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INTRODUCTION: The attentional boost effect, characterized by better memory for background scenes coinciding with a detection target than a nontarget, is believed to stem from a temporary increase in attentional capacity at the time of an acute behavior-related event occurring. Sisk and Jiang's study found that the attentional boost effect also occurs when the target's appearance was predictable. Unfortunately, the duration of the predictive interval in Sisk and Jiang's study was fixed. Since different predictive intervals had different weakening degrees to the acuteness of the target, this fixed duration hindered further investigation into the impact of different levels of predictability on the attentional boost effect. METHOD: Using the encoding-recognition paradigm and the remembering/knowing paradigm, and setting target stimuli with different predictive interval in target detection tasks, the current study aimed to explore the influence of varying the duration of the predictive interval on the attentional boost effect. RESULTS: The attentional boost effect was observed only in the short and medium predictive duration conditions, but not in the long predictive duration condition. Moreover, as the duration of the predictive interval increased, participants' memory performance on target-paired words gradually declined, while their memory performance on distractor-paired and baseline-paired words gradually improved. CONCLUSIONS: Predictability may alter the task demands, allowing participants to more effectively allocate attentional resources to the two tasks at hand.
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Atención , Humanos , Atención/fisiología , Masculino , Femenino , Adulto Joven , Adulto , Reconocimiento en Psicología/fisiología , Factores de Tiempo , Memoria/fisiología , Tiempo de Reacción/fisiologíaRESUMEN
Apolipoprotein E (ApoE) plays a crucial role in iron homeostasis in the body, while macrophages are the principal cells responsible for handling iron in mammals. However, it is unknown whether ApoE can affect the functional subtypes and the iron handling capacity of splenic macrophages (SM). Here, we investigated the effects of ApoE deficiency (ApoE-/-) on the polarization and iron content of SM and its potential mechanisms. ApoE-/- was found to induce a significant increase in the expressions of M1 marker genes CD86, IL-1ß, IL-6, IL-12, TNF-α and iNOS and a reduction in M2 marker genes CD206, Arg-1, IL-10 and Ym-1 in SM of mice aged 28 weeks, Meanwhile, ApoE-/- caused a significant increase in iron content and expression of ferritin, transferrin receptor 1 (TfR1), iron regulatory protein 1 (IRP1) and heme oxygenase-1 (HO-1) and a reduction in ferroportin1 (Fpn1) in spleen and/or SM of mice aged 28 weeks. It was concluded that ApoE-/- can increase iron content through increased iron uptake mediated by TfR/ IRPs and decreased iron release mediated by Fpn1, leading to polarization of the SM to M1 phenotype.
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The main objective of this work was to investigate the mechanism of Astragalus aqueous extract ulcer healing in diabetic foot model rats through the hypoxia-inducible factor 1-alpha (HIF-1É)/vascular endothelial growth factor (VEGF) signalling pathway. Fifty specific-pathogen-free male Sprague Dawley rats were divided into blank (A), model control (B), Astragalus extract (C) and mupirocin (D) treatment groups. Group A received a regular diet, whereas the other groups received a high-fat/high-sugar diet and intraperitoneal streptozotocin injections to induce diabetes. Diabetic foot ulcers were created via skin excision. Subsequently, ulcers were debrided daily. Groups B, C and D received wet saline gauze, wet gauze with Astragalus extract and gauze with mupirocin, respectively, on the affected area. Group A received no treatment. After 14 days, the rats were assessed for ulcer healing and general condition. Immunohistochemistry was used to detect HIF-1É and VEGF levels in the dorsalis pedis artery, and ELISA was used to determine serum IL-6 and CRP levels. The results revealed that Groups C and D had significantly faster ulcer healing compared with Group B (p < 0.01), and ulcer healing was faster in Group C than in Group D (p < 0.01). Group C exhibited notably higher HIF-1É and VEGF protein expression levels compared with Groups B and D (p < 0.01). IL-6 and CRP expression levels in Groups C and D were significantly lower than those in Group B (p < 0.01). In summary, Astragalus aqueous extract effectively treats diabetic foot ulcers by up-regulating HIF-1É and VEGF expression, activating the HIF-1É/VEGF pathway, improving local tissue ischaemia and hypoxia, promoting collateral circulation and enhancing dorsalis pedis artery formation, thereby accelerating ulcer repair in diabetic rats.
