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1.
Lancet Glob Health ; 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33939956

RESUMO

BACKGROUND: Medical male circumcision (MMC) reduces HIV infection among heterosexual men. There are concerns MMC might prompt higher-risk sexual behaviours because of lower self-perceived risk of HIV infection. We reviewed the published literature to examine associations between MMC and both condom use and number of sex partners among heterosexual men. METHODS: In this systematic review and meta-analysis, we searched PubMed, Embase, and the Cochrane Library for studies published before Nov 15, 2020. Interventional and observational studies were included if they contained original quantitative data describing the association between MMC and condom use or number of sex partners among heterosexual men. We excluded data from men whose circumcisions were ritual or religious and data from men who have sex with men. We extracted odds ratios (ORs) and 95% CIs for the associations between MMC and condomless sex and MMC and multiple sex partners directly from the publications if available, selecting adjusted ORs when provided; when necessary, we calculated ORs and 95% CIs using original study data provided in the publication. We used the Mantel-Haenszel random effects model to calculate pooled ORs and 95% CIs. FINDINGS: Our search yielded 3035 results, of which 471 were duplicates and 2537 did not meet the inclusion criteria. From the remaining 27 eligible studies, we identified 99 292 men from 31 independent population samples. 24 studies were done in Africa. We found no statistically significant associations between MMC and condomless sex (OR 0·91, 95% CI 0·80-1·05; k=30; I2=88·7%) or multiple sex partners (1·02, 0·88-1·18; k=27; I2=90·1%). No associations between MMC and condomless sex or multiple sexual partners were found in any subgroup analyses by study design, income of country, age, recruitment setting, circumcision assessment, circumcision prevalence, and risk of publication bias. INTERPRETATION: The promotion of circumcision as an HIV preventive measure does not appear to increase higher-risk sexual behaviours in heterosexual men. Ongoing sexual health education should be maintained as a vital component of effective MMC programmes. FUNDING: National Science and Technology Major Project of China, the Fundamental Research Funds for the Central Universities, and the Shenzhen Science and Technology Innovation Commission Basic Research Program.

2.
Mol Plant ; 2021 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-33962063

RESUMO

Reactive oxygen signaling regulates numerous biological processes, including stress responses in plants. Redox sensors transduce reactive oxygen signals into cellular responses. We present biochemical evidence that a plant quiescin sulfhydryl oxidase homolog (QSOX1) is a redox sensor that negatively regulates immunity against a bacterial pathogen. The expression level of QSOX1 is inversely correlated with pathogen-induced ROS accumulation. QSOX1 both senses and regulates ROS levels through interaction with and redox-mediated regulation of S-nitrosoglutathione reductase that, consistent with previous findings, influences reactive nitrogen-mediated regulation of ROS generation. Collectively, our data indicate that QSOX1 is a redox sensor that negatively regulates plant immunity by linking reactive oxygen- and reactive nitrogen-signaling to limit ROS production.

3.
Nat Metab ; 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33859429

RESUMO

Obesity is mainly due to excessive food intake. IRX3 and IRX5 have been suggested as determinants of obesity in connection with the intronic variants of FTO, but how these genes contribute to obesity via changes in food intake remains unclear. Here, we show that mice doubly heterozygous for Irx3 and Irx5 mutations exhibit lower food intake with enhanced hypothalamic leptin response. By lineage tracing and single-cell RNA sequencing using the Ins2-Cre system, we identify a previously unreported radial glia-like neural stem cell population with high Irx3 and Irx5 expression in early postnatal hypothalamus and demonstrate that reduced dosage of Irx3 and Irx5 promotes neurogenesis in postnatal hypothalamus leading to elevated numbers of leptin-sensing arcuate neurons. Furthermore, we find that mice with deletion of Irx3 in these cells also exhibit a similar food intake and hypothalamic phenotype. Our results illustrate that Irx3 and Irx5 play a regulatory role in hypothalamic postnatal neurogenesis and leptin response.

