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1.
J Virol ; 96(22): e0095422, 2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36326277

RESUMO

The H240R protein (pH240R), encoded by the H240R gene of African swine fever virus (ASFV), is a 241-amino-acid capsid protein. We previously showed that the deletion of H240R from the ASFV genome, creating ASFV-ΔH240R, resulted in an approximately 2-log decrease in infectious virus production compared with the wild-type ASFV strain (ASFV-WT), and ASFV-ΔH240R induced higher interleukin 1ß (IL-1ß) production in porcine alveolar macrophages (PAMs) than did ASFV-WT, but the underlying mechanism remains to be elucidated. Here, we demonstrate that the activation of the NF-κB signaling and NLRP3 inflammasome was markedly induced in PAMs upon ASFV-ΔH240R infection compared with ASFV-WT. Moreover, pH240R inhibited NF-κB activation by interacting with NEMO and promoting the autophagy-mediated lysosomal degradation of NEMO, resulting in reduced pro-IL-1ß transcription. Strikingly, NLRP3 deficiency in PAMs inhibited the ASFV-ΔH240R-induced IL-1ß secretion and caspase 1 activation, indicating an essential role of NLRP3 inflammasome activation during ASFV-ΔH240R replication. Mechanistically, pH240R interacted with NLRP3 to inhibit its oligomerization, leading to decreased IL-1ß production. Furthermore, the inhibition of the NF-κB signaling and NLRP3 inflammasome activation promoted ASFV-ΔH240R replication in PAMs. Taken together, the results of this study reveal an antagonistic mechanism by which pH240R suppresses the host immune response by manipulating activation of the NF-κB signaling and NLRP3 inflammasome, which might guide the rational design of live attenuated vaccines or therapeutic strategies against ASF in the future. IMPORTANCE African swine fever (ASF), a lethal hemorrhagic disease, is caused by African swine fever virus (ASFV). There are no commercially available vaccines or antivirals for the disease. Here, we showed that ASFV with a deletion of the H240R gene exhibits high-level expression of interleukin 1ß (IL-1ß), a proinflammatory cytokine, in porcine alveolar macrophages and that the H240R protein (pH240R) exhibits robust inhibitory effects on IL-1ß transcription and production. More specifically, pH240R inhibited NF-κB activation via the autophagy-mediated lysosomal degradation of NEMO, leading to the decrease of pro-IL-1ß transcription. In addition, pH240R interacted with NLRP3 to inhibit its oligomerization, leading to decreased IL-1ß production. Our results indicate that pH240R is involved in the evasion of host innate immunity and provide a novel target for the development of a live attenuated vaccine against ASF.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Animais , Suínos , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Vírus da Febre Suína Africana/genética , Vírus da Febre Suína Africana/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , NF-kappa B/metabolismo
2.
Read Writ ; : 1-29, 2022 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-36438429

RESUMO

Children who speak one language at home and a different language at school may be at higher risk of falling behind in their academic achievement when schooling is disrupted. The present study examined the effects of COVID-19-related school disruptions on English language and literacy development among monolingual and bilingual children in the US. All children attended English-only schools that implemented varied forms of virtual and hybrid schooling during the pandemic. Pre-COVID-19 and during-COVID-19 examinations were conducted with 237 children (M(SD) age = 7.78 (1.54) at Time 1) from relatively high SES homes, including 95 monolinguals, 75 Spanish-English and 67 Chinese-English bilinguals. The findings revealed different impacts of COVID-19 school disruptions on the present bilingual and monolingual participants. Specifically, between Time 1 and Time 2, monolingual children made age-appropriate improvements in all literacy measurements. Relative to monolinguals, both bilingual groups showed greater gains in vocabulary but lower gains in reading comprehension. Moreover, across groups, children's independent reading practices during COVID-19 were positively associated with children's literacy growth during the pandemic-related schooling disruptions. Taken together, these findings inform theoretical perspectives on learning to read in linguistically diverse children experiencing COVID-19-related schooling disruptions. Supplementary Information: The online version contains supplementary material available at 10.1007/s11145-022-10388-x.