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Planta del Astrágalo , Pie Diabético , Subunidad alfa del Factor 1 Inducible por Hipoxia , Extractos Vegetales , Ratas Sprague-Dawley , Transducción de Señal , Factor A de Crecimiento Endotelial Vascular , Cicatrización de Heridas , Animales , Pie Diabético/tratamiento farmacológico , Pie Diabético/metabolismo , Masculino , Factor A de Crecimiento Endotelial Vascular/metabolismo , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Transducción de Señal/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Planta del Astrágalo/química , Cicatrización de Heridas/efectos de los fármacos , Diabetes Mellitus Experimental/tratamiento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Ratas , Interleucina-6/metabolismo , Interleucina-6/sangre , Proteína C-Reactiva/metabolismoRESUMEN
BACKGROUND: A cross-sectional population-based survey in the Beichen district of Tianjin was conducted to estimate the prevalence of dry eye disease (DED) among the population over 50 years old with Dry Eye Workshop (DEWS) II and Chinese expert consensus (CEC) criteria. METHODS: A total of 5791 subjects over 50 years old were enrolled. Ocular surface disease index (OSDI) questionnaire, lipid layer thickness (LLT), partial blink ratio (PBR), fluorescein tear film breakup time (FBUT), Schirmer I test (SIT), fluorescein staining, meibomian gland dropout, meibomian gland expression scores (MES) and quantity scores (MQS) was assessed. Additionally, basic information, weight, disease history, living habits, anxiety, and depression condition were collected. RESULTS: According to the CEC, the prevalence of DED was 39.0%, whereas 44.0% based on DEWS II. The prevalence of DED increased with age and was substantially greater among women (41.1%, 95% CI, 39.5-42.6%) than males (35.1%, 95% CI, 33.1 -37.2%) (p < 0.001). Furthermore, the severity of DED was more severe in women (p = 0.006). The associated risk factors were age, female, depression, smoking, insomnia, and glaucoma. On the other hand, 53.6% of these populations were diagnosed as asymptomatic DED, and the morbidity was higher in males (p = 0.007). CONCLUSIONS: The prevalence of DED in China was relatively high, which was associated with aging, female(sex), depression, smoking and sleep problems. Hence, it is crucial for clinicians and caregivers to be aware of the existence of asymptomatic DED within the susceptible population.
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Síndromes de Ojo Seco , Humanos , Estudios Transversales , Femenino , Masculino , Síndromes de Ojo Seco/epidemiología , Persona de Mediana Edad , China/epidemiología , Prevalencia , Anciano , Anciano de 80 o más Años , Encuestas y Cuestionarios , Factores de RiesgoRESUMEN
BACKGROUND: R2R3-MYB transcription factors belong to one of the largest gene subfamilies in plants, and they are involved in diverse biological processes. However, the role of R2R3-MYB transcription factor subfamily genes in the response of rice (Oryza sativa L.) to salt stress has been rarely reported. RESULTS: In this study, we performed a genome-wide characterization and expression identification of rice R2R3-MYB transcription factor subfamily genes. We identified a total of 117 R2R3-MYB genes in rice and characterized their gene structure, chromosomal location, and cis-regulatory elements. According to the phylogenetic relationships and amino acid sequence homologies, the R2R3-MYB genes were divided into four groups. qRT-PCR of the R2R3-MYB genes showed that the expression levels of 10 genes significantly increased after 3 days of 0.8% NaCl treatment. We selected a high expression gene OsMYB2-115 for further analysis. OsMYB2-115 was highly expressed in the roots, stem, leaf, and leaf sheath. OsMYB2-115 was found to be localized in the nucleus, and the yeast hybrid assay showed that OsMYB2-115 has transcriptional activation activity. CONCLUSION: This result provides important information for the functional analyses of rice R2R3-MYB transcription factor subfamily genes related to the salt stress response and reveals that OsMYB2-115 may be an important gene associated with salt tolerance in rice.