4.
Front Immunol ; 12: 614436, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33790892

RESUMO

The novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of the coronavirus disease 2019 (COVID-19), which elicits a wide variety of symptoms, ranging from mild to severe, with the potential to lead to death. Although used as the standard method to screen patients for SARS-CoV-2 infection, real-time PCR has challenges in dealing with asymptomatic patients and those with an undetectable viral load. Serological tests are therefore considered potent diagnostic tools to complement real-time PCR-based diagnosis and are used for surveillance of seroprevalence in populations. However, the dynamics of the antibody response against SARS-CoV-2 currently remain to be investigated. Here, through analysis of plasma samples from 84 patients with COVID-19, we observed that the response of virus-specific antibodies against three important antigens, RBD, N and S, dynamically changed over time and reached a peak 5-8 weeks after the onset of symptoms. The antibody responses were irrespective of sex. Severe cases were found to have higher levels of antibody response, larger numbers of inflammatory cells and C-reactive protein levels. Within the mild/moderate cases, pairwise comparison indicated moderate association between anti-RBD vs. anti-N, anti-RBD vs. anti-S1S2, and anti-N vs. anti-S1S2. Furthermore, the majority of cases could achieve IgM and IgG seroconversion at 2 weeks since the disease onset. Analysis of neutralizing antibodies indicated that these responses were able to last for more than 112 days but decline significantly after the peak. In summary, our findings demonstrate the longitudinally dynamic changes in antibody responses against SARS-CoV-2, which can contribute to the knowledge of humoral immune response after SARS-CoV-2 infection and are informative for future development of vaccine and antibody-based therapies.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , /imunologia , Glicoproteína da Espícula de Coronavírus/imunologia , Adulto , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Pequim , China , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Masculino , Pessoa de Meia-Idade , Fosfoproteínas/imunologia , Domínios Proteicos/imunologia , Soroconversão , Índice de Gravidade de Doença , Centros de Atenção Terciária
5.
Artigo em Inglês | MEDLINE | ID: mdl-33793060

RESUMO

We report the development of a highly sensitive ratiometric fluorescent lateral flow immunoassay (RFLFIA) strip for rapid and accurate detection of acute myocardial infarction biomarker, namely heart-type fatty acid binding protein (H-FABP). The RFLFIA strip works in terms of ratiometric change of fluorescence signal, arising from blending of fluorescence emitted by two composite nanostructures conjugated to capture and probe antibodies and inner filter effect of gold nanoparticles. In conjunction with using custom smartphone-based analytical device and tonality analysis, quantitative detection of H-FABP was achieved with a low limit of detection at 0.21 ng mL-1 . The RFLFIA strip can generate a visually distinguishable green-to-red color change around the threshold concentration of H-FABP (6.2 ng mL-1 ), thus allowing the semi-quantitative diagnosis by the naked eye.

6.
Biosens Bioelectron ; 185: 113265, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33930755

RESUMO

As a severe stage of cancers, peritoneal carcinomatosis should be frequently monitored by means of ascites analysis. Nevertheless, the analysis process is traumatic and time-consuming in clinical practice. In this study, an implantable platinum nanotree microelectrode with a wireless, battery-free and flexible electrochemical patch was developed for in vivo and real-time peritoneal glucose detection to monitor peritoneal carcinomatosis. As the core of implantable microelectrode, platinum trees were synthesized by one-step electrodeposition method and highly sensitive to glucose detection. The platinum nanotree microelectrode was implantable in peritoneal cavity in minimally invasive way. A flexible circuit patch could execute electrochemical test and realize wireless power harvesting and data interaction with a near field communication (NFC)-enabled smartphone. The whole system could detect glucose dynamics in vivo in rat peritoneal cavity. Furthermore, the accuracy of this system was validated in ascites of patients. In this way, the system could offer hassle-free, rapid and minimally invasive opportunities toward peritoneal carcinomatosis monitoring.

