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Metabolic dysfunction of the extracellular matrix (ECM) is one of the primary causes of intervertebral disc degeneration (IVDD). Previous studies have demonstrated that the transcription factor Brachyury (Bry) has the potential to promote the synthesis of collagen II and aggrecan, while the specific mechanism is still unknown. In this study, we used a lipopolysaccharide (LPS)-induced model of nucleus pulposus cell (NPC) degeneration and a rat acupuncture IVDD model to elucidate the precise mechanism through which Bry affects collagen II and aggrecan synthesis in vitro and in vivo. First, we confirmed Bry expression decreased in degenerated human nucleus pulposus (NP) cells (NPCs). Knockdown of Bry exacerbated the decrease in collagen II and aggrecan expression in the lipopolysaccharide (LPS)-induced NPCs degeneration in vitro model. Bioinformatic analysis indicated that Smad3 may participate in the regulatory pathway of ECM synthesis regulated by Bry. Chromatin immunoprecipitation followed by quantitative polymerase chain reaction (ChIP-qPCR) and luciferase reporter gene assays demonstrated that Bry enhances the transcription of Smad3 by interacting with a specific motif on the promoter region. In addition, Western blot and reverse transcription-qPCR assays demonstrated that Smad3 positively regulates the expression of aggrecan and collagen II in NPCs. The following rescue experiments revealed that Bry-mediated regulation of ECM synthesis is partially dependent on Smad3 phosphorylation. Finally, the findings from the in vivo rat acupuncture-induced IVDD model were consistent with those obtained from in vitro assays. In conclusion, this study reveals that Bry positively regulates the synthesis of collagen II and aggrecan in NP through transcriptional activation of Smad3.NEW & NOTEWORTHY Mechanically, in the nucleus, Bry enhances the transcription of Smad3, leading to increased expression of Smad3 protein levels; in the cytoplasm, elevated substrate levels further lead to an increase in the phosphorylation of Smad3, thereby regulating collagen II and aggrecan expression. Further in vivo experiments provide additional evidence that Bry can alleviate IVDD through this mechanism.
Assuntos
Agrecanas , Matriz Extracelular , Proteínas Fetais , Regulação da Expressão Gênica , Núcleo Pulposo , Proteína Smad3 , Adulto , Animais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ratos , Agrecanas/metabolismo , Agrecanas/genética , Células Cultivadas , Colágeno Tipo II/metabolismo , Colágeno Tipo II/genética , Matriz Extracelular/metabolismo , Proteínas Fetais/genética , Proteínas Fetais/metabolismo , Degeneração do Disco Intervertebral/genética , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/patologia , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Ratos Sprague-Dawley , Proteína Smad3/metabolismo , Proteína Smad3/genética , Proteínas com Domínio T/genética , Proteínas com Domínio T/metabolismoRESUMO
Intervertebral disk degeneration (IDD) is a significant cause of low back pain, characterized by excessive senescence and apoptosis of nucleus pulposus cells (NPCs). However, the precise mechanisms behind this senescence and apoptosis remain unclear. This study aimed to investigate the role of T-box transcription factor T (Tbxt) in IDD both in vitro and in vivo, using a hydrogen peroxide (H2O2)-induced NPCs senescence and apoptosis model, as well as a rat acupuncture IDD model. First, the expression of p16 and cleaved-caspase 3 significantly increased in degenerated human NPCs, accompanied by a decrease in Tbxt expression. Knockdown of Tbxt exacerbated senescence and apoptosis in the H2O2-induced NPCs degeneration model. Conversely, upregulation of Tbxt alleviated these effects induced by H2O2. Mechanistically, bioinformatic analysis revealed that the direct downstream target genes of Tbxt were highly enriched in autophagy-related pathways, and overexpression of Tbxt significantly activated autophagy in NPCs. Moreover, the administration of the autophagy inhibitor, 3-methyladenine, impeded the impact of Tbxt on the processes of senescence and apoptosis in NPCs. Further investigation revealed that Tbxt enhances autophagy by facilitating the transcription of ATG7 through its interaction with a specific motif within the promoter region. In conclusion, this study suggests that Tbxt mitigates H2O2-induced senescence and apoptosis of NPCs by activating ATG7-mediated autophagy.NEW & NOTEWORTHY This study investigates the role of Tbxt in IDD. The results demonstrate that knockdown of Tbxt exacerbates H2O2-induced senescence and apoptosis in NPCs and IDD, whereas upregulation of Tbxt significantly protects against IDD both in vivo and in vitro. Mechanistically, in the nucleus, Tbxt enhances the transcription of ATG7, leading to increased expression of ATG7 protein levels. This, in turn, promotes elevated autophagy levels, ultimately alleviating IDD.