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Regulación de la Expresión Génica de las Plantas , Oryza , Filogenia , Proteínas de Plantas , Estrés Salino , Factores de Transcripción , Oryza/genética , Oryza/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Estrés Salino/genética , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Genoma de Planta , Familia de Multigenes , Perfilación de la Expresión Génica , Cromosomas de las Plantas/genéticaRESUMEN
BACKGROUND: Calculus bovis (CB), used in traditional Chinese medicine, exhibits anti-tumor effects in various cancer models. It also constitutes an integral component of a compound formulation known as Pien Tze Huang, which is indicated for the treatment of liver cancer. However, its impact on the liver cancer tumor microenvironment, particularly on tumor-associated macrophages (TAMs), is not well understood. AIM: To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/ß-catenin pathway modulation. METHODS: This study identified the active components of CB using UPLC-Q-TOF-MS, evaluated its anti-neoplastic effects in a nude mouse model, and elucidated the underlying mechanisms via network pharmacology, transcriptomics, and molecular docking. In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs, and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis. RESULTS: This study identified 22 active components in CB, 11 of which were detected in the bloodstream. Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth. An integrated approach employing network pharmacology, transcriptomics, and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization. In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/ß-catenin pathway activation. The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001, confirming its pathway specificity. CONCLUSION: This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/ß-catenin pathway, contributing to the suppression of liver cancer growth.
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Neoplasias Hepáticas , Ratones Desnudos , Simulación del Acoplamiento Molecular , Microambiente Tumoral , Macrófagos Asociados a Tumores , Vía de Señalización Wnt , Vía de Señalización Wnt/efectos de los fármacos , Animales , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/metabolismo , Humanos , Ratones , Células Hep G2 , Macrófagos Asociados a Tumores/metabolismo , Macrófagos Asociados a Tumores/efectos de los fármacos , Macrófagos Asociados a Tumores/inmunología , Microambiente Tumoral/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/metabolismo , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Proliferación Celular/efectos de los fármacos , Ratones Endogámicos BALB C , Masculino , Farmacología en Red , beta Catenina/metabolismo , Medicina Tradicional China/métodosRESUMEN
Purpose: P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC. Methods: We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal. Results: We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10-1.48) and 0.77 (0.66-0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (P trend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells. Conclusion: We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.
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Lactoferrin (Lf) is a multifunctional protein in the transferrin family. It is involved in many physiological functions, including the regulation of iron absorption and immune response. It also has antibacterial, antiviral, anti-inflammatory, anticancer and antioxidant capabilities under pathophysiological conditions. The mammalian lactoferrin receptor (LfR) plays a key role in mediating multiple functions of Lf. Studies have shown that Lf/LfR is abnormally expressed in the brain of Parkinson's disease, and the excessive accumulation of iron in the brain caused by the overexpression of Lf and LfR is considered to be one of the initial causes of the degeneration of dopaminergic neurons in Parkinson's disease. On the other hand, a number of recent studies have reported that Lf/LfR has a significant neuroprotective effect on Parkinson's disease. In other words, it seems paradoxical that Lf/LfR has both neurodegenerative and neuroprotective effects in Parkinson's disease. This article focuses on recent advances in the possible mechanisms of the neurodegenerative and neuroprotective effects of Lf/LfR in Parkinson's disease and discusses why Lf/LfR has a seemingly contradictory role in the development of Parkinson's disease. Based on the evidence obtained so far, we believed that Lf/LfR has a neuroprotective effect on Parkinson's disease, while as to whether the overexpressed Lf/LfR is the cause of the development of Parkinson's disease, the current evidence is insufficient and further investigation needed.
