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Oral ingestion is the primary route for human exposure to nanoplastics, making the gastrointestinal tract one of the first and most impacted organs. Given the presence of the gut-brain axis, a crucial concern arises regarding the potential impact of intestinal damage on the neurotoxic effects of nanoplastics (NPs). The intricate mechanisms underlying NP-induced neurotoxicity through the microbiome-gut-brain axis necessitate further investigation. To address this, we used mice specifically engineered with nuclear factor erythroid-derived 2-related factor 2 (Nrf2) deficiency in their intestines, a strain whose intestines are particularly susceptible to polystyrene NPs (PS-NPs). We conducted a 28-day repeated-dose oral toxicity study with 2.5 and 250 mg/kg of 50 nm PS-NPs in these mice. Our study delineated how PS-NP exposure caused gut microbiota dysbiosis, characterized by Mycoplasma and Coriobacteriaceae proliferation, resulting in increased levels of interleukin 17C (IL-17C) production in the intestines. The surplus IL-17C permeated the brain via the bloodstream, triggering inflammation and brain damage. Our investigation elucidated a direct correlation between intestinal health and neurological outcomes in the context of PS-NP exposure. Susceptible mice with fragile guts exhibited heightened neurotoxicity induced by PS-NPs. This phenomenon was attributed to the elevated abundance of microbiota associated with IL-17C production in the intestines of these mice, such as Mesorhizobium and Lwoffii, provoked by PS-NPs. Neurotoxicity was alleviated by in vivo treatment with anti-IL-17C-neutralizing antibodies or antibiotics. These findings advanced our comprehension of the regulatory mechanisms governing the gut-brain axis in PS-NP-induced neurotoxicity and underscored the critical importance of maintaining intestinal health to mitigate the neurotoxic effects of PS-NPs.
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Nonalcoholic fatty liver disease (NAFLD) is a clinicopathological syndrome characterized by excessive intracellular fat deposition in the hepatocytes, and the development is exacerbated by gut microbiota and bile acids metabolism disorders. Ilex hainanensis Merr. is a traditional medicine of the Zhuang nationality, historically esteemed for its efficacy in lowering blood pressure and lipid levels. This study aimed to investigate the pharmacodynamic effects in NAFLD mice and impacts on gut microbiota and bile acids (BAs) metabolism of I. hainanensis extract (IHA). 16 compounds were identified from IHA by HPLC-DAD-MS analysis. IHA significantly reduced body weight indexs, alanine transaminase (ALT) and aspartate transaminase (AST) activities, improved dyslipidemia and insulin resistance (IR), and effectively ameliorated hepatic steatosis in HFD-induced NAFLD mice. IHA also altered gut microbiota composition, particularly enhancing the abundance of bacteria involved in BAs metabolism, as well as augmented BAs synthesis in the liver and increased fecal excretion. In conclusion, our findings suggest that IHA holds promise in improving NAFLD conditions and modulating gut microbiota and BAs metabolism. These insights contribute to a deeper understanding of the mechanisms underlying IHA-mediated alleviation of lipid accumulation in NAFLD.
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In organic-inorganic hybrid perovskite solar cells (PSCs), hydrogen defects introduce deep-level trap states, significantly influencing non-radiative recombination processes. Those defects are primarily observed in MA-PSCs rather than FA-PSCs. As a result, MA-PSCs demonstrated a lower efficiency of 23.6% compared to 26.1% of FA-PSCs. In this work, both hydrogen vacancy (VH -) and hydrogen interstitial (Hi -) defects in MAPbI3 bulk and on surfaces, respectively are investigated. i) Bulk VH - defects have dramatic impact on non-radiative recombination, with lifetime varying from 67 to 8 ns, depending on whether deprotonated MA0 are ion-bonded or not. ii) Surface H-defects exhibited an inherent self-healing mechanism through a chemical bond between MA0 and Pb2+, indicating a self-passivation effect. iii) Both VH - and Hi - defects can be mitigated by alkali cation passivation; while large cations are preferable for VH - passivation, given strong binding energy of cation/perovskite, as well as, weak band edge non-adiabatic couplings; and small cations are suited for Hi - passivation, considering the steric hindrance effect. The dual passivation strategy addressed diverse experimental outcomes, particularly in enhancing performance associated with cation selections. The dynamic connection between hydrogen defects and non-radiative recombination is elucidated, providing insights into hydrogen defect passivation essential for high-performance PSCs fabrication.
