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1.
Front Cardiovasc Med ; 8: 735794, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34616788

RESUMO

Objectives: Perivascular adipose tissue plays a key role in atherosclerosis, but its effects on the composition of carotid atherosclerotic plaques are unknown. This study aimed to investigate the association between inflammatory carotid artery and intraplaque hemorrhage (IPH) in the carotid artery. Methods: This is a single-center retrospective study. Carotid inflammation was assessed by perivascular fat density (PFD) in 72 participants (mean age, 65.1 years; 56 men) who underwent both computed tomography angiography (CTA) and magnetic resonance imaging (MRI) within 2 weeks. The presence of IPH was assessed with MRI. Carotid stenosis, maximum plaque thickness, calcification, and ulceration were evaluated through CTA. The association between PFD and the occurrence of IPH was studied using generalized estimating equations analysis. Results: Of 156 plaques, 72 plaques (46.2%) had IPH. Plaques with IPH showed higher PFD than those without [-41.4 ± 3.9 vs. -55.8 ± 6.5 Hounsfield unit (HU); p < 0.001]. After age, calcification, degree of stenosis, maximum plaque thickness, and ulceration were adjusted for, PFD (OR, 1.96; 95% CI, 1.41-2.73; p < 0.001) was found to be strongly associated with the presence of IPH. Conclusions: A higher PFD is associated with the presence of IPH in the carotid artery. These findings may provide a novel marker to identify carotid IPH and risk stratification.

2.
Front Oncol ; 11: 750875, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631589

RESUMO

Objective: To develop and evaluate a deep learning model (DLM) for predicting the risk stratification of gastrointestinal stromal tumors (GISTs). Methods: Preoperative contrast-enhanced CT images of 733 patients with GISTs were retrospectively obtained from two centers between January 2011 and June 2020. The datasets were split into training (n = 241), testing (n = 104), and external validation cohorts (n = 388). A DLM for predicting the risk stratification of GISTs was developed using a convolutional neural network and evaluated in the testing and external validation cohorts. The performance of the DLM was compared with that of radiomics model by using the area under the receiver operating characteristic curves (AUROCs) and the Obuchowski index. The attention area of the DLM was visualized as a heatmap by gradient-weighted class activation mapping. Results: In the testing cohort, the DLM had AUROCs of 0.90 (95% confidence interval [CI]: 0.84, 0.96), 0.80 (95% CI: 0.72, 0.88), and 0.89 (95% CI: 0.83, 0.95) for low-malignant, intermediate-malignant, and high-malignant GISTs, respectively. In the external validation cohort, the AUROCs of the DLM were 0.87 (95% CI: 0.83, 0.91), 0.64 (95% CI: 0.60, 0.68), and 0.85 (95% CI: 0.81, 0.89) for low-malignant, intermediate-malignant, and high-malignant GISTs, respectively. The DLM (Obuchowski index: training, 0.84; external validation, 0.79) outperformed the radiomics model (Obuchowski index: training, 0.77; external validation, 0.77) for predicting risk stratification of GISTs. The relevant subregions were successfully highlighted with attention heatmap on the CT images for further clinical review. Conclusion: The DLM showed good performance for predicting the risk stratification of GISTs using CT images and achieved better performance than that of radiomics model.

3.
Arthritis Res Ther ; 23(1): 266, 2021 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-34702315

RESUMO

BACKGROUND: Connective tissue growth factor (CTGF)-induced angiogenesis is a crucial factor in rheumatoid arthritis (RA), but CTGF-interacting protein and related molecular mechanism of their interaction have not been fully elucidated. METHODS: CTGF-interacting proteins were identified through the LC-MS/MS analysis of the Co-IP products from fibroblast-like synoviocyte (FLS) lysates, and the interaction between CTGF and annexin A2 (ANXA2) was further confirmed through Co-IP and BiFC assay. The binding domain, mutant, mechanism, and angiogenesis function were assessed by homology modeling, molecular docking, MTT, cell scratch, tube formation, and chick chorioallantoic membrane (CAM) assays. Additionally, severe combined immunodeficiency (SCID) mouse co-implantation model was constructed to confirm the effect of ANXA2/CTGF-TSP1 in the process of RA in vivo. RESULTS: ANXA2 was identified and verified as an interaction partner of CTGF for the first time by Co-IP and LC-MS/MS analysis. Co-localization of CTGF and ANXA2 was observed in RA-FLS, and direct interaction of the TSP-1 domain of CTGF and ANXA2 was determined in HEK293T cells. The spatial conformation and stable combination of the ANXA2/CTGF-TSP1 complex were assessed by homology modeling in the biomimetic environment. The function of the ANXA2/CTGF-TSP1 complex was proved on promoting FLS proliferation, migration, and angiogenesis in vitro and deteriorating FLS invasion and joint damage in SCID mice. CONCLUSIONS: TSP-1 is the essential domain in CTGF/ANXA2 interaction and contributes to FLS migration and pannus formation, inducing the process of RA.


