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1.
Cancers (Basel) ; 13(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805946

RESUMO

Background and Aims-Transforming growth factor-beta (TGF-ß) signaling orchestrates tumorigenesis and one of the family members, TGF-ß receptor type III (TGFßR3), are distinctively under-expressed in numerous malignancies. Currently, the clinical impact of TGFßR3 down-regulation and the underlying mechanism remains unclear in hepatocellular carcinoma (HCC). Here, we aimed to identify the tumor-promoting roles of decreased TGFßR3 expression in HCC progression. Materials and Methods-For clinical analysis, plasma and liver specimens were collected from 100 HCC patients who underwent curative resection for the quantification of TGFßR3 by q-PCR and ELISA. To study the tumor-promoting mechanism of TGFßR3 downregulation, HCC mouse models and TGFßR3 knockout cell lines were applied. Results-Significant downregulation of TGFßR3 and its soluble form (sTGFßR3) were found in HCC tissues and plasma compared to healthy individuals (p < 0.01). Patients with <9.4 ng/mL sTGFßR3 exhibited advanced tumor stage, higher recurrence rate and shorter disease-free survival (p < 0.05). The tumor-suppressive function of sTGFßR3 was further revealed in an orthotopic mouse HCC model, resulting in 2-fold tumor volume reduction. In TGFßR3 knockout hepatocyte and HCC cells, increased complement component C5a was observed and strongly correlated with shorter survival and advanced tumor stage (p < 0.01). Interestingly, C5a activated the tumor-promoting Th-17 response in tumor associated macrophages. Conclusion-TGFßR3 suppressed tumor progression, and decreased expression resulted in poor prognosis in HCC patients through upregulation of tumor-promoting complement C5a.

3.
Commun Biol ; 4(1): 475, 2021 04 12.
Artigo em Inglês | MEDLINE | ID: mdl-33846513

RESUMO

COVID-19 is a respiratory illness caused by a novel coronavirus called SARS-CoV-2. The viral spike (S) protein engages the human angiotensin-converting enzyme 2 (ACE2) receptor to invade host cells with ~10-15-fold higher affinity compared to SARS-CoV S-protein, making it highly infectious. Here, we assessed if ACE2 polymorphisms can alter host susceptibility to SARS-CoV-2 by affecting this interaction. We analyzed over 290,000 samples representing >400 population groups from public genomic datasets and identified multiple ACE2 protein-altering variants. Using reported structural data, we identified natural ACE2 variants that could potentially affect virus-host interaction and thereby alter host susceptibility. These include variants S19P, I21V, E23K, K26R, T27A, N64K, T92I, Q102P and H378R that were predicted to increase susceptibility, while variants K31R, N33I, H34R, E35K, E37K, D38V, Y50F, N51S, M62V, K68E, F72V, Y83H, G326E, G352V, D355N, Q388L and D509Y were predicted to be protective variants that show decreased binding to S-protein. Using biochemical assays, we confirmed that K31R and E37K had decreased affinity, and K26R and T92I variants showed increased affinity for S-protein when compared to wildtype ACE2. Consistent with this, soluble ACE2 K26R and T92I were more effective in blocking entry of S-protein pseudotyped virus suggesting that ACE2 variants can modulate susceptibility to SARS-CoV-2.

4.
Medicine (Baltimore) ; 100(12): e25229, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761712

RESUMO

ABSTRACT: This study aimed to explore the relationship between H558R polymorphism of the SCN5A gene and atrial fibrillation (AF) in Tibetan and Han nationalities at high altitude.A total of 50 Tibetan and 50 Han patients with AF at the same altitude (2260 m) were included. Meanwhile, the general clinical data of patients without AF (50 Tibetan and 50 Han) matched with the data of patients with AF were included during the same period. The blood samples of patients were collected to extract DNA. The DNA sequencing was performed by Xi'an Zhenpin Biotechnology Co., Ltd. The mutation loci of the sequence were located and identified by DNA sequencing. The general information, laboratory examination, color Doppler echocardiography, and genotypes and alleles of each group were analyzed. The multivariate logistic regression analysis was used to determine the independent risk factors for AF.The genotype and allele frequencies of the H558R locus of the SCN5A gene in the AF groups of Tibetan and Han nationalities were significantly different from those in the non-AF groups (P < .05). The genotype and allele frequency of the H558R locus of the SCN5A gene in the AF group of Tibetan nationalities were not significantly different from those in the AF group of Han nationalities (P > .05). The logistic regression analysis of the total population revealed that coronary heart disease, age, total cholesterol (TC), left atrial diameter, and G allele were independent risk factors for AF occurrence.The occurrence of AF in Tibetan and Han nationalities at high altitude is associated with the polymorphism of H558R locus of the SCN5A gene. The G allele is an independent risk factor for the occurrence of AF in Tibetan and Han nationalities.


