Chitosan (CS) is becoming increasingly popular in food packaging due to its natural degradability and great film-forming properties. Nevertheless, its poor antibacterial properties and inadequate antioxidant properties prevent it from being used effectively. In this study, β-cyclodextrin-epichlorohydrin (β-CD-EP) oligomers were prepared and encapsulated with natural essential oils cinnamaldehyde and thymol, and then the inclusion complexes (IC) were incorporated into chitosan in various contents to afford a series of CS-IC composite films. The impacts of IC on the morphological, mechanical, thermal, and water resistance properties, antioxidant and antibacterial activities of chitosan films, as well as the loading and sustained release behavior of IC, were thoroughly examined. The results turned out that the essential oils were well-loaded with high encapsulation efficiency and showed a significant slow-release effect. It was also found that the tensile strength and the elongation at break decreased with increasing IC contents, while the thermal stability was enhanced. The incorporation of IC dramatically promoted the antioxidant and antibacterial properties of the chitosan films towards Gram-positive bacteria. Based on our findings, chitosan films containing essential oils-loaded β-CD-EP oligomers may serve as an effective food packaging material.
A novel nanobody-drug conjugate (NDC) was constructed by incorporating an amphipathic peptide, GALA, which improved the cytotoxicity by one to two orders of magnitude. Mechanistic studies demonstrate that tethering to lipids induces GALA to form a helix, which dramatically enhances endocytosis. Our work provides a general strategy not only for improving the anti-cancer efficacy of protein-drug conjugates but also for increasing the efficiency of other types of endocytosis-dependent cell delivery.
基于 RS和POI数据,采用样方密度、分区识别法、Arc GIS空间分析和数理统计等,分析2013-2019年北京市城六区的功能区及产业用地分布变化特征。结果表明:2013-2019年间,研究区域关于产业调整的相关政策初见成效;其中中心城区仓储物流和批发市场转换为公园绿地和公共服务用地显著。本研究聚焦北京市中心城区,总结其城市产业用地布局和功能布局的发展演变规律,以期为优化首都空间布局和产业结构提出合理建议。
A novel nanobody-drug conjugate (NDC) was constructed by incorporating an amphipathic peptide, GALA, which improved the cytotoxicity by one to two orders of magnitude. Mechanistic studies demonstrate that tethering to lipids induces GALA to form a helix, which dramatically enhances endocytosis. Our work provides a general strategy not only for improving the anti-cancer efficacy of protein-drug conjugates but also for increasing the efficiency of other types of endocytosis-dependent cell delivery.
SARM1, an NAD-utilizing enzyme, regulates axonal degeneration. We show that CZ-48, a cell-permeant mimetic of NMN, activated SARM1 in vitro and in cellulo to cyclize NAD and produce a Ca2+ messenger, cADPR, with similar efficiency as NMN. Knockout of NMN-adenylyltransferase elevated cellular NMN and activated SARM1 to produce cADPR, confirming NMN was its endogenous activator. Determinants for the activating effects and cell permeability of CZ-48 were identified. CZ-48 activated SARM1 via a conformational change of the auto-inhibitory domain and dimerization of its catalytic domain. SARM1 catalysis was similar to CD38, despite having no sequence similarity. Both catalyzed similar set of reactions, but SARM1 had much higher NAD-cyclizing activity, making it more efficient in elevating cADPR. CZ-48 acted selectively, activating SARM1 but inhibiting CD38. In SARM1-overexpressing cells, CZ-48 elevated cADPR, depleted NAD and ATP, and induced non-apoptotic death. CZ-48 is a specific modulator of SARM1 functions in cells.
以D500 nm和TBARS为指标分别考察玉米蛋白水解物对吐温20-壳聚糖双层膜O/W乳状液在4、25、37℃下贮藏7 d过程中物理和氧化稳定性的影响.以脂肪酸的释放量为指标,通过静态胃-肠消化和动态胃-肠消化体外模拟模型考察玉米蛋白水解物对吐温20-壳聚糖双层膜乳状液脂肪消化的影响.结果表明,尽管玉米蛋白水解物(2.5~10.0 mg/mL)降低了乳状液的物理稳定性,但是并未降低乳状液的氧化稳定性.玉米蛋白水解物促进了乳状液中脂肪的消化,乳状液中脂肪在动态胃-肠消化模型中的消化速率和程度低于在静态胃-肠消化模型中.说明玉米蛋白水解物可以改善乳状液中脂肪的氧化和消化.
