Mechanisms of Reciprocal Regulation of Gonadotropin-Releasing Hormone (GnRH)-Producing and Immune Systems: The Role of GnRH,Cytokines and Their Receptors in Early Ontogenesis in Normal and Pathological Conditions

Different aspects of the reciprocal regulatory influence on the development of gonadotropin-releasing hormone (GnRH)-producing- and immune systems in the perinatal ontogenesis and their functioning in adults in normal and pathological conditions are discussed. The influence of GnRH on the development of the immune system, on the one hand, and the influence of proinflammatory cytokines on the development of the hypothalamic-pituitary-gonadal system, on the other hand, and their functioning in adult offspring are analyzed. We have focused on the effects of GnRH on the formation and functional activity of the thymus, as the central organ of the immune system, in the perinatal period. The main mechanisms of reciprocal regulation of these systems are discussed. The reproductive health of an individual is programmed by the establishment and development of physiological systems during critical periods. Regulatory epigenetic mechanisms of development are not strictly genetically controlled. These processes are characterized by a high sensitivity to various regulatory factors, which provides possible corrections for disorders.     

Two Methods,One Goal: Structural Differences between Cocrystallization and Crystal Soaking to Discover Ligand Binding Poses

In lead optimization, protein crystallography is an indispensable tool to analyze drug binding. Binding modes and non-covalent interaction inventories are essential to design follow-up synthesis candidates. Two protocols are commonly applied to produce protein–ligand complexes: cocrystallization and soaking. Because of its time and cost effectiveness, soaking is the more popular method. Taking eight ligand hinge binders of protein kinase A, we demonstrate that cocrystallization is superior. Particularly for flexible proteins, such as kinases, and larger ligands cocrystallization captures more reliable the correct binding pose and induced protein adaptations. The geometrical discrepancies between soaking and cocrystallization appear smaller for fragment-sized ligands. For larger flexible ligands that trigger conformational changes of the protein, soaking can be misleading and underestimates the number of possible polar interactions due to inadequate, highly impaired positions of protein amino-acid side and main chain atoms. Thus, if applicable cocrystallization should be the gold standard to study protein–ligand complexes.     

High-Efficiency Organic Solar Cells Based on a Low-Cost Fully Non-Fused Electron Acceptor

A series of tetrathiophene-based fully non-fused ring acceptors (4T-1, 4T-2, 4T-3, and 4T-4), which can be paired with the star donor polymer PBDB-T to fabricate highly efficient organic solar cells are developed. Tailoring the size of lateral chains can tune the solubility and packing mode of acceptor molecules in neat and blend films. It is found that the incorporation of 2-ethylhexyl chains can effectively change the compatibility with the donor polymer PBDB-T, and an encouraging power conversion efficiency of 10.15% is accomplished by 4T-3-based organic solar cells. It also presents good compatibility with the other polymer donor and an even higher power conversion efficiency (PCE) of 12.04% is achieved based on D18:4T-3 blend, which is the champion PCE for the fully non-fused acceptors. Importantly, these inexpensive tetrathiophene fully non-fused ring acceptors provide cost-effective photovoltaic performance. The results demonstrate a high photovoltaic performance from synthetically inexpensive materials could be achieved by the rational design of non-fused ring acceptor molecules.     

Electrochemical Quantification of Neurotransmitters in Single Live Cell Vesicles Shows Exocytosis is Predominantly Partial

Exocytosis plays an essential role in the communication between cells in the nervous system. Understanding the regulation of neurotransmitter release during exocytosis and the amount of neurotransmitter content that is stored in vesicles is of importance, as it provides fundamental insights to understand how the brain works and how neurons elicit a certain behavior. In this minireview, we summarize recent progress in amperometric measurements for monitoring exocytosis in single cells and electrochemical cytometry measurements of vesicular neurotransmitter content in individual vesicles. Important steps have increased our understanding of the different mechanisms of exocytosis. Increasing evidence is firmly establishing that partial release is the primary mechanism of release in multiple cell types.     

Ir(III) and Ru(II) Complexes in Photoredox Catalysis and Photodynamic Therapy: A New Paradigm towards Anticancer Applications

Individually, photoredox catalysis (PC) and photodynamic therapy (PDT) are well-established concepts that have experienced a remarkable resurgence in recent years, leading to significant progress in organic synthesis for PC and clinical approval of anticancer drugs for PDT. But, very recently, new photoredox catalyst systems based on Ir(III) and Ru(II) complexes have garnered significant interest because they can simultaneously be used as PDT agents apart from their demonstrated PC activity. This highlight discusses the unique PC behavior of emerging Ir(III)- and Ru(II)-based systems while also examining their potential PDT activity in cancer treatment.     