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To understand the land use development trends in Shaanxi Province under different scenarios and effectively assess the spatiotemporal evolution of terrestrial ecological carbon stocks in Shaanxi Province under land use changes, the study used Markov-FLUS and InVEST models to analyze the impact of land use changes in Shaanxi Province from 2000 to 2020. The impact of carbon storage changes and the spatiotemporal changes in land use structure, carbon storage, and carbon density under three different scenarios were simulated and assessed in Shaanxi Province in 2025 and 2030. The results showedï¼ â The ROC values of various categories in the coupled Markov-FLUS model were all above 0.7, showing high accuracy and excellent classification performance. The model had a good ability to explain the land use driving factors in the study area, with high accuracy and excellent classification performance. â¡ From 2000 to 2020, the cultivated land in Shaanxi Province increased significantly. Forest land increased significantly, and the increase in forest land area with high carbon sequestration efficiency caused the carbon storage in Shaanxi Province to increase from 1 546.95 Tg to 1 616.25 Tg. The changes in various regions in Shaanxi Province from 2000 to 2020 were different, among which the carbon storage in Yan'an was significantly increased by 18.89 Tg, whereas the carbon storage in Yulin significantly decreased by 3.29 Tg in 20 years. ⢠Altitude, precipitation, and temperature became the main factors affecting the spatiotemporal changes in carbon storage in Shaanxi Province from 2020 to 2030. In three of the years between 2025 and 2030, under different scenarios, the carbon stocks under the ecological priority scenario were 1 632.27 Tg and 1 647.43 Tg, respectively. The carbon storage and its growth rate were significantly higher than in the natural development scenario and the cultivated land protection scenario. ⣠The proportion of carbon storage increase areas under the ecological priority scenario was high. In the cultivated land protection scenario, the proportion of reduction areas was lower than that of the natural development scenario, and the distribution of carbon storage was the most balanced. At the same time, the southern and northern areas of the Loess Plateau in northern Shaanxi need to focus on the protection of the ecological environment in future development. The research results can, to a certain extent, provide reference for promoting the construction of ecological Shaanxi and formulating carbon neutral strategic planning.
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BACKGROUND: BCR::ABL1-like or Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukemia (ALL) was first reported in 2009. Ph-like ALL is characterized by gene signature similar to Philadelphia chromosome ALL, but without BCR::ABL1 fusions. Molecularly, Ph-like ALL is divided into seven categories, with CRLF2 and ABL-class rearrangements being the two most common subtypes, exhibiting alterations in distinct downstream signaling cascades. CASE PRESENTATION: We report a rare case of pediatric Ph-like ALL with concomitant CRLF2 and ABL1 rearrangements. CRLF2 was fused with P2RY8, its most common fusion partner, whereas ABL1 was fused with MYO18B, a novel fusion partner that has not been previously reported. The 4-year-old female patient was treated using the national multicenter CCCG-ALL-2020 protocol with the addition of dasatinib at the end of induction when ABL1 rearrangement was confirmed by RNA-seq. Morphologically and molecularly, the patient remained in continuous remission until the last follow-up. To the best of our knowledge, this is the first case of Ph-like ALL harboring two distinct rearrangement categories. CONCLUSIONS: Our results identified that ABL1 rearrangement and CRLF2 rearrangement can coexist. The application of FISH, whole transcription sequencing, PCR can help us to have a more comprehensive understanding of ALL cytogenetics and molecular biology. Further studies are needed to explore the role of targeted therapies in such rare clinical scenarios.
