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1.
Artigo em Inglês | MEDLINE | ID: mdl-33059045

RESUMO

The complement C1r/C1s, Uegf, and Bmp1 (CUB) domains, which are most exclusively found in extracellular and plasma membrane-related proteins, are involved in various biological processes. In this study, a CUB domain-containing protein (designed as HcCDCP) was cloned and characterized from freshwater pearl mussel (Hyriopsis cumingii). The 2280 bp complete cDNA of the HcCDCP contained a 1002 bp open reading frame, which encoded a protein with 333 amino acids. The predicted HcCDCP protein contained a typical CUB domain and a transmembrane region. The tissue distribution analysis indicated that the HcCDCP was detected in all tissues, and the highest expression was found in hepatopancreas followed by gills. After infection with bacteria (i.e., Staphylococcus aureus and Vibrio parahaemolyticus), virus (white spot syndrome virus) and virus analogs (poly[I:C]), the mRNA level of the HcCDCP was significantly upregulated, suggesting that the HcCDCP might be involved in host immune defense response. The RNA interference revealed that the silencing of the HcCDCP could evidently inhibit the expression levels of lysozyme and tumor necrosis factor. Moreover, the recombinant protein of the CUB domain (rCUB) possessed binding capacity to eight different kinds of bacteria. The polysaccharide binding assay showed that the rCUB specifically bound to lipopolysaccharide, peptidoglycan, and D-mannose. This study provided valuable information for exploring the biological roles of CDCPs in the host defense system of mollusks.

2.
Sci Total Environ ; 753: 141710, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-32891988

RESUMO

Respiratory and fecal aerosols play confirmed and suspected roles, respectively, in transmitting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). An extensive environmental sampling campaign of both toilet and non-toilet environments was performed in a dedicated hospital building for patients with coronavirus disease 2019 (COVID-19), and the associated environmental factors were analyzed. In total, 107 surface samples, 46 air samples, two exhaled condensate samples, and two expired air samples were collected within and beyond four three-bed isolation rooms. The data of the COVID-19 patients were collected. The building environmental design and the cleaning routines were reviewed. Field measurements of airflow and CO2 concentrations were conducted. The 107 surface samples comprised 37 from toilets, 34 from other surfaces in isolation rooms, and 36 from other surfaces outside the isolation rooms in the hospital. Four of these samples were positive, namely two ward door handles, one bathroom toilet seat cover, and one bathroom door handle. Three were weakly positive, namely one bathroom toilet seat, one bathroom washbasin tap lever, and one bathroom ceiling exhaust louver. Of the 46 air samples, one collected from a corridor was weakly positive. The two exhaled condensate samples and the two expired air samples were negative. The fecal-derived aerosols in patients' toilets contained most of the detected SARS-CoV-2 in the hospital, highlighting the importance of surface and hand hygiene for intervention.


Assuntos
Aparelho Sanitário , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Síndrome Respiratória Aguda Grave , Betacoronavirus , Hospitais , Humanos
3.
Sci Total Environ ; 753: 142289, 2021 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-33207437

RESUMO

In the fight against the outbreak of COVID-19 in China, we treated some asymptomatic infected individuals. This study aimed to detect pathogens in biological and environmental samples of these asymptomatic infected individuals and analyse their association. Using a cross-sectional study design, we collected biological and environmental samples from 19 patients treated in the isolation ward of Nanjing No.2 Hospital. Biological samples included saliva, pharyngeal swabs, blood, anal swabs, and exhaled breath condensate. Swab samples from the ward environment included inside masks, outside masks, palm swabs, bedside handrails, bedside tables, cell phone screens, toilet cell phone shelves, toilet pads and toilet lids. We also obtained some samples from public areas. We used RT-PCR to detect pathogens and colloidal gold to detect antibodies. As results, 19 asymptomatic infected individuals participated in the survey, with 8 positives for pathogens and 11 positives only for antibodies. Three positive samples were detected from among 96 environmental samples, respectively, from a cell phone surface, a cell phone shelf and a bedside handrail. No positive samples were detected in the exhaled breath condensate in this work. All patients identified pathogens in the environment had positive anal swabs. There was a statistical association between positive anal swabs and positive environmental samples. The association of positive samples from the surrounding of asymptomatically infected patients with positive anal swabs suggested that patients might secrete the virus for a more extended period.


