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1.
J Neurosci ; 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34759031

RESUMO

The human sense of smell plays an important role in appetite and food intake, detecting environmental threats, social interactions, and memory processing. However, little is known about the neural circuity supporting its function. The olfactory tracts project from the olfactory bulb along the base of the frontal cortex, branching into several striae to meet diverse cortical regions. Historically, using diffusion magnetic resonance imaging (dMRI) to reconstruct the human olfactory tracts has been prevented by susceptibility and motion artifacts. Here, we used a dMRI method with readout segmentation of long variable echo-trains (RESOLVE) to minimize image distortions and characterize the human olfactory tracts in vivo We collected high-resolution dMRI data from 25 healthy human participants (12 male and 13 female) and performed probabilistic tractography using constrained spherical deconvolution. At the individual subject level, we identified the lateral, medial, and intermediate striae with their respective cortical connections to the piriform cortex and amygdala, olfactory tubercle, and anterior olfactory nucleus. We combined individual results across subjects to create a normalized, probabilistic atlas of the olfactory tracts. We then investigated the relationship between olfactory perceptual scores and measures of white matter integrity, including mean diffusivity. Importantly, we found that olfactory tract mean diffusivity negatively correlated with odor discrimination performance. In summary, our results provide a detailed characterization of the connectivity of the human olfactory tracts and demonstrate an association between their structural integrity and olfactory perceptual function.SIGNIFICANCE STATEMENTThis study provides the first detailed in vivo description of the cortical connectivity of the three olfactory tract striae in the human brain, using diffusion magnetic resonance imaging. Additionally, we show that tract microstructure correlates with performance on an odor discrimination task, suggesting a link between the structural integrity of the olfactory tracts and odor perception. Lastly, we generated a normalized probabilistic atlas of the olfactory tracts that may be used in future research to study its integrity in health and disease.

2.
eNeuro ; 8(5)2021.
Artigo em Inglês | MEDLINE | ID: mdl-34544760

RESUMO

Epilepsy affects 3.4 million people in the United States, and, despite the availability of numerous antiepileptic drugs, 36% of patients have uncontrollable seizures, which severely impact quality of life. High-frequency oscillations (HFOs) are a potential biomarker of epileptogenic tissue that could be useful in surgical planning. As a result, research into the efficacy of HFOs as a clinical tool has increased over the last 2 decades. However, detection and identification of these transient rhythms in intracranial electroencephalographic recordings remain time-consuming and challenging. Although automated detection algorithms have been developed, their results are widely inconsistent, reducing reliability. Thus, manual marking of HFOs remains the gold standard, and manual review of automated results is required. However, manual marking and review are time consuming and can still produce variable results because of their subjective nature and the limitations in functionality of existing open-source software. Our goal was to develop a new software with broad application that improves on existing open-source HFO detection applications in usability, speed, and accuracy. Here, we present HFOApp: a free, open-source, easy-to-use MATLAB-based graphical user interface for HFO marking. This toolbox offers a high degree of intuitive and ergonomic usability and integrates interactive automation-assist options with manual marking, significantly reducing the time needed for review and manual marking of recordings, while increasing inter-rater reliability. The toolbox also features simultaneous multichannel detection and marking. HFOApp was designed as an easy-to-use toolbox for clinicians and researchers to quickly and accurately mark, quantify, and characterize HFOs within electrophysiological datasets.


Assuntos
Epilepsia , Qualidade de Vida , Eletroencefalografia , Humanos , Reprodutibilidade dos Testes , Convulsões
3.
Interdiscip Sci ; 13(4): 615-623, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34472046