Assuntos
Anexina A2 , Artrite Reumatoide , Animais , Anexina A2/genética , Cromatografia Líquida , Fator de Crescimento do Tecido Conjuntivo/genética , Fator de Crescimento do Tecido Conjuntivo/metabolismo , Células HEK293 , Humanos , Camundongos , Simulação de Acoplamento Molecular , Pannus , Espectrometria de Massas em Tandem
4.
Int J Biol Sci ; 17(10): 2606-2621, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34326697

RESUMO

Cisplatin (DDP) was reported to improve pathological complete response (pCR) rates in triple-negative breast cancer (TNBC) patients, however, the molecular mechanism still remains largely unknown. Emerging evidence suggested that some chemotherapeutic drugs played anti-tumor effects by inducing cell pyroptosis. Nevertheless, whether pyroptosis contributes to the DDP-induced anti-tumor effect in TNBC remains unexploited. In the present study, NLRP3/caspase-1/GSDMD pyroptosis pathway was involved in the DDP-induced anti-tumor effect of TNBC in vitro and in vivo, providing evidence that DDP might induce pyroptosis in TNBC. Moreover, DDP activated NLRP3/caspase-1/GSDMD pyroptosis pathway by up-regulating the long non-coding RNA (lncRNA) maternally expressed gene 3 (MEG3). Furthermore, knockdown of MEG3 not only partly abolished the activation effect of DDP on NLRP3/caspase-1/GSDMD pathway-mediated pyroptosis, but also reversed the suppression of DDP on tumor growth and metastasis ability in vitro and in vivo, further confirming that MEG3 may partially mediate the pyroptotic signaling upon DDP treatment. Thus, our data uncovered a novel mechanism that DDP induced pyroptosis via activation of MEG3/NLRP3/caspase-1/GSDMD pathway in TNBC to exert anti-tumor effects, which may help to develop new strategies for the therapeutic interventions in TNBC.

5.
Parasit Vectors ; 14(1): 241, 2021 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-33962671

RESUMO

BACKGROUND: Transmission-blocking vaccine (TBV) is a promising strategy for malaria elimination. It is hypothesized that mixing or fusing two antigens targeting different stages of sexual development may provide higher transmission-blocking activity than these antigens used individually. METHODS: A chimeric protein composed of fragments of Pbg37 and PSOP25 was designed and expressed the recombinant protein in Escherichia coli Rosetta-gami B (DE3). After immunizing mice with individual recombinant proteins Pbg37 and PSOP25, mixed proteins (Pbg37+PSOP25), or the fusion protein (Pbg37-PSOP25), the antibody titers of individual sera were analyzed by ELISA. IFA and Western blot were performed to test the reactivity of the antisera with the native proteins in the parasite. The transmission-blocking activity of the different immunization schemes was assessed using in vitro and in vivo assays. RESULTS: When Pbg37 and PSOP25 were co-administered in a mixture or as a fusion protein, they elicited similar antibody responses in mice as single antigens without causing immunological interference with each other. Antibodies against the mixed or fused antigens recognized the target proteins in the gametocyte, gamete, zygote, and ookinete stages. The mixed proteins or the fusion protein induced antibodies with significantly stronger transmission-reducing activities in vitro and in vivo than individual antigens. CONCLUSIONS: There was no immunological interference between Pbg37 and PSOP25. The bivalent vaccines, which expand the portion of the sexual development during which the transmission-blocking antibodies act, produced significantly stronger transmission-reducing activities than single antigens. Altogether, these data provide the theoretical basis for the development of combination TBVs targeting different sexual stages.