7.
Transl Psychiatry ; 11(1): 230, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879778

RESUMO

Most psychiatric disorders are characterized by deficits in the ability to interact socially with others. Ghrelin, a hormone normally associated with the regulation of glucose utilization and appetite, is also implicated in the modulation of motivated behaviors including those associated with food and sex rewards. Here we hypothesized that deficits in ghrelin receptor (growth hormone secretagogue receptor; GHSR) signaling are also associated with deficits in social motivation in male mice. To test this hypothesis, we compared social motivation in male mice lacking GHSR or mice treated with the GHSR antagonist JMV2959 with that of WT or vehicle-treated mice. GHSR signaling in dopamine cells of the ventral tegmental area (VTA) has been implicated in the control of sexual behavior, thus we further hypothesized that GHSR signaling in the VTA is important for social motivation. Thus, we conducted studies where we delivered JMV2959 to block GHSR in the VTA of mice, and studies where we rescued the expression of GHSR in the VTA of GHSR knockout (KO) mice. Mice lacking GHSR or injected with JMV2959 peripherally for 3 consecutive days displayed lower social motivation as reflected by a longer latency to approach a novel conspecific and shorter interaction time compared to WT or vehicle-treated controls. Furthermore, intra-VTA infusion of JMV2959 resulted in longer latencies to approach a novel conspecific, whereas GHSR KO mice with partial rescue of the GHSR showed decreased latencies to begin a novel social interaction. Together, these data suggest that GHSR in the VTA facilitate social approach in male mice, and GHSR-signaling deficits within the VTA result in reduced motivation to interact socially.

8.
J Clin Neurosci ; 87: 1-7, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33863515

RESUMO

PURPOSE: Whether M1 occlusions proximal (pM1) and distal (dM1) to the lenticulostriate perforators result in different clinical outcomes after mechanical thrombectomy (MT) is unknown. We retrospectively compared the clinical outcomes and baseline characteristics of patients with these two types of occlusions. METHODS: From March 2010 to May 2019, we performed MT for 141 M1 occlusions, including pM1 occlusions (n = 58) and dM1 occlusions (n = 83). RESULTS: Good clinical outcomes (modified Rankin Scale score 0 to 2) were achieved in 28 out of 58 (48.3%) patients with pM1 occlusions and 46 out of 83 (55.4%) patients with dM1 occlusions without significance (p = 0.493). Cardioembolic occlusions represented 19 out of 58 (32.6%) pM1 occlusions and 53 out of 83 (63.9%) dM1 occlusions, and atherosclerotic occlusions represented 37 out of 58 (63.8%) pM1 occlusions and 27 out of 83 (32.5%) dM1 occlusions, with significance (p = 0.001). Rescue treatments, such as balloon angioplasty or stenting, were needed more for pM1 occlusions than dM1 occlusions (21 out of 58 (36.2%) vs. 8 out of 83 (9.8%), p < 0.001). The multivariable logistic regression analysis demonstrated that the need for rescue treatment was associated with pM1 occlusions (adjusted odds ratio; 3.804, 95% confidence interval; 1.306-11.082, p = 0.014). CONCLUSIONS: In our series, pM1 and dM1 occlusions did not significantly differ in good clinical outcomes. Our study also showed that pM1 occlusions were more strongly associated with atherosclerotic occlusions, while dM1 occlusions were more strongly associated with cardioembolic occlusions, and rescue treatments were needed more often for pM1 occlusions than dM1 occlusions.

9.
Biomacromolecules ; 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33840195

RESUMO

Three-dimensional (3D) bioprinting is a technology under active study for use in tissue engineering and regenerative medicine. Bioink comprises cells and polymers and is the essential material for 3D bioprinting. The characteristics of the bioink affect its printability, gelation behavior, and cell compatibility. In this study, alginate derivatives were synthesized to induce rapid gelation, and a bioink was prepared by mixing these alginate derivatives with silk fibroin to enhance cell compatibility. A low-concentration (3 wt %) alginate/silk fibroin (Alg/SF) bioink was pregelated by the ionic cross-linking of Alg to increase the viscosity for 3D printing. The rheological and mechanical properties were analyzed using a rheometer and a texture meter, respectively. Analysis of cell viability and proliferation using fibroblasts (NIH-3T3) in the bioinks showed that the Alg/SF bioink has improved cytocompatibility compared to that of conventional Alg bioinks, making it a promising material for tissue engineering.

