The cumulative effects of polymorphisms in the DNA mismatch repair genes and tobacco smoking in oesophageal cancer risk

The DNA mismatch repair (MMR) enzymes repair errors in DNA that occur during normal DNA metabolism or are induced by certain cancer-contributing exposures. We assessed the association between 10 single-nucleotide polymorphisms (SNPs) in 5 MMR genes and oesophageal cancer risk in South Africans. Prior to genotyping, SNPs were selected from the HapMap database, based on their significantly different genotypic distributions between European ancestry populations and four HapMap populations of African origin. In the Mixed Ancestry group, the MSH3 rs26279 G/G versus A/A or A/G genotype was positively associated with cancer (OR?=?2.71; 95% CI: 1.34-5.50). Similar associations were observed for PMS1 rs5742938 (GG versus AA or AG: OR?=?1.73; 95% CI: 1.07-2.79) and MLH3 rs28756991 (AA or GA versus GG: OR?=?2.07; 95% IC: 1.04-4.12). In Black individuals, however, no association between MMR polymorhisms and cancer risk was observed in individual SNP analysis. The interactions between MMR genes were evaluated using the model-based multifactor-dimensionality reduction approach, which showed a significant genetic interaction between SNPs in MSH2, MSH3 and PMS1 genes in Black and Mixed Ancestry subjects, respectively. The data also implies that pathogenesis of common polymorphisms in MMR genes is influenced by exposure to tobacco smoke. In conclusion, our findings suggest that common polymorphisms in MMR genes and/or their combined effects might be involved in the aetiology of oesophageal cancer.     

细胞周期调控因子在肺癌活检组织中的表达

目的：探讨P^21waf1和CyclinE在肺鳞癌组织中表达,方法：应用细胞周期调控因子P^21waf1、CyclinE单克隆抗体,对54例肺鳞状细胞的纤支镜活检标本和10例正常肺组织进行免疫组化染色研究。结果：在肺鳞癌组织中P^21waf1呈低水平表达,其阳性表达率（11／54）仅为20．4％,在肺鳞癌组织中CyclinE阳性表达率（17／54）为31．5％,低分化及有淋巴结转移的病例,其CyclinE表达量明显高于高中分化及无淋巴结转移的病例。结论：P^21waf1在肺鳞癌组织中呈低表达,CyclinE表达可以作为判断肺鳞癌恶性程度的一个指标。     

A new point mutation in the iron–sulfur subunit of succinate dehydrogenase confers resistance to boscalid in Sclerotinia sclerotiorum

Research has established that mutations in highly conserved amino acids of the succinate dehydrogenase (SDH) complex in various fungi confer SDH inhibitor (SDHI) resistance. For Sclerotinia sclerotiorum (Lib.) de Bary, a necrotrophic fungus with a broad host range and a worldwide distribution, boscalid resistance has been attributed to the mutation H132R in the highly conserved SdhD subunit protein of the SDH complex. In our previous study, however, only one point mutation, A11V in SdhB (GCA to GTA change in SdhB), was detected in S. sclerotiorum boscalid‐resistant (BR) mutants. In the current study, replacement of the SdhB gene in a boscalid‐sensitive (BS) S. sclerotiorum strain with the mutant SdhB gene conferred resistance. Compared with wild‐type strains, BR and GSM (SdhB gene in the wild‐type strain replaced by the mutant SdhB gene) mutants were more sensitive to osmotic stress, lacked the ability to produce sclerotia and exhibited lower expression of the pac1 gene. Importantly, the point mutation was not located in the highly conserved sequence of the iron–sulfur subunit of SDH. These results suggest that resistance based on non‐conserved vs. conserved protein domains differs in mechanism. In addition to increasing our understanding of boscalid resistance in S. sclerotiorum, the new information will be useful for the development of alternative antifungal drugs.     

