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1.
Methods Mol Biol ; 2069: 89-94, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31523767

RESUMO

Staphylococcal protein A (SPA) consists of Fc-partial-region, X-region, and C-terminal. Spa typing is a genotyping method based on the presence of gene polymorphism in a variable number of 24 bp repeat sequences in the X-region. Spa typing allows highly discriminatory and rapid characterization and prediction of multilocus sequence typing (MLST), ribotyping, and pulsed-field gel electrophoresis (PFGE). DNA sequence-based approaches are becoming more frequently used because of the ease with which sequence data can be transferred between laboratories via the Internet.

2.
J Pharm Biomed Anal ; 177: 112880, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31546137

RESUMO

Hepatitis E, which is caused by infection with hepatitis E virus (HEV), is a global health problem in both developed and developing countries. An efficacious hepatitis E vaccine was licensed (by China) in 2011 with a trade name of Hecolin®. The antigen contained in this vaccine is a truncated version of the sole capsid protein encoded by open reading frame 2, which is designated p239. In this study, the real-time and real-condition stability and accelerated stability of five lots of hepatitis E vaccine products at the end of the designated shelf life, were assessed by a well-established quality analysis platform. The protein integrity of p239 that was recovered from the vaccine lots was demonstrated using CE-SDS, LC-MS and MALDI-TOF MS. The particle characteristics of the recovered vaccine antigen were assessed by TEM and HPSEC. The immunogenicity of hepatitis E vaccines was assessed by a mouse potency assay, which is part of product release and stability testing. Several methods were employed to assess the antigenicity of vaccines with or without adjuvant dissolution. Specifically, the well-established methods of sandwich ELISA and surface plasma resonance (SPR)-based BIAcore were used with unique murine monoclonal antibodies. Most interesting, two 'dissolution-free' immunoassays were also used for in situ antigenicity assessment of the vaccines. In addition to the confirmation of vaccine stability at the end of expiry dating, i.e., after storage in recommended conditions (2-8 °C) for 36 months, the mouse potency assay and sandwich ELISA were used to assess the accelerated stability of prefilled syringes to demonstrate the feasibility of out-of-cold-chain storage. In summary, molecular and functional characterization confirmed the shelf life stability of the vaccine at the end of expiry dating and the feasibility of transporting the hepatitis E vaccine for a given period of time out of cold chains.

3.
Glia ; 68(1): 27-43, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31429156

RESUMO

Ischemic stroke leads to neuronal damage induced by excitotoxicity, inflammation, and oxidative stress. Astrocytes play diverse roles in stroke and ischemia-induced inflammation, and autophagy is critical for maintaining astrocytic functions. Our previous studies showed that the activation of G protein-coupled receptor 30 (GPR30), an estrogen membrane receptor, protected neurons from excitotoxicity. However, the role of astrocytic GPR30 in maintaining autophagy and neuroprotection remained unclear. In this study, we found that the neuroprotection induced by G1 (GPR30 agonist) in wild-type mice after a middle cerebral artery occlusion was completely blocked in GPR30 conventional knockout (KO) mice but partially attenuated in astrocytic or neuronal GPR30 KO mice. In cultured primary astrocytes, glutamate exposure induced astrocyte proliferation and decreased astrocyte autophagy by activating mammalian target of rapamycin (mTOR) and c-Jun N-terminal kinase (JNK) and inhibiting p38 mitogen-activated protein kinase (MAPK) pathway. G1 treatment restored autophagy to its basal level by regulating the p38 pathway but not the mTOR and JNK signaling pathways. Our findings revealed a key role of GPR30 in neuroprotection via the regulation of astrocyte autophagy and support astrocytic GPR30 as a potential drug target against ischemic brain damage.

