Enhancement of autophagy can alleviate oxidative stress, inflammation, and apoptosis induced by ammonia stress in yellow catfish Pelteobagrus fulvidraco.

Ammonia in aquatic environments is toxic to fish, directly impacting their growth performance and development. Activation of autophagy can facilitate intracellular component renewal and enhance an organism's adaptability to adverse environments. Therefore, this study investigates the impact of autophagy on the yellow catfish under acute ammonia stress. In this study, the yellow catfish intraperitoneally injected with 0.9 % sodium chloride were placed with 0 (CON group) and 125 (HA group) mg/L T-AN (Total ammonia nitrogen) dechlorinated water. The yellow catfish intraperitoneally injected with 30 mg/kg fish CQ (Chloroquine, HA + CQ group) and 1.5 mg/kg fish RAPA (rapamycin, HA + RAPA group) were placed in dechlorinated water containing 125 mg/L T-AN. The results showed that activation of autophagy by injecting with RAPA can alleviate oxidative stress (catalase, superoxide dismutase, total antioxidant capacity significantly increased, H2O2 content significantly decreased), and inflammatory response (pro-inflammatory factors TNF-α, MyD88, IL 1-ß gene expression decreased significantly), apoptosis (baxa, Bcl2, Tgf-ß, Smad2, Caspase3, Caspase 9 gene expression decreased significantly) induced by ammonia stress. In addition, activation of autophagy in yellow catfish can enhance ammonia detoxification by promoting the urea cycle and synthesis of glutamine (the mRNA level of CPS Ⅰ, ARG, OTC, ASS, ASL, and GS increased in the HA + RAPA group). The data above demonstrates that activating autophagy can alleviate oxidative stress, inflammatory responses, and cell apoptosis induced by ammonia stress. Therefore, enhancing autophagy is proposed as a potential strategy to mitigate the detrimental impacts of ammonia stress on yellow catfish.

LncRNA CASC19 promotes gastric cancer progression through preventing CREB1 protein ubiquitin/proteasome-dependent degradation.

Cancer susceptibility candidate 19 (CASC19) is a novel long non-coding RNA (lncRNA) that has been reported to implicate in the development and therapeutic resistance of various cancers. However, the biological functions and the underlying mechanisms of CASC19 in gastric cancer (GC) remain unclear. In this study, GC-related lncRNAs were screened by lnCAR-database analysis. Based on Gene Expression Profiling Interactive Analysis (GEPIA) database, GC survival analysis associated with CASC19 was carried out. Quantitative real-time PCR (qRT-PCR) and chromogenic in situ hybridization were adopted to determine the expression level of CASC19. 5-ethynyl-2'-deoxyuridine (EdU) assay, 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium inner salt (MTS) assay and cell cycle assay were used to measure the proliferation capabilities of GC cells. Wound healing assay, transwell migration and invasion assay were performed to detect the metastatic ability of GC cells. Furthermore, subcellular fractionation assay, mass spectrometry, RNA pull-down, RNA immunoprecipitation, western blot and protein stability assay were conducted to investigate the mechanism of CASC19 in GC. Here, we report that CASC19 exerts an oncogenic effect on GC. CASC19 was found to be elevated in GC and overexpression of CASC19 was associated with advanced TNM (tumor node metastasis) stage and poor prognosis. Functionally, CASC19 knockdown inhibited GC cells proliferation, migration and invasion, and induced cell cycle arrest. Mechanistically, CASC19 interacted with cAMP response element-binding protein 1 (CREB1) and enhanced its stability by preventing its ubiquitin/proteasome-dependent degradation. In conclusion, these findings suggest that CASC19 may act as a cancer accelerator in GC by regulating CREB1 stability and highlight CASC19 as a potential biomarker and a valuable therapeutic target for advanced GC.

Prognostic Value of Temporary Pacemaker Insertion in Patients with Acute Myocardial Infarction in the Era of Percutaneous Coronary Revascularization.