10.
Artigo em Inglês | MEDLINE | ID: mdl-33709454

RESUMO

Cell junctions are protein structures located at specific cell membrane domains that determine key processes in multicellular development. Here we report spatially selective imaging of cell junctions by electrochemiluminescence (ECL) microscopy. By regulating the concentrations of luminophore and/or co-reactant, the thickness of ECL layer can be controlled to match with the spatial location of different cell junctions. At a low concentration of luminophore, ECL generation is confined to the electrode surface, thus revealing only cell-matrix adhesions at the bottom of cells. While at a high concentration of luminophore, the ECL layer can be remarkably extended by decreasing the co-reactant concentration, thus allowing the sequential imaging of cell-matrix and cell-cell junctions at the bottom and near the apical surface of cells, respectively. This strategy not only provides new insights into the ECL mechanisms but also promises wide applications of ECL microscopy in bioimaging.

11.
ACS Appl Mater Interfaces ; 13(13): 15727-15737, 2021 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-33779131

RESUMO

Healthcare monitoring, especially for respiration, has attracted tremendous attention from academics considering the great significance of health information feedback. The respiratory rate, as a critical health indicator, has been used to screen and evaluate potential illness risks in early medical diagnoses. A self-powered sensing system for medical monitoring is critical and imperative due to needless battery replacement and simple assembly. However, the development of a self-powered respiratory sensor with highly sensitive performance is still a daunting challenge. In this work, a compressible and stretchable magnetoelectric sensor (CSMS) with an arch-shaped air gap is reported, enabling self-powered respiratory monitoring driven by exhaled/inhaled breath. The CSMS contains two key functional materials: liquid metals and magnetic powders both with low Young's modulus, allowing for sensing compressibility and stretchability simultaneously. More importantly, such a magnetoelectric sensor exhibits mechanoelectrical converting capacity under an external force, which has been verified by Maxwell numerical simulation. Owing to the air-layer introduction, the magnetoelectric sensors achieve high sensitivity (up to 17.73 kPa-1), fast response, and long-term stability. The highly sensitive and self-powered magnetoelectric sensor can be further applied as a noninvasive, miniaturized, and portable respiratory monitoring system with the aim of warning for potential health risks. We anticipate that this technique will create an avenue for self-powered respiratory monitoring fields.

12.
Int J Mol Sci ; 22(5)2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33652858

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease characterized by severe brain damage and dementia. There are currently few therapeutics to treat this disease, and they can only temporarily alleviate some of the symptoms. The pathogenesis of AD is mainly preceded by accumulation of abnormal amyloid beta (Aß) aggregates, which are toxic to neurons. Therefore, modulation of the formation of these abnormal aggregates is strongly suggested as the most effective approach to treat AD. In particular, numerous studies on natural products associated with AD, aiming to downregulate Aß peptides and suppress the formation of abnormal Aß aggregates, thus reducing neural cell death, are being conducted. Generation of Aß peptides can be prevented by targeting the secretases involved in Aß-peptide formation (secretase-dependent). Additionally, blocking the intra- and intermolecular interactions of Aß peptides can induce conformational changes in abnormal Aß aggregates, whereby the toxicity can be ameliorated (structure-dependent). In this review, AD-associated natural products which can reduce the accumulation of Aß peptides via secretase- or structure-dependent pathways, and the current clinical trial states of these products are discussed.


Assuntos
Doença de Alzheimer/tratamento farmacológico , Peptídeos beta-Amiloides/metabolismo , Produtos Biológicos/farmacologia , Doença de Alzheimer/metabolismo , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Produtos Biológicos/química , Descoberta de Drogas , Humanos , Terapia de Alvo Molecular , Agregados Proteicos/efeitos dos fármacos , Conformação Proteica/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
13.
ACS Sens ; 6(4): 1604-1612, 2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33752324

RESUMO

In the present study, a novel electrochemical sensor for the direct detection of caffeine in the crude sample has been prepared by plasma-triggered polydimethylsiloxane (PDMS) deposition on the indium tin oxide electrodes supported with silica nanochannels. The deposited PDMS contains both the original hydrophobic and oxidized hydrophilic PDMS oligomers. Nanochannels modified with these two kinds of PDMS with opposite wettability only allow the passage of small amphiphilic molecules such as caffeine, while other molecules including hydrophilic, hydrophobic, and large ones were all rejected. With the excellent shielding properties, the modified nanochannel electrode exhibits excellent anti-interference and antifouling capability, which could be directly used for the detection of caffeine in real crude food such as tea, milk, coffee, and coke without sample pretreatments. Moreover, the modified electrode has good repeatability and stability. In contrast, severe interference was observed when conventional electrodes were used directly in these unprocessed samples. The linear ranges of caffeine were determined to be between 50 nmol/L and 700 µmol/L, with a limit of detection of 20 nmol/L. The developed sensor provides a very simple, rapid, and cost-effective way for the interference-free and fouling-free analysis of specific amphiphilic compounds and can be extended to a wide range of applications.

