Identification of a novel germline BRCA2 variant in a Chinese breast cancer family

Breast cancer is the most frequently diagnosed cancer and the leading cause of cancer‐related deaths in women worldwide. In this study, a large Chinese pedigree with breast cancer including a proband and two female patients was recruited and a familial history of breast cancer was collected by questionnaire. Clinicopathological assessments and neoadjuvant therapy‐related information were obtained for the proband. Blood samples were taken, and gDNA was extracted. The BRCA1/2 and PALB2 genes were screened using next‐generation sequencing by a targeted gene panel. We have successfully identified a novel, germline heterozygous, missense mutation of the gene BRCA2: c.7007G>T, p.R2336L, which is likely to be pathogenic in the proband and her elder sister who both had breast cancer. Furthermore, the risk factors for developing breast cancer in this family are discussed. Thus, genetic counselling and long‐term follow‐up should be provided for this family of breast cancer patients as well as carriers carrying a germline variant of BRCA2: c.7007G>T (p.R2336L).     

Ultrathin Co3O4 Layers with Large Contact Area on Carbon Fibers as High‐Performance Electrode for Flexible Zinc–Air Battery Integrated with Flexible Display

A facile and binder‐free method is developed for the in situ and horizontal growth of ultrathin mesoporous Co₃O₄ layers on the surface of carbon fibers in the carbon cloth (ultrathin Co₃O₄/CC) as high‐performance air electrode for the flexible Zn–air battery. In particular, the ultrathin Co₃O₄ layers have a maximum contact area on the conductive support, facilitating the rapid electron transport and preventing the aggregation of ultrathin layers. The ultrathin feature of Co₃O₄ layers is characterized by the transmission electron microscopy, Raman spectra, and X‐ray absorption fine structure spectroscopy. Benefiting from the high utilization degree of active materials and rapid charge transport, the mass activity for oxygen reduction and evolution reactions of the ultrathin Co₃O₄/CC electrode is more than 10 times higher than that of the carbon cloth loaded with commercial Co₃O₄ nanoparticles. Compared to the commercial Co₃O₄/CC electrode, the flexible Zn–air battery using ultrathin Co₃O₄/CC electrode exhibits excellent rechargeable performance and high mechanical stability. Furthermore, the flexible Zn–air battery is integrated with a flexible display unit. The whole integrated device can operate without obvious performance degradation under serious deformation and even during the cutting process, which makes it highly promising for wearable and roll‐up optoelectronics.     

新生鼠大脑皮质和中脑多巴胺神经元原代培养中NGF诱导c-jun mRNA表达的研究

用神经生长因子（nervegrowthfactor,NGF）分别处理原代培养的新生大鼠大脑皮质和中脑腹侧部神经元,应用免疫组织化学和原位杂交双重标记方法,观察不同时间NGF处理的神经元表达原癌基因c－junmRNA的情况。结果发现,神经特异性烯醇化酶（neuronspecificenolase,NSE）阳性的大脑皮层神经细胞在NGF处理15分钟即可表达c－junmRNA,2小时达高峰,4小时后开始下降,到8小时后基本消失．未经NGF处理的大鼠大脑皮层神经细胞不表达c－junmRNA;酪氨酸羟化酶（tyrosinehydroxylase,TH）阳性的中脑多巴胺能（Dopaminergic,DA）神经元经NGF处理也不表达c－jun基因。提示NGF与其受体结合可以激活神经细胞快速,短暂的一过性表达c-jun基因,作为第三信使,调节从细胞质膜到核的信号传递,同时也间接证明了新生大鼠大脑皮层神经细胞膜上存在神经生长因子受体（nervegrowthfactorreceptor,NGFR）,而中脑DA神经细胞对NGF无应答反应。     

Violet bioluminescence and fast kinetics from W92F obelin: structure-based proposals for the bioluminescence triggering and the identification of the emitting species

