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OBJECTIVE: Growing research highlights the negative impact of sleep problems on adolescent mental health. However, the developmental trajectory of sleep problems during adolescence and their relationship with mental health difficulties, including both internalizing and externalizing symptoms, remain unclear. Additionally, the direction of the effects between sleep problems and mental health difficulties is not well established. This study aims to identify the developmental trajectories of sleep problems and examine their association with mental health difficulties in both internalizing and externalizing domains. METHOD: The study involved 1,281 Chinese middle school students (645 males, mean age at initial assessment = 12.73, SD = 0.68). Data were collected at four time points (T1, T2, T3, T4) over approximately 6-month intervals, spanning from the first semester of seventh grade to the second semester of 8th grade. RESULTS: Latent growth modeling revealed an overall increasing trend in sleep problems. Parallel latent growth modeling indicated that trajectories of sleep problems were positively related to the developmental trends of mental health difficulties, as shown by intercept-intercept and slope-slope associations. The cross-lagged panel model demonstrated significant bidirectional associations between sleep problems and internalizing symptoms. In contrast, we observed unidirectional associations between sleep problems and externalizing symptoms. Hence, sleep problems were a significant predictor of subsequent externalizing symptoms, with no significant reverse effect observed. CONCLUSION: These findings suggest that future research should explore whether interventions targeting sleep problems can reduce the incidence of both internalizing and externalizing symptoms. Additionally, interventions aimed at internalizing symptoms may potentially improve adolescent sleep, while those targeting externalizing symptoms may not have the same effect.
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Construction and functionalization of a 3D graphene architecture are crucial to harness and extend the unique features of graphene and thus essential for its numerous conventional and novel applications. Herein, a 3D honeycomb-patterned porous graphene architecture is constructed through a facile and low-cost self-assembly process and then integrated with Cu2O nanoparticles via a simple electrodeposition procedure. The 3D porous graphene structure is prepared by the breath figure method using a graphene oxide (GO)-based complex in which GO is modified by a surfactant as the casting material. Benefiting from the intercalation of the surfactant between the GO nanosheets and the fabrication of a 3D porous structure, the aggregation inhibition of GO nanosheets and increases in accessible surface area are realized at both nano- and microscales, resulting in good electrochemical performance. Moreover, the deposition of Cu2O nanoparticles can further improve the electrochemical sensing performance of the porous reduced graphene oxide (rGO) structure. Extremely low detection limit (30.72 nM) with a linear range of 0 µM to 30 µM, excellent anti-interference, repeatability, reproducibility, stability, and high accuracy for actual sample testing are shown when the 3D porous Cu2O/rGO film is applied as an electrochemical sensor for DA detection. This work provides not only a superior electrochemical biosensor but also a simple, yet effective and general strategy for the construction and functionalization of a 3D graphene structure.
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Despite the increasing use of motor vehicles, the impact of airborne pollutants and their health risks inside public transportation, such as commuter buses, is not well understood. This study assessed air quality inside an urban commuter bus by continuously monitoring PM10, PM2.5, and CO concentrations during both driving and parking periods. Our findings revealed that the ventilation system of the bus significantly reduced the infiltration of outdoor particulate matter and water vapor. However, CO concentrations were considerably higher inside the bus than outside, primarily due to vehicular self-emission. The ineffection of the ventilation system to remove CO potentially increases long-term exposure risks for passengers. The study identified ozone as a key oxidant in the cabin. Besides vehicle emissions, C3-C10 saturated aldehydes and carbonyl compounds were detected, including acetone, propanal, and hexanal. The presence of 6-MHO, an oxidation product of squalene, suggests that passengers contribute to VOCs load through direct emissions or skin surface reactions. Additionally, human respiration was found to significantly contribute to isoprene levels, estimated at 81.7 %. This research underscores the need for further investigation into the cumulative effects of stable compounds in cabin air and provides insights for developing healthier public transportation systems.
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Contaminantes Atmosféricos , Monitoreo del Ambiente , Vehículos a Motor , Emisiones de Vehículos , Contaminantes Atmosféricos/análisis , Emisiones de Vehículos/análisis , Material Particulado/análisis , Contaminación del Aire Interior/análisis , HumanosRESUMEN
Four pillar-layered AIEgen-based MOFs exhibit higher thermal stability, tunable emission colors and improved QYs compared with that of non-pillar-layered AIEgen-based MOFs by confining the AIE ligands into layers. These results reveal that rationally manipulating AIE ligands into layers of pillar-layered MOFs is an effective strategy for the design and construction of tunable luminescent MOF systems.
