Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 713
Filtrar
1.
Radiat Oncol ; 16(1): 201, 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34641928

RESUMO

PURPOSE: To develop a nomogram model for predicting local progress-free survival (LPFS) in esophageal squamous cell carcinoma (ESCC) patients treated with concurrent chemo-radiotherapy (CCRT). METHODS: We collected the clinical data of ESCC patients treated with CCRT in our hospital. Eligible patients were randomly divided into training cohort and validation cohort. The least absolute shrinkage and selection operator (LASSO) with COX regression was performed to select optimal radiomic features to calculate Rad-score for predicting LPFS in the training cohort. The univariate and multivariate analyses were performed to identify the predictive clinical factors for developing a nomogram model. The C-index was used to assess the performance of the predictive model and calibration curve was used to evaluate the accuracy. RESULTS: A total of 221 ESCC patients were included in our study, with 155 patients in training cohort and 66 patients in validation cohort. Seventeen radiomic features were selected by LASSO COX regression analysis to calculate Rad-score for predicting LPFS. The patients with a Rad-score ≥ 0.1411 had high risk of local recurrence, and those with a Rad-score < 0.1411 had low risk of local recurrence. Multivariate analysis showed that N stage, CR status and Rad-score were independent predictive factors for LPFS. A nomogram model was built based on the result of multivariate analysis. The C-index of the nomogram was 0.745 (95% CI 0.7700-0.790) in training cohort and 0.723(95% CI 0.654-0.791) in validation cohort. The 3-year LPFS rate predicted by the nomogram model was highly consistent with the actual 3-year LPFS rate both in the training cohort and the validation cohort. CONCLUSION: We developed and validated a prediction model based on radiomic features and clinical factors, which can be used to predict LPFS of patients after CCRT. This model is conducive to identifying the patients with ESCC benefited more from CCRT.

2.
Int J Mol Med ; 48(6)2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34643254

RESUMO

Schizandrin A (SchA) can be extracted from the vine plant Schisandra chinensis and has been reported to confer various biologically active properties. However, its potential biological effects on non­small cell lung cancer (NSCLC) remain unknown. Therefore, the present study aims to address this issue. NSCLC and normal lung epithelial cell lines were first treated with SchA. Cell viability and proliferation were measured using CellTiter­Glo Assay and colony formation assays, respectively. PI staining was used to measure cell cycle distribution. Cell cycle­related proteins p53, p21, cyclin D1, CDK4, CDK6, cyclin E1, cyclin E2, CDK2 and DNA damage­related protein SOX4 were detected by western blot analysis. Annexin V­FITC/PI staining, DNA electrophoresis and Hoechst 33342/PI dual staining were used to detect apoptosis. JC­1 and DCFH­DA fluorescent dyes were used to measure the mitochondrial membrane potential and reactive oxygen species concentrations, respectively. Apoptosis­related proteins caspase­3, cleaved caspase­3, poly(ADP­ribose) polymerase (PARP), cleaved PARP, BimEL, BimL, BimS, Bcl2, Bax, caspase­9 and cleaved caspas­9 were measured by western blot analysis. Dansylcadaverine was used to detect the presence of the acidic lysosomal vesicles. The expression levels of the autophagy­related proteins LC3­I/II, p62/SQSTM and AMPKα activation were measured using western blot analysis. In addition, the autophagy inhibitor 3­methyladenine was used to inhibit autophagy. SchA treatment was found to reduce NSCLC cell viability whilst inhibiting cell proliferation. Low concentrations of SchA (10­20 µM) mainly induced G1/S­phase cell cycle arrest. By contrast, as the concentration of SchA used increases (20­50 µM), cells underwent apoptosis and G2/M­phase cell cycle a13rrest. As the treatment concentration of SchA increased from 0 to 50 µM, the expression of p53 and SOX4 protein also concomitantly increased, but the expression of p21 protein was increased by 10 µM SchA and decreased by higher concentrations (20­50 µM). In addition, the mRNA and protein expression levels of Bcl­like 11 (Bim)EL, BimL and BimS increased following SchA application. SchA induced the accumulation of acidic vesicles and induced a marked increase in the expression of LC3­II protein, suggsting that SchA activated the autophagy pathway. However, the expression of the p62 protein was found to be increased by SchA, suggesting that p62 was not degraded during the autophagic flux. The 3­methyladenine exerted no notable effects on SchA­induced apoptosis. Taken together, results from the present study suggest that SchA exerted inhibitory effects on NSCLC physiology by inducing cell cycle arrest and apoptosis. In addition, SchA partially induced autophagy, which did not result in any cytoprotective effects.