In order to guarantee the national food safety,the basic condition of cultivated land and its lim-ited types must be taken into account for well-facilitied capital farmland evaluation and construction.However, the construction project of high quality capital farmland is currently lacking in scientific instruction in line with local conditions in respect of project site selection and design approach.With Puyang County,Henan,as the study area,this study managed to establish the zoning approach of comprehensive suitability evaluation.Based on the theory of ecological niche and the construction target of well-facilitied capital farmland,this paper proposes the concept of high quality capital farmland niche,and has established the index system from different aspects of land fertility level,land leveling project,infrastructure in cropland,economic society and ecological security of cultivated land.Thirteen indicators including surface soil texture,profile pattern,soil organic matter,degree of salinity,drainage conditions,etc,were selected during the evaluation.The weight of each evaluation indicator was determined with AHP and entropy method.Then this paper has built the identification model of cultivated land comprehensive suitability and diagnosis model of obstacle indicators.Finally,the zone partition of high quality farmland construction and the concrete project of construction were discussed by using the diagnosis model combined with relative limited types.The results showed that the value of comprehensive suitability was between 0.56 and 0.95,and the area of primary and secondary suitable region accounted for 80.5% of the total area of cultivated land.The obstacle degree was between low and middle,and the ecological condition,land fer-tility level and infrastructure in cropland were the main obstacle indicators.The cultivated land to be evaluated was divided into three levels including priority construction,secondary construction,and conditionally construc-tion based on the evaluation model for comprehensive suitability of well-facilitated capital farmland construc-tion.Simultaneously,the use of the niche-fitness model to establish the niche of high quality capital farmland could solve the problems including indeterminate key rectification regions and provide the scientific basis for project site selection and design approach.The classification of cultivated land can provide a reference for the functional zoning and regulation of cultivated land.
Background: CD38 is a surface membrane antigen highly expressed in malignant blood cells, such as multiple myeloma (MM). A soluble form of CD38 (sCD38) is also present in the plasma, deriving likely from the shedding from the cells. The plasma levels of sCD38 should thus correlate closely with the proliferation of the MM cells, allowing the development of a simple diagnostic blood test for monitoring the progress of the disease. However, the plasma sCD38 levels are extremely low, requiring the design of a highly sensitive and specific assay. Results: In this study, we developed an ultra-sensitive assay, based on two nanobodies (Nbs) targeting two distinct epitopes of sCD38. One Nb acts as a capturer, and the other is fused with the firefly luciferase serving as a reporter to ensure sensitivity. We showed that this Dual epitopes protein IDentification (DepID) assay has sensitivity reaching 10 pg/mL, which is 10 times higher than that of a commercial ELISA kit. By this method, we were able to precisely quantify the levels of sCD38 in the plasma of MM patients, which were significantly higher than those from healthy donors. We further showed that the increase plasma levels of sCD38 correlated with the progress of MM. Conclusion: We have developed a Nb-based luminescence sandwich assay, named as DepID, for quantification of the soluble CD38 in MM patients' plasma and showed the potency of this method as a tool for general diagnosis of MM or companion diagnosis of the CD38-targeted therapies. (C) 2018 Elsevier B.V. All rights reserved.
Nicotinic acid adenosine dinucleotide phosphate (NAADP) is a Ca2+-mobilizing second messenger that regulates a wide range of biological activities. However, the mechanism of its biogenesis remains controversial. CD38 is the only enzyme known to catalyze NAADP synthesis from NADP and nicotinic acid. CD38-mediated catalysis requires an acidic pH, suggesting that NAADP may be produced in acidic endolysosomes, but this hypothesis is untested. In this study, using human cell lines, we specifically directed CD38 to the endolysosomal system and assessed cellular NAADP production. First, we found that nanobodies targeting various epitopes on the C-terminal domain of CD38 could bind to cell surface-localized CD38 and induce its endocytosis. We also found that CD38 internalization occurred via a clathrin-dependent pathway, delivered CD38 to the endolysosome, and elevated intracellular NAADP levels. We also created a CD38 variant for lysosome-specific expression, which not only withstood the degradative environment in the lysosome, but was also much more active than WT CD38 in elevating cellular NAADP levels. Supplementing CD38-expressing cells with nicotinic acid substantially increased cellular NAADP levels. These results demonstrate that endolysosomal CD38 can produce NAADP in human cells. They further suggest that CD38's compartmentalization to the lysosome may allow for its regulation via substrate access, rather than enzyme activation, thereby providing a reliable mechanism for regulating cellular NAADP production.
