基于midas Gen的单层球形网壳结构分析及应用研究

基于midas Gen软件模型,在不同应力比下对实体工程金属网壳模型进行分析,获得了工程实体金属网壳模型静力荷载下铸钢铰支座反力、罕遇地震时铸钢铰支座反力、静力荷载销轴反力、罕遇地震销轴反力分布情况。将设计模型得到的实体工程金属网壳荷载–位移曲线与有关设计模型网壳荷载–位移曲线进行对比,通过实体工程金属网壳模型设计实例,分析了不同应力下的杆件位移情况,从而证明了实体工程金属网壳模型设计的准确性及合理性。

Genipin relieves diabetic retinopathy by down-regulation of advanced glycation end products via the mitochondrial metabolism related signaling pathway

BACKGROUND Glycation is an important step in aging and oxidative stress,which can lead to endothelial dysfunction and cause severe damage to the eyes or kidneys of diabetics.Inhibition of the formation of advanced glycation end products(AGEs)and their cell toxicity can be a useful therapeutic strategy in the prevention of diabetic retinopathy(DR).Gardenia jasminoides Ellis(GJE)fruit is a selective inhibitor of AGEs.Genipin is an active compound of GJE fruit,which can be employed to treat diabetes.AIM To confirm the effect of genipin,a vital component of GJE fruit,in preventing human retinal microvascular endothelial cells(hRMECs)from AGEs damage in DR,to investigate the effect of genipin in the down-regulation of AGEs expression,and to explore the role of the CHGA/UCP2/glucose transporter 1(GLUT1)signal pathway in this process.METHODS In vitro,cell viability was tested to determine the effects of different doses of glucose and genipin in hRMECs.Cell Counting Kit-8(CCK-8),colony formation assay,flow cytometry,immunofluorescence,wound healing assay,transwell assay,and tube-forming assay were used to detect the effect of genipin on hRMECs cultured in high glucose conditions.In vivo,streptozotocin(STZ)induced mice were used,and genipin was administered by intraocular injection(IOI).To explore the effect and mechanism of genipin in diabetic-induced retinal dysfunction,reactive oxygen species(ROS),mitochondrial membrane potential(MMP),and 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose(2-NBDG)assays were performed to explore energy metabolism and oxidative stress damage in high glucose-induced hRMECs and STZ mouse retinas.Immunofluorescence and Western blot were used to investigate the expression of inflammatory cytokines[vascular endothelial growth factor(VEGF),SCG3,tumor necrosis factor-alpha(TNF-α),interleukin(IL)-1β,IL-18,and nucleotide-binding domain,leucine-rich-containing family,pyrin domain-containing 3(NLRP3)].The protein expression of the receptor of AGEs(RAGE)and the mitochondria-related signal molecules CHGA,GLUT1,and UCP2 in high glucose-induced hRMECs and STZ mouse retinas were measured and compared with the genipin-treated group.RESULTS The results of CCK-8 and colony formation assay showed that genipin promoted cell viability in high glucose(30 mmol/L D-Glucose)-induced hRMECs,especially at a 0.4μmol/L dose for 7 d.Flow cytometry results showed that high glucose can increase apoptosis rate by 30%,and genipin alleviated cell apoptosis in AGEs-induced hRMECs.A high glucose environment promoted ATP,ROS,MMP,and 2-NBDG levels,while genipin inhibited these phenotypic abnormalities in AGEs-induced hRMECs.Furthermore,genipin remarkably reduced the levels of the pro-inflammatory cytokines TNF-α,IL-1β,IL-18,and NLRP3 and impeded the expression of VEGF and SCG3 in AGEs-damaged hRMECs.These results showed that genipin can reverse high glucose induced damage with regard to cell proliferation and apoptosis in vitro,while reducing energy metabolism,oxidative stress,and inflammatory injury caused by high glucose.In addition,ROS levels and glucose uptake levels were higher in the retina from the untreated eye than in the genipin-treated eye of STZ mice.The expression of inflammatory cytokines and pathway protein in the untreated eye compared with the genipin-treated eye was significantly increased,as measured by Western blot.These results showed that IOI of genipin reduced the expression of CHGA,UCP2,and GLUT1,maintained the retinal structure,and decreased ROS,glucose uptake,and inflammation levels in vivo.In addition,we found that SCG3 expression might have a higher sensitivity in DR than VEGF as a diagnostic marker at the protein level.CONCLUSION Our study suggested that genipin ameliorates AGEs-induced hRMECs proliferation,apoptosis,energy metabolism,oxidative stress,and inflammatory injury,partially via the CHGA/UCP2/GLUT1 pathway.Control of advanced glycation by IOI of genipin may represent a strategy to prevent severe retinopathy and vision loss.