3.
Zhongguo Zhong Yao Za Zhi ; 46(12): 3106-3115, 2021 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-34467702

RESUMO

To obtain the difference of the fungal and bacterial community diversity between wild Cordyceps sinensis, artificial C. sinensis and their habitat soil, Illmina Hiseq high-throughput sequencing technology was applied. The results show that Proteobacteria was the dominant bacterial phylum in C. sinensis, Actinobacteria was the dominant bacterial phylum in soil microhabitat, Ophiocordyceps sinensis was the predominant dominant fungus of C. sinensis. The α diversity analysis showed that the fungal diversity of stroma was lower than other parts, and the fungal diversity of wild C. sinensis was lower than that of artificial C. sinensis. The ß diversity analysis showed that the fungal and bacterial community diversity of soil microhabitat samples was significantly different from that of C. sinensis. The fungal community diversity was less different between wild and artificial C. sinensis, especially in sclerotia. LEfSe analysis showed a lot of species diversity between wild and artificial C. sinensis. Those different species between wild C. sinensis, artificial C. sinensis and their habitat soil provide ideas for further research on breed and components of C. sinensis.


Assuntos
Cordyceps , Microbiota , Cordyceps/genética , Sequenciamento de Nucleotídeos em Larga Escala , Microbiota/genética , Solo , Microbiologia do Solo
4.
Virus Res ; 305: 198553, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34487767

RESUMO

COVID-19 is seriously threatening human health all over the world. A comprehensive understanding of the genetic mechanisms driving the rapid evolution of its pathogen (SARS-CoV-2) is the key to controlling this pandemic. In this study, by comparing the entire genome sequences of SARS-CoV-2 isolates from Asia, Europe and America, and analyzing their phylogenetic histories, we found a lineage derived from a recombination event that likely occurred before March 2020. More importantly, the recombinant offspring has become the dominant strain responsible for more than one-third of the global cases in the pandemic. These results indicated that the recombination might have played a key role in the pandemic of the virus.

5.
Reproduction ; 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34591784

RESUMO

As a multifunctional transcription factor, YY1 regulates the expression of many genes essential for early embryonic development. RTCB is an RNA ligase that plays a role in tRNA maturation and Xbp1 mRNA splicing. YY1 can bind in vitro to the response element in the proximal promoter of Rtcb and regulate Rtcb promoter activity. However, the in vivo regulation and whether these two genes are involved in the mother-fetal dialogue during early pregnancy remain unclear. In this study, we validated that YY1 bound in vivo to the proximal promoter of Rtcb in mouse uterus of early pregnancy. Moreover, via building a variety of animal models, our study suggested that both YY1 and RTCB might play a role in mouse uterus decidualization and embryo implantation during early pregnancy.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34585912

RESUMO

Electrocatalytic nitrogen reduction reaction (NRR) is a promising method for sustainable production of NH3, which provides an alternative to the traditional Haber-Bosch process. However, the poor Faraday efficiency caused by N≡N triple bond activation and competitive hydrogen evolution reaction (HER) have seriously hindered the application of NRR. In this work, a novel strategy to promote NRR through boron-transition-metal (TM) hybrid double-atom catalysts (HDACs) has been proposed. The excellent catalytic activity of HDACs is attributed to a significant difference of valence electron distribution between boron and TMs, which could better activate N≡N bonds and promote the conversion of NH2 to NH3 compared with boron or metal single-atom catalysts and traditional double-atom catalysts (DACs). Hence, by means of DFT computations, the stability, activity, and selectivity of 29 HDACs are systematically investigated to evaluate their catalytic performance. B-Ti@g-CN and B-Ta@g-CN are screened as excellent nitrogen-fixing catalysts with particularly low limiting potentials of 0.13 and 0.11 V for NRR and rather high potentials of 0.54 and 0.82 V for HER, respectively. This work provides a new idea for the rational design of efficient nitrogen-fixing catalysts and could also be widely used in other catalytic reactions.

