Effects of PCSK-9 Inhibition by Alirocumab Treatments on Biliary Cirrhotic Rats

Hyperlipidemia and oxidative stress with elevated oxidized low-density lipoprotein (ox-LDL) exacerbate hepatic inflammation and fibrosis. The plasma level of low-density lipoprotein (LDL) is controlled by proprotein convertase subtilisin/kexin 9 (PCSK9). Alirocumab is a monoclonal antibody that decreases LDL via inhibiting PCSK9 function. Apart from lipid-lowering effects, alirocumab exerts anti-inflammation, anti-angiogenesis and anti-oxidant effects. This study aims to investigate the impact of alirocumab treatment on common bile duct ligation (BDL)-induced biliary cirrhotic rats. After a 4-week treatment of alirocumab, the hemodynamic data, blood biochemistry, ox-LDL level, oxidative stress markers, severity of hepatic encephalopathy and abnormal angiogenesis of BDL rats were measured and compared to the control group. BDL rats presented cirrhotic pictures and elevated ammonia, total cholesterol, LDL and ox-LDL levels compared to the control group. Alirocumab decreased plasma levels of total cholesterol, LDL, and oxidative stress markers; however, it did not affect the hemodynamics, liver and renal biochemistry, and the plasma levels of ammonia and ox-LDL. The motor activities, portal-systemic collaterals and mesenteric vascular density were not significantly different between alirocumab-treated and control groups. In addition, it did not affect hepatic inflammation, intrahepatic angiogenesis, liver fibrosis and free cholesterol accumulation in the liver of BDL rats. In conclusion, PCSK9 inhibition by alirocumab treatment ameliorates hyperlipidemia and systemic oxidative stress in biliary cirrhotic rats. However, it does not affect the plasma level of ox-LDL, intrahepatic inflammation and fibrosis. In addition, PCSK9 inhibition has a neutral effect on abnormal angiogenesis and hepatic encephalopathy in biliary cirrhotic rats.     

Crosstalk between Growth and Osmoregulation of GHRH-SST-GH-IGF Axis in Triploid Rainbow Trout (Oncorhynchus mykiss)

Smolting is an important development stage of salmonid, and an energy trade-off occurs between osmotic regulation and growth during smolting in rainbow trout (Oncorhynchus mykiss). Growth hormone releasing hormone, somatostatin, growth hormone and insulin-like growth factor (GHRH-SST-GH-IGF) axis exhibit pleiotropic effects in regulating growth and osmotic adaptation. Due to salmonid specific genome duplication, increased paralogs are identified in the ghrh-sst-gh-igf axis, however, their physiology in modulating osmoregulation has yet to be investigated. In this study, seven sst genes (sst1a, sst1b, sst2, sst3a, sst3b, sst5, sst6) were identified in trout. We further investigated the ghrh-sst-gh-igf axis of diploid and triploid trout in response to seawater challenge. Kidney sst (sst1b, sst2, sst5) and sstr (sstr1b1, sstr5a, sstr5b) expressions were changed (more than 2-fold increase (except for sstr5a with 1.99-fold increase) or less than 0.5-fold decrease) due to osmoregulation, suggesting a pleiotropic physiology of SSTs in modulating growth and smoltification. Triploid trout showed significantly down-regulated brain sstr1b1 and igfbp2a1 (p < 0.05), while diploid trout showed up-regulated brain igfbp1a1 (~2.61-fold, p = 0.057) and igfbp2a subtypes (~1.38-fold, p < 0.05), suggesting triploid trout exhibited a better acclimation to the seawater environment. The triploid trout showed up-regulated kidney igfbp5a subtypes (~6.62 and 7.25-fold, p = 0.099 and 0.078) and significantly down-regulated igfbp5b2 (~0.37-fold, p < 0.05), showing a conserved physiology of teleost IGFBP5a in regulating osmoregulation. The IGFBP6 subtypes are involved in energy and nutritional regulation. Distinctive igfbp6 subtypes patterns (p < 0.05) potentially indicated trout triggered energy redistribution in brain and kidney during osmoregulatory regulation. In conclusion, we showed that the GHRH-SST-GH-IGF axis exhibited pleiotropic effects in regulating growth and osmoregulatory regulation during trout smolting, which might provide new insights into seawater aquaculture of salmonid species.     

Early Expression of Tet1 and Tet2 in Mouse Zygotes Altered DNA Methylation Status and Affected Embryonic Development

Ten-eleven translocation (Tet) dioxygenases can induce DNA demethylation by catalyzing 5-methylcytosine(5mC) to 5-hydroxymethylcytosine(5hmC), and play important roles during mammalian development. In mouse, Tet1 and Tet2 are not expressed in pronucleus-staged embryos and are not involved in the genomic demethylation of early zygotes. Here, we investigated the influence of Tet1 and Tet2 on methylation of parental genomes by ectopically expressing Tet1 and Tet2 in zygotes. Immunofluorescence staining showed a marked 5hmC increase in the maternal pronucleus after injection of Tet1 or Tet2 mRNA into zygotes. Whole-genome bisulfite sequencing further revealed that Tet2 greatly enhanced the global demethylation of both parental genomes, while Tet1 only promoted the paternal demethylation. Tet1 and Tet2 overexpression altered the DNA methylation across genomes, including various genic elements and germline-specific differently methylated regions. Tet2 exhibited overall stronger demethylation activity than Tet1. Either Tet1 or Tet2 overexpression impaired preimplantation embryonic development. These results demonstrated that early expression of Tet1 and Tet2 could substantially alter the zygotic methylation landscape and damage embryonic development. These findings provide new insights into understanding the function of Tet dioxygenases and the mechanism of DNA methylation in relation to embryogenesis.     