Assuntos
Infecções por Coronavirus , Pandemias , Pneumonia Viral , Betacoronavirus , China/epidemiologia , Estudos Transversais , Humanos
4.
Drug Alcohol Depend ; : 108384, 2020 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-33158665

RESUMO

BACKGROUND: Over the course of the past decade, psychostimulants such as methamphetamines have been increasingly reported in overdose deaths in the United States (US). Methamphetamine use has recently risen among individuals who use opioids, yet it is unclear what role the opioid crisis has played in the increase in psychostimulant-involved overdose mortality in states across the US. METHODS: Mortality data from the Centers for Disease Control and Prevention were used to examine recent state-level changes in overdose deaths involving psychostimulants with abuse potential, excluding cocaine. Psychostimulant-involved overdose mortality rates, changes in rates, and opioid co-involvement were compared by state and plotted on choropleth maps. Ordinary least squares regression analyses were used to test the associations between a state's psychostimulant-involved overdose mortality rate change and several state-level indicators related to the opioid crisis. RESULTS: From 2015/2016-2017/2018, significant increases in psychostimulant-involved overdose mortality rates were observed in 42 of 47 states with data available. Each of the three state-level indicators examined in the study (opioid prescribing rate in 2012, past-year prevalence of opioid use disorder from 2015-2018, and increase in drug overdose mortality during the earliest stages of the opioid crisis from 1999-2012) was positively associated with the absolute rate change in psychostimulant-involved overdose mortality from 2015/2016-2017/2018. CONCLUSIONS: Although deaths involving methamphetamine have historically been primarily concentrated in the western US, results of the study reflect the alarming increase in psychostimulant-involved overdose mortality across the nation, especially in some of the states heavily impacted by the opioid crisis.

5.
Artigo em Inglês | MEDLINE | ID: mdl-33166668

RESUMO

BACKGROUND: Repetitive transcranial magnetic stimulation (rTMS) is the current treatment option for major depression (MD). Theta-burst stimulation (TBS), a variation of rTMS, affords a short stimulation duration, low stimulation pulse intensity, and possibility to improve rTMS efficiency. This systematic review and meta-analysis examined the studies on efficacy and tolerability of TBS in patients with MD. METHODS: This study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We searched the literature from 1990 until May 24, 2020, and performed a random-effects meta-analysis by including response and remission rates of depression and dropout rates as main outcome measures. RESULTS: In total, 10 studies including 6 randomized controlled trials (RCTs; n = 294) and 4 uncontrolled clinical trials (non-RCTs; n = 297) were included. The overall effect size of response rate and remission rates were 0.38 (95% confidence interval [CI]: 0.29-0.48) and 0.20 (95% CI: 0.13-0.29), respectively. Notably, the TBS group showed favorable efficacy without major adverse events. CONCLUSIONS: TBS treatment was more efficient in terms of time and energy than the standard rTMS was. Our meta-analysis provided evidence that the application of TBS to the dorsolateral prefrontal cortex is associated with significant antidepressant effects along with favorable tolerability.

6.
J Mol Diagn ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33217553

RESUMO

The 2016 International Myeloma Working Group consensus recommendations emphasize the importance of high sensitivity methods for minimal residual disease (MRD) detection, treatment response assessment and prognostication. Next generation sequencing (NGS) of IGH gene rearrangements is highly specific and sensitive, but its description in routine clinical practice and performance comparison with high sensitivity flow cytometry (hsFC) remain limited. In this large single institution study including 438 samples from 251 patients, we describe our use of NGS targeting the IGH and IGK genes for clonal characterization and monitoring, with comparison to hsFC. The index clone characterization success rate was 93.6% (235/251), which depended on plasma cell (PC) cellularity, reaching 98% when PC≥10% and below 80% when PC<5%. 85% of cases were successfully characterized using leader and FR1 primer sets, and most clones showed high somatic hypermutation rate (median 8.1%). Among monitoring samples from 124 patients, 78.6% (147/187) had detectable disease by NGS. Concordance with hsFC was 92.9% (170/183). Discordant cases encompassed 8/124 hsFC MRD+/NGS MRD- (6.5%) patients and 4/124 hsFC MRD-/NGS MRD+ (3.2%) patients, all with low-level disease near detection limits for both assays. Among concordant hsFC MRD-/NGS MRD- cases, only 5/24 patients (20.8%) showed subsequent overt relapse with 3-year follow-up. HsFC and NGS showed similar operational sensitivity, and the choice of test may depend on practical, rather than test performance, considerations.

