Augmented cellular trafficking and endosomal escape of porous silicon nanoparticles via zwitterionic bilayer polymer surface engineering

The development of a stable vehicle with low toxicity, high cellular internalization, efficient endosomal escape, and optimal drug release profile is a key bottleneck in nanomedicine. To overcome all these problems, we have developed a successful layer-by-layer method to covalently conjugate polyethyleneimine (PEI) and poly(methyl vinyl ether-co-maleic acid) (PMVE-MA) copolymer on the surface of undecylenic acid functionalized thermally hydrocarbonized porous silicon nanoparticles (UnTHCPSi NPs), forming a bilayer zwitterionic nanocomposite containing free positive charge groups of hyper-branched PEI disguised by the PMVE-MA polymer. The surface smoothness, charge and hydrophilicity of the developed NPs considerably improved the colloidal and plasma stabilities via enhanced suspensibility and charge repulsion. Furthermore, despite the surface negative charge of the bilayer polymer-conjugated NPs, the cellular trafficking and endosomal escape were significantly increased in both MDA-MB-231 and MCF-7 breast cancer cells. Remarkably, we also showed that the conjugation of surface free amine groups of the highly toxic UnTHCPSi-PEI (Un-P) NPs to the carboxylic groups of PMVE-MA renders acceptable safety features to the system and preserves the endosomal escape properties via proton sponge mechanism of the free available amine groups located inside the hyper-branched PEI layer. Moreover, the double layer protection not only controlled the aggregation of the NPs and reduced the toxicity, but also sustained the drug release of an anticancer drug, methotrexate, with further improved cytotoxicity profile of the drug-loaded particles. These results provide a proof-of-concept evidence that such zwitterionic polymer-based PSi nanocomposites can be extensively used as a promising candidate for cytosolic drug delivery.     

基于权重基因共表达网络分析挖掘人参皂苷Rh1生物合成相关基因

目的 通过权重基因共表达网络分析（weighted gene co-expression network analysis,WGCNA）挖掘人参皂苷Rh1生物合成相关基因。方法 以种植于吉林省人参主产区304个农家品种的转录组测序数据为基础,以人参皂苷Rh1含量为表型进行差异表达基因的挖掘。结果 通过WGCNA获得6个与人参皂苷Rh1含量密切相关的基因共表达模块,根据关联分析结果确定Green模块为与人参皂苷Rh1含量显著相关的关键模块。功能注释结果显示Green模块内的基因富集到m RNA结合、蛋白修饰等多个相关途径。通过构建基因互作网络筛选获得7个核心基因,功能预测表明这些基因可能在人参皂苷Rh1的生物合成途径中起着重要作用。对7个候选基因进行茉莉酸甲酯（methyl jasmonate,Me JA）体外调控分析。对人参不定根进行MeJA诱导处理,随Me JA的诱导,comp9517＿c0＿seq1、comp10896＿c0＿seq1、comp43180＿c0＿seq2、comp64014＿c0＿seq8的表达量与人参皂苷Rh1的含量同时呈现显著变化,但只有comp64014＿c0...     

川西合耳菊中1个新的艾里莫芬烷倍半萜

目的 研究川西合耳菊Synotis solidaginea的化学成分。方法 采用硅胶、聚酰胺、反相C₁₈柱色谱及制备高效液相色谱等技术进行分离纯化;根据波谱数据和文献对比进行化合物结构鉴定。结果 从川西合耳菊的醋酸乙酯萃取部位共分离得到18个化合物,分别鉴定为 (2R,4S,5R,8R,10S)-2-angeloyloxy-8,10-dihydroxy-eremophil-7(11)-en-8,12-olide（1）、(1R,4S,5S, 6S,8R,10S)-1,10-epoxy-6,8-dihydroxy-eremophil-7(11)-en-8,12-olide（2）、(4S,5R,8S,10S)-8,10-dihydroxy-eremophil-7(11)-en- 8,12-olide（3）、(4S,5R,8R,10S)-10-hydroxy-eremophil-7(11)-en-8,12-olide（4）、橐吾内酯（5）、4,5-O-二咖啡酰奎宁酸甲酯（6）、异绿原酸C（7）、3,5-O-二咖啡酰基奎宁酸甲酯（8）、异绿原酸A（9）、1,4-O-二咖啡酰奎宁酸甲酯（10）、绿原酸（11）、咖啡酰苹果酸（12）、咖啡酸甲酯（13）、反式咖啡酸（14）、山柰酚-3-O-(6''-O-乙酰基)-β-D-吡喃葡萄糖苷（15）、紫云英苷（16）、2-苯乙基-β-D-吡喃葡萄糖苷（17）、桦褐孔菌二糖（18）。结论 化合物1为新的艾里莫芬烷倍半萜类化合物,命名为川西合耳菊内酯A;化合物2、4、5、10、12、13、15、17、18为首次从合耳菊属中分离得到。     

