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1.
ACS Chem Biol ; 2020 May 13.
Artigo em Inglês | MEDLINE | ID: mdl-32401486

RESUMO

The development of a tumor-targeted immunotherapy is highly required. The most advanced application is the use of CD19 chimeric antigen receptor (CAR) T (CAR-T) cells to B-cell malignancies, but there are still side effects including potential carcinogenicity of lentiviral or retroviral insertion into the host cell genome. Here we developed a non-viral aptamer-T-cell targeted strategy for tumor therapy. Tumor cells surface-specific ssDNA aptamers were conjugated to CD3+T cells (aptamer-T cells) using N-azidomannosamine (ManNAz) sugar metabolic cell labeling and click chemistry. We found that the aptamer-T cells could specifically target and bind to tumor cells (such as SGC-7901 gastric cancer cell and CT26 colon carcinoma cell) in vitro and in mice after adoptively transfer in. Aptamer-T cells led to significant regression in tumor volume due to being enriched at tumor microenvironment and producing strong cytotoxicity activities of CD3+T cells with enhanced perforin, granzyme B, CD107a, CD69 and FasL expression. Moreover, aptamer-T displayed even stronger anti-tumor effects than an anti-PD1 immune-checkpoint monoclonal antibody (mAb) treatment in mice and combination with anti-PD1 yielded synergic anti-tumor effects. This study uncovers the strong potential of the adoptive non-viral aptamer-T cell strategy as a feasible and efficacious approach for tumor-targeted immunotherapy application.

2.
Anal Chem ; 2020 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-32393024

RESUMO

The relationship between calcium ion (Ca2+) concentration and temperature variation during the oxidative phosphorylation (OXPHOS) process has become an essential focus for exploration of signalling pathways and neurodegenerative disease. However, there have been limited reports of fluorescent probes for simultaneous Ca2+ detection and temperature sensing. Herein, a new water-soluble fluorescent probe that combines a thermoresponsive polymer, curcumin and Fluo-4 AM for intracelllar temperature and Ca2+ sensing is described. Furthermore, this fluorescent polymer was successfully applied for intracelluar temperature and Ca2+ gradient monitoring generated by exogenous heating in HeLa cells. It was discovered that within 10 minutes after the OXPHOS process was induced by an inhibitor, the temperature increased 0.51.0 °C and the Ca2+ level decreased by about 5.7 µM. These results confirmed that the fluorescent polymer enabled investigation of the relationship between intracelluar temperature and Ca2+induced neurotransmitter release.

3.
Hum Vaccin Immunother ; : 1-7, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32343618

RESUMO

Purpose: To estimate influenza-associated excess mortality rates (EMRs) in Chongqing from 2012 to 2018.Methods: We obtained weekly mortality data for all-cause and four underlying causes of death (circulatory and respiratory disease (CRD), pneumonia and influenza (P&I), chronic obstructive pulmonary disease (COPD) and ischemic heart disease (IDH)), and influenza surveillance data, from 2012 to 2018. A negative-binomial regression model was used to estimate influenza-associated EMRs in two age groups (<65 years and ≥65 years).Results: It was estimated that an annual average of 10025 influenza-associated deaths occurred in Chongqing, corresponding to 5.2% of all deaths. The average EMR for all-cause death associated with influenza was 33.5 (95% confidence interval (CI): 31.5-35.6) per 100 000 persons, and in separate cause-specific models we attributed 24.7 (95% CI: 23.3-26.0), 0.8 (95% CI: 0.7-0.8), 8.5 (95% CI: 8.1-9.0) and 5.0 (95% CI: 4.7-5.3) per 100 000 persons EMRs to CRD, P&I, COPD and IDH, respectively. The estimated EMR for influenza B virus was 20.6 (95% CI: 20.3-21.0), which was significantly higher than the rates of 5.3 (95% CI: 4.5-6.1) and 7.5 (95% CI: 6.7-8.3) for A(H3N2) and A(H1N1) pdm09 virus, respectively. The estimated EMR was 152.3 (95% CI: 136.1-168.4) for people aged ≥65 years, which was significantly higher than the rate for those aged <65 years (6.8, 95% CI: 6.3-7.2).Conclusions: Influenza was associated with substantial EMRs in Chongqing, especially among elderly people. Influenza B virus caused a relatively higher excess mortality impact compared with A(H1N1)pdm09 and A(H3N2). It is advisable to optimize future seasonal influenza vaccine reimbursement policy in Chongqing to curb disease burden.

