Pathogenic contribution of cholesteryl ester accumulation in the brain to neurodegenerative disorders

Cholesteryl esters(CEs) have been increasingly implicated in neurodegenerative disorders such as Alzheimer's disease(AD).Alois Alzheimer noted three prominent neuropathologic features in his original analysis of the AD brain:senile plaques,neurofibrillary tangles,and lipid granule accumulation.Senile plaques,which are aggregates of amyloid-beta(Aβ),and neurofibrillary tangles,which are aggregates of phosphorylated tau,have been regarded as more consistent characteristics of the AD brain compared with lipid granule accumulation and thus have been studied more intensively(Foley,2010).

Exploring Ester Prodrugs: A Comprehensive Review of Approaches, Applications, and Methods

The review provides an overview of the approaches, applications, and methods for ester prodrugs. Ester prodrugs are pharmacologically inactive compounds in their original form but become active drugs on biotransformation within the body, which offers advantages concerning the solubility, stability, and targeted delivery of the active drug. Several approaches of ester prodrugs have been reviewed in this review, including simple ester prodrugs, amino acid ester prodrugs, sugar ester prodrugs, lipid ester prodrugs, and polymeric ester prodrugs. This review incorporates in vitro and in vivo methods as well as the characterization of physical and chemical properties for ester prodrugs, cell culture systems, enzymatic assays, and animal models—all of these having a very important bearing on the evaluation of stability, bioavailability, and efficacy for ester prodrugs. While the benefits of using ester prodrugs are significant, there are also disadvantages like instability, poor or variable enzymatic hydrolysis, and toxicity from released promoieties or by-products. This review discusses solutions to the various limitations that include enhancing stability with ionizable promoieties and using physiologically-based pharmacokinetic modeling. The review also highlights the application of ester prodrugs in neurological disorders, such as Parkinson’s disease, and the ongoing efforts to address the critical limitations in treatment efficacy. Future prodrug strategies are poised to advance significantly by harnessing diverse transport mechanisms across the blood-brain barrier and integrating nanotechnology.

Structural characteristics of phenylboronic acid-modified astaxanthin ester and its effect on DSS-induced ulcerative colitis by blocking reactive oxygen species and maintaining intestinal homeostasis

A novel and reactive oxygen species(ROS)responsive astaxanthin phenylboronic acid derivative(AstaDPBA)was constructed by grafting phenylboronic acid(PBA)onto astaxanthin succinate diester(AstaD),and its chemical structure and physicochemical property were identified.AstaD-PBA could effectively improve the ROS quenching ability in the lipopolysaccharide(LPS)-induced RAW264.7 cell inflammation model.Then,the bioactivity of AstaD-PBA was studied by 4 zebrafish ROS-responsive infl ammatory models induced by LPS,copper(Cu^(2+)),high-fat diet,and dextran sodium sulfate(DSS).The results suggest that AstaD-PBA might have high biosafety and the best effect on ulcerative colitis(UC)induced by DSS.Furtherly,AstaDPBA significantly alleviated and treated weight loss and colonic shrinkage,inhibited infl ammatory cytokines,and maintained microbiota homeostasis to improve UC in C57BL/6J mice.Alistipes and Oscillibacter were expected to be considered UC marker fl ora according to the Metastats analysis and Pearson correlation Mantel test(P<0.01)of 16S rRNA gene sequencing data.In conclusion,AstaD-PBA has been promised to be a functional compound to improve UC and maintain intestinal microbiota homeostasis.

Carboxyl Ester Lipase Protects Against Metabolic Dysfunction-Associated Steatohepatitis by Binding to Fatty Acid Synthase