4.
Toxicol In Vitro ; 62: 104668, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31629073

RESUMO

Methamphetamine (MA) has a high uptake in lung, but the precise mechanism of MA-induced lung toxicity remains unclear. The aim of this study is to investigate the role of MA abuse in remodeling of pulmonary arteries and to explore the possible correlation of the association of the remodeling with the redox imbalance in pulmonary arterial smooth muscle cells (PASMCs). Wistar rats were randomly divided into control group and MA group for the experimental study. We employed H&E staining, western blot, immunofluorescence, knockdown, flow in our experimental approach. Our studies shows that chronic exposure to MA led to weight loss, increased pulmonary arterial pressure, hypertrophy of right ventricle and remodeling of pulmonary arterial wall of rats. Our cell culture study with PASMCs indicates that MA significantly induced the imbalance between proliferation and apoptosis by upregulating the level of PCNA, Bcl-2 and reduction in the expression of BAX and Caspase 3. MA markedly prevented the nuclear translocation of Nrf2 to inhibit antioxidation. The knockdown of Nrf2 expression using siRNA significantly elevated the expression of SOD2/GCS and the production of ROS in PASMCs and even scaled up the amount of PASMCs induced by MA. Linear regression analysis showed that knockdown of Nrf2 promoted the positive correlation of relative ROS level with proliferation of PASMCs. Therefore, chronic exposure to MA induces pulmonary arterial remodeling by Nrf2-mediated imbalance of redox system to aggravate oxidative stress, and Nrf2 is a possible target for the treatment of MA-lung toxicity.

5.
Food Microbiol ; 86: 103337, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31703870

RESUMO

Coenzyme Q0 (CoQ0) has demonstrated antitumor, anti-inflammatory, and anti-angiogenic activities. Cronobacter sakazakii is an opportunistic foodborne pathogen associated with high mortality in neonates. In this study, the antimicrobial activity and possible antimicrobial mechanism of CoQ0 against C. sakazakii were investigated. Moreover, the inactivation effect of CoQ0 on C. sakazakii in biofilms was also evaluated. The minimum inhibitory concentration (MIC) of CoQ0 against C. sakazakii strains ranged from 0.1 to 0.2 mg/mL. Treatment caused cell membrane dysfunction, as evidenced by cell membrane hyperpolarization, decreased intracellular ATP concentration and cell membrane integrity, and changes in cellular morphology. CoQ0 combined with mild heat treatment (45, 50, or 55 °C) decreased the number of viable non-desiccated and desiccated C. sakazakii cells in a time- and dose-dependent manner in reconstituted infant milk. Furthermore, CoQ0 showed effective inactivation activity against C. sakazakii in biofilms on stainless steel, reducing the number of viable cells and damaging the structure of the biofilm. These findings suggest that CoQ0 has a strong inactivate effect on C. sakazakii and could be used in food production environments to effectively control C. sakazakii and reduce the number of illnesses associated with it.

6.
Nanotechnology ; 31(7): 072001, 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-31627201

RESUMO

Near infrared (NIR) excited lanthanide-doped upconversion nanoparticles (UCNPs) are emerging as a new type of fluorescent tag for biological applications, which can emit multi-photon ultraviolet, visible or NIR luminescence for imaging or activation of photosensitive molecules. Here, we present a comprehensive review on recent advances of UCNPs for a manifold of biological applications, including upconversion mechanisms, building bright multicolor upconversion nanocrystals, single nanoparticle and super resolution imaging, in vivo optical and multimodal imaging, photodynamic therapy, light-controlled drug release, biosensing, and toxicities. Our perspectives on the future development of UCNPs are also described.

7.
Int J Offender Ther Comp Criminol ; 64(1): 22-37, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31221027

RESUMO

Chinese education system comprises high schools and vocational school, and their differences on delinquency have seldom been investigated. From the perspective of general strain theory, the present study examined the differences among high school and vocational school students for delinquency, strain, and other explanatory variables. General strain theory delineates the effect of strain on delinquency or deviance and presents the paths from strain to delinquency or deviance through social control and social learning variables. Using a sample of 1,852 tenth-grade students in Guangzhou City, the present study tests the intervening paths from strains to deviance among high school and vocational school students. Results indicated that vocational school students have higher likelihood to be strained and delinquent, and have lower social control and higher interactions with delinquent peers. School type is a significant predictor for strain, as well as social control and delinquent peers.

