6-Shogaol induces apoptosis in acute lymphoblastic leukaemia cells by targeting p53 signalling pathway and generation of reactive oxygen species

Combination therapies, using medicinal herbs, are broadly recommended to attenuate the chemotherapy adverse effects. Based on our previous findings considering the anti-leukaemic effects of ginger extract on acute lymphoblastic leukaemia (ALL) cells, the present study was aimed to investigate the anti-cancer role of this pharmaceutical plant on ALL mice models. Moreover, we worked towards identifying the most anti-leukaemic derivative of ginger and the mechanism through which it may exert its cytotoxic impact. In vivo experiments were performed using five groups of six C57BL/6 nude mice, and the anti-leukaemic activity of ginger extract alone or in combination with methotrexate (MTX) was examined. Results showed increased survival rate and reduced damages in mice brain and liver tissues. Subsequently, MTT assay demonstrated synergistic growth inhibitory effect of 6-shogaol (6Sh) and MTX on ALL cell lines and patients primary cells. Eventually, the molecular anti-neoplastic mechanism of 6Sh was evaluated using Bioinformatics. Flow cytometry illustrated 6Sh-mediated apoptosis in Nalm-6 cells confirmed by Western blotting and RT-PCR assays. Further analyses exhibited the generation of reactive oxygen species (ROS) through 6Sh. The current study revealed the in vivo novel anti-leukaemic role of ginger extract, promoted by MTX. Moreover, 6-shogaol was introduced as the major player of ginger cytotoxicity through inducing p53 activity and ROS generation.     

陕西省新型城镇化与生态环境协调度研究

城镇化与生态环境之间相互影响、相互促进，两系统间耦合协调状态对于区域绿色可持续发展意义重大。以陕西省2005—2019年数据为例，在构建新型城镇化与生态环境系统评价指标体系的基础上结合耦合协调度模型、相对发展模型及面板向量自回归(PVAR)模型分析新型城镇化系统与生态环境系统间的耦合协调时空规律及互动关系。结果表明：(1)陕西省耦合协调度总体呈现“基本不协调—基本协调—中度协调”的演变规律。(2)各市耦合协调发展状态空间差异明显，2005年、2013年、2019年陕西省10个城市新型城镇化与生态环境耦合协调发展状态存在较大差异性，相对发展状态整体上由新型城镇化滞后状态发展为生态环境滞后状态。(3)脉冲响应图反映出新型城镇化与生态环境两系统间存在明显互动关系，前期生态环境受新型城镇化冲击的负向抑制作用，后期影响逐渐减小，受自身冲击较大，而新型城镇化发展前后期均主要受自身影响。本研究认为新型城镇化发展必须以生态为优先，在提高生态承载力的基础上，加速提升陕西省各区域空间人口等不同维度城镇化发展水平，从而实现高质量可持续的绿色发展目标。     

Morphogenia: a new genus of the Neotropical tribe Jubini (Coleoptera,Staphylinidae, Pselaphinae) from the Brazilian Amazon

A new genus and species of the large Neotropical pselaphine tribe Jubini is described from Manaus, Brazil, based on material preserved in the Natural History Museum, London. Morphogenia struhli gen. et sp. n. represents the possible sister taxon of the abundant and speciose genus Barrojuba Park, sharing with it the putatively derived condition of anterolaterally shifted vertexal foveae, producing a smoothly convex vertex devoid of fovea or sulci. However, unlike Barrojuba, Morphogenia retains a plesiomorphic antebasal sulcus on the pronotum in both sexes, and additionally lacks elaborate abdominal fovea-like pockets and teeth on the lateral margins of the pronotum that are typical of Barrojuba. The genus is also unusual among jubine genera in lacking the characteristic V- or Y-shaped gular carina. In contrast to the commonly-collected Barrojuba, specimens of Morphogenia are absent in extensive jubine collections housed in museums in the United States, indicating that the new taxon may be relatively scarce or localised.     

Effect of redox-responsive DTSSP crosslinking on poly(l-lysine)-grafted-poly(ethylene glycol) nanoparticles for delivery of proteins

Therapeutic proteins are utilized in a variety of clinical applications, but side effects and rapid in vivo clearance still present hurdles. An approach that addresses both drawbacks is protein encapsulation within in a polymeric nanoparticle, which is effective but introduces the additional challenge of destabilizing the nanoparticle shell in clinically relevant locations. This study examined the effects of crosslinking self-assembled poly(l -lysine)-grafted-poly(ethylene glycol) nanoparticles with redox-responsive 3,3′-dithiobis(sulfosuccinimidyl propionate) (DTSSP) to achieve nanoparticle destabilization in a reductive environment. The polymer-protein nanoparticles (DTSSP NPs) were formed through electrostatic self-assembly and crosslinked with DTSSP, which contains a glutathione-reducible disulfide. As glutathione is upregulated in various cancers, DTSSP NPs could display destabilization within cancer cells. A library of DTSSP NPs was formed with varying copolymer to protein (C:P) and crosslinker to protein (X:P) mass ratios and characterized by size and encapsulation efficiency. DTSSP NPs with a 7:1 C:P ratio and 2:1 X:P ratio were further characterized by stability in the presence proteases and reducing agents. DTSSP NPs fully encapsulated the model protein and displayed 81% protein release when incubated with 5 mM dithiothreitol for 12 hr. This study contributes to understanding stimulus-responsive crosslinking of polymeric nanoparticles and could be foundational to clinical administration of therapeutic proteins.     