Carboxyl ester lipase(CEL),a pivotal enzyme involved in lipid metabolism,is recurrently mutated in obese mice.Here,we aimed to elucidate the functional significance,molecular mechanism,and therapeutic potential of CEL in metabolic dysfunction-associated steatohepatitis(MASH).Hepatocyte-specific carboxyl ester lipase gene(Cel)knockout(Cel^(DHEP))and wildtype(WT)littermates were fed with cholinedeficient high-fat diet(CD-HFD)for 16 weeks,or methionine-and choline-deficient diet(MCD)for three weeks to induce MASH.Liquid chromatography–mass spectrometry and co-immunoprecipitation were employed to identify the downstream targets of CEL.CD-HFD/MCD-fed WT mice received intravenous injections of CEL-adeno-associated viral,serotype 8(AAV8)to induce specific overexpression of CEL in the liver.We observed a decrease in CEL protein levels in MASH induced by CD-HFD or MCD in mice.Cel^(DHEP) mice fed with CD-HFD or MCD exhibited pronounced hepatic steatosis,inflammation,lipid peroxidation,and liver injury compared to WT littermates,accompanied by increased hepatic nuclear factor kappa-light-chain-enhancer of activated B cell(NF-jB)activation.Consistently,Cel knockdown in mouse primary hepatocytes and AML12 cells aggravated lipid accumulation and inflammation,whereas CEL overexpression exerted the opposite effect.Mechanistically,CEL directly bound to fatty acid synthase(FASN),resulting in reduced FASN SUMOylation,which in turn promoted FASN degradation through the proteasome pathway.Furthermore,inhibition of FASN ameliorated hepatocyte lipid accumulation and inflammation induced by Cel knockdown in vivo and in vitro.Hepatocyte-specific CEL overexpression using AAV8-Cel significantly mitigated steatohepatitis in mice fed with CD-HFD or MCD.CEL protects against steatohepatitis development by directly interacting with FASN and suppressing its expression for de novo lipogenesis.CEL overexpression confers a therapeutic benefit in steatohepatitis.

Research progress on classification,source,application of phytosterol esters,and their thermal oxidation stability

Phytosterol esters can effectively decrease serum cholesterol concentration in the human body and prevent cardio-cerebrovascular diseases.It was found that phytosterol esters exhibited better solubility and bioavailability than free phytosterols.In recent years,phytosterol esters have attracted increasing attention.However,during food processing,phytosterol esters are susceptible to degradation at high temperatures,resulting in certain losses and formation of potentially harmful substances for humans.This paper reviews the relevant literatures and updates on the thermal oxidation stability of phytosterol esters in recent years from the following aspects:(i)Sources,physiological activities,and applications of phytosterol esters;(ii)Oxidation mechanism of phytosterol esters;(iii)Effects of phytosterols species,the volume of addition,food matrix,heating temperature and time,and antioxidants on the thermal loss and oxidation stability of phytosterol esters.The research progress on the safety of phytosterol esters is also discussed in detail.Additionally,the prospects for future research are highlighted.

Non-flammable long chain phosphate ester based electrolyte via competitive solventized structures for high-performance lithium metal batteries

Safety remains a persistent challenge for high-energy-density lithium metal batteries(LMBs).The development of safe and non-flammable electrolytes is especially important in harsh conditions such as high temperatures.Herein,a flame-retardant,low-cost and thermally stable long chain phosphate ester based(tributyl phosphate,TBP)electrolyte is reported,which can effectively enhance the cycling stability of highly loaded high-nickel LMBs with high safety through co-solvation strategy.The interfacial compatibility between TBP and electrode is effectively improved using a short-chain ether(glycol dimethyl ether,DME),and a specially competitive solvation structure is further constructed using lithium borate difluorooxalate(LiDFOB)to form the stable and inorganic-rich electrode interphases.Benefiting from the presence of the cathode electrolyte interphase(CEI)and solid electrolyte interphase(SEI)enriched with LiF and Li_(x)PO_(y)F_(z),the electrolyte demonstrates excellent cycling stability assembled using a 50μm lithium foil anode in combination with a high loading NMC811(15.4 mg cm^(-2))cathode,with 88%capacity retention after 120 cycles.Furthermore,the electrolyte exhibits excellent high-temperature characteristics when used in a 1-Ah pouch cell(N/P=0.26),and higher thermal runaway temperature(238℃)in the ARC(accelerating rate calorimeter)demonstrating high safety.This novel electrolyte adopts long-chain phosphate as the main solvent for the first time,and would provide a new idea for the development of extremely high safety and high-temperature electrolytes.