3.
BMC Public Health ; 22(1): 2025, 2022 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-36335401

RESUMO

BACKGROUND: Gastric cancer is a major public health problem worldwide. Social media has affected public's daily lives in ways no one ever thought possible. Both TikoTok and its Chinese version Douyin are the most popular short video posting platform. This study aimed to evaluate the quality, accuracy, and completeness of videos for gastric cancer on TikTok and Douyin. METHODS: The terms "gastric cancer" was searched on TikTok in both English and Japanese, and on Douyin in Chinese. The first 100 videos in three languages (website's default setting) were checked. QUality Evaluation Scoring Tool (QUEST) and DISCERN as the instrument for assessing the quality of the information in each video. Content was analysed under six categories (aetiology, anatomy, symptoms, preventions, treatments, and prognosis). The educational value and completeness were evaluated with a checklist developed by the researchers. RESULTS: A total of 78 videos in English, 63 in Japanese, and 99 in Chinese were analyzed. The types of sources were as follows: 6.4% in English, 4.8% in Japanese, and 57.6% in Chinese for health professionals; 93.6% in English, 95.2% in Japanese, and 3.0% in Chinese for private users; none in English and Japanese, but 39.4% in Chinese for other sources. In all, 20.5% in English, 17.5% in Japanese, and 93.9% in Chinese of videos had useful information about gastric cancer. Among the useful videos, the videos published in Chinese had the highest QUEST(p < 0.05) and DISCERN scores(p < 0.05), followed by those published in Japanese. Among the educational videos, prognosis in English (37.5%), symptoms in Japanese (54.5%), and prevention in Chinese (47.3%) were the most frequently covered topic. CONCLUSIONS: TikTok in English and Japanese might not fully meet the gastric cancer information needs of public, but Douyin in Chinese was the opposite.


Assuntos
Neoplasias , Mídias Sociais , Humanos , Disseminação de Informação , Gravação em Vídeo , Idioma
4.
Vaccines (Basel) ; 10(9)2022 Sep 19.
Artigo em Inglês | MEDLINE | ID: mdl-36146640

RESUMO

BACKGROUND: The plasma membrane provides a highly dynamic barrier for cancer cells to interact with their surrounding microenvironment. Membrane tension, a pivotal physical property of the plasma membrane, has attracted widespread attention since it plays a role in the progression of various cancers. This study aimed to identify a prognostic signature in colon cancer from membrane tension-related genes (MTRGs) and explore its implications for the disease. METHODS: Bulk RNA-seq data were obtained from The Cancer Genome Atlas (TCGA) database, and then applied to the differentially expressed gene analysis. By implementing a univariate Cox regression and a LASSO-Cox regression, we developed a prognostic model based on four MTRGs. The prognostic efficacy of this model was evaluated in combination with a Kaplan-Meier analysis and receiver operating characteristic (ROC) curve analysis. Moreover, the relationships between the signature and immune cell infiltration, immune status, and somatic mutation were further explored. Lastly, by utilizing single-cell RNA-seq data, cell type annotation, pseudo-time analysis, drug sensitivity, and molecular docking were implemented. RESULTS: We constructed a 4-MTRG signature. The risk score derived from the model was further validated as an independent variable for survival prediction. Two risk groups were divided based on the risk score calculated by the 4-MTRG signature. In addition, we observed a significant difference in immune cell infiltration, such as subsets of CD4 T cells and macrophages, between the high- and low-risk groups. Moreover, in the pseudo-time analysis, TIMP1 was found to be more highly expressed with the progression of time. Finally, three small molecule drugs, elesclomol, shikonin, and bryostatin-1, exhibited a binding potential to TIMP-1. CONCLUSIONS: The novel 4-MTRG signature is a promising biomarker in predicting clinical outcomes for colon cancer patients, and TIMP1, a member of the signature, may be a sensitive regulator of the progression of colon cancer.

5.
Viruses ; 14(8)2022 08 08.
Artigo em Inglês | MEDLINE | ID: mdl-36016361

RESUMO

The pandemics caused by emerging viruses such as severe acute respiratory syndrome coronavirus 2 result in severe disruptions to public health. Vaccines and antibody drugs play essential roles in the control and prevention of emerging infectious diseases. However, in contrast with the neutralizing antibodies (NAbs), sub- or non-NAbs may facilitate the virus to enter the cells and enhance viral infection, which is termed antibody-dependent enhancement (ADE). The ADE of most virus infections is mediated by the Fc receptors (FcRs) expressed on the myeloid cells, while others are developed by other mechanisms, such as complement receptor-mediated ADE. In this review, we comprehensively analyzed the characteristics of the viruses inducing FcRs-mediated ADE and the new molecular mechanisms of ADE involved in the virus entry, immune response, and transcription modulation, which will provide insights into viral pathogenicity and the development of safer vaccines and effective antibody drugs against the emerging viruses inducing ADE.


