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Recently, substantial evidence has demonstrated that pseudogene-derived long noncoding RNAs (lncRNAs) as regulatory RNAs have been implicated in basic physiological processes and disease development through multiple modes of functional interaction with DNA, RNA, and proteins. Here, we report an important role for GBP1P1, the pseudogene of guanylate-binding protein 1, in regulating influenza A virus (IAV) replication in A549 cells. GBP1P1 was dramatically upregulated after IAV infection, which is controlled by JAK/STAT signaling. Functionally, ectopic expression of GBP1P1 in A549 cells resulted in significant suppression of IAV replication. Conversely, silencing GBP1P1 facilitated IAV replication and virus production, suggesting that GBP1P1 is one of the interferon-inducible antiviral effectors. Mechanistically, GBP1P1 is localized in the cytoplasm and functions as a sponge to trap DHX9 (DExH-box helicase 9), which subsequently restricts IAV replication. Together, these studies demonstrate that GBP1P1 plays an important role in antagonizing IAV replication.IMPORTANCELong noncoding RNAs (lncRNAs) are extensively expressed in mammalian cells and play a crucial role as regulators in various biological processes. A growing body of evidence suggests that host-encoded lncRNAs are important regulators involved in host-virus interactions. Here, we define a novel function of GBP1P1 as a decoy to compete with viral mRNAs for DHX9 binding. We demonstrate that GBP1P1 induction by IAV is mediated by JAK/STAT activation. In addition, GBP1P1 has the ability to inhibit IAV replication. Importantly, we reveal that GBP1P1 acts as a decoy to bind and titrate DHX9 away from viral mRNAs, thereby attenuating virus production. This study provides new insight into the role of a previously uncharacterized GBP1P1, a pseudogene-derived lncRNA, in the host antiviral process and a further understanding of the complex GBP network.
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RNA Helicases DEAD-box , Vírus da Influenza A , Pseudogenes , Replicação Viral , Humanos , Células A549 , RNA Helicases DEAD-box/metabolismo , RNA Helicases DEAD-box/genética , Vírus da Influenza A/genética , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Transdução de Sinais , Influenza Humana/virologia , Influenza Humana/genética , Influenza Humana/metabolismo , Animais , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Células HEK293 , Interações Hospedeiro-Patógeno , Cães , Proteínas de NeoplasiasRESUMO
A nonlinear holographic technique is capable of processing optical information in the newly generated optical frequencies, enabling fascinating functions in laser display, security storage, and image recognition. One popular nonlinear hologram is based on a periodically poled lithium niobate (LN) crystal. However, due to the limitations of traditional fabrication techniques, the pixel size of the LN hologram is typically several micrometers, resulting in a limited field-of-voew (FOV) of several degrees. Here, we experimentally demonstrate an ultra-high-resolution LN hologram by using the laser poling technique. The minimal pixel size reaches 200 nm, and the FOV is extended above 120° in our experiments. The image distortions at large view angles are effectively suppressed through the Fourier transform. The FOV is further improved by combining multiple diffraction orders of SH fields. The ultimate FOV under our configuration is decided by a Fresnel transmission. Our results pave the way for expanding the applications of nonlinear holography to wide-view imaging and display.
