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To explore the differential expression of messenger RNA (mRNA) in myocardial tissues of rats with sudden coronary death (SCD), and to provide ideas for the forensic identification of SCD.The rat SCD model was established, and the transcriptome sequencing was performed by next-generation sequencing technology. Differentially expressed genes (DEGs) in myocardial tissues of SCD rats were screened by using the R package limma. A protein-protein interaction (PPI) network was constructed by using the STRING database and Cytoscape 3.8.2 on DEG, and hub genes were screened based on cytoHubba plug-in. Finally, the R package clusterProfiler was used to analyze the biological function and signal pathway enrichment of the selected DEG.A total of 177 DEGs were associated with SCD and were mainly involved in the renin-angiotensin system and PI3K-Akt signaling pathway. The genes including angiotensinogen (AGT), complement component 4a (C4a), Fos proto-oncogene (FOS) and others played key roles in the development of SCD.Genes such as

It has been well known that the free ion concentration of metals plays a vital role in metal bioavailability. However, measurement of this fraction is still not easy over years of development. Nowadays, rare earth elements (REEs) are drawing more attentions as an emerging contaminant due to their wide applications in our daily life. To analyze the free ion concentration of neodymium (Nd), we adopted ion-exchange technique (IET) to investigate the changes on Nd free ion concentration in the presence of fulvic acid (FA). With the dynamic mode of IET analysis, the concentrations of Nd free ion were in the range of 0.85–36.8 × 10–8 M at the total Nd concentration of 5 × 10–7 M when FA varied from 0.4 to 10 M. However, these concentrations were 3–58 times higher than the one calculated by WHAM 7.0, which may be due to the particulate Nd spontaneously formed in solution. With single particle ICP-MS analysis, we found 0.25%–2.36% of Nd was in the form of colloids when the total Nd concentrations varied from 8.5 × 10–9 to 4.7 × 10–7 M, with the average particle sizes in the range of 26.5–39.2 nm. The presence of FA significantly decreased the number of Nd colloids, but increased the average particle size. Under the TEM, we found that Nd colloids were amorphous, with the size less than 200 nm. The present study provided a relatively new perspective on REE speciation in water. The natural organic matters not only affect the free ion concentration of Nd, but also influenced the size and numbers of Nd colloids in solution.

Background & Aims Enterochromaffin-like (ECL) cells in the stomach express gastrin/cholecystokinin 2 receptor CCK2R and are known to expand under hypergastrinemia, but whether this results from expansion of existing ECL cells or increased production from progenitors has not been clarified. Methods We used mice with green fluorescent protein fluorescent reporter expression in ECL cells (histidine decarboxylase [Hdc]-green fluorescent protein), as well as Cck2r- and Hdc-driven Tamoxifen inducible recombinase Cre (Cck2r-CreERT2, Hdc-CreERT2) mice combined with Rosa26Sor-tdTomato (R26-tdTomato) mice, and studied their expression and cell fate in the gastric corpus by using models of hypergastrinemia (gastrin infusion, omeprazole treatment). Results Hdc-GFP marked the majority of ECL cells, located in the lower third of the gastric glands. Hypergastrinemia led to expansion of ECL cells that was not restricted to the gland base, and promoted cellular proliferation (Ki67) in the gastric isthmus but not in basal ECL cells. Cck2r-CreERT2 mice marked most ECL cells, as well as scattered cell types located higher up in the glands, whose number was increased during hypergastrinemia. Cck2r-CreERT2+ isthmus progenitors, but not Hdc+ mature ECL cells, were the source of ECL cell hyperplasia during hypergastrinemia and could grow as 3-dimensional spheroids in vitro. Moreover, gastrin treatment in vitro promoted sphere formation from sorted Cck2r+Hdc- cells, and increased chromogranin A and phosphorylated- extracellular signal-regulated kinase expression in CCK2R-derived organoids. Gastrin activates extracellular signal-regulated kinase pathways in vivo and in vitro, and treatment with the Mitogen-activated protein kinase kinase 1 inhibitor U0126 blocked hypergastrinemia-mediated changes, including CCK2R-derived ECL cell hyperplasia in vivo as well as sphere formation and chromogranin A expression in vitro. Conclusions We show here that hypergastrinemia induces ECL cell hyperplasia that is derived primarily from CCK2R+ progenitors in the corpus. Gastrin-dependent function of CCK2R+ progenitors is regulated by the extracellular signal-regulated kinase pathway.

