Melanin Distribution in Human Skin: Influence of Cytoskeletal,Polarity, and Centrosome-Related Machinery of Stratum basale Keratinocytes

Melanin granules cluster within supra-nuclear caps in basal keratinocytes (KCs) of the human epidermis, where they protect KC genomic DNA against ultraviolet radiation (UVR) damage. While much is known about melanogenesis in melanocytes (MCs) and a moderate amount about melanin transfer from MC to KC, we know little about the fate of melanin once inside KCs. We recently reported that melanin fate in progenitor KCs is regulated by rare asymmetric organelle movement during mitosis. Here, we explore the role of actin, microtubules, and centrosome-associated machinery in distributing melanin within KCs. Short-term cultures of human skin explants were treated with cytochalasin-B and nocodazole to target actin filaments and microtubules, respectively. Treatment effects on melanin distribution were assessed by the Warthin–Starry stain, on centrosome-associated proteins by immunofluorescence microscopy, and on co-localisation with melanin granules by brightfield microscopy. Cytochalasin-B treatment disassembled supra-nuclear melanin caps, while nocodazole treatment moved melanin from the apical to basal KC domain. Centrosome and centriolar satellite-associated proteins showed a high degree of co-localisation with melanin. Thus, once melanin granules are transferred to KCs, their preferred apical distribution appears to be facilitated by coordinated movement of centrosomes and centriolar satellites. This mechanism may control melanin’s strategic position within UVR-exposed KCs.     

基于批发价格事前和事后决策的供应链合作促销策略研究

针对单一供应商和单一零售商组成的二级供应链系统,构建了批发价格事前和事后决策下的合作促销模型,探讨了批发价格事前和事后决策对合作促销的影响,并求得Stackelber主从博弈下的均衡合作促销策略。研究结果表明,在批发价格事前决策且零售商努力影响需求、或批发价格事后决策且供应商努力影响需求的情形下,合作促销均不是一个有效的激励策略;在批发价格事前决策且供应商努力影响需求的情形下,只有当促销努力成本共担系数小于一定的阈值时,合作促销才是一个有效的激励策略;在批发价格事后决策且零售商努力影响需求的情形下,合作促销始终是有效的激励策略。最后通过算例分析验证了上述结论的有效性。     

白象山铁矿主井原矿仓综合施工技术

通过对白象山铁矿主井原矿仓工程地质及水文地质的综合分析,提出了探水注浆、反井钻机导硐施工、扩刷帮、砼支护综合施工技术,从而保证原矿仓掘进、支护和安装安全可靠地进行。     

野生金雀花营养成分研究

对金雀花的基本营养成分作了较为全面的分析测定.结果表明:金雀花鲜品粗蛋白含量为4.20%,氨基酸种类齐全,并含有VB1、VB2、尼克酸、VC、VE及胡萝卜素等多种维生素,矿质元素含量丰富,还含有适量的纤维素、碳水化合物、酸及果胶等营养成分;重金属、硝酸盐、亚硝酸盐含量均未超过国家标准.因此,金雀花营养成分种类齐全,含量丰富,具有较高的营养价值.     

Platelet-Released Growth Factors Influence Wound Healing-Associated Genes in Human Keratinocytes and Ex Vivo Skin Explants

Platelet-released growth factors (PRGFs) or other thrombocyte concentrate products, e.g., Platelet-Rich Fibrin (PRF), have become efficient tools of regenerative medicine in many medical disciplines. In the context of wound healing, it has been demonstrated that treatment of chronic or complicated wounds with PRGF or PRF improves wound healing in the majority of treated patients. Nevertheless, the underlying cellular and molecular mechanism are still poorly understood. Therefore, we aimed to analyze if PRGF-treatment of human keratinocytes caused the induction of genes encoding paracrine factors associated with successful wound healing. The investigated genes were Semaphorin 7A (SEMA7A), Angiopoietin-like 4 (ANGPLT4), Fibroblast Growth Factor-2 (FGF-2), Interleukin-32 (IL-32), the CC-chemokine-ligand 20 (CCL20), the matrix-metalloproteinase-2 (MMP-2), the chemokine C-X-C motif chemokine ligand 10 (CXCL10) and the subunit B of the Platelet-Derived Growth Factor (PDGFB). We observed a significant gene induction of SEMA7A, ANGPLT4, FGF-2, IL-32, MMP-2 and PDGFB in human keratinocytes after PRGF treatment. The CCL20- and CXCL10 gene expressions were significantly inhibited by PRGF therapy. Signal transduction analyses revealed that the PRGF-mediated gene induction of SEMA7A, ANGPLT4, IL-32 and MMP-2 in human keratinocytes was transduced via the IL-6 receptor pathway. In contrast, EGF receptor signaling was not involved in the PRGF-mediated gene expression of analyzed genes in human keratinocytes. Additionally, treatment of ex vivo skin explants with PRGF confirmed a significant gene induction of SEMA7A, ANGPLT4, MMP-2 and PDGFB. Taken together, these results describe a new mechanism that could be responsible for the beneficial wound healing properties of PRGF or related thrombocytes concentrate products such as PRF.     

