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1.
Artigo em Inglês | MEDLINE | ID: mdl-33004280

RESUMO

OBJECTIVE: Thoracic aortic dissection (TAD) is associated with matrix changes, biochemical changes, and inflammatory markers like interleukin-1 beta (IL-1ß). However, the exact mechanism remains unknown. This study aimed to investigate the role of IL-1ß, matrix metalloproteinase (MMP)-2, MMP-9, smooth muscle cell apoptosis, and elastic fibre fracture in the development of TAD in a rat model. METHODS: The TAD rat model was induced by ß-aminopropionitrile (BAPN). TAD was investigated in 112 male Sprague-Dawley rats, which were equally divided into four groups of 28 rats (Control, BAPN, BAPN + IL-1ß, and BAPN + IL-1ß antibody). Systolic blood pressure, survival, and the development of TAD were measured after six weeks. Expression of IL-1ß, MMP-2, and MMP-9 was measured by Western blot. Apoptosis, aortic elastin concentration, and biomechanical characteristics were measured by the TdT mediated dUTP nick end labelling assay, Victoria blue staining, and in vitro testing. RESULTS: During six weeks, the mortality was 0% (0/28) in the control group, 53.6% (15/28) in the BAPN group (p < .001 compared with the control group), 75.0% (21/28) in the BAPN + IL-1ß group (p = .007 compared with the BAPN group), and 35.7% (10/28) in the BAPN + IL-1ß antibody group (p = .023 compared with BAPN group and p < .001 compared with the BAPN + IL-1ß group). IL-1ß treatment deteriorates BAPN induced mortality and aneurysm expansion, which were attenuated by anti-IL-1ß treatment. In BAPN + IL-1ß group, stress and strain parameters were decreased by 13.5%-53.5% and elastin content was decreased by 14%, and IL-1ß, MMP-2, and MMP-9 were expressed higher by 117%, 108%, and 75% when compared with the rats in the BAPN group. Contrarily, in the BAPN + IL-1ß antibody group, the above changes could be completely (strain, elastin content, and expression of MMP-2) or partly (elasticity modulus, stress, and expression of MMP-9) blocked by anti-IL-1ß treatment. CONCLUSION: IL-1ß plays a critical role in TAD formation by altering the expression of MMP-2 and MMP-9, degrading the aortic wall matrix, causing elastic fibre rupture, and changing the stress or strain of the aortic wall. Anti-IL-1ß reduces the later effects and could be one of the molecular targets for prognosis and drug treatment of TAD in the future.

2.
Stem Cell Res Ther ; 11(1): 434, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032649

RESUMO

BACKGROUND: The transplantation of bone marrow mesenchymal stem cells (BMSCs) is a promising therapeutic strategy for wound healing. However, the poor migration capacity and low survival rate of transplanted BMSCs in wounds weaken their potential application. OBJECTIVE: To identify the optimal protocol for BMSCs preconditioned with H2O2 and improve the therapeutic efficacy using H2O2-preconditioned BMSCs in wound healing. METHODS: Mouse BMSCs were exposed to various concentrations of H2O2, and the key cellular functional properties were assessed to determine the optimal precondition with H2O2. The H2O2-preconditioned BMSCs were transplanted into mice with full-thickness excisional wounds to evaluate their healing capacity and tissue engraftment. RESULTS: Treatment BMSCs with 50 µM H2O2 for 12 h could significantly enhance their proliferation, migration, and survival by maximizing the upregulation of cyclin D1, SDF-1, and its receptors CXCR4/7 expressions, and activating the PI3K/Akt/mTOR pathway, but inhibiting the expression of p16 and GSK-3ß. Meanwhile, oxidative stress-induced BMSC apoptosis was also significantly attenuated by the same protocol pretreatment with a decreased ratio of Bax/Bcl-2 and cleaved caspase-9/3 expression. Moreover, after the identification of the optimal protocol of H2O2 precondition in vitro, the migration and tissue engraftment of transfused BMSCs with H2O2 preconditioning were dramatically increased into the wound site as compared to the un-preconditioned BMSCs. The increased microvessel density and the speedy closure of the wounds were observed after the transfusion of H2O2-preconditioned BMSCs. CONCLUSIONS: The findings suggested that 50 µM H2O2 pretreated for 12 h is the optimal precondition for the transplantation of BMSCs, which gives a considerable insight that this protocol may be served as a promising candidate for improving the therapeutic potential of BMSCs for wound healing.

