Quantitative regulation of the thermal stability of enveloped virus vaccines by surface charge engineering to prevent the self-aggregation of attachment glycoproteins

The development of thermostable vaccines can relieve the bottleneck of existing vaccines caused by thermal instability and subsequent poor efficacy, which is one of the predominant reasons for the millions of deaths caused by vaccine-preventable diseases. Research into the mechanism of viral thermostability may provide strategies for developing thermostable vaccines. Using Newcastle disease virus (NDV) as model, we identified the negative surface charge of attachment glycoprotein as a novel determinant of viral thermostability. It prevented the temperature-induced aggregation of glycoprotein and subsequent detachment from virion surface. Then structural stability of virion surface was improved and virus could bind to and infect cells efficiently after heat-treatment. Employing the approach of surface charge engineering, thermal stability of NDV and influenza A virus (IAV) vaccines was successfully improved. The increase in the level of vaccine thermal stability was determined by the value-added in the negative surface charge of the attachment glycoprotein. The engineered live and inactivated vaccines could be used efficiently after storage at 37°C for at least 10 and 60 days, respectively. Thus, our results revealed a novel surface-charge-mediated link between HN protein and NDV thermostability, which could be used to design thermal stable NDV and IAV vaccines rationally.     

LRG‐1 promotes fat graft survival through the RAB31‐mediated inhibition of hypoxia‐induced apoptosis

Autologous adipose tissue is an ideal soft tissue filling material, and its biocompatibility is better than that of artificial tissue substitutes, foreign bodies and heterogeneous materials. Although autologous fat transplantation has many advantages, the low retention rate of adipose tissue limits its clinical application. Here, we identified a secretory glycoprotein, leucine‐rich‐alpha‐2‐glycoprotein 1 (LRG‐1), that could promote fat graft survival through RAB31‐mediated inhibition of hypoxia‐induced apoptosis. We showed that LRG‐1 injection significantly increased the maintenance of fat volume and weight compared with the control. In addition, higher fat integrity, more viable adipocytes and fewer apoptotic cells were observed in the LRG‐1‐treated groups. Furthermore, we discovered that LRG‐1 could reduce the ADSC apoptosis induced by hypoxic conditions. The mechanism underlying the LRG‐1‐mediated suppression of the ADSC apoptosis induced by hypoxia was mediated by the upregulation of RAB31 expression. Using LRG‐1 for fat grafts may prove to be clinically successful for increasing the retention rate of transplanted fat.     

Design,synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties

The DNA methyltransferases (DNMTs) were found in mammals to maintain DNA methylation. Among them, DNMT1 was the first identified, and it is an attractive target for tumour chemotherapy. DC_05 and DC_517 have been reported in our previous work, which is non-nucleoside DNMT1 inhibitor with low micromolar IC₅₀ values and significant selectivity towards other S-adenosyl-_L-methionine (SAM)-dependent protein methyltransferases. In this study, through a process of similarity-based analog searching, a series of DNMT1 inhibitors were designed, synthesized, and evaluated as anticancer agents. SAR studies were conducted based on enzymatic assays. And most of the compounds showed strong inhibitory activity on human DNMT1, especially WK-23 displayed a good inhibitory effect on human DNMT1 with an IC₅₀ value of 5.0 µM. Importantly, the pharmacokinetic (PK) profile of WK-23 was obtained with quite satisfying oral bioavailability and elimination half-life. Taken together, WK-23 is worth developing as DNMT1-selective therapy for the treatment of malignant tumour.     

溶解性有机碳在红壤水稻土中的吸附及其影响因素

吸附作用是影响土壤中溶解性有机碳(DOC)迁移转化及生物有效性的重要反应过程,研究DOC在土壤中的吸附行为,对正确阐明土壤有机碳的循环和转化特征以及进行污染风险评估有重要意义.采用平衡法研究了红壤水稻土对DOC的吸附特征,并分析土壤有机质、粘粒含量及pH值与DOC吸附量之间的关系.结果表明,供试土壤对DOC的吸附等温线符合Freundlich和Linear方程.不同土壤对DOC的吸附能力有明显差异.在相同浓度下,DOC吸附量以第四纪红色粘土发育的低肥力水稻土最大,第三纪红砂岩风化物发育的低肥力水稻土次之,两种高肥力水稻土最小.土壤对DOC的吸附过程分为快、慢两个阶段,0-0.25 h内DOC的吸附速率最大,随着时间的推移,吸附速率渐小,2-4 h后基本达到吸附平衡.描述供试土壤对DOC吸附动力学过程的最优模型为一级扩散方程,其次为Elovich方程和抛物扩散方程.粘粒含量和有机质是影响土壤DOC吸附量的重要因素,随着粘粒含量的增加,有机质含量的降低,DOC的吸附量增大.     

