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Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Diabetes Mellitus Tipo 2/prevención & control , Trastornos Respiratorios/prevención & control , Trastornos Respiratorios/epidemiología , Enfermedades Respiratorias/prevención & control , Hipoglucemiantes/uso terapéuticoRESUMEN
Osteosarcoma is a malignant tumor originating from bone tissue that progresses rapidly and has a poor patient prognosis. Immunotherapy has shown great potential in the treatment of osteosarcoma. However, the immunosuppressive microenvironment severely limits the efficacy of osteosarcoma treatment. The dual pH-sensitive nanocarrier has emerged as an effective antitumor drug delivery system that can selectively release drugs into the acidic tumor microenvironment. Here, we prepared a dual pH-sensitive nanocarrier, loaded with the photosensitizer Chlorin e6 (Ce6) and CD47 monoclonal antibodies (aCD47), to deliver synergistic photodynamic and immunotherapy of osteosarcoma. On laser irradiation, Ce6 can generate reactive oxygen species (ROS) to kill cancer cells directly and induces immunogenic tumor cell death (ICD), which further facilitates the dendritic cell maturation induced by blockade of CD47 by aCD47. Moreover, both calreticulin released during ICD and CD47 blockade can accelerate phagocytosis of tumor cells by macrophages, promote antigen presentation, and eventually induce T lymphocyte-mediated antitumor immunity. Overall, the dual pH-sensitive nanodrug loaded with Ce6 and aCD47 showed excellent immune-activating and anti-tumor effects in osteosarcoma, which may lay the theoretical foundation for a novel combination model of osteosarcoma treatment.
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Neoplasias Óseas , Clorofilidas , Nanopartículas , Neoplasias , Osteosarcoma , Fotoquimioterapia , Humanos , Antígeno CD47 , Línea Celular Tumoral , Osteosarcoma/tratamiento farmacológico , Inmunoterapia , Neoplasias Óseas/tratamiento farmacológico , Concentración de Iones de Hidrógeno , Microambiente TumoralRESUMEN
AIMS: Vascular calcification is highly prevalent in atherosclerosis, diabetes, and chronic kidney disease. It is associated with increased morbidity and mortality in patients with cardiovascular disease. Matrix metalloproteinase 3 (MMP-3), also known as stromelysin-1, is part of the large matrix metalloproteinase family. It can degrade extracellular matrix components of the arterial wall including elastin, which plays a central role in medial calcification. In this study, we sought to determine the role of MMP-3 in medial calcification. METHODS AND RESULTS: We found that MMP-3 was increased in rodent models of medial calcification as well as in vascular smooth muscle cells (SMCs) cultured in a phosphate calcification medium. It was also highly expressed in calcified tibial arteries in patients with peripheral arterial disease (PAD). Knockdown and inhibition of MMP-3 suppressed phosphate-induced SMC osteogenic transformation and calcification, whereas the addition of a recombinant MMP-3 protein facilitated SMC calcification. In an ex vivo organ culture model and a rodent model of medial calcification induced by vitamin D3, we found that MMP-3 deficiency significantly suppressed medial calcification in the aorta. We further found that medial calcification and osteogenic transformation were significantly reduced in SMC-specific MMP-3-deficient mice, suggesting that MMP-3 in SMCs is an important factor in this process. CONCLUSION: These findings suggest that MMP-3 expression in vascular SMCs is an important regulator of medial calcification and that targeting MMP-3 could provide a therapeutic strategy to reduce it and address its consequences in patients with PAD.