Background: Patients with acute myocardial infarction (AMI) complicated with arrhythmia are not uncommon. Insertion of temporary pacemakers (tPMs) in patients with arrythmia during acute myocardial infarction (AMI) is imperative support therapy. Arrhythmias include high-degree atrioventricular block (AVB), sinus arrest/bradycardia, and ventricular arrythmia storm. To date, no study has evaluated the prognosis of tPMs in patients with AMI complicated with arrhythmia. Especially in the era of thrombolysis or emergency percutaneous coronary intervention (PCI) for coronary artery revascularization, our study was designed to investigate the value of tPMs implantation in cases of AMI complicated with various arrhythmias. Methods: From January 2009 to January 2019, 35,394 patients with AMI, including 62.0% (21,935) with ST-segment elevation myocardial infarction (STEMI) and 38.0% (13,459) with non-ST-segment elevation myocardial infarction (NSTEMI) in four hospitals, were reviewed. A total of 552 patients with AMI associated with arrythmia were included in the cohort. Among the 552 patients, there were 139 patients with tPM insertions. The incidence trend of myocardial infarction complicated with various arrhythmias in the past 10 years was analysed, and the clinical characteristics, in-hospital mortality, postdischarge mortality, composite endpoints of modality, and independent risk factors were compared in patients with and without tPM in the era of coronary artery revascularization. Results: In patients with AMI-associated arrythmia, high-degree AVB was the major cause of tPM insertion (p = 0.045). In the past 10 years, the number of patients with high-degree AVB, tPM implantation, ventricular arrythmia storm, and in-hospital mortality has decreased year by year in the era of coronary artery revascularization. In the tPM group, the culprit vessel was the left main artery, and cardiogenic shock, acute renal injury and high brain natriuretic peptide (BNP) levels were independent risk factors for patients with AMI complicated with arrhythmia. The in-hospital mortality in the tPM group was higher than that in the non-tPM group. The patients with tPM insertion showed better postdischarge survival than patients without tPM insertion. Conclusions: In the era of emergency thrombolysis or PCI, coronary revascularization can ameliorate the prognosis of patients with AMI complicated with various arrhythmias. Temporary pacemaker insertion in patients with AMI complicated with arrhythmia can reduce the postdischarge mortality of these patients.

Proteomic profiling of urinary small extracellular vesicles in children with pneumonia: a pilot study.

BACKGROUND: Small extracellular vesicles (sEV) play a crucial role in immune responses to viral infection. However, the composition of sEV derived from children with viral pneumonia remains ill defined. METHODS: First, we performed mass spectrometry-based label-free proteomic analysis of urinary sEV in 7 children with viral pneumonia, 4 children with Mycoplasma pneumoniae pneumonia and 20 healthy children. Then a total of 33 proteins were selected to validate by multiple reaction monitoring analysis in an independent cohort of 20 healthy children and 29 children with pneumonia. RESULTS: In the discovery phase, a total of 1621 proteins were identified, while 260 proteins have differential expression in children with viral pneumonia compared to healthy children. Biological pathways primarily associated with neutrophil degranulation, carbohydrate metabolism and endocytosis were enriched in children with viral pneumonia. Finally, the abundance of eight proteins was verified to be significantly higher in children with viral pneumonia than in healthy children. CONCLUSIONS: This pilot study with proteomic profiles of urinary sEV provided insights to the host response to viral pathogen exposure and potential diagnostic biomarkers for children with viral pneumonia, and served as the basis for understanding the fundamental biology of infection. IMPACT: There were significant differences in the proteomic features of urinary sEV between children with viral pneumonia and those with Mycoplasma pneumoniae pneumonia. Many viral infection-related proteins were identified in urinary sEV and overrepresented in children with viral pneumonia, which facilitates our understanding of the fundamental biology of viral infection. A total of eight proteins (ANPEP, ASAH1, COL11A1, EHD4, HEXB, LGALS3BP, SERPINA1 and SERPING1) were verified as potential biomarkers for the diagnosis of viral pneumonia in children.

Effects of ammonia and roxithromycin exposure on skin mucus microbiota composition and immune response of juvenile yellow catfish Pelteobagrus fulvidraco.

