Milk fat globule membrane supplementation protects againstβ-lactoglobul-ininduced food allergy in mice via upregulation of regulatory T cells and enhancement of intestinal barrier in a microbiota-derived short-chain fatty acids manner

Milk fat globule membrane(MFGM),which contains abundant glycoproteins and phospholipids,exerts beneficial effects on intestinal health and immunomodulation.The aim of this study was to evaluate the protective effects and possible underlying mechanisms of MFGM on cow’s milk allergy(CMA)in aβ-lactoglobulin(BLG)-induced allergic mice model.MFGM was supplemented to allergic mice induced by BLG at a dose of 400 mg/kg body weight.Results demonstrated that MFGM alleviated food allergy symptoms,decreased serum levels of lipopolysaccharide,pro-inflammatory cytokines,immunoglobulin(Ig)E,Ig G1,and Th2 cytokines including interleukin(IL)-4,while increased serum levels of Th1 cytokines including interferon-γand regulatory T cells(Tregs)cytokines including IL-10 and transforming growth factor-β.MFGM modulated gut microbiota and enhanced intestinal barrier of BLG-allergic mice,as evidenced by decreased relative abundance of Desulfobacterota,Rikenellaceae,Lachnospiraceae,and Desulfovibrionaceae,while increased relative abundance of Bacteroidetes,Lactobacillaceae and Muribaculaceae,and enhanced expressions of tight junction proteins including Occludin,Claudin-1 and zonula occludens-1.Furthermore,MFGM increased fecal short-chain fatty acids(SCFAs)levels,which elevated G protein-coupled receptor(GPR)43 and GPR109A expressions.The increased expressions of GPR43 and GPR109A induced CD103+dendritic cells accumulation and promoted Tregs differentiation in mesenteric lymph node to a certain extent.In summary,MFGM alleviated CMA in a BLG-induced allergic mice model through enhancing intestinal barrier and promoting Tregs differentiation,which may be correlated with SCFAs-mediated activation of GPRs.These findings suggest that MFGM may be useful as a promising functional ingredient against CMA.

Additive neurorestorative effects of exercise and docosahexaenoic acid intake in a mouse model of Parkinson’s disease

There is a need to develop interventions to slow or reverse the degeneration of dopamine neurons in Parkinson’s disease after diagnosis.Given that preclinical and clinical studies suggest benefits of dietary n-3 polyunsaturated fatty acids,such as docosahexaenoic acid,and exercise in Parkinson’s disease,we investigated whether both could synergistically interact to induce recovery of the dopaminergic pathway.First,mice received a unilateral stereotactic injection of 6-hydroxydopamine into the striatum to establish an animal model of nigrostriatal denervation.Four weeks after lesion,animals were fed a docosahexaenoic acid-enriched or a control diet for the next 8 weeks.During this period,the animals had access to a running wheel,which they could use or not.Docosahexaenoic acid treatment,voluntary exercise,or the combination of both had no effect on(i)distance traveled in the open field test,(ii)the percentage of contraversive rotations in the apomorphine-induction test or(iii)the number of tyrosine-hydroxylase-positive cells in the substantia nigra pars compacta.However,the docosahexaenoic acid diet increased the number of tyrosine-hydroxylase-positive terminals and induced a rise in dopamine concentrations in the lesioned striatum.Compared to docosahexaenoic acid treatment or exercise alone,the combination of docosahexaenoic acid and exercise(i)improved forelimb balance in the stepping test,(ii)decreased the striatal DOPAC/dopamine ratio and(iii)led to increased dopamine transporter levels in the lesioned striatum.The present results suggest that the combination of exercise and docosahexaenoic acid may act synergistically in the striatum of mice with a unilateral lesion of the dopaminergic system and provide support for clinical trials combining nutrition and physical exercise in the treatment of Parkinson’s disease.

