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1.
BMC Med Genomics ; 13(Suppl 5): 45, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32241267

RESUMO

BACKGROUND: Initially characterized as axon guidance factors, semaphorins also have been implicated to have critical roles in multiple physiological and developmental functions, including the regulation of immune responses, angiogenesis, organ formation, and the etiology of multiple forms of cancer. Moreover, their contribution in immunity and the regulation of tumour microenvironment is becoming increasingly recognized. Here, we provide a comprehensive analysis of class-3 semaphorins, the only secreted family of genes among veterbrate semaphorins, in terms of their expression profiles and their association with patient survival. We also relate their role with immune subtypes, tumour microenvironment, and drug sensitivity using a pan-cancer study. RESULTS: Expression profiles of class-3 semaphorins (SEMA3s) and their association with patient survival and tumour microenvironment were studied in 31 cancer types using the TCGA pan-cancer data. The expression of SEMA3 family varies in different cancer types with striking inter- and intra- cancer heterogeneity. In general, our results show that SEMA3A, SEMA3C, and SEMA3F are primarily upregulated in cancer cells, while the rest of SEMA3s are mainly down-regulated in the tested tumours. The expression of SEMA3 family members was frequently associated with patient overall survival. However, the direction of the association varied with regards to the particular SEMA3 isoform queried and the specific cancer type tested. More specifically, SEMA3A and SEMA3E primarily associate with a poor prognosis of survival, while SEMA3G typically associates with survival advantage. The rest of SEMA3s show either survival advantage or disadvantage dependent on cancer type. In addition, all SEMA3 genes show significant association with immune infiltrate subtypes, and they also correlate with level of stromal cell infiltration and tumour cell stemness with various degrees. Finally, our study revealed that SEMA3 genes, especially SEMA3C and SEMA3F may contribute to drug induced cancer cell resistance. CONCLUSIONS: Our systematic analysis of class-3 semaphorin gene expression and their association with immune infiltrates, tumour microenvironment and cancer patient outcomes highlights the need to study each SEMA3 member as a separate entity within each specific cancer type. Also our study validated the identification of class-3 semaphorin signals as promising therapeutic targets in cancer although further laboratory validation still needed.

2.
Small ; : e2000441, 2020 Apr 03.
Artigo em Inglês | MEDLINE | ID: mdl-32243095

RESUMO

Efficient organic solar cells (OSCs) are fabricated using polymer PM6 as donor, and IPTBO-4Cl and MF1 as acceptors. The power conversion efficiency (PCE) of IPTBO-4Cl based and MF1 based binary OSCs individually arrive to 14.94% and 12.07%, exhibiting markedly different short circuit current density (JSC ) of 23.18 mA cm-2 versus 17.01 mA cm-2 , fill factor (FF) of 72.17% versus 78.18% and similar open circuit voltage (VOC ) of 0.893 V versus 0.908 V. The two acceptors, IPTBO-4Cl and MF1, have similar lowest unoccupied molecular orbital levels, which is beneficial for efficient electron transport in the ternary active layer. The PCE of optimized ternary OSCs arrives to 15.74% by incorporating 30 wt% MF1 in acceptors, resulting from the simultaneously increased JSC of 23.20 mA cm-2 , VOC of 0.897 V, and FF of 75.64% in comparison with IPTBO-4Cl based binary OSCs. The gradually increased FFs of ternary OSCs indicate the well-optimized phase separation and molecular arrangement with MF1 as morphology regulator. This work may provide a new viewpoint for selecting an appropriate third component to achieve efficient ternary OSCs from materials and photovoltaic parameters of two binary OSCs.

3.
Int J Biol Macromol ; 155: 103-109, 2020 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-32224180

RESUMO

Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most common causes of hospital infection. Here, we showed that hyaluronic acid modified organic metal framework material ZIF-8 could be a Trojan horse of vancomycin (Van) for effective treatment of MRSA infections. The Van-loaded nanoparticles were readily up-taken by macrophages via a CD44-mediated process and collapsed in the acidic condition of endosome/lysosome, as a consequence, it could eradicate MRSA with high efficiency in macrophages. This drug delivery system with negligible toxicity could resolve MRSA infections in a well-established mouse pneumonia model.