As an inevitable factor in aquaculture, ammonia plays a critical role in macrolide antibiotic resistance, leading to accumulating of antibiotic-resistant bacteria in fish skin mucus. In this study, four experimental groups were implemented to test the effects of ammonia alone or in combination with roxithromycin for 28 days on skin mucus microbial composition and the immune response of yellow catfish: CON (control), AN (50.00 mg L-1 total ammonia nitrogen, TA-N), ROX (100 µg L-1 roxithromycin), and HR (50.00 mg L-1 TA-N, 100 µg L-1 ROX). This study demonstrated that ammonia or roxithromycin exposure resulted in increased plasma ammonia content and decreased total antioxidant capacity. Compared with AN group, the combined exposure of ammonia and roxithromycin inhibited the skin mucus immune response. Microbial composition analysis showed that combined exposure of ammonia and roxithromycin had no significant effect on skin mucus α-diversity as compared with CON group. The abundance of Cetobacterium, Rhizobiales_Incertae_Sedis_uncultured and Acinetobacter was increased significantly with the combined effect of ammonia and roxithromycin, these bacteria may be potentially antibiotic-resistant. As compared with CON group, the combined exposure of ammonia and roxithromycin did not affect skin goblet cell counts. This study suggests that combined exposure to ammonia and ROX increases the risk of the emergence of antibiotic-resistant bacteria.

Multicolor Phosphorescence Modulated by Excitation and Temperature in Zn-Based Coordination Polymers.

Color-tunable room-temperature phosphorescence (RTP) with potential in many fields is of great importance but extremely challenging. It is necessary to comprehend the correlation between the molecular structure and property to design and synthesize such materials. Metal-organic coordination polymers (CPs) with good predesignability and precise structure have become a platform to construct RTP materials. Herein, three zinc-based CPs containing halogen and a flexible tetradentate ligand are synthesized. All of these CPs present two constant emission regions and an excitation-dependent emission region. Structure-property analysis shows that these emissions originate from isolated chromophores and dimerized chromophores as well as various charge transfers. The phosphorescence colors of these CPs can be modulated by excitation and temperature. This study provides a novel strategy to construct multicolor and multiresponsive RTP materials based on metal-organic coordination polymers.

Air pollution control or economic development? Empirical evidence from enterprises with production restrictions.

Production restriction is an environmental regulation adopted in China to curb the air pollution of industrial enterprises. Frequent production restrictions may cause economic losses for enterprises and further hinder their green transformation. Polluting enterprises are faced with the dilemma of choosing environmental protection or economic development. Using panel data on industrial enterprises in China from 2016 to 2019, this paper evaluates the impact of production restrictions on both enterprises' environmental and economic performance with regression models. The results show that production restrictions significantly drop the concentrations of SO2 and NOx emitted from polluting enterprises. Meanwhile, production restrictions have significant negative effects on operating income, financial expenses, net profit, and environmental protection investment. The mechanism analysis reveals that production restrictions mitigate air pollutant concentrations by increasing the number of green patents and improving total factor productivity, which also verifies the Porter hypothesis. However, there is a masking mediating effect of environmental investment, which indicates that the reduction of environmental investment hinders the enterprise's efforts to control air pollution. In addition, heterogeneous analysis shows that the economic shock on microenterprises is larger than that on small enterprises. Implementing production restrictions for microenterprises may be a way to eliminate their backwards production capacity.

Network meta-analysis on the effects of finerenone versus SGLT2 inhibitors and GLP-1 receptor agonists on cardiovascular and renal outcomes in patients with type 2 diabetes mellitus and chronic kidney disease.