14.
Cell ; 184(7): 1895-1913.e19, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657410

RESUMO

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.


Assuntos
/imunologia , Megacariócitos/imunologia , Monócitos/imunologia , RNA Viral , /genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China , Estudos de Coortes , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/isolamento & purificação , Análise de Célula Única , Transcriptoma/imunologia , Adulto Jovem
15.
Front Immunol ; 12: 632119, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33679779

RESUMO

Background: HIV infection results in immune homeostasis perturbations, which is characterized by CD4+ T-cell depletion, immune activation, and inflammation. Effective antiretroviral therapy (ART) does not fully restore immunologic and clinical health in people living with HIV (PLWH). Various drugs have been used to improve their immune status and CD4+ T-cell counts, but no measures have been tested effective. Here we conduct a systematic review and meta-analysis of existing clinical studies on improving CD4+ T-cell count while decreasing inflammation and immune activation. Methods: We retrieved possible relevant publications from a total of five electronic databases and selected eligible studies, which dealt with outcomes of medical therapy for CD4+ T-cell count recovery, inflammation, and immune activation with or without ART. We paid particular attention to immunologic non-responders with a favorable treatment regimen. Results: Thirty-three articles were included in the systematic review and meta-analysis. However, there were no safe and effective medications specific for improving CD4+ T-cell reconstitution. The immunological benefits or adverse events mainly depend on the safety, dosage, and duration of the candidate medication use, as well as whether it is combined with ART. Conclusion: Under the "safe, combined, adequate and long (SCAL)" principles, alternative approaches are needed to accelerate the recovery of CD4+ T-cells, and to prevent adverse long-term outcomes in PLWH with standard ART treatment.

16.
Front Immunol ; 12: 602492, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33717085

RESUMO

TIGIT expression on natural killer (NK) cells is associated with dysfunction during chronic HIV infection, but the phenotype and biological functions of these cells in the context of acute HIV-1 infection remain poorly understood. Here, 19 acutely infected HIV-1 patients traced at first, third and twelfth month, and age-matched patients with chronic HIV-1 infection were enrolled to investigate the phenotype and functions of TIGIT expression on NK cells. We found that TIGIT-expressing NK cells did not increase in frequency in the first, third and twelfth month of infection until chronic HIV-1 infection lasted over 2 years. The number of TIGIT+NK cells in acute infection was positively associated with HIV-1 viral load (r = 0.53, P = 0.0009). CD96 was significantly upregulated on NK cells after acute infection for 1 month and in chronic infection over 2 years, while CD226 was downregulated in chronic infection over 2 years. Further, at different stages of infection, CD96-CD226+ cells diminished among total NK cells, TIGIT+NK and TIGIT-NK cells, while CD96+CD226- cells expanded. Reduced CD96-CD226+ cells and elevated CD96+CD226- cells among NK cells especially TIGIT-NK cells, had opposite associations with viral load in the first month of infection, as well as CD4 T-cell counts in including the twelfth month and more than 2 years of chronic infection. In both HIV-1-infected individuals and healthy donors, TIGIT was predominantly expressed in NKG2A-NKG2C+NK cells, with a significantly higher proportion than in NKG2A+NKG2C-NK cells. Moreover, the frequencies of TIGIT+NK cells were positively associated with the frequencies of NKG2A-NKG2C+NK cells in acute infection (r = 0.62, P < 0.0001), chronic infection (r = 0.37, P = 0.023) and healthy donors (r = 0.36, P = 0.020). Enhanced early activation and coexpression of CD38 and HLA-DR in TIGIT+NK cells were detected compared to TIGIT-NK cells, both of which were inversely associated with the decrease in CD4 T-cell counts in both acute and chronic HIV-1 infection. The ability of TIGIT+NK cells to produce TNF-α, IFN-γ and CD107a degranulation substance were consistently weaker than that of TIGIT-NK cells in both acute and chronic infection. Moreover, the functionalities of TIGIT+NK cells were lower than those of TIGIT-NK cells, except for TNF-α-CD107a+IFN-γ-NK cells. These findings highlight the phenotype and functional characteristics of TIGIT-expressing NK cells which have poor capabilities in inhibiting HIV-1 replication and maintaining CD4 T-cell counts.