Assuntos
COVID-19 , Viroses , Vírus , Anticorpos Neutralizantes , Anticorpos Antivirais , Anticorpos Facilitadores , Humanos , Receptores Fc , Viroses/prevenção & controle
6.
Front Immunol ; 13: 939836, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35898512

RESUMO

Gastric cancer (GC) is a disease characterized by high molecular and phenotypic heterogeneity and represents a leading cause of cancer-related death worldwide. The tumor immune microenvironment (TIME) affects the response to immunotherapy and the prognosis of patients with GC. Explorations of the TIME in GC and characterization of molecular subtypes might enhance personalized treatment and facilitate clinical decision-making. In this study, two molecular subtypes were defined through unsupervised consensus clustering based on immune-related dysregulated genes. Then, patients with different molecular subtypes of GC were shown to have distinct differences in sensitivity to immune checkpoint blockers (ICBs). The immune-related prognostic signature was established utilizing least absolute shrinkage and selection operator (LASSO)-Cox regression analysis. Three independent external cohorts and the IMvigor210 cohort were introduced to validate the robustness of IPRS. scRNA-seq data of GC samples were used to decipher the underlying mechanisms of how IPRS contributes to the TIME. GC biospecimens were collected for RT-qPCR to further validate our findings. In summary, we characterized the abnormal TIME of GC and constructed a reliable immune-related prognostic signature correlating with the response to immunotherapy. This study may provide new strategies for developing individualized treatments for patients with GC.


Assuntos
Neoplasias Gástricas , Biomarcadores Tumorais/genética , Humanos , Fatores Imunológicos , Imunoterapia , Prognóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/terapia , Microambiente Tumoral
7.
Front Pharmacol ; 13: 894981, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35694250

RESUMO

Background and aims: Saikosaponin d (SSd) has a steroidal structure and significant anti-inflammatory effects. The purpose of this study was to explore the mechanism underlying SSd's inhibitory effects on liver fibrosis. Methods: Wild-type and estrogen receptor knockout (ERKO) mice were treated with CCl4 to establish liver fibrosis mouse models. The effects of SSd on hepatic fibrogenesis were studied in these mouse models. Hepatic stellate cells (HSCs) were activated by H2O2 to investigate the potential molecular mechanisms. The establishment of the models and the degrees of inflammation and liver tissue fibrosis were evaluated by detecting changes in serum liver enzymes and liver histopathology. The expression of α-SMA and TGF-ß1 was determined by immunohistochemistry. The expression and significance of NLRP3 inflammasome proteins were explored by RT-PCR and Western blotting analyses. The mitochondrial ROS-related indexes were evaluated by MitoSOX Red. Results: In wild-type and ERKO mice treated with CCl4, the fluorescence expression of mitochondrial ROS was up-regulated, while the mitochondrial membrane potential and ATP content were decreased, suggesting that the mitochondria were damaged. In addition, the expression of NLRP3 inflammatory bodies and fibrosis markers (α-SMA, TGF-ß, TIMP-1, MMP-2, and Vimentin) in liver tissue increased. Furthermore, the above indexes showed the same expression trend in activated HSCs. In addition, the peripheral serum ALT and AST levels increased in CCl4-induced liver injury model mice. And HE staining showed a large number of inflammatory cell infiltration in the liver of model mice. Picric acid-Sirius staining and Masson staining showed that there was significant collagen fibrous tissue deposition in mice liver sections. IHC and WB detection confirmed that the expression of α-SMA and TGF-ß1 increased. Liver fibrosis scores were also elevated. Then, after SSd intervention, the expression of ROS in wild-type mice and αERKO mice decreased, mitochondrial membrane potential recovered, ATP level increased, NLRP3 inflammasome and fibrosis indexes decreased, liver enzyme levels decreased, and liver pathology showed liver inflammation. The damage and collagen deposition were significantly relieved, the expression of α-SMA and TGF-ß1 was decreased, and the fibrosis score was also decreased. More importantly, the effect of SSd in alleviating liver injury and liver fibrosis had no effect on ßERKO mice. Conclusion: SSd alleviated liver fibrosis by negatively regulating the ROS/NLRP3 inflammasome through activating the ERß pathway. By establishing liver fibrosis models using wild-type and ERKO mice, we demonstrated that SSd could alleviate liver fibrosis by inhibiting the ROS/NLRP3 inflammasome axis through activating the ERß pathway.