8.
J Infect Dis ; 220(Supplement_4): S175-S181, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31671436

RESUMO

Laboratories play critical roles in bacterial meningitis disease surveillance in the African meningitis belt, where the highest global burden of meningitis exists. Reinforcement of laboratory capacity ensures rapid detection of meningitis cases and outbreaks and a public health response that is timely, specific, and appropriate. Since 2008, joint efforts to strengthen laboratory capacity by multiple partners, including MenAfriNet, beginning in 2014, have been made in countries within and beyond the meningitis belt. Over the course of 10 years, national reference laboratories were supported in 5 strategically targeted areas: specimen transport systems, laboratory procurement systems, laboratory diagnosis, quality management, and laboratory workforce with substantial gains made in each of these areas. To support the initiative to eliminate meningitis by 2030, continued efforts are needed to strengthen laboratory systems.

9.
J Infect Dis ; 220(Supplement_4): S190-S197, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31671437

RESUMO

In 2016, Mali reported a bacterial meningitis outbreak consisting of 39 suspected cases between epidemiologic weeks 9 and 17 with 15% case fatality ratio in the health district of Ouéléssebougou, 80 kilometers from the capital Bamako. Cerebrospinal fluid specimens from 29 cases were tested by culture and real-time polymerase chain reaction; 22 (76%) were positive for bacterial meningitis pathogens, 16 (73%) of which were Neisseria meningitidis (Nm). Of the Nm-positive specimens, 14 (88%) were N meningitidis serogroup C (NmC), 1 was NmW, and 1 was nongroupable. Eight NmC isolates recovered by culture from the outbreak were characterized using whole genome sequencing. Genomics analysis revealed that all 8 isolates belonged to a new sequence type (ST) 12446 of clonal complex 10217 that formed a distinct clade genetically similar to ST-10217, a NmC strain that recently caused large epidemics of meningitis in Niger and Nigeria. The emergence of a new ST of NmC associated with an outbreak in the African meningitis belt further highlights the need for continued molecular surveillance in the region.

10.
J Infect Dis ; 220(Supplement_4): S206-S215, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31671439

RESUMO

BACKGROUND: In 2010, Niger and other meningitis belt countries introduced a meningococcal serogroup A conjugate vaccine (MACV). We describe the epidemiology of bacterial meningitis in Niger from 2010 to 2018. METHODS: Suspected and confirmed meningitis cases from January 1, 2010 to July 15, 2018 were obtained from national aggregate and laboratory surveillance. Cerebrospinal fluid specimens were analyzed by culture and/or polymerase chain reaction. Annual incidence was calculated as cases per 100 000 population. Selected isolates obtained during 2016-2017 were characterized by whole-genome sequencing. RESULTS: Of the 21 142 suspected cases of meningitis, 5590 were confirmed: Neisseria meningitidis ([Nm] 85%), Streptococcus pneumoniae ([Sp] 13%), and Haemophilus influenzae ([Hi] 2%). No NmA cases occurred after 2011. Annual incidence per 100 000 population was more dynamic for Nm (0.06-7.71) than for Sp (0.18-0.70) and Hi (0.01-0.23). The predominant Nm serogroups varied over time (NmW in 2010-2011, NmC in 2015-2018, and both NmC and NmX in 2017-2018). Meningococcal meningitis incidence was highest in the regions of Niamey, Tillabery, Dosso, Tahoua, and Maradi. The NmW isolates were clonal complex (CC)11, NmX were CC181, and NmC were CC10217. CONCLUSIONS: After MACV introduction, we observed an absence of NmA, the emergence and continuing burden of NmC, and an increase in NmX. Niger's dynamic Nm serogroup distribution highlights the need for strong surveillance programs to inform vaccine policy.

