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1.
Food Chem ; 371: 131114, 2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-34638013

RESUMO

This study aimed to examine the gelation and microstructural properties of scallop male gonad hydrolysates (SMGHs) in the presence of low-acyl gellan gum (GG) at different mass ratios. The rheological results showed that both elastic modulus and thermal stability of SMGHs were significantly improved by the addition of GG. Meanwhile, the relaxation time T23 was significantly reduced in SMGHs/GG by low-field nuclear magnetic resonance, indicating a strong interaction between SMGHs and GG. Fourier transform infrared spectroscopy indicated the blueshift of amide I and II peaks in SMGHs/GG further demonstrated the electrostatic interaction between SMGHs and GG. The network structure of SMGHs/GG binary complexes was more compact and the surface was smoother than that of SMGHs by cryo-scanning electron microscopy. Furthermore, increasing the content of GG in the SMGHs/GG binary complex significantly reinforced the gel strength and promoted the gelation process.


Assuntos
Pectinidae , Hidrolisados de Proteína , Animais , Gônadas , Masculino , Polissacarídeos Bacterianos
2.
Front Cell Dev Biol ; 9: 750023, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722533

RESUMO

The small muscle protein, x-linked (SMPX) encodes a small protein containing 88 amino acids. Malfunction of this protein can cause a sex-linked non-syndromic hearing loss, named X-linked deafness 4 (DFNX4). Herein, we reported a point mutation and a frameshift mutation in two Chinese families who developed gradual hearing loss with age. To explore the impaired sites in the hearing system and the mechanism of DFNX4, we established and validated an Smpx null mouse model using CRISPR-Cas9. By analyzing auditory brainstem response (ABR), male Smpx null mice showed a progressive hearing loss starting from high frequency at the 3rd month. Hearing loss in female mice was milder and occurred later compared to male mice, which was very similar to human beings. Through morphological analyses of mice cochleas, we found the hair cell bundles progressively degenerated from the shortest row. Cellular edema occurred at the end phase of stereocilia degeneration, followed by cell death. By transfecting exogenous fluorescent Smpx into living hair cells, Smpx was observed to be expressed in stereocilia. Through noise exposure, it was shown that Smpx might participate in maintaining hair cell bundles. This Smpx knock-out mouse might be used as a suitable model to explore the pathology of DFNX4.

3.
EMBO Mol Med ; : e14544, 2021 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-34672091

RESUMO

An essential step for SARS-CoV-2 infection is the attachment to the host cell receptor by its Spike receptor-binding domain (RBD). Most of the existing RBD-targeting neutralizing antibodies block the receptor-binding motif (RBM), a mutable region with the potential to generate neutralization escape mutants. Here, we isolated and structurally characterized a non-RBM-targeting monoclonal antibody (FD20) from convalescent patients. FD20 engages the RBD at an epitope distal to the RBM with a KD of 5.6 nM, neutralizes SARS-CoV-2 including the current Variants of Concern such as B.1.1.7, B.1.351, P.1, and B.1.617.2 (Delta), displays modest cross-reactivity against SARS-CoV, and reduces viral replication in hamsters. The epitope coincides with a predicted "ideal" vulnerability site with high functional and structural constraints. Mutation of the residues of the conserved epitope variably affects FD20-binding but confers little or no resistance to neutralization. Finally, in vitro mode-of-action characterization and negative-stain electron microscopy suggest a neutralization mechanism by which FD20 destructs the Spike. Our results reveal a conserved vulnerability site in the SARS-CoV-2 Spike for the development of potential antiviral drugs.