4.
Clin Infect Dis ; 2020 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-32211844

RESUMO

BACKGROUND: The outbreak of COVID-19 has become a big threat to China, with high contagious capacity and varied mortality. This study aimed to investigate the epidemiological and clinical characteristics of older patients with COVID-19 out of Wuhan. METHODS: A retrospective study was performed, with collecting data from medical records of confirmed COVID-19 patients in Zhejiang province from Jan 17 to Feb 12, 2020. Epidemiological, clinical and treatment data were analyzed between those older (≥60y) and younger (<60y) patients. RESULTS: Total 788 patients with confirmed COVID-19 were selected, where 136 were older patients with corresponding age of 68.28y±7.314y. There was a significantly higher frequency of women in the older patients compared with the younger patients (57.35% vs 46.47%, P=0.021). The presence of coexisting medical condition was significantly higher in older patients compared with younger patients (55.15% vs 21.93%, P<0.001), including the rate of hypertension, diabetes, heart diseases and COPD. Significantly higher rates of severe (older vs younger groups: 16.18% vs 5.98%, P<0.001)/critical (8.82% vs 0.77%, P<0.001) type, shortness of breath (12.50% vs 3.07%, P<0.001) and high temperature of >39.0℃ (13.97% vs 7.21%, P=0.010) were observed in older patients compared with younger patients. Finally, Higher rates of ICU admission (9.56% vs 1.38%, P<0.001) and methylprednisolone application (28.68% vs 9.36%, P<0.001) were also identified in older patients. CONCLUSIONS: The specific epidemiological and clinical features of older COVID-19 patients included significantly higher female gender, body temperature, co-existing of basic diseases and rate of severe and critical type.

5.
Int J Infect Dis ; 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32205284

RESUMO

PURPOSE: To investigate the epidemiological, clinical characteristics of COVID-19 patients with abnormal imaging findings. METHODS: Patients confirmed with SARS-CoV-2 infection of Zhejiang province from Jan 17 to Feb 8 underwent CT or x-ray were enrolled. Epidemiological, clinical data were analyzed between those with abnormal or normal imaging findings. RESULTS: Excluding 72 patients with normal images, 230 of 573 patients affected more than two lobes. The median radiograph score was 2.0 and there's negative correlation between the score and oxygenation index (ρ=-0.657,P < 0.001). Patients with abnormal images were older (46.65 ± 13.82), with higher rate of coexisting condition(28.8%), lower rate of exposure history and longer time between onset and confirmation(5d) than non-pneumonia patients(all P < 0.05). Higher rate of fever, cough, expectoration, and headache, lower lymphocytes, albumin, serum sodium levels and higher total bilirubin, creatine kinase, lactate dehydrogenase and C-reactive protein levels and lower oxygenation index were observed in pneumonia patients (all P < 0.05). Muscle ache, shortness of breath, nausea and vomiting, lower lymphocytes levels and higher serum creatinine and radiograph score at admission were predictive factors for severe/critical subtype. CONCLUSION: Patients with abnormal images have more obvious clinical manifestations and laboratory changes. Combing clinical features and radiograph score can effectively predict severe/critical type.