7.
Food Funct ; 11(11): 10033-10046, 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33135040

RESUMO

Luteolin (LU) is a flavonoid compound and metformin hydrochloride (MH) is a kind of drug. Studies have shown that both LU and MH have the function of hypoglycemic effect. However, there are few reports indicating that LU cooperated with MH (LU·MH) can relieve lipid metabolism disorders and optimize intestinal flora compositions of high-fat diet mice. In this research, we investigated the effects of LU, MH and LU·MH on lipid metabolism disorders and intestinal flora composition in high-fat diet mice. The study found that compared with high-fat diet (HFD) alone, LU, MH and LU·MH could significantly reduce the lipid metabolism disorder. Furthermore, compared with LU or MH alone, the biochemical indicators of LU·MH were significantly improved and the results of the histopathological section also showed that LU·MH has stronger liver repair ability. It revealed that the potential mechanisms of the LU·MH alleviating lipid metabolism disorders were involved in the simultaneous regulation of SREBP-1c/FAS and SREBP-1c/ACC/Cpt-1. In addition, LU·MH could regulate the intestinal flora compositions. This includes significantly reducing the ratio of Firmicutes and Bacteroidetes(F/B) and at the family level, increasing the relative abundance of Lachnospiraceae, Helicobacteraceae, Marinifilaceae and Peptococcaceae to relieve lipid metabolism disorders. In conclusion, the work found that LU·MH regulates the signal pathway of SREBP-1c/FAS and SREBP-1c/ACC/Cpt-1 simultaneously and decreases the ratio of F/B, as well as increases the relative abundance of certain microbiota to alleviate the lipid metabolism disorders of HFD-fed mice.

8.
Artigo em Inglês | MEDLINE | ID: mdl-33191758

RESUMO

Background While previous studies have analyzed cross-level CRF01_AE viral genomic data in populations, less is known about intrapatient viral evolutionary dynamics during antiviral treatment (ART) failure. Methods We longitudinally sampled plasma and peripheral blood mononuclear cells (PBMC) at different time points from one HIV-1 infected patient. The evolution of viral quasispecies was inferred from viral phylogenies. Results Prior to treatment, no drug resistant mutations were found in this patient's plasma, and all viruses had CCR5 tropism. Two months after treatment, the majority of the virus population in plasma and PBMC were drug resistant and X4-tropic. By five months after treatment, the viral load increased significantly, and viruses reversed tropism from X4 to R5 in plasma and PBMC. During treatment failure, the effective population of the pol DNA reservoir in PBMC remained stable, while the env DNA reservoir increased. The effective population of the R5 tropism virus increased more rapidly than that of the X4 tropism virus. The ratio of non-synonymous to synonymous substitutions in the env gene of R5 tropism virus (0.43) was lower than X4 tropism (0.52). However, four env positive selection sites were identified in R5 tropism viruses (HXB2: 364, 398, 399 and 400) but none were identified in X4 tropism viruses. Conclusions Our data demonstrated the different intrapatient evolutionary dynamics patterns of env and pol genes in an individual who experienced periods of ART failure. Our findings also suggest the importance of the R5 tropism virus in the DNA reservoir during ART failure.