Nowadays rare earth elements (REEs) are widely applied in high-technology and clean energy products, but their environmental risks are still largely unknown. To estimate the ecological risk of REEs, soil samples were collected from REE mine tailings with and without phytoremediation. The results showed that the tailings had rather low organic matter and high total REE concentrations, up to 808.5 mg/kg. The 10% effective concentration (EC10) of neodymium (Nd) and yttrium (Y) were calculated based on the toxicity tests of seed germination and root growth. For both wheat and mung bean, the EC10 of Nd and Y in soils were in the range of 1053.1-1300.1 mg/kg. The average hazard quotient of mine tailing soil without phytoremediation was higher than that with phytoremediation. All the hazard quotient of Nd and Y were less than 1, indicating that Nd or Y alone was unlikely to cause adverse ecological effects. Given to the coexistence of REEs on mine sites, the ecological risk of REE mixture could be potentially high towards local soil environments, even for soils with phytoremdiation.

Rare-earth elements (REEs) are known to be a group of emerging pollutants, but the geochemistry of REEs in river waters in ion-adsorption rare-earth mining areas has attracted little attention. In this study, samples of the 90% of the acidified bulk water). Furthermore, REE patterns indicated that the REE-associated large colloids were mineral or mixed mineral-organic matter (OM) at upstream sites and OM-dominated or functionalized at downstream sites. The particles were mainly coated by inorganic matter substances (e.g., Fe/Al oxyhydroxides). In summary, our results reveal that REE patterns provide a useful tool to study the fate of REEs in ion-adsorption rare-earth mining catchments.

Objective: The aim of the present study was repositioning of ivermectin in treatment of gastric cancer (GC) by computational prediction based on gene expression profiles of human and mouse model of GC and validations with in silico, in vitro and in vivo approaches.Methods: Computational drug repositioning was performed using connectivity map (cMap) and data/pathway mining with the Ingenuity Knowledge Base. Tissue samples of GC were collected from 16 patients and 57 mice for gene expression profiling. Additional seven independent datasets of gene expression of human GC from the TCGA database were used for validation. In silico testing was performed by constructing interaction networks of ivermectin and the downstream effects in targeted signaling pathways. In vitro testing was carried out in human GC cell lines (MKN74 and KATO-III). In vivo testing was performed in a transgenic mouse model of GC (INS-GAS mice).Results: GC gene expression “signature” and data/pathway mining but not cMAP revealed nine molecular targets of ivermectin in both human and mouse GC associated with WNT/β-catenin signaling as well as cell proliferation pathways. In silico inhibition of the targets of ivermectin and concomitant activation of ivermectin led to the inhibition of WNT/β-catenin signaling pathway in “dose-depended” manner. In vitro, ivermectin inhibited cell proliferation in time- and concentration-depended manners, and cells were arrested in the G1 phase at IC50 and shifted to S phase arrest at >IC50. In vivo, ivermectin reduced the tumor size which was associated with inactivation of WNT/β-catenin signaling and cell proliferation pathways and activation of cell death signaling pathways.Conclusion: Ivermectin could be recognized as a repositioning candidate in treatment of gastric cancer.

Summary Tumors comprise cancer cells and the associated stromal and immune/inflammatory cells, i.e., tumor microenvironment (TME). Here, we identify a metabolic signature of human and mouse model of gastric cancer and show that vagotomy in the mouse model reverses the metabolic reprogramming, reflected by metabolic switch from glutaminolysis to OXPHOS/glycolysis and normalization of the energy metabolism in cancer cells and TME. We next identify and validate SNAP25, mTOR, PDP1/α-KGDH, and glutaminolysis as drug targets and accordingly propose a therapeutic strategy to target the nerve-cancer metabolism. We demonstrate the efficacy of nerve-cancer metabolism therapy by intratumoral injection of BoNT-A (SNAP25 inhibitor) with systemic administration of RAD001 and CPI-613 but not cytotoxic drugs on overall survival in mice and show the feasibility in patients. These findings point to the importance of neural signaling in modulating the tumor metabolism and provide a rational basis for clinical translation of the potential strategy for gastric cancer., Graphical Abstract, Highlights • Metabolic reprogramming in gastric cancer cells and tumor microenvironment • SNAP25, mTOR, PDP1/α-KGDH, and glutaminolysis as potential drug targets • Combination of botulinum toxin type A, RAD001, and CPI-613 as a potential treatment, Cancer; Cancer Systems Biology

The number of people who are overweight and obese are continuously increasing both in the adult and adolescent populations. Coinciding with this is the increased prevalence of health problems such as type 2 diabetes (T2D). Bariatric surgery is the only proven long-term treatment of obesity and may induce remission of T2D, although the underlying mechanisms are unknown. The translational studies presented here might provide insight on the mechanism of steady-state energy balance of the obese phenotype using a special time-restricted feeding regimen for weight loss during the steady-state energy balance; mechanism by vagal blocking therapy (vBLoc® therapy) as a new treatment for obesity; and possible mechanism behind the remission of T2D following gastric bypass surgery.