4.
Blood Adv ; 5(17): 3362-3372, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34477819

RESUMO

The use of umbilical cord blood transplant has been substantially limited by the finite number of hematopoietic stem and progenitor cells in a single umbilical cord blood unit. Small molecules that not only quantitatively but also qualitatively stimulate enhancement of hematopoietic stem cell (HSC) self-renewal ex vivo should facilitate the clinical use of HSC transplantation and gene therapy. Recent evidence has suggested that the cyclin-dependent kinase inhibitor, p18INK4C (p18), is a critical regulator of mice HSC self-renewal. The role of p18 in human HSCs and the effect of p18 inhibitor on human HSC expansion ex vivo need further studies. Here we report that knockdown of p18 allowed for an increase in long-term colony-forming cells in vitro. We then identified an optimized small molecule inhibitor of p18, 005A, to induce ex vivo expansion of HSCs that was capable of reconstituting human hematopoiesis for at least 4 months in immunocompromised mice, and hence, similarly reconstituted secondary recipients for at least 4 more months, indicating that cells exposed to 005A were still competent in secondary recipients. Mechanistic studies showed that 005A might delay cell division and activate both the Notch signaling pathway and expression of transcription factor HoxB4, leading to enhancement of the self-renewal of long-term engrafting HSCs and the pool of progenitor cells. Taken together, these observations support a role for p18 in human HSC maintenance and that the p18 inhibitor 005A can enhance the self-renewal of long-term HSCs.


Assuntos
Inibidor de Quinase Dependente de Ciclina p18 , Células-Tronco Hematopoéticas , Animais , Benzoatos , Ciclo Celular , Inibidor de Quinase Dependente de Ciclina p18/genética , Hematopoese , Humanos , Camundongos
6.
Viruses ; 13(8)2021 07 22.
Artigo em Inglês | MEDLINE | ID: mdl-34452287

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Most of the currently approved SARS-CoV-2 vaccines use the prototype strain-derived spike (S) protein or its receptor-binding domain (RBD) as the vaccine antigen. The emergence of several novel SARS-CoV-2 variants has raised concerns about potential immune escape. In this study, we performed an immunogenicity comparison of prototype strain-derived RBD, S1, and S ectodomain trimer (S-trimer) antigens and evaluated their induction of neutralizing antibodies against three circulating SARS-CoV-2 variants, including B.1.1.7, B.1.351, and B.1.617.1. We found that, at the same antigen dose, the RBD and S-trimer vaccines were more potent than the S1 vaccine in eliciting long-lasting, high-titer broadly neutralizing antibodies in mice. The RBD immune sera remained highly effective against the B.1.1.7, B.1.351, and B.1.617.1 variants despite the corresponding neutralizing titers decreasing by 1.2-, 2.8-, and 3.5-fold relative to that against the wild-type strain. Significantly, the S-trimer immune sera exhibited comparable neutralization potency (less than twofold variation in neutralizing GMTs) towards the prototype strain and all three variants tested. These findings provide valuable information for further development of recombinant protein-based SARS-CoV-2 vaccines and support the continued use of currently approved SARS-CoV-2 vaccines in the regions/countries where variant viruses circulate.


Assuntos
Anticorpos Amplamente Neutralizantes/imunologia , Vacinas contra COVID-19/imunologia , COVID-19/virologia , SARS-CoV-2/imunologia , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , COVID-19/imunologia , COVID-19/prevenção & controle , Vacinas contra COVID-19/genética , Humanos , Camundongos , Testes de Neutralização , SARS-CoV-2/classificação , SARS-CoV-2/genética , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/imunologia , Vacinas Sintéticas/genética , Vacinas Sintéticas/imunologia
7.
Cell Discov ; 7(1): 71, 2021 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-34408130

RESUMO

Massive production of efficacious SARS-CoV-2 vaccines is essential for controlling the ongoing COVID-19 pandemic. We report here the preclinical development of yeast-produced receptor-binding domain (RBD)-based recombinant protein SARS-CoV-2 vaccines. We found that monomeric RBD of SARS-CoV-2 could be efficiently produced as a secreted protein from transformed Pichia pastoris (P. pastoris) yeast. Yeast-derived RBD-monomer possessed functional conformation and was able to elicit protective level of neutralizing antibodies in mice. We further designed and expressed a genetically linked dimeric RBD protein in yeast. The engineered dimeric RBD was more potent than the monomeric RBD in inducing long-lasting neutralizing antibodies. Mice immunized with either monomeric RBD or dimeric RBD were effectively protected from live SARS-CoV-2 virus challenge even at 18 weeks after the last vaccine dose. Importantly, we found that the antisera raised against the RBD of a single SARS-CoV-2 prototype strain could effectively neutralize the two predominant circulating variants B.1.1.7 and B.1.351, implying broad-spectrum protective potential of the RBD-based vaccines. Our data demonstrate that yeast-derived RBD-based recombinant SARS-CoV-2 vaccines are feasible and efficacious, opening up a new avenue for rapid and cost-effective production of SARS-CoV-2 vaccines to achieve global immunization.