快速、准确开展耕地质量评价是当前农地保护的重要课题,随着高空间、高光谱和高时间分辨率遥感数据使高效了解我国耕地质量状况,实现耕地质量的长期监测成为可能.为推进耕地质量信息快速获取及实时动态评价,从耕地生产力评价、土壤环境评价和土壤健康质量评价3个方面界定耕地质量的复杂内涵,系统分析、总结了遥感技术在耕地质量评价中的识别指标集,最后从耕地质量评价的聚焦转移、耕地质量信息提取技术的多元发展、耕地质量评价成果的应用3个方面对遥感技术在耕地质量评价应用的发展方向进行展望.
农田土壤重金属问题长期以来一直备受各界关注,科学揭示重金属空间分异特征及影响因素,成为新常态下耕地质量管理的重要组成部分.以海伦市耕地为研究对象,通过反距离权重插值法得到整个研究区8种重金属元素空间分布特征,利用地理探测器模型诊断自然因素、区位因素、生产生活因素对8种重金属空间分异的解释力.结果表明,Cr、Cu、Ni、Pb、Zn变异程度强,As、Hg、Cd变异程度较弱.8种重金属空间分异显著,不同重金属元素含量空间分布也存在差异,空间分布呈现西北向东南方向阶梯变化.不同影响因素具有不同的作用机制,对不同重金属元素空间分异的影响具有差异性,Hg、Cd、Pb、Zn的主要因素是区位因素与自然因素,As、Cr、Cu、Ni的主要影响因素是区位因素和生活生产活动因素,总体上区位因素的影响力大于生产生活因素,生产生活因素的影响力大于自然因素,土壤重金属在原本固有含量的基础上受到类人为因素的强烈扰动进行了新的空间排列,逐渐改变了原有的空间分布特征形成新的分布格局.
CD38 catalyzes the synthesis of the Ca2+ messenger, cyclic ADP-ribose (cADPR). It is generally considered to be a type II protein with the catalytic domain facing outside. How it can catalyze the synthesis of intracellular cADPR that targets the endoplasmic Ca2+ stores has not been resolved. We have proposed that CD38 can also exist in an opposite type III orientation with its catalytic domain facing the cytosol. Here, we developed a method using specific nanobodies to immunotarget two different epitopes simultaneously on the catalytic domain of the type III CD38 and firmly established that it is naturally occurring in human multiple myeloma cells. Because type III CD38 is topologically amenable to cytosolic regulation, we used yeast-two-hybrid screening to identify cytosolic Ca2+ and integrin-binding protein 1 (CIB1), as its interacting partner. The results from immunoprecipitation, ELISA, and bimolecular fluorescence complementation confirmed that CIB1 binds specifically to the catalytic domain of CD38, in vivo and in vitro. Mutational studies established that the N terminus of CIB1 is the interacting domain. Using shRNA to knock down and Cas9/guide RNA to knock out CIB1, a direct correlation between the cellular cADPR and CIB1 levels was demonstrated. The results indicate that the type III CD38 is functionally active in producing cellular cADPR and that the activity is specifically modulated through interaction with cytosolic CIB1.
CD38, as a cell surface antigen is highly expressed in several hematologic malignancies including multiple myeloma (MM) and has been proven to be a good target for immunotherapy of the disease. CD38 is also a signaling enzyme responsible for the metabolism of two novel calcium messenger molecules. To be able to target this multifunctional protein, we generated a series of nanobodies against CD38 with high affinities. Crystal structures of the complexes of CD38 with the nanobodies were solved, identifying three separate epitopes on the carboxyl domain. Chromobodies, engineered by tagging the nanobody with fluorescence proteins, provide fast, simple and versatile tools for quantifying CD38 expression. Results confirmed that CD38 was highly expressed in malignant MM cells compared with normal white blood cells. The immunotoxin constructed by splicing the nanobody with a bacterial toxin, PE38 shows highly selective cytotoxicity against patient-derived MM cells as well as the cell lines, with half maximal effective concentration reaching as low as 10(-11) molar. The effectiveness of the immunotoxin can be further increased by stimulating CD38 expression using retinoid acid. These results set the stage for the development of clinical therapeutics as well as diagnostic screening for myeloma.