3.
J Agric Food Chem ; 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33030895

RESUMO

Fruit and leaf possess distinctly different metabolites. Here, metabolites and transcriptome were compared between mature leaves (ML) and juice sacs (JS) of Citrus grandis "Hirado Buntan" to investigate the possible reasons. Results indicated that the remarkable difference in starch, total flavonoids and carotenoids, l-ascorbate, and jasmonic acid between ML and JS was tightly related to the expression levels of their biosynthesis-related genes, while the significant difference in abscisic acid and citrate was mainly related to the gene expression level(s) of 9-cis-epoxycarotenoid dioxygenase and proton pump genes, respectively. In addition, ATP citrate lyase probably plays a key role in the levels of flavonoids between ML and JS via providing different levels of acetyl-CoA. Taken together, these results identified some key candidate genes responsible for the content of a given metabolite and will contribute to research in regulating such metabolite content in citrus fruits.

4.
Pediatr Infect Dis J ; 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33044433

RESUMO

BACKGROUND: There are limit studies about pediatric brain abscess in China. The aim of this study was to analyze clinical characteristics and outcomes of pediatric brain abscess in recent years in China. METHODS: The clinical information of children with brain abscess hospitalized in Beijing Children's Hospital between January 1, 2007 and December 31, 2016 were retrospectively reviewed. RESULTS: Ninety-four children were enrolled in this study. A Streptococcus milleri group (13.8%) was identified as the most common causative organisms, followed by Staphylococcus aureus (6.4%). The overall mortality was 21.6%, with 50.0% of deaths happening in the first week after diagnosis. Long-term outcomes of 74 patients were assessed with Glasgow Outcome Scale-Extended Pediatric Reversion: 50 patients with a score of 1-2 (favorable outcome) and 24 patients with a score of 3-8 (unfavorable outcome). Patients with multiple abscesses (P = 0.029) and intraventricular rupture of brain abscess/hydrocephalus (P = 0.024) had higher risk of unfavorable outcomes. CONCLUSIONS: Brain abscess is a serious disease with high mortality in children; more aggressive treatments should be considered in the first week of diagnosis because of high risk of death, and for patients with multiple brain abscesses and intraventricular rupture of brain abscess/hydrocephalus because of their higher risk of unfavorable.

5.
Nat Commun ; 11(1): 4913, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33004813

RESUMO

Reprograming of proline metabolism is critical for tumor growth. Here we show that PINCH-1 is highly expressed in lung adenocarcinoma and promotes proline synthesis through regulation of mitochondrial dynamics. Knockout (KO) of PINCH-1 increases dynamin-related protein 1 (DRP1) expression and mitochondrial fragmentation, which suppresses kindlin-2 mitochondrial translocation and interaction with pyrroline-5-carboxylate reductase 1 (PYCR1), resulting in inhibition of proline synthesis and cell proliferation. Depletion of DRP1 reverses PINCH-1 deficiency-induced defects on mitochondrial dynamics, proline synthesis and cell proliferation. Furthermore, overexpression of PYCR1 in PINCH-1 KO cells restores proline synthesis and cell proliferation, and suppresses DRP1 expression and mitochondrial fragmentation. Finally, ablation of PINCH-1 from lung adenocarcinoma in mouse increases DRP1 expression and inhibits PYCR1 expression, proline synthesis, fibrosis and tumor growth. Our results identify a signaling axis consisting of PINCH-1, DRP1 and PYCR1 that regulates mitochondrial dynamics and proline synthesis, and suggest an attractive strategy for alleviation of tumor growth.