6.
Sci Rep ; 10(1): 5095, 2020 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198420

RESUMO

The mode of action for oncolytic viruses (OVs) in cancer treatment is thought to depend on a direct initial cytotoxic effect against infected tumor cells and subsequent activation of immune cell responses directed against the neoplasm. To study both of these effects in a mouse model of glioblastoma (GBM), we employed murine GBM cells engineered to constitutively express the type I Herpes Simplex Virus (HSV1) HSV-1 receptor, nectin-1, to allow for more efficient infection and replication by oncolytic HSV (oHSV). These cells were further engineered with a surrogate tumor antigen to facilitate assays of T cell activity. We utilized MRI-based volumetrics to measure GBM responses after injection with the oHSV and bioluminescent imaging (BLI) to determine oHSV replicative kinetics in the injected tumor mass. We found increased infiltration of both surrogate tumor antigen- and oHSV antigen-specific CD8+ T cells within 7 days after oHSV injection. There was no increase in tumor infiltrating CD8+ T cells expressing "exhaustion" markers, yet oHSV infection led to a reduction in PD-1+ CD8+ T cells in injected GBMs and an increase in IFNγ+ CD8+ T cells. There was a significant direct correlation between oHSV-mediated reduction in GBM volume and increased infiltration of both viral and tumor antigen-specific CD8+ T cells, as well as oHSV intratumoral gene activity. These findings imply that CD8+ T cell cytotoxicity against both tumor and viral antigens as well as intratumoral oHSV gene expression are important in oHSV-mediated GBM therapy.

7.
Microb Drug Resist ; 2020 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-32150494

RESUMO

Background: The aim of this study was to investigate the characteristics of carbapenem-resistant Klebsiella pneumoniae (CRKP) ST76 isolates collected during an outbreak in a hospital's intensive care unit and neurosurgery unit. Methods: Seventeen separate clinical isolates of CRKP were collected from patients from March 2016 to February 2017. Bacterial isolates were identified, and antimicrobial susceptibility testing was conducted using the VITEK-2 compact system. Isolates containing antibiotic resistance genes were characterized by polymerase chain reaction and DNA sequencing. Clonal relatedness was assessed by multilocus sequence typing and pulsed-field gel electrophoresis. Conjugation experiments were performed to determine the transferability of plasmids with antibiotic resistance. The genomic features and mobile genetic elements of ST76 CRKP were detected by whole genome sequencing. Results: ST76 KPC-2-producing CRKP prevailed in our hospital, causing an outbreak. The strains also carried blaSHV-1, blaCTX-M-15, blaTEM-1, qnrB, and acc(6')Ib-cr resistance genes. Plasmids from 17.7% of the isolated strains bearing these resistance genes could be transferred into the recipient Escherichia coli J53 through conjugation. Sequencing results showed that the KP4 genome mainly consisted of a circular chromosome and three antibiotic resistance plasmids. The plasmid carrying the blaKPC-2 gene was located on a 437 kb IncFIB (pQil) plasmid with Tn1721-blaKPC-2-ΔT3 gene structure. Genes conferring resistance against aminoglycosides, quinolones, fluoroquinolones, beta-lactamase, phenicols, sulfonamides, and trimethoprims and the presence of virulence-associated genes related to iron acquisition or adhesins were determined. Conclusion: This is the first report of the whole genome sequence of a KPC-2-producing K. pneumoniae ST76 isolate. This work provides a basis for understanding antibiotic resistance and resistant plasmid transmission. Relevant departments should implement infection control and prevention measures to reduce the incidence of nosocomial infections.

8.
Gut ; 2020 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-32213556

RESUMO

OBJECTIVE: The SARS-CoV-2-infected disease (COVID-19) outbreak is a major threat to human beings. Previous studies mainly focused on Wuhan and typical symptoms. We analysed 74 confirmed COVID-19 cases with GI symptoms in the Zhejiang province to determine epidemiological, clinical and virological characteristics. DESIGN: COVID-19 hospital patients were admitted in the Zhejiang province from 17 January 2020 to 8 February 2020. Epidemiological, demographic, clinical, laboratory, management and outcome data of patients with GI symptoms were analysed using multivariate analysis for risk of severe/critical type. Bioinformatics were used to analyse features of SARS-CoV-2 from Zhejiang province. RESULTS: Among enrolled 651 patients, 74 (11.4%) presented with at least one GI symptom (nausea, vomiting or diarrhoea), average age of 46.14 years, 4-day incubation period and 10.8% had pre-existing liver disease. Of patients with COVID-19 with GI symptoms, 17 (22.97%) and 23 (31.08%) had severe/critical types and family clustering, respectively, significantly higher than those without GI symptoms, 47 (8.14%) and 118 (20.45%). Of patients with COVID-19 with GI symptoms, 29 (39.19%), 23 (31.08%), 8 (10.81%) and 16 (21.62%) had significantly higher rates of fever >38.5°C, fatigue, shortness of breath and headache, respectively. Low-dose glucocorticoids and antibiotics were administered to 14.86% and 41.89% of patients, respectively. Sputum production and increased lactate dehydrogenase/glucose levels were risk factors for severe/critical type. Bioinformatics showed sequence mutation of SARS-CoV-2 with m6A methylation and changed binding capacity with ACE2. CONCLUSION: We report COVID-19 cases with GI symptoms with novel features outside Wuhan. Attention to patients with COVID-19 with non-classic symptoms should increase to protect health providers.