8.
Environ Pollut ; 289: 117899, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34358865

RESUMO

To prevent the spread of the COVID-19 epidemic, the Chinese megacity Wuhan has taken emergent lockdown measures starting on January 23, 2020. This provided a natural experiment to investigate the response of air quality to such emission reductions. Here, we decoupled the influence of meteorological and non-meteorological factors on main air pollutants using generalized additive models (GAMs), driven by data from the China National Environmental Monitoring Center (CNEMC) network. During the lockdown period (Jan. 23 - Apr. 8, 2020), PM2.5, PM10, NO2, SO2, and CO concentrations decreased significantly by 45 %, 49 %, 56 %, 39 %, and 18 % compared with the corresponding period in 2015-2019, with contributions by S(meteos) of 15 %, 17 %, 13 %, 10 %, and 6 %. This indicates an emission reduction of NOx at least 43 %. However, O3 increased by 43 % with a contribution by S(meteos) of 6 %. In spite of the reduced volatile organic compound (VOC) emissions by 30 % during the strict lockdown period (Jan. 23 - Feb. 14, 2020), which likely reduced the production of O3, O3 concentrations increased due to a weakening of the titration effect of NO. Our results suggest that conventional emission reduction (NOx reduction only) measures may not be sufficient to reduce (or even lead to an increase of) surface O3 concentrations, even if reaching the limit, and VOC-specific measures should also be taken.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , COVID-19 , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Poluição do Ar/prevenção & controle , China , Controle de Doenças Transmissíveis , Monitoramento Ambiental , Humanos , Material Particulado/análise , SARS-CoV-2
9.
Food Funct ; 12(12): 5407-5416, 2021 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-33988217

RESUMO

In this paper, some cationic dipeptides from scallop (Patinopecten yessoensis) male gonads (SMGs), which can synergistically gel with ι-carrageenan (ι-C), were screened by the in silico approach. Fourteen protein sequences of SMGs were obtained by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and nano liquid chromatography-mass spectrometry/mass spectrometry (nanoLC-MS/MS) analysis and were then hydrolyzed via in silico simulation. A total of 414 sequences were obtained with 56 duplicates, half of which were positively charged at pH 7. Among the cation sequences, 171 had good water solubility, including two amino acids (Lys and Arg). The molecular weight analysis of the cationic water-soluble sequences showed that 0.2-0.3 kDa accounted for the highest proportion. Based on the obvious synergistic effect of Lys and ι-C, 11 Lys-containing dipeptides, including Ser-Lys (SK), Thr-Lys (TK), Trp-Lys (WK), Ala-Lys (AK), Leu-Lys (LK), Gly-Lys (GK), Val-Lys (VK), Cys-Lys (CK), Asn-Lys (NK), Phe-Lys (FK), and Met-Lys (MK), were finally screened out to study gelation with ι-C. It was found that the dipeptides/ι-C formed firm gels except WK/ι-C. The values of the storage modulus (G') of 11 dipeptides/ι-C were investigated by a rheometer. The G' of 8 dipeptides/ι-C was higher than 1000 Pa. These results indicated that the in silico-screened dipeptides from SMGs can form composite gels with ι-C, which can be used for the design and development of functional hydrogels.


Assuntos
Carragenina/química , Cátions , Dipeptídeos/química , Géis/química , Pectinidae/metabolismo , Sequência de Aminoácidos , Aminoácidos/análise , Animais , Simulação por Computador , Feminino , Masculino , Fragmentos de Peptídeos , Reologia , Espectrometria de Massas em Tandem , Tripsina
10.
Ecotoxicol Environ Saf ; 220: 112329, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34020282