8.
Front Oncol ; 12: 844990, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35686089

RESUMO

Objective: This study was conducted in order to gain a better understanding of the molecular mechanisms of stomach adenocarcinoma (STAD), which is necessary to predict the prognosis of STAD and develop novel gene therapy strategies. Methods: In this study, the gene expression profile of GSE118916 in the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas Program (TCGA) was used to explore the differential co-expression genes of STAD and normal tissues. Results: A total of 407 STAD samples were collected, consisting of 375 from stomach adenocarcinoma tissues and 32 from normal tissues, as well as RNA-seq count data for 19,600 genes. Forty-two differentially expressed genes were screened by weighted gene co-expression network analysis (WGCNA) and differentially expressed gene analysis. According to the functional annotation analysis of the clusterProfiler R package, these genes were analyzed for GO function enrichment, digestion (biological process), tube bottom material membrane (cell component), and oxidoreductase activity (molecular function). The KEGG pathway was enriched in gastric acid secretion and chemical carcinogenesis. In addition, Cytoscape's cytoHubba plug-in was used to identify seven hub genes (EWSR1, ESR1, CLTC, PCMT1, TP53, HUWE1, and HDAC1) in a protein-protein interaction (PPI) network consisting of 7 nodes and 11 edges. Compared with normal tissues, CLTC and TP53 genes were upregulated in stomach adenocarcinoma (P < 0.05). TP53 was expressed differently in stages II and IV, EWSR1 was expressed differently in stages II and III, and ESR1 was expressed differently in stages I-III. Among the seven hub genes, Kaplan-Meier analysis and TCGG showed that the expression levels of HDAC1 and CLTC were significantly correlated with OS in patients with stomach adenocarcinoma (P < 0.05). GEPIA2 analysis showed that ESR1 expression was closely correlated with OS and DFS in gastric adenocarcinoma (P < 0.05). Then, the expression of the genes and their correlations were revealed by the R2 Platform (http://r2.amc.nl). Finally, we collected 18 pairs of gastric mucosal tissues from normal people and cancer tissues from patients with stomach adenocarcinoma. The expression levels of the above seven hub genes and their relative protein expression were detected by RT-PCR and immunohistochemistry (IHC). The results showed that the gene and protein expression levels in stomach adenocarcinoma tissues were increased than those in the normal group. Conclusion: In summary, we believe that the identified hub genes were related to the occurrence of stomach adenocarcinoma, especially the expression of ESR1, HDAC1, and CLTC genes, which are related to the prognosis and overall survival of patients and may become the potential for the future diagnosis and treatment of STAD.

9.
Bioorg Med Chem Lett ; 71: 128825, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35644299

RESUMO

The synergistic anti-tumor effect by simultaneous inhibitions of PI3K and HDAC has been verified to provide the rationality of PI3K/HDAC dual inhibitors for cancer treatment. Notably, the outstanding effect of PI3K/HDAC dual inhibitors against DLBCL has been paid much attention, especially for RR-DLBCL. Our previously reported 4-methylquinazoine scaffold based PI3K/HDAC dual inhibitors could suppress the growth of solid tumors and hematologic malignancies both in vitro and in vivo, validating the potential as new therapeutic agents for cancer. In this research, we further investigated the anti-tumor activity of one of our compounds against DLBCL cell lines and in vivo zebrafish xenograft model as well as the underlying mechanism, hoping to provide a novel therapeutic agent for treating DLBCL.


Assuntos
Inibidores de Histona Desacetilases , Linfoma Difuso de Grandes Células B , Animais , Apoptose , Linhagem Celular Tumoral , Inibidores de Histona Desacetilases/farmacologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/metabolismo , Linfoma Difuso de Grandes Células B/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase/farmacologia , Ensaios Antitumorais Modelo de Xenoenxerto , Peixe-Zebra
10.
Viruses ; 14(5)2022 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-35632808