4.
Analyst ; 145(10): 3564-3568, 2020 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-32307504

RESUMO

Gold nanoclusters (AuNCs) have emerged as a new generation of "nanozymes" based on their intrinsic catalytic activity. However, highly selective and colorimetric detection of drugs is still far from adequately developed due to the lack of means of regulating the catalytic activity of nanozymes. Herein, d-histidine stabilized AuNCs (d-His@AuNCs) were synthesized and their nanozyme ability was demonstrated in the catalytic oxidation of the peroxidase substrate, 3,3',5,5'-tetramethylbenzidine, for the promotion of hydrogen peroxide. Copper ions led to the aggregation of d-His@AuNCs and inhibited their peroxidase-like activity. The addition of doxycycline restored the enzyme-mimicking catalytic activity of d-His@AuNCs, which was based on the strong coordination interaction between copper ions and doxycycline. A highly sensitive and colorimetric assay for determining the amount of doxycycline was developed at a detection wavelength of 650 nm. The color intensity and ultraviolet-visible absorbance intensity of the testing assay displayed a good linear relationship in the doxycycline concentration range of 5.0-12.5 µM, with a limit of detection of 1.0 µM. Moreover, the metabolic process of doxycycline in serum was further investigated with the proposed monitoring system after the drug was abdominally injected into rats. Notably, the tunable catalytic activity performance of the nanozymes indicates their significant potential in clinical application.

5.
Insect Sci ; 2020 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-32283000

RESUMO

Krüppel homolog 1 (Kr-h1), a zinc finger transcription factor, is involved in the metamorphosis and adult reproduction of insects. However, the role of Kr-h1 in reproduction of holometabolic insects remains to be elucidated. The regulation network of Kr-h1-associated genes in the reproduction in Bombyx mori was investigated in this study. The higher expression level of BmKr-h1 in the ovaries was detected during the late pupal stage and adults. RNA interference (RNAi)-mediated depletion of BmKr-h1 in the female at day 6 of pupae resulted in abnormal oocytes at 48 h post-double-stranded RNA treatment, which showed less yolk protein deposition and partially transparent chorion. RNA-seq and subsequent differentially expressed transcripts analysis showed that knockdown of BmKr-h1 caused a decrease in the expression of 2882 genes and an increase in the expression of 2565 genes in the oocytes at day 8 of pupae. Totally, 27 genes coding for transcription factors were down-regulated, while six genes coding for other transcription factors were up-regulated. BmKr-h1 bound to the Kr-h1 binding site of the transcription factors AP-1 (activating protein-1) and FOXG1 to increase their messenger RNA transcripts in the BmN cells, respectively. Gene Ontology enrichment and Kyoto Encyclopedia of Genes and Genomes pathway analyses of that positively co-expressed with AP-1 and FOXG1 transcripts showed mainly enrichment in the metabolic-related pathways, the nutrient absorption and the yolk protein absorption processes. These data suggested that BmKr-h1 might directly regulate the metabolic-related pathways, the nutrient absorption and the yolk protein absorption processes or probably through AP-1 and /or FOXG1 to regulate oocyte development.