药物检测机构营销策略研究——以GEN公司为例

当下处于经济迅速复苏的后疫情时代,政府及人民对于药物安全性提出了更高要求,而当前市场中存在大量的药物公司,其运营过程中需要药物检测企业的深度参与。随着药品研发环境的不断发展变化,药物检测机构作为新兴的社会力量在社会活动中的角色越来越重要。文章基于案例实证分析的研究思路,以GEN公司为研究对象,客观分析其所面对的宏观及微观环境,明晰当下的可利用优势及市场机遇,制定合理可行的实施计划及相适应的职能策略。文章的主要研究目标是通过对GEN公司自身运营资源、技术能力、市场环境等情况的剖析,充分发挥自身优势,有效规避市场风险,建立健全企业管理体系,优化内部运行机制,为企业的运营管理充分赋能,提升药物检测企业的核心竞争能力,助力企业实现高质量经营发展。目前,我国药物检测认证企业尚处于高速发展阶段,GEN公司当前所面临的问题具有一定的代表性,文章研究讨论的意见及观点既能对GEN公司的经营管理产生有效促进作用,亦对药物市场上的多数同质公司有一定的参考借鉴意义。

基于BIM的Midas Gen钢结构有限元分析

目前,BIM模型参与有限元分析的实际案例相对较少,因此,急需解决通过结合BIM和有限元分析进行应用的问题。本文主要基于BIM和Midas Gen对钢结构设计安全性能进行有限元分析研究,首先,通过对本工程钢结构的材料进行构件属性定义;其次,使用BIM软件Revit将兼职建筑信息模型导入Midas Gen,根据实际工程条件定义设计参数,并说明结构的荷载定义及边界条件;再次,通过有限元软件Midas Gen分别对钢结构进行静力分析和动力分析,获取结构的应力和变形结果;最后,得出结构最大应力为192.4 MPa,最大位移数值为14.8 mm,均满足规范要求。

Midas Gen在输水工程水池结构计算中的应用

为解决输水工程大型水池结构计算适用性问题,结合工程实例,采用通用有限元软件Midas Gen对某工程高位水池进行有限元分析,建立高位水池整体分析模型,得到高位水池在各种荷载工况及荷载组合下的变形及内力分布结果。针对水池不同部位,分析其水平向和竖直向弯矩,得出弯矩分布规律,用以进行针对性配筋设计。同时,内力结果不至过大,说明高位水池立柱和梁形成的纵、横向框架结构增强了水池的整体性和受力性能,结构体系是合理的。该计算实例可为类似工程设计提供参考。

基于理正与midas Gen的污泥浓缩池结构设计分析

针对计算软件假设条件与实际结构会有出入的问题,以污水处理厂中常见的圆形污泥浓缩池为研究对象,采用midas Gen中的梁、板单元,对其顶面梁及板、池壁、中心部位局部异形锥壳状底板等关键构件建立1∶1有限元模型,以理正与midas Gen计算结果进行内力对比分析,探讨了这两种方式计算结果的实用性,并对污泥浓缩池的结构设计工作提出优化建议。

应用于ICS PCIE Gen2的扩频时钟模块电路

为了满足ICS(internet connection sharing,因特网连接共享)PCIE Gen2协议,可提供输入时钟信号给PC、PCIE桥芯片以及以太网等芯片,利用时钟扩频技术的研究来减少系统的电磁干扰问题。基于应用于ICS PCIE Gen2协议的设计要求,通过采用SMIC 0.18μm工艺设计传统锁相环结构,包括鉴频鉴相器、电荷泵、环路滤波器、环形振荡器、分频器以及相位插值器所设计的扩频时钟模块电路,实现了在满足指标400 MHz输出频率的基础上对扩频深度控制在-5×10-3以内,频谱峰值能量降低了10.32 dB,输出相位噪声在1 MHz频偏下为-107.378 dBc/Hz。未扩频模式下输出时钟的确定性抖动为31.6 ps,周期间RMS抖动为5.1 ps;进行扩频后,周期间RMS抖动为8.6 ps,满足了ICS PCIE Gen2的协议要求。