Mucoadhesive Electrospun Nanofiber-Based Hybrid System with Controlled and Unidirectional Release of Desmopressin

The sublingual mucosa is an attractive route for drug delivery, although challenged by a continuous flow of saliva that leads to a loss of drug by swallowing. It is of great benefit that drugs absorbed across the sublingual mucosa avoid exposure to the harsh environment of the gastro-intestinal lumen; this is especially beneficial for drugs of low physicochemical stability such as therapeutic peptides. In this study, a two-layered hybrid drug delivery system was developed for the sublingual delivery of the therapeutic peptide desmopressin. It consisted of peptide-loaded mucoadhesive electrospun chitosan/polyethylene oxide-based nanofibers (mean diameter of 183 ± 20 nm) and a saliva-repelling backing film to promote unidirectional release towards the mucosa. Desmopressin was released from the nanofiber-based hybrid system (approximately 80% of the loaded peptide was released within 45 min) in a unidirectional manner in vitro. Importantly, the nanofiber–film hybrid system protected the peptide from wash-out, as demonstrated in an ex vivo flow retention model with porcine sublingual mucosal tissue. Approximately 90% of the loaded desmopressin was retained at the surface of the ex vivo porcine sublingual mucosa after 15 min of exposure to flow rates representing salivary flow.     

Disassembly and Mislocalization of AQP4 in Incipient Scar Formation after Experimental Stroke

There is an urgent need to better understand the mechanisms involved in scar formation in the brain. It is well known that astrocytes are critically engaged in this process. Here, we analyze incipient scar formation one week after a discrete ischemic insult to the cerebral cortex. We show that the infarct border zone is characterized by pronounced changes in the organization and subcellular localization of the major astrocytic protein AQP4. Specifically, there is a loss of AQP4 from astrocytic endfoot membranes that anchor astrocytes to pericapillary basal laminae and a disassembly of the supramolecular AQP4 complexes that normally abound in these membranes. This disassembly may be mechanistically coupled to a downregulation of the newly discovered AQP4 isoform AQP4ex. AQP4 has adhesive properties and is assumed to facilitate astrocyte mobility by permitting rapid volume changes at the leading edges of migrating astrocytes. Thus, the present findings provide new insight in the molecular basis of incipient scar formation.     

基于新Dirichlet先验分布的指数寿命型产品多阶段可靠性增长Bayes分析

本文基于新的Dirichlet先验分布,建立了多阶段指数寿命型产品可靠性增长的Bayes模型。本模型充分利用先验信息和阶段试验信息,采用最优化方法解决了新的Dirichlet先验分布超参数因物理意义不明确而难以确定的问题;利用Gibbs抽样算法进行后验推断,合理估算出当前阶段和后续试验阶段产品可靠性的Bayes点估计和置信下限,并利用该模型研究实现了对产品可靠性的预测。实例证明了该模型在多阶段指数产品可靠性增怅分析中的直观性与有效性。     

酸枣果三萜皂苷抑菌和抗氧化活性的研究

对纯化的酸枣果三萜皂苷进行抑菌和抗氧化活性研究。结果表明,三萜皂苷具有广谱抗菌效果,对实验所用的致病菌有较强的抑制和灭活作用。对金黄色葡萄球菌、乙型溶血性链球菌和炭疽杆菌的MIC可达0.078mg/mL。MBC值范围为0.180～0.712mg/mL,尤其对绿脓假单胞菌和白色假丝酵母菌显示明显的抑制作用。通过清除DPPH自由基、铁还原抗氧化能力法、降低能量、硫代巴比妥酸法和抑制β-胡萝卜素漂白等体外抗氧化反应来研究其抗氧化性能,并以人工合成的抗氧化剂BHT作对照,结果表明三萜皂苷具有显著的抗氧化效应。因此,酸枣果可作为食品、化妆品和药品行业的天然原料来源。