阿片受体影响雄性睾酮分泌的外周机制研究

目的:研究阿片μ受体对雄性睾酮的影响和外周机制。方法:通过在体动物模型的睾丸内吗啡注射和离体培养睾丸组织的特异性μ受体拮抗剂和激动剂处理，检测血浆、培养基和睾丸匀浆睾酮水平、睾丸匀浆睾酮合成酶mRNA水平、睾丸匀浆胰岛素样生长因子1（IGF1）蛋白和mRNA表达水平。结果:睾丸内注射吗啡后血清睾酮水平下降［（722.11±121.02）vs. (346.91±75.31) pg/mL；t=7.898，P=0.001］，睾丸匀浆中的睾酮水平下降［（133.61±16.82）vs. (66.56±14.96) pg/mg总蛋白；t=8.941，P=0.001］，同时下调睾酮合成酶的表达；吗啡睾丸内注射显著降低睾丸内IGF1蛋白［（7.93±2.13）vs. (2.54±0.74) ng/mg总蛋白，t=7.155，P=0.001］和mRNA［（3.22±1.12） vs. (1.66±0.55)，t=3.751，P=0.001］的表达。睾丸体外培养模型中阿片μ受体特异性的激动剂（DAMGO）下调培养基的睾酮水平及睾丸匀浆合成酶、IGF1的表达；阿片μ受体抑制剂（CTOP）则上调睾酮水平及合成酶、IGF1的表达。结论:阿片类药物作用于睾丸Sertoli细胞（支持细胞）表面的阿片μ受体，抑制IGF1的合成，进而减少睾丸Leydig细胞（间质细胞）睾酮合成酶Scarb1（清道夫受体B1）、Star（类固醇合成快速调节蛋白）、3βHsd（3-羟基-5类固醇脱氢酶）、Cyp17α1（17α-羟化酶）和17βHsd（17β羟基固醇脱氢酶）的表达，最终导致睾酮合成减少。     

Peripheral Nerve Regeneration and Muscle Reinnervation

Injured peripheral nerves but not central nerves have the capacity to regenerate and reinnervate their target organs. After the two most severe peripheral nerve injuries of six types, crush and transection injuries, nerve fibers distal to the injury site undergo Wallerian degeneration. The denervated Schwann cells (SCs) proliferate, elongate and line the endoneurial tubes to guide and support regenerating axons. The axons emerge from the stump of the viable nerve attached to the neuronal soma. The SCs downregulate myelin-associated genes and concurrently, upregulate growth-associated genes that include neurotrophic factors as do the injured neurons. However, the gene expression is transient and progressively fails to support axon regeneration within the SC-containing endoneurial tubes. Moreover, despite some preference of regenerating motor and sensory axons to “find” their appropriate pathways, the axons fail to enter their original endoneurial tubes and to reinnervate original target organs, obstacles to functional recovery that confront nerve surgeons. Several surgical manipulations in clinical use, including nerve and tendon transfers, the potential for brief low-frequency electrical stimulation proximal to nerve repair, and local FK506 application to accelerate axon outgrowth, are encouraging as is the continuing research to elucidate the molecular basis of nerve regeneration.     

The Potential Role of Hepatocyte Growth Factor in Degenerative Disorders of the Synovial Joint and Spine

This paper aims to provide a comprehensive review of the changing role of hepatocyte growth factor (HGF) signaling in the healthy and diseased synovial joint and spine. HGF is a multifunctional growth factor that, like its specific receptor c-Met, is widely expressed in several bone and joint tissues. HGF has profound effects on cell survival and proliferation, matrix metabolism, inflammatory response, and neurotrophic action. HGF plays an important role in normal bone and cartilage turnover. Changes in HGF/c-Met have also been linked to pathophysiological changes in degenerative joint diseases, such as osteoarthritis (OA) and intervertebral disc degeneration (IDD). A therapeutic role of HGF has been proposed in the regeneration of osteoarticular tissues. HGF also influences bone remodeling and peripheral nerve activity. Studies aimed at elucidating the changing role of HGF/c-Met signaling in OA and IDD at different pathophysiological stages, and their specific molecular mechanisms are needed. Such studies will contribute to safe and effective HGF/c-Met signaling-based treatments for OA and IDD.     