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Reordenamiento Génico , Cromosoma Filadelfia , Leucemia-Linfoma Linfoblástico de Células Precursoras , Receptores de Citocinas , Humanos , Femenino , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Preescolar , Receptores de Citocinas/genética , Proteínas Proto-Oncogénicas c-abl/genéticaRESUMEN
Acquired resistance to endocrine treatments remains a major clinical challenge. In this study, we found that desmoglein-2 (DSG2) plays a major role in acquired endocrine resistance and cellular plasticity in ER+ breast cancer (BC). By analysing the well-established fulvestrant-resistant ER+ BC model using single-cell RNA-seq, we revealed that ER inhibition leads to a specific increase in DSG2 in cancer cell populations, which in turn enhances desmosome formation in vitro and in vivo and cell phenotypic plasticity that promotes resistance to treatment. DSG2 depletion reduced tumorigenesis and metastasis in fulvestrant-resistant xenograft models and promoted fulvestrant efficiency. Mechanistically, DSG2 forms a desmosome complex with JUP and Vimentin and triggers Wnt/PCP signalling. We showed that elevated DSG2 levels, along with reduced ER levels and an activated Wnt/PCP pathway, predicted poor survival, suggesting that a DSG2high signature could be exploited for therapeutic interventions. Our analysis highlighted the critical role of DSG2-mediated desmosomal junctions following antiestrogen treatment.
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Neoplasias de la Mama , Desmogleína 2 , Desmosomas , Resistencia a Antineoplásicos , Vía de Señalización Wnt , Desmogleína 2/metabolismo , Desmogleína 2/genética , Humanos , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Femenino , Animales , Desmosomas/metabolismo , Ratones , Fulvestrant/farmacología , Antineoplásicos Hormonales/farmacología , Receptores de Estrógenos/metabolismo , Línea Celular Tumoral , Fenotipo , Placofilinas/metabolismo , Placofilinas/genética , Plasticidad de la Célula/efectos de los fármacos , Ensayos Antitumor por Modelo de Xenoinjerto , Células MCF-7 , Regulación Neoplásica de la Expresión Génica , gamma CateninaRESUMEN
Electrocatalytic CO2 reduction serves as an effective strategy to tackle energy crises and mitigate greenhouse gas effects. The development of efficient and cost-effective electrocatalysts has been a research hotspot in the field. In this study, we designed four Co-doped single-atom catalysts (Co-Nχ@C) using carbon nanotubes as carriers, these catalysts included tri- and dicoordinated N-doped carbon nanoribbons, as well as tri- and dicoordinated N-doped graphene, respectively denoted as H3(H2)-Co/CNT and 3(2)-Co/CNT. The stable configurations of these Co-Nχ@C catalysts were optimized using the PBE+D3 method. Additionally, we explored the reaction mechanisms of these catalysts for the electrocatalytic reduction of CO2 into four C1 products, including CO, HCOOH, CH3OH and CH4, in detail. Upon comparing the limiting potentials (UL) across the Co-Nχ@C catalysts, the activity sequence for the electrocatalytic reduction of CO2 was H2-Co/CNT > 3-Co/CNT > H3-Co/CNT > 2-Co/CNT. Meanwhile, our investigation of the hydrogen evolution reaction (HER) with four catalysts elucidated the influence of acidic conditions on the electrocatalytic CO2 reduction process. Specifically, controlling the acidity of the solution was crucial when using the H3-Co/CNT and H2-Co/CNT catalysts, while the 3-Co/CNT and 2-Co/CNT catalysts were almost unaffected by the solution's acidity. We hope that our research will provide a theoretical foundation for designing more effective CO2 reduction electrocatalysts.
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The ongoing efforts to optimize rechargeable Li-ion batteries led to the interest in intercalation of nanoscale layered compounds, including bilayer graphene. Its lithium intercalation has been demonstrated recently but the mechanisms underpinning the storage capacity remain poorly understood. Here, using magnetotransport measurements, we report in-operando intercalation dynamics of bilayer graphene. Unexpectedly, we find four distinct intercalation stages that correspond to well-defined Li-ion densities. Transitions between the stages occur rapidly (within 1 sec) over the entire device area. We refer to these stages as 'in-plane', with no in-plane analogues in bulk graphite. The fully intercalated bilayers represent a stoichiometric compound C14LiC14 with a Li density of â¼2.7·1014 cm-2, notably lower than fully intercalated graphite. Combining the experimental findings and DFT calculations, we show that the critical step in bilayer intercalation is a transition from AB to AA stacking which occurs at a density of â¼0.9·1014 cm-2. Our findings reveal the mechanism and limits for electrochemical intercalation of bilayer graphene and suggest possible avenues for increasing the Li storage capacity.