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The heterotrophic nitrification aerobic denitrification bacteria (HNDS) can perform nitrification and denitrification at the same time. Two HNDS strains, Achromobacter sp. HNDS-1 and Enterobacter sp. HNDS-6 which exhibited an amazing ability to solution nitrogen (N) removal have been successfully isolated from paddy soil in our lab. When peptone or ammonium sulfate as sole N source, no significant difference in gene expression related to nitrification and denitrification of the strains was found according to the transcriptome analysis. The expression of phosphomethylpyrimidine synthase (thiC), ABC transporter substrate-binding protein, branched-chain amino acid ABC transporter substrate-binding protein, and RNA polymerase (rpoE) in HNDS-1 were significantly upregulated when used peptone as N source, while the expression of exopolysaccharide production protein (yjbE), RNA polymerase (rpoC), glutamate synthase (gltD) and ABC-type branched-chain amino acid transport systems in HNDS-6 were significantly upregulated. This indicated that these two strains are capable of using organic N and converting it into NH4+-N, then utilizing NH4+-N to synthesize amino acids and proteins for their own growth, and strain HNDS-6 can also remove NH4+-N through nitrification and denitrification.
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Desnitrificación , Perfilación de la Expresión Génica , Nitrificación , Nitrógeno , Nitrógeno/metabolismo , Microbiología del Suelo , Procesos Heterotróficos , Aerobiosis , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/genética , Achromobacter/metabolismo , Achromobacter/genética , Achromobacter/aislamiento & purificación , Transcriptoma , Regulación Bacteriana de la Expresión GénicaRESUMEN
BACKGROUND: Despite the growing body of longitudinal research linking sleep problems and externalizing symptoms, regarding the direction of the effects of both variables, the results have been inconsistent. Given the mixed findings and inconsistent results in the literature, we propose that emotion dysregulation may link sleep problems and externalizing symptoms. METHODS: The participants (N = 1281, 49.65 % female; M = 12.73 years at time 1, SD = 0.68) were middle school students who completed assessments for sleep problems, externalizing symptoms, and emotion dysregulation. The interval between each wave was six months, for two consecutive years. Autoregressive mediation models using longitudinal data and cross-sectional mediation models using baseline data were evaluated and compared through structural equation modeling. RESULTS: The results revealed that severe sleep problems (at T1, T2, or T3) were associated with higher levels of externalizing symptoms later in adolescence (at T2, T3, or T4), but not vice versa. In addition, analyses of indirect effects indicated that emotion dysregulation mediated this link, such that greater sleep problems led to more emotion dysregulation, which, in turn, led to more externalizing symptoms. CONCLUSION: The findings highlight the critical role that emotional regulation plays in the link between sleep problems and externalizing symptoms and emphasize the need for students as well as middle school administration to pay close attention to both the sleep and externalizing symptoms of early adolescents.
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Regulación Emocional , Trastornos del Sueño-Vigilia , Humanos , Femenino , Masculino , Adolescente , Estudios Longitudinales , Trastornos del Sueño-Vigilia/psicología , Trastornos del Sueño-Vigilia/epidemiología , Niño , Regulación Emocional/fisiología , Estudios Transversales , Síntomas Afectivos/fisiopatología , Síntomas Afectivos/psicología , Conducta del Adolescente/psicologíaRESUMEN
Complex ecosystems often exhibit a tipping point around which a small perturbation can lead to the loss of the basic functionality of ecosystems. It is challenging to develop a control strategy to bring ecosystems to the desired stable states. Typically, two methods are employed to restore the functionality of ecosystems: abundance control and ecological regulation. Abundance control involves directly managing species abundance through methods such as trapping, shooting, or poisoning. On the other hand, ecological regulation is a strategy for ecosystems to self-regulate through environment improvement. To enhance the effectiveness of ecosystem recovery, we propose adaptive regulation by combining the two control strategies from mathematical and network science perspectives. Criteria for controlling ecosystems to reach equilibrium with or without noise perturbation are established. The time and energy costs of restoring an ecosystem to equilibrium often determine the choice of control strategy, thus, we estimate the control costs. Furthermore, we observe that the regulation parameter in adaptive regulation affects both time and energy costs, with a trade-off existing between them. By optimizing the regulation parameter based on a performance index with fixed weights for time and energy costs, we can minimize the total cost. Moreover, we discuss the impact of the complexity of ecological networks on control costs, where the more complex the networks, the higher the costs. We provide corresponding theoretical analyses for random networks, predator-prey networks, and mixture networks.