The widespread use of rare earth elements (REEs) in numerous sectors have resulted in their release into the environment. Existing knowledge about the effects of REEs were acquired mainly based on toxicity tests with aquatic organisms and a fixed exposure time, Here, the dynamic accumulation and toxicity of REEs (La, Ce, and Gd) in soil organism Enchytraeus crypticus were determined and modeled by a first-order one-compartment model and a time-toxicity logistic model, respectively. Generally, the accumulation and toxicity of REEs were both exposure level- and time-dependent. The overall uptake rate constants were 2.97, 2.48, and 2.38 L kg−1d−1 for La, Ce, and Gd, respectively. The corresponding elimination rate constants were 0.99, 0.78, and 0.56 d−1, respectively. The worms exhibited faster uptake and elimination ability for light REEs (La and Ce) than for heavy REEs (Gd). For all three REEs, the LC50 values based on exposure concentrations decreased with time and reached ultimate values after approximately 10 d exposure. The estimated ultimate LC50 values (LC50∞) were 279, 334, and 358 mg L−1 for Ce, Gd, and La, respectively. When expressed as body concentration, the LC50inter value was almost constant with time, demonstrating that internal body concentration could be a better indicator of dynamic toxicity of REEs than external dose. This study highlights that specific REE and exposure time should be taken into account in accurately assessing risk of REEs.

Background & Aims Enterochromaffin-like (ECL) cells in the stomach express gastrin/cholecystokinin 2 receptor CCK2R and are known to expand under hypergastrinemia, but whether this results from expansion of existing ECL cells or increased production from progenitors has not been clarified. Methods We used mice with green fluorescent protein fluorescent reporter expression in ECL cells (histidine decarboxylase [Hdc]-green fluorescent protein), as well as Cck2r- and Hdc-driven Tamoxifen inducible recombinase Cre (Cck2r-CreERT2, Hdc-CreERT2) mice combined with Rosa26Sor-tdTomato (R26-tdTomato) mice, and studied their expression and cell fate in the gastric corpus by using models of hypergastrinemia (gastrin infusion, omeprazole treatment). Results Hdc-GFP marked the majority of ECL cells, located in the lower third of the gastric glands. Hypergastrinemia led to expansion of ECL cells that was not restricted to the gland base, and promoted cellular proliferation (Ki67) in the gastric isthmus but not in basal ECL cells. Cck2r-CreERT2 mice marked most ECL cells, as well as scattered cell types located higher up in the glands, whose number was increased during hypergastrinemia. Cck2r-CreERT2+ isthmus progenitors, but not Hdc+ mature ECL cells, were the source of ECL cell hyperplasia during hypergastrinemia and could grow as 3-dimensional spheroids in vitro. Moreover, gastrin treatment in vitro promoted sphere formation from sorted Cck2r+Hdc- cells, and increased chromogranin A and phosphorylated- extracellular signal-regulated kinase expression in CCK2R-derived organoids. Gastrin activates extracellular signal-regulated kinase pathways in vivo and in vitro, and treatment with the Mitogen-activated protein kinase kinase 1 inhibitor U0126 blocked hypergastrinemia-mediated changes, including CCK2R-derived ECL cell hyperplasia in vivo as well as sphere formation and chromogranin A expression in vitro. Conclusions We show here that hypergastrinemia induces ECL cell hyperplasia that is derived primarily from CCK2R+ progenitors in the corpus. Gastrin-dependent function of CCK2R+ progenitors is regulated by the extracellular signal-regulated kinase pathway., Graphical abstract

Background Pain is often observed in pediatric patients after craniotomy procedures, which could lead to some serious postoperative complications. However, the optimal formula for postoperative analgesia for pediatric neurosurgery has not been well established. This study aimed to explore the optimal options and formulas for postoperative analgesia in pediatric neurosurgery. Methods Three hundred and twenty patients aged 1 to 12-years old who underwent craniotomy were randomly assigned to receive 4 different regimens of patient-controlled analgesia. The formulas used were as follows: Control group included normal saline 100 ml, with a background infusion of 2 ml/h, bolus 0.5 ml; Fentanyl group was used with a background infusion of 0.1–0.2 μg/k·h, bolus 0.1–0.2 μg/kg; Morphine group was used with a background infusion of 10–20 μg/kg·h, bolus 10–20 μg/kg; while Tramadol group was used with a background infusion of 100–400 μg/kg·h, bolus 100–200 μg/kg. Postoperative pain scores and analgesia-related complication were recorded respectively. Comparative analysis was performed between the four groups. Results In comparison of all groups with each other, lower pain scores were shown at 1 h and 8 h after surgery in Morphine group versus Tramadol, Fentanyl and Control groups (P

