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1.
Ital J Pediatr ; 45(1): 78, 2019 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-31288826

RESUMO

BACKGROUND: Diagnostic value of procalcitonin (PCT) for acute appendicitis (AA) has been evaluated in adult patients, but the application in children remains controversial. The aim of this study was to evaluate the diagnostic value of PCT for overall and complicated AA in children. METHODS: The PubMed, EMBASE, Web of Science, Cochrane Database of Systematic Reviews, Chinese National Knowledge Infrastructure, and Wanfang were searched along with reference lists of relevant articles up to January 2018 without language restrictions. Original articles that reported the performance of PCT in the diagnosis of pediatric AA and associated complications were selected. To assess the diagnostic value of PCT, sensitivity, specificity, diagnostic odds ratios (DORs), summary receiver operating characteristic (ROC) curves, area under the curve (AUC), and 95% confidence intervals (95% CIs) were estimated. RESULTS: Seven qualifying studies (504 confirmed AA and 368 controls) from 6 countries for overall AA and 4 studies (187 complicated AA and 185 uncomplicated AA) for complicated AA from 3 countries were identified. The pooled sensitivity and specificity of PCT for the diagnosis of pediatric AA were 0.62 (95% CI: 0.57-0.66) and 0.86 (95% CI: 0.82-0.89), respectively. The DOR was 21.4 (95% CI: 3.64-126.1) and the AUC was 0.955. PCT was more accurate in diagnosing complicated appendicitis, with a pooled sensitivity of 0.89 (95% CI: 0.84-0.93), specificity of 0.90 (95% CI: 0.86-0.94), and DOR of 76.73 (95% CI: 21.6-272.9). CONCLUSION: This meta-analysis showed that PCT may have potential value in diagnosing pediatric AA. Moreover, PCT had greater diagnostic value in identifying pediatric complicated appendicitis.

2.
Nat Neurosci ; 22(8): 1357-1370, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31285615

RESUMO

The medial prefrontal cortex (mPFC) contains populations of GABAergic interneurons that play different roles in cognition and emotion. Their local and long-range inputs are incompletely understood. We used monosynaptic rabies viral tracers in combination with fluorescence micro-optical sectioning tomography to generate a whole-brain atlas of direct long-range inputs to GABAergic interneurons in the mPFC of male mice. We discovered that three subtypes of GABAergic interneurons in two areas of the mPFC are innervated by same upstream areas. Input from subcortical upstream areas includes cholinergic neurons from the basal forebrain and serotonergic neurons (which co-release glutamate) from the raphe nuclei. Reconstruction of single-neuron morphology revealed novel substantia innominata-anteromedial thalamic nucleus-mPFC and striatum-anteromedial thalamic nucleus-mPFC circuits. Based on the projection logic of individual neurons, we classified cortical and hippocampal input neurons into several types. This atlas provides the anatomical foundation for understanding the functional organization of the mPFC.

3.
Chem Res Toxicol ; 32(8): 1583-1590, 2019 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-31293154

RESUMO

Cabozantinib is a multityrosine kinase inhibitor and has a wide range of applications in the clinic, whose metabolism is predominately dependent on CYP3A4. This study was performed to characterize the enzymatic properties of 29 CYP3A4 alleles toward cabozantinib and the functional changes of five selected alleles (the wild-type, CYP3A4.2.8.14 and .15) toward cabozantinib in the presence of ketoconazole. Cabozantinib, 1-100 µM, with/without the presence of ketoconazole and CYP3A4 enzymes in the incubation system went through 30 min incubation at 37 °C, and the concentrations of cabozantinib N-oxide were quantified by UPLC-MS/MS to calculate the corresponding kinetic parameters of each variant. Collectively, without the presence of ketoconazole, most variants displayed defective enzymatic activities in different degrees, and only CYP3A4.14 and .15 showed significantly augmented enzymatic activities. With the presence of ketoconazole, five tested CYP3A4 alleles, even CYP3A4.14 and .15, exhibited obvious reductions in intrinsic clearance. Besides, we compared cabozantinib with regorafenib in relative clearance to confirm that CYP3A4 has the property of substrate specificity. As the first study of CYP3A4 genetic polymorphisms toward cabozantinib, our observations can provide prediction of an individual's capability in response to cabozantinib and guidance for medication and treatment of cabozantinib.

