Novel rhino-like SHJH^(hr) mice with thyroid dysfunction

A new Hairless(Hr)gene mutant mouse line(SHJH^(hr))was identified,which showed hairless skin in adult individuals as reported in rhino mice.Through Hr gene mutant identification with polymerase chain reaction(PCR)amplification and sequencing,seven mutants were identified,including nonsense mutant site 2134C→T(R467X),which produced a truncated Hr protein.Metabolic activity and heart rate were measured using a metabolic cage and blood pressure instrument,respectively.The SHJH^(hr) mice showed a strong metabolic rate,high heart rate,and low blood pressure.Histological analysis of the thyroid gland of SHJH^(hr) mice showed abnormal follicular structure and hypertrophic thyrocytes.Compared to ICR mice,thyroid function in 4-month-old SHJH^(hr) mice showed lower thyroid stimulating hormone(TSH)levels,and in 9-month-old SHJH^(hr) mice showed significantly higher TSH and thyroid hormone levels.These data indicate that SHJH^(hr) mice may be in a hyperthyroid state with increasing age.Thus,based on the above results,we successfully established a novel mouse model with thyroid dysfunction.

Translocator protein ligand, YL-IPA08, attenuates lipopolysaccharide-induced depression-like behavior by promoting neural regeneration

Translocator protein has received attention for its involvement in the pathogenesis of depression. This study assessed the effects of the new translocator protein ligand, YL-IPA08, on alleviating inflammation-induced depression-like behavior in mice and investigated its mechanism of action. Mice were intracerebroventricularly injected with 1, 10, 100 or 1000 ng lipopolysaccharide. The tail-suspension test and the forced swimming test confirmed that 100 ng lipopolysaccharide induced depression-like behavior. A mouse model was then established by intraventricular injection of 100 ng lipopolysaccharide. On days 16-24 after model establishment, mice were intragastrically administered 3 mg/kg YL-IPA08 daily. Immunohistochemistry was used to determine BrdU and NeuN expression in the hippocampus. YL-IPA08 effectively reversed the depression-like behavior of lipopolysaccharide-treated mice, restored body mass, increased the number of BrdU-positive cells, and the number and proportion of BrdU and NeuN double-positive cells. These findings indicate that YL-IPA08 can attenuate lipopolysaccharide-induced depression-like behavior in mice by promoting the formation of hippocampal neurons.

New material of Coniopteris simplex from the Middle Jurassic of the Ordos Basin,Inner Mongolia,China and implications on its spatio-temporal distribution and paleogeography

Coniopteris simplex is a common component in many Jurassic floras.However,due to morphological variations in sterile fronds and incomplete preservation of reproductive organs,its classification has been controversial for a long time.Here,we present new material collected from the Middle Jurassic Yan’an Formation in the Ordos Basin,Inner Mongolia.The new material reveals important morphological characters,including hemi-dimorphic fronds,two forms of sterile pinnae,short-stalked sori and sporangia on fertile fronds,annulus of sporangium composed of about 30 cells,in situ rounded triangular spores with protruded suture,and the lips of trilete laesura encircled by one or two rows of small ostioles.Based on these observations,we emended the diagnosis of this common species.The spatio-temporal distribution of Coniopteris simplex shows that the iconic species was restricted to the paleolatitudes ranging from 19.5°N to 48.9°N in the Northern Hemisphere during the Early—Late Jurassic,mainly distributed in the tropical to paratropical zones,and the paleolongitude ranging from 9.6°E to 129.3°E,which may be limited by the opening of the Viking Corridor and the splitting of the Central Atlantic Ocean.

Surface properties of superfine alumina trihydrate after surface modification with stearic acid

The surface properties of superfine alumina trihydrate （ATH） after surface modification were studied by measuring the contact angle, active ratio, oil adsorption, total organic carbon, adsorption ratio, and Fourier transform infrared （FTIR） spectrum. The contact angle increased initially and then slowly decreased with an increase of the amount of stearic acid. However, the surface flee energy decreased ini- tially and then increased. Surface modification with stearic acid or sodium stearate can benefit from elevating temperature. The base surface tension component and the free energy of Lewis acid-base both declined sharply following the surface modification. Excess stearic acid was physically adsorbed in the form of multilayer adsorption, and an interaction between oxygen on the ATH surface and hydroxyl in stearic acid was subsequently determined. Our results further indicated that the contact angle and adsorption ratio can be used as control indicators for surface modification compared with active ratio, oil adsorption and total organic carbon.

Elevated Neurosteroids in the Lateral Thalamus Relieve Neuropathic Pain in Rats with Spared Nerve Injury

Neurosteroids are synthesized in the nervous system from cholesterol or steroidal precursors imported from peripheral sources. These compounds are important allosteric modulators of γ-aminobutyric acid A receptors （GABAARs）, which play a vital role in pain modulation in the lateral thalamus, a main gate where somatosensory information enters the cerebral cortex. Using high-perfor mance liquid chromatography/tandem mass spectrometry, we found increased levels of neurosteroids （pregnenolone, progesterone, deoxycorticosterone, allopregnanolone, and tetrahydrodeoxycorticosterone） in the chronic stage of neuropathic pain （28 days after spared nerve injury） in rats.The expression of the translocator protein TSPO, the upstream steroidogenesis rate-limiting enzyme, increased at the same time. In vivo stereotaxic microinjection of neurosteroids or the TSPO activator AC-5216 into the lateral thalamus （AP -3.0 mm, ML 4-3.0 mm, DV 6.0 mm） alleviated the mechanical allodynia in neuropathic pain, while the TSPO inhibitor PK 11195 exacerbated it. The analgesic effects of AC-5216 and neurosteroids were sig- nificantly attenuated by the GABAAR antagonist bicuculline. These results suggested that elevated neurosteroids in the lateral thalamus play a protective role in the chronic stage of neuropathic pain.