Genipin对糖尿病小鼠下丘脑细胞凋亡指数及解偶联蛋白2表达的影响

目的探讨genipin对糖尿病小鼠下丘脑细胞凋亡指数(AI)及解偶联蛋白2(UCP2)表达的影响。方法 48只健康雄性小鼠随机分为正常对照组、糖尿病模型组和genipin低、高剂量干预组,每组12只小鼠。采用长期高脂饮食及链脲佐菌素胰岛破坏法建立2型糖尿病小鼠模型。Genipin低、高剂量干预组小鼠分别给予5 mg/(kg.d)、10 mg/(kg.d)的genipin 0.1 ml连续灌胃2周,正常对照组和糖尿病模型组用等量生理盐水替代。分别采用TUNEL染色法和免疫组化染色检测并计算各组小鼠下丘脑AI和UCP2蛋白阳性细胞率;采用实时PCR和Western Blot法检测下丘脑UCP2 mRNA和蛋白的表达水平。结果糖尿病模型组、genipin低剂量和高剂量干预组下丘脑AI明显高于正常对照组(均P<0.05);而genipin低剂量和高剂量干预组下丘脑AI明显低于糖尿病模型组(均P<0.05);且genipin低剂量干预组和genipin高剂量干预组间差异无统计学意义。糖尿病模型组UCP2蛋白阳性细胞率明显高于正常对照组(P<0.05),而genipin低剂量和高剂量干预组UCP2蛋白阳性细胞率均明显低于糖尿病模型组(均P<0.05)。Genipin低剂量和高剂量干预组UCP2 mRNA和蛋白的表达水平均明显低于糖尿病模型组(均P<0.05)。与genipin低剂量干预组比较,geni-pin高剂量干预组UCP2蛋白阳性细胞率、UCP2 mRNA和蛋白的表达水平明显降低(均P<0.05)。结论 Ge-nipin可以减少糖尿病小鼠下丘脑细胞凋亡和UCP2的表达。

基于MIDAS/Gen的自立塔桅结构设计

为提升自立塔桅的结构设计水平,在满足安全的前提下降低自立塔桅的重量,降本增效,对结构的设计要求进一步提高。采用MIDAS/Gen有限元分析软件建模,对自立塔桅结构进行风载荷分析与研究,以供参考与借鉴。

应用MIDAS/GEN辅助“材料力学”课程的教学方法研究

“材料力学”课程在工科专业的课程体系中起着承上启下的作用,由于课程的特点和传统教学方法的不足,无论是教师讲授还是学生学习该课程都会遇到不少的困难。为提高“材料力学”课程的教学、学习效果,利用有限元软件辅助其教学是一条可行的教学方法,有限元软件辅助教学的方法既可以用于课程的理论教学,又可以用于实验教学,并且已有不少学者先后进行了这方面的探索。MIDAS/GEN不仅具有优秀的建模和丰富结果查看功能,并且具有易学、易操作的特点,因此文章以MIDAS/GEN平台探索利用其辅助“材料力学”课程教学,并以具体举例形式说明该辅助教学方法的有益效果。

基于MIDAS Gen的多层钢筋混凝土框架结构倒塌数值模拟分析

汶川地震中大量钢筋混凝土(reinforced concrete,RC)框架结构破坏严重,极震区其倒塌率却远超过多层砖混结构。2022年9月以来,四川频发地震,为重新探讨倒塌机理及抗震性能,本文研究通过实地震害及多层RC框架结构破坏形式,结合数值模型并应用MIDAS Gen有限元计算方法,研究了RC框架结构的倒塌机理、地震响应分析。结果表明:框架柱的破坏与屈服是RC框架倒塌的主要因素,模拟增设填充墙,当地震烈度达到10度时,层间位移角大约1/46,降低柱的轴压比,提高柱的破坏延性,增大结构的极限抗侧能力,起到抗震第一道防线的作用,避免整体屈服破坏。

基于midas Gen的纤绳桅杆在风载荷作用下静力分析

针对纤绳铁塔结构几何非线性的特点,介绍风载荷和铁塔的整体稳定系数,采用midas Gen进行风载荷下的静力分析,并提取数据计算出桅杆和纤绳的安全系数。

Correlation of discoloration and biomechanical properties in porcine sclera induced by genipin

·AIM: To study the feasibility of using the discoloration to evaluate the biomechanical properties after treating with genipin.·METHODS: Porcine cadaver eyes were treated for30 min with 1.0%(by w/v) genipin. Untreated samples were used as controls. After treatment, scleral strips of4.0 ×10.0-mm2 were cut. The denaturation temperature(Td) measurement and stress-strain test were performed after taking photograph to analyze the color.·RESULTS: Within 24 h after treating with genipin, the sclera exhibited a bluish color which became deeper with time. And the denaturation temperature also was increased gradually. Compared with untreated groups, at1, 6, 12, 24 and 36 h after treatment, the ultimate stress were increased by 56%, 153%, 173%, 225% and 211%respectively. The Young’s modulus at 10% strain also increased by 170%, 246%, 264%, 389% and 288%respectively. There were strong correlation between the discoloration and the biomechanical properties(ΔE-Ultimate stress:R2=0.892, P =0.00; ΔE-Young’s modulus:R2=0.602, P =0.00).·CONCLUSION: Genipin could be used to strengthen collagen gradually in a relatively short time span. And the biomechanical properties could be reliably evaluated via simple visible discoloration.