9.
Mol Metab ; 34: 174-186, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32180557

RESUMO

OBJECTIVE: It is well established that the liver-specific miR-122, a bona fide tumor suppressor, plays a critical role in lipid homeostasis. However, its role, if any, in amino acid metabolism has not been explored. Since glutamine (Gln) is a critical energy and anaplerotic source for mammalian cells, we assessed Gln metabolism in control wild type (WT) mice and miR-122 knockout (KO) mice by stable isotope resolved metabolomics (SIRM) studies. METHODS: Six-to eight-week-old WT and KO mice and 12- to 15-month-old liver tumor-bearing mice were injected with [U-13C5,15N2]-L-Gln, and polar metabolites from the liver tissues were analyzed by nuclear magnetic resonance (NMR) imaging and ion chromatography-mass spectrometry (IC-MS). Gln-metabolism was also assessed in a Gln-dependent hepatocellular carcinoma (HCC) cell line (EC4). Expressions of glutaminases (Gls and Gls2) were analyzed in mouse livers and human primary HCC samples. RESULTS: The results showed that loss of miR-122 promoted glutaminolysis but suppressed gluconeogenesis in mouse livers as evident from the buildup of 13C- and/or 15N-Glu and decrease in glucose-6-phosphate (G6P) levels, respectively, in KO livers. Enhanced glutaminolysis is consistent with the upregulation of expressions of Gls (kidney-type glutaminase) and Slc1a5, a neutral amino acid transporter in KO livers. Both Gls and Slc1a5 were confirmed as direct miR-122 targets by the respective 3'-UTR-driven luciferase assays. Importantly, expressions of Gls and Slc1a5 as well as glutaminase activity were suppressed in a Gln-dependent HCC (EC4) cell line transfected with miR-122 mimic that resulted in decreased 13C-Gln, 13C-á-ketoglutarate, 13C-isocitrate, and 13C-citrate levels. In contrast, 13C-phosphoenolpyruvate and 13C-G6P levels were elevated in cells expressing ectopic miR-122, suggesting enhanced gluconeogenesis. Finally, The Cancer Genome Atlas-Liver Hepatocellular Carcinoma (TCGA-LIHC) database analysis showed that expression of GLS is negatively correlated with miR-122 in primary human HCCs, and the upregulation of GLS RNA is associated with higher tumor grade. More importantly, patients with higher expressions of GLS or SLC1A5 in tumors exhibited poor survival compared with those expressing lower levels of these proteins. CONCLUSIONS: Collectively, these results show that miR-122 modulates Gln metabolism both in vitro and in vivo, implicating the therapeutic potential of miR-122 in HCCs that exhibit relatively high GLS levels.