长期连作农田土壤细菌群落结构和共现网络拓扑性质对土壤理化性质的响应

【目的】为探究长期连作土壤细菌群落结构和分子生态网络与土壤环境演化的关联性。【方法】本研究利用16S rRNA基因高通量测序技术,解析了湖南省浏阳市两块连作十二年农田(表现连作障碍的GD和健康的YA)土壤微生物群落组成结构和分子生态网络拓扑性质与土壤理化性质的关系。【结果】GD土壤总氮和有效磷含量显著高于YA,而土壤硝态氮和速效钾含量显著低于YA(P<0.05)。GD土壤细菌群落多样性高于YA,两地土壤细菌群落结构存在显著差异(P<0.01),且与土壤pH和有效磷含量相关。进一步分析表明,GD土壤细菌群落之间比YA具有更复杂的生态网络,主要体现在能量代谢、碳循环和氮循环功能模块。【结论】综上所述,连作会引起土壤细菌群落多样性、组成结构和生态网络变化,这可能与土壤理化性质恶化、土壤肥力下降密切相关,进而影响作物生长发育。     

Improved SnO2 Electron Transport Layers Solution‐Deposited at Near Room Temperature for Rigid or Flexible Perovskite Solar Cells with High Efficiencies

Electron transport layer (ETL) is a functional layer of great significance for boosting the power conversion efficiency (PCE) of perovskite solar cells (PSCs). To date, it is still a challenge to simultaneously reduce the surface defects and improve the crystallinity in ETLs during their low‐temperature processing. Here, a novel strategy for the mediation of in situ regrowth of SnO₂ nanocrystal ETLs is reported: introduction of controlled trace amounts of surface absorbed water on the fluorinated tin oxide (FTO) or indium–tin oxide (ITO) surfaces of the substrates using ultraviolet ozone (UVO) pretreatment. The optimum amount of adsorbed water plays a key role in balancing the hydrolysis–condensation reactions during the structural evolution of SnO₂ thin films. This new approach results in a full‐coverage SnO₂ ETL with a desirable morphology and crystallinity for superior optical and electrical properties, as compared to the control SnO₂ ETL without the UVO pretreatment. Finally, the rigid and flexible PSC devices based on the new SnO₂ ETLs yield high PCEs of up to 20.5% and 17.5%, respectively.     

Expression of Semaphorin 4A and its potential role in rheumatoid arthritis

IntroductionSemaphorin 4A (Sema4A) plays critical roles in many physiological and pathological processes including neuronal development, angiogenesis, immune response regulation, autoimmunity, and infectious diseases. The present study aimed to investigate its expression and biological activity in rheumatoid arthritis (RA).MethodsRNA and protein were isolated from synovial tissues in RA and osteoarthritis (OA) patients. Treatment with recombinant human Sema4A (rhSema4A) or small interfering RNA (siRNA) was applied to examine its effect on the biological activity of synovial fibroblasts of RA (RASFs). Expression of Sema4A and NF-κB were measured by quantitative RT-PCR (qRT-PCR) and Western blot after lipopolysaccharide (LPS) stimulation. Chromatin immunoprecipitation (ChIP) and siRNA targeting p50 and p60 were applied to detect the regulation of Nuclear factor kappa (NF-κB) on Sema4A. Sema4A, interleukin 1β (IL-1β), interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) secretion were measured by ELISA-based assays.ResultsIncreased levels of Sema4A were detected in the synovial tissue and fluid of patients with RA compared with those with OA. Furthermore, synovial fluid level of Sema4A correlated with Disease Activity Score (DAS) in RA. Treatment with rhSema4A promoted invasion of RASFs by upregulating the expression of Matrix metallopeptidase3 (MMP3), MMP9, alpha-smooth muscle actin(α-SMA), and Vimentin, and exacerbated inflammation by promoting the production of IL-6 in RASFs, as well as IL-1β and TNF-α in THP-1 cells. The induction of IL-6 and TNF-α by Sema4A was confirmed at the protein level in fluid samples from patients with RA. Knock-down experiments showed the participation of Plexin B1 towards rhSema4A in the induction of cytokines. In addition, LPS stimulation induced Sema4A expression in RASFs in an NF-κB-dependent manner, and rhSema4A treatment could also activate NF-κB signaling.ConclusionsThese findings suggest an NF-κB-dependent modulation of Sema4A in the immune response. Further, increased expression of Sema4A is required to promote inflammation of RA.

Electronic supplementary material

The online version of this article (doi:10.1186/s13075-015-0734-y) contains supplementary material, which is available to authorized users.     

