Degradation kinetic study of lysine in lysine hydrochloride solutions for injection by determining its main degradation product

AbstractA limited number of researches have been reported to apply the Arrhenius equation to study the relationship between drugs and its degradation products so far. In the present work, the thermal degradation kinetics of lysine hydrochloride solutions for injection, the special solvent for ademetionine 1, 4-butanedisulfonate (SAM) for injection, was investigated at selected temperatures and pH values. The main degradation product of lysine was separated, purified, and confirmed as lysine lactam. A reversed-phase high performance liquid chromatographic (RP-HPLC) method without derivation was developed for the simultaneous determination of lysine and lysine lactam. The results confirmed that both the lysine degradation and lysine lactam generation followed zero-order reaction kinetics. The degradation and generation rate constants increased with increasing temperatures and decreasing pH values. The temperature-dependent degradation and generation reaction could be sufficiently modeled on the Arrhenius equation with the activation energy of 80.14 and 83.22 kJ/mol, respectively. Meanwhile, a linear relationship existed between the amount of lysine degradation and lysine lactam generation since the approximate activation energy. Considering there could be other side effects, we established an upper limit of lysine lactam (500 μg/ml), as the acceptable criteria for stability to estimate the shelf life together with lysine, which made the prediction more accurate and credible. Extrapolation data demonstrated that the lysine hydrochloride solutions for injection could be stable for two years stored at room temperature

Optimized properties of innovative ElectroChromic Device using ITO / Ag / ITO electrodes

The “Dielectric/Metal/Dielectric” (DMD) stacked films being used as transparent and conductive (TC) electrodes, have demonstrated excellent application in the ElectroChromic (EC) process and devices. In this work, multilayers (IAI) made of 50 nm of Indium Tin Oxide (ITO)/5 nm of metallic silver (Ag)/30 nm of ITO that exhibit band-gap, low resistance of 7.4 Ω and the high figure of merit of 9.9 × 10−3 Ω−1 were introduced in a complete five-layer Glass/IAI/NiOx/LiClO4-PC-PMMA/WO3/IAI/Glass ElectroChromic Device (ECD). The single IAI electrode as well as the two actives EC layers Glass/IAI/NiOx and Glass/IAI/WO3 were firstly characterized for their TC and EC properties respectively. Then, the EC properties of the complete five-layer ECD were analyzed. Fast response time (2.02 s for the bleaching and 2.25 s for complete coloration), wide optical modulation in the visible light region (∼55% at 550 nm), long lifetime (more than 6000 s), large capacity and good stability as well as high coloration efficiency (31.7 cm2 C−1) were obtained. The improved EC performance of ECD were related to the good electrical and optical properties of IAI electrode

Trimetazidine Attenuates Cardiac Dysfunction in Endotoxemia and Sepsis by Promoting Neutrophil Migration

Aims: Cardiac dysfunction can be a fatal complication during severe sepsis. The migration of neutrophils is significantly impaired during severe sepsis. We sought to determine the role of trimetazidine (TMZ) in regulation of neutrophil migration to the heart in a mouse model of sepsis and endotoxemia, and to identify the mechanism whereby TMZ confers a survival advantage.Methods and Results: C57/BL6 mice were (1) injected with LPS followed by 24-h TMZ administration, or (2) treated with TMZ (20 mg/kg/day) for 1 week post cecal ligation and puncture (CLP) operation. Echocardiography and Millar system detection showed that TMZ alleviated cardiac dysfunction and histological staining showed the failure of neutrophils migration to heart in both LPS- and CLP-induced mice. Bone marrow transplantation revealed that TMZ-pretreated bone marrow cells improved LPS- and CLP-induced myocardial dysfunction and enhanced neutrophil recruitment in heart. In CXCL2-mediated chemotaxis assays, TMZ increased neutrophils migration via AMPK/Nrf2-dependent up-regulation of CXCR2 and inhibition of GRK2. Furthermore, using luciferase reporter gene and chromatin immunoprecipitation assays, we found that TMZ promoted the binding of the Nrf2 and CXCR2 promoter regions directly. Application of CXCR2 inhibitor completely reversed the protective effects of TMZ in vivo. Co-culture of neutrophils and cardiomyocytes further validated that TMZ decreased LPS-induced cardiomyocyte pyroptosis by targeting neutrophils.Conclusion: Our findings suggested TMZ as a potential therapeutic agent for septic or endotoxemia associated cardiac dysfunction in mice.STUDY HIGHLIGHTS What is the current knowledge on the topic?Migration of neutrophils is significantly impaired during severe sepsis, but the underlying mechanisms remain unknown.What question did this study address?The effects of TMZ on cardiac dysfunction via neutrophils migration.What this study adds to our knowledgeTMZ attenuated LPS-induced cardiomyocyte pyroptosis and cardiac dysfunction by promoting neutrophils recruitment to the heart tissues via CXCR2.How this might change clinical pharmacology or translational scienceOur findings suggested TMZ as a potential therapeutic agent for septic cardiac dysfunction