9.
J Formos Med Assoc ; 2020 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-33158697

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) has been linked to pediatric asthma patients treated with montelukast. This study is the first to use a nationwide health insurance research database (NHIRD) to study whether asthmatic children using montelukast are at an increased risk of ADHD. METHODS: We used data from the Taiwan NHIRD, which is a longitudinal database of one million randomly selected subjects. The enrolled patients were followed up until 2013. Patients younger than and equal to 12 years old with new-onset asthma (ICD-9 CM code 493.X) diagnosed between 1997 and 2013 were enrolled. A multivariate Cox regression analysis was conducted to evaluate the association between montelukast treatment and the risk of ADHD (ICD-9-CM code 314.X). RESULTS: We enrolled a total of 54,487 asthmatic children younger than and equal to 12 years old who had at least one claim of inpatient admission or at least three claims of an ambulatory visit. Montelukast users and match controls were identified by matching age, gender, residence, the comorbidities including allergic rhinitis and atopic dermatitis, admission or emergency department visits due to asthma attack, and index date of starting montelukast in a 1:1 ratio, with 12,806 in the montelukast group and 12,806 in the non-montelukast group. The montelukast group had a similar risk of ADHD (n = 632, 4.94%) as the non-montelukast group (n = 610, 4.76%) [adjusted hazard ratio 1.04; 95% confidence interval, 0.93 to 1.17]. In children treated with montelukast, high cumulative days of montelukast use did not increase the risk of ADHD. CONCLUSION: This nationwide population-based cohort study reveals that asthma children treated with montelukast were not at an increased risk of developing ADHD. Nevertheless, validation of our retrospective survey requires further prospective study.

10.
Pulm Pharmacol Ther ; 64: 101976, 2020 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-33152467

RESUMO

BACKGROUND: The Phase III KRONOS study (NCT02497001) found the fixed-dose combination triple therapy budesonide/glycopyrrolate/formoterol fumarate metered dose inhaler (BGF MDI) to be efficacious and well tolerated versus corresponding dual therapies in patients with moderate-to-very severe COPD from North America, China and Japan. However, pharmacokinetic (PK) studies of other drugs have shown that ethnic factors (e.g. genetic factors affecting drug metabolism) can affect the bioavailability of drugs which may impact upon efficacy and safety outcomes. METHODS: This was a post-hoc analysis of data from four randomised, double-blind Phase I studies of BGF MDI 320/18/9.6 µg and 160/18/9.6 µg in Chinese (NCT03075267), Japanese (NCT02197975) and Western (NCT01980615, NCT02189304) healthy subjects. PK properties (area under the plasma concentration-time curve 0-12 h post-dose [AUC0-12] and maximum plasma concentration, [Cmax]) were recorded following single and repeated dosing of BGF MDI 320/18/9.6 µg or 160/18/9.6 µg. Potential ethnic differences in the PK properties of budesonide, glycopyrrolate and formoterol in Chinese, Japanese and Western healthy subjects were derived by non-compartmental analysis, and ethnic insensitivity factors evaluated based on criteria from the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use, Guideline E5 Ethnic Factors in the Acceptability of Foreign Clinical Data. RESULTS: The analyses included data from 64 Chinese, 31 Japanese and 169 Western subjects. Overall, PK properties following single or repeated dosing of BGF MDI were similar across Chinese, Japanese and Western subjects. After single dosing at either dose level, AUC0-12 and Cmax for budesonide, glycopyrrolate and formoterol appeared generally similar for Asian (Chinese and Japanese) versus Western subjects, with most geometric least squares mean ratios within the range of 0.92-1.22. The exception was that Cmax for glycopyrrolate was slightly lower in Asian versus Western subjects (0.6-0.7). Of the 10 ethnic insensitivity factors evaluated, six were met for budesonide, nine for glycopyrrolate and nine for formoterol, suggesting that BGF MDI can be classified as an ethnically insensitive drug. CONCLUSIONS: Overall, these analyses suggest no appreciable ethnic differences in the PK of BGF MDI across Chinese, Japanese and Western healthy subjects.