6.
Cancer Lett ; 483: 12-21, 2020 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-32330514

RESUMO

Prostate cancer (PCa) is characterized by a unique dependence on optimal androgen receptor (AR) activity where physiological androgen concentrations induce proliferation but castrate and supraphysiological levels suppress growth. This feature has been exploited in bipolar androgen therapy (BAT) for castrate resistant malignancies. Here, we investigated the role of the tumor suppressor protein p14ARF in maintaining optimal AR activity and the function of the AR itself in regulating p14ARF levels. We used a tumor tissue array of differing stages and grades to define the relationships between these components and identified a strong positive correlation between p14ARF and AR expression. Mechanistic studies utilizing CWR22 xenograft and cell culture models revealed that a decrease in AR reduced p14ARF expression and deregulated E2F factors, which are linked to p14ARF and AR regulation. Chromatin immunoprecipitation studies identified AR binding sites upstream of p14ARF. p14ARF depletion enhanced AR-dependent PSA and TMPRSS2 transcription, hence p14ARF constrains AR activity. However, p14ARF depletion ultimately results in apoptosis. In PCa cells, AR co-ops p14ARF as part of a feedback mechanism to ensure optimal AR activity for maximal prostate cancer cell survival and proliferation.

7.
Insect Sci ; 2020 Mar 13.
Artigo em Inglês | MEDLINE | ID: mdl-32166878

RESUMO

Spodoptera litura is a destructive agricultural pest in tropical and subtropical areas. Understanding the molecular mechanisms of S. litura adaptation to its preferred host plants may help identify target genes useful for pest control. We used high-throughput sequencing to characterize the expression patterns of mRNAs and microRNAs (miRNAs) in the midgut of S. litura fed on Brassica juncea for 6 h and 48 h. A total of 108 known and 134 novel miRNAs were identified, 29 miRNAs and 237 mRNAs were differentially expressed at 6 h of B. juncea feeding, 26 miRNAs and 433 mRNAs were differentially expressed at 48 h. For the mRNAs, the up-regulated genes were mostly enriched in detoxification enzymes (cytochrome P450, esterase, glutathione S-transferase, UDP-glucuronosyl transferase), while the down-regulated genes were mostly enriched in proteinases and immune related genes. Furthermore, most detoxification enzymes begin to up-regulated at 6 h, while most digestion and immune related gene begin to up or down-regulated at 48 h. 18 and 37 differently expressed transcription factors were identified at 6 h and 48 h, which may regulate the functional genes. We acquired 136 and 41 miRNA vs mRNA pairs at 6 h and 48 h, respectively. Some down-regulated and up-regulated miRNAs were predicted to targeting detoxification enzymes and proteinases, respectively. RT-qPCR of 9 randomly selected miRNAs and 28 genes confirmed the results of RNA-seq. This analyses of miRNA and mRNA transcriptomes provided useful information about the molecular mechanisms of S. litura response to B. juncea. This article is protected by copyright. All rights reserved.

8.
Anal Chem ; 92(6): 4445-4450, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32142270

RESUMO

To monitor d-glucose (Glu) in complex aqueous media with a high specificity, a conceptually new "selective capture and controllable detection" nanoreactor was explored. We designed and synthesized poly maleic anhydride-styrene-N-isopropylacrylamide-(4-aminophenyl) boronic acid [P(MAn-St-NIPAm-PBA)] to fabricate the nanoreactor. On the surface of the self-assembled, micelle-based nanoreactor, the stereo precise placement PBA provided a recognition unit in the block copolymer structure to boost the selective capture of Glu over other saccharides. P(MAn-St-NIPAm) served as the thermal sensitive moiety of the nanoreactor, which embedded with glucose oxidase and myoglobin-based catalyst in order to realize the controllable enzymolysis of Glu through temperature alteration. Once the nanoreactor was mixed with Glu, an obvious change in the UV-visible intensity of quinine produced in the multienzymolysis was observed. Glu in the rat microdialysates of brain ischemia was successfully monitored by the nanoreactor method, demonstrating the feasibility of constructing high-specificity nanoreactors for cerebral system applications.

