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1.
Cell Mol Life Sci ; 79(5): 240, 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35416530

RESUMO

Ischemic stroke is a leading cause of death and disability worldwide. Increasing evidence indicates that ischemic stroke is a thromboinflammatory disease in which the contact-kinin pathway has a central role by activating pro-coagulant and pro-inflammatory processes. The blocking of distinct members of the contact-kinin pathway is a promising strategy to control ischemic stroke. Here, a plasma kallikrein and active FXII (FXIIa) inhibitor (sylvestin, contained 43 amino acids, with a molecular weight of 4790.4 Da) was first identified from forest leeches (Haemadipsa sylvestris). Testing revealed that sylvestin prolonged activated partial thromboplastin time without affecting prothrombin time. Thromboelastography and clot retraction assays further showed that it extended clotting time in whole blood and inhibited clot retraction in platelet-rich plasma. In addition, sylvestin prevented thrombosis in vivo in FeCl3-induced arterial and carrageenan-induced tail thrombosis models. The potential role of sylvestin in ischemic stroke was evaluated by transient and permanent middle cerebral artery occlusion models. Sylvestin administration profoundly protected mice from ischemic stroke by counteracting intracerebral thrombosis and inflammation. Importantly, sylvestin showed no signs of bleeding tendency. The present study identifies sylvestin is a promising contact-kinin pathway inhibitor that can proffer profound protection from ischemic stroke without increased risk of bleeding.


Assuntos
AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Animais , Inflamação/tratamento farmacológico , Inflamação/prevenção & controle , Cininas , Camundongos , Acidente Vascular Cerebral/tratamento farmacológico , Trombose/tratamento farmacológico
2.
Front Cardiovasc Med ; 9: 813085, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35310976

RESUMO

Purpose: This study aimed to evaluate the feasibility of differentiating the atrial fibrillation (AF) subtype and preliminary explore the prognostic value of AF recurrence after ablation using radiomics models based on epicardial adipose tissue around the left atrium (LA-EAT) of cardiac CT images. Method: The cardiac CT images of 314 patients were collected wherein 251 and 63 cases were randomly enrolled in the training and validation cohorts, respectively. Mutual information and the random forest algorithm were used to screen for the radiomic features and construct the radiomics signature. Radiomics models reflecting the features of LA-EAT were built to differentiate the AF subtype, and the multivariable logistic regression model was adopted to integrate the radiomics signature and volume information. The same methodology and algorithm were applied to the radiomic features to explore the ability for predicting AF recurrence. Results: The predictive model constructed by integrating the radiomic features and volume information using a radiomics nomogram showed the best ability in differentiating AF subtype in the training [AUC, 0.915; 95% confidence interval (CI), 0.880-0.951] and validation (AUC, 0.853; 95% CI, 0.755-0.951) cohorts. The radiomic features have shown convincible predictive ability of AF recurrence in both training (AUC, 0.808; 95% CI, 0.750-0.866) and validation (AUC, 0.793; 95% CI, 0.654-0.931) cohorts. Conclusions: The LA-EAT radiomic signatures are a promising tool in the differentiation of AF subtype and prediction of AF recurrence, which may have clinical implications in the early diagnosis of AF subtype and disease management.