Assuntos
Altitude , Fibrilação Atrial/genética , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/etnologia , Fibrilação Atrial/fisiopatologia , China/epidemiologia , Ecocardiografia Doppler em Cores/métodos , Ecocardiografia Doppler em Cores/estatística & dados numéricos , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Tibet/epidemiologia
5.
Clin Cancer Res ; 2021 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-33712511

RESUMO

On April 10, 2020, the FDA approved selumetinib (KOSELUGO, AstraZeneca) for the treatment of pediatric patients 2 years of age and older with neurofibromatosis type 1 who have symptomatic, inoperable plexiform neurofibromas. Approval was based on demonstration of a durable overall response rate per Response Evaluation in Neurofibromatosis and Schwannomatosis criteria and supported by observed clinical improvements in plexiform neurofibroma-related symptoms and functional impairments in 50 pediatric patients with inoperable plexiform neurofibromas in a single-arm, multicenter trial. The overall reponse rate per NCI investigator assessment was 66% (95% confidence interval, 51-79) with at least 12 months of follow-up. The median duration of response was not reached, and 82% of responding patients experienced duration of response ≥12 months. Clinical outcome assessment endpoints provided supportive efficacy data. Risks of selumetinib are consistent with MAPK (MEK) inhibitor class effects, including ocular, cardiac, musculoskeletal, gastrointestinal, and dermatologic toxicities. Safety was assessed across a pooled database of 74 pediatric patients with plexiform neurofibromas and supported by adult and pediatric selumetinib clinical trial data in cancer indications. The benefit-risk assessment for selumetinib in patients with inoperable plexiform neurofibromas was considered favorable.

6.
Nanotechnology ; 2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33765675

RESUMO

A novel preparation process has been developed to synthesize MgH2nanoparticles by combining ball milling and thermal hydrogenolysis of di-n-butylmagnesium (C4H9)2Mg, denoted as MgBu2). With the aid of mechanical impact and the dispersant, the hydrogenolysis temperature of MgBu2in heptane solution was considerably lowered down to 100 ºC, and the MgH2nanoparticles with an average particle size ofca.8.9 nm were obtained without scaffolds. The nano-size effect of the MgH2nanoparticles causes a significant decrease in the onset dehydrogenation temperature of 225 ºC and enthalpy of 69.78 kJ/mol∙H2. This thermally-assisted milling and hydrogenolysis process may also be extended for synthesizing other nanoscale hydrides and catalysts.

7.
Anal Methods ; 13(12): 1527-1534, 2021 03 28.
Artigo em Inglês | MEDLINE | ID: mdl-33710182

RESUMO

Trimethylamine N-oxide (TMAO), a gut microbial metabolite involved in cardiovascular and kidney diseases, has great potential as a biomarker, thus making TMAO quantification of great significance. The current assay methods are mainly established on mass spectrometry. However, the classic enzymatic approach is absent, which may be because there is no appropriate single-enzyme reaction. Here, we prepared TMAO demethylase and formaldehyde dehydrogenase and found that these two bacterial enzymes catalyze an efficient coupled reaction that produces NADH from TMAO conversion. With the participation of another enzyme, diaphorase, the multienzymatic coupling system was constructed, which realizes the output of fluorescence signals from TMAO input using resazurin as a probe, thus laying the foundation for fluorescent assay. Through optimization, the sensitivity and specificity were improved. A pretreatment procedure was developed to eliminate formaldehyde that pre-exists with TMAO to avoid an interference effect. Our assay is suitable for quantifying serum TMAO in the range of 2.05-50 µM, covering actual levels in clinical samples, and exhibits a high degree of accordance with mass spectrometry. Therefore, the established fluorometric microplate assay is facile, sensitive and accurate and may enable low-cost and high-throughput analysis of TMAO in clinical laboratory diagnosis.