7.
Environ Res ; : 112077, 2021 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-34560060

RESUMO

The negative consequences, such as healthy and environmental issues, brought by rapid urbanization and interactive human activities result in increasing social uncertainties, unreliable predictions, and poor management decisions. For instance, the Coronavirus Disease (COVID-19) occurred in 2019 has been plaguing many countries. Aiming at controlling the spread of COVID-19, countries around the world have adopted various mitigation and suppression strategies. However, how to comprehensively eva luate different mitigation strategies remains unexplored. To this end, based on the Artificial societies, Computational experiments, Parallel execution (ACP) approach, we proposed a system model, which clarifies the process to collect the necessary data and conduct large-scale computational experiments to evaluate the effectiveness of different mitigation strategies. Specifically, we established an artificial society of Wuhan city through geo-environment modeling, population modeling, contact behavior modeling, disease spread modeling and mitigation strategy modeling. Moreover, we established an evaluation model in terms of the control effects and economic costs of the mitigation strategy. With respect to the control effects, it is directly reflected by indicators such as the cumulative number of diseases and deaths, while the relationship between mitigation strategies and economic costs is built based on the CO2 emission. Finally, large-scale simulation experiments are conducted to evaluate the mitigation strategies of six countries. The results reveal that the more strict mitigation strategies achieve better control effects and less economic costs.

8.
Virus Res ; 304: 198525, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34339774

RESUMO

Novirhabdoviruses belong to the Rhabdoviridae family of RNA viruses. All of the four members are pathogenic for bony fish. Particularly, Infectious hematopoietic necrosis virus (IHNV) and Viral hemorrhagic septicemia virus (VHSV) often cause mass animal deaths and huge economic losses, representing major obstacles to fish farming industry worldwide. The interactions between fish and novirhabdoviruses are becoming better understood. In this review, we will present our current knowledge of fish innate immunity, particularly type I interferon (IFN-I) response, against novirhabdoviral infection, and the evasion strategies exploited by novirhabdoviruses. Members of Toll-like receptors (TLRs) and RIG-I-like receptors (RLRs) appear to be involved in novirhabdovirus surveillance. NF-κB activation and IFN-I induction are primarily triggered for antiviral defense. Autophagy can also be induced by viral glycoprotein (G). Although sensitive to IFN-I, novirhabdoviruses have nucleoprotein (N), matrix protein (M), and non-virion protein (NV) to interfere with host signal transduction and gene expression steps toward antiviral state establishment. Moreover, novirhabdoviruses may exploit some microRNAs for immunosuppression.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34374788

RESUMO

Heavy metal pollution in agricultural soils poses a direct threat to food safety and human health. It has been shown that the colloids is the carrier of heavy metal transport in the polluted soil by heavy metals, but the sources of heavy metals in the soil and colloids and their interrelations are not transparent at present. This study aims to investigate the distribution characteristics of heavy metals in agricultural soils near mining areas, and reveal the relevance of heavy metal content in colloids with total content in soils and their chemical species in soils. Results showed that the concentrations of Mn, Zn, and Pb in agricultural soils and colloids were higher than those of other heavy metals. The content of heavy metals in colloids was positively correlated with the total content of heavy metals in soil. Heavy metals in soil could be easily combined by humus-like substances and tryptophan-like protein in the colloids. The primary source of heavy metals in soil and colloids was mining activities. This study provides theoretical support for revealing the pollution characteristics and migration of heavy metals in agricultural soils and colloids around mining areas.

10.
ChemSusChem ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34383996

RESUMO

Clusters of nitrogen- and carbon-coordinated transition metals dispersed in a carbon matrix (e. g., Fe-N-C) have emerged as an inexpensive class of electrocatalysts for the oxygen reduction reaction (ORR). Here, it was shown that optimizing the interaction between the nitrogen-coordinated transition metal clusters embedded in a more stable and corrosion-resistant carbide matrix yielded an ORR electrocatalyst with enhanced activity and stability compared to Fe-N-C catalysts. Utilizing first-principles calculations, an electrostatics-based descriptor of catalytic activity was identified, and nitrogen-coordinated iron (FeN4 ) clusters embedded in a TiC matrix were predicted to be an efficient platinum-group metal (PGM)-free ORR electrocatalyst. Guided by theory, selected catalyst formulations were synthesized, and it was demonstrated that the experimentally observed trends in activity fell exactly in line with the descriptor-derived theoretical predictions. The Fe-N-TiC catalyst exhibited enhanced activity (20 %) and durability (3.5-fold improvement) compared to a traditional Fe-N-C catalyst. It was posited that the electrostatics-based descriptor provides a powerful platform for the design of active and stable PGM-free electrocatalysts and heterogenous single-atom catalysts for other electrochemical reactions.