3.
Lung Cancer ; 164: 14-22, 2022 02.
Artigo em Inglês | MEDLINE | ID: mdl-34974221

RESUMO

BACKGROUND: This study was conducted to explore the clinical significance of the maximum standard uptake value (SUVmax) in the clinical stage IA lung adenocarcinoma with tumor size ≤ 2 cm and consolidation to tumor ratio (CTR) > 0.5. METHODS: We retrospectively reviewed non-small cell lung cancer patients who underwent surgeries between January 2014 and March 2017. Clinical stage IA lung adenocarcinoma patients with tumor of size ≤ 2 cm and CTR > 0.5 were enrolled. The patients were divided into two groups: part-solid and pure-solid based on whether CTR = 1.0 or not. Nodules with any amount of solid or micropapillary components were regarded as the high-risk subtype. Time-dependent ROC curve was used to determine the best cut-off value. Finally, we analyzed the relationship between SUVmax, high-risk subtypes, node metastasis and 5-year relapse-free survival and overall survival. RESULTS: Totally, 270 patients were included. The distribution of pathological subtypes (p < 0.001), SUVmax (p < 0.001), and pathological N stage (p < 0.001) were different between the two groups. Multivariable analysis indicated that SUVmax could predict high-risk subtypes in cases of part-solid nodules (p < 0.001) and both high-risk subtypes (p = 0.022) and node metastasis (p < 0.001) in cases of pure-solid ones. SUVmax ≥ 2.6 and SUVmax ≥ 5.1 were strongly associated with 5-year relapse-free survival (p < 0.001) and 5-year overall survival (p < 0.001) among all the patients, respectively. CONCLUSION: Part-solid nodules with 0.5 < CTR < 1 and pure-solid nodules in lung adenocarcinoma show different clinicopathological characteristics, especially in SUVmax. SUVmax is significantly associated with high-risk subtypes, node metastasis, 5-year relapse-free survival and overall survival.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Fluordesoxiglucose F18 , Humanos , Neoplasias Pulmonares/patologia , Recidiva Local de Neoplasia , Estadiamento de Neoplasias , Tomografia por Emissão de Pósitrons , Prognóstico , Compostos Radiofarmacêuticos , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
4.
IEEE Trans Med Imaging ; 41(4): 771-781, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34705640

RESUMO

Lung cancer is the leading cause of cancer deaths worldwide. Accurately diagnosing the malignancy of suspected lung nodules is of paramount clinical importance. However, to date, the pathologically-proven lung nodule dataset is largely limited and is highly imbalanced in benign and malignant distributions. In this study, we proposed a Semi-supervised Deep Transfer Learning (SDTL) framework for benign-malignant pulmonary nodule diagnosis. First, we utilize a transfer learning strategy by adopting a pre-trained classification network that is used to differentiate pulmonary nodules from nodule-like tissues. Second, since the size of samples with pathological-proven is small, an iterated feature-matching-based semi-supervised method is proposed to take advantage of a large available dataset with no pathological results. Specifically, a similarity metric function is adopted in the network semantic representation space for gradually including a small subset of samples with no pathological results to iteratively optimize the classification network. In this study, a total of 3,038 pulmonary nodules (from 2,853 subjects) with pathologically-proven benign or malignant labels and 14,735 unlabeled nodules (from 4,391 subjects) were retrospectively collected. Experimental results demonstrate that our proposed SDTL framework achieves superior diagnosis performance, with accuracy = 88.3%, AUC = 91.0% in the main dataset, and accuracy = 74.5%, AUC = 79.5% in the independent testing dataset. Furthermore, ablation study shows that the use of transfer learning provides 2% accuracy improvement, and the use of semi-supervised learning further contributes 2.9% accuracy improvement. Results implicate that our proposed classification network could provide an effective diagnostic tool for suspected lung nodules, and might have a promising application in clinical practice.


Assuntos
Neoplasias Pulmonares , Nódulo Pulmonar Solitário , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/patologia , Estudos Retrospectivos , Nódulo Pulmonar Solitário/diagnóstico por imagem , Nódulo Pulmonar Solitário/patologia , Aprendizado de Máquina Supervisionado , Tomografia Computadorizada por Raios X/métodos
5.
Chemosphere ; 288(Pt 3): 132658, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34710452