γ—干扰素和地塞米松对肝素促成纤维细胞增殖的抑制作用

目的和方法 :用MTT比色 ,AgNORs (核仁组成区相关嗜银蛋白 )银染结合图像分析以及抗Ⅲ型胶原单抗免疫组化技术观察了γ 干扰素 (γ IFN)和地塞米松 (Dexa)对成纤维细胞生长的抑制作用。结果和结论 :①培养第 3d ,2 5 0× 10 3u/L的γ IFN和 10 0mg/L的Dexa对正常成纤维细胞生长的抑制率分别为 4 3 %和 3 3 % ;而培养第 5d ,相同浓度的γ IFN对 0 .0 5和 0 .10mg/L肝素刺激的成纤维细胞生长的抑制率分别为 3 4%和 4 0 % ;②照后 3d或5d ,两种抑制剂对肝素刺激的正常和照射成纤维细胞增殖均显示明显抑制作用 ;③ 2 5 0× 10 3u/L的γ IFN和 15 0mg/L的Dexa对成纤维细胞AgNORs合成显示出较强的抑制作用 ,在肝素组其AgNORs颗粒数分别为对照值的60 %和 71% ,而AgNORs 3个定量参数的均值分别为对照值的 61%和 65 % ;④培养第 3d ,上述两种浓度的抑制剂对肝素组Ⅲ型胶原阳性的成纤维细胞抑制率分别为 62 %和 66%。     

Carbendazim-resistance associated β2-tubulin substitutions increase deoxynivalenol biosynthesis by reducing the interaction between β2-tubulin and IDH3 in Fusarium graminearum

Microtubule is a well-known structural protein participating in cell division, motility and vesicle traffic. In this study, we found that β₂-tubulin, one of the microtubule components, plays an important role in regulating secondary metabolite deoxynivalenol (DON) biosynthesis in Fusarium graminearum by interacting with isocitrate dehydrogenase subunit 3 (IDH3). We found IDH3 negatively regulate DON biosynthesis by reducing acetyl-CoA accumulation in F. graminearum and DON biosynthesis was stimulated by exogenous acetyl-CoA. In addition, the expression of IDH3 significantly decreased in the carbendazim-resistant mutant nt167 (Fgβ₂^F167Y). Furthermore, we found that carbendazim-resistance associated β₂-tubulin substitutions reducing the interaction intensity between β₂-tubulin and IDH3. Interestingly, we demonstrated that β₂-tubulin inhibitor carbendazim can disrupt the interaction between β₂-tubulin and IDH3. The decreased interaction intensity between β₂-tubulin and IDH3 resulted in the decreased expression of IDH3, which can cause the accumulation of acetyl-CoA, precursor of DON biosynthesis in F. graminearum. Thus, we revealed that carbendazim-resistance associated β₂-tubulin substitutions or carbendazim treatment increases DON biosynthesis by reducing the interaction between β₂-tubulin and IDH3 in F. graminearum. Taken together, the novel findings give the new perspectives of β₂-tubulin in regulating secondary metabolism in phytopathogenic fungi.     

工频磁场急性暴露对PC12细胞生长和凋亡的影响

将体外传代培养的PC12细胞,经50 Hz、100μT的工频磁场暴露24 h。采用噻唑蓝比色法检测细胞增殖活力,流式细胞术检测细胞周期,吖啶橙/溴化乙锭免疫荧光双染色法检测细胞凋亡。结果表明:1)细胞增殖活力于磁场暴露终止后0 h明显下降(P<0.01);4 h未见著变;8 h(P<0.05)和12 h(P<0.01)显著升高。2)磁场暴露终止后0 h,G0/G1期细胞百分比显著增高(P<0.01),S期细胞百分比显著下降(P<0.05);6 h的G2/M期细胞百分比显著增高(P<0.05);12 h的G0/G1期细胞百分比明显下降(P<0.01),S期细胞百分比显著升高(P<0.05);24 h未见著变。3)磁场暴露期间,6 h细胞凋亡率未见显著改变,12、18和24 h凋亡明显增加,至暴露终止后4、8、12和24 h均显著升高,未见恢复。以上结果说明50 Hz、100μT的工频磁场急性暴露,可导致PC12细胞周期和增殖活力的改变,以及细胞凋亡增多。