Long-term wastewater irrigation impacts soil geochemical properties (salinity, pH and soil aggregates) and promotes the bioaccumulation of heavy metals to plants, which may change soil function, decrease soil health, decrease the productivity of farmland, and even cause land degradation. In this study, we explored the impact of saline stress on soil bacterial communities and Cd availability in long-term wastewater-irrigated field soil. Different amounts of saline stress by adding 0.1, 0.3 and 0.5% salts in a fixed proportion (NaCl: Na2SO4: NaHCO3: Na2CO3 = 1:9:9:1) were applied in a 1-year, multiple cropping system with winter wheat (Triticum aestivum L.) and summer maize (Zea mays L.) in wastewater-polluted soil. Increased salinity in the soil increased Cd availability: compared with CK (no extra salts addition), addition of 0.5% mixed salts significantly increased soil available Cd up by 67.5% and grain Cd concentration by 43.7%, and adding 0.5% salts also resulted in the increases of soil pH (∼0.5 unit) and electric conductivity (97.4%). Soil saline stress significantly changed major soil microbes in Cd-contaminated soil. Increased saline stress enriched taxa in the Bacillaceae, Staphylococcaceae and Pseudomonadaceae bacterial families, while one family within Proteobacteria (Sphingomonadaceae) was the most sensitive biomarker, based on Cd contamination without saline stress in CK-treated soils. Structural equation modeling (SEM) analysis revealed that soil saline stress induced an increase in soil Cd availability that was regulated by the bacterial community.

Vagotomy reduces gastric acid secretion and was therefore introduced as a surgical treatment for peptic ulcers in the 1970s. Later, it was replaced by acid reducing medication, such as histamine type 2 (H2) receptor antagonists and proton pump inhibitors (PPIs). A large body of evidence has indicated that drug-induced hypochlorhydria per se does not increase the risk of gastric cancer. Early studies on the effects of vagotomy in chemically-induced rodent models of gastric cancer reported an increased risk of developing gastric cancer. This was most likely due to a delayed gastric emptying, which later has been accounted for by including an additional drainage procedure, e.g. pyloroplasty. In a recent study using three different mouse models of gastric cancer (including genetically engineered, chemically-induced and Helicobacter pylori-infected mice), either unilateral vagotomy or bilateral truncal vagotomy with pyloroplasty was found to significantly attenuate tumorigenesis in the denervated side of the stomach at early preneoplastic stages as well as at later stages of tumorigenesis. Consistently, pharmacological denervation using botulinum toxin A or muscarinic acetylcholine receptor 3 (M3R) blockade inhibited tumorigenesis. Moreover, it was found that recurrence of gastric cancer was reduced in patients following vagotomy. Thus, these new findings suggest the potential treatment strategies to target the nerve, neurotransmitters, corresponding receptors and their downstream signaling pathways for the malignancy. Copyright © 2016 Bentham Science. This is the authors' manuscript to the article. Preprint.

Background Bariatric surgery leads to early and long-lasting remission of type 2 diabetes (T2D). However, the mechanisms behind this phenomenon remain unclear. Among several factors, gut hormones are thought to be crucial mediators of this effect. Unlike GLP-1, the role of the hormone peptide tyrosine tyrosine (PYY) in bariatric surgery in humans has been limited to appetite regulation and its impact on pancreatic islet secretory function and glucose metabolism remains under-studied. Methods Changes in PYY concentrations were examined in obese patients after bariatric surgery and compared to healthy controls. Human pancreatic islet function was tested upon treatment with sera from patients before and after the surgery, in presence or absence of PYY. Alterations in intra-islet PYY release and insulin secretion were analysed after stimulation with short chain fatty acids (SCFAs), bile acids and the cytokine IL-22. Findings We demonstrate that PYY is a key effector of the early recovery of impaired glucose-mediated insulin and glucagon secretion in bariatric surgery. We establish that the short chain fatty acid propionate and bile acids, which are elevated after surgery, can trigger PYY release not only from enteroendocrine cells but also from human pancreatic islets. In addition, we identify IL-22 as a new factor which is modulated by bariatric surgery in humans and which directly regulates PYY expression and release. Interpretation This study shows that some major metabolic benefits of bariatric surgery can be emulated ex vivo. Our findings are expected to have a direct impact on the development of new non-surgical therapy for T2D correction.