17.
Plant Dis ; 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33719543

RESUMO

Brugmansia suaveolens, known as angel's trumpet, is a perennial ornamental shrub in the Solanaceae with large fragrant flowers. In June 2018, a leaf sample of B. suaveolens that showed virus-like symptoms including chlorotic spots, yellowing and mottle on leaves was collected from a greenhouse in Seongnam, South Korea for disease diagnosis (Supplementary Figure S1a, b). Disease incidence in the greenhouse was greater than 80% for about 2,000 B. suaveolens plants. To identify a causal virus, transmission electron microscopy (TEM) was used to analyze symptomatic leaf samples using leaf dips and thin section methods. Filamentous virus particles and pinwheel structures were observed, indicating the presence of a potyvirus (Supplementary Figure S1c, d). To confirm the TEM results, a symptomatic leaf sample was further analyzed by reverse-transcription polymerase chain reaction (RT-PCR) using species-specific detection primers for three potyviruses that infect Brugmansia spp.: Colombian datura virus (CDV), Brugmansia mosaic virus (BruMV), and Brugmansia suaveolens mottle virus (BsMoV) (Lucinda et al, 2008; Park et al., 2014; Verma et al., 2014). The sample was positive only for CDV. CDV is transmitted by aphids in a nonpersistent manner and mechanical inoculation and can infect plants in the Solanaceae family including tomato and tobacco (Kahn and Bartels 1968; Schubert et al. 2006; Verhoeven et al. 1996) and has been designated a quarantine virus in Korea. Additional analysis of 13 symptomatic B. suaveolens plants from the infected greenhouse found that all samples except one were infected with CDV. To isolate CDV from B. suaveolens, leaf extracts from symptomatic samples were mechanically inoculated on an assay host, Nicotiana tabacum cv. BY via three single-lesion passages followed by propagation in N. benthamiana. For the bioassay of the CDV isolate (CDV-AT-Kr), sap from infected N. benthamiana was mechanically inoculated on 31 indicator plants, including B. suaveolens (Supplementary Table S2). CDV-AT-Kr induced chlorotic local lesions, necrotic local lesions, mottle, and/or mosaic systemically in 10 Nicotiana spp., and mottle and yellowing in tomato. On inoculated B. suaveolens, te mild mottle symptom was reproduced. No symptoms were observed in pepper or Datura stramonium. These results were confirmed by RT-PCR. To characterize CDV-AT-Kr genetically, the complete genome sequence of CDV-AT-Kr was obtained by RT-PCR using specific primers (Supplementary Table S3) and deposited in GenBank (accession no. MW075268). The CDV-AT-Kr RNA consists of 9,620 nt, encoding a polyprotein of 3,076 aa. BLASTn analysis showed that CDV-AT had maximum nucleotide identities of 98.9% at the complete genome level with a CDV isolate (accession no. JQ801448) from N. tabacum in the UK. To our knowledge, this is the first report of CDV infection in B. suaveolens in Korea and the second report in the world of the complete genome sequence. As B. suaveolens is cultivated by vegetative propagation, production and maintenance of virus-free, healthy B. suaveolens is needed. In addition, as new CDV hosts have been repeatedly reported (Pacifico et al., 2016; Salamon et al., 2015; Tomitaka et al., 2014; Verma et al., 2014), we are monitoring nationwide occurrence to prevent the spread of the virus to other crops.