OBJECTIVE: To evaluate the cardiovascular and renal benefits of finerenone, sodium-glucose cotransporter-2 inhibitors (SGLT2i) and glucagonlike peptide-1 receptor agonists (GLP-1 RA) in patients with Type 2 Diabetes Mellitus (T2DM) and chronic kidney disease (CKD) with network meta-analysis. METHODS: Systematic literature searches were conducted of PubMed, Cochrane Library, Web of Science, Medline and Embase covering January 1, 2000 to December 30, 2021. Randomized control trials (RCTs) comparing finerenone, SGLT-2i and GLP-1 RA in diabetics with CKD were selected. We performed a network meta-analysis to compare the two drugs and finerenone indirectly. Results were reported as risk ratio (RR) with corresponding 95% confidence interval (CI). RESULTS: 18 RCTs involving 51,496 patients were included. Finerenone reduced the risk of major adverse cardiovascular events (MACE), renal outcome and hospitalization for heart failure (HHF) (RR [95% CI]; 0.88 [0.80-0.97], 0.86 [0.79-0.93], 0.79 [0.67,0.92], respectively). SGLT-2i were associated with reduced risks of MACE (RR [95% CI]; 0.84 [0.78-0.90]), renal outcome (RR [95% CI]; 0.67 [0.60-0.74], HHF (RR [95% CI]; 0.60 [0.53-0.68]), all-cause death (ACD) (RR [95% CI]; 0.89 [0.81-0.91]) and cardiovascular death (CVD) (RR [95% CI]; 0.86 [0.77-0.96]) compared to placebo. GLP-1 RA were associated with a lower risk of MACE (RR [95% CI]; 0.86 [0.78-0.94]). SGLT2i had significant effect in comparison to finerenone (finerenone vs SGLT2i: RR [95% CI]; 1.29 [1.13-1.47], 1.31 [1.07-1.61], respectively) and GLP-1 RA (GLP-1 RA vs SGLT2i: RR [95% CI]; 1.36 [1.16-1.59], 1.49 [1.18-1.89], respectively) in renal outcome and HHF. CONCLUSIONS: In patients with T2DM and CKD, SGLT2i, GLP-1 RA and finerenone were comparable in MACE, ACD and CVD. SGLT2i significantly decreased the risk of renal events and HHF compared with finerenone and GLP-1 RA. Among GLP-1 RA, GLP-1 analogues showed significant effect in reducing cardiovascular events compared with exendin-4 analogues.

Glutamine synthetase (GS) deficiency can affect ammonia tolerance of yellow catfish Pelteobagrus fulvidraco.

Glutamine synthetase (GS) plays a crucial role in the regulation of glutamine synthesis in fish which is a very effective ammonia detoxification strategy. In this study, the full-length GS was cloned from the liver of yellow catfish. The full-length cDNA sequence of GS was 1928 bp in length and encoded 371 amino acids. The amino acid sequence of GS showed high homology (99%) with that of channel catfish. The highest mRNA expression of GS was found in the brain of yellow catfish. Acute ammonia stress (96 h LC50) significantly increased ammonia levels in plasma, liver, and brain, and GS gene expression was significantly up-regulated in the liver and brain. RNA interference inhibited the GS mRNA expression level in primary cultured hepatocytes after acute ammonia stress and reduced hepatocyte survival rate. It is suggested that GS plays a key role in ammonia detoxification in yellow catfish by regulating glutamine synthesis.

Ammonia induces changes in carbamoyl phosphate synthetase I and its regulation of glutamine synthesis and urea cycle in yellow catfish Pelteobagrus fulvidraco.

Fishes can adapt to certain levels of environmental ammonia in water, but the strategies utilized to defend against ammonia toxicity are not exactly the same. The carbamyl phosphate synthase I (CPS I) plays an important role in the regulation of glutamine synthesis and urea cycle, which are the most common strategies for ammonia detoxification. In this study, CPS I was cloned from the yellow catfish. The full-length cDNAs of the CPS I was 5 034 bp, with open reading frames of 4 461 bp. Primary amino acid sequence alignment of CPS I revealed conserved similarity between the functional domains of the yellow catfish CPS I protein with CPS I proteins of other animals. The mRNA expression of CPS I was significantly up-regulated in liver and kidney tissues after acute ammonia stress. The CPS I RNA interference (RNAi) down-regulated the mRNA expressions of CPS I and ornithine transcarbamylase (OTC), but up-regulated glutamine synthetase (GS) and glutamate dehydrogenase (GDH) expressions in primary culture of liver cell after acute ammonia stress. Similarly, the activity of enzymes related to urea cycle decreased significantly, while the activity of enzymes related to glutamine synthesis increased significantly. The results of RNAi in vitro suggested that when the urea cycle is disturbed, the glutamine synthesis will be activated to cope with ammonia toxicity.