The objective of this study was to understand the effect of biofertilizers on cadmium (Cd)-induced phytotoxicity and the rhizosphere bacterial community. The crop specie rice (Oryza sativa L.) was planted in Cd-contaminated soils, and Illumina high-throughput sequencing was performed to investigate how the composition of the rhizosphere bacterial community responded to the addition of biofertilizers. Biofertilizers were effective in alleviating Cd phytotoxicity as indicated by the significant increase in plant biomass (up to 85.2% and 48.4% for roots and shoots, respectively) and decrease in tissue Cd concentration (up to 72.2% in roots) of rice receiving fertilizer treatments compared with the CK (no treatment). These positive effects were likely due to the increase in soil pH, which can be attributed primarily to Cd immobilization, and the promotion of beneficial taxa such as Proteobacteria, Bacteroidetes, Gemmatimonadetes, and Firmicutes. In addition, autoclaved biofertilizers tended to have similar beneficial effects and similar bacterial community alpha diversities as the original biofertilizer treatments. This suggests that the change in soil physicochemical properties by biofertilizer addition might drive the structure of rhizosphere bacterial community, and not the biofertilizer microbes themselves. In both the original and sterilized biofertilizer treatments, the effectiveness in mitigating of Cd phytotoxicity was found to be dependent on the type of biofertilizer applied. Comparatively, the biofertilizer denoted as DY was more effective in mitigating Cd phytotoxicity than others. These results demonstrate that biofertilizer addition could be a promising approach to immobilize soil Cd by manipulating the rhizosphere bacterial community, thus to facilitate plant growth.

Due to their specific properties, ion-adsorption rare earth mine sites may be a threat for adjacent environments. This work was undertaken to assess whether former mining operations on ion-adsorption rare earth mine sites have a significant impact on water bodies and soils of the surrounding environments. Tailing soil materials, stream waters and sediments, and farmland soils were collected from one of the largest ion-adsorption rare earth mine sites worldwide (Southern China). Total concentrations of rare earth elements (REEs), Fe, Al, etc., and pH were measured. Results revealed high concentrations of REEs in tailing soils (392 mg kg−1), stream waters (4460 μg L−1), sediments (462 mg kg−1) and farmland soils (928 mg kg−1) in comparison with control sites. In the tailing profiles, light REEs (LREEs) were preferentially leached compared to middle REEs (MREEs) and heavy REEs (HREEs). Anomalies in tailings and stream water indicated strong soil weathering (Eu) and leaching activities (Ce) within the tailings. The MREE enriched pattern in stream water was more related to water parameters such as Al and Fe oxides, and ligands, than to the source of REEs. Anomalies also indicated that REEs contamination in the farmland soils was mainly originated from the stream water contaminated by the leaching from the tailings. In conclusion, a heavy REEs pollution was recorded in the surrounding environment of ion-adsorption rare earth mine. REEs fractionation, Ce and Eu anomalies provided an insight to the understanding of REEs leaching and soil weathering processes, and REEs environmental fate in rare earth mining area.

Aims To compare gastric acid suppression by netazepide, a gastrin/CCK2 receptor antagonist, with that by a proton pump inhibitor (PPI), and to determine if netazepide can prevent the trophic effects of PPI-induced hypergastrinaemia. Methods Thirty healthy subjects completed a double-blind, randomized, parallel group trial of oral netazepide and rabeprazole, alone and combined, once daily for 6 weeks. Primary end points were: basal and pentagastrin-stimulated gastric acid and 24 h circulating gastrin and chromogranin A (CgA) at baseline, start and end of treatment, gastric biopsies at baseline and end of treatment and basal and pentagastrin-stimulated gastric acid and dyspepsia questionnaire after treatment withdrawal. Results All treatments similarly inhibited pentagastrin-stimulated gastric acid secretion. All treatments increased serum gastrin, but the combination and rabeprazole did so more than netazepide alone. The combination also reduced basal acid secretion. Rabeprazole increased plasma CgA, whereas netazepide and the combination reduced it. None of the biopsies showed enterochromaffin-like (ECL) cell hyperplasia. Withdrawal of treatments led neither to rebound hyperacidity nor dyspepsia. Conclusions Netazepide suppressed pentagastrin-stimulated gastric acid secretion as effectively as did rabeprazole. The reduction in basal acid secretion and greater increase in serum gastrin by the combination is consistent with more effective acid suppression. Despite our failure to show rabeprazole-induced ECL cell hyperplasia and rebound hyperacidity, the increase in plasma CgA after rabeprazole is consistent with a trophic effect on ECL cells, which netazepide prevented. Thus, netazepide is a potential treatment for the trophic effects of hypergastrinaemia and, with or without a PPI, is a potential treatment for acid-related conditions.

Objects To observe the effects of bundle care on preventing unplanned extubation (UEX) of nasobiliary drainage catheter after endoscopic retrograde cholangiopancreatography (ERCP). Background Preventing UEX has become a difficult problem for nursing staff because the catheter is stiff, fine and long. Design A total of 114 cases that experienced nasobiliary drainage after ERCP for the first time in our hospital from April 2015 to July 2016, were enrolled in this study. According to receiving routine nurse or bundle nurse, these cases were randomly divided into control (n=56) and intervention (n=58) group. Method The UEX incidence, contact area between tape and catheter and tensile resistance were compared between the two groups. Results The contact area was one square centimeter in the control group and 5 cm2 in the intervention group. Tensile resistance was significantly higher in the intervention group than in the control (all P

Isothiocyanates (ITCs) are plant phytochemicals derived from vegetables consumed by human. ITCs comprise potent anti-carcinogenic agents of which the consumption has been linked to a reduced risk of cancer at several locations in the body. However, the studies on coping with gastric cancer remain unsatisfied. In the present review, ITCs are discussed in this context as ITCs may target gastric tumorigenesis at multiple levels. ITCs are taken up in the stomach, exposing mucosal and muscle layer cells as well as affecting Helicobacter pylori residing in the stomach. The natural and potent anti-cancer ITCs from vegetables have a great potential against gastric cancer, a disease in need of new treatment or preventive modalities.