Epigenetic control of embryo–uterine crosstalk at peri-implantation

Abstract(#br)Embryo implantation is one of the pivotal steps during mammalian pregnancy, since the quality of embryo implantation determines the outcome of ongoing pregnancy and fetal development. A large number of factors, including transcription factors, signalling transduction components, and lipids, have been shown to be indispensable for embryo implantation. Increasing evidence also suggests the important roles of epigenetic factors in this critical event. This review focuses on recent findings about the involvement of epigenetic regulators during embryo implantation

Analysis of Characteristic Quality Indexes of Gaoyou Duck Eggs

To explore the quality characteristics of Gaoyou duck eggs, metabolomics was used to analyze the quality indexes, basic nutritional indexes and small molecule metabolites. The results showed that the mass, egg shape index, egg yolk color, Haugh unit, egg white height, egg yolk index and crude protein content of Gaoyou duck eggs were higher than those of the other studied breeds. The contents of total amino acids, umami amino acids, branched-chain amino acids, total fatty acids and unsaturated fatty acids were higher, and the content of saturated fatty acids was lower, indicating that sensory quality parameters, amino acids and fatty acids can characterize the quality of Gaoyou duck eggs. The characteristic components of Gaoyou duck eggs were uncovered by metabolomic fingerprinting, principal component analysis (PCA), partial least squares discriminant analysis (PLS-DA), and hierarchical cluster analysis (HCA). Totally 252 compounds and 22 differential compounds were identified in egg yolk, and 184 compounds and 40 differential compounds in egg white. Among them, uridine 5’-monophosphate, guanosine 5’-monophosphate, and N-acetyl-D-glucosamine were the main differential nutrients, and arachidonic acid in egg yolk was the unique nutrient of Gaoyou duck eggs, while indole was not detected in the egg white of Gaoyou duck eggs

Genomic monitoring of SARS-CoV-2 uncovers an Nsp1 deletion variant that modulates type I interferon response

The SARS-CoV-2 virus, the causative agent of COVID-19, is undergoing constant mutation. Here, we utilized an integrative approach combining epidemiology, virus genome sequencing, clinical phenotyping, and experimental validation to locate mutations of clinical importance. We identified 35 recurrent variants, some of which are associated with clinical phenotypes related to severity. One variant, containing a deletion in the Nsp1-coding region (D500-532), was found in more than 20% of our sequenced samples and associates with higher RT-PCR cycle thresholds and lower serum IFN-beta levels of infected patients. Deletion variants in this locus were found in 37 countries worldwide, and viruses isolated from clinical samples or engineered by reverse genetics with related deletions in Nsp1 also induce lower IFN-beta responses in infected Calu-3 cells. Taken together, our virologic surveillance characterizes recurrent genetic diversity and identified mutations in Nsp1 of biological and clinical importance, which collectively may aid molecular diagnostics and drug design.Peer reviewe

Édouard Chavannes, Lu Xun et la Mission archéologique dans la Chine septentrionale

