Synthesis of lipid A derivatives and their interactions with polymyxin B and polymyxin B nonapeptide

Lipid A is the causative agent of Gram-negative sepsis, a leading cause of mortality among hospitalized patients. Compounds that bind lipid A can limit its detrimental effects. Polymyxin B, a cationic peptide antibiotic, is one of the simplest molecules capable of selectively binding lipid A and may serve as a model for further development of lipid A binding agents. However, association of polymyxin B with lipid A is not fully understood, primarily due to the low solubility of lipid A in water and inhomogeneity of lipid A preparations. To better understand lipid A-polymyxin B interaction, pure lipid A derivatives were prepared with incrementally varied lipid chain lengths. These compounds proved to be more soluble in water than lipid A, with higher aggregation concentrations. Isothermal titration calorimetric studies of these lipid A derivatives with polymyxin B and polymyxin B nonapeptide indicate that binding stoichiometries (peptide to lipid A derivative) are less than 1 and that affinities of these binding partners correlate with the aggregation states of the lipid A derivatives. These studies also suggest that cooperative ionic interactions dominate association of polymyxin B and polymyxin B nonapeptide with lipid A.     

Luminescent heteronuclear Au(I)5Ag(I)8 complexes of [1,2,3-C6(C6H4R-4)3]3- (R = H, CH3, But) by cyclotrimerization of arylacetylides

Unusual AuI-AgI heterometallic complexes [Au5Ag8(mu-dppm)4{1,2,3-C6(C6H4R-4)3}(CCC6H4R-4)7]3+ (R = H 1, CH3 2, But 3) were isolated by reactions of polymeric silver arylacetylides (AgCCC6H4R-4)n with binuclear gold component [Au2(mu-dppm)2(MeCN)2]2+ (dppm = bis(diphenylphosphino)methane), in which cyclotrimerization of arylacetylide -CCC6H4R-4 affords trianion {1,2,3-C6(C6H4R-4)3}3- with an unprecedented mu5-bonding mode. Compounds 1(SbF6)3-3(SbF6)3 exhibit intense photoluminescence derived from an MLCT (Au5Ag8 --> CCC6H4R-4) transition, mixed with a metal cluster-centered excited states.     

气溶胶前向散射大气能见度测量系统传递系数的标定及校准方法

分析了气溶胶的前向角散射特性,利用标准的大气透射仪标定前向散射大气能见度测量系统的传递系数。当系统结构发生变化时,传递系数也随之改变,为保证系统测量的准确性和简化系统传递系数的标定过程,提出了一种利用标准漫透射板校准系统传递系数的方法。该方法使用了两块具有相同透射系数的漫透射板,使气溶胶粒子团在前向半球上产生漫散射,此时探测器的测量值即为包含了仪器常数的定值。当系统结构改变时,这个测量值相对于原测量值的变化率作为比例系数代入系统传递系数的计算,实现校准。     

N-Butyrylated Hyaluronic Acid Achieves Anti-Inflammatory Effects In Vitro and in Adjuvant-Induced Immune Activation in Rats

Previously synthesized N-butyrylated hyaluronic acid (BHA) provides anti-inflammatory effects in rat models of acute gouty arthritis and hyperuricemia. However, the mechanism of action remains to be elucidated. Herein, the anti-inflammatory and antioxidative activities of BHA and the targeted signaling pathways were explored with LPS-induced RAW264.7 and an adjuvant-induced inflammation in a rat model. Results indicated that BHA inhibited the generation of pro-inflammatory cytokines TNFα, IL-1β and IL-6, reduced ROS production and down-regulated JAK1-STAT1/3 signaling pathways in LPS-induced RAW264.7. In vivo, BHA alleviated paw and joint swelling, decreased inflammatory cell infiltration in paw tissues, suppressed gene expressions of p38 and p65, down-regulated the NF-κB and MAPK signaling pathways and reduced protein levels of TNFα, IL-1β and IL-6 in joint tissues of arthritis rats. This study demonstrated the pivotal role of BHA in anti-inflammation and anti-oxidation, suggesting the potential clinical value of BHA in the prevention of inflammatory arthritis and is worthy for development as a new pharmacological treatment.     

高频聚焦超声声场和温度场的仿真研究*

为探究临床常用的7 MHz高频聚焦超声在多层生物组织中的声传播以及毫秒级时间内的生物传热规律问题,基于Westervelt方程和Pennes传热方程,使用有限元方法建立高频聚焦超声辐照多层组织的非线性热黏性声传播及传热模型。首先分析了线性模型和非线性模型之间的差异,然后在非线性模型下探究换能器的参数对声场和温度场的影响。仿真结果显示：在7 MHz频率下,当换能器输出声功率超过5 W时,声波传播的非线性效应不可忽视(p <0.05);当声功率从5 W增大到15 W时,非线性模型与线性模型预测的温度偏差从20%增加到34.703%;高频聚焦超声波的非线性行为比低频更加显著,基频能量向高次谐波转移的程度增大,声功率为10 W和15 W时4次谐波与基波之比分别达到7.33%和12.12%;高频换能器参数的改变对组织中声场和温度场分布的影响较大,换能器焦距从12 mm减小到11.2 mm,焦点处最高温度增加了77%。结果表明,7 MHz聚焦超声的非线性声传播需要考虑到4次谐波的影响。该文提出的多层组织非线性仿真模型可为高频聚焦超声换能器参数优化及制定安全、有效的术前治疗方案提供理论参考。     

The Intervention of Prebiotics on Depression via the Gut–Brain Axis

The imbalance of intestinal microbiota can cause the accumulation of endotoxin in the main circulation system of the human body, which has a great impact on human health. Increased work and life pressure have led to a rise in the number of people falling into depression, which has also reduced their quality of life. The gut–brain axis (GBA) is closely related to the pathological basis of depression, and intestinal microbiota can improve depressive symptoms through GBA. Previous studies have proven that prebiotics can modulate intestinal microbiota and thus participate in human health regulation. We reviewed the regulatory mechanism of intestinal microbiota on depression through GBA, and discussed the effects of prebiotics, including plant polysaccharides and polyphenols on the regulation of intestinal microbiota, providing new clues for the prevention and treatment of depression.