RESUMO

Studying the characteristics of new particle formation (NPF) is conducive to exploring the impact of atmospheric particulate matter on the climate, environment, and human health. The particle number size distributions (5.6-560 nm) of aerosols were measured using a fast mobility particle sizer (FMPS) from 1 to 11 May 2019. The clean atmosphere was one of the basic conditions for the occurrence of this continuous new particle formation events. It started between 9:00 and 12:00, and it mainly ended after 20:00. The growth rate (GR) and condensation sink (CS) values in Hefei were 2.98 ± 0.97 nm·h-1 and (3.0 ± 0.4) × 10-2 s-1, respectively. Back trajectory clustering analysis revealed that the mass concentration of the air masses from the southeastern part of Henan Province and the southern part of Anhui Province surrounding the study area were relatively high. The analysis results of the potential source contribution function (PSCF) and the concentration weighted trajectory (CWT) methods show that in addition to local pollution, the long-distance transport of pollutants in the Yangtze River Delta (YRD) greatly contributed to the accumulation modal particulate concentration in Hefei. Moreover, the population affected by PM2.5 during the observation period reached 8.19 × 104, accounting for 1.08% to the total population in Hefei. The premature death cases associated with PM2.5 reached 8.35 × 102. This study is helpful to understand the main influencing factors of consecutive NPF events and the health risks of fine particles.


Assuntos
Aerossóis/análise , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Monitoramento Ambiental , Material Particulado/análise , China , Férias e Feriados
11.
J Food Sci ; 86(5): 2024-2034, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33884631

RESUMO

This study evaluated the gel and microstructure properties of scallop (Patinopecten yessoensis) male gonads hydrolysates (SMGHs) combined with xanthan gum (XG). SMGHs/XG hydrogel matrix properties and structures were elucidated via different analysis tools such as rheometry, LF-NMR, FTIR, AFM, and Cryo-SEM. The addition of XG significantly improved the rheological properties of SMGHs, as indicated by 3.1-fold G' and 1.3-fold melting temperature with increasing the XG dose to 5.6 mg/ml. The corresponding decrease in the T23 relaxation time from 450.3 to 365.6 ms also signified the strong binding between SMGHs and XG. SMGHs/XG also had a higher proton density (T1 and T2 weighted images) due to the higher bound and free water content of the hybrid gel systems, respectively. Additionally, the blueshift in the amide I and II bands in SMGHs/XG further indicated stronger electrostatic interactions between SMGHs and XG. Such scenarios resulted in a well-distributed and compact network with a rougher surface of SMGHs/XG in comparison to pure SMGHs and XG, as assessed by AFM and SEM. These results suggest that SMGHs/XG gel could be a potential hybrid gel applied in the food industry. PRACTICAL APPLICATION: Scallop (Patinopecten yessoensis) male gonads are edible, but are usually discarded during processing of scallop adductor. Because of its rich nutrition and gelation properties, scallop male gonads have a potential role in developing marine source-protein as a functional food base. The SMGHs/XG binary gel would be potentially applied in delivery system in food and biological fields. Further study is undergoing to apply SMGHs/XG binary gel to embed bioactive compounds, such as curcumin and ß-carotene.


Assuntos
Gônadas/química , Hidrogéis/química , Pectinidae/química , Polissacarídeos Bacterianos/química , Alimentos Marinhos/análise , Extratos de Tecidos/química , Animais , Masculino , Reologia
12.
Sci Total Environ ; 778: 146271, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33721636

RESUMO

Lake eutrophication has attracted the attention of the government and general public. Chlorophyll-a (Chl-a) is a key indicator of algal biomass and eutrophication. Many efforts have been devoted to establishing accurate algorithms for estimating Chl-a concentrations. In this study, a total of 273 samples were collected from 45 typical lakes across China during 2017-2019. Here, we proposed applicable machine learning algorithms (i.e., linear regression model (LR), support vector machine model (SVM) and Catboost model (CB)), which integrate a broad scale dataset of lake biogeochemical characteristics using Multispectral Imager (MSI) product to seamlessly retrieve the Chl-a concentration. A K-means clustering approach was used to cluster the 273 normalized water leaving reflectance spectra [Rrs (λ)] extracted from MSI imagery with Case 2 Regional Coast Colour (CR2CC) processor into three groups. The pH, electrical conductivity (EC), total suspended matter (TSM) and dissolved organic carbon (DOC) from three clustering groups had significant differences (p < 0.05**), indicating that water quality parameters have an integrated impact on Rrs(λ)-spectra. The results of machine learning algorithms integrating demonstrated that SVM obtained a better degree of measured- and derived- fitting (calibration: slope = 0.81, R2 = 0.91; validation: slope = 1.21, R2 = 0.88). On the contrary, the documented nine Chl-a algorithms gave poor results (fitting 1:1 linear slope < 0.4 and R2 < 0.70) with synchronous train and test datasets. It demonstrated that machine learning provides a robust model for quantifying Chl-a concentration. Further, considering three Rrs(λ) clustering groups by k-means, Chl-a SVM model indicated that cluster 1 group gave a better retrieving performance (slope = 0.71, R2 = 0.78), followed by cluster 3 group (slope = 0.77, R2 = 0.64) and cluster 2 group (slope = 0.67, R2 = 0.50). These are related to the low TSM and high DOC levels for cluster-1 and cluster-3 Rrs(λ) spectra, which reduce the influence of particle in red bands for Rrs(λ) signal. Our results highlighted the quantification of lake Chl-a concentrations using MSI imagery and SVM, which can realize the large-scale monitoring and more appropriate for medium/low Chl-a level. The remote estimation of Chl-a based on artificial intelligence can provide an effective and robust way to monitor the lake eutrophication on a macro-scale; and offer a better approach to elucidate the response of lake ecosystems to global change.