谭清苏铁性别相关的RAPD标记研究

以谭清苏铁(Cycas tanqingii D.Y.Wang)雌雄植株半年生羽叶为材料,用优化的CTAB法分别提取其全基因组DNA,进行RAPD单因子梯度实验和正交实验以优化扩增条件。应用160个RAPD随机引物检测基因组DNA,雌雄植株均扩增出1450多条带,其中引物S0465扩增出与谭清苏铁雌株高度相关的RAPD标记,其大小约为500bp,该标记与雄株没有关联。     

Hemin with Peroxidase Activity Can Inhibit the Oxidative Damage Induced by Ultraviolet A

Excessive reactive oxygen species (ROS), a highly reactive substance that contains oxygen, induced by ultraviolet A (UVA) cause oxidative damage to skin. We confirmed that hemin can catalyze the reaction of tyrosine (Tyr) and hydrogen peroxide (H₂O₂). Catalysis was found to effectively reduce or eliminate oxidative damage to cells induced by H₂O₂ or UVA. The scavenging effects of hemin for other free-radical ROS were also evaluated through pyrogallol autoxidation, 1,1-diphenyl-2-picrylhydrazyl radical (DPPH·)-scavenging assays, and phenanthroline–Fe²⁺ assays. The results show that a mixture of hemin and tyrosine exhibits strong scavenging activities for H₂O₂, superoxide anion (O₂⁻·), DPPH·, and the hydroxyl radical (·OH). Furthermore, the inhibition of oxidative damage to human skin keratinocyte (HaCaT) cells induced by H₂O₂ or UVA was evaluated. The results show that catalysis can significantly reduce the ratio of cell apoptosis and death and inhibit the release of lactate dehydrogenase (LDH), as well as accumulation of malondialdehyde (MDA). Furthermore, the resistance to apoptosis was found to be enhanced. These results show that the mixture of hemin and tyrosine has a significantly protective effect against oxidative damage to HaCaT cells caused by UVA, suggesting it as a protective agent for combating UVA damage.     

森林群落类型分布的方位信息识别

本文通过对森林航空遥感图片经光学付里叶变换所获得的频谱分布曲线,应用模糊数学中的方位信息比较法,在不同类型森林的遥感图片的频谱之间建立了——对应的模糊关系,进行了对森林遥感图象的模式识别,并给出了与实际情况相一致的判别结果。     

柄杆菌对固氮蓝藻生物量及色素的影响

柄杆菌对固氮蓝藻生物量和色素的影响研究结果表明:多态柄杆菌(Caulobacter polymorphus)017-41或新月柄杆菌(Caulobacter creseentus)CB_2的活菌、死菌及破碎细胞悬液分别与鱼腥藻(Anabaena)、念珠藻(Nostoc)不同藻珠混合培养时,试验组生长量均优于对照组;对衰老黄化的藻培养物的生长刺激作用尤为显著;试验组藻培养物的藻蓝或藻红素含量亦明显高于对照组。其作用机理尚待进一步阐明。     

Cd、Fe及其复合污染对烟草叶片几项生理指标的影响

本文通过盆栽和大田模拟试验,研究了Cd,Fe,Cd+Fe,Fe+Cd处理下烟草红花大金元(Nicotiana tabacurm L.)叶片的几项生理指标的变化情况。试验表明:烟草叶片叶绿素a、叶绿素b、叶绿素a+b含量均随Cd处理浓度的增加而下降,随Fe处理浓度的增加而上升。总烟碱含量随Cd处理浓度的增加(0—100ppm)而下降,Cd 150ppm时略有上升,随Fe处理浓度的增加而上升。蛋白质含量随Cd处理浓度的增加而上升,随Fe处理浓度的增加而下降。烟草的3个生理指标表明,Cd抑制Fe对生理指标的作用,Fe抑制Cd对它们的作用,Cd与Fe相互拮抗。Cd处理的烟草叶片过氧化物酶活性和细胞膜透性的测定结果表明,过氧化物酶活性和细胞膜透性均随Cd处理浓度的增加而上升。     

Quantification of microtubule stutters: dynamic instability behaviors that are strongly associated with catastrophe

Microtubules (MTs) are cytoskeletal fibers that undergo dynamic instability (DI), a remarkable process involving phases of growth and shortening separated by stochastic transitions called catastrophe and rescue. Dissecting DI mechanism(s) requires first characterizing and quantifying these dynamics, a subjective process that often ignores complexity in MT behavior. We present a Statistical Tool for Automated Dynamic Instability Analysis (STADIA) that identifies and quantifies not only growth and shortening, but also a category of intermediate behaviors that we term “stutters.” During stutters, the rate of MT length change tends to be smaller in magnitude than during typical growth or shortening phases. Quantifying stutters and other behaviors with STADIA demonstrates that stutters precede most catastrophes in our in vitro experiments and dimer-scale MT simulations, suggesting that stutters are mechanistically involved in catastrophes. Related to this idea, we show that the anticatastrophe factor CLASP2γ works by promoting the return of stuttering MTs to growth. STADIA enables more comprehensive and data-driven analysis of MT dynamics compared with previous methods. The treatment of stutters as distinct and quantifiable DI behaviors provides new opportunities for analyzing mechanisms of MT dynamics and their regulation by binding proteins.