Assuntos
Vacinas Antimaláricas/administração & dosagem , Malária/prevenção & controle , Plasmodium berghei/crescimento & desenvolvimento , Plasmodium berghei/imunologia , Proteínas de Protozoários/administração & dosagem , Vacinas Combinadas/administração & dosagem , Animais , Anticorpos Antiprotozoários/sangue , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Feminino , Humanos , Imunização , Malária/sangue , Malária/parasitologia , Malária/transmissão , Vacinas Antimaláricas/genética , Vacinas Antimaláricas/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Plasmodium berghei/genética , Proteínas de Protozoários/genética , Proteínas de Protozoários/imunologia , Vacinas Combinadas/genética , Vacinas Combinadas/imunologia
6.
Cell Res ; 31(8): 886-903, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33692492

RESUMO

The pancreatic islet contains multiple hormone+ endocrine lineages (α, ß, δ, PP and ε cells), but the developmental processes that underlie endocrinogenesis are poorly understood. Here, we generated novel mouse lines and combined them with various genetic tools to enrich all types of hormone+ cells for well-based deep single-cell RNA sequencing (scRNA-seq), and gene coexpression networks were extracted from the generated data for the optimization of high-throughput droplet-based scRNA-seq analyses. These analyses defined an entire endocrinogenesis pathway in which different states of endocrine progenitor (EP) cells sequentially differentiate into specific endocrine lineages in mice. Subpopulations of the EP cells at the final stage (EP4early and EP4late) show different potentials for distinct endocrine lineages. ε cells and an intermediate cell population were identified as distinct progenitors that independently generate both α and PP cells. Single-cell analyses were also performed to delineate the human pancreatic endocrinogenesis process. Although the developmental trajectory of pancreatic lineages is generally conserved between humans and mice, clear interspecies differences, including differences in the proportions of cell types and the regulatory networks associated with the differentiation of specific lineages, have been detected. Our findings support a model in which sequential transient progenitor cell states determine the differentiation of multiple cell lineages and provide a blueprint for directing the generation of pancreatic islets in vitro.

7.
Front Bioeng Biotechnol ; 9: 615920, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33718337

RESUMO

Icariin is a class IV drug of low solubility, permeability, and poor bioavailability. Synthetic nanomaterials have developed rapidly. However, some literatures point out that synthetic nanomaterials such as liposomes, aptamers, metal nanoparticles, and nanogels have high toxicity and are affected by the reticuloendothelial system or mononuclear phagocyte system. It is known that exosomes could be used as an ideal clinical drug delivery vehicle to avoid the above-mentioned problems to a certain extent. Studies have shown that drugs can be loaded into exosomes by passive and active loading. We used Fetal bovine serum (FBS) exosomes to carry Icariin for the first time in this experiment, FBS exosomes-Icariin (FBS EXO-ICA) more effectively promoted the proliferation of osteoblasts and bone regeneration than Icariin alone. FBS EXO-ICA could become a new nano scale drug formulation for treating diseases associated with bone loss.

8.
J Surg Oncol ; 123(5): 1336-1344, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33523526

RESUMO

BACKGROUND: Pulmonary mucosa-associated lymphoid tissue lymphoma (MALToma) is the most frequent subset of primary pulmonary lymphoma. This study aimed to identify radiologic characteristics of pulmonary MALToma based on computed tomography (CT) observations and pathologic features, and further investigate its prognosis. METHODS: Sixty-six patients (55.4 ± 10.9 years; 51.5% male) diagnosed as pulmonary MALToma by pathology were retrospectively enrolled. According to distributions and features of lesions shown on CT, patients were divided into three patterns, including single nodular/mass, multiple nodular/mass, and pneumonia-like consolidative. RESULTS: Variety of the location and extent of the lymphomatous infiltration accounted for different characteristics demonstrated at CT. The pneumonia-like consolidative pattern was the most frequent pattern observed in 42 patients (63.6%), followed by single nodular/mass (21.2%) and multiple nodular/mass (15.2%). CT features included air bronchogram (72.7%), well-marginated halo sign (53.0%), coarse spiculate with different lengths (72.7%), angiogram sign (77.1% of 35 patients), peribronchovascular thickening (48.5%), irregular cavitation (16.7%) and pulmonary cyst (7.6%). The estimated 5-year cumulative overall survival rate of pulmonary MALToma was 100.0%. CONCLUSIONS: Pulmonary MALToma demonstrates several characteristics at CT. Identification of the significant pulmonary abnormalities of this indolent disease entity might be helpful for early diagnosis and optimal treatment.