Simplified aminocoumarin analogues as anticancer agents:Amino isosteric replacement in the noviose moiety resulted in substantial enhancement of antiproliferative activity

Simplified aminocoumarin analogues,either noviosylated or simple basic heterocycle attached 3-amido-coumarin compounds,are known to be promising anticancer agents targeting the C-terminal ATP-binding site of Hsp90.In this study,3＇-amino isosteric replacement in the noviose moiety of two known noviose containing Hsp90 C-terminal inhibitors was synthetically realized for the first time.In vitro evaluation of these compounds suggested that the introduction of a basic amino group into the noviose subunit resulted in significant improvement of their cytotoxicities.

间甲钴黏合体系在轮胎骨架材料中的黏合机理研究

为验证与进一步探索黏合树脂及钴盐对轮胎与镀铜钢丝帘线的增黏作用机理,选取传统黏合树脂R80与2种新型黏合树脂HT1005和H620,通过对2种新型黏合树脂的结构分析、橡胶硫化特性、静态T抽出测试与力学性能测试,并设计了一种新的黏合层强度测试方法与黏合层表征方法,进行机理探索,得出如下结论:含有羟基的极性黏合树脂在橡胶硫化时,会由于与非极性天然橡胶的极性差异产生的热力学不相容从而产生自动相分离,向橡胶与镀铜钢丝的界面层进行迁移汇集,且极性越高迁移能力越强,产生一个介于橡胶与镀铜钢丝之间的树脂富集层.因为黏合树脂交联反应温度为140℃左右,会在天然橡胶硫化反应时发生同步交联反应,黏合树脂形成的网络模量高于橡胶硫化网络,会增强镀铜钢丝与橡胶之间的黏合层强度,并形成一个镀铜钢丝与橡胶之间的模量过渡层,进一步增强黏合层.且极性越强,树脂网络交联程度与橡胶硫化网络交联程度越接近,增黏效果越好;钴盐会活化橡胶中的S,使更多的S迁移到镀铜钢丝表面从生成更多硫化亚铜键,增强黏合.

Effect of Slab Subsurface Microstructure Evolution on Transverse Cracking of Microalloyed Steel during Continuous Casting

As to the continuous casting process of low carbon microalloyed steel, subsurface microstructure evolution plays an important role in the slab surface cracking. In order to study the effect of the slab subsurface microstructure evolution on the transverse cracking, three different secondary cooling patterns （i. e. , mild cooling, strong cooling and controlled cooling） were performed in the corresponding slab curved continuous caster. Based on the metallo- graphic results, three transformation regions were found to be formed with the evolution of microstructures at different depths in the slab subsurface. The three regions are strong cooling transformation （SCT） region, double phase transformation （DPT） region and mild cooling transformation （MCT） region, respectively. Meanwhile, it was also found that the crack index used for evaluating slab surface cracking susceptibility was decreased when the range of the DPT region was increased. This can be explained by the fact that the double phase transformation （austenite-ferrite-austenite） occurred resulting from thermal cycling in DPT region, which resulted in promoting the refinement of prior austenite grains and inhibiting the precipitation of film-like ferrite and chain-like precipitates. Under the con- trolled cooling pattern, the widely-distributed DPT region was formed in the range of 3.5--8.0 mm to the slab surface. And compared with other cooling patterns, the cracking susceptibility is lowest with a crack index of 0.4.

Inhibition of Ubiquitin-specific Peptidase 8 Suppresses Adrenocorticotropic Hormone Production and Tumorous Corticotroph Cell Growth in AtT20 Cells

Background： Two recent whole-exome sequencing researches identifying somatic mutations in the ubiquitin-specific protease 8 （USP8） gene in pituitary corticotroph adenomas provide exciting advances in this field. These mutations drive increased epidermal growth factor receptor （EGFR） signaling and promote adrenocorticotropic hormone （ACTH） production. This study was to investigate whether the inhibition of USP8 activity could be a strategy/br the treatment of Cushing＇s disease （CD）. Methods： The anticancer effect of USP8 inhibitor was determined by testing cell viability, colony tbrmation, apoptosis, and ACTH secretion. The immunoblotting and quantitative reverse transcription polymerase chain reaction were conducted to explore the signaling pathway by USP8 inhibition. Results： Inhibition of USP8-induced degradation of receptor tyrosine kinases including EGFR, EGFR-2 （ERBB2）, and Met leading to a suppression of ArT20 cell growth and ACTH secretion. Moreover, treatment with USP8 inhibitor markedly induced AtT20 cells apoptosis. Conclusions： Inhibition of USP8 activity could be an effective strategy for CD. It might provide a novel pharmacological approach for the treatment of CD.