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GNA13 (Gα13) is one of two alpha subunit members of the G12/13 family of heterotrimeric G-proteins which mediate signaling downstream of GPCRs. It is known to be essential for embryonic development and vasculogenesis and has been increasingly shown to be involved in mediating several steps of cancer progression. Recent studies found that Gα13 can function as an oncogene and contributes to progression and metastasis of multiple tumor types, including ovarian, head and neck and prostate cancers. In most cases, Gα12 and Gα13, as closely related α-subunits in the subfamily, have similar cellular roles. However, in recent years their differences in signaling and function have started to emerge. We previously identified that Gα13 drives invasion of Triple Negative Breast Cancer (TNBC) cells in vitro. As a highly heterogenous disease with various well-defined molecular subtypes (ER+ /Her2-, ER+ /Her2+, Her2+, TNBC) and subtype associated outcomes, the function(s) of Gα13 beyond TNBC should be explored. Here, we report the finding that low expression of GNA13 is predictive of poorer survival in breast cancer, which challenges the conventional idea of Gα12/13 being universal oncogenes in solid tumors. Consistently, we found that Gα13 suppresses the proliferation in multiple ER+ breast cancer cell lines (MCF-7, ZR-75-1 and T47D). Loss of GNA13 expression drives cell proliferation, soft-agar colony formation and in vivo tumor formation in an orthotopic xenograft model. To evaluate the mechanism of Gα13 action, we performed RNA-sequencing analysis on these cell lines and found that loss of GNA13 results in the upregulation of MYC signaling pathways in ER+ breast cancer cells. Simultaneous silencing of MYC reversed the proliferative effect from the loss of GNA13, validating the role of MYC in Gα13 regulation of proliferation. Further, we found Gα13 regulates the expression of MYC, at both the transcript and protein level in an ERα dependent manner. Taken together, our study provides the first evidence for a tumor suppressive role for Gα13 in breast cancer cells and demonstrates for the first time the direct involvement of Gα13 in ER-dependent regulation of MYC signaling. With a few exceptions, elevated Gα13 levels are generally considered to be oncogenic, similar to Gα12. This study demonstrates an unexpected tumor suppressive role for Gα13 in ER+ breast cancer via regulation of MYC, suggesting that Gα13 can have subtype-dependent tumor suppressive roles in breast cancer.
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Proliferação de Células , Receptor alfa de Estrogênio , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP , Regulação Neoplásica da Expressão Gênica , Proteínas Proto-Oncogênicas c-myc , Humanos , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/metabolismo , Subunidades alfa G12-G13 de Proteínas de Ligação ao GTP/genética , Feminino , Receptor alfa de Estrogênio/metabolismo , Receptor alfa de Estrogênio/genética , Animais , Linhagem Celular Tumoral , Camundongos , Proteínas Proto-Oncogênicas c-myc/genética , Proteínas Proto-Oncogênicas c-myc/metabolismo , Neoplasias de Mama Triplo Negativas/genética , Neoplasias de Mama Triplo Negativas/patologia , Neoplasias de Mama Triplo Negativas/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Neoplasias da Mama/metabolismo , Transdução de Sinais , Regulação para CimaRESUMO
BACKGROUND: Weed control is essential for agricultural floor management in vineyards and the inter-row mulching is an eco-friendly practice to inhibit weed growth via filtering out photosynthetically active radiation. Besides weed suppression, inter-row mulching can influence grapevine growth and the accumulation of metabolites in grape berries. However, the complex interaction of multiple factors in the field challenges the understanding of molecular mechanisms on the regulated metabolites. In the current study, black geotextile inter-row mulch (M) was applied for two vintages (2016-2017) from anthesis to harvest. Metabolomics and transcriptomics analysis were conducted in two vintages, aiming to provide insights into metabolic and molecular responses of Cabernet Sauvignon grapes to M in a semi-arid climate. RESULTS: Upregulation of genes related to photosynthesis and heat shock proteins confirmed that M weakened the total light exposure and grapes suffered heat stress, resulting in lower sugar-acid ratio at harvest. Key genes responsible for enhancements in phenylalanine, glutamine, ornithine, arginine, and C6 alcohol concentrations, and the downward trend in ε-viniferin, anthocyanins, flavonols, terpenes, and norisoprenoids in M grapes were identified. In addition, several modules significantly correlated with the metabolic biomarkers through weighted correlation network analysis, and the potential key transcription factors regulating the above metabolites including VviGATA11, VviHSFA6B, and VviWRKY03 were also identified. CONCLUSION: This study provides a valuable overview of metabolic and transcriptomic responses of M grapes in semi-arid climates, which could facilitate understanding the complex regulatory network of metabolites in response to microclimate changes.