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Objective: Both camrelizumab plus paclitaxel and carboplatin (CTC) and sintilimab plus gemcitabine and cisplatin or carboplatin (SGP) have been approved by the National Medical Products Administration of China (NMPA) for the first-line treatment of local advanced or metastatic sqNSCLC. However, the comparison of the two treatments as first-line treatments in efficacy or pharmacoeconomics has barely been studied. To deeply understand the costs and outcomes of the two treatments, this work directly compared the cost-effectiveness for the first-line treatment of local advanced or metastatic squamous NSCLC in the Chinese mainland. Methods: A network meta-analysis was first performed based on the three clinical trials, namely, CameL-Sq, ORIENT-12, and C-TONG1002, to compare the clinical benefits of the two treatments. The Weibull approximation was applied to further calculate the life expectancy of the two treatments. The partitioned survival model (PSM) was next established, and one-way sensitivity analysis and probabilistic sensitivity analysis were also performed to evaluate the stability of the underlying parameter values and assumptions within the model. Results: CTC treatment gained 0.68 QALYs and cost $14,764. SGP treatment gained 0.54 QALYs and cost $14,584. The CTC arm gained 0.14 additional QALYs and cost $179 more than the SGP arm, and the ICERs was $1,269/QALY, which was lower than one-fold GDP per capita in the Chinese mainland ($12,734 GDP per capita in 2022). In probabilistic sensitivity analysis, when the WTP ranged from $12,734-38,202 (1-3 folds, 2022 GDP per capita in China), the CTC group had higher probabilities than the SGP group for being cost effective, which ranged from 85.65% to 88.38%. Conclusion: From the perspective of the payers, camrelizumab plus chemotherapy was cost-effective compared with sintilimab plus chemotherapy for the first-line treatment of local advanced or metastatic squamous NSCLC in the Chinese mainland.
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Plants generally enhance their root growth in the form of greater biomass and/or root length to boost nutrient uptake in response to short-term low nitrogen (LN). However, the underlying mechanisms of short-term LN-mediated root growth remain largely elusive. Our genome-wide association study, haplotype analysis, and phenotyping of transgenic plants showed that the crucial nitrate signaling component NIN-LIKE PROTEIN3.2 (ZmNLP3.2), a positive regulator of root biomass, is associated with natural variations in root biomass of maize (Zea mays L.) seedlings under LN. The monocot-specific gene AUXIN/INDOLE-3-ACETIC ACID14 (ZmAux/IAA14) exhibited opposite expression patterns to ZmNLP3.2 in ZmNLP3.2 knockout and overexpression lines, suggesting that ZmNLP3.2 hampers ZmAux/IAA14 transcription. Importantly, ZmAux/IAA14 knockout seedlings showed a greater root dry weight (RDW), whereas ZmAux/IAA14 overexpression reduced RDW under LN compared with wild-type plants, indicating that ZmAux/IAA14 negatively regulates the RDW of LN-grown seedlings. Moreover, in vitro and vivo assays indicated that AUXIN RESPONSE FACTOR19 (ZmARF19) binds to and transcriptionally activates ZmAux/IAA14, which was weakened by the ZmNLP3.2-ZmARF19 interaction. The zmnlp3.2 ZmAux/IAA14-OE seedlings exhibited further reduced RDW compared to ZmAux/IAA14 overexpression lines when subjected to LN treatment, corroborating the ZmNLP3.2-ZmAux/IAA14 interaction. Thus, our study reveals a ZmNLP3.2-ZmARF19-ZmAux/IAA14 module regulating root biomass in response to nitrogen limitation in maize.
