Subunit-based mucosal vaccine delivery systems for pulmonary delivery - Are they feasible?

Pulmonary infections are the most common cause of death globally. However, the development of mucosal vaccines that provide protective immunity against respiratory pathogens are limited. In contrast to needle-based vaccines, efficient vaccines that are delivered via noninvasive mucosal routes (such as via the lungs and nasal passage) produce both antigen-specific local mucosal IgA and systemic IgG protective antibodies. One major challenge in the development of pulmonary vaccines using subunit antigens however, is the production of optimal immune responses. Subunit vaccines therefore rely upon use of adjuvants to potentiate immune responses. While the lack of suitable mucosal adjuvants has hindered progress in the development of efficient pulmonary vaccines, particle-based systems can provide an alternative approach for the safe and efficient delivery of subunit vaccines. In particular, the rational engineering of particulate vaccines with optimal physicochemical characteristics can produce long-term protective immunity. These protect antigens against enzymatic degradation, target antigen presenting cells and initiate optimal humoral and cellular immunity. This review will discuss our current understanding of pulmonary immunology and developments in fabricating particle characteristics that may evoke potent and durable pulmonary immunity.     

贝氏体精细结构的透射电镜观察

使用ＴＥＭ研究了钢中贝氏体的精细结构、碳化物形貌及分布和Ｃｕ－Ｚｎ－Ａｌ合金中贝氏体的形貌。采用ＨＲＥＭ观察了Ｃｕ－Ｚｎ－Ａｌ合金的界面结构台阶和晶面晶格像。结果表明：加入微量元素可以使贝氏体铁素体组织明显细化。贝氏体铁素体由亚单元或亚块组成，碳化物形貌这五，分布在条间、片内和亚块边界。贝氏体铁素体内有大量的精细组织。Ｃｕ－Ｚｎ－Ａｌ合金初生贝氏体有台阶存在，界面结构台阶高度３－４０ｎｍ，相当于１     

A Modular Vaccine Platform Combining Self‐Assembled Peptide Cages and Immunogenic Peptides

Subunit vaccines use delivery platforms to present minimal antigenic components for immunization. The benefits of such systems include multivalency, self‐adjuvanting properties, and more specific immune responses. Previously, the design, synthesis, and characterization of self‐assembling peptide cages (SAGEs) have been reported. In these, de novo peptides are combined to make hubs that assemble into nanoparticles when mixed in aqueous solution. Here it is shown that SAGEs are nontoxic particles with potential as accessible synthetic peptide scaffolds for the delivery of immunogenic components. To this end, SAGEs functionalized with the model antigenic peptides tetanus toxoid_632‐651 and ovalbumin_323‐339 drive antigen‐specific responses both in vitro and in vivo, eliciting both CD4⁺ T cell and B cell responses. Additionally, SAGEs functionalized with the antigenic peptide hemagglutinin_518‐526 from the influenza virus are also able to drive a CD8⁺ T cell response in vivo. This work demonstrates the potential of SAGEs to act as a modular scaffold for antigen delivery, capable of inducing and boosting specific and tailored immune responses.     

Enhancement of lipid productivity in green microalgae Chlorella sp. via fast neutron irradiation

Microalgae is becoming a promising candidate for biofuel production and energetic lipid production, which urges the need to develop efficient methods for improvement of the lipid production. In this study, the neutron irradiation was employed to improve lipid production under different dosage irradiation. Effects of different dosages (No.1:8.14 × 10⁹, No.2:5.64 × 10⁸, No.4:9.42 × 10⁷ n/cm²) were compared by investigating associated algae cell growth, total lipid production, metabolization and enzyme activity. Dosages No.2 and No.4 improved the lipid content without negative influence on the growing, whereas irradiations shortened the period of biomass accumulation. The neutron irradiation in No.2 accelerated the synthesis of lipid from the carbohydrate transition process. In addition, the neutron irradiation not only increased the total lipid production by 20% but also speeded up the reaction rate to reach the maximal total lipid production in 28 days. Our results can provide a better understanding of the lipid production in microalgae Chlorella sp. by neutron irradiation, which are critical for evaluation of neutron irradiation based technologies for the sustainable and renewable biofuel production.     