Assuntos
Apoptose , Proteína 7 Relacionada à Autofagia , Autofagia , Senescência Celular , Degeneração do Disco Intervertebral , Núcleo Pulposo , Ratos Sprague-Dawley , Núcleo Pulposo/metabolismo , Núcleo Pulposo/patologia , Autofagia/efeitos dos fármacos , Degeneração do Disco Intervertebral/patologia , Degeneração do Disco Intervertebral/metabolismo , Degeneração do Disco Intervertebral/genética , Proteína 7 Relacionada à Autofagia/metabolismo , Proteína 7 Relacionada à Autofagia/genética , Animais , Senescência Celular/efeitos dos fármacos , Humanos , Ratos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Peróxido de Hidrogênio/toxicidade , Peróxido de Hidrogênio/farmacologia , Peróxido de Hidrogênio/metabolismo , Células CultivadasRESUMO
Electrowetting displays (EWDs) based on microfluidics are highly sought after in the fields of electronic devices, smart homes, and information communication. However, the power supply of the EWD systems for visually engaging multi-color displays remains a big challenge. Herein, self-powered colorful dynamic display systems are developed by integrating the triboelectric nanogenerator (TENG) with the EWD device. The TENG is designed with a nanotube-patterned surface and can generate open-circuit voltages ranging from 30 to 295 V by controlling the contact area. The wetting property of the micro-droplet exhibits a response to the applied voltage, enabling the triboelectricity-triggered electrowetting-on-dielectric. Driven by the voltage of 160 V, the monochromatic EWD exhibits bright color switching from magenta to transparent with a pixel aperture ratio of 78%, and the recovery process can be rapidly completed. Furthermore, the self-powered colorful dynamic EWD system can be achieved. By selectively applying the voltage to the pixels in the three monochromatic layers that constitute the colorful EWD, the wetting properties of the fluids can be controlled, allowing for colorful dynamic display. This work contributes to the advancement of color display technology for portable and wearable electronic ink displays, indoor and outdoor sports equipment, and information communication.
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A cross-sectional study in 2021-23 collected oral rinse gargle samples from an human papillomaviruses (HPV) vaccine-naïve general adult population in Hong Kong. HPV was detected by a PCR using SPF10 primers, and genotyped by a linear array covering 25 genotypes. Epidemiologic information including sociodemographics, medical history, oral health, and sexual behavior were collected by a self-administered questionnaire. Altogether, 2323 subjects aged 18-75 (median 47) years with 50.1% male were recruited. The prevalence for oral HPV infection with all genotypes combined, high-risk, and low-risk genotypes was 1.5%, 0.7%, and 0.7%, respectively; and with no statistically significant difference between participant gender. The prevalence increased with age and was highest in women at 45-54 years (2.7% for all genotypes combined), and highest in men aged >64 years (4.1% for all genotypes combined). HPV52 was the most common genotype among all participants. Univariate analysis suggested more lifetime sexual or oral sexual partners as risk factors, but they did not reach statistical significance upon multivariate analysis; whereas higher educational level had an independent protective effect. To conclude, oral HPV prevalence increased with age in Hong Kong. Strategies to prevent oral HPV infection and the associated cancers are urgently needed.