Assuntos
Inteligência Artificial , Lagos , Algoritmos , China , Clorofila/análise , Clorofila A/análise , Ecossistema , Monitoramento Ambiental , Eutrofização
13.
Nat Commun ; 12(1): 264, 2021 01 11.
Artigo em Inglês | MEDLINE | ID: mdl-33431876

RESUMO

The ongoing pandemic of coronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Neutralizing antibodies against SARS-CoV-2 are an option for drug development for treating COVID-19. Here, we report the identification and characterization of two groups of mouse neutralizing monoclonal antibodies (MAbs) targeting the receptor-binding domain (RBD) on the SARS-CoV-2 spike (S) protein. MAbs 2H2 and 3C1, representing the two antibody groups, respectively, bind distinct epitopes and are compatible in formulating a noncompeting antibody cocktail. A humanized version of the 2H2/3C1 cocktail is found to potently neutralize authentic SARS-CoV-2 infection in vitro with half inhibitory concentration (IC50) of 12 ng/mL and effectively treat SARS-CoV-2-infected mice even when administered at as late as 24 h post-infection. We determine an ensemble of cryo-EM structures of 2H2 or 3C1 Fab in complex with the S trimer up to 3.8 Å resolution, revealing the conformational space of the antigen-antibody complexes and MAb-triggered stepwise allosteric rearrangements of the S trimer, delineating a previously uncharacterized dynamic process of coordinated binding of neutralizing antibodies to the trimeric S protein. Our findings provide important information for the development of MAb-based drugs for preventing and treating SARS-CoV-2 infections.


Assuntos
Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacologia , Anticorpos Antivirais/química , Anticorpos Antivirais/farmacologia , COVID-19/tratamento farmacológico , SARS-CoV-2/efeitos dos fármacos , Animais , Anticorpos Monoclonais/imunologia , Anticorpos Monoclonais/uso terapêutico , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Anticorpos Antivirais/uso terapêutico , Microscopia Crioeletrônica , Mapeamento de Epitopos , Epitopos , Feminino , Camundongos , Camundongos Endogâmicos BALB C , Modelos Moleculares , Ligação Proteica/efeitos dos fármacos , Conformação Proteica , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/imunologia
14.
J Cell Mol Med ; 24(19): 11146-11157, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32910534

RESUMO

The lack of efficient ex vivo expansion methods restricts clinical use of haematopoietic stem cells (HSC) for the treatment of haematological malignancies and degenerative diseases. Umbilical cord blood (UCB) serves as an alternative haematopoietic stem cell source. However, currently what limits the use of UCB-derived HSC is the very low numbers of haematopoietic stem and progenitor cells available for transplantation in a single umbilical cord blood unit. Here, we report that TNFSF15, a member of the tumour necrosis factor superfamily, promotes the expansion of human umbilical cord blood (UCB)-derived HSC. TNFSF15-treated UCB-HSC is capable of bone marrow engraftment as demonstrated with NOD/SCID or NOD/Shi-SCID/IL2Rgnull (NOG) mice in both primary and secondary transplantation. The frequency of repopulating cells occurring in the injected tibiae is markedly higher than that in vehicle-treated group. Additionally, signal proteins of the Notch pathway are highly up-regulated in TNFSF15-treated UCB-HSC. These findings indicate that TNFSF15 is useful for in vitro expansion of UCB-HSC for clinical applications. Furthermore, TNFSF15 may be a hopeful selection for further UCB-HSC application or study.