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Psoriasis (PS) is a chronic inflammatory skin disease with a long course and tendency to recur, the pathogenesis of which is not fully understood. This article aims to identify the key differentially expressed genes (DEGs) and microRNA (miRNAs) of PS, construct the core miRNA-mRNA regulatory network, and investigate the underlying molecular mechanism through integrated bioinformatics approaches. Two gene expression profile datasets and 2 miRNA expression profile datasets were downloaded from the gene expression omnibus (GEO) database and analyzed by GEO2R. Intersection DEGs and intersection differentially expressed miRNAs (DEMs) were each screened. The Metascape database and R software were used to perform enrichment analysis of intersecting DEGs and study their functions. Target genes of DEMs were predicted from the online database miRNet. The protein-protein interaction files of the overlapping target genes were obtained from string and the miRNA-mRNA network was constructed by Cytoscape software. In addition, the online web tool CIBERSORT was used to analyze the immune infiltration of dataset GSE166388, and the relative abundance of 22 immune cells in the diseased and normal control tissues was calculated and assessed. Finally, quantitative reverse transcription polymerase chain reaction (qRT-PCR) was used to verify the relative expression of the screened miRNAs and mRNAs to assess the applicability of DEMs and DEGs as biomarkers in PS. A total of 205 mating DEGs and 6 mating DEMs were screened. 103 dysregulated crossover genes from 205 crossover DEGs and 7878 miRNA target genes were identified. The miRNA-mRNA regulatory network was constructed and the top 10 elements were obtained from CytoHubba, including hsa-miR-146a-5p, hsa-miR-17-5p, hsa-miR-106a-5p, hsa-miR-18a-5p, CDK1, CCNA2, CCNB1, MAD2L1, RRM2, and CCNB2. QRT-PCR revealed significant differences in miRNA and gene expression between inflammatory and normal states. In this study, the miRNA-mRNA core regulator pairs hsa-miR-146a-5p, hsa-miR-17-5p, hsa-miR-106a-5p, hsa-miR-18a-5p, CDK1, CCNA2, CCNB1, MAD2L1, RRM2, and CCNB2 may be involved in the course of PS. This study provides new insights to discover new potential targets and biomarkers to further investigate the molecular mechanism of PS.
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Biomarcadores , Perfilación de la Expresión Génica , Redes Reguladoras de Genes , MicroARNs , Psoriasis , Psoriasis/genética , Humanos , MicroARNs/genética , Perfilación de la Expresión Génica/métodos , Biomarcadores/metabolismo , Biología Computacional/métodos , ARN Mensajero/genética , ARN Mensajero/metabolismo , Mapas de Interacción de Proteínas/genética , Bases de Datos GenéticasRESUMEN
Holistic study of glacial lakes and glacial lake outburst floods (GLOFs) in the strategically important China-Nepal transportation corridors is imperative for regional connectivity and disaster risk reduction. This study focuses on four China-Nepal transportation corridors, namely Chentang-Kimathanka, Zhangmu-Kodari, Keyrung-Kathmandu and Taklakot-Hilsa from east to west in the Himalayan region. Within a remote integrated framework, we present the latest high-resolution inventory of glacial lakes, assess their decadal spatio-temporal changes (1992-2022), identify potentially dangerous glacial lakes, and apply hydrodynamic model to assess downstream impacts of possible GLOFs along the study area. The results show 2688 glacial lakes (≥0.001 km2) with a total area of 116.10 ± 8.53 km2 over the study area in 2022. Glacial lakes exhibited spatiotemporal heterogeneity in expansion, with overall expansion of 32 % during 30 years. Keyrung-Kathmandu corridor, among others, was assessed with high GLOF susceptibility. Furthermore, hydrodynamic modeling of four highly dangerous lakes in each transportation area reveals that GLOFs have cross-border effects, impacting â¼103 km of China-Nepal highway, 103 bridges, two major dry ports and 3301 buildings in both countries. Based on these findings, we emphasize the joint efforts of both countries for integrated disaster management for smooth connectivity between two countries and saving downstream population through joint cooperation from central to local government levels by initiating artificial lake lowering, developing cross-border early warning systems and cooperation. This study is valuable for presenting a synergistic study of glacial lakes and GLOF for informing decision- and policy-makers of both China and Nepal for a joint approach to disaster mitigation.
