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Objective: Oxidative stress is one of the major mechanisms of cyclophosphamide (CPX)-induced toxicities. However, it is unknown how CPX induces oxidative stress. Based on the available information, we speculated that CPX could increase iron content in the tissues and then induce oxidative stress. Method: We tested this hypothesis by investigating the effects of CPX on iron and ferritin contents, expression of transferrin receptor 1 (TfR1), ferroportin 1 (Fpn1), iron regulatory proteins (IRPs), hepcidin, and nuclear factor erythroid 2-related factor-2 (Nrf2) in the liver and spleen, and also on reticulocyte count, immature reticulocyte fraction, and hemoglobin (Hb) in the blood in c57/B6 mouse. Results: We demonstrated that CPX could induce a significant increase in iron contents and ferritin expression in the liver and spleen, notably inhibit erythropoiesis and Hb synthesis and lead to a reduction in iron usage. The reduced expression in TfR1 and Fpn1 is a secondary effect of CPX-induced iron accumulation in the liver and spleen and also partly associated with the suppressed IRP/iron-responsive element system, upregulation of hepcidin, and downregulation of Nrf2. Conclusions: The reduced iron usage is one of the causes for iron overload in the liver and spleen and the increased tissue iron might be one of the mechanisms for CPX to induce oxidative stress and toxicities.

The biological behavior of carcinoma of the esophagogastric junction (CEGJ) is different from that of gastric or esophageal cancer. Differentiating squamous cell carcinoma of the esophagogastric junction (SCCEG) from adenocarcinoma of the esophagogastric junction (AEG) can indicate Siewert stage and whether the surgical route for patients with CEGJ is transthoracic or transabdominal, as well as aid in determining the extent of lymph node dissection. With the development of neoadjuvant therapy, preoperative determination of pathological type can help in the selection of neoadjuvant radiotherapy and chemotherapy regimens.To establish and evaluate computed tomography (CT)-based multiscale and multiphase radiomics models to distinguish SCCEG and AEG preoperatively.We retrospectively analyzed the preoperative contrasted-enhanced CT imaging data of single-center patients with pathologically confirmed SCCEG (The 2D-venous model (5 features, AUC: 0.849) performed better than 2D-arterial (5 features, AUC: 0.808). The 2D-arterial-venous combined model could further enhance the performance (AUC: 0.869). The 3D-venous model (7 features, AUC: 0.877) performed better than 3D-arterial (10 features, AUC: 0.876). And the 3D-arterial-venous combined model (AUC: 0.904) outperformed other single-phase-based models. The venous model showed a positive improvement compared with the arterial model (NRI0, IDI0), and the 3D-venous and combined models showed a significant positive improvement compared with the 2D-venous and combined models (The combined arterial-venous CT radiomics model based on 3D segmentation can improve the performance in differentiating EGJ squamous cell carcinoma from adenocarcinoma.

The reduced iron usage induced by the suppression of erythropoiesis is a major cause of the systemic iron overload in CBS knockout (CBS−/−) mice. However, the relevant mechanisms are unknown. Here, we examined changes in granulocyte/erythroid cell ratios, iron content, and expression of iron-metabolism proteins, including; two key enzymes involved in the heme biosynthetic pathway, ALAS2 (delta-aminolevulinate synthase 2) and FECH (ferrochelatase), a heme exporter from the cytosol and mitochondria, FLVCR (feline leukemia virus subgroup C cellular receptor) as well as EPO (erythropoietin), EPOR (erythropoietin receptor) and HIF-2α (hypoxia inducible factor-2 subunit α), in the blood, bone marrow or liver of CBS−/− (homozygous), CBS+/− (heterozygous) and CBS+/+ (Wild Type) mice. Our findings demonstrate that CBS deficiency can induce a significant reduction in the expression of ALAS2, FECH, FLVCR, HIF-2α, EPO, and EPOR as well as an increase in interleukin-6 (IL-6), hepcidin and iron content in the blood, bone marrow or liver of mice. We conclude that the suppression of erythropoiesis is mainly due to the CBS deficiency-induced disruption in the expression of heme biosynthetic enzymes and heme-transporter.