RESUMO

Gastrointestinal reaction is an important symptom of fluorosis and is associated with intestinal morphological and functional impairment. Regular moderate exercise may reduce the incidence of infection and contribute to the maintenance of intestinal mucosal function and immune homeostasis. In this study, the mice were randomly divided to four groups: control group (C, distilled water), exercise group (E, distilled water and treadmill exercise), fluoride group (F, 100 mg/L NaF), and exercise plus fluoride group (EF, 100 mg/L NaF and treadmill exercise). The treadmill exercise was performed as 5 m/min, 5 min; 10 or 12 m/min, 20 min; 5 m/min, 5 min, with 5 consecutive days per week. After 6 months, exercise alleviated the intestinal morphological structure damage and restored the villus height (VH) and VH/crypt depth (VH/CD) in the duodenum of fluoride-exposed mice. Exercise decreased the mRNA expressions of IL-1ß, IL-6, TNF-α, TLR2 and NF-κB (p65) in fluoride-exposed mice, and restored the gene levels of Occludin and ZO-1 in the duodenum, as well as Occludin, ZO-1, and Claudin-1 in the colon. Although there were no significant differences in the Occludin and ZO-1 protein expressions between F and EF, two proteins in EF presented statistical homogeneousness when compared with the C. The 16S rDNA high-throughput sequencing found that exercise restored the variations in intestinal microbiota composition and the abundances of specific bacteria in fluoride-exposed mice, including increasing the abundances of Epsilonbacteraenta and Firmicutes, reducing the Bacteroidetes abundance at the phylum level, and restoring the abundances of 13 bacterial genera. In conclusion, exercise improved intestinal morphological structure damage in fluoride-exposed mice, inhibited the secretion of duodenal inflammatory factors, increased the expression of tight junctions, and alleviated the microbial disorder in mice caused by fluoride exposure for 6 months through actively regulating the composition of intestinal microorganisms and the abundance of specific bacteria.


Assuntos
Fluoretos , Microbioma Gastrointestinal , Animais , Colo , Fluoretos/toxicidade , Mucosa Intestinal , Camundongos , Ocludina
6.
Biol Trace Elem Res ; 200(2): 678-688, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33825162

RESUMO

Fluoride exposure caused anxiety- and depression-like behavior in mice. Meanwhile, exercise contributes to relieve anxiety and depression. However, the effects of exercise on anxiety- and depression-like behavior in fluorosis mice remain unclear. In the current study, thirty-six Institute of Cancer Research (ICR) female mice were randomly assigned to four groups: control group (C, gavage with distilled water); exercise group (E, gavage with distilled water and treadmill exercise (speed, 10 m/min; time, 30 min/day)); fluoride group (F, gavage with 24 mg/kg sodium fluoride (NaF)); and exercise plus fluoride group (EF, gavage with 24 mg/kg NaF and treadmill exercise). All treatments lasted for 8 weeks. A number of entries into and time spent in the open zone in the elevated zero maze (EZM), resting time in the tail suspension test (TST) and levels of serotonin (5-HT) and gamma-aminobutyric acid (GABA), were significantly altered in F when compared to C. Meanwhile, the anxiety-like behavior in the EZM and the depression-like behavior in the TST were significantly improved in EF when compared to group F. Exercise significantly enhanced fluoride-induced low GABA level, with less effect on the concentration of 5-HT. Moreover, the mRNA and protein expressions of GABA synthesis and transport-related proteins of glutamic acid decarboxylase (GAD) 65 and GAD67 and vesicular GABA transporter (VGAT) were all strikingly decreased in F, while those in EF were increased. In conclusion, exercise ameliorates anxiety- and depression-like behavior in fluorosis mice through increasing the expressions of GABA synthesis and transport-related proteins, rather than 5-HT system.


Assuntos
Depressão , Fluoretos , Animais , Ansiedade/induzido quimicamente , Comportamento Animal , Depressão/induzido quimicamente , Feminino , Fluoretos/toxicidade , Camundongos , Serotonina , Ácido gama-Aminobutírico
9.
Aging Cell ; 20(10): e13482, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34582091