6.
Br J Cancer ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32958824

RESUMO

BACKGROUND: The liver is the central organ for cholesterol homoeostasis, and its dysfunction might cause liver pathological alterations including hepatocellular carcinomas (HCCs). 3ß-hydroxysteroid-Δ24 reductase (DHCR24), a crucial enzyme of cholesterol biosynthetic pathway, is involved in lipid rafts formation. Genkwadaphnin (GD) is a daphnane diterpene isolated from the flower buds of Daphne genkwa Siebold et Zuccarini (Thymelaeaceae). METHODS: We evaluated in vitro and in vivo effect of GD using HCC cells and BALB/c nude mice. Microarray assays were used to identify the differential genes by GD. DHCR24 expression and activity, cholesterol level, lipid rafts structure and the role of DHCR24 in human HCC specimens were tested by various molecular biology techniques. RESULTS: High expression of DHCR24 in human HCC specimens was correlated with poor clinical outcome. Interfering DHCR24 altered growth and migration of HCC cells. GD inhibited growth and metastasis of HCC cells both in vivo and in vitro. GD suppressed DHCR24 expression and activity, as well as DHCR24-mediated cholesterol biosynthesis and lipid rafts formation, then further inhibited HCC cell invasion and migration. CONCLUSIONS: Our data suggest that DHCR24-mediated cholesterol metabolism might be an effective therapeutic strategy in HCC, and natural product GD might be a promising agent for HCC therapy.

7.
Mol Med Rep ; 22(4): 3255-3262, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945430

RESUMO

The occurrence and development of hyperglycemia­induced inflammation is associated with increased expression of receptor for advanced glycation end products (RAGE) and inflammatory factors, including IL­1ß, TNF­α and IL­6. Previous studies have reported that the nucleotide­binding oligomerization domain­like receptor protein 3 (NLRP3) inflammasome interacts with thioredoxin­interacting protein (TXNIP) and serves a crucial role in inflammation. FPS­ZM1 has been identified as target inhibitor of RAGE and has been shown to exert an anti­inflammatory effect in vitro. However, the underlying mechanism by which FPS­ZM1 impacts high glucose (HG)­induced inflammation in bone marrow mesenchymal stem cells (BMSCs) remains unclear. The present study explored the regulatory effect of FPS­ZM1 on HG­induced inflammation in BMSCs. Furthermore, the role of the TXNIP/NLRP3 inflammasome signaling pathway in the regulatory effects of FPS­ZM1 on HG­induced inflammation was studied. Cell viability was determined using Cell Counting Kit­8 and western blotting was used to assess the protein expression levels of RAGE. ELISA was used to determine the levels of inflammatory markers. Reverse transcription­quantitative PCR and western blotting were used to measure the mRNA and protein expression levels of TXNIP, caspase­1, thioredoxin (TRX), NLRP3 and apoptosis­related speck­like protein containing CARD (ASC). The results revealed that in BMSCs, RAGE expression was stimulated by HG, an effect which was reversed by treatment with FPS­ZM1. In addition, HG activated inflammatory factors, such as TNF­α, IL­1ß and IL­6; however, their levels were suppressed when cells were treated with FPS­ZM1 or the TXNIP/NLRP3 pathway inhibitor, resveratrol (Res). Furthermore, FPS­ZM1 inhibited the mRNA and protein expression levels of TXNIP, caspase­1, NLRP3 and ASC, and promoted TRX expression, which was consistent with the effects of Res. These findings indicated that FPS­ZM1 may attenuate HG­induced inflammation in BMSCs. Furthermore, the TXNIP/NLRP3 inflammasome signaling pathway mediated the molecular mechanism underlying this effect.