Biomechanics of sclera crosslinked using genipin in rabbit

AIM：To strengthen the biomechanics of collagen by crosslinking rabbit scleral collagen with genipin to develop a new therapy for preventing myopic progression. METHODS：Ten New Zealand rabbits were treated with 0.5 mmol/L genipin injected into the sub-Tenon＇s capsule in the right eyes. Untreated contralateral eyes served as the control. The treated area was cut into scleral strips measuring 4.0 mm×10.0 mm for stress-strain measurements（n=5）. The remaining five treated eyes were prepared for histological examination.RESULTS：Compared to the untreated scleral strips,the genipin-crosslinked scleral strips showed that the ultimate stress and Young＇s modulus at 10% strain were increased by the amplitude of 130% and 303% respectively,ultimate strain was decreased by 24%. There had no α-smooth muscle actin（α-SMA）positive cells in control and treated sclera. Histologically,there was no sign of apoptosis in the sclera,choroid,and retina; and no side effects were found in the peripheral cornea and optic nerve adjacent to the treatment area.CONCLUSION：Genipin induced crosslinking of collagen can increase its biomechanical behavior by direct strengthening of the extracellular matrix in rabbit sclera,with no α-SMA expression seen in the myofibroblasts. As there is no evidence of cytotoxicity in the scleral,choroidal,and retinal cells,genipin is likely a promising agent to strengthen the weakened sclera to prevent myopic progression.

Antimicrobial Activity of Minocycline-Loaded Genipin-Crosslinked Nano-Fibrous Chitosan Mats for Guided Tissue Regeneration

Antimicrobial delivery has been advocated for guided tissue regeneration (GTR) or guided bone regeneration (GBR) therapies involving patients with aggressive or unresolved periodontitis/peri-implantitis. Electrospun chitosan membranes demonstrate several advantages over traditional GTR barrier membranes because they stimulate healing, mimic the topology of the extracellular matrix, and allow for diffusion of nutrients and wastes into/out of the graft site, and were shown to stimulate bone formation in a rabbit calvarial criticalsize defect model. Previously, we have shown improvements in mechanical properties and degradation kinetics by crosslinking electrospun membranes with 5 mM or 10 mM genipin. We have also demonstrated the ability of elecrospun chitosan membranes to inhibit lippopolysaccharide (LPS)-induced monocyte activation. In this study, minocycline was incorporated into the chitosan membrane by passive absorption at 5 or 10 mg/mL. The minocycline-loaded membranes and control membranes (carrier only) were tested against Porphyromonas gingivalis (P. gingivalis) by repeated zone of inhibition (ZOI) measurements. Testing showed that uncrosslinked and genipin-crosslinked membranes have similar capacity to absorb aqueous solutions (swelling ratio 1.7 - 2.2). Minocycline loading resulted in bacterial inhibition for up to 8 days from crosslinked membranes (with 11 mm initial ZOI) whereas uncrosslinked membranes loaded with minocycline only inhibited bacteria for 4 days (with 8 mm initial ZOI). These in vitro results suggest that genipin-crosslinked electrospun chitosan membranes loaded with minocycline may be able to reduce early bacterial contamination of GTR graft sites.

Preparation and characterization of genipin-cross-linked chitosan microparticles by water-in-oil emulsion solvent diffusion method

Chitosan (CS) microparticles with and without cross-linking were prepared by a water-in-oil emulsion solvent diffusion method without any surfactants. Aqueous CS solution and ethyl ace- tate were used as water and oil phases, respectively. Genipin was used as a cross-linker. Influ- ences of genipin ratios and cross-linking times on CS microparticle characteristics were investigated. Non-cross-linked and cross-linked CS microparticles were spherical in shape and rough in surface. Microparticle matrices showed porous structures. Surface roughness, mean par- ticle sizes and bulk density of CS microparticles increased and their dissolutions in acetic acid solution decreased when genipin ratio and cross- linking time increased.