11.
Exp Brain Res ; 2020 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-33180154

RESUMO

Cerebral ischemia/reperfusion (I/R) injury may lead to a poor prognosis for ischemic stroke patients after reperfusion therapy, and currently, lacks effective therapeutic intervention. This study aimed to investigate the effects of L-3-n-butylphthalide (L-NBP) on cerebral I/R injury in rats. Rat models of cerebral I/R injury were established using the middle cerebral artery occlusion/refusion (MACO/R) surgery and were administrated intragastrically with L-NBP or vehicle. We found that L-NBP attenuated the histological damages and reduced the brain hematoma in MACO/R rats. L-NBP also significantly improved the neurological function, alleviated the brain edema, and reduced the permeability of blood-brain barrier of MACO/R rats. Moreover, we detected that L-NBP considerably facilitated microvessel formation in the lesion area of brain in MACO/R rats. Finally, we found that L-NBP significantly increased the protein and mRNA expression levels of Nrf2, HIF-1α, and VEGF in the brain of MACO/R rats. In conclusion, our results demonstrated that L-NBP exerted significant beneficial effects on cerebral I/R injury in rats through promoting angiogenesis, which may be associated with the activation of Nrf2/HIF-1α/VEGF signaling pathway. Our results suggested that L-NBP could be a potential therapeutic drug for cerebral I/R injury.

12.
Artigo em Inglês | MEDLINE | ID: mdl-33196408

RESUMO

Six aerobic, non-motile, non-haemolytic, Gram-stain-negative, oxidase-negative strains (185T, 187, 323-1T, 194, dk386T and dk771) were recovered from different faecal samples of Equus kiang on the Qinghai-Tibet Plateau. In the 16S rRNA gene sequences, one strain pair, 185T/187, shared highest similarity to Acinetobacter equi 114T (97.9 %), and the other two (323-1T/194 and dk771T/dk386) to Acinetobacter harbinensis CGMCC 1.12528T (98.6 and 97.0 %, respectively). Phylogenomic tree analysis showed that these six strains formed three separate clades in the genus Acinetobacter. Digital DNA-DNA hybridization values of each pair of the isolates with all members of the genus Acinetobacter were far below 70 %. The main cellular fatty acids of all six strains were C18 : 1 ω9c, C16 : 0 and summed feature 3 (C16 : 1 ω7c/C16 : 1 ω6c). Q-9 was the predominant respiratory quinone for strains 185T, 323-1T and dk386T. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. Based on the genotypic, phenotypic and biochemical analyses, these six strains represent three novel species of the genus Acinetobacter, for which the names Acinetobacter lanii sp. nov., Acinetobacter shaoyimingii sp. nov. and Acinetobacter wanghuae sp. nov. are proposed. The type strains are 185T (=CGMCC 1.13636T=JCM 33607T), 323-1T (=CGMCC 1.13940T=JCM 33608T) and dk386T (=CGMCC 1.16589T=JCM 33592T), respectively.

13.
J Mol Cell Biol ; 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33196842

RESUMO

Accumulating evidence indicates that the alternative splicing program undergoes extensive changes during cancer development and progression. The RNA-binding protein QKI-5 is frequently down-regulated and exhibits anti-tumor activity in lung cancer. However, little is known about the functional targets and regulatory mechanism of QKI-5. Here, we report that up-regulation of exon 14 inclusion of cytoskeletal gene Adducin 3 (ADD3) significantly correlates with a poor prognosis in lung cancer. QKI-5 inhibits cell proliferation and migration in part through suppressing the splicing of ADD3 exon 14. Through genome-wide mapping of QKI-5 binding sites in vivo at nucleotide resolution by iCLIP-seq analysis, we found that QKI-5 regulates alternative splicing of its target mRNAs in a binding position-dependent manner. By binding to multiple sites in an upstream intron region, QKI-5 represses the splicing of ADD3 exon 14. We also identified several QKI mutations in tumors, which cause dysregulation of the splicing of QKI targets ADD3 and NUMB. Taken together, our results reveal that QKI-mediated alternative splicing of ADD3 is a key lung cancer-associated splicing event, which underlies in part the tumor suppressor function of QKI.

