Loss of TAB3 expression by shRNA exhibits suppressive bioactivity and increased chemical sensitivity of ovarian cancer cell lines via the NF‐κB pathway

Ovarian cancer is a leading cause of death among gynaecologic malignancies. Despite many years of research, it still remains sparing in reliable diagnostic markers and methods for early detection and screening. Transforming growth factor β‐activated protein kinase 1 (TAK1)‐binding protein 3 (TAB3) was initially characterized as an adapter protein essential for TAK1 activation in response to IL‐1β or TNFα, however, the physiological role of TAB3 in ovarian cancer tumorigenesis is still not fully understood. In this study, we evaluated the effects of TAB3 on ovarian cancer cell lines. Expressions of TAB3 and PCNA (proliferating cell nuclear antigen) were found to be gradually increased in EOC tissues and cell lines, by western blot analysis and qRT‐PCR. Distribution of TAB3 was further analysed by immunohistochemistry. In vitro, knockdown of TAB3 expression in HO8910 or SKOV3 ovarian cancer cells significantly inhibited bioactivity of ovarian cancer cells, including proliferation and cell‐cycle distribution, and promoted chemical sensitivity to cisplatin and paclitaxel treatment via inhibiting NF‐κB pathways. In conclusion, our study strongly suggests a novel function of TAB3 as an oncogene that could be used as a biomarker for ovarian cancer. It provides a new insight into the potential mechanism for therapeutic targeting, in chemotherapy resistance, common in ovarian cancer.     

Enrichment and characteristics of mixed methane-oxidizing bacteria from a Chinese coal mine

In methane-rich environments, methane-oxidizing bacteria usually occur predominantly among consortia including other types of microorganisms. In this study, artificial coal bed gas and methane gas were used to enrich mixed methanotrophic cultures from the soil of a coal mine in China, respectively. The changes in microbial community structure and function during the enrichment were examined. The microbial diversity was reduced as the enrichment proceeded, while the capacity for methane oxidation was significantly enhanced by the increased abundance of methanotrophs. The proportion of type II methanotrophs increased greatly from 7.84 % in the sampled soil to about 50 % in the enrichment cultures, due to the increase of methane concentration. After the microbial community of the cultures got stable, Methylomonas and Methylocystis became the dominant type I and type II methanotrophs, while Methylophilus was the prevailing methylotroph. The sequences affiliated with pigment-producing strains, Methylomonas rubra, Hydrogenophaga sp. AH-24, and Flavobacterium cucumis, could explain the orange appearance of the cultures. Comparing the two cultures, the multi-carbon sources in the artificial coal bed gas caused more variety of non-methanotrophic bacteria, but did not help to maintain the diversity or to increase the quantity and activity of methanotrophs. The results could help to understand the succession and interaction of microbial community in a methane-driven ecosystem.     

Co–B Nanoflakes as Multifunctional Bridges in ZnCo2O4 Micro‐/Nanospheres for Superior Lithium Storage with Boosted Kinetics and Stability

Transition metal oxides hold great promise as high‐energy anodes in next‐generation lithium‐ion batteries. However, owing to the inherent limitations of low electronic/ionic conductivities and dramatic volume change during charge/discharge, it is still challenging to fabricate practically viable compacted and thick TMO anodes with satisfactory electrochemical performance. Herein, with mesoporous cobalt–boride nanoflakes serving as multifunctional bridges in ZnCo₂O₄ micro‐/nanospheres, a compacted ZnCo₂O₄/Co–B hybrid structure is constructed. Co–B nanoflakes not only bridge ZnCo₂O₄ nanoparticles and function as anchors for ZnCo₂O₄ micro‐/nanospheres to suppress the severe volume fluctuation, they also work as effective electron conduction bridges to promote fast electron transportation. More importantly, they serve as Li⁺ transfer bridges to provide significantly boosted Li⁺ diffusivity, evidenced from both experimental kinetics analysis and density functional theory calculations. The mesopores within Co–B nanoflakes help overcome the large Li⁺ diffusion barriers across 2D interfaces. As a result, the ZnCo₂O₄/Co–B electrode delivers high gravimetric/volumetric/areal capacities of 995 mAh g^?1/1450 mAh cm^?3/5.10 mAh cm^?2, respectively, with robust rate capability and long‐term cyclability. The distinct interfacial design strategy provides a new direction for designing compacted conversion‐type anodes with superior lithium storage kinetics and stability for practical applications.     