11.
Nat Commun ; 12(1): 5092, 2021 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34429430

RESUMO

Development of a versatile, sustainable and efficient photosynthesis system that integrates intricate catalytic networks and energy modules at the same location is of considerable future value to energy transformation. In the present study, we develop a coenzyme-mediated supramolecular host-guest semibiological system that combines artificial and enzymatic catalysis for photocatalytic hydrogen evolution from alcohol dehydrogenation. This approach involves modification of the microenvironment of a dithiolene-embedded metal-organic cage to trap an organic dye and NADH molecule simultaneously, serving as a hydrogenase analogue to induce effective proton reduction inside the artificial host. This abiotic photocatalytic system is further embedded into the pocket of the alcohol dehydrogenase to couple enzymatic alcohol dehydrogenation. This host-guest approach allows in situ regeneration of NAD+/NADH couple to transfer protons and electrons between the two catalytic cycles, thereby paving a unique avenue for a synergic combination of abiotic and biotic synthetic sequences for photocatalytic fuel and chemical transformation.


Assuntos
Etanol/química , Fotossíntese/fisiologia , Luz Solar , Catálise , Corantes , Elétrons , Hidrogênio/química , Hidrogenase/química , Cinética , Ligantes , Simulação de Acoplamento Molecular
12.
Phys Chem Chem Phys ; 23(30): 16023-16032, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34286764

RESUMO

The effects of small organic molecule (SOM) adsorption with benzene (C6H6), hexafluorobenzene (C6F6), and p-difluorobenzene (C6H4F2) on the electronic properties of stanene under external electric fields are investigated through first-principles calculations. Different adsorption sites and molecular orientations are considered to determine the most stable configurations of small organic molecule (SOM) adsorption on the surface of stanene. The results show that the internal electric field caused by the adsorption of small organic molecules destroys the symmetry of the two sublattices of stanene in C6H6/stanene, C6F6/stanene and C6H4F2/stanene systems with the most stable configurations, opening the band gaps of stanene with 39.5, 18.9 and 14.5 meV, respectively. Under an external electric field, a wide range of linearly tunable and sizable direct band gaps (31.6-420.1 meV for the C6H6/stanene system, 14.8-587.2 meV for the C6F6/stanene system and 14.5-490.2 meV for the C6H4F2/stanene system) are merely determined by the strength of the composite electric field despite its direction. The mechanism of charge transfer between stanene and organic molecules under an external electric field can be revealed using an equivalent capacitor model to explain the tunable charge transfer. More importantly, the high carrier mobility of the stable SOM/stanene systems under an external electric field is largely retained due to the weak interactions at the interface. These results indicate that the electronic properties of stanene can be effectively modulated by the surface adsorption of organic molecules under an external electric field, providing effective and reversible routes to enhance the performance of stanene for novel electronic devices in the future.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34270436

RESUMO

Despite the remarkable successes of convolutional neural networks (CNNs) in computer vision, it is time-consuming and error-prone to manually design a CNN. Among various neural architecture search (NAS) methods that are motivated to automate designs of high-performance CNNs, the differentiable NAS and population-based NAS are attracting increasing interests due to their unique characters. To benefit from the merits while overcoming the deficiencies of both, this work proposes a novel NAS method, RelativeNAS. As the key to efficient search, RelativeNAS performs joint learning between fast learners (i.e., decoded networks with relatively lower loss value) and slow learners in a pairwise manner. Moreover, since RelativeNAS only requires low-fidelity performance estimation to distinguish each pair of fast learner and slow learner, it saves certain computation costs for training the candidate architectures. The proposed RelativeNAS brings several unique advantages: 1) it achieves state-of-the-art performances on ImageNet with top-1 error rate of 24.88%, that is, outperforming DARTS and AmoebaNet-B by 1.82% and 1.12%, respectively; 2) it spends only 9 h with a single 1080Ti GPU to obtain the discovered cells, that is, 3.75x and 7875x faster than DARTS and AmoebaNet, respectively; and 3) it provides that the discovered cells obtained on CIFAR-10 can be directly transferred to object detection, semantic segmentation, and keypoint detection, yielding competitive results of 73.1% mAP on PASCAL VOC, 78.7% mIoU on Cityscapes, and 68.5% AP on MSCOCO, respectively. The implementation of RelativeNAS is available at https://github.com/EMI-Group/RelativeNAS.