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Vitis , Vinho , Vitis/metabolismo , Transcriptoma , Antocianinas/metabolismo , Microclima , Fazendas , Frutas , Vinho/análiseRESUMO
OBJECTIVE: This study aimed to investigate the structure of the mitral valve in patients undergoing mitral valvuloplasty (MVP) using real-time three-dimensional transesophageal echocardiography (RT-3D-TEE). The main objective was to study the relationship between intraoperative annuloplasty ring size and mitral valve structure dimensions, with a focus on exploring the application value of RT-3D-TEE in MVP. METHODS: A total of 28 patients with degenerative mitral regurgitation (DMR), who underwent MVP between February and September 2022, as well as 12 normal control cases, were enrolled in this study. The MV annulus and leaflets were quantitatively analyzed using MVN software. RESULTS: The DMR group exhibited significantly greater dimensions in various parameters of the mitral valve, including the anterolateral-to-posteromedial diameter (DAlPm ), anterior-to-posterior diameter (DAP ), annulus height (HA ), three-dimensional annulus circumference (CA3D ), two-dimensional annulus area (AA2D ), anterior leaflet area (Aant ), posterior leaflet area (Apost ), anterior leaflet length (Lant ), posterior leaflet length (Lpost ), and tenting volume (Vtent ) compared to the control group. CONCLUSION: Real-time three-dimensional transesophageal echocardiography provides valuable insights into the morphological structure of the mitral valve and lesion location. It can aid in surgical decision-making, validate the success of MVP, and potentially reduce mortality and complications associated with mitral valve repair procedures.
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Valvuloplastia com Balão , Ecocardiografia Tridimensional , Ecocardiografia Transesofagiana , Insuficiência da Valva Mitral , Humanos , Ecocardiografia Tridimensional/métodos , Ecocardiografia Transesofagiana/métodos , Eletrocardiografia , Valva Mitral/diagnóstico por imagem , Valva Mitral/cirurgia , Insuficiência da Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/cirurgiaRESUMO
Spinal muscular atrophy (SMA) is a neuromuscular disorder with an autosomal recessive inheritance pattern. Patients with severe symptoms may suffer respiratory failure, leading to death. The homozygous deletion of exon 7 in the SMN1 gene accounts for nearly 95% of all cases. Population carrier screening for SMA and prenatal diagnosis by amniocentesis for high-risk couples can assist in identifying the risk of fetal disease. We provided the SMA carrier screening process to 55,447 pregnant women in Yancheng from October 2020 to December 2022. Among them, 8185 participated in this process, with a participation rate of around 14.76% (95% CI 14.47-15.06%). Quantitative real-time polymerase chain reaction (qPCR) was used to detect deletions of SMN1 exons 7 and 8 (E7, E8) in screened pregnant women. 127 were identified as carriers (111 cases of E7 and E8 heterozygous deletions, 15 cases of E7 heterozygous deletions, and 1 case of E7 heterozygous deletions and E8 homozygous deletions), resulting in a carrying rate of around 1.55% (95% CI 1.30-1.84%). After genetic counseling, 114 spouses of pregnant women who tested positive underwent SMA carrier screening; three of them were screened as SMA carriers. Multiplexed ligation-dependent probe amplification (MLPA) was used for the prenatal diagnosis of the fetuses of high-risk couples. Two of them exhibited two copies of SMN1 exon 7 (normal), and the pregnancy was continued; one exhibited no copies of SMN1 exon 7 and exon 8 (SMA patient), and the pregnancy was terminated. Analyzing SMN1 mutations in Yancheng and provide clinical evidence for SMA genetic counseling and birth defect prevention. Interventional prenatal diagnosis for high-risk families can promote informed reproductive selection and prepare for the fetus's early treatment.
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The purpose of this study was to investigate the effects of early castration and eucalyptus oil (EUC) supplementation on dry matter intake (DMI), growth performance, and immune response of Holstein calves. Fifty-six male Holstein calves 52 d old and with an initial body weight (BW) of 63.5 ± 5.27 kg were used. The animals were blocked by BW and randomly assigned into 1 of the 4 treatment groups in a randomized complete block design with a 2 (no castration vs. castration) × 2 (without vs. with EUC) factorial arrangement of treatments. The treatments were (1) uncastrated calves fed without EUC, (2) uncastrated calves fed 0.5 g/d EUC (EUC group), (3) castrated calves (steers) fed without EUC (castrated group), and (4) steers fed with 0.5 g/d EUC (castrated + EUC). The experiment was 8 wk long, including pre- and postweaning (weaned at 72 d). The EUC × castrated interactions were not significant for DMI, growth performance, nutrient digestibility, and immune response. Castration did not affect the DMI, final BW, average daily gain (ADG), or feed efficiency, except that the ADG was greater for bull calves than for steers at postweaning. Supplementation with EUC increased DMI pre- and postweaning and increased the ADG of weaned calves. Digestibility in the total digestive tract was not affected by castration (except for organic matter digestibility), whereas adding EUC improved the digestibility of dry matter, acid detergent fiber, and crude protein. Blood concentration of IL-6 at d 94 was decreased by feeding EUC. These results indicate that the EUC could be fed to either intact or castrated dairy calves to promote growth and health postweaning; castration before weaning may reduce ADG and cause inflammatory stress without affecting feed intake or feed efficiency.