18.
Int J Mol Sci ; 22(3)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540582

RESUMO

Methanol dehydrogenase (Mdh), is a crucial enzyme for utilizing methane and methanol as carbon and energy sources in methylotrophy and synthetic methylotrophy. Engineering of Mdh, especially NAD-dependent Mdh, has thus been actively investigated to enhance methanol conversion. However, its poor catalytic activity and low methanol affinity limit its wider application. In this study, we applied a transcriptional factor-based biosensor for the direct evolution of Mdh from Lysinibacillus xylanilyticus (Lxmdh), which has a relatively high turnover rate and low KM value compared to other wild-type NAD-dependent Mdhs. A random mutant library of Lxmdh was constructed in Escherichia coli and was screened using formaldehyde-detectable biosensors by incubation with low methanol concentrations. Positive clones showing higher fluorescence were selected by fluorescence-activated cell sorting (FACS) system, and their catalytic activities toward methanol were evaluated. The successfully isolated mutants E396V, K318N, and K46E showed high activity, particularly at very low methanol concentrations. In kinetic analysis, mutant E396V, K318N, and K46E had superior methanol conversion efficiency, with 79-, 23-, and 3-fold improvements compared to the wild-type, respectively. These mutant enzymes could thus be useful for engineering synthetic methylotrophy and for enhancing methanol conversion to various useful products.


Assuntos
Oxirredutases do Álcool/genética , Bacillaceae/enzimologia , Mutação , Oxirredutases do Álcool/metabolismo , Bacillaceae/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Técnicas Biossensoriais , Cinética , Metanol/metabolismo
19.
Am J Trop Med Hyg ; 2021 Feb 16.
Artigo em Inglês | MEDLINE | ID: mdl-33591933

RESUMO

Knowledge of the clinical progress of severe fever with thrombocytopenia syndrome (SFTS) and the associated predictors of mortality is important for providing appropriate treatment in severe cases. A multihospital retrospective study was conducted in three SFTS-endemic cities, in 2018. Of the 208 SFTS-confirmed cases, there were 189 survivors and 19 deaths. The median age was 64 years; 104 (50.0%) patients were men, and 188 (90.4%) were farmers. Furthermore, 203 (97.6%) patients reported fever and 70 (33.7%) reported fatigue. Most fatal cases had complications including multiple-organ failure, central nervous syndrome (CNS) abnormalities, and disseminated intravascular coagulation. During the fever phase, alanine transaminase, aspartate aminotransferase (AST), blood urea nitrogen (BUN), creatinine, D-dimer, glucose, hydroxybutyrate dehydrogenase, lactate dehydrogenase (LDH), procalcitonin, prothrombin time, and uric acid levels were higher in fatal than in nonfatal cases (P < 0.05). Creatine kinase (CK), CK-MB (CKMB), AST, and LDH levels were significantly lower in nonfatal than in fatal cases (P < 0.05). Central nervous syndrome abnormalities (odds ratio [OR] = 20.9, 95% CI: 4.3, 100), body temperature ≥ 38.5°C (OR = 23.2, 95% CI: 3.4, 158), BUN levels ≥ 6.4 mmol/L (OR = 9.9, 95% CI: 2.2, 44), CKMB levels ≥ 100 U/L (OR = 33.2, 95% CI: 5.8, 192), and LDH levels ≥ 1,000 U/L (OR = 8.3, 95% CI: 1.9, 37) were predictors of mortality. Our findings reveal that the presence of specific complications and laboratory parameters may serve as predictors of mortality and aid in early identification of severe SFTS cases in clinical practice.

20.
Cell Death Dis ; 12(2): 221, 2021 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-33637683

RESUMO

Gastric mucosal injury is a less well known complication of obesity. Its mechanism remains to be further elucidated. Here, we explored the protective role of lipocalin 2 (LCN2) against endoplasmic reticulum stress and cell apoptosis in gastric mucosa in patients and mice with obesity. Through molecular and genetic analyses in clinical species, LCN2 secreted by parietal cells expression is elevated in obese. Immunofluorescence, TUNEL, and colorimetry results show that a more significant upregulation of pro-inflammatory factors and increased amount of apoptotic cells in gastric tissue sections in obese groups. Loss- and gain-of-function experiments in gastric epithelial cells demonstrate that increased LCN2 protected against obesity associated gastric injury by inhibiting apoptosis and improving inflammatory state. In addition, this protective effect was mediated by repressing ER stress. Our findings identify LCN2 as a gastric hormone could be a compensatory protective factor against gastric injury in obese.

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