14.
World Neurosurg ; 154: e222-e235, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34252631

RESUMO

OBJECTIVE: To conduct a systematic review and meta-analysis comparing the fusion rate after spinal fusion surgery between smokers and nonsmokers. METHODS: We searched PubMed, Embase, Cochrane Library, and Web of Science electronic databases through March 10, 2021 for cohort and case-control studies assessing the effect of smoking on the fusion rate of spinal fusion surgery. Two researchers independently screened the literature and extracted data according to the inclusion and exclusion criteria. Statistical analysis was performed using RevMan, version 5.4. RESULTS: A total of 26 studies, including 4 case-control studies and 22 cohort studies, with 4409 patients, were included in the present meta-analysis. Follow-up was at least 6 months. Overall, the pooled results demonstrated that the fusion rate of smokers after spinal fusion was significantly lower than that of nonsmokers. The odds ratio (OR) was 0.55 (95% confidence interval [CI] 0.45-0.67, P < 0.0001). Subgroup analyses by fusion level showed the adverse effect of smoking on the fusion rate at single level (OR 0.61, 95% CI 0.41-0.91, P = 0.02) was more significant than that of multiple levels (OR 0.55, 95% CI 0.38-0.80, P = 0.0010). Subgroup analysis according to the type of bone graft revealed an apparent association between smoking and fusion rate in the autograft subgroup (OR 0.47, 95% CI 0.33-0.66, P < 0.0001) but not in the allograft subgroup (OR 0.69, 95% CI 0.47-1.01, P = 0.06). CONCLUSIONS: The fusion rate of smokers is significantly lower than that of nonsmokers in spinal fusion surgery. Smokers should be encouraged to quit smoking to improve the outcome of spinal fusion surgery.

15.
Se Pu ; 39(8): 775-780, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34212579

RESUMO

A critical need in analytical chemistry is the efficient fabrication of selective and sensitive sensors to detect trace analytes in complicated samples. In recent years, fluorescence analysis has been widely used in environmental research and the life sciences due to its high sensitivity and simple operation. Quantum dots (QDs) are a new type of fluorescent nanomaterials. Owing to the quantum confinement effect, QDs possess excellent optical properties such as strong anti-bleaching ability, a narrow excitation and emission band, and tunable emission wavelength. As a hot labeling material, QDs are suitable for use in surface-modified analytical sensors employed in fields such as analytical chemistry, biology, and medicine. However, QD materials have a notable disadvantage, in that the actual sample matrix may contain some interferents with luminescent responses similar to those of the target; this decreases the selective ability of the fluorescence sensor. The surface modification of QDs via the molecular imprinting technique (MIT) is a promising solution to overcome this drawback. Molecularly imprinted polymers (MIPs) are a kind of "bionic" material that can carry out specific recognition and selective adsorption and hence, possess the unique properties of recognition specificity, structural predictability, good reproducibility, and excellent stability. Accordingly, MIPs have been widely employed in sensors as well as for drug delivery, catalysis, and solid phase extraction. Notably, QD-based molecularly imprinted fluorescence sensors combine the advantages of QDs and the MIT. Owing to their specific selectivity and high sensitivity, such sensors have been extensively developed for environmental monitoring, food detection, and biological analysis. However, there remain challenges associated with the preparation and application of the sensors: (i) single recognition: it is important to develop a composite sensor that can detect multiple target analytes from the actual samples at the same time during practical application; (ii) poor hydrophilicity: the actual sample is usually a liquid matrix; hence, it is imperative to determine an approach for improving the hydrophilicity of the sensor; (iii) the accuracy of fluorescence response and the resolution of visual detection need to be further improved; (iv) imprinting: it remains challenging to imprint biological macromolecules, viruses, and bacteria. Thus far, many researchers have made progress with regard to the preparation and application of the sensors. Accordingly, this work reviews approximately 20 papers published by the American Chemical Society, Elsevier, and other databases in the last five years to highlight progress in novel preparation methods and practical applications of QD-based molecularly imprinted fluorescence sensors for the sensitive analysis and rapid detection of trace substances. First, according to the different numbers of emission peaks in the fluorescence spectrum, three kinds of QD-based molecularly imprinted fluorescence sensors are introduced and the related recognition mechanisms are explained. Second, according to the different substances to be detected, this mini-review summarizes the latest research progress in sensors for the detection of ions, organic small molecules, biological macromolecules, as well as for the analysis of bacteria and viruses. Finally, existing challenges associated with the preparation and application of the sensors, as well as future development trends, are discussed.