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Identifying genomic markers for phosphate-solubilizing bacteria (PSB) is vital for advancing agricultural sustainability. This study utilizes whole-genome sequencing and comprehensive bioinformatics analysis, examining the genomes of 76 PSB strains with the aid of specialized genomic databases and analytical tools. We have identified the pqq gene cluster, particularly the pqqC gene, as a key marker for (P) solubilization capabilities. The pqqC gene encodes an enzyme that catalyzes the conversion of precursors to 2-keto-D-gluconic acid, which significantly enhances P solubilization in soil. This gene's importance lies not only in its biochemical function but also in its prevalence and effectiveness across various PSB strains, distinguishing it from other potential markers. Our study focuses on Burkholderia cepacia 51-Y1415, known for its potent solubilization activity, and demonstrates a direct correlation between the abundance of the pqqC gene, the quantitative release of P, and the production of 2-keto-D-gluconic acid over a standard 144-h cultivation period under standardized conditions. This research not only underscores the role of the pqqC gene as a universal marker for the rapid screening and functional annotation of PSB strains but also highlights its implications for enhancing soil fertility and crop yields, thereby contributing to more sustainable agricultural practices. Our findings provide a foundation for future research aimed at developing targeted strategies to optimize phosphate solubilization, suggesting areas for further investigation such as the integration of these genomic insights into practical agricultural applications to maximize the effectiveness of PSB strains in real-world soil environments.
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High-definition near-eye display technology has extremely close sight distance, placing a higher demand on the size, performance, and array of light-emitting pixel devices. Based on the excellent photoelectric performance of metal halide perovskite materials, perovskite light-emitting diodes (PeLEDs) have high photoelectric conversion efficiency, adjustable emission spectra, and excellent charge transfer characteristics, demonstrating great prospects as next-generation light sources. Despite their potential, the solubility of perovskite in photoresist presents a hurdle for conventional micro/nano processing techniques, resulting in device sizes typically exceeding 50 µm. This limitation impedes the further downsizing of perovskite-based components. Herein, we propose a plane-structured PeLED device that can achieve microscale light-emitting diodes with a single pixel device size < 2 µm and a luminescence lifetime of approximately 3 s. This is accomplished by fabricating a patterned substrate and regulating ion distribution in the perovskite through self-doping effects to form a PN junction. This breakthrough overcomes the technical challenge of perovskite-photoresist incompatibility, which has hindered the development of perovskite materials in micro/nano optoelectronic devices. The strides made in this study open up promising avenues for the advancement of PeLEDs within the realm of micro/nano optoelectronic devices.
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The unsafe action of miners is one of the main causes of mine accidents. Research on underground miner unsafe action recognition based on computer vision enables relatively accurate real-time recognition of unsafe action among underground miners. A dataset called unsafe actions of underground miners (UAUM) was constructed and included ten categories of such actions. Underground images were enhanced using spatial- and frequency-domain enhancement algorithms. A combination of the YOLOX object detection algorithm and the Lite-HRNet human key-point detection algorithm was utilized to obtain skeleton modal data. The CBAM-PoseC3D model, a skeleton modal action-recognition model incorporating the CBAM attention module, was proposed and combined with the RGB modal feature-extraction model CBAM-SlowOnly. Ultimately, this formed the Convolutional Block Attention Module-Multimodal Feature-Fusion Action Recognition (CBAM-MFFAR) model for recognizing unsafe actions of underground miners. The improved CBAM-MFFAR model achieved a recognition accuracy of 95.8% on the NTU60 RGB+D public dataset under the X-Sub benchmark. Compared to the CBAM-PoseC3D, PoseC3D, 2S-AGCN, and ST-GCN models, the recognition accuracy was improved by 2%, 2.7%, 7.3%, and 14.3%, respectively. On the UAUM dataset, the CBAM-MFFAR model achieved a recognition accuracy of 94.6%, with improvements of 2.6%, 4%, 12%, and 17.3% compared to the CBAM-PoseC3D, PoseC3D, 2S-AGCN, and ST-GCN models, respectively. In field validation at mining sites, the CBAM-MFFAR model accurately recognized similar and multiple unsafe actions among underground miners.