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BACKGROUND: Adults with cognitive impairment are prone to living alone in large numbers but receive relatively little attention. This study aimed to evaluate whether living alone with cognitive impairment was associated with a higher burden of functional disability but lack of informal care. METHODS: 982 observations of adults living alone with cognitive impairment and 50,695 observations of adults living with others and with normal cognition were identified from 4 waves (2011/2012, 2013, 2015, and 2018) of the China Health and Retirement Longitudinal Study (CHARLS). A matched comparator was selected using propensity score matching (1:2). Functional disability included disability in Activities of Daily Living (ADL), Instrumental Activities of Daily Living (IADL), and mobility. The time of receiving informal care was measured in monthly hours. RESULTS: Adults living alone with cognitive impairment demonstrated significantly higher odds ratio of ADL disability (OR = 1.59, 95 % CI: 1.30, 1.95), IADL disability (OR = 1.19, 95 % CI: 1.00, 1.44), mobility disability (OR = 1.38, 95 % CI: 1.12, 1.70), but received fewer hours of informal care (ß = -127.7 h per month, standard error = 25.83, P < 0.001), compared to the adults living with others and with normal cognition. CONCLUSIONS: This study highlights the high burden of functional disability but low coverage of informal care among Chinese adults living alone with cognitive impairment and calls for more resources to be allocated to this vulnerable subpopulation to improve the functional health and to increase the provision of long-term care services.
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Actividades Cotidianas , Disfunción Cognitiva , Humanos , Masculino , Femenino , China/epidemiología , Anciano , Estudios Longitudinales , Persona de Mediana Edad , Personas con Discapacidad , Anciano de 80 o más Años , Vida Independiente , Cuidadores/psicología , Puntaje de Propensión , Atención al Paciente , Pueblos del Este de AsiaRESUMEN
The aim of this study is to validate the activity of hazelnut (Corylus avellana L.)-derived immunoactive peptides inhibiting the main protease (Mpro) of SARS-CoV-2 and further unveil their interaction mechanism using in vitro assays, molecular dynamics (MD) simulations, and binding free energy calculations. In general, the enzymatic hydrolysis components, especially molecular weight < 3 kDa, possess good immune activity as measured by the proliferation ability of mouse splenic lymphocytes and phagocytic activity of mouse peritoneal macrophages. Over 866 unique peptide sequences were isolated, purified, and then identified by nanohigh-performance liquid chromatography/tandem mass spectrometry (NANO-HPLC-MS/MS) from hazelnut protein hydrolysates, but Trp-Trp-Asn-Leu-Asn (WWNLN) and Trp-Ala-Val-Leu-Lys (WAVLK) in particular are found to increase the cell viability and phagocytic capacity of RAW264.7 macrophages as well as promote the secretion of the cytokines nitric oxide (NO), tumor necrosis factor-α (TNF-α), and interleukin-1ß (IL-1ß). Fluorescence resonance energy transfer assay elucidated that WWNLN and WAVLK exhibit excellent inhibitory potency against Mpro, with IC50 values of 6.695 and 16.750 µM, respectively. Classical all-atom MD simulations show that hydrogen bonds play a pivotal role in stabilizing the complex conformation and protein-peptide interaction. Molecular Mechanics/Generalized Born Surface Area (MM/GBSA) calculation indicates that WWNLN has a lower binding free energy with Mpro than WAVLK. Furthermore, adsorption, distribution, metabolism, excretion, and toxicity (ADMET) predictions illustrate favorable drug-likeness and pharmacokinetic properties of WWNLN compared to WAVLK. This study provides a new understanding of the immunomodulatory activity of hazelnut hydrolysates and sheds light on peptide inhibitors targeting Mpro.