Assuntos
Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Linfoma de Zona Marginal Tipo Células B/diagnóstico por imagem , Linfoma de Zona Marginal Tipo Células B/patologia , Tomografia Computadorizada por Raios X/métodos , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/cirurgia , Linfoma de Zona Marginal Tipo Células B/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
9.
Food Chem ; 350: 129139, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33588281

RESUMO

ß-Lactoglobulin (ß-LG) is one of the major food allergens. Enzymatic hydrolysis is a promising strategy to reduce the antigenicity of ß-LG in industrial production. The relationship between the cleavage sites of ß-LG by protease and its antigenic active sites were explored in this study. Molecular docking and molecular dynamics (MD) were used to analyze the active sites and interaction force of ß-LG and IgG antibody. Whey protein was hydrolyzed by four specific enzymes and the antigenicity of the hydrolysates were determined by ELISA. The results of MD showed that the amino acid residue Gln155 (-4.48 kcal mol-1) played the most important roles in the process of binding. Hydrolysates produced by AY-10, which was the only one with specificity towards cleavage sites next to a Gln, had the lowest antigenicity at the same hydrolysis degree. Antigenicity decrease was related to the energy contribution of the cleavage site in the active sites.


Assuntos
Lactoglobulinas/imunologia , Lactoglobulinas/metabolismo , Simulação de Dinâmica Molecular , Peptídeo Hidrolases/metabolismo , Animais , Domínio Catalítico , Hidrólise , Imunoglobulina G/imunologia , Lactoglobulinas/química , Simulação de Acoplamento Molecular , Proteínas do Soro do Leite/metabolismo
10.
Proc Natl Acad Sci U S A ; 118(9)2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-33619103

RESUMO

We evaluated the potential for a monoclonal antibody antagonist of the glucagon receptor (Ab-4) to maintain glucose homeostasis in type 1 diabetic rodents. We noted durable and sustained improvements in glycemia which persist long after treatment withdrawal. Ab-4 promoted ß-cell survival and enhanced the recovery of insulin+ islet mass with concomitant increases in circulating insulin and C peptide. In PANIC-ATTAC mice, an inducible model of ß-cell apoptosis which allows for robust assessment of ß-cell regeneration following caspase-8-induced diabetes, Ab-4 drove a 6.7-fold increase in ß-cell mass. Lineage tracing suggests that this restoration of functional insulin-producing cells was at least partially driven by α-cell-to-ß-cell conversion. Following hyperglycemic onset in nonobese diabetic (NOD) mice, Ab-4 treatment promoted improvements in C-peptide levels and insulin+ islet mass was dramatically increased. Lastly, diabetic mice receiving human islet xenografts showed stable improvements in glycemic control and increased human insulin secretion.


Assuntos
Anticorpos Monoclonais/farmacologia , Diabetes Mellitus Experimental/terapia , Células Secretoras de Glucagon/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Células Secretoras de Insulina/efeitos dos fármacos , Receptores de Glucagon/antagonistas & inibidores , Animais , Glicemia/metabolismo , Peptídeo C/metabolismo , Linhagem da Célula/efeitos dos fármacos , Transdiferenciação Celular/efeitos dos fármacos , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 1/genética , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 1/terapia , Expressão Gênica , Glucagon/antagonistas & inibidores , Glucagon/metabolismo , Células Secretoras de Glucagon/metabolismo , Células Secretoras de Glucagon/patologia , Humanos , Insulina/metabolismo , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/fisiologia , Transplante das Ilhotas Pancreáticas , Camundongos , Camundongos Endogâmicos NOD , Tamanho do Órgão/efeitos dos fármacos , Receptores de Glucagon/genética , Receptores de Glucagon/metabolismo , Resultado do Tratamento
11.
Theranostics ; 11(3): 1446-1457, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33391544