2-氯酮与Meldrum’s acid的反应研究

探讨了2-氯(?)酮与Meldrum’s acid在不同条件下的反应结果,合成了化合物2-氧代-3-羧基-1-氧杂薁。并用1HN- MR,13CNMR和IR表征了其结构。

A Convenient Synthesis of Novel Meldrum＇s Acid C60 Fullerene Derivatives

A series of novel Meldrum＇s acid C60 derivatives were prepared in moderate yields from a convenient one-pot reaction of C60, the Meldrum＇s acid derivatives, 12 and 1,8-diazabicyclo-[5,4,0]-undec-7-ene （DBU） in toluene at room temperature under nitrogen atmosphere. All the new compounds were fully characterized by the spectral data and elemental analysis. A carbene intermediate mechanism was proposed for this reaction.

研磨条件下SbCl_3促进的Meldrum’ acid与芳香醛的缩合反应

研磨条件下,以SbCl3为催化剂有效的促进了丙二酸亚异丙酯与芳香醛之间的Knovegenel缩合反应,与其它方法相比,主要优点在于反应条件温和,反应速度快,收率高,为Knovegenel缩合反应找到了一条有效途径。

血清S-100B蛋白、可溶性凝集素样氧化低密度脂蛋白受体-1、胶质纤维酸性蛋白检测在新生儿缺血缺氧性脑病病情严重程度中的诊断价值

目的:探讨血清S-100B蛋白、可溶性凝集素样氧化低密度脂蛋白受体-1(sLOX-1)、胶质纤维酸性蛋白(GFAP)与新生儿缺血缺氧性脑病(HIE)病情严重程度的关系。方法:选择80例HIE患儿作为观察组,另选择90例健康新生儿作为对照组,收集所有患儿一般资料,并检测两组患儿血清S-100B蛋白、sLOX-1、GFAP水平,分析HIE患儿血清S-100B蛋白、sLOX-1、GFAP与病情严重程度的相关性及预后不良的影响因素。结果:对照组血清S-100B蛋白、sLOX-1、GFAP水平低于观察组(均P<0.05)。重度组血清S-100B蛋白、sLOX-1、GFAP水平高于中度组、轻度组和对照组(均P<0.05)。Pearson相关分析显示,疾病严重程度与HIE患儿血清S-100B蛋白、sLOX-1、GFAP水平呈正相关(均P<0.001)。随访预后良好患儿59例,预后不良21例,经多因素Logistic回归分析显示,产程异常、病情重度、S-100B蛋白、sLOX-1、GFAP为影响HIE患儿预后的危险因素(均P<0.05)。结论:HIE患儿病情严重程度和预后与血清S-100B蛋白、sLOX-1、GFAP水平有关,监测其水平变化有利于临床早期完善干预方案改善预后。

STAT3 ameliorates truncated tau-induced cognitive deficits

Proteolytic cleavage of tau by asparagine endopeptidase(AEP)creates tau-N368 fragments,which may drive the pathophysiology associated with synaptic dysfunction and memory deterioration in the brain of Alzheimer’s disease patients.Nonetheless,the molecular mechanisms of truncated tau-induced cognitive deficits remain unclear.Evidence suggests that signal transduction and activator of transcription-3(STAT3)is associated with modulating synaptic plasticity,cell apoptosis,and cognitive function.Using luciferase reporter assays,electrophoretic mobility shift assays,western blotting,and immunofluorescence,we found that human tau-N368 accumulation inhibited STAT3 activity by suppressing STAT3 translocation into the nucleus.Overexpression of STAT3 improved tau-N368-induced synaptic deficits and reduced neuronal loss,thereby improving the cognitive deficits in tau-N368 mice.Moreover,in tau-N368 mice,activation of STAT3 increased N-methyl-D-aspartic acid receptor levels,decreased Bcl-2 levels,reversed synaptic damage and neuronal loss,and thereby alleviated cognitive deficits caused by tau-N368.Taken together,STAT3 plays a critical role in truncated tau-related neuropathological changes.This indicates a new mechanism behind the effect of tau-N368 on synapses and memory deficits.STAT3 can be used as a new molecular target to treat tau-N368-induced protein pathology.