Auditory anatomy of beaked whales and other odontocetes: Potential for cochlear stimulation via a “vibroacoustic duct mechanism”

Computed tomography (CT) and microcomputed tomography (microCT) were used to examine the structures involved in cochlear stimulation in odontocetes and terrestrial mammals. Cranial CT examined the osseous attachment of the skull to the tympanoperiotic complex (TPC) and the path of the endocranial foramen of the vestibulocochlear nerve (EFVN), which was assumed to contain the perilymphatic duct. Additional CTs of TPC were taken postextraction to examine the gross morphology of this structure. MicroCT was used to examine the acoustic windows of the cochlea, including the round and oval windows and the apertures of the cochlear and vestibular aqueducts. Cranial CT scans demonstrated an osseous connection between the skull and TPC in beaked whales and Physeter macrocephalus. EFVN traveled through a greater length of cranial bone and communicated more closely with the periotic bone in beaked whales than in other species. Ziphius cavirostris was observed to have a reduced medial sulcus of the mallear ridge (MSMR) and tympanic plate and an enlarged aperture of the cochlear aqueduct, respectively. The potential significance of these findings, including the role of the perilymphatic duct as a novel route of cochlear stimulation referred to as the “vibroacoustic duct mechanism,” are discussed.     

过氧亚硝基阴离子通过JAK/STAT信号途径促进系膜细胞纤连蛋白的合成

氧化应激是糖尿病肾病的重要发病机制之一。过氧亚硝基阴离子(peroxynitrite,ONOO–)是参与氧化应激损伤的重要成员,与糖尿病及其并发症密切相关。该文观察高糖环境下ONOO–对系膜细胞合成纤连蛋白(fibronectin,FN)的影响,并探讨其作用机制。实验中,人肾小球系膜细胞分为4组:正常对照组、高糖组、高糖+尿酸组及高糖+AG490组。培养12,24,48 h后收集细胞及其上清液、并提取细胞总蛋白。采用酶联免疫吸附实验(ELISA)检测细胞上清液中FN的含量,采用免疫细胞化学和Western blot检测NT总蛋白(ONOO–生成的生物标志物)、p-JAK2及p-STAT3蛋白的表达。结果显示,与同期正常组相比,高糖组NT总蛋白、p-JAK2及p-STAT3的表达及FN含量明显增高(P<0.05),并且随着时间的延长表达逐渐增多,以48 h组最为显著;高糖+尿酸组,NT、p-JAK2、p-STAT3及FN较高糖组明显减少(P<0.05);高糖+AG490组,p-JAK2、p-STAT3及FN较高糖组明显减少(P<0.05),但NT表达与高糖组差异无统计学意义(P>0.05)。由此可见,高糖环境下系膜细胞中存在ONOO–的过量表达,ONOO–通过JAK/STAT信号途径促进系膜细胞FN的合成。     

Induction of multiple cytotoxic T lymphocyte responses in mice by a multiepitope DNA vaccine against dengue virus serotype 1