To obtain a compromise between complexity and performance of the VBLAST system,a new detection algorithm based on SIC is proposed.The algorithm sorts by estimation error from big to small and combines with ML.The ways of sorting can ensure the reliability of the back layer to increase gradually.The ML detection of the first layer can cut error propagation problems.Making hypothesis to the first detected layer and choosing the best as the final detection output when all signals are detected to improve the performance of the whole system.The simulation results show that,no matter in fast fading Rayleigh channel or space related channel,compared with the traditional OSIC,the complexity of the algorithm increases slightly,while the bit error rate is lower,the performance is significantly improved,and it is more suitable for VBLAST signal detection system.
Iron content in TMA,by FAAS and ICP-AES were described in the paper.Samples were ashed at 600 ℃ in an oven.Under the optimum conditions,the values of recovery of FAAS and ICP-AES were 94.6 % and 95.7 %,respectively.Two different samples results detected by ICP-AES were consistent with those detected by FAAS.
Electronic commerce is an important growth point in modern economy.Jiangmen has made great strides in the development of e-commerce,but compared with other Pearl River Delta cities,it is lagging behind.Jiangmen should improve its basic facilities,speed up the construction of its industry chain,develop public service platforms,promote online retailing,actively explore foreign markets,strengthen personnel training and support for entrepreneurship,and make use of e-commerce to promote the transformation and upgrading of its enterprises and enhance their competitiveness.
This paper proposes a method of empirical mode decomposition (EMD) modal parameter identification based on Laplace wavelet matching, on the basis of synchronization test for pressure switch. Taking a pressure switch which is used in the air-conditioning of automotives as a object, the paper conducts a lot experiments with hammering test and white noise for vibrating identification of diaphragm. Results proves that the method is able to overcome the disturbance of white noise and impulse noise, extract accurate modal parameters from multimoding aliasing and crowded modals, and finally identify the vibrating signal of diaphragm which solves the problem of synchronization test for pressure switch, and has the guidance significance to the related profession.
OBJECTIVE:To study the optimum preparation process of the volatile oil of Dalbergia odorifera-beta-cyclodextrin.METHODS:The saturated water solution mixing method was compared with microwave method and ultrasonic method by determining the ultilization ratio of the volatile oil in Dalbergia odorifera. The optimum preparation conditions were investigated by the orthogonal design. The quality of the volatile oil before and after included were analyzed by TLC.RESULTS:The optimum preparation conditions for inclusion were as follows: m(volatile oil of Dalbergia odorifera): m (beta-CD) = 1:10 (g/g), ultrasonic time was 1h, the temperature was 70 degrees C. The ultilization ratio of the volatile oil was 82.02%.CONCLUSION:Ultrasonic method is the best method.
Under the condition of plate culture,the effects of Cd,Pb and their combined stress on the growth of hyphae of Agrocybe praecox as well as the Cd and Pb bioaccumulation in the solid potato dextrose agar medium was studied.The mycelial growth vigor,colony diameter and dry mycelial weight were reduced as responding to the inreasing Cd and Pb stress in the culture media.The results also showed that bioaccumulation of Cd and Pb in hyphae of Agrocybe praecox increased accompanying with the increments of the Cd and Pb concentrations in the media,and bioaccumulation of Pb in hyphae was promoted while that of Cd was inhibited under the combined stress of Cd and Pb.
Under the condition of laboratory simulation,the toxic effects of oxidation hair dyes on Perinereis aibuhiteusis Grube and its acetylcholinesterase(AChE)and superoxide dismutase(SOD)were examined. Results indicated that: 1) The value of LC50 was 1849.6mg·L-1 after a 3-day exposure to oxidation hair dyes. 2) The activities of AChE and SOD were influenced significantly by the exposure concentrations of oxidation hair dyes: After a 3-day exposure,the activities of AChE and SOD in exposure groups were higher than those of the control. With the increase of exposure concentrations(0~320mg·L-1),both AChE and SOD showed a tendency of inducement first and inhibition then. 3) The activities of AChE and SOD were influenced significantly by the exposure time(0~10d): The activity of SOD showed a tendency of inhibition first and inducement gradually then,however the activity of AChE changed irregularly. 4) Changes in the activity of SOD could reflect the toxic effect of oxidation hair dyes on Perinereis aibuhiteusis Grube better than that of AChE.