Electrochemical Biosensor for Detection of Staphylococcus aureus Based on Nucleic Acid Aptamers

Staphylococcus aureus is a gram-staining positive cocci bacillus baterium and also one of the foodborne pathogens, which is a serious potential hazard to human health and food safety. We constructed an electrochemical biosensor for the detection of S. aureus based on nucleic acid aptamers to achieve highly specific detection of S. aureus. The detection of S. aureus was realized by using Aptamer (Apt) to capture S. aureus, which resulted in a change in the spatial conformation of Apt and a decrease in the electrochemical signal. Under the optimized experimental conditions, the detected electrochemical signals were positively correlated with the concentration of S. aureus with a linear range of 1 × 101 - 1 × 105 CFU/mL, a detection limit of 4.76 CFU/mL, and an experimental recovery of 97.43% - 99.37%. Therefore, we successfully constructed an electrochemical biosensor for the specific detection of S. aureus, which has the advantages of high specificity, sensitive detection and convenient operation.

Encapsulated peracetic acid as a valid broad‑spectrum antimicrobial alternative,leading to beneficial microbiota compositional changes and enhanced performance in broiler chickens

Background Antimicrobial alternatives are urgently needed,including for poultry production systems.In this study,we tested the potential broad-range antimicrobial alternative peracetic acid,delivered in feed via the hydrolysis of encapsulated precursors through a 28-day study using 375 Ross 308 broiler chickens.We tested two peracetic acid concentrations,30 and 80 mg/kg on birds housed on re-used litter,and we evaluated the impact of both levels on gut microbial communities,bacterial concentration,antimicrobial resistance genes relative abundance and growth performance when compared to control birds housed on either clean or re-used litter.Results Body weight gain and feed conversion ratio improved in peracetic acid fed birds.At d 28,birds given 30 mg/kg of peracetic acid had a decreased Firmicutes and an increased Proteobacteria abundance in the jejunum,accompanied by an increase in Bacillus,Flavonifractor and Rombustia in the caeca,and a decreased abundance of tetracycline resistance genes.Chicken given 80 mg/kg of peracetic acid had greater caecal abundance of macrolides lincosamides and streptogramins resistance genes.Growth performance on clean litter was reduced compared to reused litter,which concurred with increased caecal abundance of Blautia,decreased caecal abundance of Escherichia/Shigella,Anaerostipes and Jeotgalicoccus,and greater gene abundance of vancomycin,tetracycline,and macrolides resistance genes.Conclusions Peracetic acid could be used as a safe broad-spectrum antimicrobial alternative in broilers.Encapsulated precursors were able to reduce the bacterial concentration in the jejunum whilst promoting the proliferation of probiotic genera in the caeca,especially at the low peracetic acid concentrations tested,and improve growth performance.Moreover,our findings offer further insights on potential benefits of rearing birds on re-used litter,suggesting that the latter could be associated with better performance and reduced antimicrobial resistance risk compared to clean litter rearing.

S-(-)-尼古丁-己二酸盐的制备、特性及其应用研究

S-(-)-尼古丁的获取主要是通过从烟叶等植物中提取,获取途径受限,本研究以2′-羟基尼古丁为原料通过还原、化学拆分制备S-(-)-尼古丁;选用己二酸与S-(-)-尼古丁通过超声法制备S-(-)-尼古丁-己二酸盐,优化了合成工艺。产物利用ESI-MS、^(1)H NMR、HPLC进行表征;采用HPLC进行抗氧化性分析;利用热重分析仪进行热稳定性分析。结果表明在反应的最佳工艺条件下S-(-)-尼古丁总产率达55.1%,比旋光度为-141.5°,光学纯度为99.23%;S-(-)-尼古丁-己二酸盐的产率达94.4%,纯度为99.36%;S-(-)-尼古丁-己二酸盐的抗氧化性和热稳定性均优于S-(-)-尼古丁。本研究提供了一条切实可行的S-(-)-尼古丁及其己二酸盐的合成路线;S-(-)-尼古丁-己二酸盐有效避免了S-(-)-尼古丁易氧化、受热不稳定等不足,具有良好的应用前景。

Rapid, accurate and serotype independent pipeline for in silico epitope mapping of SARS-CoV-2 antigens: a combined machine learning and Chou’s pseudo amino acid composition method