RESUMO

PURPOSE: This study was aimed to identify biomarker associated with membranous nephropathy (MN) progression by integration of expression profiles and competitive endogenous RNA (ceRNA) network analysis. METHODS: The gene (GSE108113) and microRNAs (miRNAs) expression profiles (GSE64306) were downloaded to identify the differentially expressed mRNAs, miRNAs and long non-coding RNAs (lncRNAs) between MN and control groups. The functions and pathways enriched by the differentially expressed mRNAs were analyzed. The mRNA-lncRNA co-expression network was constructed followed by and the ceRNA network construction. RESULTS: Total 264 upregulated and 196 downregulated differentially expressed mRNAs, 79 upregulated and 4 downregulated lncRNAs, as well as 115 upregulated and 93 downregulated miRNAs were obtained between MN and control groups. After analysis, the differential mRNAs were significantly involved in multiple immune-related processes, and cell proliferation, apoptosis and differentiation processes, as well as pathways of taste transduction and lysosome. Finally, a ceRNA network consisting of 4 mRNAs (EPB41L5, FAM43A, PRKG1 and TTC14), 3 lncRNAs (LINC00052, LINC00641 and N4BP2L2-IT2) and 5 miRNAs (hsa-miR-145-5p, hsa-miR-3605-5p, hsa-miR-148a-3p, hsa-miR-497-5p and hsa-miR-148b-3p) was constructed. CONCLUSION: Our study indicated dysregulation of immune- and apoptosis-associated functions and taste transduction and lysosome pathways may play important roles in MN progression. Deregulated ceRNAs, such as LINC00052-hsa-miR-145-5p-EPB41L5, LINC00052-hsa-miR-148a-3p-FAM43A and LINC00641-hsa-497-5p-PRKG1, may be associated with MN development.


Assuntos
Glomerulonefrite Membranosa , MicroRNAs , RNA Longo não Codificante , Biomarcadores , Redes Reguladoras de Genes/genética , Glomerulonefrite Membranosa/genética , Humanos , Proteínas de Membrana , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Mensageiro/genética
4.
Front Psychol ; 12: 740450, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456837
5.
Small ; 17(43): e2102624, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34378338

RESUMO

Targeting B7-H3 chimeric antigen receptor (CAR) T cells has antitumor potential for therapy of non-small cell lung cancer (NSCLC) in preclinical studies. However, CAR T cell therapy remains a formidable challenge for the treatment of solid tumors due to the heterogeneous and immunosuppressive tumor microenvironment (TME). Nanozymes exhibit merits modulating the immunosuppression of the tumor milieu. Here, a synergetic strategy by combination of nanozymes and CAR T cells in solid tumors is described. This nanozyme with dual photothermal-nanocatalytic properties is endowed to remodel TME by destroying its compact structure. It is found that the B7-H3 CAR T cells infused in mice engrafted with the NSCLC cells have superior antitumor activity after nanozyme ablation of the tumor. Importantly, it is found that the changes altered immune-hostile cancer environment, resulting in enhanced activation and infiltration of B7-H3 CAR T cells. The first evidence that the process of combination nanozyme therapy effectively improves the therapeutic index of CAR T cells is presented. Thus, this study clearly supports that the TME-immunomodulated nanozyme is a promising tool to improve the therapeutic obstacles of CAR T cells against solid tumors.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Receptores de Antígenos Quiméricos , Animais , Carcinoma Pulmonar de Células não Pequenas/terapia , Linhagem Celular Tumoral , Imunoterapia Adotiva , Camundongos , Linfócitos T , Microambiente Tumoral , Ensaios Antitumorais Modelo de Xenoenxerto
6.
Curr Psychol ; : 1-10, 2021 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-34155429