RESUMO

Pseudorabies virus (PRV) is the causative agent of pseudorabies (PR). It can infect a wide range of mammals. PRV infection can cause severe acute neuropathy (the so-called "mad itch") in nonnatural hosts. PRV can infect the peripheral nervous system (PNS), where it can establish a quiescent, latent infection. The dorsal root ganglion (DRG) contains the cell bodies of the spinal sensory neurons, which can transmit peripheral sensory signals, including itch and somatic pain. Little attention has been paid to the underlying mechanism of the itch caused by PRV in nonnatural hosts. In this study, a mouse model of the itch caused by PRV was elaborated. BALB/c mice were infected intramuscularly with 105 TCID50 of PRV TJ. The frequency of the bite bouts and the durations of itch were recorded and quantified. The results showed that the PRV-infected mice developed spontaneous itch at 32 h postinfection (hpi). The frequency of the bite bouts and the durations of itch were increased over time. The mRNA expression levels of the receptors and the potential cation channels that are relevant to the itch-signal transmission in the DRG neurons were quantified. The mRNA expression levels of tachykinin 1 (TAC1), interleukin 2 (IL-2), IL-31, tryptases, tryptophan hydroxylase 1 (TPH1), and histidine decarboxylase (HDC) were also measured by high-throughput RNA sequencing and real-time reverse transcription PCR. The results showed that the mean mRNA level of the HDC in the DRG neurons isolated from the PRV-infected mice was approximately 25-fold higher than that of the controls at 56 hpi. An immunohistochemistry (IHC) was strongly positive for HDC in the DRG neurons of the PRV-infected mice, which led to the high expression of histamine at the injected sites. The itch of the infected mice was inhibited by chlorphenamine hydrogen maleate (an antagonist for the histamine H1 receptor) in a dose-dependent manner. The mRNA and protein levels of the HDC in the DRG neurons were proportional to the severity of the itch induced by different PRV strains. Taken together, the histamine synthesized by the HDC in the DRG neurons was responsible for the PRV-induced itch in the mice.


Assuntos
Herpesvirus Suídeo 1 , Pseudorraiva , Animais , Modelos Animais de Doenças , Herpesvirus Suídeo 1/metabolismo , Histamina , Mamíferos , Camundongos , Prurido/induzido quimicamente , RNA Mensageiro/metabolismo
11.
Dev Psychol ; 58(7): 1298-1317, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35511516

RESUMO

The sustaining environments hypothesis theorizes that the lasting effects of PreK programs are contingent on the quality of the subsequent learning environment in early elementary school. The current study tests this theory by leveraging data from students (N = 462) who did and did not enroll in the Boston Public Schools (BPS) prekindergarten (PreK) program as well as features of their kindergarten instruction measured at the child- and classroom-levels using surveys and observations. Taken together, findings revealed limited evidence for the sustaining environments hypothesis. The bulk of the results were null, indicating that in general, associations between enrollment in BPS PreK and language, literacy, and math skills through the spring of kindergarten did not vary by kindergarten instructional experiences. When examining distinct types of instructional experiences, there were some inklings that child-level observational measures of kindergarten learning experiences-particularly those capturing constrained versus unconstrained instruction-were more predictive of PreK persistence than observed global classroom quality measures or survey-based measures of advanced instruction. However, these associations were not always specific to outcomes matching the content delivered during this instruction (math vs. literacy), consistent with the possibility of either cross-domain effects or that instructional variables are proxies for more general instructional practices. Findings for future research and theory are discussed. (PsycInfo Database Record (c) 2022 APA, all rights reserved).


Assuntos
Instituições Acadêmicas , Estudantes , Escolaridade , Humanos , Aprendizagem , Alfabetização
12.
Proc Natl Acad Sci U S A ; 119(19): e2201288119, 2022 05 10.
Artigo em Inglês | MEDLINE | ID: mdl-35507870

RESUMO

African swine fever virus (ASFV) is the causative agent of African swine fever, a highly contagious and usually fatal disease in pigs. The pathogenesis of ASFV infection has not been clearly elucidated. Here, we used single-cell RNA-sequencing technology to survey the transcriptomic landscape of ASFV-infected primary porcine alveolar macrophages. The temporal dynamic analysis of viral genes revealed increased expression of viral transmembrane genes. Molecular characteristics in the ASFV-exposed cells exhibited the activation of antiviral signaling pathways with increased expression levels of interferon-stimulated genes and inflammatory- and cytokine-related genes. By comparing infected cells with unexposed cells, we showed that the unfolded protein response (UPR) pathway was activated in low viral load cells, while the expression level of UPR-related genes in high viral load cells was less than that in unexposed cells. Cells infected with various viral loads showed signature transcriptomic changes at the median progression of infection. Within the infected cells, differential expression analysis and coregulated virus­host analysis both demonstrated that ASFV promoted metabolic pathways but inhibited interferon and UPR signaling, implying the regulation pathway of viral replication in host cells. Furthermore, our results revealed that the cell apoptosis pathway was activated upon ASFV infection. Mechanistically, the production of tumor necrosis factor alpha (TNF-α) induced by ASFV infection is necessary for cell apoptosis, highlighting the importance of TNF-α in ASFV pathogenesis. Collectively, the data provide insights into the comprehensive host responses and complex virus­host interactions during ASFV infection, which may instruct future research on antiviral strategies.