Assuntos
Impressão Molecular , Pontos Quânticos , Fluorescência , Polímeros Molecularmente Impressos , Reprodutibilidade dos Testes
16.
Genome Biol ; 22(1): 175, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108023

RESUMO

BACKGROUND: The maize inbred line A188 is an attractive model for elucidation of gene function and improvement due to its high embryogenic capacity and many contrasting traits to the first maize reference genome, B73, and other elite lines. The lack of a genome assembly of A188 limits its use as a model for functional studies. RESULTS: Here, we present a chromosome-level genome assembly of A188 using long reads and optical maps. Comparison of A188 with B73 using both whole-genome alignments and read depths from sequencing reads identify approximately 1.1 Gb of syntenic sequences as well as extensive structural variation, including a 1.8-Mb duplication containing the Gametophyte factor1 locus for unilateral cross-incompatibility, and six inversions of 0.7 Mb or greater. Increased copy number of carotenoid cleavage dioxygenase 1 (ccd1) in A188 is associated with elevated expression during seed development. High ccd1 expression in seeds together with low expression of yellow endosperm 1 (y1) reduces carotenoid accumulation, accounting for the white seed phenotype of A188. Furthermore, transcriptome and epigenome analyses reveal enhanced expression of defense pathways and altered DNA methylation patterns of the embryonic callus. CONCLUSIONS: The A188 genome assembly provides a high-resolution sequence for a complex genome species and a foundational resource for analyses of genome variation and gene function in maize. The genome, in comparison to B73, contains extensive intra-species structural variations and other genetic differences. Expression and network analyses identify discrete profiles for embryonic callus and other tissues.

17.
Cancer Med ; 10(13): 4387-4396, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34061467

RESUMO

Moreau score has been used to differentiate chronic lymphocytic leukemia (CLL) from other mature B-cell neoplasms. However, it showed limitations in Asian patients. Therefore, we conducted a new score system replacing CD5 and CD23 with CD43 and CD180 to evaluate its diagnostic value of CLL. 237 untreated samples diagnosed with mature B-cell neoplasms were collected and were randomly divided into an exploratory and a validation cohort by a 2:1 ratio. The expression of CD5, CD19, CD20, CD23, CD43, CD79b, CD180, CD200, FMC7, and surface immunoglobulin (SmIg) were analyzed among all the samples. A proposed score was developed based on the logistic regression model. The sensitivity and specificity of the proposed score were calculated by ROC curves. CD43/CD180, CD200, FMC7, and CD79b were included in our new CLL score, which showed a sensitivity of 91.8% and a specificity of 83.1%. These results were confirmed in a validation cohort with a sensitivity of 90.5% (p = 0.808) and a specificity of 79.5% (p = 0.639). In CD5 negative or CD23 negative CLL group, the new CLL score displayed improved sensitivity of 79.4% compared to Moreau score and CLLflow score (41.2% and 47.1%, respectively). In atypical CLL group, the new CLL score showed improved sensitivity of 84.2% compared to Moreau score and CLLflow score (61.4% and 64.9%, respectively). This proposed atypical CLL score helped to offer an accurate differentiation of CLL from non-CLL together with morphological and molecular methods, particularly in Chinese patients with atypical immunophenotype.