11.
J Infect Dis ; 220(Supplement_4): S266-S273, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31671445

RESUMO

Whole-genome sequencing (WGS) is invaluable for studying the epidemiology of meningococcal disease. Here we provide a perspective on the use of WGS for meningococcal molecular surveillance and outbreak investigation, where it helps to characterize pathogens, predict pathogen traits, identify emerging pathogens, and investigate pathogen transmission during outbreaks. Standardization of WGS workflows has facilitated their implementation by clinical and public health laboratories (PHLs), but further development is required for metagenomic shotgun sequencing and targeted sequencing to be widely available for culture-free characterization of bacterial meningitis pathogens. Internet-accessible servers are being established to support bioinformatics analysis, data management, and data sharing among PHLs. However, establishing WGS capacity requires investments in laboratory infrastructure and technical knowledge, which is particularly challenging in resource-limited regions, including the African meningitis belt. Strategic WGS implementation is necessary to monitor the molecular epidemiology of meningococcal disease in these regions and construct a global view of meningococcal disease epidemiology.

12.
Life Sci ; 239: 117016, 2019 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-31678281

RESUMO

The current study aimed to investigate the effects of tetramethylprazine (TMP) on myocardial ischemia/reperfusion (MI/R) injury and its underlying mechanisms. MI/R rat model and hypoxia/reoxygenation (H/R) cardiomyocytes model were established. CK level and LDH activity were detected to evaluate MI/R and H/R injury. Cell viability was determined by cell counting kit-8 (CCK-8) assay. Cell apoptosis were identified by flow cytometry and autophagy were detected by western blot. Treatment with TMP significantly reduced CK level and LDH activity and decreased myocardial infarct size in MI/R rats. TMP reduced autophagy dysfunction induced by MI/R. Moreover, TMP treatment decreased H/R-induced injury and attenuated autophagy dysfunction in cardiomyocytes. Inhibiting autophagic flux with chloroquine (CQ) decreased the cardioprotection exerted by TMP in vivo and in vitro. Additionally, the effects of TMP on the modulation of autophagy were inhibited by LY294002 (a PI3K inhibitor) in H/R cardiomyocytes. Our findings suggested TMP exerted cardioprotection against MI/R injury by decreasing Beclin-1 associated autophagy dysfunction through PI3K pathway.

13.
Waste Manag ; 102: 330-339, 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711027

RESUMO

Single-step synthesis of porous carbon (PC) from biomass is a challenge via microwave heating, because biomass rarely absorbs the microwave energy. Herein, wheat-straw-derived char, as a good microwave absorber, was used to achieve rapidly single-step synthesis of PC from an agricultural waste (wheat straw). KOH was used to generate abundant micropores in the PCs. High heating rate caused by microwave heating combined with the pyrolysis gases resulted in the formation of meso-/macropores. A series of post-oxidation reactions between active sites in the PCs and oxygen in the air led to the doping of oxygen-containing chemical groups. Consequently, the obtained PC possessed a high specific surface area of 1905 m2 g-1, a balanced pore distribution with abundant micropores (0.62 cm3 g-1), considerable content of meso-/macropores (0.53 cm3 g-1), and an oxygen-enriched structure (oxygen content up to 21.6%). These characteristics not only contributed to the achievement of a high specific capacitance of 268.5 F g-1 at 0.5 A g-1 for the resultant supercapacitor, but also resulted in an excellent rate capability with a high capacitance retention of 81.2% at 10 A g-1 in a gel electrolyte (polyvinyl alcohol/LiCl). This supercapacitor can extract a high energy density of 21.5 W h kg-1 at 0.5 A g-1 and a high power density of 7.2 kW kg-1 at 10 A g-1.