4.
Chem Biol Interact ; 310: 108744, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-31299239

RESUMO

The epidemic of loperamide abuse and misuse in the patients for the alternative to opioids has become an increasing worldwide concern and has led to considerations about the potential for drug-drug interactions between loperamide and other combined drugs, especially inhibitors of cytochrome P450 (CYP450) enzymes, such as axitinib. This study assessed the effects of axitinib on the metabolism of loperamide and its main metabolite N-demethylated loperamide in rats and in rat liver microsomes (RLM), human liver microsomes (HLM) and recombinant human CYP3A4*1. The concentrations of both compounds were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The exposures (AUC(0-t), AUC(0-∞) and Cmax) of loperamide and N-demethylated loperamide showed a conspicuous increase when loperamide was co-administered with axitinib. The Tmax of loperamide increased while CLz/F decreased under the influence of axitinib. In vitro, axitinib inhibited loperamide metabolism with the IC50 of 18.34 µM for RLM, 1.705 µM for HLM and 1.604 µM for CYP3A4*1, and it was confirmed as a non-competitive inhibitor in all enzymes. Taken together, the results indicated that axitinib had an obvious inhibitory impact on loperamide metabolism both in vivo and in vitro. Thus, more attention should be paid to the concurrent use of loperamide and axitinib to reduce the risk of unexpected clinical outcomes.

5.
Autophagy ; 15(9): 1671-1673, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31216956

RESUMO

Liver-specific deletion of autophagy-related genes in mice leads to hepatomegaly, liver injury and spontaneous liver tumorigenesis. Accumulating evidence indicates that p62/SQSTM1-mediated NFE2L2/Nrf2/(nuclear factor, erythroid 2 like 2) activation plays a critical role in promoting liver injury and tumorigenesis in autophagy-defective livers. However, the mechanisms of how persistent NFE2L2 activation induces liver injury and tumorigenesis are unknown. In a recent study, it was found that deletion of Mtor (mechanistic target of rapamycin kinase) or Rptor/Raptor attenuates hepatomegaly and liver injury in young liver-specific atg5 knockout mice but accelerates liver tumorigenesis in old mice likely due to feedback AKT activation. Overall, these findings suggest that both hyper- and hypo-activation of MTOR are detrimental to the liver resulting in the development of liver tumors. A balanced MTOR activity is critical to maintain the normal physiological functions of the liver, and caution should be exercised when treating hepatocellular carcinomas using MTOR inhibitors. Abbreviations: Atg5: autophgy related 5; DKO: double-knockout; HCC: hepatocellular carcinoma; INS: insulin; INSR: insulin receptor; KEAP1: kelch-like ECH-associated protein 1; KO: knockout; MTOR: mechanistic target of rapamycin kinase; NFE2L2: nuclear factor, erythroid 2 like 2; raptor: regulatory associated protein of MTOR, complex 1; SQSTM1: sequestosome 1: tsc1: TSC complex subunit 1.

6.
Sci Total Environ ; 686: 497-504, 2019 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-31185398

RESUMO

In China, the total annual atmospheric emission of 16 polycyclic aromatic hydrocarbons (PAHs) reach up to approximate 100 thousand tons, part of which is preserved in soils. In this study, the contribution of soil erosion to PAHs in surface water nationwide was quantified. The results indicate that a major portion of the annual PAHs emission is lost from soils via rainfall erosivity and subsequently transported to the ocean. The national annual flux of PAHs from soil to surface water by the natural physical forces of water measures up to ~70 thousand tons, which accounts for ~62% of the annual emission of PAHs with 19% entering the sea directly. In general, both the soil erosion intensity and flux of PAHs for the regions located in the Southeast of China are over those in the Northwest of China, with the regions being divided into two different parts by the famous geographic "Hu Huanyong line", reflecting the intensive impact of human activities on environmental degradation. Comparative analysis suggested that there must be a big fraction of PAHs lost during transmission due to the river sedimentation and lake dispersion. This study closes a major gap in the national budget of PAHs and provides critical information in the context of regional environment risk assessment.

