Drivers of Echinococcus multilocularis Transmission in China: Small Mammal Diversity,Landscape or Climate?

Background

Human alveolar echinococcocosis (AE) is a highly pathogenic zoonotic disease caused by the larval stage of the cestode E. multilocularis. Its life-cycle includes more than 40 species of small mammal intermediate hosts. Therefore, host biodiversity losses could be expected to alter transmission. Climate may also have possible impacts on E. multilocularis egg survival. We examined the distribution of human AE across two spatial scales, (i) for continental China and (ii) over the eastern edge of the Tibetan plateau. We tested the hypotheses that human disease distribution can be explained by either the biodiversity of small mammal intermediate host species, or by environmental factors such as climate or landscape characteristics.

Methodology/findings

The distributions of 274 small mammal species were mapped to 967 point locations on a grid covering continental China. Land cover, elevation, monthly rainfall and temperature were mapped using remotely sensed imagery and compared to the distribution of human AE disease at continental scale and over the eastern Tibetan plateau. Infection status of 17,589 people screened by abdominal ultrasound in 2002–2008 in 94 villages of Tibetan areas of western Sichuan and Qinghai provinces was analyzed using generalized additive mixed models and related to epidemiological and environmental covariates. We found that human AE was not directly correlated with small mammal reservoir host species richness, but rather was spatially correlated with landscape features and climate which could confirm and predict human disease hotspots over a 200,000 km² region.

Conclusions/Significance

E. multilocularis transmission and resultant human disease risk was better predicted from landscape features that could support increases of small mammal host species prone to population outbreaks, rather than host species richness. We anticipate that our study may be a starting point for further research wherein landscape management could be used to predict human disease risk and for controlling this zoonotic helminthic.     

Complete Genome Sequence of a Novel Avian-Like H3N2 Swine Influenza Virus Discovered in Southern China

We report here the complete genomic sequence of a novel avian-like H3N2 swine influenza virus containing an H5N1 highly pathogenic avian influenza virus segment that was obtained from swine in southern China. Phylogenetic analysis indicated that this virus might originate from domestic aquatic birds. The sequence information provided herein suggests that continuing study is required to determine if this virus can be established in the swine population and pose potential threats to public health.     

Dual-drug loaded nanoneedles with targeting property for efficient cancer therapy

Background

Since the anticancer drugs have diverse inhibited mechanisms to the cancer cells, the use of two or more kinds of anticancer agents may achieve excellent therapeutic effects, especially to the drug-resistant tumors.

Results

In this study, we developed a kind of dual drug [methotrexate (MTX) and 10-hydroxycamptothecine (HCPT)] loaded nanoneedles (DDNDs) with pronounced targeting property, high drug loading and prolonged drug release. The anti-solvent precipitation of the HCPT and MTX modified PEG-b-PLGA (PEG-b-PLGA-MTX, PPMTX) leads to nucleation of nanoneedles with nanocrystalline HCPT as the core wrapped with PPMTX as steric stabilizers. In vitro cell uptake studies showed that the DDNDs revealed an obviously targeting property and entered the HeLa cells easier than the nanoneedles without MTX modification. The cytotoxicity tests illustrated that the DDNDs possessed better killing ability to HeLa cells than the individual drugs or their mixture in the same dose, indicating its good synergistic effect and targeting property. The in vivo studies further confirmed these conclusions.

Conclusions

This approach led to a promising sustained drug delivery system for cancer diagnosis and treatment.

     

高强度酒精连续发酵

从多株酒精酵母菌株中筛选出S.cerevisiaeKG作为酒精生产菌株。该菌株具有较好的酒精发酵活力和絮凝性。使用具有细胞循环的连续发酵双罐系统,酒精生产强度达到30.5（g／1.h）。根据该系统的动力学模型,讨论了获得高强度酒精连续发酵的途径。     

High-light-induced superoxide anion radical formation in cytochrome <Emphasis Type="Italic">b</Emphasis><Subscript><Emphasis Type="Italic">6</Emphasis></Subscript><Emphasis Type="Italic">f</Emphasis> complex from spinach as detected by EPR spectroscopy

The generation of superoxide anion radical (O₂ ^·−) in the cytochrome b ₆ f complex (Cyt b ₆ f) of spinach under high-light illumination was studied using electron paramagnetic resonance spectroscopy. The generation of O₂ ^·− was lost in the absence of molecular oxygen. It was also suppressed in the presence of NaN₃ and could be scavenged by extraneous antioxidants such as ascorbate, β-carotene, and glutathione. The results also indicate that O₂ ^·−, which is produced under high-light illumination of the Cyt b ₆ f from spinach, might be generated from a reaction involing ¹O₂, and the Rieske Fe-S protein could serve as the electron donor in the O₂ ^·− production. The mechanism of photoprotection of the Cyt b ₆ f complex by antioxidants is discussed.     