9.
Expert Rev Hematol ; 13(5): 565-575, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32178541

RESUMO

Objectives: Authors assessed the impact of ruxolitinib (RUX) on steroid-refractory graft-versus-host disease (SR-GVHD) patients.Methods: Studies published before January 2019 were identified by electronic search of MEDLINE, EMBASE, Cochrane Library, Clinical Trials.Gov and Web of Science databases.Results: Sixteen cohort studies (414 adults) were included whose methodological quality ranged from poor to good. Pooled outcomes such as the response rates, steroid dose reduction, 1-year overall survival, overall infection, and grade 3 to 4 cytopenia were calculated separately for adults with steroid-refractory acute GVHD (aGVHD) and chronic GVHD (cGVHD). Further, the overall response rates were analyzed according to the affected organ. Adults with aGVHD as well as cGVHD showed high response with RUX, and steroid dose reduction was observed in both cases. Infection rates and cytopenia were important safety concerns for both aGVHD and cGVHD.Conclusion: Notwithstanding the need of randomized controlled trials to confirm the effect of RUX on SR-GVHD, response rates among adults with aGVHD and cGVHD seem to be high with the use of RUX as a salvage treatment, particularly in cases with gastrointestinal and cutaneous involvement. However, high rates of myelosuppression and infection remain a cause for concern regardless of aGVHD or cGVHD.

10.
BMC Infect Dis ; 20(1): 224, 2020 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-32171271

RESUMO

BACKGROUND: Cervical lymphadenopathy refers to a frequently observed clinical presentation in numerous pathological conditions. A wide spectrum of diseases can cause cervical lymphadenopathy, irrespective of the fact that the patients are infected with HIV or not. The present study focuses on validating whether the causes of cervical lymphadenopathy differ significantly in HIV and non-HIV patients by using fine-needle aspiration cytology (FNAC) combining cell block. METHODS: A total of 589 patients with cervical lymphadenopathy were recruited in the FNA clinic. The samples were obtained by an auto-vacuumed syringe that benefited the sampling more materials. The cytological smears were prepared by Hematoxylin and Eosin (HE), Periodic Acid Schiff (PAS), Gomori's methenamine silver (GMS) and acid-fast staining. Cell blocks were made if required, and immunohistochemistry stain was performed on the cell block section. RESULTS: The study found 453 (76.9%) patients with HIV and 136 (23.1%) patients without HIV infection. The average age of HIV-infected patients was 34.8 ± 10.2 years, which was significantly lower than that of non-HIV-infected patients (42.9 ± 18.1 years) (p < 0.01). Of all patients infected with HIV, 390 (86.1%) were males. This proportion was significantly higher than that of non-HIV-infected patients [65/136 (47.8%)] (p < 0.01). The major causes of cervical lymphadenopathy in HIV positive patients were mycobacterial infection (38.4%), reactive hyperplasia (28.9%), non-specific inflammation (19.9%), and malignant lesions (4.2%). In contrast, the most common causes in HIV negative patients were reactive hyperplasia (37.5%), malignancy (20.6%), non-specific inflammation (19.1%) and mycobacterial infection (12.5%). Opportunistic infections such as non-tuberculous mycobacteria (4.2%), cryptococcosis (1.5%), Talaromyces marneffei (1.5%) and other fungi (0.4%) were found only in HIV-infected individuals. Non-Hodgkin's lymphoma (2.4%) was the most common malignant lesion in patients with HIV infection, followed by Kaposi's sarcoma (0.9%) and metastatic squamous cell carcinomas (0.7%). However, the most common malignancy in non-HIV-infected patients was metastatic carcinomas (14%) including small cell carcinomas, adenocarcinomas, squamous cell carcinomas and hepatocellular carcinoma, which were noticeably greater than the HIV patients (p < 0.01). CONCLUSIONS: There were significantly different causes of cervical lymphadenopathy in HIV infected and non-HIV infected patients. FNAC was a useful diagnostic method for differential diagnosis of cervical lymphadenopathy.