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Periodontitis is a multifactorial chronic inflammatory disease that destroy periodontium. Apart from microbial infection and host immune responses, emerging evidence shows aging and endoplasmic reticulum stress (ER stress) play a key role in periodontitis pathogenesis. The aim of this study is to identify aging-related genes (ARGs) and endoplasmic reticulum stress-related genes (ERGs) in periodontitis. Data were obtained from the Gene Expression Omnibus (GEO), Human Ageing Genomic Resources (HAGR) and GeneCards databases to identify differentially expressed mRNAs/miRNAs/lncRNAs (DEmRNAs/DEmiRNAs/DElncRNAs), ARGs and ERGs, respectively. We used the MultiMiR database for the reverse prediction of miRNAs and predicted miRNA-lncRNA interactions using the STARBase database. Afterwards, we constructed a mRNA-miRNA-lncRNA ceRNA network. A total of 10 hub genes, namely LCK, LYN, CXCL8, IL6, HCK, IL1B, BTK, CXCL12, GNAI1 and FCER1G, and 5 DEmRNAs-ARGs-ERGs were then discovered. Further, weighted gene co-expression network analysis (WGCNA) and single sample gene set enrichment analysis (ssGSEA) were performed to explore co-expression modules and immune infiltration respectively. Finally, we used transmission electron microscope (TEM), inverted fluorescence microscopy, quantitative real-time polymerase chain reaction (qRT-PCR) and Western Blot to verify the bioinformatic results in periodontal ligament stem cells (PDLSCs) infected with Porphyromonas gingivalis (P. gingivalis). The experimental results broadly confirmed the accuracy of bioinformatic analysis. The present study established an aging- and ER stress-related ceRNA network in periodontitis, contributing to a deeper understanding of the pathogenesis of periodontitis.
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Endosomal membrane trafficking is mediated by specific protein coats and formation of actin-rich membrane domains. The Retromer complex coordinates with sorting nexin (SNX) cargo adaptors including SNX27, and the SNX27-Retromer assembly interacts with the Wiskott-Aldrich syndrome protein and SCAR homolog (WASH) complex which nucleates actin filaments establishing the endosomal recycling domain. Crystal structures, modeling, biochemical, and cellular validation reveal how the FAM21 subunit of WASH interacts with both Retromer and SNX27. FAM21 binds the FERM domain of SNX27 using acidic-Asp-Leu-Phe (aDLF) motifs similar to those found in the SNX1 and SNX2 subunits of the ESCPE-1 complex. Overlapping FAM21 repeats and a specific Pro-Leu containing motif bind three distinct sites on Retromer involving both the VPS35 and VPS29 subunits. Mutation of the major VPS35-binding site does not prevent cargo recycling; however, it partially reduces endosomal WASH association indicating that a network of redundant interactions promote endosomal activity of the WASH complex. These studies establish the molecular basis for how SNX27-Retromer is coupled to the WASH complex via overlapping and multiplexed motif-based interactions required for the dynamic assembly of endosomal membrane recycling domains.