Transposable Elements and Stress in Vertebrates: An Overview

Since their identification as genomic regulatory elements, Transposable Elements (TEs) were considered, at first, molecular parasites and later as an important source of genetic diversity and regulatory innovations. In vertebrates in particular, TEs have been recognized as playing an important role in major evolutionary transitions and biodiversity. Moreover, in the last decade, a significant number of papers has been published highlighting a correlation between TE activity and exposition to environmental stresses and dietary factors. In this review we present an overview of the impact of TEs in vertebrate genomes, report the silencing mechanisms adopted by host genomes to regulate TE activity, and finally we explore the effects of environmental and dietary factor exposures on TE activity in mammals, which is the most studied group among vertebrates. The studies here reported evidence that several factors can induce changes in the epigenetic status of TEs and silencing mechanisms leading to their activation with consequent effects on the host genome. The study of TE can represent a future challenge for research for developing effective markers able to detect precocious epigenetic changes and prevent human diseases.     

AAOA-MBR工艺在工程中的应用分析

通过对AAOA-MBR工艺在实际工程中的应用,分析该工艺处理城市污水的节能减排效能。实践表明AAOA-MBR工艺具有很强的抗冲击负荷能力,在进水质水量大幅度波动、且碳源匮乏的情况下,仍能取得良好的处理效果。实际工程运行四年来,厂区出水各项指标均稳定优于城镇污水处理厂污染物排放标准(GB 18918-2002)中的一级A标准,其中COD、BOD₅、SS、NH₃^-N去除率分别达到可分别达到90.14%、98.25%、95.58%和98.2%;通过对运行期间污水处理量与耗电量相关关系进行回归分析可知,当处理水量达到设计规模时,其吨水耗电量预测为0.31kWh/m³。同时,基于对污水处理系统的沿程水质检测,优化进水水量分配和内循环回流比并进行产水泵联动改造,可进一步提高系统节能减排效果。     

Molding,patterning and driving liquids with light

When a laser beam induces surface tension gradient at the free surface of a liquid, a weak surface depression is expected and has been observed. Here we report giant depression and rupture in “optothermocapillary fluids” under the illumination of laser and sunlight. Computational fluid dynamics models were developed to understand the surface deformation and provided desirable physical parameters of the fluid for maximum deformation. New optothermocapillary fluids were created by mixing transparent lamp oil with different candle dyes. They can be cut open by sunlight and be patterned to different shapes and sizes using an ordinary laser show projector or a common laser pointer. Laser driving and elevation of optothermocapillary fluids, in addition to the manipulation of different droplets on their surface, were demonstrated as an efficient controlling method and platform for optofluidic operations. The fundamental understanding of light-induced giant depression and creation of new optothermocapillary fluids encourage the fundamental research and applications of optofluidics.     

Alkylated indolo[3,2,1-jk]carbazoles as new building blocks for solution processable organic electronics

A facile strategy for the introduction of tert-butyl and hexyl chains to the indolo[3,2,1-jk]carbazole scaffold is presented. With these building blocks six materials based on three different 4,4′-bis(N-carbazolyl)-1,1-biphenyl derivatives with varying degree of planarization were prepared. Characterization of the materials showed that the alkyl chains have only minor effects on the photophysical properties of the compounds. In contrast, thermal robustness towards decomposition and electrochemical stability are increased by the introduced alkyl chains. Detailed investigation of the solubility in five different solvents revealed that the incorporation of the alkyl chains increases the solubility significantly. The increased solubility of the materials allowed the application as host materials in red, green and sky-blue solution processed phosphorescent organic light emitting diodes. Hence, this work presents the first solution processed light emitting devices based on the indolo[3,2,1-jk]carbazole scaffold.     

Lactones in the Synthesis of Prostaglandins and Prostaglandin Analogs

In the total stereo-controlled synthesis of natural prostaglandins (PGs) and their structural analogs, a vast class of compounds and drugs, known as the lactones, are encountered in a few key steps to build the final molecule, as: δ-lactones, γ-lactones, and 1,9-, 1,11-, and 1,15-macrolactones. After the synthesis of 1,9-PGF_2α and 1,15-PGF_2α lactones, many 1,15-lactones of E₂, E₃, F₂, F₃, A₂, and A₃ were found in the marine mollusc Tethys fimbria and the quest for understanding their biological role stimulated the research on their synthesis. Then 1,9-, 1,11-, and 1,15-PG lactones of the drugs were synthesized as an alternative to the corresponding esters, and the first part of the paper describes the methods used for their synthesis. The efficient Corey procedure for the synthesis of prostaglandins uses the key δ-lactone and γ-lactone intermediates with three or four stereocenters on the cyclopentane fragment to link the PG side chains. The paper describes the most used procedures for the synthesis of the milestone δ-Corey-lactones and γ-Corey-lactones, their improvements, and some new promising methods, such as interesting, new stereo-controlled and catalyzed enantioselective reactions, and methods based on the chemical/enzymatic resolution of the compounds in different steps of the sequences. The many uses of δ-lactones not only for the synthesis of γ-lactones, but also for obtaining 9β-halogen-PGs and halogen-substituted cyclopentane intermediates, as synthons for new 9β-PG analogs and future applications, are also discussed.