Stable isotopes and hydrogeochemical evolutions of groundwater from a typical seismic fault zone in the Mt. Lushan region, Eastern China

We analyzed the major chemical components, hydrogen (δD) and oxygen isotopes (δ18O), and tritium activity in groundwater from Jiujiang well number 2 (JJ2) as well as atmospheric precipitation and water from the Maweishui spring and Tianhuajing reservoir in the Mt. Lushan region, Eastern China. The results show that the water in JJ2 is of the HCO3-Ca·Mg type, with ionic components mainly arising from calcite and dolomite mineral dissolution. According to the δD and δ18O data, the groundwater of JJ2 mainly comes from atmospheric precipitation, and the recharge elevation is 554 m. Results for tritium activity indicate that JJ2 is fed by both an ancient water supply and a new water supply within a period of 10 years. These results demonstrate that JJ2 has characteristics of both shallow and deep circulating water, which implies that aquifers involving two different recharge sources rise to the well surface via different circulation paths. That is exactly why JJ2 is tectonically sensitive and could display a remarkable gas radon anomaly before the Ruichang-Yangxin ML 5.0 earthquake in 2011. Our results also indicate that ascertaining the hydrological characteristics and cycling process of groundwater are crucial for understanding the earthquake anomalies and judging whether a seismic groundwater monitoring well is reliable or not

TBR2 coordinates neurogenesis expansion and precise microcircuit organization via Protocadherin 19 in the mammalian cortex.

Cerebral cortex expansion is a hallmark of mammalian brain evolution; yet, how increased neurogenesis is coordinated with structural and functional development remains largely unclear. The T-box protein TBR2/EOMES is preferentially enriched in intermediate progenitors and supports cortical neurogenesis expansion. Here we show that TBR2 regulates fine-scale spatial and circuit organization of excitatory neurons in addition to enhancing neurogenesis in the mouse cortex. TBR2 removal leads to a significant reduction in neuronal, but not glial, output of individual radial glial progenitors as revealed by mosaic analysis with double markers. Moreover, in the absence of TBR2, clonally related excitatory neurons become more laterally dispersed and their preferential synapse development is impaired. Interestingly, TBR2 directly regulates the expression of Protocadherin 19 (PCDH19), and simultaneous PCDH19 expression rescues neurogenesis and neuronal organization defects caused by TBR2 removal. Together, these results suggest that TBR2 coordinates neurogenesis expansion and precise microcircuit assembly via PCDH19 in the mammalian cortex

Variations in the fecal microbiota and their functions of Thoroughbred, Mongolian, and Hybrid horses

The horse gut is colonized by a rich and complex microbial community that has important roles in horse physiology, metabolism, nutrition, and immune functions. Fewer across-breed variations in horse gut microbial diversity have been illustrated. In this article, the gut microbiota of Thoroughbred, Mongolian, and Hybrid horses [first filial generation (F1) of Mongolian (maternal) and Thoroughbred (paternal)] were studied by second-generation high-throughput sequencing technology. Differences in gut microbiota composition and function between breeds were determined using diversity and functional prediction analysis. The alpha diversity analysis showed that Thoroughbred horses had a more abundant and diverse gut microbiota, while the diversity of gut microbiota in Hybrid horses was intermediate between Thoroughbred and Mongolian horses. Subsequent cluster analysis showed that Hybrid horses have a microbiota composition more similar to Mongolian horses. LEfSe analysis revealed that the bacterial biomarkers for Thoroughbred horses at the family level were Prevotellaceae, Rikenellaceae, Fibrobacteraceae, p_251_o5, Lactobacillaceae, and uncultured_bacterium_o_WCHB1_41; the bacterial biomarker for Mongolian horses was Planococcaceae; and the bacterial biomarkers for Hybrid horses were Moraxellaceae, Enterobacteriaceae, and Ruminococcaceae. The functional prediction results indicated that the metabolic pathways differ significantly between the breeds. Regarding metabolism, the Hybrid horses had the lowest proportion of the carbohydrate metabolic pathways, while the energy metabolic pathway had the highest proportion. The abundance ratios of the remaining eight metabolic pathways in Hybrid horses were between Thoroughbred and Mongolian horses. In conclusion, the results of this study showed an association between horse breeds and gut microbiota