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OBJECTIVE: The purpose of this study was to investigate the efficacy and safety of lenvatinib in various types of solid tumors. METHOD: By searching PubMed, Web of Science, Cochrane, CNKI, Wanfang and other databases, all the literatures about the comparison of clinical efficacy of lenvatinib in the treatment of various solid tumors. According to the criteria of inclusion and exclusion of literature, two participants screened the literature, collated the data and evaluated the literature. RevMan 5.4 software was used for meta-analysis of the included literatures. RESULTS: A total of 12 studies were included, including 5213 patients. Meta-analysis showed that, in terms of efficacy, the risk (HR) of prolonging PFS in the treatment of various solid tumors in the lenvatinib group was 1.91 times that in the control group (HR = 1.91, 95% CI: 1.58-2.31, p < 0.00001), and the risk (HR) of prolonging OS was 1.27 times that in the single targeted drug group (HR = 1.27, 95% CI: 1.15-1.40, p < 0.00001). In terms of safety, the risk of adverse events in the treatment of various solid tumors in the lenvatinib group was higher than that in the control group, especially in Endocrine Toxicities, Renal/Urinary Toxicities, Vascular Toxicities, Musculoskeletal/a Connective Tissue Toxicities and Metabolism/Nutrition Toxicities. CONCLUSIONS: Lenvatinib in various solid tumors can prolong OS and disease PFS of patients, improve the clinical benefit rate and improve the quality of life of patients. At the same time, there is a certain incidence of adverse events, and symptomatic intervention should be given in clinical medication.
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Antineoplásicos , Neoplasias , Compostos de Fenilureia , Quinolinas , Humanos , Antineoplásicos/efeitos adversos , Antineoplásicos/uso terapêutico , Neoplasias/tratamento farmacológico , Compostos de Fenilureia/efeitos adversos , Compostos de Fenilureia/uso terapêutico , Compostos de Fenilureia/administração & dosagem , Inibidores de Proteínas Quinases/efeitos adversos , Inibidores de Proteínas Quinases/uso terapêutico , Quinolinas/efeitos adversos , Quinolinas/uso terapêutico , Quinolinas/administração & dosagem , Resultado do TratamentoRESUMO
OBJECTIVES: Subepithelial lesions (SELs) are associated with various endoscopic resection (ER) outcomes and diagnostic challenges. We aimed to establish a tool for predicting ER-related outcomes and diagnosing SELs and to investigate the predictive value of endoscopic ultrasound (EUS). METHODS: Phase 1 (system development) was performed in a retrospective cohort (n = 837) who underwent EUS before ER for SELs at eight hospitals. Prediction models for five key outcomes were developed using logistic regression. Models with satisfactory internal validation performance were included in a mobile application system, SEL endoscopic resection predictor (SELERP). In Phase 2, the models were externally validated in a prospective cohort of 200 patients. RESULTS: An SELERP was developed using EUS characteristics, which included 10 models for five key outcomes: post-ER ulcer management, short procedure time, long hospital stay, high medication costs, and diagnosis of SELs. In Phase 1, 10 models were derived and validated (C-statistics, 0.67-0.99; calibration-in-the-large, -0.14-0.10; calibration slopes, 0.92-1.08). In Phase 2, the derived risk prediction models showed convincing discrimination (C-statistics, 0.64-0.73) and calibration (calibration-in-the-large, -0.02-0.05; calibration slopes, 1.01-1.09) in the prospective cohort. The sensitivities and specificities of the five diagnostic models were 68.3-95.7% and 64.1-83.3%, respectively. CONCLUSION: We developed and prospectively validated an application system for the prediction of ER outcomes and diagnosis of SELs, which could aid clinical decision-making and facilitate patient-physician consultation. EUS features significantly contributed to the prediction. TRIAL REGISTRATION: Chinese Clinical Trial Registry, http://www.chictr.org.cn (ChiCTR2000040118).