Assuntos
Vírus da Febre Suína Africana , Febre Suína Africana , Vírus da Febre Suína Africana/genética , Animais , Antivirais/metabolismo , Perfilação da Expressão Gênica , Macrófagos/metabolismo , Suínos , Replicação Viral/fisiologia
13.
Data Brief ; 42: 108048, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35313503

RESUMO

This article documents a functional Near-Infrared Spectroscopy (fNIRS) neuroimaging dataset deposited in Deep Blue Data. The dataset included neuroimaging and behavioral data from N = 343 children aged 5-11 with a diverse linguistic background, including children who are English monolingual, Chinese-English, and Spanish-English bilingual. Children completed phonological and morphological awareness tasks in each of their languages during fNIRS neuroimaging. They also completed a wide range of language and reading tasks. Parents filled in questionnaires to report children's demographic information as well as their home language and literacy backgrounds. The dataset is valuable for researchers in the field of developmental cognitive neuroscience to further investigate questions such as the effects of bilingualism on children's neural basis for literacy development.

15.
Anal Bioanal Chem ; 414(9): 2991-3003, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35106612

RESUMO

Ratiometric electrochemical assays have been demonstrated to be more sensitive and selective in various sensing events, mainly due to their affordable built-in correction and good self-reference capability. But it is known that complicated modification and labeling operations usually are necessary for the construction of ratiometric electrochemical assays, therefore is a hot and important issue needing consideration carefully. We herein report a new yet simple bare electrode-based ratiometric electrochemical bioassay to achieve sensitive and selective analysis of alkaline phosphatase (ALP), using a liquid phase system that contains CoOOH nanozymes and commercially available indicator substrate. This proposed bioassay works based on the ratiometric change of dual electrochemical signals, arising from an exclusive target ALP-triggered hydrolysis of electrochemical substrate p-nitrophenyl phosphate (PNPP). In this design, the two hydrolyzed products of electrochemically active p-nitrophenol (PNP) and electrochemically inactive phosphate anion (PO43-) are responsible together for the ratiometric electrochemical analysis of ALP. PNP exhibits a straightforward current response toward ALP content; however, PO43- cannot show a direct electrochemical signal thus is rationally designed to offer an alternative response by linking it with the specific CoOOH nanozyme-catalyzed reaction of 3,3',5,5'-tetramethylbenzidine (TMB) and H2O2, in which the nanozyme-catalyzed product oxTMB shows a direct reduction current at the GCE, and significantly decreases with increasing PO43- species due to the good inhibition of PO43- toward CoOOH nanozyme activity. As a result, a ratiometric electrochemical strategy for ALP analysis with a low limit of detection of 0.366 U/L (S/N = 3) was successfully achieved by integrating the above direct and indirect dual electrochemical responses. This developed bioassay can allow the quantitative diagnosis of ALP activity especially with a label-free and modification-free merit, therefore paving the way for simple, convenient, and portable electroanalytical tools in biosensing design and application.


Assuntos
Fosfatase Alcalina , Peróxido de Hidrogênio , Fosfatase Alcalina/análise , Eletrodos
16.
Dev Sci ; : e13251, 2022 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-35188687

RESUMO

How do early bilingual experiences influence children's neural architecture for word processing? Dual language acquisition can yield common influences that may be shared across different bilingual groups, as well as language-specific influences stemming from a given language pairing. To investigate these effects, we examined bilingual English speakers of Chinese or Spanish, and English monolinguals, all raised in the US (N = 152, ages 5-10). Children completed an English morphological word processing task during fNIRS neuroimaging. The findings revealed both language-specific and shared bilingual effects. The language-specific effects were that Chinese and Spanish bilinguals showed principled differences in their neural organization for English lexical morphology. The common bilingual effects shared by the two groups were that in both bilingual groups, increased home language proficiency was associated with stronger left superior temporal gyrus (STG) activation when processing the English word structures that are most dissimilar from the home language. The findings inform theories of language and brain development during the key periods of neural reorganization for learning to read by illuminating experience-based plasticity in linguistically diverse learners.

