas receptor seems to play a protective role by frequently opposing Ang Ⅱ action. Chronic hepatitis B(CHB) is one of the leading causes of liver fibrosis,accounting for the death of nearly one million people worldwide. Liver fibrosis is a key factor to determine therapeutic interventions for patients with CHB. However,the establishment of non-invasive and accurate methods to detect reversible stages of liver fibrosis is still a challenge. In an elegant study published in the 36 th issue of the World Journal of Gastroenterology,Noguchi et al showed the predictive value of serum ACE levels in detecting not only advanced stages of liver fibrosis but also initial and intermediate fibrotic stages. The serum levels of ACE might represent an accurate,non-invasive,widely available,and easy method to evaluate fibrosis related to CHB. Moreover,therapies involving the inhibition of the classical RAS axis components might be promising in the control of CHB-related liver fibrosis.

Functioned Calix[4]arenes as Artificial Enzymes Catalyze Aldol Condensation

Aldolase models derived from calix[4]arene were designed and synthesized. The aldol condensation of p-nitrobenzaldehyde with acetone was catalyzed by the synthetic enzymes proceeded under mild conditions to offer chiefly aldol-type product in good yield.