The therapeutic effects of edaravone on collagen-induced arthritis in rats

Current research suggests that synovial phagocytic cells remove excessive amounts of free oxygen radicals (reactive oxygen species [ROS]), thereby preventing damage to synovial tissues. Moreover, ROS may affect the expression of growth arrest and DNA damage inducible α (GADD45A), thus further promoting the activation of synovial fibroblasts. Male adult rats were assessed for progression of collagen-induced arthritis (CIA) using a macroscopic arthritis scoring system of the hind paws and by measuring the changes in the rat's body weight, and activity level before and after diagnosis of CIA. Rats were intraperitoneally injected twice daily with edaravone at doses of 3, 6, and 9 mL/kg. Samples were taken at 2, 4, and 6 weeks, respectively. Edaravone was found to significantly reduce macroscopic arthritis and microscopic pathology scores in CIA rats. The concentration of endothelial nitric oxide synthase-6, glutathione, and heme oxygenase-1 in the serum of rats decreased, as was the production of ROS around the synovium and inflammatory factors. Moreover, ROS-1 increased the expression of the nuclear factor-κB (NF-κB) p65 protein by altering the expression level of GADD45A, causing aggravation of tissue damage. Edaravone also significantly improved the physiological condition of CIA rats, including appetite, weight changes, and loss of fur, as well as limb mobility. We believe that edaravone acts to reduce the expression of NF-ĸB p65 by clearing ROS, which causes reduced expression of GADD45A, and subsequently reduces the level of apoptosis and inflammatory response proteins, thereby reducing the symptoms of CIA. We, therefore, propose that edaravone is an effective option for clinical treatment of rheumatic arthritis.     

Genetic and biological properties of H7N9 avian influenza viruses detected after application of the H7N9 poultry vaccine in China

The H7N9 avian influenza virus (AIV) that emerged in China have caused five waves of human infection. Further human cases have been successfully prevented since September 2017 through the use of an H7N9 vaccine in poultry. However, the H7N9 AIV has not been eradicated from poultry in China, and its evolution remains largely unexplored. In this study, we isolated 19 H7N9 AIVs during surveillance and diagnosis from February 2018 to December 2019, and genetic analysis showed that these viruses have formed two different genotypes. Animal studies indicated that the H7N9 viruses are highly lethal to chicken, cause mild infection in ducks, but have distinct pathotypes in mice. The viruses bound to avian-type receptors with high affinity, but gradually lost their ability to bind to human-type receptors. Importantly, we found that H7N9 AIVs isolated in 2019 were antigenically different from the H7N9 vaccine strain that was used for H7N9 influenza control in poultry, and that replication of these viruses cannot, therefore, be completely prevented in vaccinated chickens. We further revealed that two amino acid mutations at positions 135 and 160 in the HA protein added two glycosylation sites and facilitated the escape of the H7N9 viruses from the vaccine-induced immunity. Our study provides important insights into H7N9 virus evolution and control.     

High-frequency optical measurements in shallow Lake Taihu, China: determining the relationships between hydrodynamic processes and inherent optical properties

In order to determine the effect of wind-induced waves (influenced by wind velocity and direction) on the dynamics of optical properties in shallow lakes, we determined the short-term variability of the inherent optical properties (IOPs) in Meiliang Bay, Lake Taihu, China, by examining high-frequency data collected between 8 and 21 September 2010 from meteorology and optical sensors. The absorption and beam attenuation coefficients under strong winds were significantly higher than those under weak and moderate winds (t test, P < 0.001). Significant correlations were found between absorption, scattering, beam attenuation, and wind speed, showing that the hydrodynamic process was an important factor that influenced the instantaneous IOPs of the water. However, the different wind directions have a different effect degree on the IOPs. Western wind is the most important driven wind direction of this site. In addition, significant correlations were found between b _p(440), c _p+g(440), b _p(677), c _p+g(677), b _p(440), and turbidity under each wind direction (P < 0.001). Exponential and hyperbolic exponent models of the absorption and beam attenuation coefficients were fitted, and linear models between a _p+g(677), c _p+g(677), and turbidity were developed. Thus, in shallow lakes such as Lake Taihu, using real-time high-frequency monitoring of the turbidity to deduce the water IOPs could be an efficient and practical approach. Our study will be helpful in monitoring the IOPs and in improving the accuracy of bio-optical models to estimate water quality parameters in Lake Taihu.     

Bioinformatics-Based Identification of Candidate Genes from QTLs Associated with Cell Wall Traits in Populus

Quantitative trait locus (QTL) studies are an integral part of plant research and are used to characterize the genetic basis of phenotypic variation observed in structured populations and inform marker-assisted breeding efforts. These QTL intervals can span large physical regions on a chromosome comprising hundreds of genes, thereby hampering candidate gene identification. Genome history, evolution, and expression evidence can be used to narrow the genes in the interval to a smaller list that is manageable for detailed downstream functional genomics characterization. Our primary motivation for the present study was to address the need for a research methodology that identifies candidate genes within a broad QTL interval. Here we present a bioinformatics-based approach for subdividing candidate genes within QTL intervals into alternate groups of high probability candidates. Application of this approach in the context of studying cell wall traits, specifically lignin content and S/G ratios of stem and root in Populus plants, resulted in manageable sets of genes of both known and putative cell wall biosynthetic function. These results provide a roadmap for future experimental work leading to identification of new genes controlling cell wall recalcitrance and, ultimately, in the utility of plant biomass as an energy feedstock.     