18.
BMC Biol ; 19(1): 117, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-34088313

RESUMO

BACKGROUND: The vacuole/lysosome is the final destination of autophagic pathways, but can also itself be degraded in whole or in part by selective macroautophagic or microautophagic processes. Diverse molecular mechanisms are involved in these processes, the characterization of which has lagged behind those of ATG-dependent macroautophagy and ESCRT-dependent endosomal multivesicular body pathways. RESULTS: Here we show that as yeast cells gradually exhaust available nutrients and approach stationary phase, multiple vacuolar integral membrane proteins with unrelated functions are degraded in the vacuolar lumen. This degradation depends on the ESCRT machinery, but does not strictly require ubiquitination of cargos or trafficking of cargos out of the vacuole. It is also temporally and mechanistically distinct from NPC-dependent microlipophagy. The turnover is facilitated by Atg8, an exception among autophagy proteins, and an Atg8-interacting vacuolar membrane protein, Hfl1. Lack of Atg8 or Hfl1 led to the accumulation of enlarged lumenal membrane structures in the vacuole. We further show that a key function of Hfl1 is the membrane recruitment of Atg8. In the presence of Hfl1, lipidation of Atg8 is not required for efficient cargo turnover. The need for Hfl1 can be partially bypassed by blocking Atg8 delipidation. CONCLUSIONS: Our data reveal a vacuolar membrane protein degradation process with a unique dependence on vacuole-associated Atg8 downstream of ESCRTs, and we identify a specific role of Hfl1, a protein conserved from yeast to plants and animals, in membrane targeting of Atg8.

19.
Cytometry A ; 2021 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-34173319

RESUMO

Human basophils are terminally differentiated granulocytes that are least abundant in the peripheral blood but play important roles in allergic diseases. Studies on human basophils are limited by the high cost on the isolation of human basophils by magnetic-activated cell sorting (MACS) for negative depletion of non-basophils, followed by CD123-based positive selection of basophils. Moreover, such CD123-based purification of basophils may be limited by blocking of the binding of IL-3/anti-CD123 to the surface CD123. Here we identified SSClow CD4- CD127- HLA-DR- CRTH2high as unique markers for the identification of human basophils through stringent flow cytometric analysis of leukocytes from buffy coat. We established an efficient and cost-effective method for isolating human basophils from buffy coat based on positive magnetic selection of CRTH2+ cells followed by flow cytometric sorting of SSClow CD4- CD127- HLA-DR- CRTH2high cells. Approximately 1 to 1.5 million basophils were isolated from one buffy coat with a purity of >97%. Basophils purified by this method were viable and efficiently responded to key regulators of basophils including IL-3 and anti-IgE. This method can be used for purifying human basophils for subsequent functional studies.

20.
ACS Biomater Sci Eng ; 7(7): 3242-3255, 2021 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-34189904

RESUMO

Advances in liposomal formulation carrying multiple neuroprotective drugs, such as ceftriaxone (CEF), FK506, and nilotinib, can point toward an approach to obviating the difficulties in Parkinson's disease (PD) treatment. We prepared functionalized liposomes decorated with glutathione (GSH) to penetrate the blood-brain barrier (BBB) and cardiolipin (CL) to link up apoptotic neurons. Further, the effect of CEF-FK506-nilotinib-GSH-CL-liposomes on a PD model established by SH-SY5Y cells with 1-methyl-4-phenylpyridinium-induced neurotoxicity was investigated. An increment of the mole percentage of dihexadecyl phosphate and CL increased the particle size and the absolute value of ζ potential, improved the entrapment efficiency of CEF, FK506, and nilotinib, and reduced the drug-releasing rate. The toxicity studies revealed that CEF, FK506, and nilotinib-encapsulated liposomes could enhance the survival of SH-SY5Y cells. Western blot and immunofluorescence revealed that incorporation of CL in a lipid bilayer ameliorated the docking of CEF-FK506-nilotinib-GSH-CL-liposomes at α-synuclein (α-syn), indicating a better targeting capability of the liposomes to degenerated neurons. Treatment with CEF-FK506-nilotinib-GSH-CL-liposomes reduced the expression of Bax and α-syn and promoted the expression of Bcl-2, tyrosine hydroxylase, and the dopamine transporter. GSH- and CL-conjugated liposomes showed combined activity of targeting the BBB and α-syn and augmented the efficiency of the three drugs in rescuing dopaminergic neurons for neurodegenerative therapy.


Assuntos
Dopamina , Lipossomos , Ceftriaxona/farmacologia , Neurônios Dopaminérgicos , Glutationa , Pirimidinas , Tacrolimo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...