RESUMO

Aging has many effects on the female reproductive system, among which decreased oocyte quality and impaired embryo developmental potential are the most important factors affecting female fertility. However, the mechanisms underlying oocyte aging are not yet fully understood. Here, we selected normal reproductively aging female mice and constructed a protein expression profile of metaphase II (MII) oocytes from three age groups. A total of 187 differentially expressed (DE) proteins were identified, and bioinformatics analyses showed that these DE proteins were highly enriched in RNA splicing. Next, RNA-seq was performed on 2-cell embryos from these three age groups, and splicing analysis showed that a large number of splicing events and genes were discovered at this stage. Differentially spliced genes (DSGs) in the two reproductively aging groups versus the younger group were enriched in biological processes related to DNA damage repair/response. Binding motif analysis suggested that PUF60 might be one of the core splicing factors causing a decline in DNA repair capacity in the subsequent development of oocytes from reproductively aging mice, and changing the splicing pattern of its potential downstream DSG Cdk9 could partially mimic phenotypes in the reproductively aging groups. Taken together, our study suggested that the abnormal expression of splicing regulation proteins in aged MII oocytes would affect the splicing of nascent RNA after zygotic genome activation in 2-cell embryos, leading to the production of abnormally spliced transcripts of some key genes associated with DNA damage repair/response, thus affecting the developmental potential of aged oocytes.


Assuntos
Envelhecimento/genética , Oócitos/metabolismo , Proteoma/metabolismo , Splicing de RNA/genética , Adulto , Animais , Feminino , Humanos , Camundongos
10.
Reprod Sci ; 28(12): 3448-3457, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34494234

RESUMO

Tubulin beta eight class VIII (TUBB8) is a subtype of ß-tubulin that only exists in primates. TUBB8 mutations have been reported to cause arrest of oocyte maturation and embryonic development. We aim to further investigate the mutational spectrum of TUBB8 and its relevance with female infertility. In our study, infertile patients were recruited, and their basal and clinical characteristics were analyzed. Genomic DNA was extracted from peripheral blood donated by patients. Candidate variants were identified by whole-exome sequencing, selected by relevant criteria, and validated by Sanger sequencing. We found five heterozygous variants: c.C208A(p.P70T), c.T907C(p.C303R), c.G173A(p.R58K), c.G326T(p.G109V), and c.C916T(p.R306C) in TUBB8 among six infertile patients characterized by abnormal phenotypes in oocyte maturation, fertilization, or embryo development. Most of oocytes retrieved from affected individuals were arrested at GV (germinal vesicle) stage and early embryos were arrested at variable stages. In vitro experiments were performed, and the relationship between variant c.G173A(p.R58K), c.C208A(p.P70T), and infertility phenotype was confirmed. We also discussed the possibility about patient II-1 from family 4 is affected by germinal/germline mosaicism. These results expand the kinds of variants and phenotypic spectrum of TUBB8 variants with regard to female infertility.


Assuntos
Variação Genética/genética , Infertilidade Feminina/genética , Mutação de Sentido Incorreto/genética , Fenótipo , Tubulina (Proteína)/genética , Sequenciamento Completo do Exoma/métodos , Adulto , Sequência de Aminoácidos , Animais , Células Cultivadas , Técnicas de Cultura Embrionária/métodos , Feminino , Humanos , Infertilidade Feminina/diagnóstico , Camundongos , Camundongos Endogâmicos ICR , Oócitos/metabolismo , Linhagem , Gravidez , Estrutura Secundária de Proteína , Tubulina (Proteína)/química
11.
Cell Discov ; 7(1): 64, 2021 Aug 10.
Artigo em Inglês | MEDLINE | ID: mdl-34373443