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We demonstrate the post-induction of high-quality microcavities on a silicon photonic crystal (PC) waveguide by integrating a few-layer GaSe crystal, which promises efficient on-chip optical frequency conversions. The integration of GaSe shifts the dispersion bands of the PC waveguide mode into the bandgap, resulting in localized modes confined by the bare PC waveguides. Thanks to the small contrast of refractive index at the boundaries of the microcavity, it is reliable to obtain quality factors exceeding 104. With the enhanced light-GaSe interaction by the microcavity modes and GaSe's high second-order nonlinearity, remarkable second-harmonic generation (SHG) and sum-frequency generation (SFG) are achieved with continuous-wave (CW) lasers.
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Minocycline, a broad-spectrum tetracycline antibiotic, has been shown to possess anti-inflammatory and antioxidative effects in various neurodegenerative diseases. However, its specific effects on retinitis pigmentosa (RP) have not been thoroughly investigated. Therefore, the objective of this study was to explore the potential role of minocycline in treating RP. In this investigation, we used rd1 to explore the antioxidant effect of minocycline in RP. Minocycline therapy effectively restored retinal function and structure in rd1 mice at 14 days postnatal. Additionally, minocycline inhibited the activation of microglia. Moreover, RNA sequencing analysis revealed a significant downregulation in the expression of mitochondrial genes within the retina of rd1 mice. Further KEGG and GO pathway analysis indicated impaired oxidative phosphorylation and electron transport chain processes. TEM confirmed the presence of damaged mitochondria in photoreceptors, while JC-1 staining demonstrated a decrease in mitochondrial membrane potential, accompanied by an increase in mitochondrial reactive oxygen species (ROS) levels. However, treatment with minocycline successfully reversed the abnormal expression of mitochondrial genes and reduced the levels of mitochondrial ROS, thereby providing protection against photoreceptor degeneration. Collectively, minocycline demonstrated the ability to rescue photoreceptor cells in RP by effectively modulating mitochondrial homeostasis and subsequently inflammation. These findings hold significant implications for the development of potential therapeutic strategies for RP.
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Homeostasis , Minociclina , Mitocondrias , Especies Reactivas de Oxígeno , Retinitis Pigmentosa , Minociclina/farmacología , Minociclina/uso terapéutico , Animales , Retinitis Pigmentosa/tratamiento farmacológico , Retinitis Pigmentosa/metabolismo , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Homeostasis/efectos de los fármacos , Ratones , Especies Reactivas de Oxígeno/metabolismo , Degeneración Retiniana/tratamiento farmacológico , Degeneración Retiniana/patología , Degeneración Retiniana/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Células Fotorreceptoras de Vertebrados/efectos de los fármacos , Células Fotorreceptoras de Vertebrados/patología , Células Fotorreceptoras de Vertebrados/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Microglía/efectos de los fármacos , Microglía/metabolismo , Retina/efectos de los fármacos , Retina/patología , Retina/metabolismo , Humanos , Antioxidantes/farmacología , Antioxidantes/uso terapéuticoRESUMEN
The development of liquid biopsy methods for the accurate and reliable detection of miRNAs in whole blood is critical for the early diagnosis and monitoring of diseases. However, accurate quantification of miRNA expression levels remains challenging due to the complex matrix and low abundance of miRNAs in blood samples. Herein, we report a contactless signal output strategy with low background interference that ensures "zero-contact" between the reaction system and the colorimetry system. The designed target-induced magnetic ZnS/ZIF-90/ZnS network can serve as a unique signal amplifier and transducer. It releases hydrogen sulfide (H2S) gas in an acidic solution which can be concentrated in a droplet of only a few microliters in volume, etching the silver layer of Au@Ag nanostars (NSTs) in the droplet. This will lead to changes in the localized surface plasmon resonance signals of the NSTs. Finally, quantitative detection of let-7a is realized by measuring the offset value of the UV-vis absorption peak. Therefore, by virtue of the synergistic action of quadruple signal amplification methods, including catalytic hairpin assembly, ZnS/ZIF-90/ZnS, magnetic separation, and microextraction, the "All-in-Tube" ultrasensitive detection of low-abundance let-7a in whole blood is achieved with a detection limit as low as the aM level. In addition, the "zero-contact" signal output mode effectively solves the problem of complex matrix interference, demonstrating the great potential of this method for miRNA quantification in complex samples, such as whole blood.