RESUMO

Personal hygiene including wearing facemask and washing hands are instrumental to reduce transmission of COVID-19. The present study applied the health action process approach (HAPA) to examine the process from intention to protective behaviors in the early stages of the COVID-19 pandemic. A longitudinal online survey study was conducted among 229 individuals (61.6% females; M age = 25.37 years, SD age = 8.34 years) living in Hubei province, China. Action self-efficacy, outcome expectancy, risk perception, intention, planning and action control regarding facemask wearing and hand washing were assessed at baseline (Time 1), and behaviors were assessed a week later (Time 2). Data were collected from 30 January to 16 February 2020. Two structural equation models were specified to test the theory-driven determinants of the facemask wearing and hand washing respectively. The results showed that action self-efficacy predicted intentions to wear facemasks and wash hands. Intention and action control predicted both behaviors at Time 2. Associations between planning and behaviors were mixed. Mediation analyses revealed that action control significantly mediated the relationship between intention and both behaviors (facemask wearing: 90% CI [0.01, 0.12]; hand washing: 95% CI [0.01, 0.21]). Planning did not mediate the relationship between intention and the two behaviors. The findings illustrate that action self-efficacy is positively associated with intention to facemask wearing and hand washing, and action control contributes to bridging intention to behaviors. Both motivational and volitional factors warrant consideration in interventions to improve adherence to facemask wearing and hand washing in COVID-19.

7.
Exp Cell Res ; 405(2): 112713, 2021 08 15.
Artigo em Inglês | MEDLINE | ID: mdl-34181940

RESUMO

Obesity, a global epidemic, is one of the critical causes of chronic kidney disease (CKD). R-spondin1 (RSPO1) possessing the potential to activate Wnt/ß-catenin pathway was reported to be elevated in circulation of obesity objects. However, the function of RSPO1 and the latent mechanism in obesity-related CKD are still left to be revealed. In the present study, renal RSPO1 expression was increased in mice fed on high-fat diet (HFD) for 12 weeks. Lentivirus-mediated RSPO1 knockdown partly recovered obesity-related metabolic symptoms, while distinctly remitted kidney dysfunction and renal fibrosis in obesity mice. In vitro, recombinant RSPO1 was found to elevate leucine-rich repeat-containing G protein coupled receptor 4 (LGR4) expression, promote Wnt/ß-catenin signaling pathway activation, facilitate epithelial-mesenchymal transition (EMT) and increase collagen deposition in HK2 renal tubular cells. Such pro-fibrotic effect of RSPO1 was diminished by LGR4 siRNA in HK2 cells. In summary, we demonstrate that RSPO1/LGR4 axis is involved in obesity-related renal fibrosis at least through activating Wnt/ß-catenin signaling pathway, providing a potential therapeutic target for this disease.


Assuntos
Fibrose/metabolismo , Obesidade/complicações , Trombospondinas/metabolismo , Via de Sinalização Wnt/fisiologia , beta Catenina/metabolismo , Animais , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/fisiologia , Masculino , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas G/metabolismo
8.
Environ Sci Pollut Res Int ; 28(36): 50388-50404, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33959836

RESUMO

This study uses hierarchical cluster analysis (HCA) to screen the evaluation indexes and establishes a comprehensive evaluation index system for water resources carrying capacity (WRCC), based on the VIKOR method and the obstacle degree model for the identification of the main factors affecting the WRCC of Weifang City. The results show that the WRCC of Weifang City has steadily increased from 2008 to 2018. The subsystems referred to society and water environment are currently the main obstacles affecting Weifang's WRCC, but there is still space for improvement in the future. The areas with low WRCC was Kuiwen District in 2018, which was in a seriously overloaded state, mostly affected by the water resources subsystem. The implementation of measures such as efficiently improving the level of water resources management and the development of water conservancy projects is prominent in water resource planning in Kuiwen District. This study analyzes the current situation of water resources management in order to consider it in strategic decision-making in promoting the improvement of WRCC, which in turn may ensure the realization of a green and sustainable development strategy in the future for Weifang City.


Assuntos
Conservação dos Recursos Naturais , Recursos Hídricos , China , Cidades , Análise por Conglomerados , Desenvolvimento Sustentável
9.
Psychol Health Med ; : 1-11, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879007

RESUMO

Consequences of prenatal maternal depressive symptoms on infant health are well established. But the results of infants' sex differences of such consequences are mixed. The current study examines whether any association exists between prenatal maternal depressive symptoms and infant physical health different for the sex of newborns. A sample of 84 women pregnant with twins reported depressive symptoms using the Edinburgh Postnatal Depression Scale (EPDS) in the late gestational stage. The Apgar scores of newborns were assessed by healthcare providers at 1, 5, and 10 minutes after birth. The relationship of maternal prenatal depressive symptoms and newborns' physical health was moderated by infant sex. Higher depressive symptoms were associated with a lower Apgar index among newborn boys but not girls. Fetus environment or biomarkers related to sex may be a key mechanism of the effect of prenatal depression symptoms on newborns' health. Tailored interventions targeting maternal depression symptoms may be warranted.