Here,a new integrated machine learning and Chou’s pseudo amino acid composition method has been proposed for in silico epitope mapping of severe acute respiratorysyndrome-like coronavirus antigens.For this,a training dataset including 266 linear B-cell epitopes,1,267 T-cell epitopes and 1,280 non-epitopes were prepared.The epitope sequences were then converted to numerical vectors using Chou’s pseudo amino acid composition method.The vectors were then introduced to the support vector machine,random forest,artificial neural network,and K-nearest neighbor algorithms for the classification process.The algorithm with the highest performance was selected for the epitope mapping procedure.Based on the obtained results,the random forest algorithm was the most accurate classifier with an accuracy of 0.934 followed by K-nearest neighbor,artificial neural network,and support vector machine respectively.Furthermore,the efficacies of predicted epitopes by the trained random forest algorithm were assessed through their antigenicity potential as well as affinity to human B cell receptor and MHC-I/II alleles using the VaxiJen score and molecular docking,respectively.It was also clear that the predicted epitopes especially the B-cell epitopes had high antigenicity potentials and good affinities to the protein targets.According to the results,the suggested method can be considered for developing specific epitope predictor software as well as an accelerator pipeline for designing serotype independent vaccine against the virus.

设计改造羧酸还原酶合成医药中间体(S)-2-氨基丁醇

(S)-2-氨基丁醇同时具有羟基及氨基官能团,是多种重要药物分子的关键手性中间体,生物合成(S)-2-氨基丁醇尚缺少有效的酶元件。以塞格尼氏菌(Segniliparus rugosus)来源的羧酸还原酶SrCAR为研究对象,通过对实验室已有SrCAR突变文库进行筛选测试,结合活性位点共进化分析,同时利用组合活性中心饱和突变策略(Combinatorial active-site saturation test,CAST)构建新的突变体文库,经测试最终获得优势突变体XH7(G430V/E533F/A627N)。该突变体催化底物N-Boc-(S)-2-氨基丁酸到醛产物的活性(kcat/Km)较野生型SrCAR提高2.1倍,热熔值(Tm)提升2.3℃。进一步通过引入荧光假单胞菌(Pseudomonas fluorescens)来源的醇脱氢酶PfADH,可还原N-Boc-(S)-2-氨基丁醛到醇产物。XH7和PfADH的双酶共表达体系反应5 h即可将20 mmol/L底物实现几乎完全转化,转化率达到99%,并经脱Boc保护与分离纯化获得终产物(S)-2-氨基丁醇,得率为60%。通过分子动力学模拟解析最优突变体活性及热稳定性提高的分子机制,为SrCAR酶设计改造提供新的研究思路,拓展酶法合成(S)-2氨基丁醇的生物酶工具箱,可为类似高附加值医药中间体的生物合成提供理论和实践指导。

High-performance and robust high-temperature polymer electrolyte membranes with moderate microphase separation by implementation of terphenyl-based polymers

Acid loss and plasticization of phosphoric acid(PA)-doped high-temperature polymer electrolyte membranes(HT-PEMs)are critical limitations to their practical application in fuel cells.To overcome these barriers,poly(terphenyl piperidinium)s constructed from the m-and p-isomers of terphenyl were synthesized to regulate the microstructure of the membrane.Highly rigid p-terphenyl units prompt the formation of moderate PA aggregates,where the ion-pair interaction between piperidinium and biphosphate is reinforced,leading to a reduction in the plasticizing effect.As a result,there are trade-offs between the proton conductivity,mechanical strength,and PA retention of the membranes with varied m/p-isomer ratios.The designed PA-doped PTP-20m membrane exhibits superior ionic conductivity,good mechanical strength,and excellent PA retention over a wide range of temperature(80–160°C)as well as satisfactory resistance to harsh accelerated aging tests.As a result,the membrane presents a desirable combination of performance(1.462 W cm^(-2) under the H_(2)/O_(2)condition,which is 1.5 times higher than that of PBI-based membrane)and durability(300 h at 160°C and 0.2 A cm^(-2))in the fuel cell.The results of this study provide new insights that will guide molecular design from the perspective of microstructure to improve the performance and robustness of HT-PEMs.

