海洋生物医用材料的临床应用和安全性评价

目的： 对海洋生物医用材料在医疗领域的应用情况和海洋生物材料来源医疗器械的安全性评价趋势进行分析，为推进该材料的临床转化提供参考。方法： 归纳海洋生物医用材料的分类和应用，介绍该材料的安全性评价的程序要点，探讨其安全性评价中面临的挑战。结果与结论： 常用的海洋生物医用材料主要为多糖和蛋白质，在创伤修复和组织工程领域应用广泛。海洋生物医用材料具有生物活性和良好的生物相容性，对此类材料的安全性评价应根据材料特性和预期用途，科学制定评价程序和选择检验方法。     

From the Cover: A simple nutrient-dependence mechanism for predicting the stoichiometry of marine ecosystems

It is widely recognized that the stoichiometry of nutrient elements in phytoplankton varies within the ocean. However, there are many conflicting mechanistic explanations for this variability, and it is often ignored in global biogeochemical models and carbon cycle simulations. Here we show that globally distributed particulate P:C varies as a linear function of ambient phosphate concentrations, whereas the N:C varies with ambient nitrate concentrations, but only when nitrate is most scarce. This observation is consistent with the adjustment of the phytoplankton community to local nutrient availability, with greater flexibility of phytoplankton P:C because P is a less abundant cellular component than N. This simple relationship is shown to predict the large-scale, long-term average composition of surface particles throughout large parts of the ocean remarkably well. The relationship implies that most of the observed variation in N:P actually arises from a greater plasticity in the cellular P:C content, relative to N:C, such that as overall macronutrient concentrations decrease, N:P rises. Although other mechanisms are certainly also relevant, this simple relationship can be applied as a first-order basis for predicting organic matter stoichiometry in large-scale biogeochemical models, as illustrated using a simple box model. The results show that including variable P:C makes atmospheric CO₂ more sensitive to changes in low latitude export and ocean circulation than a fixed-stoichiometry model. In addition, variable P:C weakens the relationship between preformed phosphate and atmospheric CO₂ while implying a more important role for the nitrogen cycle.Nutrient elements are used by phytoplankton to synthesize molecules, in order to accomplish biochemical functions. Some of these molecules are absolutely necessary, and the nutrient elements have no substitutes. Examples are P in nucleic acids, N in amino acids, and Fe in the photosynthetic apparatus (1). However, there is a degree of plasticity in the molecular assemblage required per phytoplankton cell, which varies between species and between clades (2, 3). Furthermore, there is a capacity for plasticity in molecular composition of even a given species, as shown in culture experiments (4, 5). Such plasticity leads to variability in the elemental ratios of nutrients in marine phytoplankton, widely documented in laboratory and field measurements (2, 6, 7). Recent analyses of global nutrient and particulate observations have shown that N:P, the most commonly discussed ratio, varies regionally, including low N:P in the high-latitude Southern Ocean and high N:P in the oligotrophic regions (7–9). Explanations of high N:P in oligotrophic waters have often invoked an enhanced reliance on N-rich proteins for gathering scarce resources (1, 10), whereas low N:P in the Southern Ocean has been variously attributed to the abundance of P-rich molecules in cold, fast-growing plankton (11), or to the availability of Si, which supports P-rich diatom communities (8, 12).Despite an abundant literature on stoichiometric variability and its potential causes, no simple predictive relationship has been widely adopted in global biogeochemical models. Instead, the vast majority of global biogeochemical models assumes fixed C:N:P in organic matter, including most participants in the recent Coupled Model Intercomparison Project, CMIP5 (13). Thus, the potential impact of changes in organic matter stoichiometry on ocean carbon storage and oxygen consumption remain largely unexplored. The neglect of stoichiometric variability is due, at least in part, to the lack of a clear predictive framework.Here, it is argued that the concentration of a nutrient element in seawater can provide a suitable predictive framework, because it is a critical determinant of the rate at which that element will tend to be taken up by the organisms in the local community. This hypothesis builds on classic resource competition theory (14), which argues that if the concentration of an element is low, such that uptake is difficult, the community will be dominated by organisms that are well adapted to a low cellular quota of that nutrient (10). If, on the other hand, the concentration is high, facilitating high uptake rates, the community will be dominated by organisms that are capable of taking advantage of that nutrient to grow faster. This suggestion leads to clear predictions with significant biogeochemical consequences, as outlined below.     