RESUMO

Coronavirus disease 2019 (COVID-19), driven by SARS-CoV-2, is a severe infectious disease that has become a global health threat. Vaccines are among the most effective public health tools for combating COVID-19. Immune status is critical for evaluating the safety and response to the vaccine, however, the evolution of the immune response during immunization remains poorly understood. Single-cell RNA sequencing (scRNA-seq) represents a powerful tool for dissecting multicellular behavior and discovering therapeutic antibodies. Herein, by performing scRNA/V(D)J-seq on peripheral blood mononuclear cells from four COVID-19 vaccine trial participants longitudinally during immunization, we revealed enhanced cellular immunity with concerted and cell type-specific IFN responses as well as boosted humoral immunity with SARS-CoV-2-specific antibodies. Based on the CDR3 sequence and germline enrichment, we were able to identify several potential binding antibodies. We synthesized, expressed and tested 21 clones from the identified lineages. Among them, one monoclonal antibody (P3V6-1) exhibited relatively high affinity with the extracellular domain of Spike protein, which might be a promising therapeutic reagent for COVID-19. Overall, our findings provide insights for assessing vaccine through the novel scRNA/V(D)J-seq approach, which might facilitate the development of more potent, durable and safe prophylactic vaccines.

12.
Clin Transl Med ; 11(4): e379, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33931972

RESUMO

BACKGROUND AND AIMS: 4-phenylbutyric acid (4-PBA) is a low molecular weight fatty acid that is used in clinical practice to treat inherited urea cycle disorders. In previous reports, it acted as a chemical chaperone inhibiting endoplasmic reticulum (ER) stress and unfolded protein response signaling. A few studies have suggested its function against hepatic fibrosis in mice models. However, its role in hepatocarcinogenesis remained unknown. METHODS: 4-PBA was administered alone or in combination with diethylnitrosamine to investigate its long-term effect on liver tumorigenesis. The role of 4-PBA in oncogene-induced hepatocellular carcinoma (HCC) mice model using sleeping beauty system co-expressed with hMet and ß-catenin point mutation (S45Y) was also observed. RNA-seq and PCR array were used to screen the pathways and genes involved. In vitro and in vivo studies were conducted to explore the effect of 4-PBA on liver and validate the underlying mechanism. RESULTS: 4-PBA alone didn't cause liver tumor in long term. However, it promoted liver tumorigenesis in HCC mice models via initiation of liver cancer stem cells (LCSCs) through Wnt5b-Fzd5 mediating ß-catenin signaling. Peroxisome proliferator-activated receptors (PPAR)-α induced by 4-PBA was responsible for the activation of ß-catenin signaling. Thus, intervention of PPAR-α reversed 4-PBA-induced initiation of LCSCs and HCC development in vivo. Further study revealed that 4-PBA could not only upregulate the expression of PPAR-α transcriptionally but also enhance its stabilization via protecting it from proteolysis. Moreover, high PPAR-α expression predicted poor prognosis in HCC patients. CONCLUSIONS: 4-PBA could upregulate PPAR-α to initiate LCSCs by activating ß-catenin signaling pathway, promoting HCC at early stage. Therefore, more discretion should be taken to monitor the potential tumor-promoting effect of 4-PBA under HCC-inducing environment.


Assuntos
Carcinoma Hepatocelular/induzido quimicamente , Neoplasias Hepáticas/induzido quimicamente , Células-Tronco Neoplásicas/efeitos dos fármacos , PPAR alfa/metabolismo , Fenilbutiratos/farmacologia , Animais , Carcinogênese/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Nus , Via de Sinalização Wnt/efeitos dos fármacos
13.
Zool Res ; 42(3): 335-338, 2021 May 18.
Artigo em Inglês | MEDLINE | ID: mdl-33998180

RESUMO

The global outbreak of coronavirus disease 2019 (COVID-19), which is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), as of 8 May 2021, has surpassed 150 700 000 infections and 3 279 000 deaths worldwide. Evidence indicates that SARS-CoV-2 RNA can be detected on particulate matter (PM), and COVID-19 cases are correlated with levels of air pollutants. However, the mechanisms of PM involvement in the spread of SARS-CoV-2 remain poorly understood. Here, we found that PM exposure increased the expression level of angiotensin-converting enzyme 2 (ACE2) and transmembrane serine protease 2 (TMPRSS2) in several epithelial cells and increased the adsorption of the SARS-CoV-2 spike protein. Instillation of PM in a hACE2 mouse model significantly increased the expression of ACE2 and Tmprss2 and viral replication in the lungs. Furthermore, PM exacerbated the pulmonary lesions caused by SARS-CoV-2 infection in the hACE2 mice. In conclusion, our study demonstrated that PM is an epidemiological factor of COVID-19, emphasizing the necessity of wearing anti-PM masks to cope with this global pandemic.