8.
Mol Med Rep ; 22(4): 3299-3306, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32945495

RESUMO

N-acetyl cysteine (NAC) has been used to inhibit lipopolysaccharide (LPS)-induced inflammation. However, the molecular mechanism underlying its anti­inflammatory effects remains to be elucidated. The present study aimed to determine the effect of NAC on the LPS­induced inflammatory response in bone marrow mesenchymal stem cells (BMSCs) and elucidate the underlying molecular mechanism. First, BMSCs were stimulated by LPS following pretreatment with NAC (0, 0.1, 0.5, 1 or 2 mM). A Cell Counting Kit 8 assay was used to determine the number of viable cells and 1 mM NAC was selected as the experimental concentration. Then, the secretion of inflammatory factors, including interleukin (IL)­1ß, IL­6 and tumor necrosis factor­α was evaluated by enzyme­linked immunosorbent assay. Finally, the expression levels of mRNA and proteins, including apoptosis­associated speck­like protein containing a CARD (ASC), nucleotide­binding oligomerization domain­like receptor protein 3 (NLRP3), caspase­1, thioredoxin­interacting protein (TXNIP), and thioredoxin (TRX), were evaluated by reverse transcription­quantitative PCR and western blot analysis, respectively. The results demonstrated that the secretion of inflammatory factors, which was increased by the administration of LPS, was reduced by pretreatment with NAC. Furthermore, NAC reduced the expression of ASC, NLRP3, caspase­1 and TXNIP, but enhanced that of TRX. To conclude, NAC had anti­inflammatory effects on LPS­stimulated BMSCs, which was closely associated with the TXNIP/NLRP3/IL­1ß signaling pathway. Thus, NAC may be a promising treatment to attenuate the inflammatory response in LPS­induced BMSCs.

9.
Chem Commun (Camb) ; 56(82): 12403-12406, 2020 Oct 21.
Artigo em Inglês | MEDLINE | ID: mdl-32935673

RESUMO

Herein, an anionic metal-organic framework, formulated as {[Zn3(OH)(bmipia)(H2O)3]4·[Zn(H2O)6.5]2}n (FCS-3), was prepared from zinc ions and semi-rigid carboxylate ligands of 5-[N,N-bis(5-methylisophthalic acid)amion] isophthalic acid (H6bmipia) and was employed as a unique fluorescence turn-on chemical sensor for the ultra-sensitive detection of various antibiotics in the aqueous phase.

10.
Vet Res ; 51(1): 102, 2020 Aug 14.
Artigo em Inglês | MEDLINE | ID: mdl-32795339

RESUMO

Glaesserella parasuis (G. parasuis) causes porcine vascular inflammation and damage. Baicalin is reported to have antioxidant and anti-inflammatory functions. However, whether baicalin protects piglets against G. parasuis challenge and the potential protective mechanism have not been investigated. Therefore, in this study, we comprehensively examined the protective efficacy of baicalin in piglets challenged with G. parasuis and the possible protective mechanism. Our results show that baicalin attenuated the release of the inflammation-related cytokines interleukin (IL) 1ß, IL6, IL8, IL10, and tumour necrosis factor α (TNF-α) and reduced high mobility group box 1 (HMGB1) production and cell apoptosis in piglets infected with G. parasuis. Baicalin also inhibited the activation of the mitogen-activated protein kinase (MAPK) signalling pathway and protected piglets against G. parasuis challenge. Taken together, our data suggest that baicalin could protect piglets from G. parasuis by reducing HMGB1 release, attenuating cell apoptosis, and inhibiting MAPK signalling activation, thereby alleviating the inflammatory response induced by the bacteria. Our results suggest that baicalin has utility as a novel therapeutic drug to control G. parasuis infection.

11.
J Agric Food Chem ; 68(35): 9299-9307, 2020 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-32786837

RESUMO

Microvirga flocculans CGMCC 1.16731 can degrade many cyano group-containing neonicotinoid insecticides. Here, its genome was sequenced, and a novel nitrile hydratase gene cluster was discovered in a plasmid. The NHase gene cluster (pnhF) has gene structure ß-subunit 1, α-subunit, and ß-subunit 2, which is different from previously reported NHase gene structures. Phylogenetic analysis of α-subunits indicated that NHases containing the three subunit (ß1αß2) structure are independent from NHases containing two subunits (αß). pnhF was successfully expressed in Escherichia coli, and the purified PnhF could convert the nitrile-containing insecticide flonicamid to N-(4-trifluoromethylnicotinoyl)glycinamide. The enzymatic properties of PnhF were investigated using flonicamid as a substrate. Homology models revealed that amino acid residue ß1-Glu56 may strongly affect the catalytic activity of PnhF. This study expands our understanding of the structures and functions of NHases and the enzymatic mechanism of the environmental fate of flonicamid.

