Circular RNA circNFKB1 promotes osteoarthritis progression through interacting with ENO1 and sustaining NF-κB signaling

Inflammatory cytokines-induced activation of the nuclear factor κB (NF-κB) pathway plays a critical role in the pathogenesis of osteoarthritis (OA). Circular RNA (circRNA) has been identified as important epigenetic factor in numerous diseases. However, the biological roles of inflammation-related circRNAs in regulating OA pathogenesis remain elusive. Here, we revealed circRNA expression profiles in human primary chondrocytes with interleukin-1β (IL-1β) stimulation by circRNA sequencing. We identified a highly upregulated circRNA, termed as circNFKB1 in inflamed chondrocytes and osteoarthritic cartilage. As a circRNA derived from exon 2–5 of NFKB1, circNFKB1 is located in both cytoplasm and nucleus of chondrocytes. Furthermore, knockdown of circNFKB1 inhibited extracellular matrix (ECM) catabolism and rescued IL-1β impaired ECM anabolism whereas ectopic expression of circNFKB1 significantly promoted chondrocytes degradation in vitro. Moreover, intraarticular injection of adenovirus-circNFKB1 in mouse joints triggered spontaneous cartilage loss and OA development. Mechanistically, circNFKB1 interacted with α-enolase (ENO1), regulated the expression of its parental gene NFKB1 and sustained the activation of NF-κB signaling pathway in chondrocytes. Therefore, this study highlights a novel ENO1-interacting circNFKB1 in OA pathogenesis, and provides valuable insights into understanding the regulatory mechanism of NF-κB signaling in chondrocytes and a promising therapeutic target for the treatment of OA.Subject terms: Osteoarthritis, Cell signalling, RNA     

ZIKV viral proteins and their roles in virus-host interactions

The re-emergence of Zika virus(ZIKV) and its associated neonatal microcephaly and Guillain-Barré syndrome have led the World Health Organization to declare a global health emergency. Until today, many related studies have successively reported the role of various viral proteins of ZIKVin the process of ZIKVinfection and pathogenicity. These studies have provided significant insights for the treatment and prevention of ZIKV infection. Here we review the current research advances in the functional characterization of the interactions between each ZIKV viral protein and its host factors.     

The dual action of glioma-derived exosomes on neuronal activity: synchronization and disruption of synchrony

Seizures represent a frequent symptom in gliomas and significantly impact patient morbidity and quality of life. Although the pathogenesis of tumor-related seizures is not fully understood, accumulating evidence indicates a key role of the peritumoral microenvironment. Brain cancer cells interact with neurons by forming synapses with them and by releasing exosomes, cytokines, and other small molecules. Strong interactions among neurons often lead to the synchronization of their activity. In this paper, we used an in vitro model to investigate the role of exosomes released by glioma cell lines and by patient-derived glioma stem cells (GSCs). The addition of exosomes released by U87 glioma cells to neuronal cultures at day in vitro (DIV) 4, when neurons are not yet synchronous, induces synchronization. At DIV 7–12 neurons become highly synchronous, and the addition of the same exosomes disrupts synchrony. By combining Ca²⁺ imaging, electrical recordings from single neurons with patch-clamp electrodes, substrate-integrated microelectrode arrays, and immunohistochemistry, we show that synchronization and de-synchronization are caused by the combined effect of (i) the formation of new neuronal branches, associated with a higher expression of Arp3, (ii) the modification of synaptic efficiency, and (iii) a direct action of exosomes on the electrical properties of neurons, more evident at DIV 7–12 when the threshold for spike initiation is significantly reduced. At DIV 7–12 exosomes also selectively boost glutamatergic signaling by increasing the number of excitatory synapses. Remarkably, de-synchronization was also observed with exosomes released by glioma-associated stem cells (GASCs) from patients with low-grade glioma but not from patients with high-grade glioma, where a more variable outcome was observed. These results show that exosomes released from glioma modify the electrical properties of neuronal networks and that de-synchronization caused by exosomes from low-grade glioma can contribute to the neurological pathologies of patients with brain cancers.Subject terms: Neuroscience, Preclinical research     