10.
Sci China Life Sci ; 2020 Mar 06.
Artigo em Inglês | MEDLINE | ID: mdl-32170627

RESUMO

Transposable elements (TEs) have been shown to have important gene regulatory functions and their alteration could lead to disease phenotypes. Acute myeloid leukemia (AML) develops as a consequence of a series of genetic changes in hematopoietic precursor cells, including mutations in epigenetic factors. Here, we set out to study the gene regulatory role of TEs in AML. We first explored the epigenetic landscape of TEs in AML patients using ATAC-seq data. We show that a large number of TEs in general, and more specifically mammalian-wide interspersed repeats (MIRs), are more enriched in AML cells than in normal blood cells. We obtained a similar finding when analyzing histone modification data in AML patients. Gene Ontology enrichment analysis showed that genes near MIRs in open chromatin regions are involved in leukemogenesis. To functionally validate their regulatory role, we selected 19 MIR regions in AML cells, and tested them for enhancer activity in an AML cell line (Kasumi-1) and a chronic myeloid leukemia (CML) cell line (K562); the results revealed several MIRs to be functional enhancers. Taken together, our results suggest that TEs are potentially involved in myeloid leukemogenesis and highlight these sequences as potential candidates harboring AML-associated variation.

11.
Autophagy ; : 1-15, 2020 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-32138578

RESUMO

Oxidative stress underlies a number of pathological conditions, including cancer, neurodegeneration, and aging. Antioxidant-rich foods help maintain cellular redox homeostasis and mitigate oxidative stress, but the underlying mechanisms are not clear. For example, sulforaphane (SFN), an electrophilic compound that is enriched in cruciferous vegetables such as broccoli, is a potent inducer of cellular antioxidant responses. NFE2L2/NRF2 (nuclear factor, erythroid 2 like 2), a transcriptional factor that controls the expression of multiple detoxifying enzymes through antioxidant response elements (AREs), is a proposed target of SFN. NFE2L2/NRF2 is a target gene of TFEB (transcription factor EB), a master regulator of autophagic and lysosomal functions, which we show here to be potently activated by SFN. SFN induces TFEB nuclear translocation via a Ca2+-dependent but MTOR (mechanistic target of rapamycin kinase)-independent mechanism through a moderate increase in reactive oxygen species (ROS). Activated TFEB then boosts the expression of genes required for autophagosome and lysosome biogenesis, which are known to facilitate the clearance of damaged mitochondria. Notably, TFEB activity is required for SFN-induced protection against both acute oxidant bursts and chronic oxidative stress. Hence, by simultaneously activating macroautophagy/autophagy and detoxifying pathways, natural compound SFN may trigger a self-defense cellular mechanism that can effectively mitigate oxidative stress commonly associated with many metabolic and age-related diseases.Abbreviations: ANOVA: analyzes of variance; AREs: antioxidant response elements; Baf-A1: bafilomycin A1; BHA: butylhydroxyanisole; CAT: catechin hydrate; CCCP: carbonyl cyanide m- chlorophenylhydrazone; CLEAR: coordinated lysosomal expression and regulation; DCFH-DA: 2',7'-dichlorofluorescin diacetate; FBS: fetal bovine serum; GFP: green fluorescent protein; HMOX1/HO-1: heme oxygenase 1; KD: knockdown; KEAP1: kelch like ECH associated protein 1; KO: knockout; LAMP1: lysosomal associated membrane protein 1; MCOLN1/TRPML1: mucolipin 1; ML-SA1: mucolipin-specific synthetic agonist 1; ML-SI3: mucolipin-specific synthetic inhibitor 3; MTOR: mechanistic target of rapamycin kinase; MTORC1: mechanistic target of rapamycin kinase complex 1; NAC: N-acetylcysteine; NFE2L2/NRF2: nuclear factor: erythroid 2 like 2; NPC: Niemann-Pick type C; PBS: phosphate-buffered saline; PPP2/PP2A: protein phosphatase 2; Q-PCR: real time polymerase chain reaction; ROS: reactive oxygen species; RPS6KB1/S6K1/p70S6K: ribosomal protein S6 kinase B1; SFN: sulforaphane; TFEB: transcription factor EB; WT, wild-type.