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Eliminación de Gen , Metaloproteinasa 3 de la Matriz , Calcificación Vascular , Humanos , Ratones , Ratas , Aorta/metabolismo , Modelos Animales de Enfermedad , Expresión Génica , Metaloproteinasa 3 de la Matriz/deficiencia , Metaloproteinasa 3 de la Matriz/genética , Metaloproteinasa 3 de la Matriz/metabolismo , Ratones Endogámicos C57BL , Músculo Liso Vascular/citología , Ratas Sprague-Dawley , Proteínas Recombinantes/farmacología , Calcificación Vascular/enzimología , Calcificación Vascular/genética , AnimalesRESUMEN
The purpose of this systematic review was to synthesise the evidence for the association of adherence to the 24-h movement guidelines with academic-related outcomes in children and adolescents. This systematic review was based on the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) statement. PubMed, PsycINFO, Scopus, WOS, SPORTDiscus, and EMBASE were searched from their inception to 12 December 2023. The Joanna Briggs Institute (JBI) Critical Appraisal Checklist was used to assess the risk of bias of included studies. In total, 4326 records were identified through database searches; 10 articles met the inclusion criteria and were included in this systematic review. There were eight cross-sectional studies and two longitudinal studies; the main academic-related outcomes were academic achievement and cognitive function. A small association between adherence to all three recommendations and academic achievement (k = 5, r = 0.17, 95% CI = 0.10-0.24, I2 = 49%) was found compared to those who did not adhere to any recommendations. Conclusion: Findings from this systematic review and meta-analysis reveal a small association between adherence to all three recommendations and greater academic achievement in children and adolescents. Nevertheless, it is imperative to underscore the need for more studies to establish robust evidence underpinning this relationship. Trial registration: PROSPERO (CRD42021295403). What is Known: ⢠Regular physical activity, reduced screen time, and optimal sleep duration are independently associated with improved academic-related outcomes in children and adolescents. ⢠The associations between adherence to the 24-h movement guidelines and academic-related outcomes in children and adolescents have not been quantitatively synthesised. What is New: ⢠There is a small but positive association between adherence to all three recommendations of the 24-h movement guidelines and greater academic achievement in children and adolescents. ⢠Further well-designed research is needed to focus on academic achievement, cognitive function and classroom behaviours in young individuals.
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Éxito Académico , Humanos , Adolescente , Niño , Ejercicio Físico , Adhesión a Directriz/estadística & datos numéricos , CogniciónRESUMEN
Human immunodeficiency virus-1 (HIV-1) infection can cause chronic activation, exhaustion, and anergy of the immune system. Cytotoxic T lymphocyte-associated antigen-4 (CTLA-4) is an immune checkpoint molecule, which plays an important role in immune homeostasis and disease. CTLA-4 expression is elevated in HIV-1-infected patients and is associated with disease progression. However, the mechanism controlling expression of CTLA-4 in HIV-1 infection is poorly characterized. In this study, we used a SIV-infected Chinese rhesus macaque (ChRM) model to explore CTLA-4 expression in SIV infection. Results showed that SIV infection significantly increased CTLA-4 expression in all T cell subsets, especially central memory T cells. CTLA-4+CD4+ T cell frequency was significantly associated with disease progression markers. Activation of the cyclic adenosine monophosphate (cAMP)-protein kinase A (PKA) signaling pathway regulated CTLA-4 expression in CD4+T cells, as confirmed by stimulation with dibutyryl cyclic adenosine monophosphate, forskolin, and 3-isobutyl-1-methylxanthine, and inhibition with H-89 ex vivo. Simultaneously, cAMP concentration in PBMCs and PKA activity in both PBMCs and CD4+ T cells were increased in acute SIV-infected ChRMs, accompanied by an increase in adenylate cyclase 6 expression and a decrease in cAMP-phosphodiesterase 3A (PDE3A), PDE4B, and PDE5A expression in PBMCs. In addition, selective inhibition of PDE4B and PDE5A activity enhanced CTLA-4 expression in CD4+ T cells. These results suggest that SIV infection alters cAMP metabolism and increases cAMP-PKA signaling pathway activation, which up-regulates the expression of CTLA-4 in acute SIVmac239-infected ChRMs. Thus, regulation of the cAMP-PKA signaling pathway may be a potential strategy for the restoration of T cell function and therapy for AIDS.