12.
J Dairy Sci ; 103(11): 9969-9979, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32861498

RESUMO

The purpose of this study was to elucidate the antibacterial activity and possible mechanism of action of Amaranthus tricolor crude extract (ATCE) against Cronobacter sakazakii isolated from powdered infant formula (PIF). The antibacterial activity of ATCE was assessed by measuring the diameter of inhibition zone (DIZ), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). The possible mechanism of action of ATCE was revealed by analyzing the effects of ATCE on growth curves and changes in cell membrane potential, intracellular pH, content of bacterial protein and genomic DNA, and cell morphology. Finally, ATCE was applied to the disinfection of C. sakazakii in biofilm on stainless steel tube. The results showed that the DIZ, MIC, and MBC of ATCE against C. sakazakii strains were from 14.35 ± 0.67 to 14.84 ± 0.67 mm, 20 mg/mL, and 40 mg/mL, respectively. Treatment with ATCE ended the logarithmic growth phase of C. sakazakii, and led to depolarization of the cell membranes, reducing intracellular pH and bacterial protein and genomic DNA contents, and resulting in cytoplasmic leakage and deformation. In addition, ATCE effectively inactivated C. sakazakii in biofilm, reducing viable bacteria by approximately 6.5 log cfu/mL bacterial count after treatment with 1 MIC (1 MIC = 20 mg/mL) of ATCE for 20 min at 25°C. Our findings showed that ATCE inactivated C. sakazakii strains isolated from PIF and has potential as a natural disinfectant to reduce the contamination of PIF by C. sakazakii.

13.
J Leukoc Biol ; 2020 Jul 03.
Artigo em Inglês | MEDLINE | ID: mdl-32620046

RESUMO

Hepatitis B virus (HBV)-specific T cells play a critical role in determining the outcome of HBV infection. However, T cell response induced by predominant Ag in chronic infection is hardly detectable owing to the lack of a suitable assay. We herein established an optimized method to enumerate HBV-specific T cells and assessed the association between HBV surface Ag (HBsAg) and HBV DNA. Sixty chronic HBV infection patients were enrolled. HBV-specific T cells were expanded by using overlapping peptide pools covering the entire sequence of HBV genotypes B and C. IFN-γ-producing HBV-specific T cells were detected by a cultured enzyme-linked immunospot (ELISPOT) assay, ex vivo ELISPOT assay, or flow cytometry staining. The association between HBV-specific T cells and serum levels of HBsAg and HBV DNA were analyzed. Cultured ELISPOT assay had a higher sensitivity than ex vivo ELISPOT in the detection of HBV-specific T cells. Moreover, consistent results were acquired by flow cytometry analysis and cultured ELISPOT assay, but the latter required only a limited number of cells for detection. Interestingly, HBV core peptide pool induced a robust HBV-specific T cell response in patients with lower levels of HBV DNA and HBsAg. Specifically, the frequency of HBV core Ag-specific IFN-γ+ spot-forming cells was inversely correlated with serum levels of HBV DNA and HBsAg. An optimized cultured ELISPOT assay reveals the association between HBV core Ag-induced T cell response and HBV control; this method may favor the investigation of HBV-specific T cell in chronic HBV infection.

14.
Yi Chuan ; 42(7): 641-656, 2020 Jul 20.
Artigo em Chinês | MEDLINE | ID: mdl-32694104

RESUMO

Gene-editing technology can artificially modify genetic material of targeted loci by precise insertion, deletion, or replacement in the genomic DNA. In recent years, with the developments of zinc-finger endonuclease (ZFN), transcription activator-like effector nuclease (TALEN), clustered regularly interspaced short palindromic repeats/CRISPR- associated protein 9 (CRISPR/Cas9) technologies, such precise modifications of the animal genomes have become possible. Although gene-editing tools, such as CRISPR/Cas9, can efficiently generate double-strand breaks (DSBs) in mammalian cells, the homology-directed repair (HDR) mediated knock-in (KI) efficiency is extremely low. In this review, we briefly describe the current development of gene-editing tools and summarize the recent strategies to enhance the CRISPR/Cas9- mediated KI efficiency, which will provide a reference for the generation of human disease models, research on gene therapy and livestock genetic improvement.