Detection of neural connections with ex vivo MRI using a ferritin-encoding trans-synaptic virus

The elucidation of neural networks is essential to understanding the mechanisms of brain functions and brain disorders. Neurotropic virus-based trans-synaptic tracing tools have become an effective method for dissecting the structure and analyzing the function of neural-circuitry. However, these tracing systems rely on fluorescent signals, making it hard to visualize the panorama of the labeled networks in mammalian brain in vivo. One MRI method, Diffusion Tensor Imaging (DTI), is capable of imaging the networks of the whole brain in live animals but without information of anatomical connections through synapses. In this report, a chimeric gene coding for ferritin and enhanced green fluorescent protein (EGFP) was integrated into Vesicular stomatitis virus (VSV), a neurotropic virus that is able to spread anterogradely in synaptically connected networks. After the animal was injected with the recombinant VSV (rVSV), rVSV-Ferritin-EGFP, into the somatosensory cortex (SC) for four days, the labeled neural-network was visualized in the postmortem whole brain with a T2-weighted MRI sequence. The modified virus transmitted from SC to synaptically connected downstream regions. The results demonstrate that rVSV-Ferritin-EGFP could be used as a bimodal imaging vector for detecting synaptically connected neural-network with both ex vivo MRI and fluorescent imaging. The strategy in the current study has the potential to longitudinally monitor the global structure of a given neural-network in living animals

CircUBXN7 promotes macrophage infiltration and renal fibrosis associated with the IGF2BP2-dependent SP1 mRNA stability in diabetic kidney disease

IntroductionInflammatory cell infiltration is a novel hallmark of diabetic kidney disease (DKD), in part, by activated macrophages. Macrophage-to-tubular epithelial cell communication may play an important role in renal fibrosis. Circular RNAs (circRNAs) have been reported in the pathogenesis of various human diseases involving macrophages activation, including DKD. However, the exact mechanism of circRNAs in macrophage infiltration and renal fibrosis of DKD remains obscure.MethodsIn our study, a novel circRNA circUBXN7 was identified in DKD patients using microarray. The function of circUBXN7 in vitro and in vivo was investigated by qRT-PCR, western blot, and immunofluorescence. Finally, a dual-luciferase reporter assay, ChIP, RNA pull-down, RNA immunoprecipitation and rescue experiments were performed to investigate the mechanism of circUBXN7.ResultsWe demonstrated that the expression of circUBXN7 was significantly upregulated in the plasma of DKD patients and correlated with renal function, which might serve as an independent biomarker for DKD patients. According to investigations, ectopic expression of circUBXN7 promoted macrophage activation, EMT and fibrosis in vitro, and increased macrophage infiltration, EMT, fibrosis and proteinuria in vivo. Mechanistically, circUBXN7 was transcriptionally upregulated by transcription factor SP1 and could reciprocally promote SP1 mRNA stability and activation via directly binding to the m6A-reader IGF2BP2 in DKD.ConclusionCircUBXN7 is highly expressed in DKD patients may provide the potential biomarker and therapeutic target for DKD

Over-Expression of LSD1 Promotes Proliferation, Migration and Invasion in Non-Small Cell Lung Cancer