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Infecciones por VIH , Síndrome de Inmunodeficiencia Adquirida del Simio , Virus de la Inmunodeficiencia de los Simios , Animales , Humanos , Linfocitos T CD4-Positivos , Macaca mulatta , Virus de la Inmunodeficiencia de los Simios/fisiología , Antígeno CTLA-4/genética , Regulación hacia Arriba , Progresión de la Enfermedad , Transducción de Señal , Adenosina MonofosfatoRESUMEN
OBJECTIVE: Emerging evidence suggests that meeting the 24-h movement guidelines is associated with optimal mental health. However, there remains some uncertainty regarding this association in children. Therefore, this study aimed to examine the association between meeting the 24-h movement guidelines and psychosocial health in children. METHODS: A cross-sectional study design was employed to investigate 2005 children aged 9-12 years from four districts of Shanghai, China. The 24-h movement behaviours were assessed using selected items from the Health Behaviour in School-aged Children (HBSC) survey questionnaire. Children's self-rated psychosocial health was evaluated using the Strengths or Difficulties Questionnaire (SDQ). Generalised Linear Models with the ordinal logistic module were employed to analyse the association between meeting the 24-h movement guidelines and psychosocial health. RESULTS: The overall prevalence of meeting all three 24-h movement recommendations was 10.2%. Among children, 7.9% of them exhibited abnormal total difficulties, with a notable difference between sex (boys: 11.2%, girls: 7.0%, p = 0.001). Meeting all three 24-h movement behaviour recommendations was associated with reduced total difficulties, emotional symptoms, conduct problems, hyperactivity and peer problems. Furthermore, a dose-response association was observed, indicating that meeting a greater number of 24-h movement behaviour recommendations was associated with enhanced psychosocial health, particularly in boys. CONCLUSION: The findings of this study highlight the positive association between meeting the 24-h movement guidelines and psychosocial health in children. Notably, meeting more of these recommendations was associated with a lower likelihood of experiencing psychosocial problems, with greater benefits observed in boys compared with girls.
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Trastornos Mentales , Masculino , Niño , Femenino , Humanos , Estudios Transversales , China , Trastornos Mentales/psicología , Encuestas y Cuestionarios , Salud Mental , Sueño/fisiologíaRESUMEN
Perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid (PFOA) are persistent environmental contaminants that are of increasing public concern worldwide. However, their relationship with colorectal cancer (CRC) is poorly understood. This study aims to comprehensively investigate the effect of PFOS and PFOA on the development and progression of CRC in vitro using a series of biological techniques and metabolic profiling. Herein, the migration of three-dimensional (3D) spheroids of two CRC cell lines, SW48 KRAS wide-type (WT) and SW48 KRAS G12A, were observed after exposure to PFOS and PFOA at 2 µM and 10 µM for 7 days. The time and dose-dependent migration phenotype induced by 10 µM PFOS and PFOA was further confirmed by wound healing and trans-well migration assays. To investigate the mechanism of action, derivatization-mass spectrometry-based metabolic profiles were examined from 3D spheroids of SW48 cell lines exposed to PFOS and PFOA (2 µM and 10 µM). Our findings revealed this exposure altered epithelial-mesenchymal transition related metabolic pathways, including fatty acid ß-oxidation and synthesis of proteins, nucleotides, and lipids. Furthermore, this phenotype was confirmed by the downregulation of E-cadherin and upregulation of N-cadherin and vimentin. These findings show novel insight into the relationship between PFOS, PFOA, and CRC.
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Ácidos Alcanesulfónicos , Neoplasias Colorrectales , Fluorocarburos , Humanos , Proteínas Proto-Oncogénicas p21(ras) , Fluorocarburos/toxicidad , Ácidos Alcanesulfónicos/toxicidad , Caprilatos/toxicidadRESUMEN
Purpose: The study aims to explore the relationship and potential mechanisms between screen time and anxiety and have a clear understanding of the role of negative emotions and emotion regulation, thus providing guidance for Chinese college students to improve mental health. Methods: We conducted a questionnaire survey by selecting 1721 academic college students from 6 colleges and universities in 5 provinces in China, and the data were analyzed through the Process program of SPSS for mediating effect and moderating effect. Results: There is a significant positive relationship between screen time and anxiety, negative emotions play a mediating role between the two (indirect effect = 0.32, p < 0.001), mediating effect accounts for 59.88% of the total effect, and emotion regulation regulates the direct relationship between screen time and anxiety (interaction effect = 0.027, p < 0.001). Conclusion: This study sheds light on the potential mechanisms by which screen time affects anxiety in academic college students, providing a fresh perspective on anxiety reduction. Screen time positively affects anxiety levels, where negative emotions have a mediating role and emotion regulation has a moderating role. In the future, we can control screen ++time, increase physical activities, reduce negative emotions, and improve the emotional regulation ability to relieve anxiety, so as to improve the mental health of academic college students, and expect to have a positive impact on future learning, life, and planning.