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Corylus , Péptidos , Animales , Ratones , Proteasas 3C de Coronavirus/química , Proteasas 3C de Coronavirus/antagonistas & inhibidores , Proteasas 3C de Coronavirus/metabolismo , Corylus/química , Macrófagos/efectos de los fármacos , Macrófagos/inmunología , Simulación de Dinámica Molecular , Péptidos/química , Péptidos/farmacología , Proteínas de Plantas/química , Proteínas de Plantas/farmacología , Proteínas de Plantas/inmunología , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , Células RAW 264.7 , SARS-CoV-2/efectos de los fármacos , SARS-CoV-2/inmunología , SARS-CoV-2/química , Células VeroRESUMEN
Hydrophilic and hydrophobic modified nanomicelles might be more conducive to passage of the gastrointestinal barrier than walnut peptide (WP). In this study, a novel double modified starch polymer, SB-CST-DCA, was synthesized by grafting sulfabetaine (SB) and deoxycholic acid (DCA) onto corn starch (CST) molecules through etherification and esterification. The modification mechanism was discussed to determine its chemical structure, morphological properties, and thermal stability. Peptide-loaded nanomicelles (SB-CST-DCA-WP) were prepared using WP as the core material. The encapsulation efficiency and peptide loading amount reached 76.90 ± 1.52% and 18.27 ± 0.53%, respectively, with good stability and pH-responsive release behavior observed to effectively control WP release and enhance its antioxidant activity. The composite exhibited safety, non-toxicity, and good blood compatibility at concentrations below 125 µg/mL. Duodenum was identified as the main absorption site with an absorption ratio of 41.16 ± 0.36%.
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Preparaciones de Acción Retardada , Portadores de Fármacos , Juglans , Micelas , Péptidos , Almidón , Almidón/química , Juglans/química , Péptidos/química , Preparaciones de Acción Retardada/química , Portadores de Fármacos/química , Humanos , Nanopartículas/química , Interacciones Hidrofóbicas e Hidrofílicas , Composición de Medicamentos , Proteínas de Plantas/química , AnimalesRESUMEN
Highly flexible and superelastic aerogels at large deformation have become urgent mechanical demands in practical uses, but both properties are usually exclusive. Here a trans-scale porosity design is proposed in graphene nanofibrous aerogels (GNFAs) to break the trade-off between high flexibility and superelasticity. The resulting GNFAs can completely recover after 1000 fatigue cycles at 60% folding strain, and notably maintain excellent structural integrity after 10000 cycles at 90% compressive strain, outperforming most of the reported aerogels. The mechanical robustness is demonstrated to be derived from the trans-scale porous structure, which is composed of hyperbolic micropores and porous nanofibers to enable the large elastic deformation capability. It is further revealed that flexible and superelastic GNFAs exhibit high sensitivity and ultrastability as an electrical sensors to detect tension and flexion deformation. As proof, The GNFA sensor is implemented onto a human finger and achieves the intelligent recognition of sign language with high accuracy by multi-layer artificial neural network. This study proposes a highly flexible and elastic graphene aerogel for wearable human-machine interfaces in sensor technology.
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BACKGROUND: Despite evidence on socioeconomic inequalities in psychosocial well-being of adolescents under the COVID-19 pandemic, the explanatory factors and their potential variations across contexts remained understudied. Hence, this cross-regional study compared the extent of inequalities and the mediating pathways across Hong Kong, Mainland China, and the Netherlands. METHODS: Between July 2021 and January 2022, 25 secondary schools from diverse socioeconomic background were purposively sampled from Hong Kong, Zhejiang (Mainland China), and Limburg (the Netherlands). 3595 junior students completed an online survey during class about their socioeconomic position, psychosocial factors, and well-being. Socioeconomic inequalities were assessed by multiple linear regressions using the Slope Index of Inequality (SII), whereas the mediating pathways through learning difficulty, overall worry about COVID-19, impact on family' financial status, resilience, trust in government regarding pandemic management, and adaptation to social distancing were examined by mediation analyses moderated by regions. RESULTS: The adverse psychosocial impact of COVID-19 was stronger in the Netherlands and Hong Kong compared with Mainland China. The greatest extent of socioeconomic inequalities in the change in psychosocial well-being was observed among students in the Netherlands (SII = 0.59 [95% CI = 0.38-0.80]), followed by Hong Kong (SII = 0.37 [0.21-0.52]) and Mainland China (SII = 0.12 [0.00-0.23]). Learning difficulty and resilience were the major mediators in Mainland China and Hong Kong, but to a lesser extent in the Netherlands. CONCLUSION: Socioeconomic inequalities in psychosocial well-being were evident among adolescents under the pandemic, with learning difficulty and resilience of students as the key mediators. Differences in the social contexts should be considered to better understand the variations in inequalities and mediating pathways across regions.