14.
AAPS PharmSciTech ; 21(8): 321, 2020 Nov 16.
Artigo em Inglês | MEDLINE | ID: mdl-33200271

RESUMO

The fluorescence dye-loaded nanoparticles are widely used as bioimaging agents in the field of nanotheranostics. However, the nanoparticles for nanotheranostics usually consist of synthetic materials, such as metal, silica, and organic polymers, which are often biologically incompatible and may arouse toxicity issues. Herein, the potential of near-infrared probe DiR-containing solid lipid nanoparticle suspensions (DiR-SLNS) as the bioimaging agent, which was prepared by lipids and surfactants with excellent biocompatibility, was investigated in this study. The nanostructure of DIR-SLNS system and the distribution of DiR were studied by dissipative particle dynamics (DPD) simulations. The stability of physicochemical properties and fluorescence spectra of DIR-SLNS system were investigated using dynamic laser scattering (DLS), nanoparticle tracking analysis (NTA), and fluorescence spectra. The fluorescence intensity-concentration correlation of DIR-SLNS was also evaluated. As a result, DiR-SLNS demonstrated a "core-shell"-like nanostructure and DiR was mainly distributed in the cetyl palmitate (CP) core rather than the surface of SLNS, which was beneficial to its potential applications in bioimaging. DiR-SLNS exhibited remarkable physicochemical stability as the nanoparticles maintained ~ 90% fluorescence intensity during the 10-day storage time. The correlation between fluorescence intensity and concentration was established and validated using a linear regression model. This study proposed a type of promising candidates in nano-scale with higher safety and fluorescence stability for bioimaging.

16.
Plant Dis ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33200971

RESUMO

Sugarcane (Saccharum officinarum L.) is the main sugar crop in China. Yunnan is the second largest sugarcane production province in China. In December 2018, leaf blight was first observed on almost every leaf of sugarcane on 'Huanan 54-11', 'Baimei' and 'Chongan' in Kaiyuan (103°27' E, 23°72' N), Yunnan. In October 2019, during our survey in the field in Lingcang (100°08' E, 23°88' N), Yunnan, this disease was also observed on 'ROC 25'. Symptoms of the disease initially appeared as wilted, which seemed to be cause by water stress. As the disease progressed, irregular straw-yellow and blighted lesion ran throughout the leaf lamina from leaf tip to entire leaf sheath, many small black conidia formed in the dead leaf tissue under humid conditions. Symptomatic leaf tissues were surface-sterilized with 70% ethanol for 30 s, 0.1% HgCl2 for 1 min, and rinsed with sterilized water three times, air dried on sterile filter paper, and plated on potato dextrose agar (PDA). Six isolates were obtained from six symptomatic leaf samples and were transferred onto potato carrot agar (PCA). Colonies on PDA were white with loose aerial hyphae at first, then turned to dark olive or dark. Colonies on PCA were grayish with sparse hyphae, then turned to dark gray. Conidiophores were brown, simple or branched, and produced numerous conidia in short chains. Conidia (n = 50) were obclavate to obpyriform or ellipsoid, brown to dark brown, with a cylindrical short beak at the tip (2.3 to 17.3 µm in length), and 15.3 to 46.6 µm × 4.2 to 17.9 µm, 2 to 7 transverse septa and 0 to 3 longitudinal septa. Morphologically, the isolates were identified as Alternaria tenuissima (Simmons 2007). Two representative isolates C4 and C5 were selected for molecular identification. The internal transcribed spacers (ITS), Histone 3 genes and plasma membrane ATPase were amplified with primer pairs ITS1/ITS4, H3-1a/H3-1b and ATPDF1/ATPDR1, respectively (Glass et al. 1995; Lawrence et al. 2013). The sequences were deposited in GenBank (ITS, MT679707-MT679708; Histone 3, MT710929-MT710930; ATPase, MT833928-MT833929). BLAST searches showed ≥99% nucleotide identity to the sequence of A. tenuissima (ITS, 100% to MN822571; Histone 3, 100% to MN481955; ATPase, 99% to JQ671875, 100% to MH492703, respectively). Thus, the fungus was identified as A. tenuissima based on morphological and molecular characteristics. For pathogenicity tests, five healthy 2-month-old potted sugarcane leaves were wounded with one sterile needle and inoculated with 20 µl of suspension of 106 conidia/ mL, and five plants were inoculated with distilled water as the controls. Plants were placed in a greenhouse at 25 to 35°C. After two months, the leaf wound inoculated with the putative pathogen displayed blighted as those observed in the field whereas the controls remained symptomless. The fungus was reisolated from symptomatic leaves with the same morphological and molecular traits as the original isolates. The fungus was not isolated from the control plants. Pathogenicity tests were repeated two times. A. tenuissima causing leaf blight on barley in China was reported in 2008 (Luo et al. 2008). Leaf spot disease of sugarcane caused by A. tenuis has been recorded in Maharashtra (Patil et al. 1974). To our knowledge, this is the first report on A. tenuissima affecting leaf blight on sugarcane in Yunnan Province, China. Identification of the causes of the disease is important to develop effective disease management strategies. The author(s) declare no conflict of interest. Funding: This research was supported by Sugar Crop Research System (CARS-170303), the Yunling Industry and Technology Leading Talent Training Program "Prevention and Control of Sugarcane Pests" (2018LJRC56), and the Yunnan Province Agriculture Research System. References: Glass, N. L., et al. 1995. Appl. Environ. Microbiol. 61:1323. Lawrence, D. P., et al. 2013. Mycologia 105:530. Luo, Z., et al. 2008. Acta Phytophy. Sin. 35(5): 469-470. Patil, A.O., et al. 1974. Res. J. Mahatma Phule Agric. Univ. 5(2): 122-123. Simmons, E. G. 2007. Alternaria: An Identification Manual. CBS Fungal Biodiversity Centre, Utrecht, The Netherlands. Caption for supplementary Figure 1 Supplementary Figure S1. Disease symptoms of sugarcane leaf blight disease and morphological characteristics of Alternaria tenuissima. (A) Typical straw-yellow and blighted lesions on naturally-infected leaves of sugarcane; (B) Infected symptoms on wounded leaves of sugarcane two months after artificial infection with A. tenuissima; (C) Colony of A. tenuissima on PDA; (D) Colony of A. tenuissima on PCA; and (E-F) Sporulation and conidia of A. tenuissima on PCA. (Scale bars = 100 µm; 20 µm).