12.
Stem Cell Res Ther ; 11(1): 113, 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32169098

RESUMO

OBJECTIVES: Microvesicles (MVs) derived from human Wharton's jelly mesenchymal stem cells (MSC-MVs) were demonstrated to ameliorate acute lung injury (ALI). We have previously found that MSC-MV-transferred hepatocyte growth factor was partly involved in their therapeutic effects. Since MSC-MVs also contained a substantial quantity of miR-100, which plays an important role in lung cancer and injury, we speculated that miR-100 might similarly account for a part of the therapeutic effects of MSC-MVs. METHODS: MSCs were transfected with miR-100 inhibitor to downregulate miR-100 in MSC-MVs. A rat model of ALI and cell injury in rat type II alveolar epithelial cell line (L2) was induced by bleomycin (BLM). A co-culture model of alveolar epithelial cells and MSC-MVs was utilized to examine the therapeutic role of MSC-MVs and mechanism. RESULTS: MSC-MV treatment attenuated BLM-induced apoptosis and inflammation in BLM-treated L2 cells and ameliorated BLM-induced lung apoptosis, inflammation, and fibrosis in BLM-induced ALI rats. The beneficial effect of MSC-MVs was partly eliminated when miR-100 was knocked down in MSCs. Moreover, MSC-MV-transferred miR-100 mediated the therapeutic effect of MSC-MVs in ALI through enhancing autophagy by targeting mTOR. CONCLUSION: MSC-MVs enhance autophagy and ameliorate ALI partially via delivery of miR-100.

13.
Inorg Chem ; 2020 Mar 18.
Artigo em Inglês | MEDLINE | ID: mdl-32186857

RESUMO

Using density functional theory calculations, we propose that the exposed Ga atom in a two-dimensional defective gallium selenide monolayer (V-GaSe) can display a good dinitrogen fixation capacity and an excellent nitrogen reduction reaction (NRR) performance. Our results show that N2 can be captured by three sp3-hybridized Ga atoms due to the pulling effect. With the enlargement in vacancy size through applying tensile strain, the adsorption of N2 is strengthened and the electrochemical NRR performance is enhanced. On 8% strained V-GaSe, the estimated onset potential is as low as 0.30 V. Inspired by the concept of "defect-size-dependent" NRR performance, we further design a Janus V-GaInSe2 structure in which the natural size of the cavity is enlarged and the electron density of the active Ga atoms is enriched. It is found that N2 adsorption is demonstrably enhanced with respect to V-GaSe. On 4% strained V-GaInSe2, the onset potential is calculated to be 0.31 V, which is the same as the 8% strained V-GaSe. Moreover, the produced NH3 can be removed rapidly with a free-energy change of less than 0.52 eV, which is much lower than those of most reported catalysts with low overpotentials. Meanwhile, the side hydrogen evolution reaction is successively suppressed as the strain increases. Our work offers a feasible method that utilizes the size of a defect to tune the NRR performance, adding a new understanding of N2 fixation and sustainable NH3 production.

14.
Sci Adv ; 6(6): eaaz2736, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32128386

RESUMO

Duchenne muscular dystrophy (DMD) is a devastating disease caused by mutations in dystrophin that compromise sarcolemma integrity. Currently, there is no treatment for DMD. Mutations in transient receptor potential mucolipin 1 (ML1), a lysosomal Ca2+ channel required for lysosomal exocytosis, produce a DMD-like phenotype. Here, we show that transgenic overexpression or pharmacological activation of ML1 in vivo facilitates sarcolemma repair and alleviates the dystrophic phenotypes in both skeletal and cardiac muscles of mdx mice (a mouse model of DMD). Hallmark dystrophic features of DMD, including myofiber necrosis, central nucleation, fibrosis, elevated serum creatine kinase levels, reduced muscle force, impaired motor ability, and dilated cardiomyopathies, were all ameliorated by increasing ML1 activity. ML1-dependent activation of transcription factor EB (TFEB) corrects lysosomal insufficiency to diminish muscle damage. Hence, targeting lysosomal Ca2+ channels may represent a promising approach to treat DMD and related muscle diseases.