CLIX: a search algorithm for finding novel ligands capable of binding proteins of known three-dimensional structure.

A computer algorithm, CLIX, capable of searching a crystallographic data-base of small molecules for candidates which have both steric and chemical likelihood of binding a protein of known three-dimensional structure is presented. The algorithm is a significant advance over previous strategies which consider solely steric or chemical requirements for binding. The algorithm is shown to be capable of predicting the correct binding geometry of sialic acid to a mutant influenza-virus hemagglutinin and of proposing a number of potential new ligands to this protein.     

A NEW RHEOCRICOTOPUS THIENEMANN & HARNISCHIA (DIPTERA: CHIRONOMIDAE) FROM TAIWAN PROVINCE CHINA

Abstract  Rheocricotopus (Psilocricotopus) taiwanensis sp. n. from Taiwan, China, is described as male imagines. The species is allied to R. (P.) chalybeatus (Edwards) but it is easily separated from the latter in lacking setae in all reins, much lower AR and more pronounced crista dorsalis in gonostylus. The genus is new to Taiwan Province, China. The specimen is deposited at the Department of Biology, Nankai University, Tianjin.     

Taxonomic Review of the Genus Eudorylas Aczél (Diptera: Pipunculidae) in Korea

The Korean species of the genus Eudorylas Aczél have been studied. A total of 16 species are arranged herein. Among them, E. paraappendiculatus sp. nov. is new to science, and E. nomurai Morakote et Yano, 1990 is newly recorded in the Korean fauna.     

Fine structural recognition specificities of IgE antibodies distinguishing amoxicilloyl and amoxicillanyl determinants in allergic subjects.

IgE antibodies in the sera of subjects allergic to beta-lactam antibiotics detect a spectrum of specificities ranging from side-chain groups to an entire penicillin or cephalosporin molecule. In addition to such structural heterogeneity of allergenic determinants, IgE antibodies in the sera of different allergic subjects show heterogeneous recognition responses. Detailed immunochemical studies were carried out on the sera of penicillin-allergic subjects that showed selective and unexpected reactions with the frequently prescribed penicillin, amoxicillin. Antibodies from one subject reacted only with the amoxicilloyl determinant while IgE from another subject showed multiple reactivity with penicilloyl and penicillanyl determinants of different penicillins but not with the amoxicilloyl determinant. Quantitative hapten inhibition studies revealed that the combining sites of the former antibodies were complementary to amoxicillin in a form that permits binding to the hydroxyaminobenzyl side-chain and the thiazolidine ring carboxyl. These conditions are satisfied with the drug in the '-oyl' but not in the '-anyl' form which involves linkage through the 2-carboxyl of the thiazolidine ring. With the second serum, adsorption studies showed that the wide-ranging reactivity of IgE was due to a single population of antibodies that detected a common specificity on the different penicillins. Combining site studies revealed clear recognition of the benzyl portion of the side-chain of benzylpenicilloyl, benzylpenicillanyl, ampicilloyl, ampicillanyl and amoxicillanyl determinants when free antibody access to the side-chain was possible but little or no recognition of the ring hydroxyl of amoxicillin. Such uninhibited access may not occur, however, when amoxicillin is conjugated in the '-oyl' form since opening the beta-lactam ring allows increased flexibility and rotation of the molecule and the possibility of close association of the hydroxyaminobenzyl side-chain of amoxicillin with the linked peptide carrier. In such close steric association, H-bonding involving the ring hydroxyl and amino acids of the carrier may prevent antibody access to the side-chain region of the amoxicilloyl determinant.     

Four New Species of Xenylla (Collembola: Hypogastruridae) from Korea

ABSTRACT Four new species of the collembolan genus Xenylla, X. convexopyga, X. longistriata, X. dotata and X. marina from Korea are described. X. convexopyga is characterized by an absence of the dorsal seta m₃ on Th. II-III. While the other three new species share similarities in dorsal chaetotaxic characters. However, they are dissimilar in the following respects: ventral chaetotaxy, body colour, presence or absence of inner teeth on unguis, the length proportion of abdominal segments and thoracic segments, arrangement of anal papillae and the general shape of apical bulb of fourth antennal segment. As a result of this study, a total of 25 species in 6 genera of Hypogastruridae have been recorded from the Korean Peninsula.