RESUMO

Objective: Tofacitinib (TOF) is a Janus kinase (JAK) inhibitor used in the treatment of rheumatoid arthritis (RA), but the mechanism of its action remains unclear. In this study, we investigated the influence of TOF on gamma delta regulatory T-cell (γδTreg)/γδT17 cell balance in RA and the role of the nucleotide-binding domain (NOD)-like receptor protein 3 (NLRP3) inflammasome in this process. Methods: We detected levels of inflammatory factors in the serum of RA patients before and after administration of TOF using an enzyme-linked immunosorbent assay (ELISA). A collagen-induced arthritis (CIA) model was constructed to investigate the effect of TOF on arthritis symptoms, γδTreg/γδT17 cell balance and the NLRP3 inflammasome. We used bone marrow-derived macrophages (BMDMs) to study the effect of TOF on NLRP3 inflammasome activation. Nlrp3-/- mice were introduced to assess the influence of NLRP3 on γδT17 cell activation in RA. Results: TOF treatment decreased levels of γδT17 cell-related cytokine interleukin-17 (IL-17) in RA patients. In addition, TOF intervention in the CIA model reduced joint inflammation and damage, rebalanced the γδTreg/γδT17 cell ratio and inhibited excessive NLRP3 inflammasome activation in draining lymph nodes and arthritic joints. BMDM intervention experiments demonstrated that TOF decreased the level of secreted IL-1ß via downregulation of NLRP3. Furthermore, experiments using Nlrp3 -/- mice verified that the NLRP3 inflammasome mediated the effect of TOF on γδT17 cell activation. Conclusions: Recovery of γδTreg/γδT17 cell balance was a novel mechanism by which TOF alleviated RA. Meanwhile, NLRP3 played a pivotal role in the process of TOF-mediated γδT17 cell activation.


Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Inflamassomos/imunologia , Linfócitos Intraepiteliais/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Piperidinas/imunologia , Pirimidinas/imunologia , Linfócitos T Reguladores/imunologia , Animais , Citocinas/imunologia , Humanos , Macrófagos/imunologia , Masculino , Camundongos , Camundongos Endogâmicos DBA
12.
Commun Biol ; 4(1): 134, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514854

RESUMO

Genome assemblies provide a powerful basis of comparative multi-omics analyses that offer insight into parasite pathogenicity, host-parasite interactions, and invasion biology. As a unique intracellular nematode, Trichinella consists of two clades, encapsulated and non-encapsulated. Genomic correlation of the distinct differences between the two clades is still unclear. Here, we report an annotated draft reference genome of non-encapsulated Trichinella, T. pseudospiralis, and perform comparative multi-omics analyses with encapsulated T. spiralis. Genome and methylome analyses indicate that, during Trichinella evolution, the two clades of Trichinella exhibit differential expansion and methylation of parasitism-related multi-copy gene families, especially for the DNase II members of the phospholipase D superfamily and Glutathione S-transferases. Further, methylome and transcriptome analyses revealed divergent key excretory/secretory (E/S) genes between the two clades. Among these key E/S genes, TP12446 is significantly more expressed across three life stages in T. pseudospiralis. Overexpression of TP12446 in the mouse C2C12 skeletal muscle cell line could induce inhibition of myotube formation and differentiation, further indicating its key role in parasitism of T. pseudospiralis. This multi-omics study provides a foundation for further elucidation of the mechanism of nurse cell formation and immunoevasion, as well as the identification of pharmacological and diagnostic targets of trichinellosis.


Assuntos
Epigenoma , Genes de Helmintos , Genoma de Protozoário , Proteínas de Helminto/genética , Músculo Esquelético/parasitologia , Trichinella/genética , Triquinelose/parasitologia , Animais , Diferenciação Celular , Linhagem Celular , Citoesqueleto/parasitologia , Citoesqueleto/patologia , Evolução Molecular , Genômica , Proteínas de Helminto/metabolismo , Interações Hospedeiro-Parasita , Camundongos , Fibras Musculares Esqueléticas/parasitologia , Fibras Musculares Esqueléticas/patologia , Músculo Esquelético/patologia , Trichinella/metabolismo , Trichinella/patogenicidade , Trichinella spiralis/genética , Trichinella spiralis/metabolismo , Trichinella spiralis/parasitologia , Triquinelose/patologia
13.
Dalton Trans ; 50(5): 1874-1886, 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33475098