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Aspiração por Agulha Fina Guiada por Ultrassom Endoscópico , Endossonografia , Humanos , Estudos Prospectivos , Estudos Retrospectivos , Endossonografia/métodos , Sensibilidade e EspecificidadeRESUMO
An integrated way to generate and manipulate higher-order Poincaré sphere beams (HOPBs) is a sought-after goal in photonic integrated circuits for high-capacity communication systems. Here, we demonstrate a novel method for on-chip generation and manipulation of HOPBs through combining metasurface with optical waveguides on lithium niobate on insulator platform. With phase modulation by a diatomic geometric metasurface, guided waves are extracted into free space with a high signal-to-noise ratio in the form of two orthogonal circularly polarized optical vortices which are linearly superposed into HOPBs. Meanwhile, a dual-port waveguide crossing is established to reconfigure the output states into an arbitrary point on a higher-order Poincaré sphere based on in-plane interference of two guided waves. Our approach provides a promising solution to generate and manipulate the HOPBs in a compact manner, which would be further enhanced by employing the electro-optical modulation on a lithium niobate waveguide to access a fully tunable scheme.
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BACKGROUND: Inflammatory bowel disease (IBD) is characterized by chronic progressive intestinal inflammation. Sacral nerve stimulation (SNS) ameliorates colon inflammation caused by IBD. The aim of this study was to investigate the antiinflammatory benefits of SNS in colitis rats and explore the roles of the cholinergic antiinflammatory pathway, macrophage autophagy, and nucleotide oligomerization domain-like receptor thermal protein domain associated protein 3 (NLRP3) inflammatory bodies. MATERIALS AND METHODS: Rats were divided into four groups: healthy control, dextran sulfate sodium (DSS), DSS + sham-SNS, and DSS + SNS groups. An electrode was surgically placed in the right sacral nerve (S3) for stimulation. The disease activity index (DAI) score was recorded each day, and the degree of inflammatory injury was evaluated using hematoxylin and eosin staining. The alpha7 nicotinic acetylcholine receptor (α7nAChR) and autophagy- and NLRP3-related factors were assessed using immunofluorescence staining and Western blotting. RESULTS: The DSS group showed a higher DAI score, colon shortening, upregulated proinflammatory action, and colon damage, and the DSS + SNS group showed significantly improved symptoms. The number of α7nAChR+ cells and the expression level of autophagy decreased in the DSS group but increased in the DSS + SNS group. Conversely, the DSS group showed increased activation of NLRP3 inflammatory bodies, whereas the DSS + SNS group showed decreased activation of NLRP3 inflammatory bodies. CONCLUSION: In this study, SNS ameliorated colon inflammation by enhancing macrophage autophagy and inhibiting the activation of NLRP3 inflammatory bodies, which may be related to the opening of the cholinergic antiinflammatory pathway.
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Colite , Doenças Inflamatórias Intestinais , Ratos , Animais , Camundongos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor Nicotínico de Acetilcolina alfa7/metabolismo , Colite/induzido quimicamente , Colite/terapia , Colite/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Inflamação/terapia , Inflamação/metabolismo , Macrófagos/metabolismo , Autofagia , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , ColoRESUMO
INTRODUCTION: Functional gastrointestinal disorders (FGIDs) are common, and they severely impair an individual's quality of life. The mechanism of pathogenesis and the effective treatments for FGIDs remain elusive. Neuromodulation-a relatively new treatment-has exhibited a good therapeutic effect on FGIDs, although there are different methods for different symptoms of FGIDs. MATERIALS AND METHODS: We used PubMed to review the history of neuromodulation for the treatment of FGIDs and to review several recently proposed neuromodulation approaches with improved effects on FGIDs. CONCLUSION: Electroacupuncture, transcutaneous electroacupuncture, transcutaneous auricular vagal nerve stimulation, sacral nerve stimulation (SNS) (which relies on vagal nerve stimulation), and gastric electrical stimulation (which works through the modulation of slow waves generated by the interstitial cells of Cajal), in addition to the noninvasive neurostimulation alternative approach method of SNS-tibial nerve stimulation and transcutaneous electrical stimulation (which is still in its infancy), are some of the proposed neuromodulation approaches with improved effects on FGIDs. This review has discussed some critical issues related to the selection of stimulation parameters and the underlying mechanism and attempts to outline future research directions backed by the existing literature.