Peripheral Nerve-Derived Stem Cell Spheroids Induce Functional Recovery and Repair after Spinal Cord Injury in Rodents

Stem cell therapy is one of the most promising candidate treatments for spinal cord injury. Research has shown optimistic results for this therapy, but clinical limitations remain, including poor viability, engraftment, and differentiation. Here, we isolated novel peripheral nerve-derived stem cells (PNSCs) from adult peripheral nerves with similar characteristics to neural-crest stem cells. These PNSCs expressed neural-crest specific markers and showed multilineage differentiation potential into Schwann cells, neuroglia, neurons, and mesodermal cells. In addition, PNSCs showed therapeutic potential by releasing the neurotrophic factors, including glial cell-line-derived neurotrophic factor, insulin-like growth factor, nerve growth factor, and neurotrophin-3. PNSC abilities were also enhanced by their development into spheroids which secreted neurotrophic factors several times more than non-spheroid PNSCs and expressed several types of extra cellular matrix. These features suggest that the potential for these PNSC spheroids can overcome their limitations. In an animal spinal cord injury (SCI) model, these PNSC spheroids induced functional recovery and neuronal regeneration. These PNSC spheroids also reduced the neuropathic pain which accompanies SCI after remyelination. These PNSC spheroids may represent a new therapeutic approach for patients suffering from SCI.     

Interventions for long-term software security: Creating a lightweight program of assurance techniques for developers

Though some software development teams are highly effective at delivering security, others either do not care or do not have access to security experts to teach them how. Unfortunately, these latter teams are still responsible for the security of the systems they build: systems that are ever more important to ever more people. We propose that a series of lightweight interventions, six hours of facilitated workshops delivered over three months, can improve a team's motivation to consider security and awareness of assurance techniques, changing its security culture even when no security experts are involved. The interventions were developed after an Appreciative Inquiry and Grounded Theory survey of security professionals to find out what approaches work best. We tested the interventions in a participatory action research field study where we delivered the workshops to three software development organizations and evaluated their effectiveness through interviews beforehand, immediately afterwards, and after twelve months. We found that the interventions can be effective with teams with limited or no security experience and that improvement is long-lasting. This approach and the learning points arising from the work here have the potential to be applied in many development teams, improving the security of software worldwide.     

Magnetic Assembly of a Multifunctional Guidance Conduit for Peripheral Nerve Repair

Nerve growth conduits are designed to support and promote axon regeneration following nerve injuries. Multifunctionalized conduits with combined physical and chemical cues, are a promising avenue aimed at overcoming current therapeutic barriers. However, the efficacious assembly of conduits that promote neuronal growth remains a challenge. Here, a biomimetic regenerative gel is developed, that integrates physical and chemical cues in a biocompatible “one pot reaction” strategy. The collagen gel is enriched with magnetic nanoparticles coated with nerve growth factor (NGF). Then, through a remote magnetic actuation, highly aligned fibrillar gel structure embedded with anisotropically distributed coated nanoparticles, combining multiple regenerating strategies, is obtained. The effects of the multifunctional gels are examined in vitro, and in vivo in a 10-mm rat sciatic nerve injury model. The magneto-based therapeutic conduits demonstrate oriented and directed axonal growth, and improve nerve regeneration in vivo. The study of multifunctional guidance scaffolds that can be implemented efficiently and remotely provides the foundation to a novel therapeutic approach to overcome current medical obstacles for nerve injuries.     

某厂大滑坡对建(构)筑物破坏的分析

介绍了某工厂大滑坡事故的挖掘、检测、分析及鉴定,阐述了滑坡的滑动体内及滑坡周线外的建(构)筑物破坏情况,并对破坏机理进行了分析。     

物业管理：开发商不可以回避

分别从企业发展,管理约束和降低交易成本角度,论述了开发商介入物业管理的必要性,并对可能出现的疑问作出了解释。