Background/Aims: The studies in the patients with iron deficiency anemia (IDA) implied the existence of the association of ghrelin with iron or hepcidin levels in the plasma under the pathophysiological conditions. We hypothesized that fasting may be able to affect iron metabolism via ghrelin under the physiological conditions. Methods: We investigated the effects of fasting on serum ghrelin and iron contents in healthy volunteers (23–31 years) and C57BL/6 male mice (8-week-olds) under the physiological conditions. Results: Fasting induced a significant elevation in both total ghrelin and acylated ghrelin and a reduction in iron levels in the serum of both human and mice. Correlation analysis demonstrated that total ghrelin or acylated ghrelin is negatively correlated with iron in the serum in human and mice. Conclusion: Ghrelin has a role to reduce serum iron under the conditions of fasting.

Background: We recently demonstrated that the reduced iron usage due to suppressed erythropoiesis is a major cause of the systemic iron overload in CBS knockout (CBS-/-) mice. However, the molecular mechanisms by which CBS deficiency suppresses erythropoiesis are unknown. Methods: Here, we therefore examined the changes in the ratio of granulocyte/erythroid cells, iron content, the expression of erythropoietin (EPO), iron-metabolism proteins including transferrin receptor 1 (TfR1), ferroportin 1 (Fpn1) and iron regulatory proteins (IRPs), and other molecules that affect iron-metabolism, including hypoxia inducible factor-2 subunit α (HIF-2α), nuclear factor erythroid 2-related factor-2 (Nrf2), and Kelch-like ECH-associated protein 1 (Keap1) in the blood, bone marrow, bone marrow-derived macrophages, liver or spleen of CBS-/- (homozygous), CBS+/- (heterozygous) and CBS+/+ (Wild Type) mice. Findings & Interpretation: Our findings demonstrated that CBS deficiency suppressed erythropoiesis by disrupting iron supply mainly via EPO/IRP/TfR1, Hepcidin/Fpn1, HIF-2α/EPO/Fpn1 and Keap1/Nrf2/Fpn1 pathways in macrophage or erythroid progenitors of rats. Funding: Supported by the National Natural Science Foundation of China (NSFC31571195), and the Competitive Earmarked Grants of the Hong Kong Research Grants Council (GRF14111815, GRF 14167817, GRF14107616). Declaration of Interest: The authors have no financial or competing interests to disclose. Ethical Approval: All animal care and experimental protocols were performed according to the Animal Management Rules of the Ministry of Health of China, and approved by the Animal Ethics Committees of Fudan University (NDFC31271132) and The Chinese University of Hong Kong (GRF14111815).

Prolonged, isocaloric, time-restricted feeding (TRF) protocols can promote weight loss, improve metabolic dysregulation, and mitigate non-alcoholic fatty liver disease (NAFLD). In addition, 3-day, severe caloric restriction can improve liver metabolism and glucose homeostasis prior to significant weight loss. Thus, we hypothesized that short-term, isocaloric TRF would improve NAFLD and characteristics of metabolic syndrome in diet-induced obese male mice. After 26 weeks of ad libitum access to western diet, mice either continued feeding ad libitum or were provided with access to the same quantity of western diet for 8 h daily, over the course of two weeks. Remarkably, this short-term TRF protocol modestly decreased liver tissue inflammation in the absence of changes in body weight or epidydimal fat mass. There were no changes in hepatic lipid accumulation or other characteristics of NAFLD. We observed no changes in liver lipid metabolism-related gene expression, despite increased plasma free fatty acids and decreased plasma triglycerides in the TRF group. However, liver Grp78 and Txnip expression were decreased with TRF suggesting hepatic endoplasmic reticulum (ER) stress and activation of inflammatory pathways may have been diminished. We conclude that two-week, isocaloric TRF can potentially decrease liver inflammation, without significant weight loss or reductions in hepatic steatosis, in obese mice with NAFLD.