Assuntos
Infecções por Papillomavirus , Adulto , Humanos , Masculino , Feminino , Hong Kong/epidemiologia , Infecções por Papillomavirus/epidemiologia , Prevalência , Estudos Transversais , Comportamento Sexual , Fatores de Risco , Papillomaviridae/genética , GenótipoRESUMO
Relevant studies have indicated the association of HCG18 with tumour occurrence and progression. In this study, we observed that PM2.5 can enhance the growth of lung adenocarcinoma cells by modulating the expression of HCG18. Further investigations, including overexpression and knockout experiments, elucidated that HCG18 suppresses miR-195, which in turn upregulates the expression of ATG14, resulting in the upregulation of autophagy. Consequently, exposure to PM2.5 leads to elevated HCG18 expression in lung tissues, which in turn increases Atg14 expression and activates autophagy pathways through inhibition of miR-195, thereby contributing to oncogenesis.
Assuntos
Adenocarcinoma de Pulmão , Proteínas Relacionadas à Autofagia , Autofagia , Progressão da Doença , Neoplasias Pulmonares , MicroRNAs , Material Particulado , Humanos , Células A549 , Proteínas Adaptadoras de Transporte Vesicular/efeitos dos fármacos , Proteínas Adaptadoras de Transporte Vesicular/metabolismo , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Autofagia/genética , Proteínas Relacionadas à Autofagia/efeitos dos fármacos , Proteínas Relacionadas à Autofagia/genética , Proteínas Relacionadas à Autofagia/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Material Particulado/efeitos adversos , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/metabolismo , Antígenos HLA/efeitos dos fármacos , Antígenos HLA/metabolismoRESUMO
PURPOSE OF REVIEW: This review assesses the effectiveness and safety of light therapy, particularly green light therapy, as an emerging non-pharmacological treatment for chronic migraine (CM). It aims to highlight alternative or complementary approaches to traditional pharmacological remedies, focusing the need for diverse treatment options. RECENT FINDINGS: Despite sensitivity to light being a defining feature of migraine, light therapy has shown promising signs in providing substantial symptom relief. Studies have provided insights into green light therapy's role in managing CM. These studies consistently demonstrate its efficacy in reducing the frequency, severity, and symptoms of migraines. Additional benefits observed include improvements in sleep quality and reductions in anxiety. Importantly, green light therapy has been associated with minimal side effects, indicating its potential as a suitable option for migraine sufferers. In addition to green light, other forms of light therapy, such as infrared polarized light, low-level laser therapy (LLLT), and intravascular irradiation of blood (ILIB), are also being explored with potential therapeutic effects. Light therapies, especially green light therapy, are recognized as promising, safe, and non-pharmacological interventions for treating CM. They have been shown to be effective in decreasing headache frequency and enhancing the overall quality of life. However, current studies, often limited by small sample sizes, prompt more extensive clinical trials to better understand the full impact of light therapies. The exploration of other light-based treatments, such as LLLT and ILIB, warrants further research to broaden the scope of effective migraine management strategies.
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Transtornos de Enxaqueca , Fototerapia , Humanos , Transtornos de Enxaqueca/terapia , Fototerapia/métodos , Doença Crônica , Resultado do TratamentoRESUMO
Accurate estimation of photovoltaic (PV) system performance is crucial for determining its feasibility as a power generation technology and financial asset. PV-based energy solutions offer a viable alternative to traditional energy resources due to their superior Levelized Cost of Energy (LCOE). A significant challenge in assessing the LCOE of PV systems lies in understanding the Performance Loss Rate (PLR) for large fleets of PV systems. Estimating the PLR of PV systems becomes increasingly important in the rapidly growing PV industry. Precise PLR estimation benefits PV users by providing real-time monitoring of PV module performance, while explainable PLR estimation assists PV manufacturers in studying and enhancing the performance of their products. However, traditional PLR estimation methods based on statistical models have notable drawbacks. Firstly, they require user knowledge and decision-making. Secondly, they fail to leverage spatial coherence for fleet-level analysis. Additionally, these methods inherently assume the linearity of degradation, which is not representative of real world degradation. To overcome these challenges, we propose a novel graph deep learning-based decomposition method called the Spatio-Temporal Graph Neural Network for fleet-level PLR estimation (PV-stGNN-PLR). PV-stGNN-PLR decomposes the power timeseries data into aging and fluctuation components, utilizing the aging component to estimate PLR. PV-stGNN-PLR exploits spatial and temporal coherence to derive PLR estimation for all systems in a fleet and imposes flatness and smoothness regularization in loss function to ensure the successful disentanglement between aging and fluctuation. We have evaluated PV-stGNN-PLR on three simulated PV datasets consisting of 100 inverters from 5 sites. Experimental results show that PV-stGNN-PLR obtains a reduction of 33.9% and 35.1% on average in Mean Absolute Percent Error (MAPE) and Euclidean Distance (ED) in PLR degradation pattern estimation compared to the state-of-the-art PLR estimation methods.