10.
BMC Pulm Med ; 21(1): 129, 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33879098

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is characterized by incomplete reversible airflow limitation and chronic inflammatory response lesions. This study mainly explored whether FGFR2 and MGAT5 polymorphisms affected the risk of COPD in the Chinese people. METHODS: Five variants in FGFR2 and MGAT5 were chosen and genotyped using Agena MassARRAY platform from 315 COPD patients and 314 healthy controls. The correlation of FGFR2 and MGAT5 with COPD susceptibility was evaluated with odds ratio (OR) and 95% confidence interval (CI) via logistic regression. RESULTS: We found rs2420915 enhanced the risk of COPD, while rs6430491, rs2593704 reduced the susceptibility of COPD (p < 0.05). Rs2420915 could promote the incidence of COPD in the elderly and nonsmokers. Rs1907240 and rs2257129 also increased the susceptibility to COPD in nonsmokers (p < 0.05). MGAT5-rs2593704 played a protective role in COPD development in different subgroups (age ≤ 70, male, smokers, and individuals with BMI ≤ 24 kg/m2). Meanwhile, rs6430491 was linked with a lower risk of COPD in nonsmoking and BMI ≤ 24 kg/m2 subgroups. CONCLUSIONS: We concluded that FGFR2 and MGAT5 genetic polymorphisms are correlated with the risk of COPD in the Chinese people. These data underscored the important role of FGFR2 and MGAT5 gene in the occurrence of COPD and provided new biomarkers for COPD treatment. TRIAL REGISTRATION: NA.


Assuntos
N-Acetilglucosaminiltransferases/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Receptor Tipo 2 de Fator de Crescimento de Fibroblastos/genética , Idoso , Idoso de 80 Anos ou mais , Estudos de Casos e Controles , China , Feminino , Predisposição Genética para Doença , Variação Genética , Estudo de Associação Genômica Ampla , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , não Fumantes , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Fumantes
11.
Prog Neurobiol ; 201: 102027, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33640412

RESUMO

During mammalian evolution, primate neocortex expanded, shifting hippocampal functional networks away from primary sensory cortices, towards association cortices. Reflecting this rerouting, human resting hippocampal functional networks preferentially include higher association cortices, while those in rodents retained primary sensory cortices. Research on human visual, auditory and somatosensory systems shows evidence of this rerouting. Olfaction, however, is unique among sensory systems in its relative structural conservation throughout mammalian evolution, and it is unknown whether human primary olfactory cortex was subject to the same rerouting. We combined functional neuroimaging and intracranial electrophysiology to directly compare hippocampal functional networks across human sensory systems. We show that human primary olfactory cortex-including the anterior olfactory nucleus, olfactory tubercle and piriform cortex-has stronger functional connectivity with hippocampal networks at rest, compared to other sensory systems. This suggests that unlike other sensory systems, olfactory-hippocampal connectivity may have been retained in mammalian evolution. We further show that olfactory-hippocampal connectivity oscillates with nasal breathing. Our findings suggest olfaction might provide insight into how memory and cognition depend on hippocampal interactions.