Assuntos
Sangue Fetal/citologia , Células-Tronco Hematopoéticas/citologia , Células-Tronco Hematopoéticas/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Membro 15 da Superfamília de Ligantes de Fatores de Necrose Tumoral/metabolismo , Animais , Antígenos CD/metabolismo , Diferenciação Celular/efeitos dos fármacos , Linhagem da Célula/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Transplante de Células-Tronco Hematopoéticas , Células-Tronco Hematopoéticas/efeitos dos fármacos , Humanos , Camundongos Endogâmicos NOD , Camundongos SCID , Transdução de Sinais/efeitos dos fármacos , Bibliotecas de Moléculas Pequenas/farmacologia
16.
Cancer Imaging ; 20(1): 53, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738913

RESUMO

BACKGROUND: Convolutional neural networks (CNNs) have been extensively applied to two-dimensional (2D) medical image segmentation, yielding excellent performance. However, their application to three-dimensional (3D) nodule segmentation remains a challenge. METHODS: In this study, we propose a multi-view secondary input residual (MV-SIR) convolutional neural network model for 3D lung nodule segmentation using the Lung Image Database Consortium and Image Database Resource Initiative (LIDC-IDRI) dataset of chest computed tomography (CT) images. Lung nodule cubes are prepared from the sample CT images. Further, from the axial, coronal, and sagittal perspectives, multi-view patches are generated with randomly selected voxels in the lung nodule cubes as centers. Our model consists of six submodels, which enable learning of 3D lung nodules sliced into three views of features; each submodel extracts voxel heterogeneity and shape heterogeneity features. We convert the segmentation of 3D lung nodules into voxel classification by inputting the multi-view patches into the model and determine whether the voxel points belong to the nodule. The structure of the secondary input residual submodel comprises a residual block followed by a secondary input module. We integrate the six submodels to classify whether voxel points belong to nodules, and then reconstruct the segmentation image. RESULTS: The results of tests conducted using our model and comparison with other existing CNN models indicate that the MV-SIR model achieves excellent results in the 3D segmentation of pulmonary nodules, with a Dice coefficient of 0.926 and an average surface distance of 0.072. CONCLUSION: our MV-SIR model can accurately perform 3D segmentation of lung nodules with the same segmentation accuracy as the U-net model.


Assuntos
Aprendizado Profundo , Imageamento Tridimensional/métodos , Nódulos Pulmonares Múltiplos/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Humanos , Processamento de Imagem Assistida por Computador , Redes Neurais de Computação , Curva ROC
17.
Int J Pharm ; 586: 119642, 2020 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-32702452

RESUMO

Rheumatoid arthritis (RA) is an autoimmune disease that is currently incurable. Clinical practice has shown significant benefits of combined therapies for RA treatment. This study aims to develop and demonstrate an efficient triple therapy for RA in vitro and in vivo. Three anti-inflammatory agents, NF-κB decoy oligodeoxynucleotides (ODNs), gold nanorods (GNRs), and dexamethasone (DEX), were encapsulated into folate (FA) modified liposomes (FA-lip(DEX + GNRs/ODNs)). The FA-lip(DEX + GNRs/ODNs) showed favorable physicochemical properties and efficient intracellular uptake by inflamed macrophages. Combined with laser irradiation, FA-lip(DEX + GNRs/ODNs) greatly reduced the secretion of proinflammatory proteins and oxidative factors in vitro. In adjuvant-induced arthritis (AIA) mice, FA-lip(DEX + GNRs/ODNs) achieved prolonged and enhanced accumulation at inflamed paws. FA-lip(DEX + GNRs/ODNs) + laser treatment reduced clinical arthritis scores and serum cytokine levels and protected cartilage. In summary, the triple therapy demonstrated significantly enhanced anti-inflammatory efficacy and is a promising strategy to treat RA via combined anti-inflammatory mechanisms.