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Constructed wetland systems have been widely used in China due to their advantages of good treatment effect, low cost and environmental friendliness. However, traditional constructed wetlands have challenges in application such as deactivation due to filler clogging, difficulty in filler replacement and low adaptability. To address the above problems, this research proposes a modular filler design constructed wetland based on the concept of assembly construction, which can quickly replace the clogged filler without destroying the overall structure of the wetland. Four commonly used fillers were selected and applied to the pilot system of the assembled constructed wetland in this study, in order to investigate the purification effect of the constructed wetland system with different filler module combinations (CW1, CW2, CW3) on the simulated wastewater. The results showed that the filler combination CW1 was the best for the removal of NH4+-N, and for TP and COD, CW2 has the best removal effect. Therefore, the assembled constructed wetland is adjustable and substantially reduces the maintenance cost, which provides technical guidance for its application in engineering.
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Contaminantes Químicos del Agua , Humedales , Purificación del Agua/métodos , Eliminación de Residuos Líquidos/métodos , Análisis de la Demanda Biológica de Oxígeno , Nitrógeno/química , Fósforo/químicaRESUMEN
Given that the ion-exchange membrane takes up more than 30% of redox flow battery (RFB) cost, considerable cost reduction is anticipated with the membrane-free design. However, eliminating the membrane/separator would expose the membrane-free RFBs to a higher risk of short-circuits, and the dendrite growth may aggravate this issue. The current strategy based on expanding distances between electrodes is proposed to address short-circuit issues. Nevertheless, this approach would decrease the energy efficiency (EE) and could not restrain dendrite growth fundamentally. Herein, an inexpensive and electron-insulating boron nitride nanosheets (BNNSs)-Nylon hybrid interlayer (BN/Nylon) is developed for general membrane-free RFBs to achieve "near-zero distance" contact between electrodes. And the Lewis acid sites (B atoms) in BNNS can interact with the Lewis base anions in electrolytes, enabling a reduced Pb2+concentration gradient. Additionally, the ultrahigh thermal conductivity and mechanical strength of BNNSs promote the uniform plating/stripping process of Pb and PbO2. Compared with conventional soluble lead RFBs, introducing BN/Nylon interlayers boosts EE by ≈38.2% at 25 mA cm-2, and extends the cycle life to 100 cycles. This innovative strategy premieres the application of the BN/Nylon interlayer concept, offering a novel perspective for the development of general membrane-free RFBs.
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Despite progress in cancer immunotherapy, ovarian cancer (OC) prognosis continues to be disappointing. Recent studies have shed light on how not just tumour cells, but also the complex tumour microenvironment, contribute to this unfavourable outcome of OC immunotherapy. The complexities of the immune microenvironment categorize OC as a 'cold tumour'. Nonetheless, understanding the precise mechanisms through which the microenvironment influences the effectiveness of OC immunotherapy remains an ongoing scientific endeavour. This review primarily aims to dissect the inherent characteristics and behaviours of diverse cells within the immune microenvironment, along with an exploration into its reprogramming and metabolic changes. It is expected that these insights will elucidate the operational dynamics of the immune microenvironment in OC and lay a theoretical groundwork for improving the efficacy of immunotherapy in OC management.
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Inmunoterapia , Neoplasias Ováricas , Microambiente Tumoral , Humanos , Microambiente Tumoral/inmunología , Femenino , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/terapia , Inmunoterapia/métodos , Animales , Resultado del TratamientoRESUMEN
Food-derived peptides with low molecular weight, high bioavailability, and good absorptivity have been exploited as angiotensin-converting enzyme (ACE) inhibitors. In the present study, in-vitro inhibition kinetics of peanut peptides, in silico screening, validation of ACE inhibitory activity, molecular dynamics (MD) simulations, and HUVEC cells were performed to systematically identify the inhibitory mechanism of ACE interacting with peanut peptides. The results indicate that FPHPP, FPHY, and FPHFD peptides have good thermal, pH, and digestive stability. MD trajectories elucidate the dynamic correlation between peptides and ACE and verify the specific binding interaction. Noteworthily, FPHPP is the best inhibitor with a strongest binding affinity and significantly increases NO, SOD production, and AT2R expression, and decreases ROS, MDA, ET-1 levels, ACE, and AT1R accumulation in Ang II-injury HUVEC cells.