RESUMO

It is challenging to develop highly stable lanthanide luminescent sensors for detecting heavy metal ions and nitroaromatics in view of the human health and environmental security. To this end, two water stable Ln-MOFs with the chemical constitution of {[Ln(HL)]·3DMF·3H2O}n (Ln = Eu, LZG-Eu and Ln = Tb, LZG-Tb) have been developed solvothermally using a multidentate ligand (H4L) with the central phenyl backbone bisubstituted by 2,6-pyridine-dicarboxylic acid at the para-position, H4L = 1,4-bis(2',2'',6',6''-tetracarboxy-1,4':4,4''-pyridyl)benzene. Single crystal analysis demonstrates that two novel Ln-MOFs feature 4,4,4-connected nets with an unprecedented topology symbol of {42·6·83}2{42·62·82}{42·84} and contain two kinds of one-dimensional channels. Powder X-ray diffraction as well as the luminescence determination results indicate that they retain their crystallinity and structural integrity in harsh acidic and basic conditions with pH in the range of 4-11. Moreover, they are highly luminescent, which makes them excellent chemical sensors for detecting Cu2+ and 4-NP (4-nitrophenol) with high selectivity and sensitivity in aqueous media such as deionized water, tap water, and river water based on distinct quenching effects. To the best of our knowledge, their detection limits are lower than those documented so far. In addition, the quenching efficiency of 4-NP was retained in the presence of interfering ions even after the compounds were used for five cycles, which makes them attractive, reliable, visual, and recyclable luminescent Ln-MOF sensor materials for 4-NP. The recognition mechanism for Cu2+ could be attributed to the dissociation of the main framework induced by Cu2+ and the subsequent formation of a Cu2+ coordination species and that for 4-NP is considered to be multi-quenching mechanisms dominated by competition absorption.


Assuntos
Cobre/análise , Elementos da Série dos Lantanídeos/química , Substâncias Luminescentes/química , Nitrofenóis/análise , Água/química , Ligantes , Modelos Moleculares , Conformação Molecular
14.
Cell Res ; 31(3): 326-344, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33106598

RESUMO

Defining the precise regionalization of specified definitive endoderm progenitors is critical for understanding the mechanisms underlying the generation and regeneration of respiratory and digestive organs, yet the patterning of endoderm progenitors remains unresolved, particularly in humans. We performed single-cell RNA sequencing on endoderm cells during the early somitogenesis stages in mice and humans. We developed molecular criteria to define four major endoderm regions (foregut, lip of anterior intestinal portal, midgut, and hindgut) and their developmental pathways. We identified the cell subpopulations in each region and their spatial distributions and characterized key molecular features along the body axes. Dorsal and ventral pancreatic progenitors appear to originate from the midgut population and follow distinct pathways to develop into an identical cell type. Finally, we described the generally conserved endoderm patterning in humans and clear differences in dorsal cell distribution between species. Our study comprehensively defines single-cell endoderm patterning and provides novel insights into the spatiotemporal process that drives establishment of early endoderm domains.

15.
Food Sci Nutr ; 8(11): 5860-5874, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33282238

RESUMO

Increasing consumption of green tea is attributed to the beneficial effects of its constituents, especially polyphenols, on human health, which can be varied during leaf processing. Processing technology has the most important effect on green tea quality. This study investigated the system dynamics of eight catechins, gallic acid, and caffeine in the processing of two varieties of tea, from fresh leaves to finished tea. It was found that complex biochemical changes can occur through hydrolysis under different humidity and heating conditions during the tea processing. This process had a significant effect on catechin composition in the finished tea. The potential application of visible and near-infrared (Vis-NIR) spectroscopy for fast monitoring polyphenol and caffeine contents in tea leaves during the processing procedure has been investigated. It was found that a combination of PCA (principal component analysis) and Vis-NIR spectroscopy can successfully classify the two varieties of tea samples and the five tea processing procedures, while quantitative determination of the constituents was realized by combined regression analysis and Vis-NIR spectra. Furthermore, successive projections algorithm (SPA) was proposed to extract and optimize spectral variables that reflected the molecular characteristics of the constituents for the development of determination models. Modeling results showed that the models had good predictability and robustness based on the extracted spectral characteristics. The coefficients of determination for all calibration sets and prediction sets were higher than 0.862 and 0.834, respectively, which indicated high capability of Vis-NIR spectroscopy for the determination of the constituents during the leaf processing. Meanwhile, this analytical method could quickly monitor quality characteristics and provide feedback for real-time controlling of tea processing machines. Furthermore, the study on complex biochemical changes that occurred during the tea processing would provide a theoretical basis for improving the content of quality components and effective controlling processes.