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Endosomas , Nexinas de Clasificación , Proteínas de Transporte Vesicular , Humanos , Endosomas/metabolismo , Nexinas de Clasificación/metabolismo , Nexinas de Clasificación/genética , Nexinas de Clasificación/química , Proteínas de Transporte Vesicular/metabolismo , Proteínas de Transporte Vesicular/genética , Proteínas de Transporte Vesicular/química , Proteínas de Microfilamentos/metabolismo , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/química , Unión Proteica , Cristalografía por Rayos X , Sitios de Unión , Modelos MolecularesRESUMEN
Background: Impact of radiotherapy (RT) for esophageal cancer (EC) patients on the development of secondary head and neck cancer (SHNC) remains equivocal. The objective of this study was to investigate the link between definitive RT used for EC treatment and subsequent SHNC. Methods: This study was conducted using the Surveillance, Epidemiology, and End Results (SEER) database to collect the data of primary EC patients. Fine-Gray competing risk regression and standardized incidence ratio (SIR) and propensity score matching (PSM) method were used to match SHNC patients with only primary head and neck cancer (HNC) patients. Overall survival (OS) rates were applied by Kaplan-Meier analysis. Results: In total, 14,158 EC patients from the SEER database were included, of which 9,239 patients (65.3%) received RT and 4,919 patients (34.7%) received no radiation therapy (NRT). After a 12-month latency period, 110 patients (1.2%) in the RT group and 36 patients (0.7%) in the NRT group experienced the development of SHNC. In individuals with primary EC, there was an increased incidence of SHNC compared to the general US population (SIR = 5.95, 95% confidence interval (CI): 5.15 - 6.84). Specifically, the SIR for SHNC was 8.04 (95% CI: 6.78 - 9.47) in the RT group and 3.51 (95% CI: 2.64 - 4.58) in the NRT group. Patients who developed SHNC after RT exhibited significantly lower OS compared to those after NRT. Following PSM, the OS of patients who developed SHNC after RT remained significantly lower than that of matched patients with only primary HNC. Conclusion: An association was discovered between RT for EC and increased long-term risk of SHNC. This work enables radiation oncologists to implement mitigation strategies to reduce the long-term risk of SHNC in patients who have received RT following primary EC.
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Advanced oxidation processes (AOPs) are the most efficient water cleaning technologies, but their applications face critical challenges in terms of mass/electron transfer limitations and catalyst loss/deactivation. Bipolar electrochemistry (BPE) is a wireless technique that is promising for energy and environmental applications. However, the synergy between AOPs and BPE has not been explored. In this study, by combining BPE with AOPs, we develop a general approach of using carbon nanotubes (CNTs) as electric-field-induced bipolar electrodes to control electron transfer for efficient water purification. This approach can be used for permanganate and peroxide activation, with superior performances in the degradation of refractory organic pollutants and excellent durability in recycling and scale-up experiments. Theoretical calculations, in situ measurements, and physical experiments showed that an electric field could substantially reduce the energy barrier of electron transfer over CNTs and induce them to produce bipolar electrodes via electrochemical polarization or to form monopolar electrodes through a single particle collision effect with feeding electrodes. This approach can continuously provide activated electrons from one pole of bipolar electrodes and simultaneously achieve "self-cleaning" of catalysts through CNT-mediated direct oxidation from another pole of bipolar electrodes. This study provides a fundamental scientific understanding of BPE, expands its scope in the environmental field, and offers a general methodology for water purification.
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Electrodos , Nanotubos de Carbono , Oxidación-Reducción , Purificación del Agua , Nanotubos de Carbono/química , Purificación del Agua/métodos , CatálisisRESUMEN
AIM: Comparing the anxiety and depression severity and their impact on subsequent birth outcomes in pregnant women before and during Omicron wave in Shanghai in 2022. METHODS: The depression-anxiety symptoms networks were compared between the pregnant women during the outbreak period (outbreak group; n = 783) and a matched control group of pregnant women before the outbreak (pre-outbreak group; n = 783). The impact of baseline mental state on follow-up pregnancy and neonatal outcomes was also explored by logistic regression. FINDINGS: Levels of depression and anxiety between the two groups were not significant different. Network analysis showed that central symptom "trouble relaxing" and bridge symptom "depressed mood" shared by both groups. Different symptom associations in different periods of the pandemic. Total scores and sub-symptom scores of prenatal depressive and anxious severities increased the odds ratios of maternal and neonatal syndromes. The influence of mental state on gestational and neonatal outcomes differed across different pandemic periods. CONCLUSION: The Omicron wave did not have a significant negative impact on the depressive and anxious mood in pregnant women. Targeting central and bridge symptoms intervention may be effective in reducing their adverse effects on co-occurring of anxious and depressive mood and birth outcomes.