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The protective blood-brain barrier (BBB) prevents most therapeutic agents from entering the brain. Currently, focused ultrasound (FUS) is mostly employed to create microbubbles that induce a cavitation effect to open the BBB. However, microbubbles pass quickly through brain microvessels, substantially limiting the cavitation effect. Here, we constructed a novel perfluoropropane-loaded microbubble, termed ApoER-Pep-MB, which possessed a siloxane bonds-crosslinked surface to increase the microbubble stability against turbulence in blood circulation and was decorated with binding peptide for apolipoprotein E receptor (ApoER-Pep). The microbubble with tailor-made micron size (2 µm) and negative surface charge (-30 mV) performed ApoER-mediated binding rather than internalization into brain capillary endothelial cells. Consequently, the microbubble accumulated on the brain microvessels, based on which even a low-energy ultrasound with less safety risk than FUS, herein diagnostic ultrasound (DUS), could create a strong cavitation effect to open the BBB. Evans Blue and immunofluorescence staining studies demonstrated that the DUS-triggered cavitation effect not only temporarily opened the BBB for 2 h but also caused negligible damage to the brain tissue. Therefore, various agents, ranging from small molecules to nanoscale objects, can be efficiently delivered to target regions of the brain, offering tremendous opportunities for the treatment of brain diseases.
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Barrera Hematoencefálica , Microburbujas , Barrera Hematoencefálica/metabolismo , Células Endoteliales , Ultrasonografía , EndotelioRESUMEN
Purpose: The purpose of this study was to examine the relationships between academic engagement and moderate-to-vigorous physical activity (MVPA), muscle-strengthening exercise (MSE) and sedentary behavior (SB) among adolescents, so as to provide evidence from the perspective of exercising for students to learn efficiently, teachers to improve classroom teaching, and schools to improve educational quality. Methods: A questionnaire survey was conducted in 12 junior high schools in Shanghai, China, which were selected by a multi-stage stratified cluster sampling method. Then, with the valid data of 2078 students collected from the survey. A data analysis was performed using SPSS Statistics 26.0. Multiple linear regression models were adopted to analyze the factors affecting adolescent academic engagement and to determine whether MVPA, MSE, and SB play roles in it. Results: (1) The differences in academic engagement depended on the exercise adherence to the recommended amount of MVPA, MSE, and screen-based SB. (2) In terms of the three independent variables of total time, MSE (ß = 0.206) and MVPA (ß = 0.175) showed a significant positive correlation with academic engagement, while SB (ß = -0.155) was negatively correlated with academic engagement. (3) From the linear regression model of eight combination groups divided by the exercise adherence to the recommended amount of MVPA, MSE and SB, the group that met none of the recommendations (ß = -0.235) showed a significant negative effect on academic engagement, while the groups that met any two or all three of the recommendations demonstrated strong positive correlations with academic engagement (P < 0.001). Conclusion: Increasing adolescents' muscle-strengthening exercise and moderate-to-vigorous physical activity and reducing sedentary behavior can effectively promote academic engagement. Therefore, adolescents are suggested to reach the recommended amounts of physical activity, muscle-strengthening exercise, and sedentary behavior so as to improve academic engagement more effectively.
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Background: The Körperkoordinationstest Für Kinder (KTK) is a reliable and low-cost motor coordination test tool that has been used in several countries. However, whether the KTK is a reliable and valid instrument for use in Chinese children has not been assessed. Additionally, because the KTK was designed to incorporate locomotor, object control, and stability skills, and there is a lack of measurement tools that include stability skills assessment for Chinese children, the KTK's value and validity are worth discussing. Methods: A total of 249 primary school children (131 boys; 118 girls) aged 9-10 years from Shanghai were recruited in this study. Against the Test of Gross Motor Development-3 (TGMD-3), the concurrent validity of the KTK was assessed. We also tested the retest reliability and internal consistency of the KTK. Results: The test-retest reliability of the KTK was excellent (overall: r = 0.951; balancing backwards: r = 0.869; hopping for height: r = 0.918; jumping sideways: r = 0.877; moving sideways: r = 0.647). Except for the boys, the internal consistency of the KTK was higher than the acceptable level of Cronbach's α > 0.60 (overall: α = 0.618; boys: α = 0.583; girls: α = 0.664). Acceptable concurrent validity was found between the total scores for the KTK and TGMD-3 (overall: r = 0.420, p < 0.001; boys: r = 0.411, p < 0.001; girls: r = 0.437, p < 0.001). Discussion: The KTK is a reliable instrument for assessing the motor coordination of children in China. As such, the KTK can be used to monitor the level of motor coordination in Chinese children.