Association between the XRCC3 T241M polymorphism and risk of cancer: Evidence from 157 case–control studies

The T241M polymorphism in the X-ray cross-complementing group 3 (XRCC3) had been implicated in cancer susceptibility. The previous published data on the association between XRCC3 T241M polymorphism and cancer risk remained controversial. Hence, we performed a meta-analysis to investigate the association between cancer susceptibility and XRCC3 T241M (61,861 cases and 84,584 controls from 157 studies) polymorphism in different inheritance models. We used odds ratios with 95% confidence intervals to assess the strength of the association. Overall, significantly increased cancer risk was observed in any genetic model (dominant model: odds ration [OR] = 1.07, 95% confidence interval [CI] = 1.00–1.13; recessive model: OR = 1.15, 95% CI = 1.08–1.23; additive model: OR = 1.17, 95% CI = 1.08–1.28) when all eligible studies were pooled into the meta-analysis. In further stratified and sensitivity analyses, the elevated risk remained for subgroups of bladder cancer and breast cancer, especially in Caucasians. In addition, significantly decreased lung cancer risk was also observed. In summary, this meta-analysis suggests the participation of XRCC3 T241M in the susceptibility for bladder cancer and breast cancer, especially in Caucasians, and XRCC3 T241M polymorphism is associated with decreased lung cancer risk. Moreover, our work also points out the importance of new studies for T241M association in some cancer types, such as gastric cancer, colorectal cancer, and melanoma skin cancer, where at least some of the covariates responsible for heterogeneity could be controlled, to obtain a more conclusive understanding about the function of the XRCC3 polymorphism in cancer development.     

Rapid comparison of a candidate biosimilar to an innovator monoclonal antibody with advanced liquid chromatography and mass spectrometry technologies

This study shows that state-of-the-art liquid chromatography (LC) and mass spectrometry (MS) can be used for rapid verification of identity and characterization of sequence variants and posttranslational modifications (PTMs) for antibody products. A candidate biosimilar IgG1 monoclonal antibody (mAb) was compared in detail to a commercially available innovator product. Intact protein mass, primary sequence, PTMs and the micro-differences between the two mAbs were identified and quantified simultaneously. Although very similar in terms of sequences and modifications, a mass difference observed by LC-MS intact mass measurements indicated that they were not identical. Peptide mapping, performed with data independent acquisition LC-MS using an alternating low and elevated collision energy scan mode (LC-MS^E), located the mass difference between the biosimilar and the innovator to a two amino acid residue variance in the heavy chain sequences. The peptide mapping technique was also used to comprehensively catalogue and compare the differences in PTMs of the biosimilar and innovator mAbs. Comprehensive glycosylation profiling confirmed that the proportion of individual glycans was different between the biosimilar and the innovator, although the number and identity of glycans were the same. These results demonstrate that the combination of accurate intact mass measurement, released glycan profiling and LC-MS^E peptide mapping provides a set of routine tools that can be used to comprehensively compare a candidate biosimilar and an innovator mAb.Key words: biosimilar mAb, innovator mAb, molecular similarity, sequence variants, posttranslational modifications, N-linked glycosylation, chemical degradations, micro-heterogeneities, characterization, intact protein mass measurement, peptide mapping, glycan profiling, LC-MS, LC-fluorescence, MALDI MS     

染料木素对MRSA外排蛋白表达的影响

[目的] 研究染料木素对耐甲氧西林金黄色葡萄球菌（MRSA）外排蛋白的影响。[方法] 通过联合药敏实验检测染料木素影响MRSA对环丙沙星的敏感性;利用等重同位素多标签相对定量蛋白质组学（iTRAQ）技术,检测染料木素作用MRSA41577后菌体蛋白表达量的变化;通过生物信息学方法对差异显著的蛋白进行系统分析;通过qPCR和尼罗红外排实验,探讨耐药相关的蛋白介导细菌耐药的作用机制。[结果] 联合药敏实验结果显示,染料木素能增强MRSA对环丙沙星的敏感性;通过iTRAQ技术检测到差异显著蛋白共有129个,包括60个表达上调的蛋白和69个表达下调的蛋白;生物信息学分析结果显示,与细菌耐药相关的蛋白约有14个,其中,通过主动外排系统介导细菌耐药的蛋白主要有PstB、PstS等;qPCR结果显示,与对照组相比,PstB、PstS的基因表达量分别下降了51.6%和78.6%;尼罗红外排实验结果显示,染料木素与尼罗红之间存在竞争关系,为MRSA41577的竞争性抑制剂。[结论] 染料木素可通过降低MRSA41577外排基因pstB和pstS的mRNA表达量,进而影响PstB、PstS外排蛋白的表达来逆转细菌耐药;此外,染料木素还是MRSA41577的竞争性外排抑制剂,可通过与底物竞争外排的方式,使抗菌药物留在菌体内发挥抗菌作用。     

Species richness of Protozoa in Japanese lakes

The protozoan fauna and species richness in the pelagic zone of 15 Japanese lakes were investigated in 1996 using polyurethane foam (PF) substrates. The most common species were flagellates, such as Cryptomonas erosa, Oikomonas termo, and Pleuromonas jaculans. Cinetochilum margaritaceum and Actinophrys sol were the most common species of the Ciliata and Sarcodina, respectively. The similarity of species occurrence was calculated from presence/absence data, but this revealed no clear trend with respect to the influence of lake properties such as trophic state, surface area, or mean depth. The occurrence pattern of Protozoa was most similar in L. Chuzenji and L. Biwa (north basin), two oligomesotrophic natural lakes. Log species richness was positively correlated with log total phosphorus (r = 0.54, P < 0.05) and negatively with log mean depth (r = −0.58, P < 0.05). The diversity index (Margalef's formula), highly correlated with the total species number (r = 0.85, P < 0.01), was negatively correlated with log lake area (r = −0.71, P < 0.01). The logarithm of Phytomastigophora number was positively correlated with log total nitrogen (r = 0.53, P < 0.05), and the logarithm of Ciliata number was negatively correlated with log lake area (r = −0.55, P < 0.05). The species richness of Protozoa on PF substrates was determined by both the nutrient status of the lake and the distance from the location of the suspended PF substrate to the lake bottom or shore. Received: September 25, 1999 / Accepted: January 6, 2000