Background and Aim Phenethyl isothiocyanate (PEITC) derives from vegetables commonly consumed by man and has been demonstrated as a promising chemopreventive agent against several types of cancer. However, the potential in preventing gastric cancer as well as the underlying mechanisms are to date not fully understood. The present study aimed at elucidating the cellular effects induced by PEITC in gastric cancer cells leading to apoptosis. Methods The human gastric cancer cell lines Kato-III and MKN74 were employed. Cell proliferation was assayed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Morphology and migration were investigated through a contrast microscope. Cell cycle distribution was analyzed using flow cytometry of PI-stained cells. Microtubules were studied by confocal detection of Kato-III cells transfected to express GFP-tagged microtubules. Commercial kits were employed to study the effect of PEITC on apoptosis, caspase-3 activity, and glutathione content in MKN74 cells. Results Kato-III and MKN74 cells responded, with different sensitivity, dose- and time-dependently in inhibition of cell proliferation to PEITC treatment. Further, PEITC induced aberrated cell morphologies and inhibited migration of MKN74 cells. Kato-III cells treated with PEITC accumulated in G2/M phase and displayed a loss of microtubuli with the subsequent formation of apoptotic bodies. Although weak responses, MKN74 cells also accumulated in G2/M phase, became apoptotic, increased caspase-3 activity, and suffered a reduction of glutathione pool. Conclusion Our findings demonstrate that PEITC induces disintegration of microtubules in human gastric cancer cells contributing to cell cycle arrest and ultimately apoptosis, contributing to an increased understanding of PEITC-induced inhibition of gastric cancer cell growth.

Background and Aim We recently reported that topical application of acetic acid promptly caused tumor necrosis in a mouse model of gastric cancer. The aim of the present study was to examine whether acetic acid can directly induce cancer cell death. Methods Rat gastric epithelial cell line (RGM-1), rat gastric carcinoma cell line (RGK-1), human gastric cancer cell line (KATO III), and human mesothelioma cell lines (ACC-MESO1 and MSTO-211H) were used. Acetic acid was added into the cell culture at different concentrations for different time periods. Cell death was analyzed by MTT assay, flow cytometry, and trypan blue exclusion test. Results Acetic acid promptly induced the cell death of RGM-1, RGK-1 cells, and KATO III cells in a concentration-dependent manner from 0.01% to 0.5%. Acetic acid at 0.5% for 1 min induced the cell death by 80%. RGK-1 cells were more sensitive to acetic acid than RGM-l cells. KATO III cells were more sensitive to acetic acid than RGK-1 cells. Acetic acid at 0.5% for 10 min induced almost complete cell death of ACC-MESO1 and MSTO-211H. Conclusions Acetic acid is a powerful anticancer agent. Topical application of acetic acid may be a feasible approach for the treatments of gastric cancer and possibly other malignancies.

Ileal pouch-anal anastomosis (IPAA) is the operation of choice following proctocolectomy for patients who suffer from ulcerative colitis and familial adenomatous polyposis. The aim of this study was to morphologically examine the neurons, endocrine cells and mast cells in the ileum of rats subjected to proctocolectomy followed by three different types of ileoanal anastomosis. Rats were subjected to either sham operation or proctocolectomy followed by ileoanal anastomosis end-to-end, side-to-end or IPAA (J-pouch). In comparison to sham-operated rats, the body weight was reduced in rats that underwent proctocolectomy with end-to-end or side-to-end, but not IPAA procedure. In all three models of ileoanal anastomosis, the ileum displayed crypt hyperplasia with a chronic inflammatory infiltrate located in the interstitium, hyperplasia of goblet cells, but reduced protein gene product 9.5 (PGP 9.5)-immunoreactive neurons in the mucosa as well as submucosa. Numbers of endocrine cells in the mucosa (chromogranin A immunostaining) and mast cells in the mucosa and submucosa (Astra blue staining) were unchanged after proctocolectomy. In conclusion, neurons, but neither endocrine cells nor mast cells, were reduced in the ileum of proctocolectomized rats followed by either of three different types of ileoanal anastomosis.