Synthesis of Al2S3/MoS2 Nanocomposite by Electrochemical Method: Correlation for Photodegradation of Trichloroacetic Acid, Chloroacetic Acid, Acetic Acid and Study of Antibacterial Efficiency

Al2S3/MoS2 nanocomposite has been synthesized through electrochemical method and characterized by UV-Visible spectroscopy, XRD, SEM and EDAX data. UV-Visible spectroscopy measurements reveal that the Al2S3/MoS2 nanocomposite has maximum absorption at 353.04 nm and this peak position reflects the band gap of particles and it is found to be 2.51 eV which was calculated using Tauc plot. X-Ray diffraction (XRD) reveals crystaline size to be 49.85 nm which was calculated using Williamson-Hall (W-H) plot method. Photocatalytic degradation of acetic acid, chloroacetic acid and trichloroacetic acid has been studied by volumetric method using NaOH solution. Photocatalytic degradation of chloroacetic acid and acetic acid follows first order kinetics. The photodegradation efficiency for Al2S3/MoS2 nanocomposite was found to be ≈97.8%. A Taft linear free energy relationship is noted for the catalysed reaction with ρ* = 0.233 and indicating electron withdrawing groups enhance the rate. An isokinetic relation is observed with β = 358 K indicating that enthalpy factor controls the reaction rate. The result of this paper suggests the possibility of degradation of organic compounds, industrial effluants and toxic organic compounds by photodegradation process by ecofriendly Al2S3/ MoS2. The antibacterial activity of Al2S3/MoS2 nanocomposite was investigated. These particles were shown to have an effective bactericide.

Therapeutic effects of Lingguizhugan decoction in a rat model of high-fat diet-induced insulin resistance

BACKGROUND Lingguizhugan(LGZG)decoction is a widely used classic Chinese medicine formula that was recently shown to improve high-fat diet(HFD)-induced insulin resistance(IR)in animal studies.AIM To assess the therapeutic effect of LGZG decoction on HFD-induced IR and explore the potential underlying mechanism.METHODS To establish an IR rat model,a 12-wk HFD was administered,followed by a 4-wk treatment with LGZG.The determination of IR status was achieved through the use of biochemical tests and oral glucose tolerance tests.Using a targeted metabolomics platform to analyze changes in serum metabolites,quantitative real-time PCR(qRT-PCR)was used to assess the gene expression of the ribosomal protein S6 kinase beta 1(S6K1).RESULTS In IR rats,LGZG decreased body weight and indices of hepatic steatosis.It effectively controlled blood glucose and food intake while protecting islet cells.Metabolite analysis revealed significant differences between the HFD and HFDLGZG groups.LGZG intervention reduced branched-chain amino acid levels.Levels of IR-related metabolites such as tryptophan,alanine,taurine,and asparagine decreased significantly.IR may be linked to amino acids due to the contemporaneous increase in S6K1 expression,as shown by qRT-PCR.CONCLUSIONS Our study strongly suggests that LGZG decoction reduces HFD-induced IR.LGZG may activate S6K1 via metabolic pathways.These findings lay the groundwork for the potential of LGZG as an IR treatment.

Storage time affects the level and diagnostic efficacy of plasma biomarkers for neurodegenerative diseases

Several promising plasma biomarker proteins,such as amyloid-β(Aβ),tau,neurofilament light chain,and glial fibrillary acidic protein,are widely used for the diagnosis of neurodegenerative diseases.However,little is known about the long-term stability of these biomarker proteins in plasma samples stored at-80°C.We aimed to explore how storage time would affect the diagnostic accuracy of these biomarkers using a large cohort.Plasma samples from 229 cognitively unimpaired individuals,encompassing healthy controls and those experiencing subjective cognitive decline,as well as 99 patients with cognitive impairment,comprising those with mild cognitive impairment and dementia,were acquired from the Sino Longitudinal Study on Cognitive Decline project.These samples were stored at-80°C for up to 6 years before being used in this study.Our results showed that plasma levels of Aβ42,Aβ40,neurofilament light chain,and glial fibrillary acidic protein were not significantly correlated with sample storage time.However,the level of total tau showed a negative correlation with sample storage time.Notably,in individuals without cognitive impairment,plasma levels of total protein and tau phosphorylated protein threonine 181(p-tau181)also showed a negative correlation with sample storage time.This was not observed in individuals with cognitive impairment.Consequently,we speculate that the diagnostic accuracy of plasma p-tau181 and the p-tau181 to total tau ratio may be influenced by sample storage time.Therefore,caution is advised when using these plasma biomarkers for the identification of neurodegenerative diseases,such as Alzheimer's disease.Furthermore,in cohort studies,it is important to consider the impact of storage time on the overall results.

