Antiglioma activity of GoPI-sugar,a novel gold(I)–phosphole inhibitor: Chemical synthesis,mechanistic studies,and effectiveness in vivo

Glioblastoma, an aggressive brain tumor, has a poor prognosis and a high risk of recurrence. An improved chemotherapeutic approach is required to complement radiation therapy. Gold(I) complexes bearing phosphole ligands are promising agents in the treatment of cancer and disturb the redox balance and proliferation of cancer cells by inhibiting disulfide reductases. Here, we report on the antitumor properties of the gold(I) complex 1-phenyl-bis(2-pyridyl)phosphole gold chloride thio-β-d-glucose tetraacetate (GoPI-sugar), which exhibits antiproliferative effects on human (NCH82, NCH89) and rat (C6) glioma cell lines. Compared to carmustine (BCNU), an established nitrosourea compound for the treatment of glioblastomas that inhibits the proliferation of these glioma cell lines with an IC₅₀ of 430 μM, GoPI-sugar is more effective by two orders of magnitude. Moreover, GoPI-sugar inhibits malignant glioma growth in vivo in a C6 glioma rat model and significantly reduces tumor volume while being well tolerated. Both the gold(I) chloro- and thiosugar-substituted phospholes interact with DNA albeit more weakly for the latter. Furthermore, GoPI-sugar irreversibly and potently inhibits thioredoxin reductase (IC₅₀ 4.3 nM) and human glutathione reductase (IC₅₀ 88.5 nM). However, treatment with GoPI-sugar did not significantly alter redox parameters in the brain tissue of treated animals. This might be due to compensatory upregulation of redox-related enzymes but might also indicate that the antiproliferative effects of GoPI-sugar in vivo are rather based on DNA interaction and inhibition of topoisomerase I than on the disturbance of redox equilibrium. Since GoPI-sugar is highly effective against glioblastomas and well tolerated, it represents a most promising lead for drug development. This article is part of a Special Issue entitled: Thiol-Based Redox Processes.     

Immunocompetence and high metabolic rates enhance overwinter survival in the root vole,Microtus oeconomus

Despite its presumed significance, the association between immune defence, energy expenditures and overwinter survival is rarely studied. We analysed individual variation in immunocompetence quantified as neutrophil-to-lymphocyte ratio (N/L), total white blood cells (WBC) and natural antibody levels, along with resting (RMR) and peak metabolic rates (PMR) and mortality during three consecutive winter seasons in a natural population of the root vole, Microtus oeconomus. In early winter, WBC count was negatively correlated with RMR, whereas N/L ratio was negatively correlated with swim-elicited PMR. We suggest that while the first correlation reflected the trade-off between energy allocation in immunocompetence and other metabolically demanding processes, the latter correlation stemmed from stress-induced immunosuppression elicited by the necessity to cope with swimming in frequently flooded habitat. In addition, the analysis carried out during the first year of study characterized by a high population density and prevalence of infestation with a blood parasite—Babesia spp., showed that its intensity was inversely correlated with the N/L ratio. In summary, our results suggest that elevated N/L ratio increases the winter survival of free-ranging rodents by increasing their ability to cope with parasitic infections.     

Trends in HSPB5 research: a 36-year bibliometric analysis

HSPB5 (heat shock protein B5), also known as αB-crystallin, is one of the most widespread and populous of the ten human small heat shock proteins (sHsps). Over the past decades, extensive research has been conducted on HSPB5. However, few studies have statistically analyzed these publications. Herein, we conducted a bibliometric analysis to track the global research trend and current development status of HSPB5 research from the Web of Science Core Collection (WoSCC) database between 1985 and 2020. Our results demonstrate that 1220 original articles cited 54,778 times in 391 scholarly journals were published. Visualization analyses reveal that the Journal of Biological Chemistry was the most influential journal with 85 articles. The USA dominated this field with 520 publications (42.62%), followed by Japan with 149 publications (12.21%), and Kato contributed the largest number of publications. Most related publications were published in journals focusing on biochemistry molecular biology, cell biology, neurosciences neurology, and ophthalmology. In addition, keyword co-occurrence analyses identify three predominant research topics: expression of HSPB5, chaperone studies for HSPB5, and pathological studies of HSPB5. This study provides valuable guidance for researchers and leads to collaborative opportunities between diverse research interests to be integrated for HSPB5 research.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12192-021-01220-6.     

Investigation of bacterioplankton in the loess-containing lake Khanka

Some characteristics of bacterioplankton—generation time, daily (P) and specific (P/B) bacterioplankton production, and bacterial metabolic coefficientK ₂—in the loess-containing Lake Khanka were determined using five modifications of the bacterial-count procedure with the fluorescent dyes fluorescamin and erythrosin. Experiments showed that the organomineral complex (OMC) in this lake is broken down by chemoorganoheterotrophic bacteria. The increase in the loess content of the lake water intensified bacterial growth and the cycles of potassium, silicon, and other biogenic elements. The addition of starch to a loess suspension activated the breakdown of OMC due to the adsorption of starch on the OMC/water interface and stimulation of the metabolism of attached bacteria.     