Relationship between high fructose corn syrup sweetened drinks, diet soft drinks, and serum sodium: NHANES 2003-2006.

BACKGROUND: Consumption of high fructose corn syrup sweetened drinks and diet soft drinks has increased in the United States. However, the relationship between the intake of high fructose corn syrup sweetened drinks and diet soft drinks, and serum sodium has been scarcely studied. Our objective is to evaluate the relation between intake of high fructose corn syrup sweetened drinks and diet soft drinks, and serum sodium, and explore the possible effect modifiers in a nationally representative sample of adults from the United States. METHODS: We conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey 2003-2006. The study participants included 6989 adults aged ≥18 years. Using survey-weighted generalized linear regression analyses, we investigated the relationship between high fructose corn syrup sweetened drink, diet soft drink consumption, and serum sodium. Consumption of high fructose corn syrup sweetened drinks and diet soft drinks was evaluated through a food-frequency questionnaire. RESULTS: Serum sodium levels increased as high fructose corn syrup sweetened drink intake increased. Serum sodium levels were higher in participants in the highest high fructose corn syrup sweetened drink consumption quantile, compared with those in the lowest high fructose corn syrup sweetened drink intake quantile (p = 0.020). The multivariate betas for serum sodium, according to the corresponding high fructose corn syrup sweetened drink intake quantiles, were 0.16, 0.19, and 0.21, respectively (P for trend = 0.051). We found no relationship between diet soft drink consumption and serum sodium after adjustment of confounding. (multivariate P > 0.05). CONCLUSION: There was a a step-wise increase in serum sodium concentration with increasing consumption of HFCS sweetened beverages. Even moderate HFCS sweetened soft drink intake was associated with an elevated serum sodium level - a risk factor for hypertension.

Ammonia stress disrupts intestinal microbial community and amino acid metabolism of juvenile yellow catfish (Pelteobagrus fulvidraco).

Ammonia has adverse effects on aquatic animals, which is also widely distributed in natural aquatic environments and intensive aquaculture systems. The intestine is a primary defensive line for aquatic animals, the accumulation of ammonia in the aquatic environment can cause irreversible damage to intestinal function. In this study, we investigated the effects of acute ammonia stress on the reaction characteristics of digestive function, amino acid metabolism, and the variation in the intestinal microbiota of juvenile yellow catfish (Pelteobagrus fulvidraco). Thus, the yellow catfish was placed in water with the addition of ammonia at 0 (control), 14.6, and 146 mg/L total ammonia nitrogen for 96-h. The present study observed that ammonia accumulated in the intestine and muscle (ammonia contents in the intestine and muscle increased) and induced the activities of protein digestive enzymes dysfunction (pepsin increased while trypsin decreased). Ammonia stress changed various amino acids composition (proline, arginine, lysine, histidine, phenylalanine, tyrosine, leucine, isoleucine, valine, alanine, glutamic acid, tyrosine, and aspartic acid contents were increased in muscle) and increased the activities of alanine aminotransferase and aspartate aminotransferase in muscle. Furthermore, through 16 S rRNA gene analysis, ammonia stress-induced reduction in diversity, richness, and evenness and structure of microbiota alteration in the intestine. At the phylum level, the abundance of Fusobacteria increased while Firmicutes and Actinobacteria decreased significantly. At the genus level, the abundance of beneficial microbiota Cetobacterium significantly increased after ammonia stress. In conclusion, activation of amino acid synthesis in muscle may be involved in ammonia detoxification after severe ammonia stress. The accumulation of ammonia can disrupt the intestinal digestive function and intestinal microbiota community. The Cetobacterium may be a new potential positive factor in the resistance of ammonia toxicity.

