自动铟封设备及其控制系统

铟封是一种重要的软金属封接方法,陀螺的玻璃腔体和金属电极采用铟封,实现谐振腔的真空。目前铟封多采用手工操作,较难实现铟环、电极和腔体孔的对准,且封接一致性差,因此本课题研制自动铟封设备,实现铟环和电极与腔体孔的自动对准放置,并施加温度和封接力。本文利用温度控制器、加热棒、Pt电阻设计了温度闭环控制系统,采用位移-力控制策略,通过控制热压头的位移,结合系统刚度,实现了压封力的稳定控制。实验表明,设备的温度控制最大偏差小于±0.3℃,压封力控制偏差小于9 N。

The novel chalcone analog L2H17 protects retinal ganglion cells from oxidative stress-induced apoptosis

Chalcone is a plant metabolite widely found in fruits,vegetables,spices and tea,and has anti-tumor,anti-inflammation,immunomodulation,antibacterial and anti-oxidation activities,as well as many other pharmacological and biological effects.Our team has shown that its analogs have antioxidant activity,and oxidative stress is a pathological hallmark of retinal ischemia/reperfusion injury that can lead to retinal damage and visual loss.This investigation aims to identify a chalcone that protects retinal ganglion cells in vitro from the effects of oxidative stress and examine its mechanism.Rat retinal ganglion cell-5 cells were pretreated with chalcones and then exposed to tert-butyl hydroperoxide that causes oxidative damage.Controls received dimethyl sulfoxide only or tert-butyl hydroperoxide in dimethyl sulfoxide.Only（E）-3,4-dihydroxy-2′-methylether ketone（L2 H17）,of the five chalcone analogs,markedly increased the survival rate of oxidatively injured RGC-5 cells.Thus,subsequent experiments only analyzed the results of the L2 H17 intervention.Cell viability and apoptosis were measured.Intracellular superoxide dismutase and reactive oxygen species levels were used to assess induced oxidative stress.The mechanism of action by L2 H17 was explored by measuring the ER stress/UPR pathway and the expression and localization of Nrf2.All results demonstrated that L2 H17 could reduce the apoptosis of oxidatively injured cells,inhibit caspase-3 activity,increase Bcl-2 expression,decrease Bad expression,increase the activity of superoxide dismutase,inhibit the production of reactive oxygen species,increase Nrf2 immunoreactivity,and reduce the activating transcription factor 4,phospho-eukaryotic initiation factor 2 and CHOP expression.L2 H17 protects retinal ganglion cells induced by oxidative stress by regulating Nrf2,which indicates that it has the potential to become a drug for retinal ischemia/reperfusion.

聚脲涂层改善路面疏水抗冻性能的试验研究

为了解决冬季道路结冰所导致的行车安全问题,本研究采用了一种新型涂料聚豚(PU)用以改善路面的疏水性和抗冻性,从而缓解行车安全问题。本文采用接触角试验研究聚豚涂层的疏水性,采用水滴凝结时间试验、钢球去冰试验和冰/路层间剪切试验研究聚豚涂层路面的抗冰性能,采用湿轮磨耗试验研究聚豚涂层路面的耐磨耗性能,采用铺砂法、英国摆锤试验机法及AMES激光纹理扫描仪测试聚豚涂层路面的抗滑性。试验结果表明,聚豚涂层可以提高路面的疏水性,抗冻性和耐磨性,但路面抗滑性能略有下降,喷涂质量为聚豚质量10%的石英砂则可以恢复路面的部分纹理特征。此种技术方法对于提高冬季行车安全性有重要意义。

Hyperglycemia activates FGFR1 via TLR4/c-Src pathway to induce inflammatory cardiomyopathy in diabetes

Protein tyrosine kinases (RTKs) modulate a wide range of pathophysiological events in several non-malignant disorders, including diabetic complications. To find new targets driving the development of diabetic cardiomyopathy (DCM), we profiled an RTKs phosphorylation array in diabetic mouse hearts and identified increased phosphorylated fibroblast growth factor receptor 1 (p-FGFR1) levels in cardiomyocytes, indicating that FGFR1 may contribute to the pathogenesis of DCM. Using primary cardiomyocytes and H9C2 cell lines, we discovered that high-concentration glucose (HG) transactivates FGFR1 kinase domain through toll-like receptor 4 (TLR4) and c-Src, independent of FGF ligands. Knocking down the levels of either TLR4 or c-Src prevents HG-activated FGFR1 in cardiomyocytes. RNA-sequencing analysis indicates that the elevated FGFR1 activity induces pro-inflammatory responses via MAPKs–NFκB signaling pathway in HG-challenged cardiomyocytes, which further results in fibrosis and hypertrophy. We then generated cardiomyocyte-specific FGFR1 knockout mice and showed that a lack of FGFR1 in cardiomyocytes prevents diabetes-induced cardiac inflammation and preserves cardiac function in mice. Pharmacological inhibition of FGFR1 by a selective inhibitor, AZD4547, also prevents cardiac inflammation, fibrosis, and dysfunction in both type 1 and type 2 diabetic mice. These studies have identified FGFR1 as a new player in driving DCM and support further testing of FGFR1 inhibitors for possible cardioprotective benefits.