7.
Sci Total Environ ; 679: 378-386, 2019 Aug 20.
Artigo em Inglês | MEDLINE | ID: mdl-31100562

RESUMO

Electronic commerce has been becoming the new driver of the retail industry. The large-scale expansion of electronic commerce with additional packaging certainly increases stress on the environment. However, a comparative analysis of environmental impacts of electronic commerce and conventional retail trade channels is unavailable. In this study, an Average Package Difference Model (APDM) was developed to evaluate CO2 emissions difference via the two retail channels in Shenzhen, China based on a life-cycle perspective. In the meanwhile, the national emission was estimated by the above results. Our results suggest that conventional retail has a higher environmental cost than that of electronic commerce, especially during shopping trips. Specifically, average CO2 emission difference per package in terms of product returns, packaging, buildings and transportation were 0.14 ±â€¯0.03, 0.84 ±â€¯0.08, 0.67 ±â€¯0.04, 1.3 ±â€¯0.26 kg, respectively. CO2 is mainly emitted from buildings and consumer trips in conventional retail trade, whereas packaging is mainly responsible for CO2 emission in e-commerce. In China, the total CO2 emission difference between conventional retail and electronic commerce was 124 million tons in 2016. Growth of the proportion of electronic commerce will contribute to lower CO2 emissions induced by the entire retail industry. Actually, carbon emissions can be reduced in both conventional retail and electronic commerce, such as the reusable packaging, opening shopping centers in dense population zones and promoting the usage of public transportation.

8.
Hepatology ; 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31095752

RESUMO

Autophagy is a lysosomal degradation pathway that degrades cytoplasmic proteins and organelles. Absence of autophagy in hepatocytes has been linked to promoting liver injury and tumorigenesis; however, the mechanisms behind why a lack of autophagy induces these complications are not fully understood. The role of mammalian target of rapamycin (mTOR) in impaired autophagy-induced liver pathogenesis and tumorigenesis was investigated by using liver-specific autophagy related 5 knockout (L-ATG5 KO) mice, L-ATG5/mTOR, and L-ATG5/Raptor double knockout (DKO) mice. We found that deletion of mTOR or Raptor in L-ATG5 KO mice at 2 months of age attenuated hepatomegaly, cell death, and inflammation but not fibrosis. Surprisingly, at 6 months of age, L-ATG5/mTOR DKO and L-ATG5/Raptor DKO mice also had increased hepatic inflammation, fibrosis, and liver injury, similar to the L-ATG5 KO mice. Moreover, more than 50% of L-ATG5/mTOR DKO and L-ATG5/Raptor DKO mice already developed spontaneous tumors, but none of the L-ATG5 KO mice had developed any tumors at 6 months of age. At 9 months of age, all L-ATG5/mTOR DKO and L-ATG5/Raptor DKO had developed liver tumors. Mechanistically, L-ATG5/mTOR DKO and L-ATG5/Raptor DKO mice had decreased levels of hepatic ubiquitinated proteins and persistent nuclear erythroid 2 p45-related factor 2 activation but had increased Akt activation compared with L-ATG5 KO mice. Conclusion: Loss of mTOR signaling attenuates the liver pathogenesis in mice with impaired hepatic autophagy but paradoxically promotes tumorigenesis in mice at a relatively young age. Therefore, the balance of mTOR is critical in regulating the liver pathogenesis and tumorigenesis in mice with impaired hepatic autophagy.