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Pueblos del Este de Asia , Desempeño Psicomotor , Niño , Femenino , Humanos , Masculino , China , Reproducibilidad de los ResultadosRESUMEN
Arteriovenous fistulae (AVF) fail to mature more frequently in female patients compared with male patients, leading to inferior outcomes and decreased utilization. Since our mouse AVF model recapitulates sex differences in human AVF maturation, we hypothesized that sex hormones mediate these differences during AVF maturation. C57BL/6 mice (9-11 wk) were treated with aortocaval AVF surgery and/or gonadectomy. AVF hemodynamics were measured via ultrasound (days 0-21). Blood was collected for FACS and tissue for immunofluorescence and ELISA (days 3 and 7); wall thickness was assessed by histology (day 21). Inferior vena cava shear stress was higher in male mice (P = 0.0028) after gonadectomy, and they had increased wall thickness (22.0 ± 1.8 vs. 12.7 ± 1.2 µm; P < 0.0001). Conversely, female mice had decreased wall thickness (6.8 ± 0.6 vs. 15.3 ± 0.9 µm; P = 0.0002). Intact female mice had higher proportions of circulating CD3+ T cells on day 3 (P = 0.0043), CD4+ (P = 0.0003) and CD8+ T cells (P = 0.005) on day 7, and CD11b+ monocytes on day 3 (P = 0.0046). After gonadectomy, these differences disappeared. In intact female mice, CD3+ T cells (P = 0.025), CD4+ T cells (P = 0.0178), CD8+ T cells (P = 0.0571), and CD68+ macrophages (P = 0.0078) increased in the fistula wall on days 3 and 7. This disappeared after gonadectomy. Furthermore, female mice had higher IL-10 (P = 0.0217) and TNF-α (P = 0.0417) levels in their AVF walls than male mice. Sex hormones mediate AVF maturation, suggesting that hormone receptor signaling may be a target to improve AVF maturation.NEW & NOTEWORTHY After arteriovenous fistula creation, females have lower rates of maturation and higher rates of failure than males. In a mouse model of venous adaptation that recapitulates human fistula maturation, sex hormones may be mechanisms of the sexual dimorphism: testosterone is associated with reduced shear stress, whereas estrogen is associated with increased immune cell recruitment. Modulating sex hormones or downstream effectors suggests sex-specific therapies and could address disparities in sex differences in clinical outcomes.
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Fístula Arteriovenosa , Derivación Arteriovenosa Quirúrgica , Humanos , Masculino , Femenino , Ratones , Animales , Linfocitos T CD8-positivos , Maduración Sexual , Ratones Endogámicos C57BL , Derivación Arteriovenosa Quirúrgica/efectos adversos , Modelos Animales de Enfermedad , Testosterona , Inmunidad , Diálisis RenalRESUMEN
BACKGROUND: The cut-off date in the education system causes a relative age difference, with developmental advantages for children who are born on the "early side" of the cut-off date and disadvantages for those born later, which is known as the relative age effect (RAE). Very few studies have examined whether there is a RAE on the development of fundamental movement skills (FMSs) in preschool children, and no studies have been conducted in China. The purpose of this study is to identify whether a RAE exists on FMS in Chinese preschool children, comparing RAEs according to gender and age. METHODS: From a total of 378 invited preschool children regularly registered at one Chinese kindergarten, a total of 288 healthy and typically developing preschoolers (4.33 ± 0.84 years-old; 56.6% boys) were included in this study. All children were required to take part in anthropometry and FMS assessments. Analysis of covariance (ANCOVA) was applied to examine the difference in each of the FMS items across quarter categories, year and gender groups, controlling for body mass index (BMI). RESULTS: For the overall sample, the data show the significant main effects on the quarter of birth factor in locomotor skills (LC; F (3, 265) = 2.811, p = 0.04, ηp2 = 0.031), object control skills (OB; F (3, 265) = 6.319, p = 0.04, ηp2 = 0.031), and total test score (TTS; F (3, 265) = 5.988, p = 0.001, ηp2 = 0.063). There were also significant differences in the age effect on all the domains of FMS (FLC (2, 265) = 100.654, p < 0.001, ηp2 = 0.432; FOB (2, 265) = 108.430, p < 0.001, ηp2 = 0.450; FTTS (2, 265) = 147.234, p < 0.001, ηp2 = 0.526) but a gender effect only in LC (F (1, 265) = 20.858; p < 0.001; ηp2 = 0.073). For gender and quarter of birth groups, RAEs in LC only exists in girls. Moreover, regarding age and quarter of birth factors, RAEs are only found at younger ages. CONCLUSIONS: This study suggests the existence of RAEs in the FMS of Chinese preschool children. Teachers need to be aware of the effect of RAEs on the FMS when approaching development, evaluation, and teaching approaches in preschools.