8.
Clin Transl Med ; 11(3): e356, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33783998

RESUMO

Pancreatic cancer is a gastrointestinal tumor with a high mortality rate, and advances in surgical procedures have only resulted in limited improvements in the prognosis of patients. Solute carriers (SLCs), which rank second among membrane transport proteins in terms of abundance, regulate cellular functions, including tumor biology. An increasing number of studies focusing on the role of SLCs in tumor biology have indicated their relationship with pancreatic cancer. The mechanism of SLC transporters in tumorigenesis has been explored to identify more effective therapies and improve survival outcomes. These transporters are significant biomarkers for pancreatic cancer, the functions of which include mainly proliferative signaling, cell death, angiogenesis, tumor invasion and metastasis, energy metabolism, chemotherapy sensitivity and other functions in tumor biology. In this review, we summarize the different roles of SLCs and explain their potential applications in pancreatic cancer treatment.

9.
Arch Biochem Biophys ; 702: 108828, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33741336

RESUMO

Eosinophils (Eos) are the canonical effector cells in allergic rhinitis (AR) and many inflammatory diseases. The mechanism of eosinophilia occurring in the lesion sites is not fully understood yet. Twist1 protein (Twist, in short) is an apoptosis inhibitor that also has immune regulatory functions. This study aims to investigate the role of Twist in the pathogenesis of eosinophilia in AR. In this study, surgically removed human nasal mucosal samples were obtained from patients with chronic sinusitis and nasal polyps with AR (the AR group) or without AR (the nAR group). Eos were isolated from the samples by flow cytometry. We found that abundant Eos were obtained from the surgically removed nasal mucosa tissues of both nAR and AR groups. Significantly higher Ras activation was detected in AR Eos than that in nAR Eos. Ras activation was associated with the apoptosis resistance in AR Eos. The Twist (an apoptosis inhibitor) expression was higher in AR Eos, which was positively correlated with the Ras activation status. The sensitization to IgG induced Twist expression in Eos, in which Ras activated the MAPK-HIF-1α pathway, the latter promoted the Twist gene transcription. Twist bound Rac GTPase activating protein-1 to sustain the Ras activation in Eos. Ras activation sustained the apoptosis resistance in Eos. In conclusion, high Ras activation was detected in the AR nasal mucosal tissue-isolated Eos. IgG-sensitization induced Ras activation and Twist expression in Eos, that conferred Eos the apoptosis resistance.

10.
Eur J Med Chem ; 217: 113372, 2021 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-33744689

RESUMO

Diabetes mellitus is one of the most challenging threats to global public health. To improve the therapy efficacy of antidiabetic drugs, numerous drug delivery systems have been developed. Polyethylene glycol (PEG) is a polymeric family sharing the same skeleton but with different molecular weights which is considered as a promising material for drug delivery. In the delivery of antidiabetic drugs, PEG captures much attention in the designing and preparation of sustainable and controllable release systems due to its unique features including hydrophilicity, biocompatibility and biodegradability. Due to the unique architecture, PEG molecules are also able to shelter delivery systems to decrease their immunogenicity and avoid undesirable enzymolysis. PEG has been applied in plenty of delivery systems such as micelles, vesicles, nanoparticles and hydrogels. In this review, we summarized several commonly used PEG-contained antidiabetic drug delivery systems and emphasized the advantages of stimuli-responsive function in these sustainable and controllable formations.

11.
Front Immunol ; 12: 648917, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33777046

RESUMO

Background: The treatment modalities for pancreatic ductal adenocarcinoma (PDAC) are limited and unsatisfactory. Although many novel drugs targeting the tumor microenvironment, such as immune checkpoint inhibitors, have shown promising efficacy for some tumors, few of them significantly prolong the survival of patients with PDAC due to insufficient knowledge on the tumor microenvironment. Methods: A single-cell RNA sequencing (scRNA-seq) dataset and seven PDAC cohorts with complete clinical and bulk sequencing data were collected for bioinformatics analysis. The relative proportions of each cell type were estimated using the gene set variation analysis (GSVA) algorithm based on the signatures identified by scRNA-seq or previous literature. Results: A meta-analysis of 883 PDAC patients showed that neutrophils are associated with worse overall survival (OS) for PDAC, while CD8+ T cells, CD4+ T cells, and B cells are related to prolonged OS for PDAC, with marginal statistical significance. Seventeen cell categories were identified by clustering analysis based on single-cell sequencing. Among them, CD8+ T cells and NKT cells were universally exhausted by expressing exhaustion-associated molecular markers. Interestingly, signatures of CD8+ T cells and NKT cells predicted prolonged OS for PDAC only in the presence of "targets" for pyroptosis and ferroptosis induction. Moreover, a specific state of T cells with overexpression of ribosome-related proteins was associated with a good prognosis. In addition, the hematopoietic stem cell (HSC)-like signature predicted prolonged OS in PDAC. Weighted gene co-expression network analysis identified 5 hub genes whose downregulation may mediate the observed survival benefits of the HSC-like signature. Moreover, trajectory analysis revealed that myeloid cells evolutionarily consisted of 7 states, and antigen-presenting molecules and complement-associated genes were lost along the pseudotime flow. Consensus clustering based on the differentially expressed genes between two states harboring the longest pseudotime span identified two PDAC groups with prognostic differences, and more infiltrated immune cells and activated immune signatures may account for the survival benefits. Conclusion: This study systematically investigated the prognostic implications of the components of the PDAC tumor microenvironment by integrating single-cell sequencing and bulk sequencing, and future studies are expected to develop novel targeted agents for PDAC treatment.