Assuntos
Infecções Oportunistas Relacionadas com a AIDS/epidemiologia , HIV/isolamento & purificação , Linfonodos/patologia , Linfadenopatia/diagnóstico , Linfadenopatia/epidemiologia , Infecções Oportunistas Relacionadas com a AIDS/virologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia por Agulha Fina/métodos , Criança , China/epidemiologia , Comorbidade , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia/complicações , Hiperplasia/diagnóstico , Incidência , Linfadenopatia/etiologia , Linfadenopatia/virologia , Masculino , Pessoa de Meia-Idade , Infecções por Mycobacterium/complicações , Infecções por Mycobacterium/diagnóstico , Pescoço , Adulto Jovem
11.
Aging (Albany NY) ; 12(6): 5140-5151, 2020 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-32182213

RESUMO

Angiopoietin-2 (Ang-2) is a proangiogenic factor that mediates inflammation and atherosclerosis. We evaluated the predictive value of circulating Ang-2 levels for periprocedural myocardial injury (PMI) in 145 patients undergoing elective percutaneous coronary intervention (PCI), and investigated whether post-PCI Ang-2 levels are influenced by PMI. PMI was defined as a post-procedural troponin elevation above the 5×99th percentile upper reference limit. Blood samples for Ang-2 analysis were collected at admission and on postoperative days 1 and 3. PMI occurred in 40 patients (28%). At baseline, there was no difference in Ang-2 levels between PMI and non-PMI patients (P=0.554). However, a significant interaction effect between PMI occurrence and time on Ang-2 levels was observed (interaction P=0.036). Although serum Ang-2 levels in non-PMI patients gradually decreased, Ang-2 levels in PMI patients did not change between different time-points. Multiple logistic regression analysis revealed that age, total stent length, and serum levels of N-terminal pro-brain natriuretic peptide were independent PMI predictors. These findings indicate that pre-procedural Ang-2 levels do not impact PMI occurrence after elective PCI. However, changes in Ang-2 levels after the procedure are closely related to PMI.

12.
Magn Reson Imaging ; 69: 28-39, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32145270

RESUMO

PURPOSE: This study aims to develop and evaluate a robust conductivity imaging method that combines total variation and wavelet regularization to enhance the accuracy of conductivity maps. THEORY AND METHODS: The proposed approach is based on a gradient-based method. The central equation is derived from Maxwell's equation and describes the relationship between conductivity and the transceive phase. A linear system equation is obtained via a finite-difference method and solved using a least-squares method. Total variation and wavelet transform regularization terms are added to the minimization problem and solved using the Split Bregman method to improve reconstruction stability. The proposed approach is compared with conventional and gradient-based methods. Numerical simulations are performed to validate the accuracy of the developed method, and the effects of noise are determined. Phantom and in vivo experiments are conducted at 3 T to verify the clinical applicability of the proposed method. RESULTS: Numerical simulations show that the proposed method is more robust than other methods and can suppress the effects of noise. The quantitative conductivity value of the phantom experiment agrees with the measured value. The in vivo experiment results present a clear structure, and the conductivity value of the tumor region is significantly higher than that around healthy tissues. CONCLUSION: The proposed electrical conductivity imaging method can improve the quality of conductivity reconstruction, and thus, has future clinical applications.

13.
Analyst ; 145(6): 2233-2237, 2020 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-32064468

RESUMO

The discriminative monitoring of biothiols in biological fluids is a great challenge. Herein, we developed a fluorescence "turn-off-on" probe based on AuNCs-AuNPs ensembles, which detected l-cysteine (l-Cys) with high selectivity. The strong blue fluorescence of l-hydroxyproline-capped gold nanoclusters (l-Hyp@AuNCs) at 465 nm was quenched by AuNPs via the inner filter effect. Interestingly, the fluorescence was recovered by interaction with l-Cys due to the electrostatic and specific Au-S interactions between l-Cys and AuNPs. The effect of the l-Cys amount on the fluorescence "off-on" efficiency showed good linearity in the range of 1.5-35.0 µM (R2 = 0.986) with a detection limit of 1.4 µM (3σ). The proposed method was successfully applied to test the serum l-Cys levels without the interference of glutathione, homocysteine and methionine. The AuNCs-AuNPs ensembles-based fluorescence "turn-off-on" protocol shows great potential in specific biothiol sensing.

