场强化——微波、超声波技术在固相多肽合成中的应用

综述了两种场强化技术——微波和超声波在固相多肽合成中的研究进展,重点介绍了它们的作用机理、在强化多肽合成中的应用及反应器设计进展情况。     

Identification of Entry Inhibitors against Delta and Omicron Variants of SARS-CoV-2

Entry inhibitors against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are urgently needed to control the outbreak of coronavirus disease 2019 (COVID-19). This study developed a robust and straightforward assay that detected the molecular interaction between the receptor-binding domain (RBD) of viral spike protein and the angiotensin-converting enzyme 2 (ACE2) receptor in just 10 min. A drug library of 1068 approved compounds was used to screen for SARS-CoV2 entry inhibition, and 9 active drugs were identified as specific pseudovirus entry inhibitors. A plaque reduction neutralization test using authentic SARS-CoV-2 virus in Vero E6 cells confirmed that 2 of these drugs (Etravirine and Dolutegravir) significantly inhibited the infection of SARS-CoV-2. With molecular docking, we showed that both Etravirine and Dolutegravir are preferentially bound to primary ACE2-interacting residues on the RBD domain, implying that these two drug blocks may prohibit the viral attachment of SARS-CoV-2. We compared the neutralizing activities of these entry inhibitors against different pseudoviruses carrying spike proteins from alpha, beta, gamma, and delta variants. Both Etravirine and Dolutegravir showed similar neutralizing activities against different variants, with EC50 values between 4.5 to 5.8 nM for Etravirine and 10.2 to 22.9 nM for Dolutegravir. These data implied that Etravirine and Dolutegravir may serve as general spike inhibitors against dominant viral variants of SARS-CoV-2.     

A Glutathione Peroxidase Gene from Litopenaeus vannamei Is Involved in Oxidative Stress Responses and Pathogen Infection Resistance

In shrimp, several glutathione peroxidase (GPX) genes have been cloned and functionally studied. Increasing evidence suggests the genes’ involvement in white spot syndrome virus (WSSV)- or Vibrio alginolyticus-infection resistance. In the present study, a novel GXP gene (LvGPX3) was cloned in Litopenaeus vannamei. Promoter of LvGPX3 was activated by NF-E2-related factor 2. Further study showed that LvGPX3 expression was evidently accelerated by oxidative stress or WSSV or V. alginolyticus infection. Consistently, downregulated expression of LvGPX3 increased the cumulative mortality of WSSV- or V. alginolyticus-infected shrimp. Similar results occurred in shrimp suffering from oxidative stress. Moreover, LvGPX3 was important for enhancing Antimicrobial peptide (AMP) gene expression in S2 cells with lipopolysaccharide treatment. Further, knockdown of LvGPX3 expression significantly suppressed expression of AMPs, such as Penaeidins 2a, Penaeidins 3a and anti-lipopolysaccharide factor 1 in shrimp. AMPs have been proven to be engaged in shrimp WSSV- or V. alginolyticus-infection resistance; it was inferred that LvGPX3 might enhance shrimp immune response under immune challenges, such as increasing expression of AMPs. The regulation mechanism remains to be further studied.     

Relevance of AIF/CypA Lethal Pathway in SH-SY5Y Cells Treated with Staurosporine

The AIF/CypA complex exerts a lethal activity in several rodent models of acute brain injury. Upon formation, it translocates into the nucleus of cells receiving apoptotic stimuli, inducing chromatin condensation, DNA fragmentation, and cell death by a caspase-independent mechanism. Inhibition of this complex in a model of glutamate-induced cell death in HT-22 neuronal cells by an AIF peptide (AIF(370-394)) mimicking the binding site on CypA, restores cell survival and prevents brain injury in neonatal mice undergoing hypoxia-ischemia without apparent toxicity. Here, we explore the effects of the peptide on SH-SY5Y neuroblastoma cells stimulated with staurosporine (STS), a cellular model widely used to study Parkinson’s disease (PD). This will pave the way to understanding the role of the complex and the potential therapeutic efficacy of inhibitors in PD. We find that AIF(370-394) confers resistance to STS-induced apoptosis in SH-SY5Y cells similar to that observed with CypA silencing and that the peptide works on the AIF/CypA translocation pathway and not on caspases activation. These findings suggest that the AIF/CypA complex is a promising target for developing novel therapeutic strategies against PD.     

华东电网CPS考核标准运行分析

介绍了华东电网目前频率质量控制的现状和考核标准,结合实际运行数据分析了现行考核标准CPS在实际运行中所表现出的约束效力和其有待改进之处,由分析结果提出了对考核标准的改进方法和今后电网的频率质量控制手段.     