Assuntos
Enzima de Conversão de Angiotensina 2/metabolismo , COVID-19/induzido quimicamente , COVID-19/imunologia , Material Particulado/efeitos adversos , SARS-CoV-2 , Adsorção/efeitos dos fármacos , Animais , Suscetibilidade a Doenças/induzido quimicamente , Suscetibilidade a Doenças/imunologia , Células Epiteliais/metabolismo , Camundongos , Camundongos Endogâmicos , Material Particulado/química , RNA Viral/análise , SARS-CoV-2/genética , Serina Endopeptidases/metabolismo , Glicoproteína da Espícula de Coronavírus/metabolismo , Internalização do Vírus/efeitos dos fármacos
14.
Food Chem ; 356: 129682, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-33812196

RESUMO

Passion fruit peel, a potential source of bioactive compounds, has been used as food stabilizing agent. However, the phenolic composition and bioactivity of passion fruit peel have rarely been reported. The effects of simulated gastrointestinal digestion on the bioactive components, bioactivity and bioaccessibility of passion fruit peel ethanol extracts (PFPE) were investigated using high performance liquid chromatography-tandem mass spectrometry analysis (quasi-targeted metabolomics). Phenols (178) were identified, of which 25 inhibited alpha-glucosidase activity. The stabilities of PFPE phenols were significantly affected by pH changes and digestive enzymes during simulated digestion. The 1,1-diphenyl-2-picrylhydrazyl free radical scavenging capacity and ferric ion reducing antioxidant power were decreased by 32% and 30%, respectively, while 2,2'-azinobis-(3-ethylbenzthiazoline-6-sulphonate) free radical scavenging capacity increased by 17%. Alpha-glucosidase inhibition decreased with decreased PFPE phenolic content. Therefore, passion fruit peel could be considered a source of natural antioxidants and alpha-glucosidase inhibitors.


Assuntos
Cromatografia Líquida de Alta Pressão , Passiflora/química , Fenóis/análise , Extratos Vegetais/química , Espectrometria de Massas em Tandem , Digestão , Etanol/química , Sequestradores de Radicais Livres/química , Frutas/química , Frutas/metabolismo , Passiflora/metabolismo , Fenóis/química , alfa-Glucosidases/química , alfa-Glucosidases/metabolismo
15.
Cell ; 184(7): 1895-1913.e19, 2021 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-33657410

RESUMO

A dysfunctional immune response in coronavirus disease 2019 (COVID-19) patients is a recurrent theme impacting symptoms and mortality, yet a detailed understanding of pertinent immune cells is not complete. We applied single-cell RNA sequencing to 284 samples from 196 COVID-19 patients and controls and created a comprehensive immune landscape with 1.46 million cells. The large dataset enabled us to identify that different peripheral immune subtype changes are associated with distinct clinical features, including age, sex, severity, and disease stages of COVID-19. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA was found in diverse epithelial and immune cell types, accompanied by dramatic transcriptomic changes within virus-positive cells. Systemic upregulation of S100A8/A9, mainly by megakaryocytes and monocytes in the peripheral blood, may contribute to the cytokine storms frequently observed in severe patients. Our data provide a rich resource for understanding the pathogenesis of and developing effective therapeutic strategies for COVID-19.