9.
Artigo em Inglês | MEDLINE | ID: mdl-31058459

RESUMO

AIM: Regorafenib is a tyrosine kinase inhibitor that is mainly metabolized by CYP3A4. The genetic polymorphism of CYP3A4 would contribute to differences in metabolism of regorafenib. Previously, we had discovered several novel CYP3A4 variants. However, the catalytic characteristics of these 27 CYP3A4 variants on oxidizing regorafenib have not being determined. The purpose of this study was to investigate the catalytic characteristics of 27 CYP3A4 protein variants on the oxidative metabolism of regorafenib in vitro. METHOD: Wild-type CYP3A4.1 or other variants was incubated with 0.5-20 µmol/L regorafenib for 30 minutes. After sample processing, regorafenib-N-oxide, a primary metabolite, was detected by ultra-performance liquid chromatography-tandem mass spectrometry system. RESULT: CYP3A4.20 had no detectable enzyme activity compared with wild-type CYP3A4.1; five variants (CYP3A4.5, .16, .19, .24, .29) exhibited similar clearance value with CYP3A4.1; four variants (CYP3A4.14, .15, .28, .31) displayed increased enzymatic activities, while remaining variants showed markedly decreased intrinsic clearance values. CONCLUSION: This study is the first to investigate the function of 27 CYP3A4 protein variants on the metabolism of regorafenib in vitro, and it may provide some valuable information for further research in clinic.

10.
Cardiovasc Pathol ; 41: 11-17, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31004933

RESUMO

Atherosclerosis is a chronic inflammatory disease with lipid accumulation. Apolipoprotein C3 (APOC3), which is an important regulator of human lipid metabolism, is associated with multiple vascular mechanisms in atherosclerosis and proinflammatory responses. We have previously reported that the expression of inflammatory cytokine TNF-α is elevated in human endothelial cells (HUVECs) after APOC3 treatment. This study investigates the APOC3 signaling pathway involved in TNF-α-mediated expression of JAM-1 in HUVECs. Cultured HUVECs were exposed to APOC3 (50 µg/ml) for 16 h. Mechanistic studies were carried out by silencing TNF-α gene with lentiviral TNF-α-shRNA. Our study was based on the eight signaling pathway inhibitors to block the effect of APOC3 in HUVECs. The expression of JAM-1 was determined by qRT-PCR, Western blotting, and flow cytometry. IKK2 degradation and NF-κB p65 phosphorylation were determined by Western blotting. Our results showed that APOC3 significantly promoted the TNF-α-induced expression of JAM-1 in HUVECs. Inhibiting APOC3 reversed the TNF-α-induced overexpression of JAM-1. Moreover, APOC3 induced the expression of NF-κB p65 and degraded IκB. In conclusion, APOC3 promoted the expression of JAM-1 via the NF-κB, IKK2, and PI3K signaling pathway.


Assuntos
Apolipoproteína C-III/farmacologia , Moléculas de Adesão Celular/metabolismo , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Quinase I-kappa B/metabolismo , Fosfatidilinositol 3-Quinase/metabolismo , Receptores de Superfície Celular/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Moléculas de Adesão Celular/genética , Células Cultivadas , Células Endoteliais da Veia Umbilical Humana/enzimologia , Humanos , Fosforilação , Proteólise , Interferência de RNA , Receptores de Superfície Celular/genética , Transdução de Sinais/efeitos dos fármacos , Junções Íntimas/efeitos dos fármacos , Junções Íntimas/enzimologia , Fator de Necrose Tumoral alfa/genética
11.
Am J Pathol ; 189(7): 1363-1374, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31026418