英红九号茶蛋白ACE抑制肽的制备、氨基酸组成及不同超滤组分的活性评价

以英红九号红茶渣经碱溶酸沉提取的茶蛋白为研究对象,血管紧张素转化酶(ACE)抑制率为评价指标,通过单因素试验和响应面优化得到茶蛋白ACE抑制肽的最佳制备工艺,并对酶解物进行氨基酸组成分析、超滤膜分离和不同分子量组分的ACE抑制活性分析。结果表明,英红九号茶蛋白ACE抑制肽的最优酶解工艺为酶解温度37℃、3.20 h、p H值7.20、底物质量分数3%、酶底质量比0.40%,在此条件下进行的验证试验ACE抑制率为83.38%,与理论值84.48%较相符。英红九号茶蛋白ACE抑制肽酶解物富含必需氨基酸(33.03%)和对ACE抑制活性有重要意义的疏水性氨基酸(47.20%),且经超滤膜分离所得<3ku组分的ACE抑制活性(IC₅₀=0.85 mg/mL)要显著强于酶解物(IC₅₀=1.37 mg/mL)和>3 ku组分(IC₅₀=2.81 mg/mL)。该研究为食源性ACE抑制肽的研究开发和英红九号茶蛋白的高值化利用提供了理论依据。     

粮油食品防霉微生物筛选及其活性物质初步研究

为开发新型防霉剂,降低粮油食品储藏、运输、流通等过程中霉变对其品质和食用安全的影响,研究筛选获得具有强防霉活性的微生物。采用抑菌圈法,以禾谷镰刀菌（Fusarium graminearum）为指示菌筛选具有防霉活性的菌株。利用形态学观察、生化特征鉴定和16S rDNA基因序列比对进行菌株鉴定;通过不同温度、pH和蛋白酶K处理对防霉活性物质进行初步分析。结果显示：通过初筛获得33株对禾谷镰刀菌具有强抑制活性的菌株,复筛后选择的7株菌归属为芽孢杆菌属（Bacillus）;活性物质分析发现7株菌的活性物质均不耐高温和强酸碱,同时蛋白酶K处理对其防霉效果没有明显影响,初步推断为肽类;通过抑菌谱测定发现菌株ASAG 62对常见霉菌（产黄青霉Penicillium flavum、黑曲霉Aspergillus Niger、赭曲霉Aspergillus ochre、黄曲霉Aspergillus flavus、禾谷镰刀菌F. graminearum）均具有良好的抑制效果。     

NGF Enhances CGRP Release Evoked by Capsaicin from Rat Trigeminal Neurons: Differential Inhibition by SNAP-25-Cleaving Proteases

Nerve growth factor (NGF) is known to intensify pain in various ways, so perturbing pertinent effects without negating its essential influences on neuronal functions could help the search for much-needed analgesics. Towards this goal, cultured neurons from neonatal rat trigeminal ganglia—a locus for craniofacial sensory nerves—were used to examine how NGF affects the Ca²⁺-dependent release of a pain mediator, calcitonin gene-related peptide (CGRP), that is triggered by activating a key signal transducer, transient receptor potential vanilloid 1 (TRPV1) with capsaicin (CAP). Measurements utilised neurons fed with or deprived of NGF for 2 days. Acute re-introduction of NGF induced Ca²⁺-dependent CGRP exocytosis that was inhibited by botulinum neurotoxin type A (BoNT/A) or a chimera of/E and/A (/EA), which truncated SNAP-25 (synaptosomal-associated protein with Mr = 25 k) at distinct sites. NGF additionally caused a Ca²⁺-independent enhancement of the neuropeptide release evoked by low concentrations (<100 nM) of CAP, but only marginally increased the peak response to ≥100 nM. Notably, BoNT/A inhibited CGRP exocytosis evoked by low but not high CAP concentrations, whereas/EA effectively reduced responses up to 1 µM CAP and inhibited to a greater extent its enhancement by NGF. In addition to establishing that sensitisation of sensory neurons to CAP by NGF is dependent on SNARE-mediated membrane fusion, insights were gleaned into the differential ability of two regions in the C-terminus of SNAP-25 (181–197 and 198–206) to support CAP-evoked Ca²⁺-dependent exocytosis at different intensities of stimulation.     

催化剂LZR-20PK的性能评价及工业应用

对中国石油兰州化工研究中心开发的催化剂LZR-20 PK在ACE装置上进行了评价,并在奇姆肯特炼油公司200万t/a催化裂化装置上进行了标定.ACE装置评价结果表明:与对比催化剂相比,采用催化剂LZR-20 PK时,产物中液化气、汽油、柴油质量分数增加,油浆和焦炭质量分数降低,H2/CH4(摩尔比)降低,汽油辛烷值略有...     

茶多酚对酪氨酸酶的抑制作用及分子机制研究

目的 研究茶多酚对酪氨酸酶的抑制作用及分子机制。方法 通过生化分析法,测定茶多酚对酪氨酸酶的抑制作用并分析其抑制动力学;采用荧光光谱、圆二色谱和分子模拟技术,剖析茶多酚对酪氨酸酶抑制作用的分子机制。结果 茶多酚对酪氨酸酶有良好的抑制作用,对其单酚和多酚活性的半数抑制浓度分别为0.66mg/mL和1.76mg/mL,为竞争性抑制;茶多酚可使酪氨酸酶出现明显的荧光淬灭和最大发射波长红移,并使酪氨酸酶二级结构中的α-螺旋结构显著增加, β-折叠、β-转角和无规则卷曲结构显著减少,显著改变酪氨酸酶的三级和二级结构。结论 茶多酚主要通过氢键和静电相互作用与酪氨酸酶进行结合,从而改变酪氨酸酶的空间结构并阻碍其与底物进行结合,进而抑制酪氨酸酶的活性。