12.
Nanoscale ; 13(12): 6105-6116, 2021 Mar 28.
Artigo em Inglês | MEDLINE | ID: mdl-33729238

RESUMO

Bleeding in outdoor environments is often accompanied by bacterial infection. Due to poor outdoor conditions, it is essential to use the same materials to achieve one-stop treatment of fast hemostasis and simultaneously sterilizing bacteria, especially multidrug-resistant bacteria. Photodynamic therapy (PDT) can kill superbacteria, and local PDT through a nanofiber platform can effectively reduce damage to normal tissue. However, current photosensitizers whether in the interior or on the surface of fibers would leak into the wound and inhibit collagen regeneration. Herein, we use a battery-powered handheld electrospinning device that can work outdoors. It directly spins fibers onto the wound, which facilitates fast hemostasis due to its excellent adhesion to the wound. Eluting holes in the hydrophobic fibers by wound tissue fluid are also proposed to accelerate the escape of reactive oxygen species (ROS) from the interior of the fibers to the wound. After photosensitizers were coated on upconverting nanoparticles (UCNPs), they formed clusters whose size (∼55 nm) was much larger than the uniform elution hole (∼4 nm), which prevented photosensitizers from leaking out into the wound tissue. This cluster structure can also tailor the photosensitizers to be triggered by near infrared (NIR) light, whose deeper penetration depth in tissue can facilitate treating deep infections. Because of the combination of the in situ fiber deposition method with the designed elution mode, ROS is effectively poured out onto the fiber surface and is quickly delivered to the wound. Thus, after rapid hemostasis (<7 s), this one-stop treatment followed by photodynamic sterilizing of superbacteria can promote collagen regeneration and reduce wound healing time from 24 to 16 days.

13.
J Am Chem Soc ; 2021 Mar 02.
Artigo em Inglês | MEDLINE | ID: mdl-33651597

RESUMO

Cu(I)-based catalysts have proven to play an important role in the formation of specific hydrocarbon products from electrochemical carbon dioxide reduction reaction (CO2RR). However, it is difficult to understand the effect of intrinsic cuprophilic interactions inside the Cu(I) catalysts on the electrocatalytic mechanism and performance. Herein, two stable copper(I)-based coordination polymer (NNU-32 and NNU-33(S)) catalysts are synthesized and integrated into a CO2 flow cell electrolyzer, which exhibited very high selectivity for electrocatalytic CO2-to-CH4 conversion due to clearly inherent intramolecular cuprophilic interactions. Substitution of hydroxyl radicals for sulfate radicals during the electrocatalytic process results in an in situ dynamic crystal structure transition from NNU-33(S) to NNU-33(H), which further strengthens the cuprophilic interactions inside the catalyst structure. Consequently, NNU-33(H) with enhanced cuprophilic interactions shows an outstanding product (CH4) selectivity of 82% at -0.9 V (vs reversible hydrogen electrode, j = 391 mA cm-2), which represents the best crystalline catalyst for electrocatalytic CO2-to-CH4 conversion to date. Moreover, the detailed DFT calculations also prove that the cuprophilic interactions can effectively facilitate the electroreduction of CO2 to CH4 by decreasing the Gibbs free energy change of potential determining step (*H2COOH → *OCH2). Significantly, this work first explored the effect of intrinsic cuprophilic interactions of Cu(I)-based catalysts on the electrocatalytic performance of CO2RR and provides an important case study for designing more stable and efficient crystalline catalysts to reduce CO2 to high-value carbon products.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33650730