覆盆子化学成分的分离鉴定及其新型大麻素2型受体激动剂的筛选和抗骨质疏松作用评价

目的 以大麻素2型受体（cannabinoid receptor type 2,CB2R）为靶点,从补肾中药覆盆子中分离、鉴定、筛选得到具有激动CB2R的激动剂,并探讨其抗骨质疏松作用的机制。方法 以激动CB2R活性为导向进行分离并筛选,采用正相硅胶柱色谱、凝胶柱色谱、大孔树脂、重结晶和半制备型高效液相色谱对二氯甲烷层和醋酸乙酯层浸膏进行分离,结合化合物理化性质和核磁共振波谱对分离得到的化合物进行结构鉴定。通过双荧光素酶方法筛选出具有可特异性激动CB2R的化合物,并通过测定转染CB2R的人胚胎肾细胞HEK293-CB2内环磷酸腺苷（cyclic adenosine monophosphate,c AMP）积聚水平和CB2R蛋白表达情况来验证筛选的化合物对CB2R的特异性激动活性,最后评价筛选得到的化合物对破骨细胞骨代谢方面的调节作用。结果 以激动CB2R为活性导向进行分离和筛选,共得到24个化合物,分别鉴定为山柰酚（1）、木犀草苷（2）、银椴苷（3）、金丝桃苷（4）、橙皮素（5）、刺芒柄花素（6）、槲皮素（7）、对羟基苯甲酸（8）、迷迭香酸（9）、对羟基苯甲酸乙酯（10）、水杨酸（11...     

Solvent-Impregnated Sorbents for Tantalum from Niobium Separation Using a Fixed-Bed Column

Reactor-grade niobium steel is used as a construction material for nuclear reactors. In this case, the presence of tantalum, which is characterized by a 20 times higher active cross section for capturing thermal neutrons than the cross section of niobium (¹⁸¹Ta: 21.3 barn), cannot exceed 100 ppm. Analytical methods for quality and new separation method development control need very pure niobium matrices—niobium compounds with a low tantalum content, which are crucial for preparing matrix reference solutions or certified reference materials (CRMs). Therefore, in this paper, a new, efficient method for separating trace amounts of Ta(V) from Nb(V) using extraction chromatography with the use of sorbents impregnated with methyl isobutyl ketone MIBK solvent is proposed. Various types of MIBK-impregnated sorbents were used (AG^® 1-X8 Anion Exchange Resin, AMBERLITE™ IRC120 Na Ion Exchange Resin, SERVACEL^® Cellulose Anion Exchangers DEAE 52, active carbons of various grain size, carbonized blackcurrant pomace, carbonized chokeberry pomace, bentonite, and polyurethane foam in lumps). The highest tantalum removal efficiency was determined using active coal-based materials (>97%). The separation effectivity of tantalum from niobium was also determined in dynamic studies using a fixed-bed column with MIBK-impregnated active carbon. Solutions of various Nb:Ta weight ratios (1:1, 100:1, 1000:1) were used. The most impressive result was obtaining 70 mL of high purity niobium solution of tantalum content 0.027 ppm (in relation to Nb) with 88.4% yield of niobium from a solution of Nb:Ta, weight ratio 1000:1 (purge factor equaled 35,000). It proves the presented system to be applicable for preparation of pure niobium compounds with very low contents of tantalum.     

一氧化氮合酶抑制剂对大肠癌裸鼠移植瘤的抗血管生成作用

目的:观察一氧化氮合酶抑制剂N-硝基精氨酸甲酯(L-NAME)对大肠癌细胞的抑制作用,以及对移植瘤内血管生成的影响.方法:建立大肠癌裸鼠移植瘤模型再随机分为生理盐水对照组(n=6,0.2 mL)、L-NAME组(n=6,1.5 mg/kg)、5-FU组(n=6,5 mg/ kg)、L-NAME 5-FU联合组(n=6,L-NAME 1.5 mg/kg,5-FU 5 mg/kg),皆以灌胃方式给药,3次/wk,共2 wk.测量各组肿瘤体积,观察L-NAME的体内抗瘤作用.采用免疫组化方法观察移植瘤的微血管密度(MVD),用Western blot方法检测肿瘤组织VEGF蛋白的表达.结果:L-NAME,5-FU,L-NAME 5-FU组抑瘤率分别为34.1%、46.0%、74.1%,与对照组比较,有显著性差异(P<0.01),联合治疗组与L-NAME,5-FU组比较,差异也有显著性(P<0.01);MVD值对照组为28.9±2.7,L-NAME组为16.2±3.1,与对照组比较,差异有显著性(P<0.05);L-NAME组移植瘤VEGF蛋白的表达(113.14±2.34),与对照组(98.56±1.76)相比,明显减弱(P<0.05).结论:L-NAME具有抑制肿瘤新生血管生成的作用,可抑制大肠癌裸鼠移植瘤的生长;和5-FU联合具有协同抗肿瘤作用.     