RESUMO

Increased hepatic ischemia-reperfusion (IR) injury in steatotic livers is a major reason for rejecting the use of fatty livers for liver transplantation. Necroptosis is implicated in the pathogenesis of fatty liver diseases. Necroptosis is regulated by three key proteins: receptor-interacting serine/threonine-protein kinase (RIPK)-1, RIPK3, and mixed-lineage kinase domain-like protein (MLKL). Here, we found that marked steatosis of the liver was induced when a Western diet was given in mice; steatosis was associated with the inhibition of hepatic proteasome activities and with increased levels of key necroptosis-related proteins. Mice fed a Western diet had more severe liver injury, as demonstrated by increases in serum alanine aminotransferase and necrotic areas of liver, after IR than did mice fed a control diet. Although hepatic steatosis was not different between Mlkl knockout mice and wild-type mice, Mlkl knockout mice had decreased hepatic neutrophil infiltration and inflammation and were protected from hepatic IR injury, irrespective of diet. Intriguingly, Ripk3 knockout or Ripk3 kinase-dead knock-in mice were protected against IR injury at the late phase but not the early phase, irrespective of diet. Overall, our findings indicate that liver steatosis exacerbates hepatic IR injury via increased MLKL-mediated necroptosis. Targeting MLKL-mediated necroptosis may help to improve outcomes in steatotic liver transplantation.

12.
Autophagy ; : 1-16, 2019 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-30894069

RESUMO

Impaired macroautophagy/autophagy has been implicated in experimental and human pancreatitis. However, the transcriptional control governing the autophagy-lysosomal process in pancreatitis is largely unknown. We investigated the role and mechanisms of TFEB (transcription factor EB), a master regulator of lysosomal biogenesis, in the pathogenesis of experimental pancreatitis. We analyzed autophagic flux, TFEB nuclear translocation, lysosomal biogenesis, inflammation and fibrosis in GFP-LC3 transgenic mice, acinar cell-specific tfeb knockout (KO) and tfeb and tfe3 double-knockout (DKO) mice as well as human pancreatitis samples. We found that cerulein activated MTOR (mechanistic target of rapamycin kinase) and increased the levels of phosphorylated TFEB as well as pancreatic proteasome activities that led to rapid TFEB degradation. As a result, cerulein decreased the number of lysosomes resulting in insufficient autophagy in mouse pancreas. Pharmacological inhibition of MTOR or proteasome partially rescued cerulein-induced TFEB degradation and pancreatic damage. Furthermore, genetic deletion of tfeb specifically in mouse pancreatic acinar cells increased pancreatic edema, necrotic cell death, infiltration of inflammatory cells and fibrosis in pancreas after cerulein treatment. tfeb and tfe3 DKO mice also developed spontaneous pancreatitis with increased pancreatic trypsin activities, edema and infiltration of inflammatory cells. Finally, decreased TFEB nuclear staining was associated with human pancreatitis. In conclusion, our results indicate a critical role of impaired TFEB-mediated lysosomal biogenesis in promoting the pathogenesis of pancreatitis. Abbreviations: AC: acinar cell; AMY: amylase; ATP6V1A: ATPase, H+ transporting, lysosomal V1 subunit A; ATP6V1B2: ATPase, H+ transporting, lysosomal V1 subunit B2; ATP6V1D: ATPase, H+ transporting, lysosomal V1 subunit D; ATP6V1H: ATPase, H+ transporting, lysosomal V1 subunit H; AV: autophagic vacuole; CDE: choline-deficient, ethionine-supplemented; CLEAR: coordinated lysosomal expression and regulation; CQ: chloroquine; EIF4EBP1: eukaryotic translation initiation factor 4E binding protein 1; EM: electron microscopy; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; GFP: green fluorescent protein; H & E: hematoxylin and eosin; KO: knockout; LAMP1: lysosomal-associated membrane protein 1; MAP1LC3/LC3: microtubule associated protein 1 light chain 3; MAPK1/ERK2: mitogen-activated protein kinase 1; MTORC1: mechanistic target of rapamycin kinase complex 1; ND: normal donor; NEU: neutrophil; PPARGC1A/PGC1α: peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha; RIPA: radio-immunoprecipitation; RPS6: ribosomal protein S6; SQSTM1/p62: sequestosome 1; TFEB: transcription factor EB; TM: tamoxifen; WT: wild-type; ZG: zymogen granule.