基于依赖矩阵的构件软件复杂性的度量模型

目前的构件软件复杂性度量模型未考虑构件之间不同依赖关系和软件构件内部复杂性两个重要因素,度量结果不够完整、准确.针对该问题,通过将软件体系结构抽象为加权的有向图,获得构件之间的依赖矩阵和影响矩阵,进而获取复杂性的度量公式.从度量公式分析和最后的示例可以得出,该度量模型可以更加真实、准确地反映构件之间不同的依赖关系和构件内部复杂性对软件复杂性的影响,而且具有简单、易于实现等特点.     

Low-latency and low-overhead encoder ASIC in the ATLAS LAr calorimeter trigger upgrade

In this article, an encoder Application Specific Integrated Circuit (ASIC) for high-speed serial data transmission is presented. The ASIC implements a low-latency and low-overhead line code and is fabricated with a commercial 0.25-µm Silicon-on-Sapphire CMOS technology. The ASIC operates at 640 MHz with a latency of no greater than 6.25 ns and the overhead of 14.3%. The encoder will be integrated with a serialiser and will be used in the A Toroidal LHC ApparatuS Liquid Argon (LAr) calorimeter Phase-I trigger upgrade.     

Fermi-Level Pinning in Nanocrystal Memories

The nanocrystal (NC) work-function engineering, which plays an important role on the NC memory characteristics such as memory window and retention time, were long regarded as a matter of choice on NC materials. In this letter, we report opposite polarities of charge storage in Au NC memories with different control oxides. The effective NC work function is found to be not only a bulk property of the NC, but also governed by the interface with surrounding dielectric, as a result of the Fermi-level pinning. By replacing Au NCs with C₆₀ molecules, we also show the pinning effect generally exists at quantum-dot-based devices with high density of interface states. This fundamental interface property should be taken into account in the selection of NC and dielectric materials for the NC memory optimization     

In situ synchrotron X-ray diffraction analysis of deformation behavior of a Nb/NiTi composite for biomedical applications

The deformation behavior involved in Nb/NiTi composite for biomedical applications within a large macroscopic strain range was investigated by tensile loading-unloading test and in situ synchrotron X-ray diffraction(SXRD).Experimental results show that during loading,the Nb/NiTi composite experiences the elastic elongation of B2-NiTi austenitic,B19'-NiTi martensitic and β-Nb phases,B2→ B19' stress-induced martensitic(SIM) transformation and tensile plastic deformation of β-Nb phase.During unloading,the deformation behavior involved in Nb/NiTi composite includes the elastic recovery of B2-NiTi austenitic,B19'-NiTi martensitic and β-Nb phases,reverse phase transformation B19'→B2 and compressive deformation of p-Nb phase.The martensitic transformation in this composite is almost reversible and occurs in a localized manner.These results might contribute to a comprehensive understanding of the deformation mechanism involved in Nb/NiTi composite and shed some light on design and development of novel composites with a combination of good biocompatibility and excellent superelasticity for biomedical applications.     

Maternal Prenatal Inflammation Increases Brain Damage Susceptibility of Lipopolysaccharide in Adult Rat Offspring via COX-2/PGD-2/DPs Pathway Activation

A growing body of research suggests that inflammatory insult contributes to the etiology of central nervous system diseases, such as depression, Alzheimer’s disease, and so forth. However, the effect of prenatal systemic inflammation exposure on offspring brain development and cerebral susceptibility to inflammatory insult remains unknown. In this study, we utilized the prenatal inflammatory insult model in vivo and the neuronal damage model in vitro. The results obtained show that prenatal maternal inflammation exacerbates LPS-induced memory impairment, neuronal necrosis, brain inflammatory response, and significantly increases protein expressions of COX-2, DP2, APP, and Aβ, while obviously decreasing that of DP1 and the exploratory behaviors of offspring rats. Meloxicam significantly inhibited memory impairment, neuronal necrosis, oxidative stress, and inflammatory response, and down-regulated the expressions of APP, Aβ, COX-2, and DP2, whereas significantly increased exploring behaviors and the expression of DP1 in vivo. Collectively, these findings suggested that maternal inflammation could cause offspring suffering from inflammatory and behavioral disorders and increase the susceptibility of offspring to cerebral pathological factors, accompanied by COX-2/PGD-2/DPs pathway activation, which could be ameliorated significantly by COX-2 inhibitor meloxicam treatment.     

Sogatella furcifera Saliva Mucin-like Protein Is Required for Feeding and Induces Rice Defences

The white-backed planthopper (WBPH), Sogatella furcifera, is one of the most important piercing-sucking pests of rice (Oryza sativa) in Asia. Mucin-like salivary protein (SFMLP) is highly expressed in the salivary glands of WBPH, which plays an important role in WBPH feeding. In this study, WBPH injected with dsSFMLP had difficulty in sucking phloem sap from rice plants, which significantly reduced their food intake, weight, and survival. In contrast, the knockdown of the SFMLP gene had only a marginal effect on the survival of WBPH fed an artificial diet. Further studies showed that silencing SFMLP resulted in the short and single-branched salivary sheaths secretion and less formation of salivary flanges in rice. These data suggest that SFMLP is involved in the formation of the salivary sheath and is essential for feeding in WBPH. Overexpression of the SFMLP gene in rice plants promoted the feeding of WBPH, whereas silencing the gene in rice plants significantly decreased WBPH performance. Additionally, it was found that overexpression of SFMLP in rice plants elicited the signalling pathway of SA (salicylic acid) while suppressing JA (jasmonic acid); in contrast, silencing of the SFMLP gene in rice plants showed the opposite results. This study clarified the function of SFMLP in WBPH feeding as well as mediating rice defences.