12.
Front Psychiatry ; 12: 635546, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33633616

RESUMO

The ongoing COVID-19 pandemic is likely to enhance the risk of addictive social media use (SMU) as people spend more time online maintaining connectivity when face-to-face communication is limited. Stress is assumed to be a critical predictor of addictive SMU. However, the mechanisms underlying the association between stress and addictive SMU in crises like the current COVID-19 situation remain unclear. The present study aimed to understand the relationship between COVID-19 stress and addictive SMU by examining the mediating role of active use and social media flow (i.e., an intensive, enjoyable experience generated by SMU that perpetuates media use behaviors). A sample of 512 Chinese college students (M age = 22.12 years, SD = 2.47; 62.5% women) provided self-report data on COVID-19 stress and SMU variables (i.e., time, active use, flow, addictive behavior) via an online survey from March 24 to April 1, 2020. The results showed that COVID-19 stress was positively associated with tendencies toward addictive SMU. Path analyses revealed that this relationship was significantly serially mediated by active use and social media flow, with SMU time being controlled. Our findings suggest that individuals who experience more COVID-19 stress are at increased risk of addictive SMU that may be fostered by active use and flow experience. Specific attention should be paid to these high-risk populations and future interventions to reduce addictive SMU could consider targeting factors of both active use and social media flow.

13.
J Hematol Oncol ; 14(1): 21, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514401

RESUMO

BACKGROUND: B7-H3, an immune-checkpoint molecule and a transmembrane protein, is overexpressed in non-small cell lung cancer (NSCLC), making it an attractive therapeutic target. Here, we aimed to systematically evaluate the value of B7-H3 as a target in NSCLC via T cells expressing B7-H3-specific chimeric antigen receptors (CARs) and bispecific killer cell engager (BiKE)-redirected natural killer (NK) cells. METHODS: We generated B7-H3 CAR and B7-H3/CD16 BiKE derived from an anti-B7-H3 antibody omburtamab that has been shown to preferentially bind tumor tissues and has been safely used in humans in early-phase clinical trials. Antitumor efficacy and induced-immune response of CAR and BiKE were evaluated in vitro and in vivo. The effects of B7-H3 on aerobic glycolysis in NSCLC cells were further investigated. RESULTS: B7-H3 CAR-T cells effectively inhibited NSCLC tumorigenesis in vitro and in vivo. B7-H3 redirection promoted highly specific T-cell infiltration into tumors. Additionally, NK cell activity could be specially triggered by B7-H3/CD16 BiKE through direct CD16 signaling, resulting in significant increase in NK cell activation and target cell death. BiKE improved antitumor efficacy mediated by NK cells in vitro and in vivo, regardless of the cell surface target antigen density on tumor tissues. Furthermore, we found that anti-B7-H3 blockade might alter tumor glucose metabolism via the reactive oxygen species-mediated pathway. CONCLUSIONS: Together, our results suggest that B7-H3 may serve as a target for NSCLC therapy and support the further development of two therapeutic agents in the preclinical and clinical studies.


Assuntos
Anticorpos Biespecíficos/uso terapêutico , Antígeno B7-H1/imunologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Imunoterapia Adotiva/métodos , Neoplasias Pulmonares/terapia , Receptores de Antígenos Quiméricos/uso terapêutico , Animais , Anticorpos Biespecíficos/imunologia , Carcinoma Pulmonar de Células não Pequenas/imunologia , Linhagem Celular Tumoral , Feminino , Humanos , Células Matadoras Naturais/imunologia , Neoplasias Pulmonares/imunologia , Ativação Linfocitária , Camundongos Endogâmicos NOD , Camundongos SCID , Receptores de Antígenos Quiméricos/imunologia , Linfócitos T/imunologia , Linfócitos T/transplante
14.
Int J Genomics ; 2020: 7524057, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33274190