15.
Parasitol Int ; 76: 102094, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32109578

RESUMO

Toxoplasma gondii is a pathogen that seriously threatens the health of humans and animals. However, the current infection status of T. gondii in slaughter pigs in Shanghai is still not clear. To investigate the seroprevalence of T. gondii infection and analyze the prevalence factors associated with the parasite infection, 1158 serum samples were collected from five slaughterhouses in three districts between 2015 and 2018. Serum antibodies against T. gondii were detected in 160 pigs (13.8%) by enzyme-linked immunosorbent assay (ELISA). Additionally, seroprevalence rates differed among different districts (ranging from 4.0% in JD-2 to 17.6% in JD-1), seasons (ranging from 6.7% in winter to 17.8% in autumn), and years (ranging from 8.0% in 2016 to 26.8% in 2015). Region, season, and year were the main factors affecting T. gondii infection in these pigs. There were few reports on serological monitoring of T. gondii in Shanghai slaughterhouses between 2015 and 2018, and the number of infections had steadily increased over the past several consecutive years. Therefore, our data are helpful to understand the epidemic status of T. gondii in Shanghai, which will strengthen the prevention and treatment of swine toxoplasmosis.

16.
Biosens Bioelectron ; 155: 112101, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32090873

RESUMO

A novel time-resolved fluorescence blocking lateral flow immunoassay (TRF-BLFIA) was developed for on-site differential diagnosis of pseudorabies virus (PRV)-infected and vaccinated pigs using europium nanoparticles (EuNPs)-labeled virion antigens and high titer PRV gE monoclonal antibodies (PRV gE-mAb). Upon application of a positive serum sample, the specific epitopes of gE protein on the EuNPs-PRV probe were blocked, inhibiting binding to the PRV gE-mAb on the T line, resulting in low or negligible fluorescence signal, whereas when a negative sample was applied, EuNPs-PRV probes would be able to bind the antibody at the T line, leading to high fluorescence signal. Under optimized conditions, TRF-BLFIA provided excellent sensitivity and selectivity. When testing swine clinical samples (n = 356), there was 96.1% agreement between this method and a most widely used commercial gE-ELISA kit. Moreover, our method was rapid (15 min), cost-efficient and easy to operate with simple training, allowing for on-site detection. Thus, TRF-BLFIA could be a practical tool to differentially diagnose PRV-infected and vaccinated pigs.

17.
Ann Clin Transl Neurol ; 7(2): 210-218, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32031755

RESUMO

OBJECTIVE: To determine the efficacy and the prognostic value of amplitude-integrated electroencephalography (aEEG) in term and near-term neonates with high risk of neurological sequelae. METHODS: Infants of ≥35 weeks of gestation diagnosed with neonatal encephalopathy or with high risk of brain injury were included. All eligible infants underwent aEEG within 6 h after clinical assessment. The infants were followed up 12 months to evaluate neurological development. RESULTS: A total of 250 infants were eligible, of which 85 had normal aEEG, 81 had mildly abnormal aEEG, and 84 had severely abnormal aEEG. Of these infants, 168 were diagnosed with different neonatal encephalopathies, 27 with congenital or metabolic diseases, and 55 with high risk of brain injury. In all, 22 infants died, 19 were lost to follow-up, and 209 completed the follow-up at 12 months, of which 62 were diagnosed with a neurological disability. Statistical analysis showed that severely abnormal aEEG predicted adverse neurological outcome with a sensitivity of 70.2%, a specificity of 87.1%, a positive predictive value of 75.6%, and a negative predictive value of 83.7%. INTERPRETATION: aEEG can predict adverse outcomes in high-risk neonates and is a useful method for monitoring neonates with high risk of adverse neurological outcomes.