Study on the regulatory effect of liver X receptor in HEK293 cells by six main diterpene esters in Semen Euphorbiae

Background:To study the effects of the main diterpene esters in Euphorbia factor L_(1),L_(2),L_(3),L_(7a),L_(7b)and L_(8)on the transcriptional activity and protein expression of liver X receptor(LXR).Methods:The effect of the main diterpene ester components in Semen Euphorbiae on the viability of HEK293 cells were studied by MTT assay.The LXR-Luc plasmid vector was transfected into HEK293 cells and treated with Euphorbia factor L_(1),L_(2),L_(3),L_(7a),L_(7b)and L_(8)for 24 h.The effect of the main diterpene ester components of Semen Euphorbiae on LXR-Luc luciferase activity was investigated by dual luciferase reporter gene system,and the expression of LXRαprotein was detected by Western Blot.Results:Euphorbia factor L_(1),L_(2),L_(3),L_(7a),L_(7b)and L_(8)could significantly reduce the relative luciferase activity(RLU)of LXRα,and the expression level of LXRαprotein was significantly down-regulated.Conclusion:Euphorbia factor L_(1),L_(2),L_(3),L_(7a),L_(7b)and L_(8)can inhibit the expression of LXR protein level,which may be achieved by inhibiting the transcriptional activity of LXR.

Recent Advances of Sensitive Electrochemical Sensing Platforms for Rapid Detection of Phthalate Acid Esters

As a kind of plasticizer,phthalic acid esters(PAEs)are often added to plastics to enhance elasticity,transparency,durability and prolong service life.However,it does not chemically bind to plastics and is easy to migrate to the environment.It is difficult to degrade in the environment,and it is also enriched in the human body through the food chain and respiration,which will lead to obvious adverse reactions such as decreased learning and memory function and neurobehavioral disorders.Due to the toxicity,universality and low concentration limitations of PAEs in the environment and food,it is essential to achieve rapid and sensitive detection of PAEs in soil,atmosphere,water and food.Electrochemical(EC)sensors have the advantages of simplicity,fast,low cost,portability,easy operation,high specificity and high sensitivity,so they are applied for the detection of PAEs.Although there are a large number of studies on the detection of PAEs by EC sensors,there is no review on this aspect.In this review,we introduce the detection of PAEs from classical EC sensors,electrochemiluminescence(ECL)sensors and photo-electrochemical(PEC)sensors in the past five years.This review is beneficial to understanding the construction of EC sensors and the detection mechanism of PAEs.We also propose that the development of rapid,accurate and real-time detection methods of PAEs is key to assessing risk and preventing related diseases.

Pollution characteristics and risk assessment of organophosphate esters in aquaculture farms and natural water bodies adjacent to the Huanghe River delta

To date,little attention has been paid to the effects of organophosphate esters(OPEs)pollution on aquacultural environment and aquatic product safety.Huanghe(Yellow)River delta area is one of the largest aquaculture centers in China,where ecological security protection is crucial in the national strategy of China.To explore the pollution characteristics,bioaccumulation,and health risks of OPEs in aquaculture farms in the Huanghe River delta and natural water bodies in the adjacent seas,five species of organisms from different farm types nearby the Huanghe River delta,and the corresponding culture water and sediments were sampled in this study.The total concentrations of Σ_(13)OPEs in water,sediments,and organisms were 51.53-272.18 ng/L,52.63-63.17 ng/g dry weight(dw),and 46.82-108.90 ng/g dw,respectively.Among the five types of culture ponds,the water samples from the swimming crab and hairy crab culture ponds exhibited higher OPEs,the concentration of OPEs in the sediments from the few ponds was relatively balanced,and the OPEs in the organism from the holothurian ponds was higher.Tris(1,3-dichloro-2-isopropyl pho sphate)(TDCP)was the main contaminant in water samples and tripropyl phosphate(TPrP)in sediments and organisms.However,trisphenyl phosphate(TPhP)showed the strongest bioaccumulation ability,followed by 2-ethylhexyl diphenyl phosphate(EHDPP)and TPrP.The bioaccumulation capacities of the five species were as follows:prawn>holothurian>hairy crab>swimming crab>carp.These five types of organisms,as main seafood in human consumption,were at low risk of negative impacts of pollution.However,the risk from the mixture of organophosphate flame retardants(OPFRs)still requires more attention due to the increasing consumption and production in the world.