He Mengying. Édouard Chavannes, Lu Xun et la Mission archéologique dans la Chine septentrionale. In: Bulletin de l'Ecole française d'Extrême-Orient. Tome 103, 2017. pp. 453-472

Edouard Chavannes (1865-1918), founder of the modern Sinology

Cette thèse est consacrée au fondateur français de la sinologie moderne, Édouard Chavannes. Elle s’intéresse autant à sa vie qu’à ses travaux, à partir de ses archives et sources inédites (documents administratifs, correspondance, manuscrits de travail, collection de livres et d’objets) et de ses œuvres. Né dans une famille protestante, il était imprégné de persévérance et d’esprit scientifique. Après des études supérieures en philosophie, histoire et chinois, il se fit envoyer à la Légation de France à Pékin pour étudier la Chine. D’abord tenté par une carrière diplomatique, il fut nommé professeur de chinois au Collège de France. En suivant la voie tracée par ses prédécesseurs, il a ouvert de nouveaux champs de recherche sur l’histoire de la Chine ancienne, l’épigraphie et l’archéologie, les rituels taoïstes et les relations entre la Chine et ses voisins. Fondée sur la traduction et l’analyse croisée des livres historiques et des sources primaires (inscriptions et bas-reliefs sur pierre, fiches de bois et de bambou), la nouveauté de son apport repose sur une approche scientifique et critique. Ses missions en Chine lui permirent de collecter de nombreux documents et d’observer tant les monuments historiques que la société contemporaine. Il a entretenu une riche collaboration avec les chercheurs de divers domaines et pays. Les lettrés chinois ont joué un rôle important dans ses traductions et ses études épigraphiques, ainsi que dans la diffusion de ses œuvres en Chine, certains s’inspirant de lui dans leurs travaux. Il a publié de multiples œuvres de qualité et formé une génération de grands sinologues. Son influence demeure considérable encore aujourd’hui.This thesis is devoted on the French founder of modern Sinology, Édouard Chavannes. It explores his life as well as his works. The research is based on archives, primary sources (administrative documents, correspondence, working manuscripts, collection of books and objects), his books and articles. Born in a Protestant family, he was characterized by perseverance and a scientific spirit. After graduate studies in philosophy, history and Chinese, he was sent to the French Legation in Beijing to study China. Initially inclined to be a diplomat, he was appointed on the chair of Chinese professor at the College de France. Following the paths laid by his predecessors, he has invested the research fields in the history of ancient China, epigraphy and archaeology, Taoist rituals and relations between China and its neighboring countries. Based on translations and cross analysis of historical books and primary sources (inscriptions and carvings on stone, records on wooden and bamboo slips), the novelty of his contribution comes from his scientific and critical approach. His missions in China allowed him to collect documents and observe historical monuments and the contemporary society. He has maintained a rich collaboration with researchers in different fields. Chinese scholars have played an important role in his translations and epigraphic works, as well as in the propagation of his works in China. Some of their thinking and methods were probably inspired by him. He has published a large number of quality works of great diversity, and has trained a generation of great Sinologists. His influence remains important until today

Predicting Volatility Based on Interval Regression Models

Considering the inferior volatility tracking capability of the point-data-based models, we propose using the more informative price interval data and building interval regression models for volatility forecasting. To characterize the heterogeneity of the market and the nonlinearity of volatility, we incorporated the heterogeneous autoregressive structure and the Markov regime switching structure in the benchmark interval regression model, respectively, and thus propose three extended models. Our empirical examination on S&P 500 index shows that: (1) the proposed interval regression models significantly improve the volatility prediction accuracy compared to the point-data-based GARCH model. (2) Incorporating the heterogeneous structure significantly improves the volatility prediction accuracy, and the corresponding models significantly outperform the range-based ECARR model. (3) Incorporating the Markov regime switching structure improves the prediction performance, and the improvement is significant when the heterogeneous structure is characterized. The above results are robust under different market conditions, including the extremely volatile periods