15.
JAMA Oncol ; 2020 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-32701129

RESUMO

Importance: The role of locoregional radiotherapy in patients with de novo metastatic nasopharyngeal carcinoma (mNPC) is unclear. Objective: To investigate the efficacy and safety of locoregional radiotherapy in de novo mNPC. Design, Setting, and Participants: Patients with biopsy-proven mNPC, who demonstrated complete or partial response (RECIST v1.1) following 3 cycles of cisplatin and fluorouracil chemotherapy, were enrolled. Eligible patients were randomly assigned (1:1) to receive either chemotherapy plus radiotherapy or chemotherapy alone. Overall, 126 of 173 patients screened were eligible to the study, and randomized to chemotherapy plus radiotherapy (n = 63) or chemotherapy alone (n = 63). Median (IQR) follow-up duration was 26.7 (17.2-33.5) months. Interventions: The chemotherapy regimens were fluorouracil continuous intravenous infusion at 5 g/m2 over 120 hours and 100 mg/m2 intravenous cisplatin on day 1, administered every 3 weeks for 6 cycles. Patients assigned to the chemotherapy plus radiotherapy group received intensity-modulated radiotherapy (IMRT) after chemotherapy. Main Outcomes and Measures: The primary end point of the study was overall survival (OS). The secondary end point was progression-free survival (PFS) and safety. Results: Overall, 126 patients were enrolled (105 men [83.3%] and 21 women [16.7%]; median [IQR] age, 46 [39-52] years). The 24-month OS was 76.4% (95% CI, 64.4%-88.4%) in the chemotherapy plus radiotherapy group, compared with 54.5% (95% CI, 41.0%-68.0%) in the chemotherapy-alone group. The study met its primary end point of improved OS (stratified hazard ratio [HR], 0.42; 95% CI, 0.23-0.77; P = .004) in favor of chemotherapy plus radiotherapy. Progression-free survival was also improved in the chemotherapy plus radiotherapy group compared with the chemotherapy-alone group (stratified HR, 0.36; 95% CI, 0.23-0.57). No significant differences in acute hematological or gastrointestinal toxic effects were observed between the treatment arms. The frequency of acute grade 3 or higher dermatitis, mucositis, and xerostomia was 8.1%, 33.9%, and 6.5%, respectively, in the chemotherapy plus radiotherapy group. The frequency of late severe grade 3 or higher hearing loss and trismus was 5.2% and 3.4%, respectively, in the chemotherapy plus radiotherapy group. Conclusions and Relevance: In this randomized clinical trial, radiotherapy added to chemotherapy significantly improved OS in chemotherapy-sensitive patients with mNPC. Trial Registration: ClinicalTrials.gov Identifier: NCT02111460.

16.
J Immunol Res ; 2020: 3530768, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32714994

RESUMO

Objective: To investigate clinical features, independent associated factors, treatment, and outcome of patients with peripheral neuropathy (PN) in eosinophilic granulomatosis with polyangiitis (EGPA). Methods: We retrospectively analyzed clinical data of 110 EGPA patients from 2007 to 2019 in Peking Union Medical College Hospital. The independent factors associated with PN in EGPA were analyzed with univariate and multivariate logistic regressions. Results: In EGPA with PN, paresthesia and muscle weakness were observed in 82% and 33% of patients, respectively. Both the upper and lower limbs were involved in 51% of patients. 30% of EGPA patients had symmetrical multiple peripheral neuropathy, whereas only 16.4% presented with mononeuritis multiplex. Compared to patients without PN, patients with PN had a higher erythrocyte sedimentation rate, C-reactive protein, rheumatoid factor, Birmingham vasculitis activity score (BVAS), and positivity of myeloperoxidase-antineutrophil cytoplasmic antibodies (MPO-ANCA). Regarding manifestations, patients with PN tended to develop weight loss and arthritis or joint pain. Notably, ANCA positivity, arthritis or joint pain, and higher BVAS were found to be independent associated factors for PN in EGPA. Patients with PN more frequently need glucocorticoid pulses and intravenous infusion of cyclophosphamide. With the longest follow-up of 11.0 years, we found that age and cardiac involvement were risk factors for survival, and female was the protective factor. Conclusion: PN in EGPA frequently displays with symmetrical multiple peripheral neuropathy in China. Positive ANCA, arthritis or joint pain, and higher BVAS are the independent associated factors of PN in EGPA. Glucocorticoids with immunosuppressants are vital therapeutic strategy.