RESUMO

Background: Chronic kidney disease (CKD) is characterized by progressive renal function loss, which may finally lead to end-stage renal disease (ESRD). The study is aimed at identifying crucial genes related to CKD progressive and constructing a disease prediction model to investigate risk factors. Methods: GSE97709 and GSE37171 datasets were downloaded from the GEO database including peripheral blood samples from subjects with CKD, ESRD, and healthy controls. Differential expressed genes (DEGs) were identified and functional enrichment analysis. Machine learning algorithm-based prediction model was constructed to identify crucial functional feature genes related to ESRD. Results: A total of 76 DEGs were screened from CDK vs. normal samples while 10,114 DEGs were identified from ESRD vs. CDK samples. For numerous genes related to ESRD, several GO biological terms and 141 signaling pathways were identified including markedly upregulated olfactory transduction and downregulated platelet activation pathway. The DEGs were clustering in three modules according to WGCNA access, namely, ME1, ME2, and ME3. By construction of the XGBoost model and dataset validation, we screened cohorts of genes associated with progressive CKD, such as FZD10, FOXD4, and FAM215A. FZD10 represented the highest score (F score = 21) in predictive model. Conclusion: Our results demonstrated that FZD10, FOXD4, PPP3R1, and UCP2 might be critical genes in CKD progression.

16.
Appl Psychol Health Well Being ; 12(4): 1019-1038, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32945123

RESUMO

BACKGROUND: Informed by the differential susceptibility to media effects model (DSMM), the current study aims to investigate associations of COVID-19-related social media use with mental health outcomes and to uncover potential mechanisms underlying the links. METHODS: A sample of 512 (62.5% women; Mage  = 22.12 years, SD = 2.47) Chinese college students participated in this study from 24 March to 1 April 2020 via online questionnaire. They completed measures of social media use, the COVID-19 stressor, negative affect, secondary traumatic stress (STS), depression, and anxiety as well as covariates. RESULTS: As expected, results from regression analyses indicated that a higher level of social media use was associated with worse mental health. More exposure to disaster news via social media was associated with greater depression for participants with high (but not low) levels of the disaster stressor. Moreover, path analysis showed negative affect mediated the relationship of social media use and mental health. CONCLUSIONS: These findings suggest that the disaster stressor may be a risk factor that amplifies the deleterious impact of social media use on depression. In addition, excessive exposure to disaster on social media may trigger negative affect, which may in turn contribute to mental health problems. Future interventions to improve mental health should consider elements of both disaster stressor and negative affect.


Assuntos
Afeto , Ansiedade/epidemiologia , COVID-19 , Depressão/epidemiologia , Desastres , Mídias Sociais/estatística & dados numéricos , Transtornos de Estresse Traumático/epidemiologia , Estresse Psicológico/epidemiologia , Adulto , Feminino , Humanos , Masculino , Redes Sociais Online , Adulto Jovem
17.
Environ Sci Technol ; 54(20): 13314-13321, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-32960572

RESUMO

Currently, improving the alkali resistance of vanadium-based catalysts still remains as an intractable issue for the selective catalytic reduction of NOx with NH3 (NH3-SCR). It is generally believed that the decrease in adsorbed NHx species deriving from the declined acidic sites is the chief culprit for the deactivation of alkali-poisoned catalysts. Herein, alkali-resistant NOx reduction over SCR catalysts via boosting NH3 adsorption rates was originally demonstrated by in situ constructing the sacrificed sites. It is interesting that the adsorbed NHx species largely decrease while the NH3 adsorption rate is well kept over the V2O5/CeO2 catalyst by in situ constructing the sacrificed sites. The SCR activity could be maintained after alkali poisoning because in situ constructed SO42- groups would prefer to be combined with K+ so that the specific V═O species can endow K-poisoned V2O5/CeO2 with high adsorption rate of NH3 and high reactivity of NHx species. This work provides a new viewpoint that NH3 adsorption rate plays more decisive roles in the performance of alkali-poisoned catalysts than the amount of NH3 adsorption and enlightens an alternative strategy to improve the alkali-resistance of catalysts, which is significant to both the academic and industrial fields.