Background: Lysine specific demethylase 1 (LSD1) has been identified and biochemically characterized in epigenetics, but the pathological roles of its dysfunction in lung cancer remain to be elucidated. The aim of this study was to evaluate the prognostic significance of LSD1 expression in patients with non-small cell lung cancer (NSCLC) and to define its exact role in lung cancer proliferation, migration and invasion. Methods: The protein levels of LSD1 in surgically resected samples from NSCLC patients were detected by immunohistochemistry or Western blotting. The mRNA levels of LSD1 were detected by qRT-PCR. The correlation of LSD1 expression with clinical characteristics and prognosis was determined by statistical analysis. Cell proliferation rate was assessed by MTS assay and immunofluorescence. Cell migration and invasion were detected by scratch test, matrigel assay and transwell invasion assay. Results: LSD1 expression was higher in lung cancer tissue more than in normal lung tissue. Our results showed that overexpression of LSD1 protein were associated with shorter overall survival of NSCLC patients. LSD1 was localized mainly to the cancer cell nucleus. Interruption of LSD1 using siRNA or a chemical inhibitor, pargyline, suppressed proliferation, migration and invasion of A549, H460 and 293T cells. Meanwhile, over-expression of LSD1 enhanced cell growth. Finally, LSD1 was shown to regulate epithelial-to-mesenchymal transition in lung cancer cells

The Temporal Relation between Cardiomyopathy and LBBB and Response to Cardiac Resynchronization Therapy: Case Series and Literature Review

Background: Left bundle branch block (LBBB)-induced cardiomyopathy has been proposed, but the association between LBBB and cardiac resynchronization therapy (CRT) response remains unclear and practical criteria for selecting CRT candidates are needed. Methods: One hundred and seventeen consecutive heart failure patients were reviewed, 24 of whom received CRT. Only two patients had a clear temporal relation between cardiomyopathy and LBBB. Results: Compared with the patient with “cardiomyopathy-induced LBBB,” the patient with “LBBB-induced cardiomyopathy” had higher left ventricular (LV) wall thickness, higher LV wall thickening rate, higher peak circumferential strain, and longer peak circumferential strain delay. The LV deformation patterns in the two patients were obviously distinct on cardiovascular magnetic resonance tissue tracking. During follow-up, the patient with LBBB-induced cardiomyopathy had a good response to CRT (LV ejection fraction 23 before CRT vs. 30% at 6 months vs. 29 at 12 months vs. 32% at 18 months; LV end-diastolic diameter 77 mm before CRT vs. 66 mm at 6 months vs. 62 mm at 12 months vs. 63 mm at 18 months), and the other patient had no response to CRT (LV ejection fraction 29 before CRT vs. 29% at 6 months vs. 26 at 12 months vs. 22% at 24 months; LV end-diastolic diameter 85 mm before CRT vs. 88 mm at 6 months vs. 85 mm at 12 months vs. 84 mm at 24 months). Conclusion: The temporal relation between cardiomyopathy and LBBB could be a determinant for CRT response. Cardiovascular magnetic resonance tissue tracking may be a useful tool to identify the chronological order and a principal consideration for selecting candidates for CRT. Larger prospective clinical trials are needed to study the prevalence of, time course of, and risk factors for LBBB-induced cardiomyopathy

ROS-dependent catalytic mechanism of melatonin metabolism and its application in the measurement of reactive oxygen

Melatonin (Mel) is an endogenous active molecule whose metabolism progress significantly influences its bioactivity. However, the detailed metabolic pathway of Mel in the pathological state has not yet been fully illustrated. In this study, 16 metabolites of Mel in cancer cells and human liver microsomes were identified, of which seven novel metabolites were newly discovered. Among them, 2-hydroxymelatonin (2-O-Mel), as the major metabolite in cancer cells, was revealed for the first time, which was different from the metabolite found in the human liver. Furthermore, CYP1A1/1A2- and reactive oxygen species (ROS)-mediated 2-hydroxylation reactions of Mel were verified to be the two metabolic pathways in the liver and cancer cells, respectively. ROS-dependent formation of 2-O-Mel was the major pathway in cancer cells. Furthermore, the underlying catalytic mechanism of Mel to 2-O-Mel in the presence of ROS was fully elucidated using computational chemistry analysis. Therefore, the generation of 2-O-Mel from Mel could serve as another index for the endogenous reactive oxygen level. Finally, based on the ROS-dependent production of 2-O-Mel, Mel was successfully used for detecting the oxygen-carrying capacity of hemoglobin in human blood. Our investigation further enriched the metabolic pathway of Mel, especially for the ROS-dependent formation of 2-O-Mel that serves as a diagnostic and therapeutic target for the rational use of Mel in clinics