14.
Sci Total Environ ; 716: 137015, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32036134

RESUMO

A large amount of spent coffee grounds is produced as a processing waste each year during making the coffee beverage. Sulfonamide antibiotics (SAs) are frequently detected in the environment and cause pollution problems. In this study, biochar (BC) and hydrochar (HC) were derived from spent coffee grounds through pyrolysis and hydrothermal carbonization, respectively. Their characteristics and sulfonamide antibiotics adsorption were investigated and compared with reference to adsorption capacity, adsorption isotherm and kinetics. Results showed BC possessed more carbonization and less oxygen-containing functional groups than HC when checked by Elemental Analysis, X-ray diffraction, X-ray photoelectron spectrometry and Fourier transform infrared. These groups affected the adsorption of sulfonamide antibiotics and adsorption mechanism. The maximum adsorption capacities of BC for sulfadiazine (SDZ) and sulfamethoxazole (SMX) were 121.5 µg/g and 130.1 µg/g at 25 °C with the initial antibiotic concentration of 500 µg/L, respectively. Meanwhile the maximum adsorption capacities of HC were 82.2 µg/g and 85.7 µg/g, respectively. Moreover, the adsorption mechanism for SAs adsorbed onto BC may be dominated by π-π electron donor-acceptor interactions, yet the SAs adsorption to HC may be attributed to hydrogen bonds. Further analysis of the adsorption isotherms and kinetics, found that physical and chemical interactions were involved in the SAs adsorption onto BC and HC. Overall, results suggested that: firstly, pyrolysis was an effective thermochemical conversion of spent coffee grounds; and secondly, BC was the more promising adsorbent for removing sulfonamide antibiotics.


Assuntos
Café , Adsorção , Antibacterianos , Carvão Vegetal , Cinética , Sulfonamidas , Poluentes Químicos da Água
15.
Sci Total Environ ; 716: 136682, 2020 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-32059319

RESUMO

OBJECTIVE: To examine the association between absolute humidity (AH) and influenza and pneumonia (P&I) mortality, and to quantify P&I mortality burden attributable to non-optimum AHs among elderly people aged ≥65 years in Chongqing, the largest municipality of China. METHODS: Daily data of P&I mortality from 2012 to 2018, and the contemporaneous meteorological data in the study area were collected. Distributed lag non-linear model (DLNM) was applied to estimate the non-linear and delayed effects of absolute humidity (AH) on P&I mortality. Then, attributable deaths were calculated for the dry and moist AH, defined as AH below and above the minimum mortality AH (MMAH), respectively. Moderate and extreme AHs were defined using cutoffs at the 2.5th and 97.5th percentiles of AH. RESULTS: The relationship between AH and P&I mortality was a U-shaped curve. The MMAH was 11.5 g/m3 (46.4th percentile). In total, 25.7% (95% confidence interval: 10.0-38.2) of P&I mortality (4673 deaths) was attributed to non-optimum AHs. Low AHs were responsible for 12.7% of the P&I death burden (95%CI: 0.2-20.1), while high AHs for 13.0% (95%CI: -9.4-25.7). Extreme low and high AHs accounted for 3.7% (95%CI: 0.1-6.8) and 3.0% (95%CI: 0-5.4) of P&I mortality. CONCLUSIONS: Our study showed that both low AHs and high AHs are responsible for considerable AH-related P&I mortality burden among elderly people. Our results may have important public health implications for the development of relevant intervention policies to reduce P&I deaths among the elderly.