Adsorption of Phthalic Acid Esters by Humic Acid and Its Research Progress

Humic acid is rich in highly electronegative oxygen-containing organic functional groups,so it has high reactivity and can adsorb phthalic acid ester(PAEs)in the environment to reduce the risk of environmental pollution from PAEs.In this paper,the extraction,characterization and adsorption models of humic acid were reviewed,and the research status of adsorption of PAEs by humic acid was further summarized.Based on these,the feasibility and observable application prospect of humic acid as a cheap adsorbent were analyzed.

Breakdown Voltage Prediction by Utilizing the Behavior of Natural Ester for Transformer Applications

This research investigates the dielectric performance of Natural Ester(NE)using the Partial Differential Equation(PDE)tool and analyzes dielectric performance using fuzzy logic.NE nowadays is found to replace Mineral Oil(MO)due to its extensive dielectric properties.Here,the heat-tolerant Natural Esters Olive oil(NE1),Sunflower oil(NE2),and Ricebran oil(NE3)are subjected to High Voltage AC(HVAC)under different electrodes configurations.The break-down voltage and leakage current of NE1,NE2,and NE3 under Point-Point(P-P),Sphere-Sphere(S-S),Plane-Plane(PL-PL),and Rod-Rod(R-R)are measured,and survival probability is presented.The electricfield distribution is analyzed using the Partial Differential Equation(PDE)tool.NE shows better HVAC with stand capacity under all the electrodes configuration,especially in the S-S shape geometry.The exponential function is developed for the oils under different elec-trode geometry;NE shows a higher survival probability.Likewise,the most influ-ential dielectric properties such as breakdown voltage,kinematic viscosity,and water content are used to develop a Mamdani-based control system model that combines two variables to produce the surface model.The surface model indi-cates that the NE subjected for investigation is less susceptible to moisture effect and higher kinematic viscosity.Based on the surface models of PDE and fuzzy,it is concluded that NE possesses a high survival rate since its breakdown voltage does not react to changes in water content.Hence the application of NE in the transformer application is highly safe and possesses extended life.

邻苯二甲酸酯降解功能内生菌群的筛选及定殖效能

为降低邻苯二甲酸酯(PAEs)污染作物对人体健康的威胁,从PAEs污染蔬菜中富集驯化具有PAEs降解高效性和广谱性的功能内生菌群,解析菌群群落组成并优化其降解条件,借助水培体系研究了功能内生菌群在作物体内的定殖效能.高通量测序结果表明,从门的分类水平看,菌群主要由变形菌门(Proteobacteria,76.57%)、拟杆菌门(Bacteroidetes,21.04%)和放线菌门(Actinobacteria,2.37%)组成;从属的分类水平看,菌群主要由鞘氨醇杆菌属(Sphingobacterium,33.03%)、代尔夫特菌属(Delftia,40.61%)、假单胞菌属(Pseudomonas,11.70%)、无色杆菌属(Achromobacter,3.04%)和根瘤菌属(Rhizobium,6.90%)组成.在无机盐纯培养体系中,该菌群在7d内对5mg/L的邻苯二甲酸二甲酯(DMP)、邻苯二甲酸二乙酯(DEP)、邻苯二甲酸二丁酯(DBP)和邻苯二甲酸丁基苄基酯(BBP)降解率分别为97.08%、94.47%、98.02%和44.82%.单因素试验结果表明,菌群降解PAEs的最佳条件为:pH值7、25℃、盐度1%、底物浓度5mg/L.水稻水培试验表明,菌群可以定殖到水稻体内并有效促进PAEs的去除,与对照组相比,处理15d后水稻体内DMP、DEP、DBP和∑PAEs含量分别降低了41.09%、45.33%、63.06%和32.3%.菌群的定殖还能够提高水稻根长、株高和生物量,促进水稻的生长.该菌群在降低作物PAEs积累、保障PAEs污染地区农产品质量安全方面具有良好的应用前景,能有效降低作物PAEs污染对人体健康的威胁.