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Gastroenteropatias , Estimulação Elétrica Nervosa Transcutânea , Estimulação do Nervo Vago , Humanos , Qualidade de Vida , Estimulação Elétrica Nervosa Transcutânea/métodos , Gastroenteropatias/terapia , Estimulação do Nervo Vago/métodos , Nervos EspinhaisRESUMO
BACKGROUND: Large and long ears are regarded as symbols of wealth and health in East Asian culture, and people with lying ears often want their ears to be more exposed and prominent. Surgeries to correct lying ears have been documented. OBJECTIVES: The aim of this study was to report the correction of lying ears and the aesthetic modification of helix and ear lobule with hyaluronic acid (HA) injections. METHODS: HA injections were performed at the auriculocephalic sulcus to increase the cranioauricular angle (CA) and correct lying ears. The injections at helix and lobule were case specific. The CA was measured and photographs were taken at baseline and at 1-, 3-, 6-, and 10-month follow-ups. Efficacy was assessed with the 5-point Global Aesthetic Improvement Scale (GAIS). Adverse events were recorded. RESULTS: Forty-six patients (92 ears) received HA injections and completed follow-ups. Instant correction outcomes were observed. Sixteen (34.8%) patients received 1 touch-up injection, the clinical efficacy of which persisted for 1 to 1.5 years. For over 90% of cases with touch-up treatment the GAIS was "very much improved" or "much improved" at all follow-ups. The GAIS for over 70% of cases without touch-up treatment was "very much improved" or "much improved" at 1-, 3-, and 6-month follow-ups. CA increased significantly compared with the baseline. Patients also reported "more V-shaped face shape" and "lifted jawline" effects. No serious adverse events occurred. CONCLUSIONS: As an alternative technique to surgeries, HA filler injections at the auriculocephalic sulcus effectively corrected lying ears. This technique produced immediate, long-lasting, and aesthetically pleasing results. The side effects and downtime were minimal.
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Povo Asiático , Técnicas Cosméticas , Preenchedores Dérmicos , Estética , Ácido Hialurônico , Humanos , Ácido Hialurônico/administração & dosagem , Ácido Hialurônico/efeitos adversos , Feminino , Adulto , Técnicas Cosméticas/efeitos adversos , Preenchedores Dérmicos/administração & dosagem , Preenchedores Dérmicos/efeitos adversos , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento , Adulto Jovem , China , Orelha Externa , Injeções , Satisfação do Paciente , Pavilhão Auricular/cirurgia , Seguimentos , População do Leste AsiáticoRESUMO
There are few short, validated tools to assess young children's obesity-related dietary behaviours, limiting the rapid screening of dietary behaviours in research and practice-based early obesity prevention. This study aimed to develop and assess the reliability and validity of a caregiver-reported short dietary questionnaire to rapidly assess obesity-related dietary behaviours in children aged 6 months to 5 years. The Early Prevention of Obesity in Childhood Dietary Questionnaire (EPOCH-DQ) was developed using a rigorous process to determine content and structural validity. Three age-appropriate versions were developed for (1) infants, aged 6-12 months, (2) toddlers, aged 1-2.9 years and (3) pre-schoolers, aged 3-5 years. The questionnaire (7-15 items) measures dietary behaviours, including diet risk from non-core food and beverage intake, diet quality from vegetable frequency, bread type and infant feeding practices. Test-retest reliability was assessed from repeated administrations 1 week apart (n = 126). Internal consistency, concurrent validity (against a comparison questionnaire, the InFANT Food Frequency Questionnaire), construct validity and interpretability were assessed (n = 209). Most scores were highly correlated and significantly associated (p < 0.05) for validity (rs: 0.45-0.89, percentage agreement 68%-100%) and reliability (intraclass correlation coefficient: 0.61-0.99) for diet risk, diet quality and feeding practice items. The EPOCH-DQ shows acceptable validity and reliability for screening of obesity-related behaviours of children under 5 years of age. The short length and, thus, low participant burden of the EPOCH-DQ allows for potential applications in various settings. Future testing of the EPOCH-DQ should evaluate culturally and socio-economically diverse populations and establish the predictive validity and sensitivity to detect change.