Genipin Cross-Linked Polyvinyl Alcohol-Gelatin Hydrogel for Bone Regeneration

Polyvinyl alcohol gelatin hydrogels were fabricated using genipin as a crosslinking agent for bone regeneration application. Optimized formulation of PVA-GE hydrogel was fabricated using genipin as crosslinking agent. Characterizations such as FTIR, morphology, porosity, pore size, degradation and swelling rate were investigated. Bone regeneration potential of optimized genipin cross-linked polyvinyl alcohol-gelatin (PVA20) hydrogels was assessed by implanting in rabbit’s femur defect for 1, 5 and 15 weeks period. Results showed interconnected porosity as observed in scanning electron microscopy and successful crosslinking as confirmed by FTIR analysis. Increased porosity (92% ± 2.46%) and pore size distribution (100 - 200 μm) were also observed as well as decrease in swelling rate (426% ± 10.50%). Bone formation was evident in micro-CT after 5 and 15 days of in vivo implantation period. Micro-CT analysis showed 32.67% increased bone formation of PVA-GE hydrogel defect compared with negative control after 15 weeks of in-vivo implantation. Histological analyses showed no inflammatory reaction post implantation and increase in cell matrix formation after 5 and 15 weeks. The combined physical and chemical method of crosslinking promises improved mechanical properties of PVA-GE hydrogel making it a potential scaffold for bone tissue engineering applications.

The Cytocompatibility of Genipin-Crosslinked Silk Fibroin Films

There is an increasing demand for crosslinking methods of silk fibroin (SF) scaffolds in biomedical applications that could maintain the biocompatibility, bioactivity as well as improve the water resistance and mechanical properties of SF materials. In this study, SF was crosslinked effectively with genipin which is a naturally occurring iridoid glucoside and the crosslinking mechanism was investigated through FTIR and amino acid analysis. The results showed that genipin could react with the -NH2 groups on the side chains of SF macromolecules and to form inter- and intra-molecular covalent bonds, and improved the stability of SF materials significantly. In vitro, the performances of genipin-crosslinked SF films were assessed by seeding L929 cells and compared with ethanol-processed SF films, glutaraldehyde and polyethylene glycol diglycidyl ether crosslinked ones. The genipin-crosslinked SF films showed a similar affinity to cells as ethanol-processed ones, and a higher bioactivity in promoting cell growth and proliferation, inhibition of cell apoptosis, and maintenance of normal cell cycle compared with glutaraldehyde and polyethylene glycol diglycidyl ether crosslinked SF films. These features, combined with the decrease of brittleness of SF films crosslinked with chemical methods, substantiated genipin as an effective and biocompatible agent for the manufacturing of bioactive SF materials which used as tissue engineering scaffolds and drug delivery carriers.

Development of genipin crosslinked gelatin matrices on surface interaction: Enhancing the biocompatibility by attenuating sterile inflammation

The inflammation can be stimulated by the surgical implantation and biomaterial presence through the foreign body via bio-interface.Macrophages play a key role in the interaction of host tissue to implant surfaces.In present study,the immuno-inflammatory responses of genipin crosslinked gelatin matrices(GCGM)to macrophages in vitro and the host tissue surfaces in rats were investigated.The results showed that the mechanical properties,swelling and degradation of gelatin matrices were improved by the crosslinking of genipin at physiological conditions.The macrophage on the surface of GCGM could avoid to be activated.The interaction of macrophage and GCGM suggested that GCGM could reduce the inflammatory response with downregulating the production and m RNA expression of pro-inflammatory cytokines.The anti-inflammatory effect of GCGM was demonstrated to be related to inhibit nuclear factor kappa-B(NF-κB)signaling pathway.Furthermore,gelatin matrices crosslinked with genipin could decrease the acute and chronic inflammatory response interacting with host tissue surfaces to enhance the biocompatibility in rats.These results showed that GCGM could avoid to active macrophages and were endowed with anti-inflammatory properties,suggesting the significant potential for clinical success with the development of immunomodulatory biomaterials.

基于Midas/Gen的复杂BAF池有限元分析

基于通用有限元软件Midas/Gen对某复杂BAF池进行有限元分析,首先对该水池整体进行分析,得到水池在各荷载工况下的变形结果及内力分布结果。针对水池边界条件、底板厚度进行了参数敏感性分析,水池底板内力分布与弹簧支座刚度、底板厚度存在明显规律性,证明了桩基采用弹簧支座模拟的必要性。本文对典型BAF池结构的分析,为该类型BAF池设计提供参考。