Assuntos
Influenza Humana , Pneumonia , Idoso , China , Cidades , Temperatura Alta , Humanos , Umidade , Mortalidade
16.
Biosystems ; 191-192: 104103, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32044422

RESUMO

Soft tissue and organ modeling is the most critical function of any virtual surgical system. This study proposes a softness-based adaptive mesh refinement algorithm to simultaneously ensure realistic and real-time soft tissue simulation. The algorithm was constructed to consider that in a virtual surgery scenario, the surgical sites involve large deformation and thus require high simulation precision, whereas the nonsurgical sites involve small deformations and thus require low simulation precision. This study used the stomach lining as an example, applying mesh refinement in the deformation sites of the stomach lining to enhance the accuracy of the simulations. In addition, low mesh models were adopted for nonsurgical sites to ensure computing efficiency.

17.
JAMA Neurol ; 77(5): 561-573, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32080711

RESUMO

Importance: Several randomized clinical trials have recently established the safety and efficacy of endovascular treatment (EVT) of acute ischemic stroke in the anterior circulation. However, it remains uncertain whether patients with acute basilar artery occlusion (BAO) benefit from EVT. Objective: To evaluate the association between EVT and clinical outcomes of patients with acute BAO. Design, Setting, and Participants: This nonrandomized cohort study, the EVT for Acute Basilar Artery Occlusion Study (BASILAR) study, was a nationwide prospective registry of consecutive patients presenting with an acute, symptomatic, radiologically confirmed BAO to 47 comprehensive stroke centers across 15 provinces in China between January 2014 and May 2019. Patients with acute BAO within 24 hours of estimated occlusion time were divided into groups receiving standard medical treatment plus EVT or standard medical treatment alone. Main Outcomes and Measures: The primary outcome was the improvement in modified Rankin Scale scores (range, 0 to 6 points, with higher scores indicating greater disability) at 90 days across the 2 groups assessed as a common odds ratio using ordinal logistic regression shift analysis, adjusted for prespecified prognostic factors. The secondary efficacy outcome was the rate of favorable functional outcomes defined as modified Rankin Scale scores of 3 or less (indicating an ability to walk unassisted) at 90 days. Safety outcomes included symptomatic intracerebral hemorrhage and 90-day mortality. Results: A total of 1254 patients were assessed, and 829 patients (of whom 612 were men [73.8%]; median [interquartile] age, 65 [57-74] years) were recruited into the study. Of these, 647 were treated with standard medical treatment plus EVT and 182 with standard medical treatment alone. Ninety-day functional outcomes were substantially improved by EVT (adjusted common odds ratio, 3.08 [95% CI, 2.09-4.55]; P < .001). Moreover, EVT was associated with a significantly higher rate of 90-day modified Rankin Scale scores of 3 or less (adjusted odds ratio, 4.70 [95% CI, 2.53-8.75]; P < .001) and a lower rate of 90-day mortality (adjusted odds ratio, 2.93 [95% CI, 1.95-4.40]; P < .001) despite an increase in symptomatic intracerebral hemorrhage (45 of 636 patients [7.1%] vs 1 of 182 patients [0.5%]; P < .001). Conclusions and Relevance: Among patients with acute BAO, EVT administered within 24 hours of estimated occlusion time is associated with better functional outcomes and reduced mortality.