甲壳素/壳聚糖在疝修补领域的研究综述

疝气是目前临床上1 种常见的外科疾病,随着疝气患者的日益增多,疝修补材料的不断革新成为临床疝气领域的研发热点,力求通过改善疝修补材料来促进疝修补术后的腹壁组织修复情况。目前海洋来源的甲壳素/壳聚糖是生物医用材料领域研究的热点材料,具有广阔的发展前景。综述疝修补材料和以甲壳素和壳聚糖为代表的海洋生物材料的生物学特性及其在疝修补领域的研究进展,评价其作为疝修补材料的可行性,为海洋生物材料在疝修补领域的广泛应用提供新思路。     

海洋来源 (+)-sclerotiorin衍生物的半合成、抗结核活性与初步构效关系研究

目的 结核病仍然是世界范围内一个重要的公共卫生问题,因此迫切需要寻找新型抗结核分子。以海洋天然产物(+)-sclerotiorin为原料半合成一系列衍生物,其中包含18个新化合物,通过考察它们的抗结核等活性,探究其初步构效关系。方法 利用Mycobacterium marinum 和 Mycobacterium tuberculosis 菌株对衍生物的生物活性进行测定。结论 衍生物4, 5, 8?10和12的抗海分枝杆菌活性与阳性药相当,MIC90值在16.1?18.9 μM之间。此外,衍生物9, 11, 12和15也显示出中等的抗结核活性。初步构效关系表明喹啉、异喹啉、联苯和联苯醚等基团有利于提升(+)-sclerotiorin衍生物的抗结核活性。衍生物12在结核杆菌蛋白酪氨酸磷酸酶B抑制试验中显示出最强的活性,分子对接的结果表明,它与蛋白的Phe98残基之间存在苯环与苯环间的π-π相互作用。该研究证实了(+)-sclerotiorin衍生物作为抗结核候选药物的潜力。     

海洋硫酸多糖对糖脂代谢及肠道菌群调节作用的研究进展

肥胖已经成为人类首要健康问题,海洋硫酸多糖对糖脂代谢及肠道菌群具有调节作用,因此在肥胖预防和缓解中展现出良好的应用前景。本文综述了海洋硫酸多糖的种类,并从糖脂代谢和肠道微生物群的角度总结了海洋硫酸多糖在肥胖预防和缓解中的作用机制,提出了海洋硫酸多糖未来的研究和发展方向,以及为海洋硫酸多糖的进一步研究及市场化应用提供参考。     

Mapping the diatom redox-sensitive proteome provides insight into response to nitrogen stress in the marine environment

Diatoms are ubiquitous marine photosynthetic eukaryotes responsible for approximately 20% of global photosynthesis. Little is known about the redox-based mechanisms that mediate diatom sensing and acclimation to environmental stress. Here we used a quantitative mass spectrometry-based approach to elucidate the redox-sensitive signaling network (redoxome) mediating the response of diatoms to oxidative stress. We quantified the degree of oxidation of 3,845 cysteines in the Phaeodactylum tricornutum proteome and identified approximately 300 redox-sensitive proteins. Intriguingly, we found redox-sensitive thiols in numerous enzymes composing the nitrogen assimilation pathway and the recently discovered diatom urea cycle. In agreement with this finding, the flux from nitrate into glutamine and glutamate, measured by the incorporation of ¹⁵N, was strongly inhibited under oxidative stress conditions. Furthermore, by targeting the redox-sensitive GFP sensor to various subcellular localizations, we mapped organelle-specific oxidation patterns in response to variations in nitrogen quota and quality. We propose that redox regulation of nitrogen metabolism allows rapid metabolic plasticity to ensure cellular homeostasis, and thus is essential for the ecological success of diatoms in the marine ecosystem.Aerobic organisms produce reactive oxygen species (ROS) as a byproduct of oxygen-based metabolic pathways, such as photosynthesis, photorespiration, and oxidative phosphorylation (1). Perturbations in oxygenic metabolism under various stress conditions can induce oxidative stress from overproduction of ROS (2, 3). Because ROS are highly reactive forms of oxygenic metabolites, critical mechanisms for ROS detoxification have evolved consisting of ROS-scavenging enzymes and small molecules, including glutathione (GSH) (4). As the most abundant low molecular weight thiol antioxidant, GSH has critical roles in maintaining a proper cellular thiol–disulfide balance and in detoxifying H₂O₂ via the ascorbate–GSH cycle (5).Although classically ROS were considered toxic metabolic byproducts that ultimately lead to cell death, it is now recognized that ROS act as central secondary messengers involved in compartmentalized signaling networks (1, 6–8). Modulation of various cell processes by ROS signaling is mediated largely by posttranslational thiol oxidation, whereby their physical structure and biochemical activity are modified upon oxidation (9). Thus, the redox states of these proteins possess crucial information needed for cell acclimation to stress conditions (10, 11). The emergence of advanced redox proteomic approaches, such as the OxICAT method (12), has created new opportunities to identify redox-sensitive proteins (e.g., redoxome) on the system level and to quantify their precise level of oxidation on exposure to environmental stress conditions.Marine photosynthetic microorganisms (phytoplankton) are the basis of marine food webs. Despite the fact that their biomass represents only approximately 0.2% of the photosynthetic biomass on earth, they are responsible for nearly 50% of the annual global carbon-based photosynthesis and greatly influence the global biogeochemical carbon cycle (13). This high ratio of productivity to biomass, reflected in high turnover rates, makes phytoplankton highly responsive to climate change. Phytoplankton can grow rapidly and form massive blooms that stretch over hundreds of kilometers in the oceans and are regulated by such environmental factors as nutrient availability and biotic interactions with grazers and viruses.Diatoms are a highly diverse clade of phytoplankton, responsible for roughly 20% of global primary productivity (14). Consequently, diatoms play a central role in the biogeochemical cycling of important nutrients, including carbon, nitrogen, and silica, which constitute part of their ornate cell wall. As members of the eukaryotic group known as stramenopiles (or heterokonts), diatoms are derived from a secondary endosymbiotic event involving red and green algae engulfed within an ancestral protest (15).The unique multilineage content of diatom genomes reveals a melting pot of biochemical characteristics that resemble bacterial, plant, and animal traits, including the integration of a complete urea cycle, fatty acid oxidation in the mitochondria, and plant C4-like related pathways (16, 17). During bloom succession, phytoplankton cells are subjected to diverse environmental stress conditions that lead to ROS production, such as allelopathic interactions (18), CO₂ availability (19, 20), UV exposure (21), iron limitation (22), and viral infection (23). Recently reported evidence suggests that diatoms possess a surveillance system based on the induction of ROS that have been implicated in response to various environmental stresses (22, 24). Nevertheless, very little is known about cell signaling processes in marine phytoplankton and their potential role in acclimation to rapid fluctuations in the chemophysical gradients in the marine environment (25).Using a mass spectrometry-based approach, we examined the diatom redoxome and quantified its degree of oxidation under oxidative stress conditions. The wealth of recently identified redox-sensitive proteins participating in various cellular functions suggests a fundamental role of redox regulation in diatom biology. We mapped the redox-sensitive enzymes into a metabolic network and evaluated their role in the adjustment of metabolic flux under variable environmental conditions. We further explored the redox sensitivity of the primary nitrogen-assimilating pathway and demonstrated the role of compartmentalized redox regulation in cells under nitrogen stress conditions using a redox-sensitive GFP sensor targeted to specific subcellular localizations.     