Monitoring and kinetic parameter estimation for the binding process of berberine hydrochloride to bovine serum albumin with piezoelectric quartz crystal impedance analysis

A new method for monitoring, in real time, the drug-binding process to protein with piezoelectric quartz crystal impedance (PQCI) is proposed. The method was used to monitor the binding process of berberine hydrochloride to bovine serum albumin (BSA). BSA was immobilized on the silver electrode surface of a piezoelectric quartz crystal and the optimized experimental conditions were established. The BSA-coated piezoelectric sensor was in contact with berberine solution. The time courses of the resonant frequency and equivalent circuit parameters of the sensor during the protein-drug binding were simultaneously obtained. On the basis of the analysis of the multidimensional information provided by PQCI, it was concluded that the observed frequency decrease was mainly ascribed to the mass increase of the sensor surface resulting from the binding. According to the frequency decrease with time, the kinetics of the binding process were quantitatively studied. A piezoelectric response model for the binding was theoretically derived. Fitting the experimental data to the model, the kinetic parameters, such as the binding and dissociation rate constants (k(1) and k(-1)) and the binding equilibrium constant (K(a)), were determined. The k(1), k(-1), and K(a) values obtained at 25 degrees C were 67.5 (+/-0.1) (mol liter(-1))(-1) s(-1), 1.7 (+/- 0.1) x 10(-3) s(-1), and 3.97 (+/- 0.06) x10(4) (mol liter(-1))(-1), respectively.     

施用控释氮肥对稻田土壤微生物生物量碳、氮的影响

借助农业部望城红壤水稻土生态环境野外观测试验站的控释氮肥试验,研究了施用控释氮肥对水稻不同生育期间稻田土壤微生物生物量碳、氮动态变化的影响。试验共设5个处理:①CK,(不施氮肥);②Urea(施用尿素);③CRNF(施用与处理②等氮量的控释氮肥);④70%CRNF(施用控释氮肥,用氮量为处理②的70%);⑤50%CRNF+M(施用控释氮肥和猪粪,总氮量为处理②的70%,其中控释氮肥用量为处理②的50%,猪粪含氮量为处理②的20%)。结果表明,施肥后10 d,施氮处理土壤微生物生物量碳和氮均达最高,随生育进程推进逐渐下降,成熟期有一定的回升;施肥初期,施用等氮量的控释氮肥处理(CRNF)土壤微生物量碳、氮含量较尿素处理(Urea)分别增加5.4%和22.5%,而水稻生育中后期,控释氮肥处理(CRNF)土壤微生物量碳、氮含量较尿素处理(Urea)下降幅度大,该处理向地上部提供氮素营养较尿素处理高;施氮量较高的CRNF处理,土壤微生物生物量碳低于控释氮肥节氮处理(70%CRNF),但在大多数取样时期,土壤微生物量氮高于控释氮肥节氮处理(70%CRNF);控释氮肥配施有机肥的节氮处理较其他单施化肥处理显著增加土壤微生物生物量碳、氮含量。控释氮肥与有机肥配施,不仅能节约氮肥用量,而且能明显地提高土壤微生物生物量碳、氮的含量。     

Study on the interaction between DNA and protein induced by anticancer drug carboplatin

The interaction of DNA and human serum albumin (HSA) in the presence of anticancer drug carboplatin was studied with piezoelectric quartz crystal impedance (PQCI) and electrochemistry techniques. In the PQCI analysis, the correlative parameters including the frequency (f0), the motional resistance (R(m)), and the static capacitance (C0) in the experiment were obtained and discussed in detail. Additionally, the kinetics parameters of the cross-linking process were investigated and a response kinetics model was deduced. The values of association rate constant k1, dissociation rate constant k(-1) and the reaction equilibrium constant K were estimated to be 1.895 mg/ml(-1) s(-1), 4.7 x 10(-5) s(-1) and 4.03 x 10(4) (mg/ml)-1, respectively. Furthermore, cyclic voltammetry (CV) and electrochemical AC impedance techniques were employed to testify the cross-linking process.     