α-呋喃丙烯酸酯类香料的合成及性能研究

通过糠醛与乙酐的Ｐｅｒｋｉｎ反应（１５０℃,７ｈ）,以５８７％的收率合成了α-呋喃丙烯酸,再经酯化反应合成六个α-呋喃丙烯酸烷基酯。该系列酯的香气特征为焦糖样甜香并兼有轻微水果香气,其紫外吸收特性是：λｍａｘ（ＭｅＯＨ）：３０４ｎｍ;摩尔消光系数ε≥２１×１０４Ｌ／ｍｏｌ·ｃｍ;Ｓａｎｄｅｌ灵敏度Ｓ≥７．８×１０－３μｇ／ｃｍ２;可有效吸收ＵＶ Ｂ区域（２８０～３２０ｎｍ）的紫外光。     

pRL-hTNF/JM103工程菌发酵和rhTNFα表达的研究

为便于下游中试规模生产,采用温度敏感型启动子PRPL构建rhTNFα工程菌,并对影响工程菌发酵培养和表达的因素进行了初步研究。结果显示,采用RTB培养基,50℃热水快速升温,诱导培养4～4．5h,湿菌体收获率和表达量均达到较高水平;50L发酵罐连续发酵3批,14000r／min连续离心,菌体收获率湿重达16．gg／L培养物,rhTNFα表达量占菌体总蛋白的10.5％,活性达1．35×107U／mg蛋白。.     

SYSTEMETIC VIE WPOINTS ON BAINITE FORMATION MECHANISM

１．ＩｎｔｒｏｄｕｃｔｉｏｎＤｕｒｉｎｇｌａｓｔｓｅｖｅｒａｌｄｅｃａｄｅｓｍｕｃｈａｃｈｉｅｖｅｍｅｎｔｓｈａｓｂｅｅｎｏｂｔａｉｎｅｄｏｎｂａｉｎｉｔｅｔｒａｎｓｆｏｒｍａｔｉｏｎｂｙｍａｎｙｓｃｉｅｎｔｉｓｔｓ,ｂｕｔｓｏｍｅｄｉｓａｇｒｅｅｍｅｎｔｓｏｎｂａｉｎｉｔｅｔｒａｎｓｆｏｒｍａｔｉｏｎｍｅｃｈａｎｉｓｍｓｔｉｌｌｒｅｍａｉｎ〔１４〕．Ｔｈｅｆｏｌｌｏｗｉｎｇｒｅｖｉｅｗｓｕｍｍａｒｉｚｅｓｔｈｅｒｅｃｅｎｔｉｎｖｅｓｔｉｇａｔｉｏｎｓｏｎｂａｉｎｉｔｅｔｒａｎｓｆｏｒｍａｔｉ…     

指状青霉V-ATP酶H亚基蛋白的功能

目的:通过基因干扰和过表达技术,研究V-ATP酶H亚基(V-ATPase membrane subunit H,VMAH)蛋白在柑橘绿霉病菌指状青霉生长中的生理功能,及其作为抗柑橘绿霉病药物作用靶点的可行性.方法:采用菌丝生长法和孢子萌发法,研究沉默和过表达VMAH基因对正常和胁迫条件下指状青霉细胞生长特性的影响.结果...     

Mutations That Affect the Surface Expression of TRPV6 Are Associated with the Upregulation of Serine Proteases in the Placenta of an Infant

Recently, we reported a case of an infant with neonatal severe under-mineralizing skeletal dysplasia caused by mutations within both alleles of the TRPV6 gene. One mutation results in an in frame stop codon (R₅₁₀stop) that leads to a truncated, nonfunctional TRPV6 channel, and the second in a point mutation (G₆₆₀R) that, surprisingly, does not affect the Ca²⁺ permeability of TRPV6. We mimicked the subunit composition of the unaffected heterozygous parent and child by coexpressing the TRPV6 G₆₆₀R and R₅₁₀stop mutants and combinations with wild type TRPV6. We show that both the G₆₆₀R and R₅₁₀stop mutant subunits are expressed and result in decreased calcium uptake, which is the result of the reduced abundancy of functional TRPV6 channels within the plasma membrane. We compared the proteomic profiles of a healthy placenta with that of the diseased infant and detected, exclusively in the latter two proteases, HTRA1 and cathepsin G. Our results implicate that the combination of the two mutant TRPV6 subunits, which are expressed in the placenta of the diseased child, is responsible for the decreased calcium uptake, which could explain the skeletal dysplasia. In addition, placental calcium deficiency also appears to be associated with an increase in the expression of proteases.