陆军某部新兵濒海训练亚健康状态调查分析

目的探讨濒海训练期间陆军某部新兵亚健康罹患率及其相关因素,为找出切实可行的干预对策提供依据。方法采取自身对照,分别对参训新兵训练前、训练中(训练开始后的20 d)和训练结束后进行"康奈尔医学指数量表(CMI)"调查分析,确定其中亚健康状态发生率及程度。结果海训过程中的亚健康状态及心理障碍发生率显著高于海训前及训练结束后,参加海训的新兵的亚健康罹患率高于未参加海训的新兵(P<0.05);此外,高中学历的亚健康发生率显著高于初中、大专及大专以上学历士兵。结论高强度的濒海训练是诱发亚健康状态的重要因素,但参训士兵的应对方式对个体的亚健康状态也有极大影响,应对方式和心理健康水平密切相关;文化程度及对海训的顾虑程度也是影响亚健康状态的相关因素。     

Axinella属海绵化学成分与生物活性研究进展

系统综述了海绵Axinella属的生物碱、三萜、甾体等化学成分,及其抗肿瘤、抗菌、神经保护等生物活性的研究进展,为该属海绵的深入研究提供有用资料。     

海洋细菌Bacillus coagulans spp.heishijiaosis 发酵液抗真菌活性及其机制研究

目的对凝结芽胞杆菌黑石礁新亚种LU-B02产生的抗白色念珠菌活性物质的作用靶位及抑菌谱进行了研究。方法采用山梨醇保护形态变异法结合扫描电镜超微结构观察研究了活性物质的作用靶位,最小抑菌浓度(MIC)法比较了该菌发酵液对不同真菌的抑菌活性。结果该活性物质抑制白色念珠菌细胞壁中的主要组分——葡聚糖的合成从而造成其细胞壁残缺。该活性物质具有抗真菌专一性,对革兰氏阳性代表菌金黄色葡萄球菌和革兰氏阴性代表菌大肠杆菌等细菌均无抑制效果,而对人体病原真菌抑菌效果较为明显,尤其是对白色念珠菌的抑制效果较好。MIC测定表明白色念珠菌对LU-B02活性物质高度敏感,相当于斯皮仁诺8~16μg,抑菌效价每毫升相当于3 500 U制霉菌素或洁尔阴活性的4倍。发酵液在酸性条件下加入0.2%冰片时,室温下存放6个月仍可保持良好的抗白色念珠菌活性。结论凝结芽孢杆菌黑石礁新亚种(Bacillus coagulans spp.heishijiaosis)产生的活性物质在控制以白色念珠菌为主的真菌感染方面具有良好应用前景。