Assuntos
Álcalis , Amônia , Adsorção , Catálise , Vanádio
18.
Front Pharmacol ; 11: 1089, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32848731

RESUMO

Chimeric antigen receptor (CAR)-modified natural killer (NK) cell therapy represents a kind of promising anti-cancer treatment because CAR renders NK cells activation and recognition specificity toward tumor cells. An immune checkpoint molecule, B7-H3, plays an inhibitory role in modulation of NK cells. To enhance NK cell functions, we generated NK-92MI cells carrying anti-B7-H3 CAR by lentiviral transduction. The expression of anti-B7-H3 CAR significantly enhanced the cytotoxicity of NK-92MI cells against B7-H3-positive tumor cells. In accordance with enhanced cytotoxicity, the secretions of perforin/granzyme B and expression of CD107a were highly elevated in anti-B7-H3 CAR-NK-92MI cells. Moreover, compared to unmodified NK-92MI cells, anti-B7-H3 CAR-NK-92MI cells effectively limited tumor growth in mouse xenografts of non-small cell lung cancer and significantly prolonged the survival days of mice. This study provides the rationale and feasibility of B7-H3-specific CAR-NK cells for application in adoptive cancer immunotherapy.

19.
J Agric Food Chem ; 68(26): 7014-7023, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32515192

RESUMO

Neonatal necrotizing enterocolitis (NEC) is a common and devastating disease. The objective of this research was to investigate the protective mechanisms of milk polar lipids (MPLs) on the attenuation of lipopolysaccharides (LPS)-induced intestinal inflammation and apoptosis. MPLs were extracted from buttermilk and analyzed using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). A neonatal NEC rat model was used to investigate the effects of MPLs on NEC and its underlying mechanisms. Hematoxylin-eosin (H&E) staining and terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling (TUNEL) assay were used to observe intestinal morphological changes and intestinal epithelial cell apoptosis, which showed that MPLs could reduce NEC symptoms and intestinal apoptosis. The expressions of IL-6, IL-8, and TNF-α in the MPL group was significantly downregulated (P < 0.05), and the expression levels of IL-10 were significantly upregulated (P < 0.05). At the same time, MPLs also significantly reduced (P < 0.05) activation of the LPS-induced TLR4/NF-κB signaling pathway. Furthermore, MPLs inhibit apoptosis by reducing the expressions of Bax, caspase-9, and caspase-3 and by increasing the expression of Bcl-2. In conclusion, MPLs could reduce NEC symptoms in mice by inhibiting cell inflammation and protecting against intestinal apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Enterocolite Necrosante/prevenção & controle , Células Epiteliais/citologia , Mucosa Intestinal/efeitos dos fármacos , Lipídeos/administração & dosagem , Leite/química , Animais , Leitelho/análise , Enterocolite Necrosante/genética , Enterocolite Necrosante/imunologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Feminino , Humanos , Mucosa Intestinal/citologia , Mucosa Intestinal/imunologia , Lipídeos/química , Masculino , Camundongos , NF-kappa B/genética , NF-kappa B/imunologia , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas em Tandem , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/imunologia , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
20.
Front Psychol ; 11: 1066, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32595556

RESUMO

It is widely acknowledged that non-compliance with smartphone security behaviors is widespread and may cause severe harm to people and devices. In addition to device-based security issues, there are psychological factors involved in these behaviors such as self-efficacy, risk awareness, and social support. The present study examines associations of these three factors with smartphone security behaviors and explores possible mechanisms among these variables. In a longitudinal survey with 192 Chinese college students (73.4% women, mean age 24.46 years, SD = 5.15), self-efficacy, risk awareness, and social support were assessed with psychometric scales at two points in time, 2 weeks apart. Hierarchical regression analyses were performed with follow-up smartphone security behaviors as the dependent variable, controlling for baseline values and demographic and IT-related covariates. Main effects of self-efficacy, risk awareness, and social support on smartphone security behaviors were identified. Moreover, a triple interaction among the three predictors emerged in a synergistic way, indicating that their combination yielded more favorable levels of secure smartphone use. The total model accounted for 50% of the behavioral variance, with all covariates included, and the triple interaction among self-efficacy, risk awareness, and social support accounted for 2.3% of variance. Results document that psychological factors are involved in smartphone security behaviors beyond demographic and IT-related covariates. Interventions could be designed to improve smartphone security behaviors not only by developing privacy-enhancing technologies but also by considering psychological factors such as self-efficacy, risk awareness, and social support.

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