17.
PLoS Pathog ; 16(11): e1008943, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33137810

RESUMO

Respiratory syncytial virus (RSV) is a global public health burden for which no licensed vaccine exists. To aid vaccine development via increased understanding of the protective antibody response to RSV prefusion glycoprotein F (PreF), we performed structural and functional studies using the human neutralizing antibody (nAb) RSB1. The crystal structure of PreF complexed with RSB1 reveals a conformational, pre-fusion specific site V epitope with a unique cross-protomer binding mechanism. We identify shared structural features between nAbs RSB1 and CR9501, elucidating for the first time how diverse germlines obtained from different subjects can develop convergent molecular mechanisms for recognition of the same PreF site of vulnerability. Importantly, RSB1-like nAbs were induced upon immunization with PreF in naturally-primed cattle. Together, this work reveals new details underlying the immunogenicity of site V and further supports PreF-based vaccine development efforts.

18.
Inflammation ; 2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33206273

RESUMO

Immune-mediated angiogenesis is important in the pathogenesis of inflammatory bowel disease and targeted treatment could alleviate the disease. Thalidomide is an effective drug in inflammatory bowel disease, which might be related to its multiple role in anti-inflammatory, immunoregulatory, and anti-angiogenesis. This study is to investigate the effect of thalidomide on angiogenesis in tissues from patients and in vitro cells. Angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), VEGF, and CD31 expressions in intestinal mucosa from pediatric CD patients before and after thalidomide treatment were measured by immunohistochemistry. Western blotting and polymerase chain reaction were performed to characterize the change of angiogenic factors before and after treatment in remission. Human umbilical vein endothelial cells (HUVECs) treated by thalidomide were used to examine its effect on endothelial cell proliferation and migration and capillary-like structures. Results showed that VEGF and Ang-2 levels were significantly greater in CD patients over controls. Thalidomide produced a significant reduction in protein expression of Ang-2 and VEGF, along with a decrease in mRNA expression of Ang-2. While, Ang-1 level did not show a statistically significant change. Thalidomide significantly inhibited cell proliferation in a dose-dependent manner. It also suppressed VEGF- and Ang-2-induced cell migration and capillary-like tube formation in HUVECs. Therefore, our study suggests that VEGF and Ang-2 levels are up-regulated in pediatric CD patients. It also indicated that thalidomide can be able to deactivate endothelium by the downregulation effect on angiogenic factors by targeting VEGF and Ang-2.