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Modelos Estatísticos , Redes Neurais de ComputaçãoRESUMO
BACKGROUND: Boars fed a mixed form of inorganic and organic iron in excess of the NRC recommended levels still develop anemia, which suggested that the current level and form of iron supplementation in boar diets may be inappropriate. Therefore, 56 healthy Topeka E line boars aged 15-21 months were randomly divided into 5 groups: basal diet supplemented with 96 mg/kg ferrous sulfate (FeSO4) and 54 mg/kg glycine chelated iron (Gly-Fe, control); 80 mg/kg or 115 mg/kg Gly-Fe; 80 mg/kg or 115 mg/kg methionine hydroxyl analogue chelated iron (MHA-Fe, from Calimet-Fe) for 16 weeks. The effects of dietary iron supplementation with different sources and levels on semen quality in boars were investigated. RESULTS: 1) Serum Fe and hemoglobin concentrations were not affected by reduced dietary iron levels in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups compared with the control group (P > 0.05). 2) Serum interleukin-6 (IL-6) and sperm malondialdehyde (MDA) levels in the 80 mg/kg or 115 mg/kg MHA-Fe groups were lower than those in the control group (P < 0.05), and higher serum superoxide dismutase levels and lower MDA levels in the 115 mg/kg MHA-Fe group (P < 0.05). 3) Boars in the 80 mg/kg or 115 mg/kg Gly-Fe and MHA-Fe groups had lower serum hepcidin (P < 0.01), ferritin (P < 0.05), and transferrin receptor (P < 0.01) concentrations, and boars in the 115 mg/kg MHA-Fe group had higher seminal plasma Fe concentrations compared with the control group. 4) Boars in the 80 mg/kg and 115 mg/kg MHA-Fe groups had lower abnormal sperm rate and in situ oscillating sperm ratio compared to the control group at weeks 12 and/or 16 of the trial. However, the effect of Gly-Fe on improving semen quality in boars was not evident. 5) Serum IL-6 level was positively correlated with hepcidin concentration (P < 0.05), which in turn was significantly positively correlated with abnormal sperm rate (P < 0.05). Furthermore, significant correlations were also found between indicators of iron status and oxidative stress and semen quality parameters. CONCLUSIONS: Dietary supplementation with 80 mg/kg or 115 mg/kg MHA-Fe did not induce iron deficiency, but rather reduced serum inflammatory levels and hepcidin concentration, alleviated oxidative stress, increased body iron utilization, and improved semen quality in adult boars.
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There is limited literature on current human papillomavirus (HPV) vaccination in the Asia-Pacific region. This integrative literature review was conducted to describe HPV vaccination programs in Hong Kong, Indonesia, Japan, South Korea, Malaysia, the Philippines, Singapore, Taiwan, Thailand, and Vietnam. Program descriptions, recommendations, fâunding, and coverage data were extracted. Twenty-five citations were included. As of 2022, eight of the 10 areas of interest include HPV in their national immunization program (NIP) for school-aged girls; full implementation in Indonesia is expected in 2023 whereas Vietnam's NIP does not include HPV. Singapore also includes HPV vaccination for women (18-26 years). None of the HPV vaccination programs include males. In most areas (n = 7), programs include only one vaccine option. While female HPV NIPs are present in the Asia-Pacific region, opportunities remain to strengthen NIPs in broader populations (e.g., males, catch-up cohorts) to expand public health impact and provide gender equity in HPV vaccination.