13.
Artigo em Inglês | MEDLINE | ID: mdl-30912712

RESUMO

Horse meat and milk are an important source of nutrition for many Chinese. Previous studies have shown a fairly high prevalence of Toxoplasma gondii infection in horses. However, there is no data concerning the molecular characterization of T. gondii in horses in China. The present study tested 231 cervical lymph node samples of horses from northern China (97 from Jilin, 54 from Liaoning, and 80 from Xinjiang) for the presence of the T. gondii B1 gene by seminested PCR. The B1-positive samples were genotyped at nine nuclear loci, that is, SAG1, alternative SAG2, SAG3, BTUB, c22-8, GRA6, c29-2, PK1, and an apicoplast locus, using PCR-restriction fragment length polymorphism technique. A total of 14 (6.06%) out of 231 samples were T. gondii positive. The overall prevalence of T. gondii in the horses was 5.15% (5/97) for Jilin Province, 5.55% (3/54) for Liaoning Province, and 7.50% (6/80) for Xinjiang Uygur Autonomous Region. Of the 14 positive samples, only 2 were successfully genotyped at all loci, 5 were successfully genotyped at 5-8 loci, and all typed samples belong to ToxoDB genotype no. 9. To our knowledge, this is the first molecular characterization of the T. gondii isolates from horses in China.

14.
Redox Biol ; 22: 101148, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30818124

RESUMO

Mitochondria damage plays a critical role in acetaminophen (APAP)-induced necrosis and liver injury. Cells can adapt and protect themselves by removing damaged mitochondria via mitophagy. PINK1-Parkin pathway is one of the major pathways that regulate mitophagy but its role in APAP-induced liver injury is still elusive. We investigated the role of PINK1-Parkin pathway in hepatocyte mitophagy in APAP-induced liver injury in mice. Wild-type (WT), PINK1 knockout (KO), Parkin KO, and PINK1 and Parkin double KO (DKO) mice were treated with APAP for different time points. Liver injury was determined by measuring serum alanine aminotransferase (ALT) activity, H&E staining as well as TUNEL staining of liver tissues. Tandem fluorescent-tagged inner mitochondrial membrane protein Cox8 (Cox8-GFP-mCherry) can be used to monitor mitophagy based on different pH stability of GFP and mCherry fluorescent proteins. We overexpressed Cox8-GFP-mCherry in mouse livers via tail vein injection of an adenovirus Cox8-GFP-mCherry. Mitophagy was assessed by confocal microscopy for Cox8-GFP-mCherry puncta, electron microscopy (EM) analysis for mitophagosomes and western blot analysis for mitochondrial proteins. Parkin KO and PINK1 KO mice improved the survival after treatment with APAP although the serum levels of ALT were not significantly different among PINK1 KO, Parkin KO and WT mice. We only found mild defects of mitophagy in PINK1 KO or Parkin KO mice after APAP, and improved survival in PINK1 KO and Parkin KO mice could be due to other functions of PINK1 and Parkin independent of mitophagy. In contrast, APAP-induced mitophagy was significantly impaired in PINK1-Parkin DKO mice. PINK1-Parkin DKO mice had further elevated serum levels of ALT and increased mortality after APAP administration. In conclusion, our results demonstrated that PINK1-Parkin signaling pathway plays a critical role in APAP-induced mitophagy and liver injury.

15.
Gene Expr ; 2019 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-30717822

RESUMO

Studies using genetic mouse models that have defective autophagy have led to the conclusion that macroautophagy/autophagy serves as a tumor suppressor. One of such models is the liver-specific Atg5 or Atg7 knockout mice, and these knockout mice develop spontaneous liver tumors. It has been generally agreed that p62-mediated Nrf2 activation plays a critical role in promoting autophagy deficiencyinduced liver injury and liver tumorigenesis. The mechanisms of how persistent Nrf2 activation induces liver injury and tumorigenesis are incompletely known. We discuss the recent progress on the new roles of HMGB1 and Yap in regulating liver injury and tumorigenesis in mice with liver-specific autophagy deficiency.

