Acceleration of Crystal Growth of Amorphous Griseofulvin by Low-Concentration Poly(ethylene oxide): Aspects of Crystallization Kinetics and Molecular Mobility

This study aims to investigate the crystallization behavior and molecular dynamics of amorphous griseofulvin (GSF) in the presence of low-concentration poly­(ethylene oxide) (PEO). We observe that the addition of 3% w/w PEO remarkably increases the crystal growth rate of GSF by two orders of magnitude in both the supercooled liquid and glassy states. The liquid dynamics of amorphous GSF in the presence and absence of PEO are characterized by dielectric spectroscopy. With an increase of the PEO content, the α-relaxation times of the systems decrease, indicating the increase of global molecular mobility. The couplings between molecular mobility and crystallization kinetics of GSF systems show strong time-dependences below <i>T</i>_g. The overlapping of α-relaxation times of GSF in presence and absence of PEO as a function of <i>T</i>_g/<i>T</i> suggest the “plasticization” effect of PEO additives. However, the crystallization kinetics of amorphous GSF containing low-concentration PEO do not overlap with those of pure GSF on a <i>T</i>_g/<i>T</i> scale. The remarkable accelerating effect of crystal growth of amorphous GSF by low-concentration PEO can be partially attributed to the increase of global mobility. The high segmental mobility of PEO is expected to strongly affect the crystal growth rates of GSF. These findings are relevant for understanding and predicting the physical stability of amorphous pharmaceutical solid dispersions

In Situ Generated HypoIodite Activator for the C2 Sulfonylation of Heteroaromatic <i>N</i>‑oxides

A mild approach for direct C2 sulfonylation of heteroaromatic <i>N</i>-oxides with sulfonyl hydrazides affording 2-sulfonyl quinolines/pyridines has been developed. A variety of heteroaromatic <i>N</i>-oxides and sulfonyl hydrazides participate effectively in this transformation which uses hypoiodites (generated in situ from NaI and TBHP) as a means of substrate activators. In this reaction, the <i>N</i>-oxide plays a dual role, acting as a traceless directing group as well as a source of oxygen atom

Meta-analysis of the hazard ratios of overall survival between bevacizumab and control therapy using random effect model.

<p>Bars, 95% confidence intervals (CI) of hazard ratio in patients receiving bevacizumab versus controls. The areas of the squares are proportional to the weights used for combining the data. The center of the lozenge gives the combined hazard ratio. The hazard ratio was considered statistically significant if the 95% CI for the overall hazard ratio did not overlap one.</p

Meta-analysis of the odds ratios of one-year survival rate between bevacizumab and control therapy.

<p>Bars, 95% confidence intervals (CI) of odds ratio in patients receiving bevacizumab versus controls. The areas of the squares are proportional to the weights used for combining the data. The center of the lozenge gives the combined odds ratio. The odds ratio was considered statistically significant if the 95% CI for the overall odds ratio did not overlap one.</p

A flow chart showing the progress of trials through the review.

<p>A flow chart showing the progress of trials through the review.</p

Meta-analysis of the hazard ratios of progression-free survival between bevacizumab and control therapy using random effect model.

<p><b>Bars, 95% confidence intervals (CI) of hazard ratio in patients receiving bevacizumab versus controls</b>. The areas of the squares are proportional to the weights used for combining the data. The center of the lozenge gives the combined hazard ratio. The hazard ratio was considered statistically significant if the 95% CI for the overall hazard ratio did not overlap one.</p

Applications and Challenges of Bacteriostatic Aptamers in the Treatment of Common Pathogenic Bacteria Infections

The continuous evolution and spread of common pathogenic bacteria is a major challenge in diagnosis and treatment with current biotechnology and modern molecular medicine. To confront this challenge, scientists urgently need to find alternatives for traditional antimicrobial agents. Various bacteriostatic aptamers obtained through SELEX screening are one of the most promising strategies. These bacteriostatic aptamers can reduce bacterial infection by blocking bacterial toxin infiltration, inhibiting biofilm formation, preventing bacterial invasion of immune cells, interfering with essential biochemical processes, and other mechanisms. In addition, aptamers may also help enhance the function of other antibacterial materials/drugs when used in combination. This paper has reviewed the bacteriostatic aptamers in the treatment of common pathogenic bacteria infections. For this aspect, first, bacteriostatic aptamers and their screening strategies are summarized. Then, the effect of molecular tailoring and modification on the performance of the bacteriostatic aptamer is analyzed, and the antibacterial mechanism and antibacterial strategy based on aptamers are introduced. Finally, the key technical challenges and their development prospects in clinical treatment are also carefully discussed