Although many studies have addressed the effects of various physicochemical and biological factors on metal bioaccumulation in aquatic organisms, the influences of metal exposure history have drawn much less attention. In the present study, we investigated the effects of different Zn exposure regimes (concentration: 1–200 μg/L, duration: 1–7 d) on the subsequent biokinetics, metallothionien-like protein (MTLP) induction and subcellular distribution of Cd and Zn in Daphnia magna. Zn body burden increased significantly with elevated exposure concentrations, but was kept within a narrow range regardless of the 200-fold variation of Zn concentrations. Significant induction (7–14 folds) of MTLP by Zn exposure was evident, but was decoupled from the Zn body accumulation. Under different regimes of Zn exposure, Zn was evenly distributed in insoluble (cellular debris, intracellular organelles and metal-rich granules) and soluble fractions (heat sensitive protein and MTLP). However, >60% of Cd was bound with MTLP regardless of the exposure concentration and duration. The biokinetic processes including uptake from the dissolved phase, food assimilation and excretion of Cd and Zn were quantified with radioactive tracers. The uptake rate constants of Cd and Zn from the dissolved phase either remained comparable or increased following Zn pre-exposure, and the efflux of Zn increased by nearly two-fold to counteract the increased uptake from water. The dietary assimilation of Zn also decreased significantly in response to Zn exposure. However, Cd assimilation efficiency was kept relatively constant in each Zn pre-exposure regime. Our results showed that Zn exposure had significant influences on the biokinetics and physiology of daphnids. Daphnids attempted to maintain the Zn body burden within a narrow range by modification of biokinetic processes instead of subcellular distribution.

Industrial heritage or problems in modern city construction has been the focus of concern and controversy, Tianjin as an important port city of China in modern, the previous light and heavy industrial production activities in the city left numbers of traces. There is no longer have traditional industry vitality in these industry base, we should be how to locate it? We have make great errors in "construction" and got the demolitions in our city, but also we accumulated a lot of experience too. Through careful investigation we found both not indulging in idle space in the old city has become a knot, also not be reckless of the cultural context in which the demolition and reconstruction, After all we are in decision-making mistakes in a short moment lost the "Tianjin ancient fossils -- old Chengxiang". To achieve sustainable city construction, we should respect the continuity of development of things, equilibrium and the public. Based on the transformation of "Tractor factory of Nankai District in Tianjin as example, we hope to explore and find some strategy in economy, balanced and sustainable development of industrial building heritages.

Exploring the distribution of soil pH and nutrients are significant to the sustainable development of tropical agricultural growth. Taking Longjiang Farm in Hainan province as the research plot, and exploring the distribution characteristics of soil nutrients in study area by applying the GIS spatial analysis tools. The results indicated that the soil is acidic and the contents of soil nutrients are varied significantly in research area. The spatial distributions of available Ca, available Mg, available Cu and available Zn were mainly determined by the distributions of soil parent materials. The contents of soil organic matters and total N are escalated gradually from north to south in study area. The spatial analysis tools can be applied to explore the distribution of soil nutrients in areas, which is significant to the regional agricultural planning.

Green architecture, a termed entitled to the architectures which dedicate great importance to the environment, is one of the characteristics of the sustainable design in which environmental sustainability is more important [1]. In the modern notion of architecture and programming, rain water is usually treated as “castoff”, or as eternal energy splurged by us. Some irrational design produces a lot of unsinkable ditches and culverts crossed underground, which leads to drainage and wastage of the water in the earth. Extensive artificial lawn accelerates the water evaporation of the earth. Large amount of unsinkable reinforced tough paving layer in cities disturbs the ecological balance of the earth, etc.. All these above give more grave non-ecological factors to the concrete jungle. When talking about the recycle and reuse of water in city, we should thinking about promoting the life system balance in ecosphere, which is the theme of this thesis. This thesis tries to give a systematic and in-depth discussion on architectural water recycle design by collecting materials, to give an ecological recycle design of preserving, saving and purifying water on the aspect of architecture and environment. Through the analysis on infiltration, storage and reuse of rain water in cities of different countries and regions, this thesis tries to expatiate the contribution of rain water collection and evaporation to the urban ecology, and proposes ecological way of water use considering regional climate to achieve the aim of eternal water use in urban ecological system.