Assuntos
COVID-19/imunologia , Megacariócitos/imunologia , Monócitos/imunologia , RNA Viral , SARS-CoV-2/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , China , Estudos de Coortes , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , RNA Viral/sangue , RNA Viral/isolamento & purificação , Análise de Célula Única , Transcriptoma/imunologia , Adulto Jovem
16.
Front Cell Dev Biol ; 9: 628649, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33614659

RESUMO

PAT1 homolog 2 (PATL2), encoding an RNA-binding protein, is a repressor involved in the translational regulation of maternal mRNAs during oocyte maturation. Previous studies have reported mutations in PATL2 those led to female infertility with oocyte maturation arrest; however, the mechanisms by which mutations affected meiotic maturation remained unclear. Here, we identified several novel and recurrent mutations of PATL2 in patients with similar phenotype, and chose the missense mutation c.649 T>A p.Tyr217Asn in PATL2 (PATL2Y217N) as a typical to investigate the underlying mechanisms. We confirmed that this mutation disturbed oocyte maturation and observed morphological defects of large polar body, symmetrical division and abnormal spindle after microinjection of corresponding mutated mRNA. We further evaluated the effect of the PATL2Y217N mutation in 293T cells, and found this mutation decreased the ubiquitination level and degradation of PATL2. Then, abnormally increased PATL2 bound mRNAs of Mos, an upstream activator of mitogen activated protein kinase (MAPK), to regulate its translational activity and subsequently impaired MAPK signaling pathway and oocyte meiosis. These results dissented from the previous view that PATL2 mutations reduced their expression and highlight the role of PATL2 in translational regulation of Mos and its association with MAPK signaling pathway during oocyte meiotic maturation.

17.
Am J Physiol Lung Cell Mol Physiol ; 320(1): L84-L98, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33146564

RESUMO

Coronavirus disease 2019 (COVID-19), driven by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was declared a global pandemic in March 2020. Pathogenic T cells and inflammatory monocytes are regarded as the central drivers of the cytokine storm associated with the severity of COVID-19. In this study, we explored the characteristic peripheral cellular profiles of patients with COVID-19 in both acute and convalescent phases by single-cell mass cytometry (CyTOF). Using a combination of algorithm-guided data analyses, we identified peripheral immune cell subsets in COVID-19 and revealed CD4+ T-cell depletion, T-cell differentiation, plasma cell expansion, and the reduced antigen presentation capacity of innate immunity. Notably, COVID-19 induces a dysregulation in the balance of monocyte populations by the expansion of the monocyte subsets. Collectively, our results represent a high-dimensional, single-cell profile of the peripheral immune response to SARS-CoV-2 infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , COVID-19/imunologia , Leucócitos Mononucleares/imunologia , Monócitos/imunologia , SARS-CoV-2/imunologia , Adulto , Idoso , Apresentação do Antígeno/imunologia , Linfócitos T CD4-Positivos/citologia , COVID-19/patologia , Síndrome da Liberação de Citocina/imunologia , Síndrome da Liberação de Citocina/patologia , Citocinas/imunologia , Células Dendríticas/citologia , Células Dendríticas/imunologia , Feminino , Humanos , Células Matadoras Naturais/citologia , Células Matadoras Naturais/imunologia , Leucócitos Mononucleares/citologia , Depleção Linfocítica , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Plasmócitos/citologia , Análise de Célula Única
18.
Transl Lung Cancer Res ; 9(4): 1516-1527, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32953523

RESUMO

BACKGROUND: Radiological manifestations of coronavirus disease 2019 (COVID-19) featured ground-glass opacities (GGOs), especially in the early stage, which might create confusion in differential diagnosis with early lung cancer. We aimed to specify the radiological characteristics of COVID-19 and early lung cancer and to unveil the discrepancy between them. METHODS: One hundred and fifty-seven COVID-19 patients and 374 early lung cancer patients from four hospitals in China were retrospectively enrolled. Epidemiological, clinical, radiological, and pathological characteristics were compared between the two groups using propensity score-matched (PSM) analysis. RESULTS: COVID-19 patients had more distinct symptoms, tended to be younger (P<0.0001), male (P<0.0001), and had a higher body mass index (P=0.014). After 1:1 PSM, 121 matched pairs were identified. Regarding radiological characteristics, patients with a single lesion accounted for 17% in COVID-19 and 89% in lung cancer (P<0.0001). Most lesions were peripherally found in both groups. Lesions in COVID-19 involved more lobes (median 3.5 vs. 1; P<0.0001) and segments (median 6 vs. 1; P<0.0001) and tended to have multiple types (67%) with patchy form (54%). Early lung cancer was more likely to have a single type (92%) with oval form (66%). Also, COVID-19 and early lung cancer either had some distinctive features on computed tomography (CT) images. CONCLUSIONS: Both COVID-19 and early lung cancers showed GGOs, with similar but independent features. The imaging characteristics should be fully understood and combined with epidemiological history, pathogen detection, laboratory tests, short-term CT reexamination, and pathological results to aid differential diagnosis.

