Metal-Organic Framework Based on Pyrazinoquinoxaline Tetracarboxylic Acid for Fluorescence Sensing for Nitro Explosives.

The rapid and selective detection of nitro explosives has become one of the current urgent environmental and safety issues. Fluorescent metal-organic frameworks (MOFs) provide strong support for the development of photoactive materials with excellent sensing performances. In this work, Zn2+ and pyrazinoquinoxaline tetracarboxylic acid with high nitrogen content were selected to construct a MOF structure termed Zn-MOF, which had excellent optical properties. The fluorescence sensing performance of Zn-MOF for nitro explosives was also investigated. The structural advantages of Zn-MOF, such as its porous structure, abundant host-guest interaction sites, and stable framework, ensure the prerequisites for various applications. Zn-MOF is not only capable of responding to a wide range of substrates, such as Fe3+, Cr2O72-, and MnO4-, to achieve fluorescence quenching detection but also able to achieve sensitive fluorescence sensing behavior for nitro explosives. In particular, for trinitrotoluene, the Ksv value can reach 8.72 × 103 M-1. The results show that the introduction of pyrazinoquinoxaline groups into MOFs can be an effective strategy for the preparation of highly efficient fluorescent sensing materials for nitro explosives.

Cardiac Toxicity Induced by Long-Term Environmental Levels of MC-LR Exposure in Mice.

Cyanobacterial blooms are considered a serious global environmental problem. Recent studies provided evidence for a positive association between exposure to microcystin-LR (MC-LR) and cardiotoxicity, posing a threat to human cardiovascular health. However, there are few studies on the cardiotoxic effects and mechanisms of long-term low-dose MC-LR exposure. Therefore, this study explored the long-term toxic effects and toxic mechanisms of MC-LR on the heart and provided evidence for the induction of cardiovascular disease by MC-LR. C57BL/6 mice were exposed to 0, 1, 30, 60, 90, and 120 µg/L MC-LR via drinking water for 9 months and subsequently necropsied to examine the hearts for microstructural changes using H&E and Masson staining. The results demonstrated fibrotic changes, and qPCR and Western blots showed a significant up-regulation of the markers of myocardial fibrosis, including TGF-ß1, α-SMA, COL1, and MMP9. Through the screening of signaling pathways, it was found the expression of PI3K/AKT/mTOR signaling pathway proteins was up-regulated. These data first suggested MC-LR may induce myocardial fibrosis by activating the PI3K/AKT/mTOR signaling pathway. This study explored the toxicity of microcystins to the heart and preliminarily explored the toxic mechanisms of long-term toxicity for the first time, providing a theoretical reference for preventing cardiovascular diseases caused by MC-LR.

Hydrolysable tannins as a potential therapeutic drug for the human fibrosis-associated disease.

Fibrosis is a pathological change with abnormal tissue regeneration due to a response to persistent injury, which is extensively related to organ damage and failure, leading to high morbidity and mortality worldwide. Although the pathogenesis of fibrosis has been comprehensively elucidated, there are few effective therapies for treating fibrotic diseases. Natural products are increasingly regarded as an effective strategy for fibrosis with numerous favorable functions. Hydrolysable tannins (HT) are a type of natural products that have the potential to treat the fibrotic disease. In this review, we describe some biological activities and the therapeutic prospects of HT in organ fibrosis. Furthermore, the underlying mechanisms of inhibition of HT on fibrotic organs in relation to inflammation, oxidative stress, epithelial-mesenchymal transition, fibroblast activation and proliferation, and extracellular matrix accumulation are discussed. Understanding the mechanism of HT against fibrotic diseases will provide a new strategy for the prevention and attenuation of fibrosis progression.

Construction of a High Nuclear Gadolinium Cluster with Enhanced Magnetocaloric Effect through Structural Transition.