RESUMO

Cyclodextrin poly-functionalization has fueled progress in their use in multiple applications such as enzyme mimicry, but also in the polymer sciences, luminescence, as sensors or for biomedical applications… However, the regioselective access to a given pattern of functions on b-cyclodextrin is still very limited. Here, we uncover a new orienting group, the thioacetate, expanding the toolbox available for cyclodextrin poly-hetero-functionalization using DIBAL-H promoted debenzylation. The usefulness of this group is illustrated in the first synthesis of a precisely hepta-hetero-functionalized b-cyclodextrin. By way of comparison, a random hepta-functionalization would give 117655 different molecules. This synthesis is not simply the vain quest for the Holy Grail of CD hetero-functionalization, but it illustrates the versatility of the DIBAL-H oriented hetero-functionalization strategy opening the way to a multitude of useful functionalization patterns for new practical applications.

15.
Inorg Chem ; 2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33756074

RESUMO

The two novel organic hybrid iodoplumbates [Hhbpt]2[H2hbpt][H4hbpt][Pb5I18]·9H2O (1, hbpt = 1H-3,5- bis(pyrazinyl)-1,2,4-triazole) and [Pb2I(bpt)2(H2O)3(I3·1/2I2)] (2) were synthesized under hydrothermal conditions. 1 contains a new type of pentanuclear cluster [Pb5I18]8- anion, while 2 comprises an unprecedented 2-D polyiodoplumbate layer. Both 1 and 2 are potential semiconductors with narrow absorption edges of 1.98 eV for 1 and 1.38 eV for 2. 2 also shows photocurrent response and photoluminescent properties.

16.
Adv Mater ; : e2005504, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33660306

RESUMO

Perovskite solar cells (PSCs) have become a promising photovoltaic (PV) technology, where the evolution of the electron-selective layers (ESLs), an integral part of any PV device, has played a distinctive role to their progress. To date, the mesoporous titanium dioxide (TiO2 )/compact TiO2 stack has been among the most used ESLs in state-of-the-art PSCs. However, this material requires high-temperature sintering and may induce hysteresis under operational conditions, raising concerns about its use toward commercialization. Recently, tin oxide (SnO2 ) has emerged as an attractive alternative ESL, thanks to its wide bandgap, high optical transmission, high carrier mobility, suitable band alignment with perovskites, and decent chemical stability. Additionally, its low-temperature processability enables compatibility with temperature-sensitive substrates, and thus flexible devices and tandem solar cells. Here, the notable developments of SnO2 as a perovskite-relevant ESL are reviewed with emphasis placed on the various fabrication methods and interfacial passivation routes toward champion solar cells with high stability. Further, a techno-economic analysis of SnO2 materials for large-scale deployment, together with a processing-toxicology assessment, is presented. Finally, a perspective on how SnO2 materials can be instrumental in successful large-scale module and perovskite-based tandem solar cell manufacturing is provided.

17.
Clin Cancer Res ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632925

RESUMO

On May 26, 2020, the FDA approved nivolumab with ipilimumab and two cycles of platinum-doublet chemotherapy as first-line treatment for patients with metastatic or recurrent non-small cell lung cancer (NSCLC), with no EGFR or anaplastic lymphoma kinase (ALK) genomic tumor aberrations. The approval was based on results from Study CA2099LA (CheckMate 9LA), an open-label trial in which 719 patients with NSCLC were randomized to receive nivolumab with ipilimumab and two cycles of chemotherapy (n = 361) or four cycles of platinum-doublet chemotherapy (n = 358). Overall survival (OS) was improved for patients who received nivolumab with ipilimumab and chemotherapy, with a median OS of 14.1 months [95% confidence interval (CI), 13.2-16.2] compared with 10.7 months (95% CI, 9.5-12.5) for patients who received chemotherapy (HR, 0.69; 96.71% CI, 0.55-0.87; P = 0.0006). Progression-free survival and overall response rate per blinded independent central review were also statistically significant. This was the first NSCLC application reviewed under FDA's Project Orbis, in collaboration with Singapore's Health Sciences Authority, Australia's Therapeutic Goods Administration, and Health Canada. The benefit-risk analysis supports FDA's approval of nivolumab with ipilimumab and chemotherapy.

