Targeted approaches to delineate neuronal morphology during early development

Understanding the developmental changes that affect neurons is a key step in exploring the assembly and maturation of neural circuits in the brain. For decades, researchers have used a number of labeling techniques to visualize neuronal morphology at different stages of development. However, the efficiency and accuracy of neuronal labeling technologies are limited by the complexity and fragility of neonatal brains. In this review, we illustrate the various labeling techniques utilized for examining the neurogenesis and morphological changes occurring during the early stages of development. We compare the advantages and limitations of each technique from different aspects. Then, we highlight the gaps remaining in our understanding of the structure of neurons in the neonatal mouse brain

Terlipressin May Decrease In-Hospital Mortality of Cirrhotic Patients with Acute Gastrointestinal Bleeding and Renal Dysfunction: A Retrospective Multicenter Observational Study

Acute gastrointestinal bleeding (GIB) rapidly reduces effective blood volume, thereby precipitating acute kidney injury (AKI). Terlipressin, which can induce splanchnic vasoconstriction and increase renal perfusion, has been recommended for acute GIB and hepatorenal syndrome in liver cirrhosis. Thus, we hypothesized that terlipressin might be beneficial for cirrhotic patients with acute GIB and renal impairment. In this Chinese multi-center study, 1644 cirrhotic patients with acute GIB were retrospectively enrolled. AKI was defined according to the International Club of Ascites (ICA) criteria. Renal dysfunction was defined as serum creatinine (sCr) > 133 μmol/L at admission and/or any time point during hospitalization. Incidence of renal impairment and in-hospital mortality were the primary end-points. The incidence of any stage ICA-AKI, ICA-AKI stages 1B, 2, and 3, and renal dysfunction in cirrhotic patients with acute GIB was 7.1%, 1.8%, and 5.0%, respectively. The in-hospital mortality was significantly increased by renal dysfunction (14.5% vs. 2.2%, P < 0.001) and ICA-AKI stages 1B, 2, and 3 (11.1% vs. 2.8%, P = 0.011), but not any stage ICA-AKI (5.7% vs. 2.7%, P = 0.083). The in-hospital mortality was significantly decreased by terlipressin in patients with renal dysfunction (3.6% vs. 20.0%, P = 0.044), but not in those with any stage ICA-AKI (4.5% vs. 6.0%, P = 0.799) or ICA-AKI stages 1B, 2, and 3 (0.0% vs. 14.3%, P = 0.326). Renal dysfunction increased the in-hospital mortality of cirrhotic patients with acute GIB. Terlipressin might decrease the in-hospital mortality of cirrhotic patients with acute GIB and renal dysfunction. NCT03846180 ( https://clinicaltrials.gov )

Interaction Mechanisms Between the NOX4/ROS and RhoA/ROCK1 Signaling Pathways as New Anti- fibrosis Targets of Ursolic Acid in Hepatic Stellate Cells

BackgroundStudies have shown that both NOX4 and RhoA play essential roles in fibrosis and that they regulate each other. In lung fibrosis, NOX4/ROS is located upstream of the RhoA/ROCK1 signaling pathway, and the two molecules are oppositely located in renal fibrosis. Currently, no reports have indicated whether the above mechanisms or other regulatory mechanisms exist in liver fibrosis.ObjectivesTo investigate the effects of the NOX4/ROS and RhoA/ROCK1 signaling pathways on hepatic stellate cell (HSC)-T6 cells, the interaction mechanisms of the two pathways, and the impact of UA on the two pathways to elucidate the role of UA in the reduction of hepatic fibrosis and potential mechanisms of HSC-T6 cell proliferation, migration, and activation.MethodsStable cell lines were constructed using the lentiviral transduction technique. Cell proliferation, apoptosis, migration, and invasion were examined using the MTS, TdT-mediated dUTP nick-end labeling, cell scratch, and Transwell invasion assays, respectively. The DCFH-DA method was used to investigate the ROS levels in each group. RT-qPCR and western blotting techniques were utilized to assess the mRNA and protein expression in each group. CoIP and the Biacore protein interaction analysis systems were used to evaluate protein interactions.ResultsThe NOX4/ROS and RhoA/ROCK1 signaling pathways promoted the proliferation, migration, and activation of HSCs. UA inhibited cell proliferation, migration, and activation by inhibiting the activation of the two signaling pathways, but the mechanism of apoptosis was independent of these two pathways. The NOX4/ROS pathway was upstream of and positively regulated the RhoA/ROCK1 pathway in HSCs. No direct interaction between the NOX4 and RhoA proteins was detected.ConclusionThe NOX4/ROS and RhoA/ROCK1 signaling pathways are two critical signaling pathways in a series of behavioral processes in HSCs, and NOX4/ROS regulates RhoA/ROCK1 through an indirect pathway to control the activation of HSCs. Additionally, NOX4/ROS and RhoA/ROCK1 constitute a new target for UA antifibrosis treatment