17.
Front Immunol ; 13: 851560, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35222444

RESUMO

Autoimmune hepatitis (AIH) is characterized by chronic progressive liver inflammatory, but there is still no safe and effective medicine. Therefore, glucocorticoid remains the top choice for AIH treatment. In previous studies, it has been confirmed that ginsenosides (GSS) can produce glucocorticoid-like effects and therapeutic effects on various autoimmune diseases. However, the mechanism of GSS for AIH remains unclear. As an important part of the innate immune system, bone marrow-derived suppressor cells (MDSC) have been identified as an important driver of follow-up acquired immune response in many autoimmune diseases, including AIH. Herein, it was found out that GSS intervention can be effective in regulating the immune microenvironment and liver impairment induced by Con A in AIH mice. In vitro, the MDSCs derived from healthy mice and the T cells deried from AIH mice were co-cultured. Then, different drugs were intervened with to explore the therapeutic mechanism. Besides, the proliferation and differentiation of MDSCs and T cells were analyzed by flow cytometry, while GR, Hippo-YAP signal pathway and the expression of MDSC-related genes and proteins were detected through qRT-PCR and Western Blot. The changes in NO and ROS levels were further analyzed. The trend of related cytokines expression (IFN- γ, TGF- ß, IL-10, IL-6, IL-17) was detected by ELISA. Furthermore, an analysis was conducted as to the ALT and liver pathology of mice for evaluating the liver function of mice. It was discovered that MDSCs proliferation was inhibited, and that T cells tended to differentiate into Th17 rather than Treg in AIH mice. Moreover, the intervention of GSS activated GR and Yap, in addition to promoting the proliferation of MDSCs, especially M-MDSCs. This further promoted the differentiation of Treg to enable immune tolerance, thus alleviating liver impairment. Therefore, it was proposed that GSS can alleviate AIH by modulating the innate immunity and adaptive T cell immunity, which may be the underlying mechanism for GSS to mitigate the liver impairment induced by AIH.


Assuntos
Ginsenosídeos , Hepatite Autoimune , Animais , Ginsenosídeos/farmacologia , Glucocorticoides , Imunidade Inata , Camundongos , Camundongos Endogâmicos C57BL , Transdução de Sinais
18.
J Virol ; 96(3): e0166721, 2022 02 09.
Artigo em Inglês | MEDLINE | ID: mdl-34787458

RESUMO

African swine fever virus (ASFV) is a complex nucleocytoplasmic large DNA virus that causes African swine fever, a lethal hemorrhagic disease that currently threatens the pig industry. Recent studies have identified the viral structural proteins of infectious ASFV particles. However, the functional roles of several ASFV structural proteins remain largely unknown. Here, we characterized the function of the ASFV structural protein H240R (pH240R) in virus morphogenesis. pH240R was identified as a capsid protein by using immunoelectron microscopy and interacted with the major capsid protein p72 by pulldown assays. Using a recombinant ASFV, ASFV-ΔH240R, with the H240R gene deleted from the wild-type ASFV (ASFV-WT) genome, we revealed that the infectious progeny virus titers were reduced by approximately 2.0 logs compared with those of ASFV-WT. Furthermore, we demonstrated that the growth defect was due to the generation of noninfectious particles with a higher particle-to-infectious titer ratio in ASFV-ΔH240R-infected primary porcine alveolar macrophages (PAMs) than in those infected with ASFV-WT. Importantly, we found that pH240R did not affect virus-cell binding, endocytosis, or egress but did affect ASFV assembly; noninfectious virions containing large aberrant tubular and bilobulate structures comprised nearly 98% of all virions observed in ASFV-ΔH240R-infected PAMs by electron microscopy. Notably, we demonstrated that ASFV-ΔH240R infection induced high-level expression of inflammatory cytokines in PAMs. Collectively, we show for the first time that pH240R is essential for ASFV icosahedral capsid formation and infectious particle production. Also, these results highlight the importance of pH240R in ASFV morphogenesis and provide a novel target for the development of ASF vaccines and antivirals. IMPORTANCE African swine fever is a lethal hemorrhagic disease of global concern that is caused by African swine fever virus (ASFV). Despite extensive research, there exist relevant gaps in knowledge of the fundamental biology of the viral life cycle. In this study, we identified pH240R as a capsid protein that interacts with the major capsid protein p72. Furthermore, we showed that pH240R was required for the efficient production of infectious progeny virions as indicated by the H240R-deleted ASFV mutant (ASFV-ΔH240R). More specifically, pH240R directs the morphogenesis of ASFV toward the icosahedral capsid in the process of assembly. In addition, ASFV-ΔH240R infection induced high-level expression of inflammatory cytokines in primary porcine alveolar macrophages. Our results elucidate the role of pH240R in the process of ASFV assembly, which may instruct future research on effective vaccines or antiviral strategies.