Surface Characteristics and Microbiological Analysis of a Vat-Photopolymerization Additive-Manufacturing Dental Resin

The wide application of additive manufacturing in dentistry implies the further investigation into oral micro-organism adhesion and biofilm formation on vat-photopolymerization (VP) dental resins. The surface characteristics and microbiological analysis of a VP dental resin, printed at resolutions of 50 μm (EG-50) and 100 μm (EG-100), were evaluated against an auto-polymerizing acrylic resin (CG). Samples were evaluated using a scanning electron microscope, a scanning white-light interferometer, and analyzed for Candida albicans (CA) and Streptococcus mutans (SM) biofilm, as well as antifungal and antimicrobial activity. EG-50 and EG-100 exhibited more irregular surfaces and statistically higher mean (Ra) and root-mean-square (rms) roughness (EG-50-Ra: 2.96 ± 0.32 µm; rms: 4.05 ± 0.43 µm/EG-100-Ra: 3.76 ± 0.58 µm; rms: 4.79 ± 0.74 µm) compared to the CG (Ra: 0.52 ± 0.36 µm; rms: 0.84 ± 0.54 µm) (p < 0.05). The biomass and extracellular matrix production by CA and SM and the metabolic activity of SM were significantly decreased in EG-50 and EG-100 compared to CG (p < 0.05). CA and SM growth was inhibited by the pure unpolymerized VP resin (48 h). EG-50 and EG-100 recorded a greater irregularity, higher surface roughness, and decreased CA and SM biofilm formation over the CG.     

牛蒡根化学成分研究

目的研究牛蒡Arctium lappa根的化学成分。方法运用正相硅胶、ODS柱色谱以及半制备型HPLC等手段进行分离纯化,并采用核磁共振等现代波谱学技术鉴定化合物结构。结果从牛蒡根55%乙醇提取物醋酸乙酯部位中分离得到14个化合物,分别鉴定为1,5-二咖啡酰-3-苹果酰奎尼酸(1)、3,5-二咖啡酰-1-(2-咖啡酰-4-苹果酰)-奎尼酸(2)、3,5-二咖啡酰-1-(2-咖啡酰-4-苹果酰甲酯)-奎尼酸(3)、3,5-二咖啡酰-1-琥珀酰甲酯奎尼酸(4)、3,4-二咖啡酰-1-琥珀酰甲酯奎尼酸(5)、1,3,5-三咖啡酰-4-琥珀酰奎尼酸(6)、1,5-二咖啡酰-3-琥珀酰奎尼酸(7)、1,5-二咖啡酰-4-琥珀酰奎尼酸(8)、1,5-二咖啡酰-4-琥珀酰甲酯奎尼酸(9)、1,5-二咖啡酰-3-琥珀酰甲酯奎尼酸(10)、1,3,4-三咖啡酰奎尼酸(11)、1,4,5-三咖啡酰奎尼酸甲酯(12)、3-咖啡酰奎尼酸(13)、4-羟基苯乙酸(14),其中13个为咖啡酰奎尼酸衍生物。结论化合物3~5、9、11、12为首次从该属植物中分离得到,化合物14为首次从该植物中分离得到。     

Association between prenatal dietary methyl mercury exposure and developmental outcomes on acquisition of articulatory-phonologic skills in children in the Republic of Seychelles

Methyl mercury (MeHg) is a neurotoxicant that with sufficient exposure can seriously impair the central nervous system and cause mental retardation, cerebral palsy, and neuromotor dysfunction. The level of exposure needed to adversely affect the nervous system is unknown. Human exposure to low levels of MeHg is common from consumption of fish. We examined the relationship between MeHg exposure and development of articulatory-phonologic speech skills in children whose mothers consumed a diet high in fish during pregnancy to determine whether any adverse associations could be detected. A total of 544 children from the Republic of Seychelles were given a speech assessment when they were 66 months of age. Exposure level was determined by measuring MeHg in maternal hair growing during pregnancy. No adverse associations between articulatory- phonologic speech skills and prenatal MeHg exposure were detected. The findings of this investigation are compatible with previous developmental assessments of Seychellois children that have indicated no adverse effects of prenatal MeHg exposure from fish consumption.