Evolutionary conservation of the circadian gene timeout in Metazoa

<i>Timeless </i>(<i>Tim</i>) is considered to function as an essential circadian clock gene in <i>Drosophila</i>. Putative homologues of the <i>Drosophila timeless </i>gene have been identified in both mice and humans. While <i>Drosophila </i>contains two paralogs, <i>timeless </i>and <i>timeout</i>, acting in clock/light entrainment and chromosome integrity/photoreception, respectively, mammals contain only one <i>Tim </i>homolog. In this paper, we study the phylogeny of the <i>timeless</i>/<i>timeout </i>family in 48 species [including 1 protozoan (<i>Guillardia theta</i>), 1 nematode (<i>Caenorhabditis elegans</i>), 8 arthropods and 38 chordates], for which whole genome data are available by using MEGA (Molecular Evolutionary Genetics Analysis). Phylogenetic Analysis by Maximum Likelihood (PAML) was used to analyze the selective pressure acting on metazoan <i>timeless</i>/<i>timeout </i>genes. Our phylogeny clearly separates insect <i>timeless </i>and <i>timeout </i>lineages and shows that non-insect animal <i>Tim </i>genes are homologs of insect <i>timeout</i>. In this study, we explored the relatively rapidly evolving <i>timeless </i>lineage that was apparently lost from most deuterostomes, including chordates, and from <i>Caenorhabditis elegans</i>. In contrast, we found that the <i>timeout </i>protein, often confusingly called “<i>timeless</i>” in the vertebrate literature, is present throughout the available animal genomes. Selection results showed that <i>timeout </i>is under weaker negative selection than <i>timeless</i>. Finally, our phylogeny of <i>timeless</i>/<i>timeout </i>showed an evolutionary conservation of the circadian clock gene <i>timeout </i>in Metazoa. This conservation is in line with its multifunctionality, being essential for embryonic development and maintenance of chromosome integrity, among others

Two DE patterns of stem proteins responding to <i>B</i>. <i>maydis</i>.

<p>S7 and S2 show enlarged images of protein spots 7 and 2, which were differentially expressed under <i>B</i>. <i>maydis</i> stress conditions; “C” refers to the protein pattern dissolved on the control gel, and “T” to the protein pattern dissolved on the treatment gel. The differential abundance of proteins was read using the PDQuest software and is plotted as the relative intensity enumerated in E7 and E2. E7 and E2 represent the relative expression of protein spots 7 and 2 in the control and treatment groups. “C” also refers to the control, and “T” to treatment. S7/E7 and S2/E2 are representative images of the differentially expressed proteins in the stems of soybean plants.</p

Proteomic Analysis of the Relationship between Metabolism and Nonhost Resistance in Soybean Exposed to <i>Bipolaris maydis</i>

<div><p>Nonhost resistance (NHR) pertains to the most common form of plant resistance against pathogenic microorganisms of other species. <i>Bipolaris maydis</i> is a non-adapted pathogen affecting soybeans, particularly of maize/soybean intercropping systems. However, no experimental evidence has described the immune response of soybeans against <i>B</i>. <i>maydis</i>. To elucidate the molecular mechanism underlying NHR in soybeans, proteomics analysis based on two-dimensional polyacrylamide gel electrophoresis (2-DE) was performed to identify proteins involved in the soybean response to <i>B</i>. <i>maydis</i>. The spread of <i>B</i>. <i>maydis</i> spores across soybean leaves induced NHR throughout the plant, which mobilized almost all organelles and various metabolic processes in response to <i>B</i>. <i>maydis</i>. Some enzymes, including ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO), mitochondrial processing peptidase (MPP), oxygen evolving enhancer (OEE), and nucleoside diphosphate kinase (NDKs), were found to be related to NHR in soybeans. These enzymes have been identified in previous studies, and STRING analysis showed that most of the protein functions related to major metabolic processes were induced as a response to <i>B</i>. <i>maydis</i>, which suggested an array of complex interactions between soybeans and <i>B</i>. <i>maydis</i>. These findings suggest a systematic NHR against non-adapted pathogens in soybeans. This response was characterized by an overlap between metabolic processes and response to stimulus. Several metabolic processes provide the soybean with innate immunity to the non-adapted pathogen, <i>B</i>. <i>maydis</i>. This research investigation on NHR in soybeans may foster a better understanding of plant innate immunity, as well as the interactions between plant and non-adapted pathogens in intercropping systems.</p></div