16.
Ann Transl Med ; 8(22): 1484, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33313229

RESUMO

Background: Gastric cancer (GC) is a heterogeneous disease, and is a leading cause of cancer deaths in Eastern Asia. Genomic analysis, such as whole-exome sequencing (WES), can help identify key genetic alterations leading to the malignancy and diversity of GC, and may help identify new drug targets. Methods: We identified genomic alterations in a cohort of 38 GC patients, including 26 metastatic and 12 non-metastatic patients. We analyzed the association between novel gene mutations and copy number variations (CNVs) with tumor metastasis and patient survival. Results: A number of significantly mutated genes in somatic and germline cells were identified. Among them, ATAD3B somatic mutation, a potential biomarker of immunotherapy in stomach cancers, was associated with better patient survival (P=0.0939) and metastasis (P=0.074). POLE germline variation was correlated with shorter overall survival (OS; P=0.0100). Novel CNVs were also identified and can potentially be used as biomarkers. These included 9p24.1 deletion (P=0.0376) and 16p11.2 amplification (P=0.0066), which were both associated with shorter OS. CNVs of several genes including MMP9, PTPN1, and SS18L1 were found to be significantly related to metastasis (P<0.05). Conclusions: We characterized the mutational landscape of 38 GC patients and discovered several potential new predictive markers of survival and metastasis in GC.

17.
Front Oncol ; 10: 579619, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33251142

RESUMO

Objectives: To develop and validate a radiomics nomogram to improve prediction of recurrence and metastasis risk in T1 stage clear cell renal cell carcinoma (ccRCC). Methods: This retrospective study recruited 168 consecutive patients (mean age, 53.9 years; range, 28-76 years; 43 women) with T1 ccRCC between January 2012 and June 2019, including 50 aggressive ccRCC based on synchronous metastasis or recurrence after surgery. The patients were divided into two cohorts (training and validation) at a 7:3 ratio. Radiomics features were extracted from contrast enhanced CT images. A radiomics signature was developed based on reproducible features by means of the least absolute shrinkage and selection operator method. Demographics, laboratory variables (including sex, age, Fuhrman grade, hemoglobin, platelet, neutrophils, albumin, and calcium) and CT findings were combined to develop clinical factors model. Integrating radiomics signature and independent clinical factors, a radiomics nomogram was developed. Nomogram performance was determined by calibration, discrimination, and clinical usefulness. Results: Ten features were used to build radiomics signature, which yielded an area under the curve (AUC) of 0.86 in the training cohort and 0.85 in the validation cohort. By incorporating the sex, maximum diameter, neutrophil count, albumin count, and radiomics score, a radiomics nomogram was developed. Radiomics nomogram (AUC: training, 0.91; validation, 0.92) had higher performance than clinical factors model (AUC: training, 0.86; validation, 0.90) or radiomics signature as a means of identifying patients at high risk for recurrence and metastasis. The radiomics nomogram had higher sensitivity than clinical factors mode (McNemar's chi-squared = 4.1667, p = 0.04) and a little lower specificity than clinical factors model (McNemar's chi-squared = 3.2, p = 0.07). The nomogram showed good calibration. Decision curve analysis demonstrated the superiority of the nomogram compared with the clinical factors model in terms of clinical usefulness. Conclusion: The CT-based radiomics nomogram could help in predicting recurrence and metastasis risk in T1 ccRCC, which might provide assistance for clinicians in tailoring precise therapy.