Microscopic Morphology and Indicative Significance of Nanoscale Au Particles in Soils and Fault Muds: A Case Study of Jiaojia, Shandong Province

In recent decades, the human demand for mineral resources has increased dramatically, and the mining of shallow deposits has basically been completed. The prospecting direction has turned to concealed deposits. For this reason, various penetrating geochemical methods have been developed to find concealed minerals and a series of geochemical exploration techniques have been proposed. At the same time, the use of the geochemical gene as a new technique presented in recent years is feasible in discussing component classification and provenance tracing. In this study, we applied these methods for mineral exploration in the Jiaojia gold deposit in Shandong Province, China. The results show that a large number of ore-forming element particles can be observed in ores, fault muds, and soils; compared with Chinese soil, Au has higher enrichment coefficients; according to the LG03 lithogene, the ores belong to a neutral composition, and the fault muds and soils belong to an acidic composition. Based on the above results, it can be found that the ore-forming elements in the Jiaojia gold deposit have migrated. Although this migration cannot change the original lithology, it can provide theoretical support for the fine-grained soil-prospecting method

Microscopic Morphology and Indicative Significance of Nanoscale Au Particles in Soils and Fault Muds: A Case Study of Jiaojia, Shandong Province

In recent decades, the human demand for mineral resources has increased dramatically, and the mining of shallow deposits has basically been completed. The prospecting direction has turned to concealed deposits. For this reason, various penetrating geochemical methods have been developed to find concealed minerals and a series of geochemical exploration techniques have been proposed. At the same time, the use of the geochemical gene as a new technique presented in recent years is feasible in discussing component classification and provenance tracing. In this study, we applied these methods for mineral exploration in the Jiaojia gold deposit in Shandong Province, China. The results show that a large number of ore-forming element particles can be observed in ores, fault muds, and soils; compared with Chinese soil, Au has higher enrichment coefficients; according to the LG03 lithogene, the ores belong to a neutral composition, and the fault muds and soils belong to an acidic composition. Based on the above results, it can be found that the ore-forming elements in the Jiaojia gold deposit have migrated. Although this migration cannot change the original lithology, it can provide theoretical support for the fine-grained soil-prospecting method

Construction, Test and Application of a Tungsten Metallogene Named MGW11: Case Studies in China

Geochemical gene is a new promising concept proposed recently in the discrimination and traceability of geological materials and is also a useful tool to recognize geochemical anomalies in mineral exploration. Based on the lithogenes of LG01 and LG03, geological materials can be classified into nine types of LG_CR compositionally. With respect to geological materials with 11 types of LG_CR, in order to eliminate the lithological influence and to further narrow the prospecting target area, a tungsten metallogene named MGW11 is proposed for geochemical tungsten exploration after the tungsten metallogene MGW. Six weathering profiles of 11 types of LG_CR developed on granitic intrusions in different areas in China are selected to test the stable properties such as heredity and inheritance of MGW11 and MGW. The results indicate that MGW11 and MGW metallogenes illustrate stable properties during rock weathering regardless of weathering degrees, although gene variations of MGW11 and MGW are also observed during extreme weathering. Based on the regional geochemistry survey data in the Lianyang area in south China, where stream sediments are mostly 11 types of LG_CR compositionally, geochemical maps of mineralization similarities of MGW11 and MGW are contoured, and the anomaly areas are determined on the mineralization similarity value of ≥40%. Comparing the tungsten deposits and anomaly areas determined on MGW11 and MGW metallogenes spatially, a total of six polymetallic W deposits recognized in the study area are all located in the anomaly areas. Therefore, mineralization similarities of MGW11 and MGW can be viewed as useful integrated indices on geochemical tungsten exploration. In areas with 11 types of LG_CR compositionally, anomaly areas determined on the MGW11 are smaller than those on the MGW, which indicates that MGW11 is more efficient than MGW in targeting W deposits during tungsten prospecting because of the elimination of the lithological influence

Risk Factors for Rebleeding after Emergency Endoscopic Treatment of Dieulafoy Lesion