16.
Sci Total Environ ; 665: 11-17, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30772539

RESUMO

With a self-designed small-scale waste incinerator, emission behaviors of parent and halogenated polycyclic aromatic hydrocarbons (PAHs and HPAHs) were simulated and visualized. According to our results, the 2-3 ring PAHs have higher emission factors (EFs) than those of the 4-6 ring PAHs during waste incineration. The EFs of individual HPAHs are comparable in all incineration products. Overall, the EFs of Æ©16PAH and Æ©3ClPAH decreased in the order of gas > bottom ash > particle > fine particle while the EF order for Æ©6BrPAH is bottom ash > particle > gas > fine particle. Based on qualitative observation, the size distributions of Σ16PAH, Σ3ClPAH, and Σ6BrPAH were characterized by trimodal peaks. Coagulation of fine particles in air may lead to enrichment of target compounds in the coarse particle fraction. The gas-particle partition did not reach theoretical equilibrium and most PAHs and HPAHs were absorbed inside the organic carbon. Estimated mass emission of target compounds in Shenzhen suggests that the gaseous phase from MSW incineration is the major contributor to the urban environment. However, automotive emissions contribute more to urban air pollution than MSW incineration in Shenzhen. Generally, compared with other real waste treatment, waste incineration is a more efficient method for waste-to-energy recovery and produces fewer pollutants, although the resultant carcinogenic substances are never truly harmless.

17.
Microb Pathog ; 129: 43-49, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30682525

RESUMO

BACKGROUND: Porcine epidemic diarrhea results from infection with porcine epidemic diarrhea virus (PEDV). It is an acute and highly contagious enteric disease in swine characterized by watery diarrhea and vomiting. Here, we performed a systematic review and meta-analysis in order to assess the prevalence of PEDV infection in pig populations from mainland China. METHODS: We conducted a literature search on the prevalence of PEDV infection in pigs between Jan 1, 1988 and Aug 20, 2018 in English and Chinese databases, including PubMed, Google scholar, Cochrane library, Clinical Trials, VIP, CNKI and WanFang database. Selections were made based on the title and the abstract of paper, and duplicated literature was excluded along with other host studies, and data incomplete literature according to the exclusion criteria we formulated. Finally, we extracted the number of swine with PEDV infection from the obtained studies and provided information that permitted us to estimate the prevalence of PEDV infection in pigs in mainland China. RESULTS: A total of 45 studies (including data from 15,990 pigs) met our evaluation criteria. In China, the overall estimated prevalence of PEDV infection in pigs was 44% (7113/15,990), while the estimated prevalence of PEDV infection in pigs from northern China was 37% (793/2136), lower than those in other regions of China. The prevalence of PEDV infection was associated with sampling season, category of pigs and clinical signs (diarrhea) in pigs. However, the prevalence of PEDV among pigs in China was not significantly associated with the effect of detected target genes, nor was it associated with date of study publication. CONCLUSION: Our findings suggest that PEDV infection is common among pigs in China. It is therefore necessary to carry out further research and monitor the prevalence of PEDV infection. Furthermore, powerful and effective regulatory measures should be taken in order to prevent the transmission and spread of PEDV among pig populations.


Assuntos
Infecções por Coronavirus/veterinária , Vírus da Diarreia Epidêmica Suína/isolamento & purificação , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/virologia , Animais , China/epidemiologia , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/virologia , Prevalência , Suínos
18.
Microb Pathog ; 128: 136-138, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30602126

RESUMO

Toxoplasma gondii is an obligate intracellular apicomplexan parasite that can infect almost all homoiothermal animals, including domestic raccoon dogs (Nyctereutes procyonoides). However, related reports on T. gondii infection in domestic raccoon dogs were limited in China. Therefore, a serological investigation was undertaken to investigate the seroprevalence and risk factors for T. gondii infection in domestic raccoon dogs. A total of 962 serum samples were collected from Jilin, Liaoning, Heilongjiang and Hebei provinces, northern China between April 2016 and November 2017, and were detected by the indirect hemagglutination test (IHA). The seroprevalence of T. gondii infection was 7.28% in the overall surveyed raccoon dogs by IHA, which was different among the four provinces ranging from 6.54% to 7.57%. The seroprevalence of T. gondii infection in male and female raccoon dogs was 6.62% and 7.79%, respectively. Based on statistical analysis, age was regarded as an important risk factor for T. gondii infection in raccoon dogs in this study (P < 0.05). This study reported the seroprevalence and risk factors of T. gondii infection in domestic raccoon dogs in northern China, which provided essential data for prevention and control of T. gondii infection in raccoon dogs in Jilin province, Liaoning province, Heilongjiang province and Hebei province.