Assuntos
Vírus da Febre Suína Africana/fisiologia , Febre Suína Africana/genética , Febre Suína Africana/metabolismo , Proteínas do Capsídeo/genética , Citocinas/metabolismo , Macrófagos/metabolismo , Deleção de Sequência , Febre Suína Africana/patologia , Vírus da Febre Suína Africana/ultraestrutura , Sequência de Aminoácidos , Animais , Proteínas do Capsídeo/química , Proteínas do Capsídeo/metabolismo , Citocinas/genética , Suscetibilidade a Doenças/imunologia , Perfilação da Expressão Gênica , Regulação Viral da Expressão Gênica , Genoma Viral , Interações Hospedeiro-Patógeno/genética , Interações Hospedeiro-Patógeno/imunologia , Macrófagos/imunologia , Suínos , Vírion/ultraestrutura , Internalização do Vírus , Replicação Viral
19.
Ann Dyslexia ; 72(2): 361-383, 2022 07.
Artigo em Inglês | MEDLINE | ID: mdl-34255265

RESUMO

Morphological awareness, or sensitivity to units of meaning, is an essential component of reading comprehension development. Current neurobiological models of reading and dyslexia have largely been built upon phonological processing models, yet reading for meaning is as essential as reading for sound. To fill this gap, the present study explores the relation between children's neural organization for morphological awareness and successful reading comprehension in typically developing and impaired readers. English-speaking children ages 6-11 (N = 97; mean age = 8.6 years, 25% reading impaired) completed standard literacy assessments as well as an auditory morphological awareness task during functional near-infrared spectroscopy (fNIRS) neuroimaging, which included root (e.g., PERSON + al) and derivational (e.g., quick + LY) morphology. Regression analyses revealed that children's morphological awareness predicted unique variance in reading comprehension above and beyond demographic factors, vocabulary knowledge, and decoding ability. Neuroimaging analyses further revealed that children with stronger reading comprehension showed greater engagement of brain regions associated with integrating sound and meaning, including left inferior frontal, middle temporal, and inferior parietal regions. This effect was especially notable for the derivational morphology condition that involved manipulating more analytically demanding and semantically abstract units (e.g., un-, -ly, -ion). Together, these findings suggest that successful reading comprehension, and its deficit in dyslexia, may be related to the ability to manipulate morpho-phonological units of word meaning and structure. These results inform theoretical perspectives on literacy and children's neural architecture for learning to read.


Assuntos
Dislexia , Leitura , Criança , Compreensão , Dislexia/diagnóstico por imagem , Dislexia/psicologia , Humanos , Fonética , Vocabulário
20.
Child Dev ; 93(1): 84-100, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34570366

RESUMO

This study investigates the cross-linguistic transfer of literacy skills in Spanish-English, Chinese-English bilingual, and English monolingual children (N = 283, 5-10 years). Research question 1 examines English literacy and asks how phonological and morpho-semantic skills contribute to word reading as a function of children's language background. Structural equation modeling revealed contrasting bilingual effects: compared to English monolinguals, Spanish-English bilinguals relied more on phonological awareness in word reading, whereas Chinese-English bilinguals relied more on lexical knowledge. Research question 2 examines relations between bilinguals' heritage language proficiency and English literacy. Results revealed direct and indirect effects of heritage language meta-linguistic skills on English word reading. The study yields implications for reading theories and instructional practices in optimizing literacy in linguistically diverse children.


Assuntos
Idioma , Multilinguismo , Criança , China , Humanos , Linguística , Leitura
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