Obelin from the hydroid Obelia longissima and aequorin are members of a subfamily of Ca(2+)-regulated photoproteins that is a part of the larger EF-hand calcium binding protein family. On the addition of Ca(2+), obelin generates a blue bioluminescence emission (lambda(max) = 485 nm) as the result of the oxidative decarboxylation of the bound substrate, coelenterazine. The W92F obelin mutant is noteworthy because of the unusually high speed with which it responds to sudden changes of [Ca(2+)] and because it emits violet light rather than blue due to a prominent band with lambda(max) = 405 nm. Increase of pH in the range from 5.5 to 8.5 and using D(2)O both diminish the contribution of the 405 nm band, indicating that excited state proton transfer is involved. Fluorescence model studies have suggested the origin of the 485 nm emission as the excited state of an anion of coelenteramide, the bioluminescence reaction product, and 405 nm from the excited neutral state. Assuming that the dimensions of the substrate binding cavity do not change during the excited state formation, a His22 residue within hydrogen bonding distance to the 6-(p-hydroxy)-phenyl group of the excited coelenteramide is a likely candidate for accepting the phenol proton to produce an ion-pair excited state, in support of recent suggestions for the bioluminescence emitting state. The proton transfer could be impeded by removal of the Trp92 H-bond, resulting in strong enhancement of a 405 nm band giving the violet color of bioluminescence. Comparative analysis of 3D structures of the wild-type (WT) and W92F obelins reveals that there are structural displacements of certain key Ca(2+)-ligating residues in the loops of the two C-terminal EF hands as well as clear differences in hydrogen bond networks in W92F. For instance, the hydrogen bond between the side-chain oxygen atom of Asp169 and the main-chain nitrogen of Arg112 binds together the incoming alpha-helix of loop III and the exiting alpha-helix of loop IV in WT, providing probably concerted changes in these EF hands on calcium binding. But this linkage is not found in W92F obelin. These differences apparently do not change the overall affinity to calcium of W92F obelin but may account for the kinetic differences between the WT and mutant obelins. From analysis of the hydrogen bond network in the coelenterazine binding cavity, it is proposed that the trigger for bioluminescence reaction in these Ca(2+)-regulated photoproteins may be a shift of the hydrogen bond donor-acceptor separations around the coelenterazine-2-hydroperoxy substrate, initiated by small spatial adjustment of the exiting alpha-helix of loop IV.     

西藏牦牛血液酶活性与生产性能的相关性研究

测定了 2 8头西藏牦牛血液中 6种酶的活性 ,探讨了 6种酶活性与生产性能的关系。相关分析表明 ,LDH活性与产奶量、CAT活性与腹毛长呈极显著的正相关 (P <0 .0 1 ) ,AKP活性与体重、Amy活性与体重呈显著正相关 (P <0 .0 5 ) ,SOD活性与体重呈显著负相关 (P <0 .0 5 )。逐步回归分析表明 ,可以用LDH活性预测牦牛产奶量 ,用AKP、CAT、Amy 3种酶活性预测牦牛体重 ,用CAT、Amy活性预测牦牛腹毛长。因此 ,有望将LDH、AKP、CAT和Amy等酶活性作为生化遗传标记应用于牦牛产奶量、体重、腹毛长的选择中     

Studies on Some Angiospermous Fossil Woods Excavated from the Central Part of HubeiProvince

Five angiospermous fossil woods of Late Tertiary have been excavated from Xinzhow County, Hubei Province. From the observation of the wood anatomical features they are pre- liminarily identified as Bischofia javanica B1., a species of Leguminosae, and two species of Lauraceae.     

Preliminary SAR and biological evaluation of antitubercular triazolothiadiazine derivatives against drug-susceptible and drug-resistant Mtb strains

Following up the SAR study of triazolothiadiazoles for their antitubercular activities targeting Mt SD in our previous study, on the principle of scaffold hopping, the C3 and C6 positions of triazolothiadiazine were examined systematically to define a preliminary structure–activity relationship (SAR) with respect to biological activity. This study herein highlights the potential of two highly potent advanced leads 6c-3, 6g-3 and several other compounds with comparable potencies as promising new candidates for the treatment of TB (6c-3, MIC-H37Rv = 0.25 μg/mL; MIC-MDRTB = 2.0 μg/mL; MIC-RDRTB = 0.25 μg/mL; Mt SD-IC₅₀ = 86.39 μg/mL; and 6g-3, MIC-H37Rv = 1.0 μg/mL; MIC-MDRTB = 4.0 μg/mL; MIC-RDRTB = 2.0 μg/mL; Mt SD-IC₅₀ = 73.57 μg/mL). Compounds 6c-3 and 6g-3 possessed a para-nitro phenyl at the 6 position showed low Vero and HepG2 cells toxicity, turning out to be two excellent lead candidates for preclinical trials. In addition, in vitro Mt SD inhibitory assay indicates that Mt SD is at least one of the targets for their antitubercular activity. Thus, they may turn out to be promising multidrug-resistance-reversing agents.