14.
Artigo em Inglês | MEDLINE | ID: mdl-31715507

RESUMO

Turbot (Scophthalmus maximus) is an economically important marine fish cultured in China. In this study, we performed transcriptome gene expression profiling of kidney tissue in turbot exposed to heat stress (20, 23, 25 and 28 °C); control fish were maintained at 14 °C. We investigated gene relationships based on weighted gene co-expression network analysis (WGCNA). Accordingly, enrichment analyses of GO terms and KEGG pathways showed that several pathways (e.g., fat metabolism, cell apoptosis, immune system, and insulin signaling) may be involved in the response of turbot to heat stress. Moreover, via WGCNA, we identified 19 modules: the dark grey module was mainly enriched in pathways associated with fat metabolism and the FOXO and Jak-STAT signaling pathways. The ivory module was significantly enriched in the P53 signaling pathway. Furthermore, the key hub genes CBP, AKT3, CCND2, PIK3r2, SCOS3, mdm2, cyc-B, and p48 were enriched in the FOXO, Jak-STAT and P53 signaling pathways. This is the first study reporting co-expression patterns of a gene network after heat stress in marine fish. Our results may contribute to our understanding of the underlying molecular mechanism of thermal tolerance.

15.
Artigo em Inglês | MEDLINE | ID: mdl-31718138

RESUMO

Bio-inspired reversible adhesives have attracted great attention because of their promising applications in the electronic, biomedical, and robotic fields. Here, to achieve in situ reversible adhesion, a new concept is demonstrated by modulating the conformations of polydimethylsiloxane (PDMS) chains. The new adhesive, termed BGPP, is composed of the graphene/PDMS composite (GP) as the backing layer and PDMS as the micropillar array. The photothermal effect of graphene under UV irradiation heats up the micropillars, resulting in an increase in the chain conformations of PDMS and thus the contact points with the counterpart surface. The more contact points together with the alignment of PDMS chains during the shearing result in an adhesion much higher than that without UV irradiation. The adhesion switching thus does not rely on the changing of the contact area, and so the macroscopic deformation of structures is avoided. The results suggest a new design principle for light-controllable structured adhesive, which could be conceptualized into other rubbery materials.

16.
Dev Comp Immunol ; 104: 103535, 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31697956

RESUMO

Karyopherin α4 (KPNA4) is an adaptor molecule that mediates type I interferon (IFN) production by facilitating the nuclear translocation of IFN transcription factors. Here, we cloned the duck KPNA4 (duKPNA4) gene and analyzed its involvement in type I IFN expression as well as antiviral response against Japanese encephalitis virus (JEV). The full-length duKPNA4 gene encoded a 520-amino acid protein that shared 97.3-98.7% sequence similarity with its orthologues in chickens, humans and mice. The duKPNA4 was extensively expressed in various duck tissues at the mRNA level. Analysis of the subcellular localization of duKPNA4 by immunofluorescence assays indicated that the duKPNA4 was primarily distributed in both the cytoplasm and nucleus in primary duck embryonic fibroblasts (DEFs). However, it translocated from the cytoplasm to the nucleus in response to poly(I:C) stimulation or JEV infection. The duKPNA4 interacted with duck IFN regulatory factor 7 and facilitated its nuclear translocation, thereby up-regulating the expression of IFN-α and IFN-ß in DEFs in the presence of poly(I:C) stimulation. Exogenous expression of duKPNA4 significantly elevated the expression of IFN-α and IFN-ß induced by JEV infection and inhibited JEV replication in DEFs. These data demonstrate the importance of duKPNA4 in type I IFN signaling as well as the antiviral response against JEV replication.

17.
Sci Rep ; 9(1): 16930, 2019 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-31729408

RESUMO

Chronic inflammation and chromosome aneuploidy are major traits of primary liver cancer (PLC), which represent the second most common cause of cancer-related death worldwide. Increased cancer fitness and aggressiveness of PLC may be achieved by enhancing tumoral genomic complexity that alters tumor biology. Here, we developed a scoring method, namely functional genomic complexity (FGC), to determine the degree of molecular heterogeneity among 580 liver tumors with diverse ethnicities and etiologies by assessing integrated genomic and transcriptomic data. We found that tumors with higher FGC scores are associated with chromosome instability and TP53 mutations, and a worse prognosis, while tumors with lower FGC scores have elevated infiltrating lymphocytes and a better prognosis. These results indicate that FGC scores may serve as a surrogate to define genomic heterogeneity of PLC linked to chromosomal instability and evasion of immune surveillance. Our findings demonstrate an ability to define genomic heterogeneity and corresponding tumor biology of liver cancer based only on bulk genomic and transcriptomic data. Our data also provide a rationale for applying this approach to survey liver tumor immunity and to stratify patients for immune-based therapy.