Starting from a dinuclear complex {Gd2(L)2(NO3)4(H2O)2}·2(CH3CN) (1) based on 2,6-dimethoxyphenol (HL), a nonanuclear cluster {Gd9(L)4(µ4-OH)2(µ3-OH)8(µ2-OCH3)4(NO3)8 (H2O)8}(OH)·2H2O (2) was obtained via modulating the amount of the ligand and base. Both of them have been structurally and magnetically characterized. Complex 1 decorates the Gd2 core bridged by double µ2-phenoxyl oxygen atoms and coordinated neutral CH3CN molecules, while 2 features the Gd9 core with a sandglass-like topology. Magnetic investigations reveal that the weaker antiferromagnetic interactions between adjacent metal ions exist in complex 2 than in 1, which is in agreement with the theoretical results. Meanwhile, the magnetocaloric effect with a maximum -ΔS m value changes from 27.32 to 40.60 J kg-1 K-1 at 2 K and 7 T.

Modulating the relaxation dynamics via structural transition from a dinuclear dysprosium cluster to a nonanuclear cluster.

A dinuclear dysprosium cluster [Dy2(NO3)4(H2O)2(L)2]·2CH3CN was successfully prepared by employing HL (HL = 2,6-dimethoxyphenol) and Dy(NO3)3·6H2O in a mixture of CH3OH and CH3CN. The conversion of this Dy2 compound by reaction with additional deprotonated ligand generated a Dy9 cluster [Dy9(µ4-OH)2(µ3-OH)8(µ2-OCH3)4(NO3)8(H2O)8(L)4](OH)·2H2O with the well-known "diabolo" topology. Magnetic investigation revealed that both of the clusters exhibit typical SMM characteristics, and variable magnetic relaxation with the energy barrier changing from 217.87 K to 9.24 K along with the transition from a dinuclear dysprosium cluster to a nonanuclear one. Ab initio calculations further confirm the corresponding structure-activity relationships that originate the different magnetic behaviours. This design may afford a feasible strategy for modulating the magnetic relaxation dynamics of polynuclear systems.

Role of PI3K/Akt signaling pathway in cardiac fibrosis.

Heart failure (HF) is considered as a severe health problem worldwide, while cardiac fibrosis is one of the main driving factors for the progress of HF. Cardiac fibrosis was characterized by changes in cardiomyocytes, cardiac fibroblasts, ratio of collagen (COL) I/III, and the excessive production and deposition of extracellular matrix (ECM), thus forming a scar tissue, which leads to pathological process of cardiac structural changes and systolic as well as diastolic dysfunction. Cardiac fibrosis is a common pathological change of many advanced cardiovascular diseases including ischemic heart disease, hypertension, and HF. Accumulated studies have proven that phosphoinositol-3 kinase (PI3K)/Akt signaling pathway is involved in regulating the occurrence, progression and pathological formation of cardiac fibrosis via regulating cell survival, apoptosis, growth, cardiac contractility and even the transcription of related genes through a series of molecules including mammalian target of rapamycin (mTOR), glycogen synthase kinase 3 (GSK-3), forkhead box proteins O1/3 (FoxO1/3), and nitric oxide synthase (NOS). Thus, the review focuses on the role of PI3K/Akt signaling pathway in the cardiac fibrosis. The information reviewed here should be significant in understanding the role of PI3K/Akt in cardiac fibrosis and contribute to the design of further studies related to PI3K/Akt and the cardiac fibrotic response, as well as sought to shed light on a potential treatment for cardiac fibrosis.

Effects of environmental contaminants in water resources on nonalcoholic fatty liver disease.

The global prevalence of nonalcoholic fatty liver disease (NAFLD) has been increasing rapidly in recent years, which is now estimated to be over 25%. NAFLD is one of the most common chronic liver diseases in the world. At present, with the rapid development of economy and industrialization, many chemicals are released into the environment. These chemical contaminants in the environment might cause harm to human health and result in lipid metabolism disorder during long-term exposure. Moreover, the incentive of many NAFLD cases is unknown, and the environmental risk factors of NAFLD need to be urgently identified. Hence, we focus on the impacts of several popular environmental contaminants in water environment on the development and progression of NAFLD. These contaminants mainly include microcystins (MCs), disinfection by-products (DBPs), heavy metals (HMs), dioxins and polychlorinated biphenyls (PCBs). Through analyzing a great many epidemiological and toxicological studies, we have found positive associations between NAFLD and chronic exposure to these contaminants at the environmental levels. This review may enhance the understanding of liver damage caused by environmental pollutants, which are considered as tangible environmental risk factors for NAFLD.