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Inhibidores de la Enzima Convertidora de Angiotensina , Arachis , Células Endoteliales de la Vena Umbilical Humana , Péptidos , Peptidil-Dipeptidasa A , Inhibidores de la Enzima Convertidora de Angiotensina/farmacología , Inhibidores de la Enzima Convertidora de Angiotensina/química , Inhibidores de la Enzima Convertidora de Angiotensina/metabolismo , Humanos , Peptidil-Dipeptidasa A/metabolismo , Peptidil-Dipeptidasa A/química , Arachis/química , Péptidos/química , Péptidos/metabolismo , Péptidos/farmacología , Simulación de Dinámica Molecular , Simulación por Computador , Cinética , Unión ProteicaRESUMEN
Background: High-grade serous ovarian carcinoma (HGSOC) is a pathologic subtype of ovarian cancer (OC) with a more lethal prognosis. Extensive heterogeneity results in HGSOC being more susceptible to treatment resistance and adverse treatment effects. Revealing the heterogeneity involved is crucial. Methods: We downloaded the single-cell RNA-seq (scRNA) data from GEO database and performed a scRNA analysis for cell landscape of HGSOC by using the Seurat package. The highly expressed genes were uploaded into the DAVID and KEGG database for enrichment analysis, and the AUCell package was used to calculate cancer-associated hallmark score. The SCENIC analysis was used for key regulons, the estrogen response enrichment scores in TCGA-OV RNA-seq dataset were calculated by using the GSVA package. Besides, the expression of STRA6 and IRF1 and the cell invasion and migration in si-STRA6 OC cells were detected by using the quantitative reverse transcription (qRT)-PCR method and Transwell assay respectively. Results: We successfully constructed a single-cell atlas of HGSOC and delineated the heterogeneity of epithelial cells therein. There were five epithelial cell subpopulations, GLDC + Epithelial cells, PEG3+ leydig cells, STRA6+ granulosa cells, POLE2+ Epithelial cells, and AURKA + Epithelial cells. STRA6+ granulosa cells have the potential to promote tumor growth as well as the highest estrogen response early activity through the biological pathways analysis of highly expressed genes and estrogen response score of ssGSEA. We found that IRF1 and STRA6 expression was remarkably upregulated in the OC cancer cell line HEY. Silencing of STRA6 markedly decreased the invasion and migration ability of the OC cancer cell line HEY. Conclusion: There is extreme heterogeneity of epithelial cells in HGSOC, and STRA6+ granulosa cells may be able to promote cancer progression. Our findings are benefit to the heterogeneity identification of HGSOC and develop targeted therapy strategy for HGSOC patients.
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OBJECTIVES: This study investigates whether differences in individual-level and provincial-level health funding could explain or mitigate health inequalities among older people in terms of non-communicable diseases within a population served by fragmented health insurance schemes. STUDY DESIGN: A national repeated cross-sectional analysis was done of the 2008, 2011, 2014, and 2018 Chinese Longitudinal Healthy Longevity Surveys. These provided a total of 44,623 persons aged 60 and over. MAIN OUTCOME MEASURES: Respondents were asked whether they had been diagnosed with any types of non-communicable diseases by doctors. A dichotomous outcome variable was constructed to indicate whether older people had any diagnosed non-communicable diseases. RESULTS: Compared with uninsured older persons, those who were enrolled in social health insurance schemes designed for civil servants as cadres, urban employees and urban residents were more likely to report a higher incidence of non-communicable diseases. There were no significant differences in the prevalence of non-communicable diseases between uninsured older people and those in the New Rural Cooperative Medical Scheme. Although the incidence of non-communicable diseases among older persons increased over the study period, greater health expenditure was significantly associated with a lower risk of non-communicable diseases. The interaction results between individual social health insurance schemes and public health expenditure indicate that disparities in the incidence of non-communicable diseases among different health insurance schemes diminish as public health expenditure increases. Older individuals with Public Free Medical Services benefited the most in provinces with higher public health expenditure compared with other health insurance schemes. CONCLUSIONS: Given the evidence of the beneficial effects of universal health coverage on non-communicable diseases among older persons, these results should encourage policy makers to increase public health funding and to raise the overall benefit packages for social health insurance schemes.