日粮添加三丁酸甘油酯对肉鸡生长性能、养分消化率和血清生化指标的影响

文章旨在研究日粮中添加不同水平三丁酸甘油酯对肉鸡综合性能的影响。本试验将160只体重相近、健康无病的1日龄肉鸡随机分为4组,每组4个重复。对照组肉鸡饲喂基础日粮。试验I、II和III组分别在基础日粮中添加1000、1500、2000mg/kg三丁酸甘油酯。预饲期7d,正试期42d。结果表明,与对照组相比,试验组肉鸡的42日龄体重和平均日增重显著增加(P <0.05),试验II、III组肉鸡的料重比显著降低(P <0.05),但平均日采食量无显著差异(P> 0.05);试验组干物质、粗蛋白质、粗纤维及能量的表观消化率均显著增加(P <0.05);试验组肉鸡血清中总蛋白质含量和高密度脂蛋白含量显著增加(P <0.05),总胆固醇和甘油三酯含量显著降低(P <0.05),各试验组肉鸡血清中低密度脂蛋白含量较对照组无显著差异(P> 0.05)。总的来讲,日粮中添加三丁酸甘油酯能有效改善肉鸡生长性能,提升养分表观消化率,改善血清生化指标,综合考虑,肉鸡日粮中三丁酸甘油酯的最适添加量为1500mg/kg。

白肋烟中糖酯类化合物的分离与鉴定

烟草中糖酯类化合物是重要的致香前体物,对烟叶的品质具有重要影响。但目前还未见关于白肋烟烟叶中糖酯类化合物的分离分析研究。本实验利用高分辨液相色谱-串联质谱(LC-MSn)技术,从白肋烟叶提取物中共分离鉴定出4类蔗糖酯和2类葡萄糖酯,每类均包含多种同系物。其中,4种蔗糖酯为首次发现,8种葡萄糖酯的结构鉴定在栽培烟草中为首次报道。本研究丰富了烟草中糖酯类化合物的种类,对烟草中不同类型蔗糖酯和葡萄糖酯的分析鉴定和代谢研究具有参考意义。

独一味化学成分和药理作用的研究进展及其质量标志物预测分析

独一味Lamiophlomis rotata(Benth.)Kudo为藏族习用药材,药用部位为干燥地上部分。现代研究表明,独一味主要含有环烯醚萜苷类、苯乙醇苷类、黄酮类、挥发油类等化学成分,具有镇痛、止血、抗菌、抗炎、免疫调节、抗肿瘤等药理作用。在对独一味化学成分及药理作用总结的基础上,结合其质量研究现状,从药性、功效、成分可测性、药动学等方面对其质量标志物(Q-marker)进行预测,槲皮素、芹菜素、山栀苷甲酯、8-O-乙酰山栀苷甲酯、胡麻属苷、连翘酯苷B、木犀草苷、马钱苷等成分可作为独一味的主要Q-marker,以期为独一味产品开发研究及质量标准的合理建立提供参考。

白酒酿造微生物酯化酶的研究进展

酯化酶是一类具有催化酯类物质合成活性的酶类。广义上的酯化酶被广泛应用于食品,化工,医药、军工及环保等领域中。白酒酿造微生物酯酶在白酒发酵生香过程中具有重要作用,其代谢产生的乙酸乙酯、乳酸乙酯、丁酸乙酯和己酸乙酯等酯类物质是中国白酒最为重要的风味物质。因此,深入研究中国白酒酿酒微生物酯化酶,对提高白酒优质品率、提升酿酒原料利用率具有重要意义。从微生物酯化酶的来源、特性、分子进化以及在白酒酿造中的应用进行了综述,旨在为中国白酒微生物资源的深入研究和发掘提供一定的思路。

PEG/PPG共聚醚酯的制备及其润滑性能

聚醚类基础油一般通过环氧化物的开环聚合反应制备,但由于环氧化物易燃易挥发的特性,对安全生产要求较为严苛。为解决上述问题,以氯化亚锡为催化剂,聚乙二醇、聚丙二醇和琥珀酸共缩聚后脱酸制备共聚醚酯,并通过红外光谱、核磁共振和凝胶渗透色谱对其结构和相对分子质量进行表征。利用运动黏度测试仪、四球摩擦试验机和3D白光干涉仪对共聚醚酯的黏温特性和润滑性能进行考察。结果表明:所制备的聚醚酯在40℃下运动黏度约为170 mm^(2)/s,黏度指数可达220左右;在392 N、30 min、1450 r/min条件下,四球试验钢球磨斑直径为0.55 mm,平均摩擦因数为0.057,说明聚醚酯的减摩效果显著优于商用基础油。