A Review of Cardiovascular Toxicity of Microcystins.

The mortality rate of cardiovascular diseases (CVD) in China is on the rise. The increasing burden of CVD in China has become a major public health problem. Cyanobacterial blooms have been recently considered a global environmental concern. Microcystins (MCs) are the secondary products of cyanobacteria metabolism and the most harmful cyanotoxin found in water bodies. Recent studies provide strong evidence of positive associations between MC exposure and cardiotoxicity, representing a threat to human cardiovascular health. This review focuses on the effects of MCs on the cardiovascular system and provides some evidence that CVD could be induced by MCs. We summarized the current knowledge of the cardiovascular toxicity of MCs, with regard to direct cardiovascular toxicity and indirect cardiovascular toxicity. Toxicity of MCs is mainly governed by the increasing level of reactive oxygen species (ROS), oxidative stress in mitochondria and endoplasmic reticulum, the inhibition activities of serine/threonine protein phosphatase 1 (PP1) and 2A (PP2A) and the destruction of cytoskeletons, which finally induce the occurrence of CVD. To protect human health from the threat of MCs, this paper also puts forward some directions for further research.

Effects of Microcystin-LR on the Microstructure and Inflammation-Related Factors of Jejunum in Mice.

The increasing cyanobacterial blooms have recently been considered a severe environmental problem. Microcystin-leucine arginine (MC-LR) is one of the secondary products of cyanobacteria metabolism and most harmful cyanotoxins found in water bodies. Studies show MC-LR negatively affects various human organs when exposed to it. The phenotype of the jejunal chronic toxicity induced by MC-LR has not been well described. The aim of this paper was to investigate the effects of MC-LR on the jejunal microstructure and expression level of inflammatory-related factors in jejunum. Mice were treated with different doses (1, 30, 60, 90 and 120 µg/L) of MC-LR for six months. The microstructure and mRNA expression levels of inflammation-related factors in jejunum were analyzed. Results showed that the microstructure of the jejunum was destroyed and expression levels of inflammation-related factors interleukin (IL)-1ß, interleukin (IL)-8, tumor necrosis factor alpha, transforming growth factor-ß1 and interleukin (IL)-10 were altered at different MC-LR concentrations. To the best of our knowledge, this is the first study that mice were exposed to a high dose of MC-LR for six months. Our data demonstrated MC-LR had the potential to cause intestinal toxicity by destroying the microstructure of the jejunum and inducing an inflammatory response in mice, which provided new insight into understanding the prevention and diagnosis of the intestinal diseases caused by MC-LR.

Loss of the Nodal modulator Nomo results in chondrodysplasia in zebrafish.

BACKGROUND: Transforming growth factor-ß (TGF-ß)/nodal signaling is involved in early embryonic patterning in vertebrates. Nodal modulator (Nomo, also called pM5) is a negative regulator of nodal signaling. Currently, the role of nomo gene in cartilage development in vertebrates remains unknown. METHODS: Nomo mutants were generated in a knockout model of zebrafish by clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (CRISPR/Cas9) targeting of the fibronectin type III domain. The expression of related genes, which are critical for chondrogenesis, was analyzed by whole-mount in situ hybridization and qRT-PCR. Whole-mount alcian staining was performed to analyze the cartilage structure. RESULTS: nomo is highly expressed in various tissues including the cartilage. We successfully constructed a zebrafish nomo knockout model. nomo homozygous mutants exhibited varying degrees of hypoplasia and dysmorphism on 4 and 5 dpf, which is similar to chondrodysplasia in humans. The key genes of cartilage and skeletal development, including sox9a, sox9b, dlx1a, dlx2a, osx, col10a1, and col11a2 were all downregulated in nomo mutants compared with the wildtype. CONCLUSION: The nomo gene positively regulates the expression of the master regulator and other key development genes involved in bone formation and cartilage development and it is essential for cartilage development in zebrafish.