19.
Sci Rep ; 10(1): 13504, 2020 08 11.
Artigo em Inglês | MEDLINE | ID: mdl-32782337

RESUMO

A. fruticosa (Amorpha fruticosa L.) is widely used for revegetation in semiarid lands that undergo secondary salinization. Understanding A. fruticosa plants response to soil water and salt stress is essential for water irrigation management and proper revegetation practices. In this study, we measured sap flow, stomatal conductance, meteorological and soil characteristics in an A. fruticosa community that recently experienced secondary salinization in northwestern China. Results of our study showed that daytime and nocturnal sap flows averaged 804.37 g·cm-2·day-1 and 46.06 g·cm-2·day-1, respectively, during the growing season. Within individual days, the highest sap flow appeared around noon local time and followed a similar pattern of photosynthetically active radiation (PAR). Despite the significant effect of meteorological factors on the characteristics of sap flow, our study highlighted that the sap flow of A. fruticosa is strongly regulated by the availability of soil relative extractable water (REW). The daytime sap flow, which is predominant compared to nocturnal sap flow, was strongly affected by PAR, air temperature and vapor-pressure deficit. With water stress in the top 40 cm of the soil (REW0-40 cm < 0.4), daytime sap flow displayed a strong relationship with soil water content (SWC) (positive) and soil electrical conductivity (EC) (negative) in the relatively shallow soil profile (up to 40 cm). For the nocturnal sap flow, our results suggest that in the absence of soil water stress (REW0-40 cm > 0.4), the nocturnal sap flow is mainly used to replenish the stem water content and sustain nocturnal transpiration. Under soil water stress, nocturnal sap flow is mainly used to replenish stem water content. The results of our study indicate that it is necessary to shorten the irrigation cycle during the primary growing period (May-July) of A. fruticosa. Moreover, in the absence of soil water stress (REW0-40 cm > 0.4), A. fruticosa can survive well in an saline environment with soil EC < 5 mS·cm-1.

20.
Radiol Infect Dis ; 7(3): 97-105, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32838005

RESUMO

OBJECTIVE: To explore the clinical and radiological characteristics of COVID-19 patients with progressive and non-progressive CT manifestations. METHODS: 160 patients with COVID-19 were retrospectively included from Wenzhou and Wuhan, China. CT features including lesion position, attenuation, form and total scores (0-4) at the segment level were evaluated. Other images signs were also assessed. 65 patients were classified as progressive (group 1) and 95 as non-progressive CT (group 2) groups according to score changes between the initial and second CT. RESULTS: Symptoms onset-initial CT interval time in group 1 [5 (2, 7) days] were significantly shorter than that in group 2 [10 (8, 14) days] (P < 0.001). Group 2 had higher radiological scores, with more lobes and segments affected, and other CT signs (P < 0.05). In group 1, radiological scores, the number of lobes and segments affected as well as lesions in both peripheral and central distribution, mixed ground grass opacity and consolidation density, and patchy form increased in the second CT (P < 0.05). More reticular pattern, subpleural linear opacity and bronchial dilatation were also found (P < 0.05). CONCLUSION: Typically radiological characteristics of progressive CT patients could potentially help to predict changes and increase understanding of the natural history of COVID-19.

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