农田土壤中邻苯二甲酸酯降解功能细菌及其应用

本文综述了我国农田土壤PAEs污染特征,重点概述了PAEs降解功能菌株筛选、菌群构建及其应用策略.详细分析了细菌介导的PAEs降解的水解和开环裂解两个途径及参与其中的关键功能基因和酶,讨论了PAEs降解功能细菌在污染土壤中的应用、影响因素及可能存在的问题,并对该技术在消减农田土壤PAEs污染中的应用进行展望,以期为我国PAEs污染农田土壤功能细菌修复及农业生产安全提供理论和技术参考.

吗替麦考酚酯联合泼尼松对IgA肾病患者尿β2-MG、U-mAlb及α1-MG水平的影响

目的 观察吗替麦考酚酯联合泼尼松治疗免疫球蛋白A(IgA)肾病对患者尿β2微球蛋白(β2-MG)、尿微量白蛋白(U-mAlb)及尿液α1微球蛋白(α1-MG)水平的影响。方法 选取秦皇岛市第一医院肾内科2019年1月至2022年1月收治的89例IgA肾病患者为研究对象,采用信封随机法分为泼尼松组(n=43)和联合组(n=46)。泼尼松组给予常规治疗联合小剂量泼尼松治疗,联合组在泼尼松组基础上联合吗替麦考酚酯治疗。比较两组尿β2-MG、U-mAlb、α1-MG、N-乙酰-β-D氨基葡萄糖苷酶(NAG)及尿足细胞蛋白的水平,检测两组肾功能、血管内皮生长因子(VEGF)、转化生长因子-β1(TGF-β1)、转化生长因子-α(TGF-α)、血尿酸、血红蛋白的差异,统计两组疗效。结果 治疗后,两组尿液β2-MG、U-mAlb、α1-MG、NAG下降,且联合组低于泼尼松组,差异有统计学意义(P<0.05)。治疗后,两组尿NPHS1蛋白、Podocin蛋白下降,且联合组低于泼尼松组,差异有统计学意义(P<0.05)。治疗后,两组VEGF、TGF-β1、TGF-α下降,且联合组低于泼尼松组,差异有统计学意义(P<0.05)。治疗后,两组Scr、BUN、24hU-TP、eGFR下降,且联合组24hU-TP、e GFR下降后水平低于泼尼松组,差异有统计学意义(P<0.05)。结论 吗替麦考酚酯联合小剂量泼尼松治疗IgA肾病可保护患者足细胞,减轻肾损伤,提高疗效。

葡萄叶片对空气中邻苯二甲酸酯的吸收累积特征

【目的】为探索葡萄叶片及其内部组成物质对空气中PAEs的吸收累积特征,阐明葡萄叶片从空气中吸收累积DBP、DEHP、DIBP的能力及规律。【方法】试验采用盆栽葡萄覆盖玻璃罩的方式,在玻璃罩内放置盛有DBP、DEHP、DIBP混合物的甲醇溶液培养皿,让PAEs自然挥发被植株吸收累积,研究叶片及其内部组成物质脂肪、糖、蛋白质对PAEs的吸收累积特征。【结果】3个品种葡萄叶片对DBP、DEHP和DIBP的累积量随着PAEs处理浓度的增高而增大,且不同污染水平各单体含量及总含量差异显著(P<0.05)。葡萄叶片对DEHP的累积量最高,在高污染处理中其累积量占比在92.90%~93.86%,其次为DBP和DIBP。叶片脂肪、糖、蛋白质中均检出DBP、DEHP和DIBP,各污染处理3种化合物的含量与空白差异显著(P<0.05),三者在脂肪中的累积量最多,最高可达87.06 mg/kg,在糖中最高仅为5.818 mg/kg,在蛋白质中最高仅为3.793 mg/kg。通过对葡萄叶片累积PAEs能力与组成物质的相关性进行分析,葡萄叶片PAEs累积量与脂肪中PAEs含量呈显著正相关相关,与糖和蛋白无显著相关性。【结论】葡萄叶片可从空气中吸收累积PAEs,其累积PAEs能力与脂肪密切相关。