Therapeutic potential of targeting protein tyrosine phosphatases in liver diseases

Protein tyrosine phosphorylation is a post-translational modification that regulates protein structure to modulate demic organisms’homeostasis and function.This physiological process is regulated by two enzyme families,protein tyrosine kinases(PTKs)and protein tyrosine phosphatases(PTPs).As an important regulator of protein function,PTPs are indispensable for maintaining cell intrinsic physiology in different systems,as well as liver physiological and pathological processes.Dysregulation of PTPs has been implicated in multiple liver-related diseases,including chronic liver diseases(CLDs),hepatocellular carcinoma(HCC),and liver injury,and several PTPs are being studied as drug therapeutic targets.Therefore,given the regulatory role of PTPs in diverse liver diseases,a collated review of their function and mechanism is necessary.Moreover,based on the current research status of targeted therapy,we emphasize the inclusion of several PTP members that are clinically significant in the development and progression of liver diseases.As an emerging breakthrough direction in the treatment of liver diseases,this review summarizes the research status of PTP-targeting compounds in liver diseases to illustrate their potential in clinical treatment.Overall,this review aims to support the development of novel PTP-based treatment pathways for liver diseases.

Costunolide covalently targets NACHT domain of NLRP3 to inhibit inflammasome activation and alleviate NLRP3-driven inflammatory diseases

The NLRP3 inflammasome’s core and most specific protein,NLRP3,has a variety of functions in inflammation-driven diseases.Costunolide(COS)is the major active ingredient of the traditional Chinese medicinal herb Saussurea lappa and has anti-inflammatory activity,but the principal mechanism and molecular target of COS remain unclear.Here,we show that COS covalently binds to cysteine 598 in NACHT domain of NLRP3,altering the ATPase activity and assembly of NLRP3 inflammasome.We declare COS’s great anti-inflammasome efficacy in macrophages and disease models of gouty arthritis and ulcerative colitis via inhibiting NLRP3 inflammasome activation.We also reveal that theα-methylene-γ-butyrolactone motif in sesquiterpene lactone is the certain active group in inhibiting NLRP3 activation.Taken together,NLRP3 is identified as a direct target of COS for its anti-inflammasome activity.COS,especially theα-methylene-γ-butyrolactone motif in COS structure,might be used to design and produce novel NLRP3 inhibitors as a lead compound.

FGF1^(△HBS) prevents diabetic cardiomyopathy by maintaining mitochondrial homeostasis and reducing oxidative stress via AMPK/Nur77 suppression

As a classically known mitogen,fibroblast growth factor 1(FGF1)has been found to exert other pleiotropic functions such as metabolic regulation and myocardial protection.Here,we show that serum levels of FGF1 were decreased and positively correlated with fraction shortening in diabetic cardiomyopathy(DCM)patients,indicating that FGF1 is a potential therapeutic target for DCM.We found that treatment with a FGF1 variant(FGF1^(△HBS))with reduced proliferative potency prevented diabetes-induced cardiac injury and remodeling and restored cardiac function.RNA-Seq results obtained from the cardiac tissues of db/db mice showed significant increase in the expression levels of anti-oxidative genes and decrease of Nur77 by FGF1AHBS treatment.Both in vivo and in vitro studies indicate that FGF1^(△HBS) exerted these beneficial effects by markedly reducing mitochondrial fragmentation,reactive oxygen species(ROS)generation and cytochrome c leakage and enhancing mitochondrial respiration rate and β-oxidation in a 5;AMP-activated protein kinase(AMPK)/Nur77-dependent manner,all of which were not observed in the AMPK null mice.The favorable metabolic activity and reduced proliferative properties of FGF1^(△HBS) testify to its promising potential for use in the treatment of DCM and other metabolic disorders.