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Obesidade Infantil , Lactente , Humanos , Pré-Escolar , Reprodutibilidade dos Testes , Dieta , Inquéritos e Questionários , Verduras , Comportamento AlimentarRESUMO
Epithelial-mesenchymal transition (EMT) contributes to airway remodeling, a predominant feature of asthma. DOCK2 (dedicator of cytokinesis 2) is an innate immune signaling molecule involved in vascular remodeling. However, it is unknown if DOCK2 plays a role in airway remodeling during asthma development. In this study, we found that DOCK2 is highly induced in both normal human bronchial epithelial cells treated with house dust mite (HDM) extract and human asthmatic airway epithelium. DOCK2 is also upregulated by TGF-ß1 (transforming growth factor ß1) during EMT of human bronchial epithelial cells. Importantly, knockdown of DOCK2 inhibits, and overexpression of DOCK2 promotes, TGF-ß1-induced EMT. Consistently, DOCK2 deficiency suppresses the EMT of airway epithelium, attenuates the subepithelial fibrosis, and improves pulmonary function in HDM-induced asthmatic lungs. These data suggest that DOCK2 plays an important role in EMT and asthma development. Mechanistically, DOCK2 interacts with transcription factor FoxM1 (forkhead box M1), which enhances FoxM1 binding to mesenchymal marker gene promoters and further promotes mesenchymal marker gene transcription and expression, leading to EMT. Taken together, our study identifies DOCK2 as a novel regulator for airway EMT in an HDM-induced asthma model, thus providing a potential therapeutic target for treatment of asthma.
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Asma , Fator de Crescimento Transformador beta1 , Humanos , Fator de Crescimento Transformador beta1/metabolismo , Brônquios/metabolismo , Transição Epitelial-Mesenquimal , Remodelação das Vias Aéreas , Asma/metabolismo , Células Epiteliais/metabolismo , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismoRESUMO
The value of peripheral blood lymphocyte subpopulations in predicting responses to lenvatinib combination with programmed death-1 (PD-1) inhibitors in unresectable hepatocellular carcinoma (HCC) was investigated. Fifteen patients received objective responses (OR) and sixteen patients had non-objective responses (NOR) were analyzed. The counts of peripheral blood lymphocyte subpopulations from patients were measured before treatment, second (at week 3), and third doses (at week 6) of the PD-1 inhibitor administration, and correlated with responses. Helper T (Th) cells and natural killers (NK) cells were more abundant in the OR group and found to be important predictors of OR in a stepwise multivariate logistic regression analysis. These cutoff values of Th and NK cells could help to distinguish OR from NOR cases accurately and provide clinical benefits.
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Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/tratamento farmacológico , Inibidores de Checkpoint Imunológico/uso terapêutico , Neoplasias Hepáticas/tratamento farmacológico , Células Matadoras NaturaisRESUMO
Structural and compositional design of multifunctional materials is critical for electrocatalysis, but their rational modulation and effective synthesis remain a challenge. Herein, a controllable one-pot synthesis for construction of trifunctional sites and preparation of porous structures is adopted for synthesizing dispersed MoCoP sites on N, P codoped carbonized substance. This tunable synthetic strategy also endorses the exploration of the electrochemical activities of Mo (Co)-based unitary, Mo/Co-based dual and MoCo-based binary metallic sites. Eventually benefiting from the structural regulation, MoCoP-NPC shows excellent oxygen reduction abilities with a half-wave potential of 0.880 V, and outstanding oxygen evolution and hydrogen evolution performance with an overpotential of 316 mV and 91 mV, respectively. MoCoP-NPC-based Zn-air battery achieves excellent cycle stability for 300 h and a high open-circuit voltage of 1.50 V. When assembled in a water-splitting device, MoCoP-NPC reaches 10 mA cm-2 at 1.65 V. Theoretical calculations demonstrate that the Co atom in the single-phase MoCoP has a low energy barrier for oxygen evolution reaction (OER) owing to the migration of Co 3d orbital toward the Fermi level. This work shows a simplified method for controllable preparation of prominent trifunctional catalysts.