Assuntos
Artrite Experimental , Artrite Reumatoide , Nanotubos , Animais , Artrite Experimental/tratamento farmacológico , Artrite Reumatoide/tratamento farmacológico , Ouro , Lipossomos , Camundongos
18.
Front Pharmacol ; 11: 399, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32300303

RESUMO

There is an increasing demand for the expansion of functional human hematopoietic stem cells (hHSCs) for various clinical applications. Based on our primary screening of antioxidant small molecule compounds library, a small molecule compound C2968 (chrysin) was identificated to expand cord blood CD34+ cells in vitro. Then we further verified the optimum concentration and explored its effect on hHSCs phenotype and biological function. C2968 could significantly increase the proportion and absolute number of CD34+CD38-CD49f+ and CD34+CD38-CD45RA-CD90+ cells under 2.5 µM. Furthermore, the total number of colony-forming units and the frequency of LT-HSCs in C2968-treated group were significantly higher than control, indicating the multipotency and long-term activity of hematopoietic stem and progenitor cells were sustained. Additionally, C2968 treatment could maintain transplantable HSCs that preserve balanced multilineage potential and promote rapid engraftment after transplantation in immunodeficient (NOG) mice. Mechanistically, the activity of chrysin might be mediated through multiple mechanisms namely delaying HSC differentiation, inhibiting ROS-activated apoptosis, and modulating of cyclin-dependent kinase inhibitors. Overall, chrysin showed good ex vivo expansion effect on hHSCs, which could maintain the self-renewal and multilineage differentiation potential of hHSCs. Through further research on its antioxidant mechanism, it may become a promising tool for further fundamental research and clinical umbilical cord blood transplantation of hHSCs.

19.
Opt Express ; 28(7): 9603-9630, 2020 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-32225565

RESUMO

Traditional imaging systems exhibit a well-known trade-off between the resolution and the field of view of their captured images. Typical cameras and microscopes can either "zoom in" and image at high-resolution, or they can "zoom out" to see a larger area at lower resolution, but can rarely achieve both effects simultaneously. In this review, we present details about a relatively new procedure termed Fourier ptychography (FP), which addresses the above trade-off to produce gigapixel-scale images without requiring any moving parts. To accomplish this, FP captures multiple low-resolution, large field-of-view images and computationally combines them in the Fourier domain into a high-resolution, large field-of-view result. Here, we present details about the various implementations of FP and highlight its demonstrated advantages to date, such as aberration recovery, phase imaging, and 3D tomographic reconstruction, to name a few. After providing some basics about FP, we list important details for successful experimental implementation, discuss its relationship with other computational imaging techniques, and point to the latest advances in the field while highlighting persisting challenges.

20.
Theranostics ; 10(6): 2587-2596, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32194821

RESUMO

Prior reports have shown optical coherence tomography (OCT) can differentiate normal colonic mucosa from neoplasia, potentially offering an alternative technique to endoscopic biopsy - the current gold-standard colorectal cancer screening and surveillance modality. To help clinical translation limited by processing the large volume of generated data, we designed a deep learning-based pattern recognition (PR) OCT system that automates image processing and provides accurate diagnosis potentially in real-time. Method: OCT is an emerging imaging technique to obtain 3-dimensional (3D) "optical biopsies" of biological samples with high resolution. We designed a convolutional neural network to capture the structure patterns in human colon OCT images. The network is trained and tested using around 26,000 OCT images acquired from 20 tumor areas, 16 benign areas, and 6 other abnormal areas. Results: The trained network successfully detected patterns that identify normal and neoplastic colorectal tissue. Experimental diagnoses predicted by the PR-OCT system were compared to the known histologic findings and quantitatively evaluated. A sensitivity of 100% and specificity of 99.7% can be reached. Further, the area under the receiver operating characteristic (ROC) curves (AUC) of 0.998 is achieved. Conclusions: Our results demonstrate that PR-OCT can be used to give an accurate real-time computer-aided diagnosis of colonic neoplastic mucosa. Future development of this system as an "optical biopsy" tool to assist doctors in real-time for early mucosal neoplasms screening and treatment evaluation following initial oncologic therapy is planned.


Assuntos
Colo/diagnóstico por imagem , Neoplasias Colorretais/diagnóstico por imagem , Aprendizado Profundo , Diagnóstico por Computador/métodos , Processamento de Imagem Assistida por Computador/métodos , Tomografia de Coerência Óptica/métodos , Idoso , Idoso de 80 Anos ou mais , Humanos , Pessoa de Meia-Idade
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