Background and Objective: Dieulafoy lesion is a rare, but life-threatening, cause of gastrointestinal hemorrhage, and endoscopic therapy is the preferred first-line treatment. The present study aims to analyze the risk factors for rebleeding after endoscopic hemostasis of gastroduodenal Dieulafoy lesion. Methods. A retrospective review of patients with Dieulafoy lesion who developed acute gastrointestinal bleeding and were treated primarily with endoscopic therapy from September 2014 to April 2019 was conducted. Results. A total of 133 patients with Dieulafoy lesion were included in the present study. The mean age of these patients was 56.05 ± 16.58 years, and 115 patients were male. Among these 133 patients, 26 patients developed rebleeding within 30 days of endoscopic therapy. The 30-day rebleeding rate for pure injection therapy (epinephrine, cyanoacrylate, or lauromacrogol injection alone), nonpure injection therapy (argon plasma coagulation, band ligation, and hemoclip application alone), and combination therapy (combination of any >2 methods) was 45.2%, 12.8%, and 11%, respectively. In the univariable analysis, endoscopic treatment, prothrombin time, gender, Rockall score, and leukocyte count were the risk factors for rebleeding. In the multivariable analysis, pure injection endoscopic treatment, white blood cells (>10 × 109/L), and prothrombin time >12 seconds were the independent risk factors for rebleeding. Conclusion. Patients who undergo pure injection endoscopic treatment and have a high leukocyte count (>10 × 109/L) or elevated prothrombin time (>12 seconds) have an increased risk of rebleeding within 30 days after endoscopic treatment for gastroduodenal Dieulafoy lesion. Combined endoscopic treatment is the most effective therapy to prevent rebleeding in gastroduodenal Dieulafoy lesion

Differentially expressed microRNAs in diapausing versus HCl-treated <i>Bombyx</i> embryos

<div><p>Differentially expressed microRNAs were detected to explore the molecular mechanisms of diapause termination. The total small RNA of diapause-destined silkworm eggs and HCl-treated eggs was extracted and then sequenced using HiSeq high-throughput method. 44 novel miRNAs were discovered. Compared to those in the diapause-destined eggs, 61 miRNAs showed significant changes in the acid-treated eggs, with 23 being up-regulated and 38 being down-regulated. The potential target genes of differentially expressed miRNAs were predicted by miRanda. Gene Ontology and KEGG pathway enrichment analysis of these potential target genes revealed that they were mainly located within cells and organelles, involved in cellular and metabolic processes, and participated in protein production, processing and transportation. Two differentially expressed genes, <i>Bombyx mori SDH</i> and <i>Bmo-miR-2761-3p</i>, were further analyzed with qRT-PCR. <i>BmSDH</i> was significantly up-regulated in the HCl-treated eggs, while <i>Bmo-miR-2761-3p</i> was down-regulated. These results suggested that these two genes were well coordinated in silkworm eggs. Dual luciferase reporter assay demonstrated that <i>Bmo-miR-2761-3p</i> inhibited the expression of <i>BmSDH</i>.</p></div

Length distribution of sRNA.

<p>(A) Length distribution of sRNA in control eggs, (B) Length distribution of sRNA in HCl-treated eggs. Y asix represents the precentage of special sRNA in total, X axis represents length of sRNA.</p

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Background. H. pylori infection induces reactive oxygen species- (ROS-) related DNA damage and activates the PI3K/Akt pathway in gastric epithelial cells. N-Acetylcysteine (NAC) is known as an inhibitor of ROS; the role of NAC in H. pylori-related diseases is unclear. Aim. The aim of this study was to evaluate the role of ROS and the protective role of NAC in the pathogenesis of H. pylori-related diseases. Method. An in vitro coculture system and an in vivo Balb/c mouse model of H. pylori-infected gastric epithelial cells were established. The effects of H. pylori infection on DNA damage and ROS were assessed by the comet assay and fluorescent dichlorofluorescein assay. The level of PI3K/Akt pathway-related proteins was evaluated by Western blotting. The protective role of N-acetylcysteine (NAC) was also evaluated with in vitro and in vivo H. pylori infection models. Results. The results revealed that, in vitro and in vivo, H. pylori infection increased the ROS level and induced DNA damage in gastric epithelial cells. NAC treatment effectively reduced the ROS level and inhibited DNA damage in GES-1 cells and the gastric mucosa of Balb/c mice. H. pylori infection induced ROS-mediated PI3K/Akt pathway activation, and NAC treatment inhibited this effect. However, the gastric mucosa pathological score of the NAC-treated group was not significantly different from that of the untreated group. Furthermore, chronic H. pylori infection decreased APE-1 expression in the gastric mucosa of Balb/c mice. Conclusions. An increased ROS level is a critical mechanism in H. pylori pathogenesis, and NAC may be beneficial for the treatment of H. pylori-related gastric diseases linked to oxidative DNA damage