Dengue virus (DENV) is still a major threat to human health in most tropical and subtropical countries and regions. In the present study, a multi‐epitope DNA vaccine that encodes 15 immunogenic and conserved HLA‐A*0201‐, HLA‐A*1101‐, HLA‐A*2402‐restricted CTL epitopes from DENV serotype 1 (DENV‐1) was constructed based on the eukaryotic expressing plasmid pcDNA^TM3.1/myc‐His(?) A. Immunization of HLA‐A*0201, HLA‐A*1101 and HLA‐A*2402 transgenic mice with the recombinant plasmid pcDNA^TM3.1/myc‐His(?) A‐DENV‐1‐Meg resulted in significantly greater IFN‐γ‐secreting T‐cell responses against most (14/15) CTL epitopes than occurred in mice immunized with the empty plasmid pcDNA^TM3.1/myc‐His(?) A. Additionally, the epitope‐specific T cells directed to some epitopes secreted not only IFN‐γ but also IL‐6 and/or TNF‐α. Finally, the induced epitope‐specific T cells also efficiently lysed epitope‐pulsed splenocytes and DENV‐1‐infected splenic monocytes. The present study confirms the immunogenicity of multi‐epitope DENV vaccine, suggesting that it may contribute to the development of a universal DENV vaccine.

     

Dietary arginine supplementation enhances intestinal expression of SLC7A7 and SLC7A1 and ameliorates growth depression in mycotoxin-challenged pigs

This study tested the hypothesis that dietary l-arginine supplementation confers beneficial effects on growing pigs fed a mold-contaminated diet. The measured variables included: (1) the average daily weight gain and feed:gain ratio; (2) activities of total superoxide dismutase, glutathione peroxidase, diamine oxidase, as well as amino acid and d-lactate concentrations in serum; (3) intestinal morphology; (4) expression of the genes for SLC7A7 (amino acid transporter light chain, y^+L system, family 7, member 7), SLC7A1 (cationic amino acid transporter, y⁺ system, family 7, member 1), SLC1A1 (neuronal/epithelial high affinity glutamate transporter, system X_AG, member 1), SLC5A1 (sodium/glucose cotransporter, family 5, member 1) in the ileum and jejunum. Mycotoxins in feedstuffs resulted in an enlarged small intestine mass, oxidative injury in tissues, and reduced growth performance in pigs. Dietary arginine supplementation enhanced (P < 0.05) expression of jejunal SLC7A7 and ileal SLC7A1, in comparison with the control and mycotoxin groups. In addition, supplementing 1 % l-arginine to the mycotoxin-contaminated feed had the following beneficial effects (P < 0.05): (1) alleviating the imbalance of the antioxidant system in the body; (2) ameliorating intestinal abnormalities; and (3) attenuating whole-body growth depression, compared with the mycotoxin group without arginine treatment. Collectively, these results indicate that dietary supplementation with l-arginine exerts a protective role in pigs fed mold-contaminated foods. The findings may have important nutritional implications for humans and other mammals.     

Analyzing the action of evolutionarily conserved modules on HMW-GS 1Ax1 promoter activity

Key message

The specific and high-level expression of 1Ax1 is determined by different promoter regions. HMW-GS synthesis occurs in aleurone layer cells. Heterologous proteins can be stored in protein bodies.

Abstract

High-molecular-weight glutenin subunit (HMW-GS) is highly expressed in the endosperm of wheat and relative species, where their expression level and allelic variation affect the bread-making quality and nutrient quality of flour. However, the mechanism regulating HMW-GS expression remains elusive. In this study, we analyzed the distribution of cis-acting elements in the 2659-bp promoter region of the HMW-GS gene 1Ax1, which can be divided into five element-enriched regions. Fragments derived from progressive 5′ deletions were used to drive GUS gene expression in transgenic wheat, which was confirmed in aleurone layer cells, inner starchy endosperm cells, starchy endosperm transfer cells, and aleurone transfer cells by histochemical staining. The promoter region ranging from ??297 to ??1 was responsible for tissue-specific expression, while fragments from ??1724 to ??618 and from ??618 to ??297 were responsible for high-level expression. Under the control of the 1Ax1 promoter, heterologous protein could be stored in the form of protein bodies in inner starchy endosperm cells, even without a special location signal. Our findings not only deepen our understanding of glutenin expression regulation, trafficking, and accumulation but also provide a strategy for the utilization of wheat endosperm as a bioreactor for the production of nutrients and metabolic products.