Assuntos
Anticorpos Antiprotozoários/sangue , Doenças do Cão/epidemiologia , Cães Guaxinins/parasitologia , Toxoplasma/imunologia , Toxoplasma/patogenicidade , Toxoplasmose Animal/epidemiologia , Toxoplasmose Animal/imunologia , Fatores Etários , Animais , Animais Domésticos/parasitologia , China/epidemiologia , Doenças do Cão/sangue , Doenças do Cão/parasitologia , Cães , Feminino , Testes de Hemaglutinação , Masculino , Fatores de Risco , Estudos Soroepidemiológicos , Fatores Sexuais , Toxoplasmose Animal/sangue , Toxoplasmose Animal/parasitologia
19.
Hepatology ; 69(5): 2164-2179, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30552702

RESUMO

Acetaminophen (APAP) overdose is one of the leading causes of hepatotoxicity and acute liver failure in the United States. Accumulating evidence suggests that hepatocyte necrosis plays a critical role in APAP-induced liver injury (AILI). However, the mechanisms of APAP-induced necrosis and liver injury are not fully understood. In this study, we found that p53 up-regulated modulator of apoptosis (PUMA), a B-cell lymphoma-2 (Bcl-2) homology domain 3 (BH3)-only Bcl-2 family member, was markedly induced by APAP in mouse livers and in isolated human and mouse hepatocytes. PUMA deficiency suppressed APAP-induced mitochondrial dysfunction and release of cell death factors from mitochondria, and protected against APAP-induced hepatocyte necrosis and liver injury in mice. PUMA induction by APAP was p53 independent, and required receptor-interacting protein kinase 1 (RIP1) and c-Jun N-terminal kinase (JNK) by transcriptional activation. Furthermore, a small-molecule PUMA inhibitor, administered after APAP treatment, mitigated APAP-induced hepatocyte necrosis and liver injury. Conclusion: Our results demonstrate that RIP1/JNK-dependent PUMA induction mediates AILI by promoting hepatocyte mitochondrial dysfunction and necrosis, and suggest that PUMA inhibition is useful for alleviating acute hepatotoxicity attributed to APAP overdose.

20.
Am J Pathol ; 189(3): 580-589, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30553835

RESUMO

Despite the growing global burden of alcoholic liver diseases, therapeutic options are limited, and novel targets are urgently needed. Accumulating evidence suggests that mitochondria adapt in response to ethanol and formation of megamitochondria in the livers of patients is recognized as a hallmark of alcoholic liver diseases. The processes involved in ethanol-induced hepatic mitochondrial changes, the impact on mitochondria-shaping proteins, and the significance of megamitochondria formation remain unknown. In this study, we investigated the mitochondrial and cellular response to alcohol in hepatoma cell line VL-17A. The mitochondrial architecture rapidly changed after 3 or 14 days of ethanol exposure with double-pronged presentation of hyperfragmentation and megamitochondria, and cell growth was inhibited. Dynamin-1-like protein (Drp1) was identified as the main mediator driving these mitochondrial alterations, and its genetic inactivation was determined to foster megamitochondria development, preserving the capacity of the cells to grow despite alcohol toxicity. The role of Drp1 in mediating megamitochondria formation in mice with liver-specific inactivation of Drp1 was further confirmed. Finally, when these mice were fed with ethanol, the presentation of hepatic megamitochondria was exacerbated compared with wild type fed with the same diet. Ethanol-induced toxicity was also reduced. Our study demonstrates that megamitochondria formation is mediated by Drp1, and this phenomenon is a beneficial adaptive response during alcohol-induced hepatotoxicity.

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