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Pueblos del Este de Asia , Destreza Motora , Masculino , Femenino , Preescolar , Humanos , Índice de Masa Corporal , Antropometría , MovimientoRESUMEN
The dense extracellular matrix (ECM) is a key barrier to tumor infiltration of cytotoxic T lymphocytes (CTLs), which greatly compromises T cell-dependent immunotherapy of hepatocellular carcinoma (HCC). Herein, hyaluronidase (HAase), IL-12, and anti-PD-L1 antibody (αPD-L1) were co-delivered using a pH and MMP-2 dual-sensitive polymer/calcium phosphate (CaP) hybrid nanocarrier. The dissolution of CaP triggered by tumor acidity facilitated the release of IL-12 and HAase responsible for ECM digestion, enhancing the tumor infiltration and proliferation of CTLs. Furthermore, the in situ-released αPD-L1 inside tumor, as triggered by an overexpressed MMP-2, prevented the tumor cell from escaping the killing effects of CTLs. Such combination strategy induced a robust antitumor immunity for efficiently suppressing HCC growth in mice. Additionally, tumor acidity-sheddable polyethylene glycol (PEG) coating enhanced the tumor accumulation of nanocarrier and reduced the immune-related adverse events (irAEs) induced by on-target off-tumor αPD-L1. This dual-sensitive nanodrug demonstrates an effective immunotherapy paradigm for other dense ECM-characterized solid tumors.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Nanopartículas , Animales , Ratones , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/patología , Metaloproteinasa 2 de la Matriz , Neoplasias Hepáticas/patología , Línea Celular Tumoral , Inmunoterapia , Interleucina-12 , Nanopartículas/uso terapéutico , Microambiente TumoralRESUMEN
Triple negative breast cancer (TNBC) as a highly aggressive and metastatic malignancy lacks targeting therapies nowadays. Moreover, although immune checkpoint blockade (ICB) is known to trigger anti-tumor immune response, most TNBC falls into the immunologically "cold" category unsuitable for ICB therapy due to insufficient lymphocyte infiltration. Herein, we develop a hierarchical targeting strategy for preparing a core-shell-structural nanodrug to concurrently block the programmed death ligand 1 (PD-L1) and deliver a stimulator of interferon gene (STING) agonist into tumor-infiltrating antigen-presenting cells (APCs). The nanodrug complexed the interferon stimulatory DNA (ISD) for STING activation in its core, conjugated PD-L1 antibody (aPD-L1) on its shell through a matrix metalloproteinase-2 (MMP-2) substrate peptide, and incorporated "hidden" mannose in its sublayer. Through aPD-L1-mediated active targeting of tumor cells and tumor-infiltrating APCs, the nanodrug efficiently accumulated in tumor sites. Then, the PD-L1-conjugating peptide was cleaved by tumor-enriched MMP-2, leaving aPD-L1 on target cells for ICB while exposing mannose to mediate targeted delivery of ISD into tumor-infiltrating dendritic cells (DCs) and tumor-associated macrophages (TAMs). Activating the STING signaling in DCs and TAMs not only stimulated the APCs maturation to prime anti-tumor immunity but also induced their chemokine secretion to promote tumor infiltration of anti-tumor effector T cells, thus sensitizing TNBC to the ICB therapy. Consequently, a potent antitumor immunity was evoked to effectively inhibit the tumor growth and metastasis in mice bearing orthotopic 4T1 breast cancer, showing the great potential in treating immunologically "cold" tumors.