Improving Bioavailability of Hydrophobic Prodrugs through Supramolecular Nanocarriers Based on Recombinant Proteins for Osteosarcoma Treatment.

Supramolecular nanodrug assembly driven by supramolecular chemistry is becoming a powerful strategy for medication. The potential of engineered proteins as building blocks for nanoformulations is rarely investigated. Here, we developed a new generation of recombinant protein-based nanodrug carriers, which is very efficient for loading and delivering the hydrophobic prodrug aldoxorubicin. Significantly enhanced anti-tumor effects in osteosarcoma (OS) models were observed. The half-life of the nanodrug reached almost two days and the corresponding bioavailability increased by 17-fold. This is significantly superior to other drug counterparts, empowering long-acting OS treatment scenarios. Importantly, off-target side effects of the prodrug, including cardiotoxicity and lung-metastasis, were greatly mitigated with our medication. Thus, our assembly strategy enables the customized design of advanced nanodelivery systems employing broader biomaterial building blocks for cancer therapy.

Can Aortic Balloon Occlusion Reduce Blood Loss During Resection of Sacral Tumors That Extend Into the Lower Lumber Spine?

BACKGROUND: Although aortic balloon occlusion has been shown to reduce blood loss during sacral tumor resections, it has not been validated in larger sacral tumors involving the lower lumbar spine. If such an approach were shown to be associated with less blood loss, it might aid the tumor surgeon in resecting these difficult tumors. QUESTIONS/PURPOSES: (1) Is the use of aortic balloon occlusion associated with reduced blood loss in sacral tumor resections when the lower lumbar spine is also involved? (2) Does the use of the aortic balloon prolong total operating time? (3) What complications are associated with the use of a balloon? METHODS: We retrospectively studied all 56 patients diagnosed with sacral tumors involving the lower lumbar spine (L4, L5) who were treated surgically between 2004 and 2015 at our institute. During that time, 30 of the patients received aortic balloon occlusion therapy, whereas 26 of the patients did not. We generally used aortic balloon occlusion during procedures for hypervascular lesions (for example, giant cell tumors or metastatic renal cancers), primary malignant lesions, and recurrent lesions. We generally avoided use of aortic balloon occlusion in patients with anatomic defects of the aorta (aortic dissection or aneurysm was strictly contraindicated), renal artery bifurcation caudal to the L2 to L3 disc, age older than 70 years or younger than 12 years, history of Stage 2 hypertension [], history of balloon use in previous surgeries, and presence of unstable plaque on abdominal CT. The demographic data, intraoperative blood loss, transfusion volume, operating time, and postoperative wound drainage between the two groups were collected and analyzed. Balloon-related complications were identified. Followup in terms of balloon-related complications was conducted in all 56 patients for at least 6 months after surgery. RESULTS: Intraoperative blood loss was determined to be less in patients treated with the balloon compared with those treated without the balloon (median volume, 2000 mL, range, 400-6000 mL versus 2650 mL, range, 550-6800 mL, respectively; median difference, 605 mL; 95% confidence interval [CI], 100-1500 mL; p = 0.035). Total operative time was not prolonged in the balloon group (including balloon insertion time) compared with those treated without it (median time, 215 minutes, range, 110-430 minutes versus 225 minutes, range, 115-340 minutes, respectively; median difference, 10 minutes; 95% CI, -40 to 30 minutes; p = 0.902). Balloon-related vascular complications included local hematoma at the puncture site in five patients, femoral artery spasm in three patients, lower limb ischemia in one patient, and femoral artery pseudoaneurysm in one patient. Acute kidney injury was found in two patients in the balloon group. CONCLUSIONS: This study demonstrated that placement of the aortic balloon at a level just caudal to the renal artery bifurcation was associated with lower intraoperative blood loss and transfusion in lumbosacral tumor resections. However, procedure-specific complications were common and there was no benefit to total operative time. We suggest that the surgical procedures still need to be further refined to minimize complications. We also recommend that prospective studies be undertaken to confirm the efficacy of aortic balloon occlusion in surgery for lumbosacral tumors. LEVEL OF EVIDENCE: Level III, therapeutic study.