Inhibition of eukaryotic elongation factor 1A1 (EEF1A1) with the marine compound didemnin B decreases lipotoxic HepG2 cell death in vitro and improves early stage non-alcoholic fatty liver disease (NAFLD) in young genetically obese mice. However, the effects of didemnin B on NAFLD in a model of long-term diet-induced obesity are not known. We investigated the effects of didemnin B on NAFLD severity and metabolic parameters in western diet-induced obese mice, and on the cell types that contribute to liver inflammation and fibrosis in vitro. Male 129S6 mice were fed either standard chow or western diet for 26 weeks, followed by intervention with didemnin B (50 μg/kg) or vehicle by intraperitoneal (i.p.) injection once every 3 days for 14 days. Didemnin B decreased liver and plasma triglycerides, improved oral glucose tolerance, and decreased NAFLD severity. Moreover, didemnin B moderately increased hepatic expression of genes involved in ER stress response (Perk, Chop), and fatty acid oxidation (Fgf21, Cpt1a). In vitro, didemnin B decreased THP-1 monocyte proliferation, disrupted THP-1 monocyte-macrophage differentiation, decreased THP-1 macrophage IL-1β secretion, and decreased hepatic stellate cell (HSteC) proliferation and collagen secretion under both basal and lipotoxic (high fatty acid) conditions. Thus, didemnin B improves hepatic steatosis, glucose tolerance, and blood lipids in obesity, in association with moderate, possibly hormetic, upregulation of pathways involved in cell stress response and energy balance in the liver. Furthermore, it decreases the activity of the cell types implicated in liver inflammation and fibrosis in vitro. These findings highlight the therapeutic potential of partial protein synthesis inhibition in the treatment of NAFLD.

Angiotensin II (ANGII) modulates expression of iron intake and export proteins in cultured neurons. However, the relevant mechanisms have not been fully elucidated. Here, we investigated the effects of ANGII and/or candesartan, a ANGII-Type-1 Receptor (AT1R) antagonist, and PD123319, a ANGII-Type-2 Receptor (AT2R) antagonist on expression of transferrin receptor 1 (TfR1), ferroportin 1 (Fpn1)and ferritin as well as iron regulatory proteins (IRPs), hepcidin and nuclear factor E2-related factor 2 (Nrf2) in Neuro-2a cells. We demonstrated that ANGII induces a significant reduction in expression of TfR1, Fpn1, IRP2 proteins and Nrf2 mRNA and an increase in ferritin protein and hepcidin mRNA, while candesartan, but not PD123319, significantly attenuated or reversed all these ANGII-induced changes in Neuro-2a cells. These findings imply that ANGII down-regulates TfR1 expression likely via the AT1R/IRP2 pathway, and Fpn1 expression via ATR1/hepcidin and AT1R/ Nrf2 pathways.

To figure out the arsenic pollution source and characteristics in the slag field around the Yangzonghai Lake, we made deep monitoring analysis. We employed the X fluorescence metal scene analyzer and also the traditional atomic fluorescence spectrometry method for precision analysis. It finds out the arsenic pollution level, spatial change regulation, the vertical distribution characteristics, and pollution diffusion path. The work could provide effectively technical support for the soil arsenic pollution prevention in the area.

Background Phalaenopsis orchid (Phal. orchid) is visually attractive and it is important economic floriculture species. Phal. orchids have many unique biological features. However, investigation of these features and validation on their biological functions are limited due to the lack of an efficient transformation method. Results We developed a heritable and efficient Agrobacterium- mediated transformation using protocorms derived from tetraploid or diploid Phal. orchids. A T-DNA vector construct containing eGFP driven by ubiquitin promoter was subjected to transformation. An approximate 1.2–5.2 % transformation rate was achieved. Genomic PCR confirmed that hygromycin selection marker, HptII gene and target gene eGFP were integrated into the orchid genome. Southern blotting indicated a low T-DNA insertion number in the orchid genome of the transformants. Western blot confirmed the expression of eGFP protein in the transgenic orchids. Furthermore, the GFP signal was detected in the transgenic orchids under microscopy. After backcrossing the pollinia of the transgenic plants to four different Phal. orchid varieties, the BC1 progenies showed hygromycin resistance and all surviving BC1 seedlings were HptII positive in PCR and expressed GFP protein as shown by western blot. Conclusions This study demonstrated a stable transformation system was generated for Phal. orchids. This useful transformation protocol enables functional genomics studies and molecular breeding. Electronic supplementary material The online version of this article (doi:10.1186/s40529-016-0146-6) contains supplementary material, which is available to authorized users.