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Ansiedad , COVID-19 , Depresión , Complicaciones del Embarazo , Resultado del Embarazo , Humanos , Femenino , Embarazo , COVID-19/psicología , COVID-19/epidemiología , Adulto , Estudios de Casos y Controles , Depresión/epidemiología , Depresión/psicología , Ansiedad/epidemiología , Ansiedad/psicología , Resultado del Embarazo/epidemiología , Estudios Prospectivos , China/epidemiología , Complicaciones del Embarazo/epidemiología , Complicaciones del Embarazo/psicología , SARS-CoV-2 , Índice de Severidad de la Enfermedad , Recién Nacido , Mujeres Embarazadas/psicologíaRESUMEN
Massive use of plastic products has caused their accumulation in soils, releasing large amounts of endogenous plastic additives (e.g., benzotriazole ultraviolet stabilizers, in short BZT-UVs) into terrestrial ecosystems. However, their plant toxicity is little known. Herein, we investigated the occurrence of BZT-UVs in contaminated farmland and selected three BZT-UV congeners to explore their toxic effects on the antioxidant, photosynthetic, and metabolic perturbation on rice (Oryza sativa). Results showed that the mean concentrations of ∑BZT-UVs in soil and plant samples were 180.7 ng/g dw and 156.4 ng/g dw, respectively. UV-P, UV-327 and UV-328 were the dominant BZT-UV congeners in both of soils and plants. Three BZT-UV congeners caused oxidative damages to rice in a dose-dependent manner, especially for UV-328. Functional genes involved in chlorophyll synthetases was inhibited by over 50 % under the stress of BZT-UVs, whereas those responsible for chlorophyll degradation were obviously promoted. The chlorophyll content was thus decreased, leading to a weakened photosynthesis system and an unbalanced carbon metabolism. The transcriptome and metabolome proved that the flux of carbohydrate metabolism and amino acid metabolism were obviously promoted in plants induced by BZT-UVs, which could inhibit the growth of rice. These findings offered insights into the coordinated responses of plants and advanced our understanding of potential ecological risks of BZT-UVs to terrestrial ecosystems.
Asunto(s)
Antioxidantes , Oryza , Fotosíntesis , Contaminantes del Suelo , Triazoles , Oryza/metabolismo , Oryza/efectos de los fármacos , Oryza/crecimiento & desarrollo , Fotosíntesis/efectos de los fármacos , Triazoles/toxicidad , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/metabolismo , Antioxidantes/metabolismo , Rayos Ultravioleta , Clorofila/metabolismo , Estrés Oxidativo/efectos de los fármacosRESUMEN
Skin cancer images have hair occlusion problems, which greatly affects the accuracy of diagnosis and classification. Current dermoscopic hair removal methods use segmentation networks to locate hairs, and then uses repair networks to perform image repair. However, it is difficult to segment hair and capture the overall structure between hairs because of the hair being thin, unclear, and similar in color to the entire image. When conducting image restoration tasks, the only available images are those obstructed by hair, and there is no corresponding ground truth (supervised data) of the same scene without hair obstruction. In addition, the texture information and structural information used in existing repair methods are often insufficient, which leads to poor results in skin cancer image repair. To address these challenges, we propose the intersection-union dual-stream cross-attention Lova-SwinUnet (IUDC-LS). Firstly, we propose the Lova-SwinUnet module, which embeds Lovasz loss function into Swin-Unet, enabling the network to better capture features of various scales, thus obtaining better hair mask segmentation results. Secondly, we design the intersection-union (IU) module, which takes the mask results obtained in the previous step for pairwise intersection or union, and then overlays the results on the skin cancer image without hair to generate the labeled training data. This turns the unsupervised image repair task into the supervised one. Finally, we propose the dual-stream cross-attention (DC) module, which makes texture information and structure information interact with each other, and then uses cross-attention to make the network pay attention to the more important texture information and structure information in the fusion process of texture information and structure information, so as to improve the effect of image repair. The experimental results show that the PSNR index and SSIM index of the proposed method are increased by 5.4875 and 0.0401 compared with the other common methods. Experimental results unequivocally demonstrate the effectiveness of our approach, which serves as a potent tool for skin cancer detection, significantly surpassing the performance of comparable methods.