Cytotoxic T-lymphocyte associated antigen 4 polymorphisms and asthma risk: a meta-analysis

Background

A number of studies assessed the association of cytotoxic T-lymphocyte associated antigen 4 (CTLA-4) gene polymorphisms with asthma in different populations. However, the results were contradictory. We performed a meta-analysis to examine the association between CTLA-4 polymorphisms and asthma susceptibility.

Methods

Pubmed, EMBASE, HuGE Navigator, and Wanfang Database were searched. Data were extracted independently by two reviewers. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations.

Results

Seventeen studies involving 6378 cases and 8674 controls were included. Significant association between +49 A/G polymorphism and asthma was observed for AA vs. AG+GG (OR = 1.18, 95% CI 1.01–1.37, P = 0.04). There were no significant associations between −318 C/T, −1147 C/T, CT60 A/G, −1722 C/T, or rs926169 polymorphisms and asthma risk.

Conclusions

This meta-analysis suggested that the +49 A/G polymorphism in CTLA-4 was a risk factor for asthma.     

气候变暖下水圈甲烷排放及其微生物学机制

大气温室气体浓度升高导致的气候变暖已对人类社会可持续发展带来了严重影响。水圈生态系统既是全球最为重要的碳汇之一,也是全球最为重要的甲烷自然排放源。因此,阐明气候变暖背景下水圈甲烷排放格局及其相关微生物调控机制,是认识未来地球气候系统演变机理、预测未来全球变化潜在情景的关键命题,也将为如何高效发挥水圈碳汇潜力提供基础理论支撑,更好应对全球气候变化问题。本文主要综述了气候变暖背景下主要水圈生态系统中微生物介导的甲烷排放研究的现状与趋势,介绍了水圈甲烷排放格局及其气候变暖背景下的演变趋势,回顾了气候变暖对甲烷代谢相关微生物群落与功能的复杂调控作用。基于目前的研究现状,未来亟需通过微观机制与宏观过程相结合的途径,并基于生态系统复杂性和气候变暖长期性开展相关研究。同时,建议应加强对海洋等相对薄弱区域的研究。     

木防己属植物中生物碱成分的研究概况

本文对木防己属植物中发现的吗啡碱类、阿扑菲碱类、苯甲基异喹啉碱类、异喹啉酮类、原小蘖碱类、刺桐碱烷类及其它结构类型共90余个生物碱成分进行了简要综述,同时探讨了它们在该属植物中的分布、生物活性、结构类型及其民间医疗用途。     

Batch, fed-batch and repeated fed-batch fermentation processes of the marine thraustochytrid Schizochytrium sp. for producing docosahexaenoic acid

Different fermentation processes, including batch, fed-batch and repeated fed-batch processes by Schizochytrium sp., were studied and compared for the effective DHA-rich microbial lipids production. The comparison between different fermentation processes showed that fed-batch process was a more efficient cultivation strategy than the batch process. Among the four different feeding strategies, the glucose concentration feed-back feeding strategy had achieved the highest fermentation results of final cell dry weight, total lipids content, DHA content and DHA productivity of 72.37, 48.86, 18.38 g l^?1 and 138.8 mg l^?1 h^?1, respectively. The repeated fed-batch process had the advantages of reducing the time and cost for seed culture and inoculation between each fermentation cycles. The results of fermentation characteristics and lipid characterization of the repeated fed-batch process indicated that this repeated fed-batch process had promising industrialization prospect for the production of DHA-rich microbial lipids.