18.
Plant Dis ; 104(4): 1041-1047, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31999220

RESUMO

The gray mold caused by Botrytis cinerea has a significant impact on tomato production throughout the world. Although the synthetic fungicide fludioxonil can effectively control B. cinerea, there have been several reports of resistance to this fungicide. This study indicated that all of the fludioxonil-resistant strains tested, including one field-resistant isolate and four laboratory strains, had reduced fitness relative to sensitive isolates. In addition to having reduced growth, sporulation, and pathogenicity, the resistant strains were more sensitive to osmotic stress and had significantly (P < 0.05) higher peroxidase activity. BOs1, a kinase in the high-osmolarity glycerol stress response signal transduction pathway, is believed to harbor mutations related to fludioxonil resistance. Sequence analysis of their BOs1 sequences indicated that the fludioxonil-resistant field isolate, XXtom1806, had four point mutations resulting in four amino acid changes (I365S, S531G, T565N, and T1267A) and three amino acids (I365S, S531G, and T565N) in the histidine kinases, adenylyl cyclases, methyl-accepting chemotaxis receptors, and phosphatases domain, which associated with fludioxonil binding. Similarly, two of the laboratory strains, XXtom-Lab1 and XXtom-Lab4, had three (Q846S, I1126S, and G415D) and two (P1051S and V1241M) point mutations, respectively. A third strain, XXtom-lab3, had a 52-bp insertion that included a stop codon at amino acid 256. Interestingly, the BOs1 sequence of the fourth laboratory strain, XXtom-lab5, was identical to those of the sensitive isolates, indicating that an alternative resistance mechanism exists. The study also found evidence of positive cross-resistance between fludioxonil and the dicarboximide fungicides procymidone and iprodione, but no cross-resistance was detected with any other fungicides tested, including boscalid, carbendazim, tebuconazole, and fluazinam.


Assuntos
Botrytis , Farmacorresistência Fúngica , China , Dioxóis , Proteínas Fúngicas , Doenças das Plantas , Pirróis
19.
J Infect Public Health ; 13(1): 46-50, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31548166

RESUMO

OBJECTIVE: We investigated the epidemiological characteristics of norovirus infection from 2011 to 2016 in Chongqing, China, in order to provide evidence for strategies on epidemic prevention and control. METHODS: We collected data on norovirus infectious diarrhea epidemics in 38 districts and counties, and analyzed the information using descriptive epidemiological methods. RESULTS: In 2011, the first case of norovirus infectious diarrhea in Chongqing was reported. From 2011 to 2015, 38 districts and counties in Chongqing reported a total of 4 epidemics. In 2016, however, the city reported 117 outbreaks. From 2011 to 2016, there were 1637 cases of norovirus infection but no deaths. In 2016, most outbreaks occurred over a 5-month period with a clear peak in December and higher incidence in major urban areas than smaller communities (83.61% vs. 16.39%). Of these 1637 cases, 99.18% occurred in urban schools and nurseries, and 80% were transmitted person-to-person. Infection by genogroup II genotype 2 (GII.2) viruses accounted for 98.71% of cases. Leukocytes were increased in 67.81% of patients, neutrophils in 65%, and lymphocytes in 50%. Medical treatment was sought by 70% of patients or guardians but only 3.66% of cases were hospitalized. The most frequent misdiagnosis was "suspected food poisoning". CONCLUSION: The frequency of norovirus infectious diarrhea epidemics increased over 20-fold from 2011 to 2016 in Chongqing, China. These epidemics occurred predominantly in urban schools and nurseries. However, epidemics showed little spread to outlying districts and counties, so prevention and control pressures were relatively high. SUGGESTIONS: Healthcare professionals and institutions should strengthen health education for groups at high-risk of norovirus infection, such as school children, and increase norovirus testing capacity to further improve emergency investigation. Prevention and control knowledge should be disseminated to the general public to reduce transmission risk and total disease burden. Finally, governments and health administrative departments should invest special funds to prevent and control norovirus epidemics.

20.
FEBS Open Bio ; 10(1): 135-146, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31729835

RESUMO

The Sry-related high-mobility group box6 (SOX6) has been implicated in the development of cancer, but its role in lung cancer is incompletely understood. Here, we report that SOX6 expression is frequently down-regulated in lung adenocarcinoma tissues. Moreover, SOX6 can inhibit the proliferation and invasion of lung adenocarcinoma cells, which may occur through cell cycle arrest at G1/S due to up-regulation of p53 and p21CIPI and down-regulation of cyclin D1 and ß-catenin. Univariate and multivariate analyses revealed that the expression of SOX6 is significantly associated with patient disease-related survival and is an independent prognostic factor for lung adenocarcinoma. These data suggest that SOX6 may act as a suppressor of lung adenocarcinoma.

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