MiR-490-5p Suppresses Cell Proliferation and Invasion by Targeting BUB1 in Hepatocellular Carcinoma Cells.

OBJECTIVE: To verify that miR-490-5p could influence hepatocellular carcinoma (HCC) cells' proliferation, invasion, cycle, and apoptosis by targeting BUB1. METHODS: Quantitative real time-PCR (QRT-PCR) was used to determine the miR-490-5p expression. Immunohistochemistry, qRT-PCR, and Western blot were employed to detect BUB1 and transforming growth factor-beta (TGFß/Smad) signaling-related proteins expression in hepatic tissues and cells. The luciferase assay was used to confirm the targeting relationship between miR-490-5p and BUB1. The Cell Counting Kit-8, colony formation, Transwell invasion, scratch healing assays, and flow cytometry analysis were conducted to evaluate HCC cells proliferation, invasion, migration, and apoptosis alteration after transfection. RESULTS: In HCC tissues and cells, lower expression of miR-490-5p was detected, while BUB1 was overexpressed than controls. The upregulation of miR-490-5p inhibited BUB1 expression and the overexpression of miR-490-5p or the under-expression of BUB1 inhibited HCC cells proliferation, migration, invasion, and increased the apoptosis rate. CONCLUSION: MiR-490-5p could regulate TGFß/Smad signaling pathways by inhibiting BUB1, which could then inhibit HCC cells proliferation, invasion, and migration as well as decrease cell viability and increase apoptosis.

BMPR2 and HIF1-α overexpression in resected osteosarcoma correlates with distant metastasis and patient survival.

OBJECTIVE: Bone morphogenetic protein receptor 2 (BMPR2) and hypoxia-inducible factor 1-α (HIF1-α) existed abnormal expression in several types of cancer. However, their expressions and related roles in osteosarcoma are largely unknown. METHODS: To investigate the clinical significance of BMPR2 and HIF1-α in osteosarcoma, we analyzed their expression levels in 103 osteosarcoma specimens by immunochemistry. Meanwhile, we conducted a follow-up to examine the metastatic behavior and overall survival (OS) of osteosarcoma patients. RESULTS: Among 103 tissues, 61 cases had BMPR2-positive expression and 57 cases had HIF1-α positive expression. A significant correlation was noticed between BMPR2 and HIF1-α expression in osteosarcoma specimens (P=0.035). Receiver-operating characteristic (ROC) curves were calculated to investigate the predictive value of the two markers in tumor metastasis. By means of univariate and multivariate analysis, BMPR2 and HIF1-α expression, as well as higher tumor grade, were identified as significant risk factors for OS in patients with osteosarcoma. Kaplan-Meier survival analysis revealed that the patients with BMPR2 and HIF1-α positive expression had worse OS compared with patients with BMPR2-negative or HIF1-α-negative staining. CONCLUSIONS: It can be concluded that BMPR2 and HIF1-α expression is highly correlated with metastatic behavior in patients with osteosarcoma and can serve as predictive markers for metastasis and OS of these patients.

GART mediates the renewal of intestinal epithelial barrier via p38/p53/PUMA cascade in colitis.

Glycinamide ribonucleotide formyltransferase (GART) has been established as a pivotal enzyme in de novo purine synthesis, and mediates cellular apoptosis in many diseases. We aimed to investigate the role of GART in the pathogenesis of Crohn's disease (CD). In our study, we demonstrated for the first time that GART expression is up-regulated in patients with active CD and in 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced acute colitis model. Moreover, the inhibition of GART induced cellular apoptosis and suppressed the migration of IECs through the activation of the MEKK3-MKK3-p38 mitogen-activated protein kinase (MAPK) pathway, following with the dys-regulation of p53 and p53 up-regulated modulator of apoptosis (PUMA). Taken together, GART plays a critical role in the protection of cellular apoptosis and migration of intestinal epithelial cells to maintain the integrity of the epithelial barrier, thus providing a new potential approach in designing a novel therapy for CD.