18.
Med Image Anal ; 69: 101956, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33550010

RESUMO

Precise characterization and analysis of anterior chamber angle (ACA) are of great importance in facilitating clinical examination and diagnosis of angle-closure disease. Currently, the gold standard for diagnostic angle assessment is observation of ACA by gonioscopy. However, gonioscopy requires direct contact between the gonioscope and patients' eye, which is uncomfortable for patients and may deform the ACA, leading to false results. To this end, in this paper, we explore a potential way for grading ACAs into open-, appositional- and synechial angles by Anterior Segment Optical Coherence Tomography (AS-OCT), rather than the conventional gonioscopic examination. The proposed classification schema can be beneficial to clinicians who seek to better understand the progression of the spectrum of angle-closure disease types, so as to further assist the assessment and required treatment at different stages of angle-closure disease. To be more specific, we first use an image alignment method to generate sequences of AS-OCT images. The ACA region is then localized automatically by segmenting an important biomarker - the iris - as this is a primary structural cue in identifying angle-closure disease. Finally, the AS-OCT images acquired in both dark and bright illumination conditions are fed into our Multi-Sequence Deep Network (MSDN) architecture, in which a convolutional neural network (CNN) module is applied to extract feature representations, and a novel ConvLSTM-TC module is employed to study the spatial state of these representations. In addition, a novel time-weighted cross-entropy loss (TC) is proposed to optimize the output of the ConvLSTM, and the extracted features are further aggregated for the purposes of classification. The proposed method is evaluated across 66 eyes, which include 1584 AS-OCT sequences, and a total of 16,896 images. The experimental results show that the proposed method outperforms existing state-of-the-art methods in applicability, effectiveness, and accuracy.

19.
Med Image Anal ; 69: 101981, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33588123

RESUMO

Deep hashing methods have been shown to be the most efficient approximate nearest neighbor search techniques for large-scale image retrieval. However, existing deep hashing methods have a poor small-sample ranking performance for case-based medical image retrieval. The top-ranked images in the returned query results may be as a different class than the query image. This ranking problem is caused by classification, regions of interest (ROI), and small-sample information loss in the hashing space. To address the ranking problem, we propose an end-to-end framework, called Attention-based Triplet Hashing (ATH) network, to learn low-dimensional hash codes that preserve the classification, ROI, and small-sample information. We embed a spatial-attention module into the network structure of our ATH to focus on ROI information. The spatial-attention module aggregates the spatial information of feature maps by utilizing max-pooling, element-wise maximum, and element-wise mean operations jointly along the channel axis. To highlight the essential role of classification in direntiating case-based medical images, we propose a novel triplet cross-entropy loss to achieve maximal class-separability and maximal hash code-discriminability simultaneously during model training. The triplet cross-entropy loss can help to map the classification information of images and similarity between images into the hash codes. Moreover, by adopting triplet labels during model training, we can utilize the small-sample information fully to alleviate the imbalanced-sample problem. Extensive experiments on two case-based medical datasets demonstrate that our proposed ATH can further improve the retrieval performance compared to the state-of-the-art deep hashing methods and boost the ranking performance for small samples. Compared to the other loss methods, the triplet cross-entropy loss can enhance the classification performance and hash code-discriminability.

20.
Immunology ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33539546

RESUMO

The mechanism of generation of regulatory T cells (Treg) remains incompletely understood. Recent studies show that CD83 has immune regulatory functions. This study aims to investigate the role of epithelial cell-derived CD83 in the restoration of immune tolerance in the airway mucosa by inducing the Treg differentiation. In this study, CD83 and ovalbumin (OVA)-carrying exosomes were generated from airway epithelial cells. An airway allergy mouse model was developed to test the role of CD83/OVA-carrying exosomes in the suppression of airway allergy by inducing Treg generation. We observed that mouse airway epithelial cells expressed CD83 that could be up-regulated by CD40 ligand. The CD83 deficiency in epithelial cells retarded the Treg generation in the airway mucosa. CD83 up-regulated transforming growth factor-ß-inducible early gene 1 expression in CD4+ T cells to promote Foxp3 expression. Exposure of primed CD4+ T cells to CD83/OVA-carrying exosomes promoted antigen-specific Treg generation. Administration of CD83/OVA-carrying exosomes inhibited experimental airway allergic response. In summary, airway epithelial cells express CD83 that is required in the Treg differentiation in the airway mucosa. Administration of CD83/OVA-carrying exosomes can inhibit airway allergy that has the translation potential in the treatment of airway allergic disorders.

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