The toxicity of manufactured silver nanoparticles (AgNPs) has been widely studied, but the influence of AgNPs on the major ions (such as sodium [Na] and calcium [Ca]) regulations are unknown. In the present study, a freshwater cladoceran Daphnia magna was exposed to commercial AgNPs coated with polyvinylpyrrolidone. After 48 h, the Na body content was significantly reduced by AgNO3 exposure, but the Ca body content was significantly increased under AgNO3 and AgNP exposures, respectively. No effect was observed on the body concentrations of Na and Ca at 50 to 500 µg/L AgNPs with 1-µM cysteine addition. Exposure of AgNO3 and AgNPs inhibited the Na influx and elevated the Na efflux. In contrast, their exposure increased the Ca influx, but did not affect the Ca efflux. The results of the present study demonstrated the significant influences of AgNO3 and AgNPs (without cysteine) on Na and Ca regulations. Such effect of AgNPs on Na and Ca regulation disappeared after cysteine addition, indicating that the soluble Ag released from AgNPs played a major role in the ionoregulatory dysfunction. Environ. Toxicol. Chem. 2013;32:913–919. © 2013 SETAC

Objective: We wanted to exam the steady-state energy balance by using high-fat diet-induced obese (DIO) rats and mice as models for positive energy balance, and gastric bypassed (GB) rats and gene knockout of muscarinic acetylcholine M3 receptor (M3KO) mice as models for negative energy balance. Methods: One hundred and thirty-two rats and mice were used. Energy balance was measured by a comprehensive laboratory animal monitoring system. Gene expression was analysed by in situ hybridisation in M3KO mice. Results: DIO rats reached the plateau of body weight 28 weeks after starting high-fat diet (25% heavier than controls), whereas DIO mice reached the plateau after 6 weeks (23% heavier than controls). At the plateau, DIO rats had higher calorie intake during the light phase but not during the dark phase, while mice had the same calorie intake per day as controls. DIO rats and mice had lower energy expenditure (EE) and respiratory exchange ratio (RER) than controls. GB-rats reached the plateau (15% weight loss) 2 weeks after surgery and had the same calorie intake as sham-operated controls. EE, but not RER, was higher in GB rats than controls during the dark phase. The lean M3KO mice (25% lighter than wild-type (WT) mice at the plateau between 6 and 15 months of age) had the same calorie intake but higher EE, RER and hypothalamic mRNA expression of NPY, AgRP and leptin receptor than WT mice. Conclusion: When body weight gain or loss reached a plateau, the steady-state energy balance was mainly maintained by EE and/or RER rather than calorie intake.

Within the gastrointestinal stem cell niche, nerves help to regulate both normal and neoplastic stem cell dynamics. Here, we reveal the mechanisms underlying the cancer-nerve partnership. We find that Dclk1+ tuft cells and nerves are the main sources of acetylcholine (ACh) within the gastric mucosa. Cholinergic stimulation of the gastric epithelium induced nerve growth factor (NGF) expression, and in turn NGF overexpression within gastric epithelium expanded enteric nerves and promoted carcinogenesis. Ablation of Dclk1+ cells or blockade of NGF/Trk signaling inhibited epithelial proliferation and tumorigenesis in a muscarinic acetylcholine receptor-3 (M3R)-dependent manner, in part through suppression of Yes-Associated Protein (YAP) function. This feed-forward ACh-NGF axis activates the gastric cancer niche and offers a compelling target for tumor treatment and prevention.

A recent study reported that a special weekly scheduled time-restricted feeding regimen (TRF), i.e., no food consumption for 15h during the light (inactive) phase per day for 5 weekdays, attenuated the outcome of diverse nutritional challenges in response to high-fat diet in mice. In the present study, we wanted to further test whether this TRF could restrict body weight gain in both juvenile and adult animals when fed a high-fat diet. Fifty male Sprague-Dawley rats at ages from 5 to 27weeks were used. First, we found that freely fed rats with 60% fat diet gained weight significantly, which was associated with more calorie intake (particularly during light phase) than those fed standard food (7% fat). Secondly, we found that TRF restricted high-fat diet-induced weight gain in both groups of juvenile rats (5 and 13weeks of age) compared to freely fed rats with high-fat diet, despite the same levels of 24h-calorie intake during either weekdays or the weekend. Thirdly, we found that TRF did not restrict high-fat diet-induce weight gain in adult rats (27weeks of age). Thus, we suggest that this special TRF regimen could be further tested in humans (particularly young adults) for the purpose of obesity prevention.

1 Department of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway 2 Department of Clinical Neuroscience and Rehabilitation, The Sahlgrenska Academy at Gothenburg University, Gothenburg, Sweden 3 Rowett Institute of Nutrition and Health, University of Aberdeen, Aberdeen, Scotland 4 Institute of Neuroscience and Physiology, The Sahlgrenska Academy at the University of Gothenburg, Gothenburg, Sweden 5 Department of Biomedical Sciences, the Panum Institute, University of Copenhagen, Copenhagen, Denmark 6 Department of Clinical Biochemistry, Rigshospitalet, Copenhagen, Denmark 7 Department of Translational Neuroscience, Brain Center Rudolf Magnus, University Medical Center Utrecht, Utrecht, Netherlands 8 Center for Obesity Research, Department of Surgery, St. Olavs Hospital, Trondheim University Hospital, Trondheim, Norway OBES SURG (2017) 27:186 DOI 10.1007/s11695-016-2370-2