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Neoplasias de la Mama Triple Negativas , Humanos , Animales , Ratones , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/genética , Metaloproteinasa 2 de la Matriz , Antígeno B7-H1 , Manosa , Interferones/farmacología , Interferones/uso terapéutico , Microambiente Tumoral , Línea Celular TumoralRESUMEN
In the context of exercise psychology, the mediating relationship between peer support, self-efficacy and self-regulation, and adolescents' exercise adherence was to be explored. METHODS: A questionnaire was distributed among 2200 teenagers from twelve middle schools in Shanghai. The "process" program in SPSS and the bootstrap method were applied to construct and analyze the direct and indirect effects of peer support on adolescents' exercise adherence. RESULTS: Peer support directly affected adolescents' exercise adherence (ß = 0.135, p < 0.001, effect size of 59%) and self-efficacy (ß = 0.493, p < 0.001, effect size accounted for 42%), and self-regulation (ß = -0.184, p < 0.001, effect size of 11%) influenced exercise adherence indirectly. In addition, self-efficacy and self-regulation could impose a chain-mediated effect on peer support and exercise adherence (effect size of 6%). CONCLUSION: Peer support could promote adolescents' exercise adherence. Self-efficacy and self-regulation are mediating factors of peer support on exercise adherence in teenagers, self-regulation as well as self-efficacy-imposed chain-mediating effects on peer support and adolescents' exercise adherence.
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In this work, we develop methods for few-shot image classification from a new perspective of optimal matching between image regions. We employ the Earth Mover's Distance (EMD) as a metric to compute a structural distance between dense image representations to determine image relevance. The EMD generates the optimal matching flows between structural elements that have the minimum matching cost, which is used to calculate the image distance for classification. To generate the important weights of elements in the EMD formulation, we design a cross-reference mechanism, which can effectively alleviate the adverse impact caused by the cluttered background and large intra-class appearance variations. To implement k-shot classification, we propose to learn a structured fully connected layer that can directly classify dense image representations with the EMD. Based on the implicit function theorem, the EMD can be inserted as a layer into the network for end-to-end training. Our extensive experiments validate the effectiveness of our algorithm which outperforms state-of-the-art methods by a significant margin on five widely used few-shot classification benchmarks, namely, miniImageNet, tieredImageNet, Fewshot-CIFAR100 (FC100), Caltech-UCSD Birds-200-2011 (CUB), and CIFAR-FewShot (CIFAR-FS). We also demonstrate the effectiveness of our method on the image retrieval task in our experiments.
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Background/Objective: Regular physical activity (PA) is beneficial to young people's health and development. In order to provide nationally representative and internationally comparable evidence on youth PA, China has participated in Global Matrix 2.0 and 3.0. The purpose of this study is to report the updated results of China's Report Card on PA for Children and Adolescents. Methods: The grades were assigned by results derived from the PA and Fitness in China--The Youth Study (PAFCTYS), conducted from October to December in 2020. The data from PAFCTYS 2020 included a nationally representative sample of Chinese school-aged children (n = 133,006, boys: 49.6%, aged 9-17 years). Self-report questionnaires were completed by the sampled students, their parents/guardians (n = 133,006), and physical education teachers (n = 1036) from each sampled school respectively. Results: The grades of China 2022 Report Card are Overall PA (C), Organized Sport Participation (F), Active Play (C-), Active Transportation (C), Sedentary behaviors (C), Physical Fitness (INC), Family and Peers (C-), School (D), Community and Environment (D-), and Government (D). Conclusion: Levels of PA among Chinese youth were low and most young people were below the recommended guidelines, although the grade of Overall PA has been improved since the modified benchmark. Prevalence of sedentary behaviors remained high. Interventions and policies at the community and environment level should be encouraged to promote PA and reduce sedentary behaviors. In addition, national policies on young people's PA should be advocated widely to ensure the policies can be transferred into action.