Gö6983 attenuates breast cancer‐induced osteolysis by the apoptotic pathway

Bone metastasis caused by breast cancer leads to significant complications in treatment, and the resulting osteolysis considerably affects patients’ overall survival and quality of life. Gö6983 is a broad spectrum protein kinase C inhibitor. In this study, based on our finding that the Gö6983 inhibits osteolysis, we applied Gö6983 to the MDA‐MB‐231 breast cancer‐induced mouse bone metastasis model. And we found that Gö6983 has a strong inhibitory effect on the tumorigenic model of breast cancer by promoting the mitochondrial apoptosis pathway. Our study, therefore, demonstrates that Gö6983 has a potential inhibitory effect on breast cancer‐induced osteoclast activation and provides mechanistic insight that may prove useful for designing future treatments.     

A candidate PpRPH gene of the D locus controlling fruit acidity in peach

Plant Molecular Biology - A candidate gene, designate PpRPH, in the D locus was identified to control fruit acidity in peach. Fruit acidity has a strong impact on organoleptic quality of fruit....     

真菌反硝化过程及其驱动的N2O产生机制研究进展

真菌反硝化过程的发现打破了反硝化过程只发生在原核生物中的传统认识,是对全球微生物氮循环过程的重要补充。真菌参与的反硝化过程由于缺乏N_2O还原酶,其终产物为具有强辐射效应的温室气体N_2O。真菌在环境中分布广泛,生物量巨大,故真菌反硝化作用对全球N_2O释放通量的贡献是不容忽视的。近年来许多研究表明,真菌反硝化过程是自然环境中N_2O产生的重要途径。本文对反硝化真菌的发现、多样性及分布、产生N_2O的机制和活性测定方法等几个方面进行综述,并对未来的研究提出展望。     

Histone Acetyltransferase 1 Promotes Homologous Recombination in DNA Repair by Facilitating Histone Turnover

Faithful repair of DNA double-strand breaks is vital to the maintenance of genome integrity and proper cell functions. Histone modifications, such as reversible acetylation, phosphorylation, methylation, and ubiquitination, which collectively contribute to the establishment of distinct chromatin states, play important roles in the recruitment of repair factors to the sites of double-strand breaks. Here we report that histone acetyltransferase 1 (HAT1), a classical B type histone acetyltransferase responsible for acetylating the N-terminal tail of newly synthesized histone H4 in the cytoplasm, is a key regulator of DNA repair by homologous recombination in the nucleus. We found that HAT1 is required for the incorporation of H4K5/K12-acetylated H3.3 at sites of double-strand breaks through its HIRA-dependent histone turnover activity. Incorporated histones with specific chemical modifications facilitate subsequent recruitment of RAD51, a key repair factor in mammalian cells, to promote efficient homologous recombination. Significantly, depletion of HAT1 sensitized cells to DNA damage compromised the global chromatin structure, inhibited cell proliferation, and induced cell apoptosis. Our experiments uncovered a role for HAT1 in DNA repair in higher eukaryotic organisms and provide a mechanistic insight into the regulation of histone dynamics by HAT1.     

Penetration of verapamil across blood brain barrier following cerebral ischemia depending on both paracellular pathway and P-glycoprotein transportation

Background

Blood brain barrier (BBB) dysfunction is a common facet of cerebral ischemia, and the alteration of drug transporter, P-glycoprotein (P-gp), has been documented.

Aims

This study explores influence of damaged BBB and elevated P-gp on cerebral verapamil penetration after ischemia both in vivo and in vitro.

Methods

Middle cerebral artery occlusion (MCAO) induced ischemia/reperfusion (I/R) of rats, and Na₂S₂O₄ induced hypoxia/reoxygenation (H/R) damage of rat brain mirovessel endothelial cells (RBMECs) respectively, served as BBB breakdown model in vivo and in vitro. Evans-Blue (EB) extravagation and ¹²⁵I-albumin were used to quantify BBB dysfunction; UPLC–MS/MS analytical method was performed to determine accurately the concentration of verapamil in brain tissue and cell. Flow cytometry, immunohistochemistry and western blotting were applied to evaluate transport function and protein expression of P-gp.

Results

Overexpressed ICAM-1 and MMP-9 mediated BBB dysfunction after ischemia, which induced EB leakage and ¹²⁵I-albumin uptake increase. Enhanced accumulation of verapamil in brain tissue, but intracellular concentration reduced evidently after H/R injury. Transcellular transportation of verapamil elevated when P-gp function or expression was inhibited after H/R injury.

Conclusion

These data indicated that BBB penetration of verapamil under ischemia condition was not only depending on BBB breakdown, but also regulated by P-gp.     

不同CO2浓度变化下干旱对冬小麦叶面积指数的影响差异

叶面积指数是作物生长状况的一个重要表征参数,也是研究陆地生态系统的一个重要的参数.当今世界温室气体排放逐年上升,气候变暖趋势明显,对气候变化敏感的农业将受到影响.在全球变化的背景下,采用农业技术转移决策支持系统(DSSAT)系统,通过在黄淮海平原典型站点模拟3种CO2浓度条件下冬小麦在水分充足和水分亏缺2种情境下的生长过程,分析不同CO2浓度下水分亏缺对冬小麦叶面积指数的影响差异.研究发现,CO2浓度升高对叶面积指数增长有促进作用,且在干旱情况下对叶面积指数的正效应比湿润情况下更为明显,在CO2浓度倍增条件下,发生水分亏缺的作物叶面积指数数倍增长.研究结论有助于分析CO2浓度变化对农作物生长过程的影响,为农田水分管理提供依据,又为估算叶面积指数提出了一种模型的方法.