Drugs Targeting the A3 Adenosine Receptor: Human Clinical Study Data

The A3 adenosine receptor (A3AR) is overexpressed in pathological human cells. Piclidenoson and namodenoson are A3AR agonists with high affinity and selectivity to A3AR. Both induce apoptosis of cancer and inflammatory cells via a molecular mechanism entailing deregulation of the Wnt and the NF-κB signaling pathways. Our company conducted phase I studies showing the safety of these 2 molecules. In the phase II studies in psoriasis patients, piclidenoson was safe and demonstrated efficacy manifested in significant improvements in skin lesions. Namodenoson is currently being developed to treat liver cancer, where prolonged overall survival was observed in patients with advanced liver disease and a Child–Pugh B score of 7. A pivotal phase III study in this patient population has been approved by the FDA and the EMA and is currently underway. Namodenoson is also being developed to treat non-alcoholic steatohepatitis (NASH). A Phase IIa study has been successfully concluded and showed that namodenoson has anti-inflammatory, anti-fibrosis, and anti-steatosis effects. A phase IIb study in NASH is currently enrolling patients. In conclusion, A3AR agonists are promising drug candidates in advanced stages of clinical development and demonstrate safety and efficacy in their targeted indications.     

前驱体法制备氮氧化硅纳米线及其光学性能研究

在Ni催化剂的存在下,通过SiCl4的水解氨解反应并在1300℃氨气气氛中进行热氮化处理制得了无定形氮氧化硅纳米线.产物经X射线衍射(XRD)、热重-差示扫描量热(TG-DSC)、扫描电镜(SEM)、透射电镜(TEM)、能量色散谱(EDS)和选区电子衍射(SAED)等表征手段进行分析,结果表明纳米线为无定形结构,直径为100～150nm.在波长为220nm的光激发下,产物的光致发光光谱(PL)在563nm和289nm处分别出现了一个强的绿光发光峰和一个弱的紫光发光峰.对纳米线的生长机理进行分析,表明纳米线的生长遵循气-液-固(VLS)机制控制模式.     

Cu3N薄膜及其研究现状

Cu3N薄膜是近10年来研究的热点材料之一.Cu3N是立方反ReO3结构,理想立方反ReO3结构的一个晶胞中Cu原子占据立方边的中心位置而N原子占据立方晶胞的八个顶点,此结构的体心位置有一较大间隙,Cu原子以及其他原子如Pd、碱金属原子等很有可能进入此位置导致Cu3N的电学性能、光学性能等发生很大的变化,这使得该材料具有很大的潜在应用价值.Cu3N的晶格常数为0.3815nm,密度5.84g/cm3,分子量204.63,颜色呈黑绿色或红褐色,空间点群Pm3m.Cu3N薄膜在室温下相当稳定并且热分解温度较低(300℃左右),热分解前后薄膜的光学反射率有较大差别,这可使Cu3N薄膜用作一次性光记录材料.此外,Cu3N薄膜还可用作在Si片上沉积金属Cu线的缓冲层、低磁阻隧道结的阻挡层、自组装材料的模板等.     

CTAB与SDBS对碳酸锶粒子生长形态调控及机理研究

以表面活性剂CTAB和SDBS为化学添加剂,采用化学共沉淀法对碳酸锶晶体的生长形态进行调控,成功地制备出了实心的树枝状和花瓣为空心的花状碳酸锶粉体,并用X射线衍射(XRD)、扫描电子显微镜(SEM)和傅里叶变换红外光谱(FT-IR)等分析手段对样品进行了表征;最后重点对化学添加剂可能产生的影响机理进行了初步的探讨.结果表明,CTAB和SDBS在晶体生长的过程中能起到显著的影响作用,两者对粒子分散性能的作用效果相反,而且后者对晶体(013)和(213)晶面表面能降低的贡献明显大于前者.     

Fe3+对KDP晶体光学质量的影响

金属离子Fe3+对KDP晶体的生长和光学性质有明显影响.本文在前期研究的基础上[1]系统考察了该杂质离子对KDP晶体光学质量的影响.实验结果表明,三价金属离子Fe3+会降低KDP晶体的透光率,同时对晶体均匀性和光损伤阈值也有明显影响.光损伤阈值降低的主要原因在于杂质诱发缺陷导致的电子崩电离、多光子电离(尤其是双光子电离)等过程的发生.     