18.
Front Oncol ; 10: 1379, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32850442

RESUMO

Background: The susceptibility of breast cancer is largely affected by the metabolic capacity of breast tissue. This ability depends in part on the expression profile of cytochrome P450 (CYPs). CYPs are a superfamily of enzymes with related catalysis to endogenous and exogenous bioactive substances, including xenobiotic metabolism, drugs, and some endogenous substances metabolism which activate cells and stimulate cell signaling pathways, such as arachidonic acid metabolism, steroid metabolism, fatty acid metabolism. Interestingly, CYP was electively expressed in different tumors, and mediated the metabolic activation of multiple carcinogens and participated in the activation and deactivation of tumor therapeutic drugs. However, the biological action of cytochrome P450 2U1 (CYP2U1) in breast carcinoma is little understood so far. Methods: To investigate the biological value of CYP2U1 in breast carcinoma, we performed immunohistochemical (IHC) analysis and survival analysis based on clinico-pathological data of breast cancer. Results: IHC analysis showed that the abundance of CYP2U1 protein was inversely proportional to the state of estrogen receptor(ER) (P < 0.05), and the lower the degree of tumor differentiation, the higher the protein abundance (P < 0.001). Additionally, compared with luminal tumors, the CYP2U1 protein content was more abundant in triple negative breast cancer (P < 0.05). Importantly, survival analysis showed that higher CYP2U1 protein levels predicted poor 5-year overall survival rate (P < 0.01), 5-year disease-free survival rate (P < 0.05), and 5-year metastatic-free survival rate (P < 0.01) for the entire enrolled breast cancer patients. Conclusions: CYP2U1 is generally closely related to the clinicopathological characteristics and is also an adverse prognostic factor for breast carcinoma patients, indicating that CYP2U1 is engaged in the malignant progression of breast carcinoma.

19.
J Chem Phys ; 153(1): 014706, 2020 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-32640820

RESUMO

In this study, high quality CsxFA1-xPbIyBr3-y perovskite thin films were successfully fabricated by an evaporation/spray-coating hybrid deposition method. In this method, CsI and PbI2 were first deposited via thermal evaporation, and then FAI/FABr mixed solution was sprayed on the CsI/PbI2 substrate to form the CsxFA1-xPbIyBr3-y film. As confirmed by x-ray diffraction, scanning electron microscopy, and atomic force microscopy, a perovskite film with full surface coverage and small surface roughness was obtained. Then, the effect of interface modification materials on the performance of perovskite solar cells (PSCs) was investigated: the devices with the [6,6]-phenyl-C61-butyric acid methyl ester (PCBM) interlayer incorporated via vacuum evaporation deposition between SnO2 and perovskite showed remarkably higher performance than those with the C60 interlayer, which was attributed to enhanced charge extraction and reduced recombination at the SnO2/PCBM/perovskite interface. As a result, a high power conversion efficiency (PCE) of 18.21% was obtained for the 0.16 cm2 device. To the best of our knowledge, it is the highest efficiency of CsxFA1-xPbIyBr3-y based PSCs fabricated by the spray technique. Furthermore, we fabricated mini-modules with the size of 5 × 5 cm2 and achieved a PCE of 14.7%.

20.
Nanoscale ; 12(21): 11746-11758, 2020 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-32458876

RESUMO

The development of flexible all-solid-state rechargeable Zn-air batteries (FS-ZABs) for wearable applications faces challenges from the balance between performance and flexibility of the battery; efficient cathode catalyst and reasonable electrode construction design are key factors. Herein, a low-cost pollen derived N,S co-doped porous carbon decorated with Co9S8/Fe3S4 nanoparticle hybrids (Co-Fe-S@NSRPC) has been synthesized. Owing to the active Co9S8/Fe3S4 nanoparticles, N,S co-doping, and large specific area of the pollen derived porous carbon matrix, the Co-Fe-S@NSRPC composite exhibits an excellent bifunctional catalytic activity with a small potential gap (ΔE = 0.80 V) between the half-wave potential for the ORR (0.80 V) and the potential at 10 mA cm-2 for the OER (1.60 V), and endows a liquid Zn-air battery with a high power density of 138 mW cm-2, a larger specific capacity of 891 mA h g-1 and a stable rechargeability of up to 331 cycles. Based on the Co-Fe-S@NSRPC cathode catalyst, a 2D coplanar FS-ZAB has been fabricated with specially designed parallel narrow strip electrodes alternately arrayed on a polyacrylamide polyacrylic acid copolymer hydrogel solid electrolyte. The presented FS-ZAB exhibits excellent battery performance with high open-circuit-voltage (1.415 V), competitive peak power density (78 mW cm-2), large specific capacity (785 mA h g-1) and stable rechargeability (150 cycles), offers robust flexibility to maintain stable charge/discharge capacity under different bending deformations, and provides convenient coplanar integrability to realize parallel or series connection of multiple cells in a relatively small area.

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