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Controlling thermal emission is essential for various infrared spectroscopy applications. Metasurfaces can be utilized to control multiple degrees of freedom of thermal emission, enabling the compact thermal emission materials and devices. Infrared spectroscopy such as FTIR (Fourier transform infrared spectroscopy), usually requires external infrared radiation source and complex spectroscopic devices for absorption spectrum measurement, which hinders the implementation of integrated compact and portable measurement equipment. Measuring absorption spectrum through the thermal emission of pixelated thermal emitter array can facilitate the integration and miniaturization of measurement setup, which is highly demanded for on-chip spectroscopy applications. Here, we experimentally demonstrate an integrated technology that allows for indirect measurement of the absorption spectrum through the thermal emission of meta-cavity array. This indirect measurement method opens a new avenue for compact infrared spectroscopy analysis.
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HELQ plays a key role in DNA damage response and cell-cycle checkpoint regulation. It has been implicated in ovarian and pituitary tumors and may play a role in germ cell maintenance. This study investigated the role of HELQ in lung cancer. The expression of HELQ in patients with non-small-cell lung cancer (NSCLC) was downregulated compared with normal human lungs. Clinical prognostic analysis of Kaplan-Meier plots revealed that patients with NSCLC with low HELQ levels had a reduced overall survival. Further, we found that HELQ depletion enhanced lung cancer cell malignancy. Furthermore, overexpression of HELQ in lung cancer cells reduced cell migration in vitro, while DNA damage repair was inhibited. Both in vitro and in vivo studies have shown that HELQ induces cell death. Mechanistically, we found that cells overexpressing HELQ showed a tendency to induce necrosis. After analyzing the database of HELQ interactors. we found that RIPK3 may interact with it and proved this conclusion by immunoprecipitation. Our findings identified the tumor suppressive role of HELQ in malignant human lung cancer and unraveled a potential therapeutic strategy for cancer treatment through HELQ activation. Moreover, HELQ may also be a predictive biomarker for the clinical predisposition, progression, and prognosis of lung cancer.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Feminino , Humanos , DNA Helicases/metabolismo , Dano ao DNA , Proliferação de Células/genética , Necrose , Linhagem Celular TumoralRESUMO
Improvements are required in the quality of life (QoL) of patients with ischemia and non-obstructive coronary artery disease (INOCA). Several patients with INOCA experience vascular endothelial dysfunction. However, the relationship between endothelial function and QoL remains unelucidated. This study aimed to initially investigate the relationship between endothelial function and QoL in patients with INOCA. This prospective observational study included 121 patients with INOCA (aged 31-85 years). Vascular endothelial function was assessed by flow-mediated dilatation (FMD) of the peripheral brachial artery. QoL was evaluated using the 36-Item Short-Form Health Survey (SF-36). Patients with INOCA were divided into two groups according to the median FMD change during the 1-year follow-up (group A, ≥ median FMD change cut-off; group B, < median FMD change cut-off). The median change in FMD was 0.92%. The mean baseline SF-36 scores were comparable between the two groups (53.95 ± 6.46 vs. 53.92 ± 4.29, p = 0.98). The QoL at follow-up was better in group A than in group B (56.61 ± 5.50 vs. 53.32 ± 5.58, p = 0.002). The change in FMD (r = 0.34, p < 0.01), rather than FMD at baseline (r = - 0.01, p = 0.89) or follow-up (r = 0.13, p = 0.15), was related to the follow-up SF-36 scores. FMD improvement was an independent predictor of increased QoL (odds ratio, 3.90; 95% confidence interval: 1.59-9.53, p = 0.003). Endothelial function change is associated with QoL, and patients with improved endothelial function have a better QoL than those without.