19.
Medicine (Baltimore) ; 99(43): e22864, 2020 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-33120825

RESUMO

Video capsule endoscopy (VCE) can detect mucosal lesions in the intestine, especially in the small bowel.Our study aims to evaluate the applications of VCE for pediatric gastrointestinal diseases.In this retrospective study, we included all patients who underwent VCE between December 2012 and December 2018. Clinical information and VCE data were analyzed.Among 828 patients, the completion rate was 99.6% (n = 825), with an average age of 10.2 ±â€Š3.3 years old. A total of 459 VCE procedures showed abnormalities, and the overall diagnostic yield was 55.6%. The most common indications for VCE were abdominal pain among 505 (61.2%) patients and hematochezia (10.1%) among 83. Among the positive results of VCE, small bowel ulcers accounted for the highest percentage (57.7%), of which 164 cases were diagnosed as inflammatory bowel disease. For obscure gastrointestinal bleeding, 12 cases were diagnosed as Meckel's diverticulum. In terms of the small bowel transit time of VCE, compared with the negative group [288 (216.5, 390.3) min] and the enteritis group [277 (192.5, 374.8) min], a longer transit time was needed in the small bowel ulcer group [332.5 (240, 451.5) min, P < .01]. There were no correlations of positive VCE findings with anemia, the white blood cell count, the C-reactive protein level or the small bowel transit time according to Spearman rank analysis.VCE is relatively well tolerated and safe in children and has great value for the diagnosis and treatment of abdominal pain, especially inflammatory bowel disease and obscure gastrointestinal bleeding.


Assuntos
Endoscopia por Cápsula/métodos , Gastroenteropatias/patologia , Úlcera/diagnóstico por imagem , Dor Abdominal/diagnóstico , Adolescente , Estudos de Casos e Controles , Criança , China/epidemiologia , Feminino , Hemorragia Gastrointestinal/diagnóstico , Humanos , Doenças Inflamatórias Intestinais/diagnóstico , Masculino , Divertículo Ileal/diagnóstico , Estudos Retrospectivos
20.
PLoS Pathog ; 16(10): e1008882, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33007046

RESUMO

Neisseria meningitidis serogroup B (MenB) is the leading cause of meningococcal meningitis and sepsis in industrialized countries, with the highest incidence in infants and adolescents. Two recombinant protein vaccines that protect against MenB are now available (i.e. 4CMenB and MenB-fHbp). Both vaccines contain the Factor H Binding Protein (fHbp) antigen, which can bind the Human Factor H (fH), the main negative regulator of the alternative complement pathway, thus enabling bacterial survival in the blood. fHbp is present in meningococcal strains as three main variants which are immunologically distinct. Here we sought to obtain detailed information about the epitopes targeted by anti-fHbp antibodies induced by immunization with the 4CMenB multicomponent vaccine. Thirteen anti-fHbp human monoclonal antibodies (mAbs) were identified in a library of over 100 antibody fragments (Fabs) obtained from three healthy adult volunteers immunized with 4CMenB. Herein, the key cross-reactive mAbs were further characterized for antigen binding affinity, complement-mediated serum bactericidal activity (SBA) and the ability to inhibit binding of fH to live bacteria. For the first time, we identified a subset of anti-fHbp mAbs able to elicit human SBA against strains with all three variants and able to compete with human fH for fHbp binding. We present the crystal structure of fHbp v1.1 complexed with human antibody 4B3. The structure, combined with mutagenesis and binding studies, revealed the critical cross-reactive epitope. The structure also provided the molecular basis of competition for fH binding. These data suggest that the fH binding site on fHbp v1.1 can be accessible to the human immune system upon immunization, enabling elicitation of human mAbs broadly protective against MenB. The novel structural, biochemical and functional data are of great significance because the human vaccine-elicited mAbs are the first reported to inhibit the binding of fH to fHbp, and are bactericidal with human complement. Our studies provide molecular insights into the human immune response to the 4CMenB meningococcal vaccine and fuel the rationale for combined structural, immunological and functional studies when seeking deeper understanding of the mechanisms of action of human vaccines.

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