Er3+:NaY(Wo.9Moo.1O4)2晶体的生长及光谱性能

采用提拉法(CZ法),生长出质量良好的Er3+:NaY(W0.9Mo0.1O4)2晶体.通过X射线粉末衍射,红外光谱分析,并与NaY(WO4)2相比较,得到Er3+:NaY(W0.9Mo0.1O4)2晶体的结构与NYW类似,仍为四方晶系的白钨矿结构,I4(1)/α空间群.测定了晶体的实际组成,得到晶体中各元素均按理论值进行掺杂,计算了掺杂离子的分凝系数约为1.15.在光谱性质上,测试了晶体的吸收光谱,及晶体在50～1000cm-1波数范围内的拉曼光谱,并计算了各吸收峰的半峰宽及吸收系数A.     

Comparison of Fatty Acid Contents and MMP-1 Inhibitory Effects of the Two Antarctic Fish,Notothenia rossii and Champsocephalus gunnari

Total fatty-acid (FA) contents of different organs (stomach, liver, brain, and skin) of two Antarctic fish, marbled rockcod (Notothenia rossii) and mackerel icefish (Champsocephalus gunnari), were examined using gas chromatography–mass spectrometry (GC–MS). N. rossii possessed higher contents of total omega-3, where eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), the most represented omega-3 FAs, were distributed throughout all parts of the fish. The highest level of EPA was observed in the skin and that of DHA was observed in the brain of N. rossii. C. gunnari showed organ peculiarity in that most of the omega-3 FAs were found in stomach and skin. Specifically, the highest levels of EPA and DHA were both observed in the stomach. Although N. rossii and C. gunnari both inhabit the Antarctic Southern Oceans, their characteristics in terms of the composition of fatty acids were shown to vary. The extracts were also evaluated for matrix metalloproteinase-1 (MMP-1)-inhibitory activities in UVB-induced human dermal fibroblasts, where extracts of the skin and liver of N. rossii showed the most significant inhibition upon MMP-1 production. These findings provide experimental evidence that the extracts of the Antarctic fish could be utilized as bioactive nutrients, particularly in the enhancement of skin health.     

The Small Molecule PPARγ Agonist GL516 Induces Feeding-Stimulatory Effects in Hypothalamus Cells Hypo-E22 and Isolated Hypothalami

PPARγ agonists are implicated in the regulation of diabetes and metabolic syndrome and have therapeutic potential in brain disorders. PPARγ modulates appetite through its central effects, especially on the hypothalamic arcuate nucleus (ARC). Previous studies demonstrated that the small molecule GL516 is a PPARγ agonist able to reduce oxidative stress and apoptosis with a potential neuroprotective role. Herein, we investigated the effects of GL516, in vitro and ex vivo, on the levels of hypothalamic dopamine (DA) and serotonin (5-HT). The gene expressions of neuropeptide Y, CART, AgRP, and POMC, which play master roles in the neuroendocrine regulation of feeding behavior and energy balance, were also evaluated. HypoE22 cells were treated with H₂O₂ (300 μM) for 2 h e 30’ and with different concentrations of GL516 (1 nM-100 µM). The cell viability was evaluated after 24 and 48 h of culturing using the MTT test. DA and 5-HT levels in the HypoE22 cell supernatants were analyzed through HPLC; an ex vivo study on isolated hypothalamic specimens challenged with scalar concentrations of GL516 (1–100 µM) and with pioglitazone (10 µM) was carried out. The gene expressions of CART, NPY, AgRP, and POMC were also determined by a quantitative real-time PCR. The results obtained showed that GL516 was able to reduce DA and 5-HT turnover; moreover, it was effective in stimulating NPY and AgRP gene expressions with a concomitant reduction in CART and POMC gene expressions. These results highlight the capability of GL516 to modulate neuropeptide pathways deeply involved in appetite control suggesting an orexigenic effect. These findings emphasize the potential use of GL516 as a promising candidate for therapeutical applications in neurodegenerative diseases associated with the reduction in food intake and stimulation of catabolic pathways.     

氟化铟基玻璃中Er^3＋离子光谱性质的研究

测定了掺Ｅｒ＾３＋氟化铟基玻璃的吸收光谱，激发光谱和荧光光谱，计算了该玻璃的强度参数Ω（ｔ＝２，４，６），给出了Ｅｒ＾３＋离子的发光特性的计算结果，并与掺Ｅｒ＾３＋的氟锆酸盐玻璃做比较，解释了基质玻璃对Ｅｒ＾３＋离子发光特性的影响。