Recent progress in the applications of presynaptic dopaminergic positron emission tomography imaging in parkinsonism

Nowadays,presynaptic dopaminergic positron emission tomography,which assesses deficiencies in dopamine synthesis,storage,and transport,is widely utilized for early diagnosis and differential diagnosis of parkinsonism.This review provides a comprehensive summary of the latest developments in the application of presynaptic dopaminergic positron emission tomography imaging in disorders that manifest parkinsonism.We conducted a thorough literature search using reputable databases such as PubMed and Web of Science.Selection criteria involved identifying peer-reviewed articles published within the last 5 years,with emphasis on their relevance to clinical applications.The findings from these studies highlight that presynaptic dopaminergic positron emission tomography has demonstrated potential not only in diagnosing and differentiating various Parkinsonian conditions but also in assessing disease severity and predicting prognosis.Moreover,when employed in conjunction with other imaging modalities and advanced analytical methods,presynaptic dopaminergic positron emission tomography has been validated as a reliable in vivo biomarker.This validation extends to screening and exploring potential neuropathological mechanisms associated with dopaminergic depletion.In summary,the insights gained from interpreting these studies are crucial for enhancing the effectiveness of preclinical investigations and clinical trials,ultimately advancing toward the goals of neuroregeneration in parkinsonian disorders.

COVID-19 mortality paradox(United States vs Africa):Mass vaccination vs early treatment

The coronavirus disease 2019(COVID-19)mortality rate in 55 African countries is almost 4.5 times lower than in the coronavirus disease 2019(COVID-19)despite Africa having over 4.2 times more people.This mortality paradox is also evident when comparing Nigeria,a heavily populated,poorly vaccinated and weakly mandated country to Israel,a small,highly vaccinated and strictly mandated country.Nigeria has almost 4 times lower COVID mortality than Israel.In this Field of Vision perspective,I explain how this paradox has evolved drawing upon my academic,clinical and social experience.Since April 2020,I’ve developed and been using the Egyptian immune-modulatory Kelleni’s protocol to manage COVID-19 patients including pediatric,geriatric,pregnant,immune-compromised and other individuals suffering from multiple comorbidities.It’s unfortunate that severe acute respiratory syndrome coronavirus 2 is still evolving accompanied by more deaths.However in Africa,we’ve been able to live without anxiety or mandates throughout the pandemic because we trust science and adopted early treatment using safe,and effective repurposed drugs that have saved the majority of COVID-19 patients.This article represents an African and Egyptian tale of honor.

基于NaIO_(3)转化NaIO_(4)回用合成S-甘油醛缩丙酮及其寡聚研究

S-甘油醛缩丙酮是合成手性药物的重要中间体。以L-抗坏血酸为原料,经缩酮化,硼氢化钠还原,高碘酸钠氧化制得S-甘油醛缩丙酮,收率为46.8%;探讨了含碘酸钠母液转化成高碘酸钠以循环套用,回收率为83.90%;初步考察了S-甘油醛缩丙酮的聚合度与时间的关系,并推测其寡聚化合物的结构和反应机理;用^(1)H NMR、IR和LC-MS等对化合物结构进行表征。

源于Alcaligenes faecalis腈水解酶基因的生物信息学分析

课题组为探究源于Alcaligenes faecalis腈水解酶突变型Mut3基因的结构与功能,以前期研究为基础,具体分析了腈水解酶的生物信息学,包括理化性质、蛋白二级结构、三级结构、蛋白的保守结构域、跨膜区、信号肽、亲水性和疏水性等。腈水解酶的生物信息学分析为其进一步分子改造提供了重要的理论依据。