Additional file 1: Table S1. Transformation efficiency in different batches of experiments. TH274 × TH601 hybrid seeds were sown in 1/2 MS containing 25 ppm hygromycin and the surviving protocorms that were recorded from the first to the third round of selections. Figure S1. Phalaenopsis orchid cultivars used for transformation in this study. a Plant type of Phalaenopsis orchid cultivars at flowering stage. b Flower morphology of Phalaenopsis orchid cultivars. 4n, tetraploid; 2n, diploid. Bars = 5 cm (a), 2 cm (b). Figure S2. Phenotype of T0 transgenic orchid seedlings overexpressing Ubi:GFP. D1 to D33 represented the individual T0 transgenic lines overexpressing Ubi:GFP. The respectively wild type is written in the right hand side.

The objective of this study was to test the hypothesis that fibrous-root plants and rhizomatic-root plants are characterized by different root morphologies, root growth and distribution, and contaminant removal capabilities. Four fibrous-root and four rhizomatic-root wetland plants were studied in mono-cultured microcosms which received wastewater. Fibrous-root plants had significantly greater (P

In the process of 3D reconstruction of the target scene with the moving vehicle-borne single-line scanner, a method of monocular visual positioning is used to locate the exact position of the moving scanner. Attitude sensor, camera and the laser scanner are located on the same platform which is installed on the vehicle. Data can be collected synchronously. We obtained a top view according to the observation of camera's attitude by IPM. A series of planform are acquired at different moment. After dealing with these pictures with operations of extraction Speeded Up Robust Features (SURF), matching characteristic points and RANSAC algorism, we calculated the transformation matrix between two adjacent vertical views. The position and direction of the scanner at this moment can be calculated. On this basis, depending on the sensors' synchronization control algorithm, the original point clouds data got by laser scanner can be registered as a reference to the traveling track of the moving scanner, and then the 3D reconstruction of the target scene is established. Experiment result shows that this method is easy to operate, time-efficient, low cost, and the accuracy of the method in reconstructing 3D scene is demonstrated.

The monocular vision odometry simplifies the hardware and the software as opposed to the stereo vision odometry, but it also has defect. When the vehicle is in motion, the camera's attitude changes inevitably, what lead that the method's performance degrades. To solve this problem, we proposed a monocular visual odometry based on the inverse perspective mapping (IPM). Attitude of the camera is monitored in real time by the attitude sensor when the vehicle is moving. Then the images of road surface photographed by camera became top view by using the IPM algorithm, after that, the characters of images can be calculated by the Speeded Up Robust Features (SURF) algorithm. By the random sample consensus (RANSAC) algorithm, the amounts of translation and rotation between two adjacent images can be concluded. Accordingly, the movement distance and the course of the vehicle can be worked out. In order to test the ranging accuracy of the method, both static and dynamic experiments were implemented. Static experiment showed that the average accuracy of ranging of this method achieved 1.6%. Dynamic experiment showed that the ranging accuracy achieved 6%, and the heading measurement error is less than 1.3°. Therefore, the method proposed in this paper is easy to operate, time-efficient, low cost, and the accuracy of the method in ranging and heading measurement are demonstrated.

A rheo-optical study of the influence of additives on crystallization rates in synthetic cis-1,4 polyisoprene (IR2200) at room temperature is presented. Nine different additives at a 1% concentration were examined. This study has found many additives which seem to be effective in enhancing the rate of stress-induced crystallization in IR2200. We have found that there is a good relation between enhancement of green strength and fraction of stress-induced crystallinity, ϕc, in IR2200 caused by additives.