广东发现濒危鸟类海南鳽

:1 998年 6月 1 7日、1 999年 8月 1 7日、1 999年 8月 2 6日在广东省始兴县车八岭国家级自然保护区范围内三次获得海南幼鸟各 1只 ;华南濒危动物研究所曾于 1 960年 3月 2 2日在英德县滑水山采获雄成鸟标本 1只。至此 ,广东省内存在濒危鸟类海南得到确切证实。近些年内桂南、粤北是国内仅有海南种群分布的地区     

金龟子绿僵菌在森林土壤中的分布及对松墨天牛致病性测定

松墨天牛是重大森林植物检疫性病害——松材线虫病的主要媒介昆虫。本研究于2005年8月～2006年8月从福建、江西两省共110个林分样区(其中松林88个样区)采集土壤样品330份,采用选择性培养基分离土壤中的金龟子绿僵菌。从21个样区的26份土样中分离出的金龟子绿僵菌占采集样区的19．1％和样品的7．9％,成菌落数(CFU)500～72500CFU/g,表明金龟子绿僵菌在森林土壤中有较为广泛的分布。对分离到的9个产孢量高的菌株,采用浸渍法(1×10~7孢子/mL)接种3～4龄健康松墨天牛幼虫,采用跗节接种法接种2～15日龄健康成虫,测定其致病力。结果表明,MaYTTR-03、MaYTTR-04菌株对松墨天牛幼虫和成虫均有较高致病力,表现出良好的生防潜力。     

Age‐related changes in mean corpuscular volumes in patients without anaemia: An analysis of large‐volume data from a single institute

Although the mean corpuscular volume (MCV) has been associated with various diseases, these associations in relation to the age‐related trends in MCV remain unclear. Therefore, we used a dataset with over one million values to identify the relationship between ageing and MCV changes. All laboratory data obtained between November 1998 and November 2019 at Chungbuk National University Hospital were retrospectively collected. After excluding cases with missing values for individual complete blood count parameters, outlier MCV values, and ages less than 1 year and more than 88 years, 977,335 MCV values were obtained from 309,393 patients. Principal component analysis of blood components with ages and analysis of the median value changes for each blood component across decade‐wise age groups were conducted to identify relationships between ageing and changes in blood components. The median values of MCV showed gradual increments with age. The linear relationship for patients aged 1–25 years had a larger slope than that for patients aged 26–88 years. For MCV, the equation for patients aged 1–25 years was 0.40*(age) + 81.24 in females and 0.45*(age) + 79.58 in males. The equation for patients aged 26–90 years was 0.04*(age) + 88.97 in females and 0.06*age + 88.30 in males. Among patients aged >40 years, the MCV value was higher in men than in women. Analysis of a large dataset showed that the MCV gradually increased with age and the linear relationship differed between patients aged 1–25 and 26–88 years.     

链球菌病类活疫苗活菌计数参考品的研制

研制链球菌病类活疫苗活菌计数参考品,可以更加科学地评价活菌计数结果的准确性和有效性。首先,制备了一批链球菌病类活疫苗活菌计数参考品,对其物理性状、纯粹性、真空度、剩余水分进行检验,并对其均一性、运输稳定性、热稳定性进行测定,另组织3家单位通过协作标定的方式对参考品活菌数进行赋值,用协作标定法统计参考品在12个月内的保存期。参考品的性状检查、纯粹检验、真空度测定和剩余水分测定结果均符合《中国兽药典》的规定;均一性试验结果显示,参考品计数结果的变异系数小于10%,均一性良好;运输稳定性试验证明,参考品在夏季和冬季用泡沫盒加冰袋的方式运输3日内数值仍能保持稳定;加速热稳定性试验验证,参考品在–20 ℃条件下保存3个月、4 ℃条件下保存21 d内均可活菌数稳定;通过协作标定,统计出参考品活菌数的赋值范围为 (8.5–12.1)×107 CFU/支;保存期试验结果证实,参考品在–70 ℃以下保存一年内活菌数可维持稳定状态。链球菌病类活疫苗活菌计数参考品,不仅可以为链球菌病类活疫苗的活菌计数实验提供参照物,而且可以用于评价马丁琼脂培养基的质量,为兽用生物制品质量控制提供保障。     

A novel homozygous 10 nucleotide deletion in BBS10 causes Bardet–Biedl syndrome in a Pakistani family

Bardet–Biedl Syndrome is a multisystem autosomal recessive disorder characterized by central obesity, polydactyly, hypogonadism, learning difficulties, rod-cone dystrophy and renal dysplasia. Bardet–Biedl Syndrome has a prevalence rate ranging from 1 in 100,000 to 1 in 160,000 births although there are communities where Bardet–Biedl Syndrome is found at a higher frequency due to consanguinity. We report here a Pakistani consanguineous family with two affected sons with typical clinical features of Bardet–Biedl Syndrome, in addition to abnormal liver functioning and bilateral basal ganglia calcification, the latter feature being typical of Fahr's disease. Homozygous regions obtained from SNP array depicted three known genes BBS10, BBS14 and BBS2. Bidirectional sequencing of all coding exons by traditional sequencing of all these three genes showed a homozygous deletion of 10 nucleotides (c.1958_1967del), in BBS10 in both affected brothers. The segregation analysis revealed that the parents, paternal grandfather, maternal grandmother and an unaffected sister were heterozygous for the deletion. Such a large deletion in BBS10 has not been reported previously in any population and is likely to be contributing to the phenotype of Bardet–Biedl Syndrome in this family.