17.
Phys Chem Chem Phys ; 2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32662487

RESUMO

Recently, Janus two-dimensional (2D) materials as a new member of 2D derivatives have been receiving much attention due to their novel properties. In this work, the lattice thermal conductivity κL of the Janus SnSSe monolayer is investigated based on first-principles calculations, while that of the SnS2 monolayer is studied for comparison. It is found the the κL values of SnSSe and SnS2 are 13.3 and 11.0 W m-1 K-1 at room temperature, and acoustic branches dominate their thermal transport. Weaker phonon anharmonicity in SnSSe leads to a slightly higher κL, though it has weaker phonon harmonicity. The smaller Grüneisen parameters of TA and LA phonons lower than 1 THz in SnSSe indicate weaker phonon anharmonicity, resulting in a higher κL. Finally, the size effect and boundary effect are also investigated, exhibiting that the κL can further decrease at the nanoscale. Our work suggests that Janus SnSSe and SnS2 have a much lower κL compared with conventional transition metal dichalcogenides (TMDs) and are potential competitors in the thermoelectric field.

18.
Sci Total Environ ; 742: 140597, 2020 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-32629271

RESUMO

Polychlorinated biphenyls (PCBs) and halogen flame retardants (HFRs) are major pollutants in e-waste recycling area. High internal exposure levels of PCBs and HFRs are harmful to human thyroid hormone (TH) equilibrium. To examine their disrupting effects on TH, we conducted a study on children (n = 114) of an e-waste recycling and a control area in South China. Concentrations of PCBs, HFRs, and TH levels were determined in serum samples. TH related proteins and their corresponding gene were also monitored as markers of such disruption. Levels of these chemicals in the exposed group were much greater than those in the control group. Results of the linear regression and generalized additive model indicated the presence of close relationships between the internal exposure levels and the responses of TH related proteins, gene expression. More extensive exposure concentrations of these chemicals led to higher expression of iodothyronine deiodinase I and decreased the concentrations of thyroid-stimulating hormone, expression of TH receptor α, indicating the exertion of discrepant and even contrary influences on equilibrium of TH, and a compensation of these mechanisms may kept the homeostasis of TH. These results for children warrant further investigation on the health risks of PCBs and HFRs exposure in e-waste area.


Assuntos
Resíduo Eletrônico/análise , Retardadores de Chama , Bifenilos Policlorados/análise , Criança , China , Halogênios , Humanos , Proteínas , Reciclagem , Hormônios Tireóideos
20.
Oncogene ; 39(30): 5307-5322, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32555330

RESUMO

Nasopharyngeal carcinoma (NPC) is a unique head and neck cancer with highly aggressive and metastatic potential in which distant metastasis is the main reason for treatment failure. Till present, the underlying molecular mechanisms of NPC metastasis remains poorly understood. Here, we identified S100 calcium-binding protein A14 (S100A14) as a functional regulator suppressing NPC metastasis by inhibiting the NF-kB signaling pathway and reversing the epithelial-mesenchymal transition (EMT). S100A14 was found to be downregulated in highly metastatic NPC cells and tissues. Immunohistochemical staining of 202 NPC samples revealed that lower S100A14 expression was significantly correlated with shorter patient overall survival (OS) and distant metastasis-free survival (DMFS). S100A14 was also found as an independent prognostic factor for favorable survival. Gain- and loss-of-function studies confirmed that S100A14 suppressed the in vitro and in vivo motility of NPC cells. Mechanistically, S100A14 promoted the ubiquitin-proteasome-mediated degradation of interleukin-1 receptor-associated kinase 1 (IRAK1) to suppress NPC cellular migration. Moreover, S100A14 and IRAK1 established a feedback loop that could be disrupted by the IRAK1 inhibitor T2457. Overall, our findings showed that the S100A14-IRAK1 feedback loop could be a promising therapeutic target for NPC metastasis.

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