Assuntos
Programas de Imunização , Infecções por Papillomavirus , Vacinas contra Papillomavirus , Vacinação , Humanos , Vacinas contra Papillomavirus/administração & dosagem , Infecções por Papillomavirus/prevenção & controle , Feminino , Masculino , Adolescente , Ásia , Vacinação/estatística & dados numéricos , Adulto Jovem , Adulto , Cobertura Vacinal/estatística & dados numéricos , Criança , Papillomavirus HumanoRESUMO
The inadequate stability of organic-inorganic hybrid perovskites remains a significant barrier to their widespread commercial application in optoelectronic devices. Aging phenomena profoundly affect the optoelectronic performance of perovskite-based devices. In addition to enhancing perovskite stability, the real-time detection of aging status, aimed at monitoring the aging progression, holds paramount importance for both fundamental research and the commercialization of organic-inorganic hybrid perovskites. In this study, the aging status of perovskite was real-time investigated by using terahertz time-domain spectroscopy. Our analysis consistently revealed a gradual decline in the intensity of the absorption peak at 0.968 THz with increasing perovskite aging. Furthermore, a systematic discussion was conducted on the variations in intensity and position of the terahertz absorption peaks as the perovskite aged. These findings facilitate the real-time assessment of perovskite aging, providing a promising method to expedite the commercialization of perovskite-based optoelectronic devices.
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Introduction: Caregivers of children with autism spectrum disorder (ASD) were reported poor quality of life (QOL). Formal social support might improve the QOL of caregivers, however, limited research to date has focused on this association in China and formal social support for this group is conspicuously lacking. The study was aim to understand the QOL in male and female caregivers with ASD children in China and to explore the relationship between QOL and formal social support for caregivers with children with ASD through a large-scale nationwide survey. Methods: An online questionnaire was used to conduct a cross-sectional study with a sample of 6,120 caregivers of children with ASD. Relationship between Quality of Life and several potential predictors is measured and analyzed. Quality of life were measured by Medical Study Short-Form Health Survey version 2 (Chinese version). Multivariate logistic regression analysis was used to analyze the factors affecting caregivers' QOL. Results: The results revealed that the QOL of caregivers of autistic children in China was poor especially male caregivers. Social support was a positive predictor. More importantly, formal social support from rehabilitation institutions can improve caregivers' physical QOL. Caregivers' satisfaction with the rehabilitation institutions affecting their physical and mental QOL. Conclusion: The formal social support provided by rehabilitation institutions plays a positive role in improving the quality of life of caregivers.
Assuntos
Transtorno do Espectro Autista , Transtorno Autístico , Criança , Humanos , Masculino , Feminino , Qualidade de Vida , Cuidadores , Estudos Transversais , Inquéritos e Questionários , Apoio Social , ChinaRESUMO
BACKGROUND: Child eating behaviors (CEBs) and parental feeding practices (PFPs) play critical roles in childhood obesity. However, the bidirectional relationships between CEBs and PFPs remain equivocal. This longitudinal study aimed to explore their bidirectional relationships. METHODS: A convenience sample of 870 parents with preschoolers was recruited in this longitudinal study (Shanghai, China). Three non-responsive feeding practices (NFPs), three responsive feeding practices (RFPs), five CEBs, and covariates were collected using validated questionnaires at baseline and the 6-month follow-up. Cross-lagged analyses using structural equation modeling (SEM) were performed to examine their bidirectional relationships. RESULTS: Eight hundred and fifty-three parents completed questionnaires, with a response rate of 98%. The mean age of their children at baseline was 4.39 years (standard deviation = 0.72 years). Eighteen out of sixty longitudinal cross-lagged paths were statistically significant. Parental encouragement of healthy eating and content-restricted feeding were found to be bidirectionally associated with child food fussiness. Four parent-driven associations and one child-driven association were identified between RFPs and CEBs. For example, monitoring was negatively associated with children's unhealthy eating habits (ß = -0.066, standard error (SE) = 0.025, p < 0.01). Eight child-driven associations and one parent-driven association were observed between NFPs and CEBs. For example, higher child satiety responsiveness predicted a higher pressure to eat (ß = 0.057, SE = 0.029, p < 0.01) and the use of food as a reward (ß = 0.083, SE = 0.031, p < 0.01). CONCLUSIONS: There were bidirectional, parent-driven, and child-driven associations. Parents should be encouraged to adopt RFPs to shape CEBs. Increasing parents' understanding of CEBs and providing them with reasonable coping strategies would help optimize PFPs.