18.
Pediatr Pulmonol ; 55(4): 882-889, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32022483

RESUMO

OBJECTIVES: Asthma affects over 6 million children in the United States alone. This study investigated the efficacy and long-term safety of mometasone furoate-formoterol (MF/F) and MF monotherapy in children with asthma. MATERIALS AND METHODS: This phase 3, multicenter, randomized controlled trial evaluated metered-dose inhaler twice daily (BID) dosing with MF/F 100/10 µg or MF 100 µg in children, aged 5 to 11 years, with a history of asthma for greater than or equal to 6 months and confirmed bronchodilator reversibility, who were adequately controlled on inhaled corticosteroid/long-acting beta-agonist combination therapy for greater than or equal to 4 weeks. After a 2-week run-in on MF 100 µg BID, eligible patients received 24 weeks of double-blind treatment and were followed for safety up to 26 weeks. The primary efficacy endpoint was the change from baseline in AM postdose 60-minute AUC %predicted FEV1% across 12 weeks of treatment. RESULTS: A total of 181 participants received at least one dose of MF/F (n = 91) or MF (n = 90). MF/F was superior to MF across the 12-week evaluation period, with a treatment advantage of 5.21 percentage points (P < .001). Superior onset of action with MF/F over MF was achieved as early as 5 minutes postdose on day 1. Overall, approximately 50% of participants experienced one or more treatment-emergent adverse events, with fewer occurring in the MF/F group. CONCLUSIONS: In children 5 to 11 years of age with persistent asthma, the addition of F to MF was well tolerated and provided significant, rapid, and sustained improvement in lung function compared with MF alone.

19.
BMC Infect Dis ; 20(1): 94, 2020 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-32005138

RESUMO

BACKGROUND: Enterobacter cloacae complex (ECC) is one of the most common extended-spectrum ß-lactamase and carbapenemase-producing pathogen that threatens millions of the elderly and vulnerable sick persons. The objective of this study was to perform the molecular characteristics of the carbapenem-resistant E. cloacae complex (CREC) emerged in Heilongjiang Province of China. METHODS: Six CREC strains were isolated from the patients with infectious diseases. The identities of ECC isolates were confirmed by sequencing the polymerase chain reaction (PCR) products of 16S rRNA gene. The characterization of the CREC isolates were analyzed by sequencing PCR products of the carbapenemase, ampC and fluoroquinolone resistance genes and performing multilocus sequence typing (MLST), pulsed-field gel electrophoresis (PFGE) and whole genome sequencing. RESULTS: All 6 isolates harbored multiple resistance genes. Of them, 5 carried metallo-ß-lactamases and one was blaKPC-2-positive. The levofloxacin and ciprofloxacin-resistant strains had substitutions of gyrA83, gyrA87, and parC80 in the quinolone-resistance determining regions. The MLST analyses revealed that 6 isolates belonged to five sequence types (ST520, ST528, ST1119, ST1120, and ST93) while the PFGE patterns of the isolates fallen into four clusters. The strain ST1120 was found to carry two separated plasmids that encode blaNDM-1 and blaIMP-4. CONCLUSIONS: Our study, for the first time, identified a CREC strain that co-produces blaNDM-1 and blaIMP-4 in the Northeast China. Our finding emphasizes an urgent need for more intensive surveillance and precaution measures to prevent the CERC spread.

20.
Nanoscale ; 12(7): 4686-4694, 2020 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-32048681

RESUMO

Hierarchical nanostructures with outstanding electrochemical properties and mechanical stability are ideal for constructing flexible hybrid supercapacitors. Herein, hierarchically hollow NiCo2S4@NiS nanostructures were designed and synthesized by sulfurizing the hierarchical NiCo double hydroxides (DHs) coated with nickel hydroxide nanostructures on carbon fabrics (NiCo-DHs@Ni(OH)2/CF), which trigger excellent electrochemical performances. The NiCo2S4@NiS/CF exhibits a high specific capacity of 1314.0 C g-1 at a current density of 1 A g-1, and maintains the rate performance at about 79.2% of the initial capacity at 30 A g-1. The hybrid supercapacitors of NiCo2S4@NiS//AC display a high energy density of 62.4 W h kg-1 at a power density of 800 W kg-1 with a remarkable cycling stability (96.2% of initial capacitance after 5000 cycles) and robust mechanical flexibility (no obvious decay of specific capacitance during various deformations). Consequently, NiCo2S4@NiS electrodes are expected to be a promising candidate for new smart energy storage devices with high security, stability and flexibility.

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