Acclimation of aerobic-activated sludge degrading benzene derivatives and co-metabolic degradation activities of trichloroethylene by benzene derivative-grown aerobic sludge.

The acclimation of aerobic-activated sludge for degradation of benzene derivatives was investigated in batch experiments. Phenol, benzoic acid, toluene, aniline and chlorobenzene were concurrently added to five different bioreactors which contained the aerobic-activated sludge. After the acclimation process ended, the acclimated phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic-activated sludge were used to explore the co-metabolic degradation activities of trichloroethylene (TCE). Monod equation was employed to simulate the kinetics of co-metabolic degradation of TCE by benzene derivative-grown sludge. At the end of experiments, the mixed microbial communities grown under different conditions were identified. The results showed that the acclimation periods of microorganisms for different benzene derivatives varied. The maximum degradation rates of TCE for phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic sludge were 0.020, 0.017, 0.016, 0.0089 and 0.0047 mg g SS(-1) h(-1), respectively. The kinetic of TCE degradation in the absence of benzene derivative followed Monod equation well. Also, eight phyla were observed in the acclimated benzene derivative-grown aerobic sludge. Each of benzene derivative-grown aerobic sludge had different microbial community composition. This study can hopefully add new knowledge to the area of TCE co-metabolic by mixed microbial communities, and further the understanding on the function and applicability of aerobic-activated sludge.

Flavonoid ingredients of Ginkgo biloba leaf extract regulate lipid metabolism through Sp1-mediated carnitine palmitoyltranferase 1A up-regulation.

BACKGROUND: Lipid accumulation is the primary evidence of non-alcoholic fatty liver disease (NAFLD). Ginkgo biloba extract (GBE) and its flavonoid ingredients (quercetin, kaempferol, and isorhamnetin) could lessen the lipid accumulation associated with up-regulation of the rate-limiting enzyme, carnitine palmitoyltransferase 1A (CPT1A), in the ß-oxidation of long-chain fatty acids. In this study, we investigated the mechanisms by which GBE and its flavonoids induced expression of CPT1A. RESULTS: CPT1A inhibition with RNAi resulted in triglyceride accumulation in HepG2 cells. Through deletion and mutation analysis of CPT1A's promoter combined with electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) experiments, the CPT1A promoter region (-50 to -5 nt) was determined to contain two putative Sp1 binding sites, namely Sp1a and Sp1b, which might act as the GBE regulation response DNA element. Sp1 might be induced to transfer from cytoplasma to nucleus to bind the promoter region of -50 to -5 nt by GBE. The regulatory effects of GBE on CPT1A were also verified on the flavonoid ingredients quercetin, kaempferol, and isorhamnetin. CONCLUSION: Sp1 was crucial in regulating CPT1A expression with GBE and its flavonoid ingredients, and the -50 to -5 nt region of CPT1A promoter played important roles in Sp1 binding.

Impacts of groundwater recharge from rubber dams on the hydrogeological environment in Luoyang Basin, China.

In the rubber dam's impact area, the groundwater total hardness (TH) has declined since 2000, ultimately dropping to 100-300 mg/L in 2012. pH levels have shown no obvious changes. NH4-N concentration in the groundwater remained stable from 2000 to 2006, but it increased from 2007 to 2012, with the largest increase up to 0.2 mg/L. NO3-N concentration in the groundwater generally declined in 2000-2006 and then increased from 2007; the largest increase was to 10 mg/L in 2012. Total dissolved solids (TDS) of the groundwater showed a general trend of decline from 2000 to 2009, but levels increased after 2010, especially along the south bank of the Luohe River where the largest increase recorded was approximately 100 mg/L. This study has shown that the increases in the concentrations of NH4-N and NO3-N were probably caused by changes in groundwater levels. Nitrates adsorbed by the silt clay of aeration zone appear to have entered the groundwater through physical and chemical reactions. TDS increased because of groundwater evaporation and some soluble ions entered the groundwater in the unsaturated zone. The distance of the contaminant to the surface of the aquifer became shorter due to the shallow depth of groundwater, resulting in the observed rise in pollutant concentrations more pronounced.