18.
BMC Biol ; 17(1): 93, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31771567

RESUMO

BACKGROUND: Cathepsin L and some other cathepsins have been implicated in the development of obesity in humans and mice. The functional inactivation of the proteases reduces fat accumulation during mammalian adipocyte differentiation. However, beyond degrading extracellular matrix protein fibronectin, the molecular mechanisms by which cathepsins control fat accumulation remain unclear. We now provide evidence from Caenorhabditis elegans and mouse models to suggest a conserved regulatory circuit in which peripheral cathepsin L inhibition lowers fat accumulation through promoting central serotonin synthesis. RESULTS: We established a C. elegans model of fat accumulation using dietary supplementation with glucose and palmitic acid. We found that nutrient supplementation elevated fat storage in C. elegans, and along with worm fat accumulation, an increase in the expression of cpl-1 was detected using real-time PCR and western blot. The functional inactivation of cpl-1 reduced fat storage in C. elegans through activating serotonin signaling. Further, knockdown of cpl-1 in the intestine and hypodermis promoted serotonin synthesis in worm ADF neurons and induced body fat loss in C. elegans via central serotonin signaling. We found a similar regulatory circuit in high-fat diet-fed mice. Cathepsin L knockout promoted fat loss and central serotonin synthesis. Intraperitoneal injection of the cathepsin L inhibitor CLIK195 similarly reduced body weight gain and white adipose tissue (WAT) adipogenesis, while elevating brain serotonin level and WAT lipolysis and fatty acid ß-oxidation. These effects of inhibiting cathepsin L were abolished by intracranial injection of p-chlorophenylalanine, inhibitor of a rate-limiting enzyme for serotonin synthesis. CONCLUSION: This study reveals a previously undescribed molecular mechanism by which peripheral CPL-1/cathepsin L inhibition induces fat loss in C. elegans and mice through promoting central serotonin signaling.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31773234

RESUMO

PURPOSE: To develop and validate an integrated model for discriminating tumor recurrence from radiation necrosis in glioma patients. METHODS: Data from 160 pathologically confirmed glioma patients were analyzed. The diagnostic model was developed in a primary cohort (n = 112). Textural features were extracted from postoperative 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET), 11C-methionine (11C-MET) PET, and magnetic resonance images. The least absolute shrinkage and selection operator regression model was used for feature selection and radiomics signature building. Multivariable logistic regression analysis was used to develop a model for predicting tumor recurrence. The radiomics signature, quantitative PET parameters, and clinical risk factors were incorporated in the model. The clinical value of the model was then assessed in an independent validation cohort using the remaining 48 glioma patients. RESULTS: The integrated model consisting of 15 selected features was significantly associated with postoperative tumor recurrence (p < 0.001 for both primary and validation cohorts). Predictors contained in the individualized diagnosis model included the radiomics signature, the mean of tumor-background ratio (TBR) of 18F-FDG, maximum of TBR of 11C-MET PET, and patient age. The integrated model demonstrated good discrimination, with an area under the curve (AUC) of 0.988, with a 95% confidence interval (CI) of 0.975-1.000. Application in the validation cohort showed good differentiation (AUC of 0.914 and 95% CI of 0.881-0.945). Decision curve analysis showed that the integrated diagnosis model was clinically useful. CONCLUSIONS: Our developed model could be used to assist the postoperative individualized diagnosis of tumor recurrence in patients with gliomas.

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