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MicroARNs , Sulfuros , MicroARNs/sangre , Humanos , Sulfuros/química , Compuestos de Zinc/química , Colorimetría , Límite de Detección , Oro/química , Plata/química , Resonancia por Plasmón de Superficie , Fenómenos Magnéticos , Nanopartículas del Metal/química , Sulfuro de Hidrógeno/sangreRESUMEN
BACKGROUND: Kerion is a severe type of tinea capitis that is difficult to treat and remains a public health problem. OBJECTIVES: To evaluate the epidemiologic features and efficacy of different treatment schemes from real-world experience. METHODS: From 2019 to 2021, 316 patients diagnosed with kerion at 32 tertiary Chinese hospitals were enrolled. We analysed the data of each patient, including clinical characteristics, causative pathogens, treatments and outcomes. RESULTS: Preschool children were predominantly affected and were more likely to have zoophilic infection. The most common pathogen in China was Microsporum canis. Atopic dermatitis (AD), animal contact, endothrix infection and geophilic pathogens were linked with kerion occurrence. In terms of treatment, itraconazole was the most applied antifungal agent and reduced the time to mycological cure. A total of 22.5% of patients received systemic glucocorticoids simultaneously, which reduced the time to complete symptom relief. Furthermore, glucocorticoids combined with itraconazole had better treatment efficacy, with a higher rate and shorter time to achieving mycological cure. CONCLUSIONS: Kerion often affects preschoolers and leads to serious sequelae, with AD, animal contact, and endothrix infection as potential risk factors. Glucocorticoids, especially those combined with itraconazole, had better treatment efficacy.
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Antifúngicos , Itraconazol , Microsporum , Tiña del Cuero Cabelludo , Humanos , Preescolar , Antifúngicos/uso terapéutico , Masculino , Femenino , Tiña del Cuero Cabelludo/tratamiento farmacológico , Tiña del Cuero Cabelludo/epidemiología , Tiña del Cuero Cabelludo/microbiología , Itraconazol/uso terapéutico , China/epidemiología , Microsporum/aislamiento & purificación , Niño , Lactante , Glucocorticoides/uso terapéutico , Resultado del Tratamiento , Dermatitis Atópica/tratamiento farmacológico , Dermatitis Atópica/epidemiología , Dermatitis Atópica/microbiología , Factores de Riesgo , Adolescente , Adulto , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The development of the Point-of-Care Testing (POCT) platform that combines convenience and cost-effectiveness is crucial for enabling the visual detection of disease biomarkers. In this work, a POCT platform for the sensitive in situ detection of prostate specific antigen (PSA) with dual-signal output was constructed by functionalizing the Eppendorf (EP) tube. This was achieved through the modification of aptamer hairpin probes (AHPs) on the lid of the EP tube and the assembly of a nanoenzyme hydrogel film on its inner wall. The target could trigger the release of Ag+ by AHP and subsequently activate Ag+-dependent DNAzyme (Ag-DNAzyme). This would initiate the cleavage of the DNA-Au/Pt NP hydrogel network, leading to the release of Au/Pt NPs. The released Au/Pt NPs exhibit both peroxidase (POD)-like and catalase (CAT)-like activity to produce a colorimetric response and induce liquid flow under pressure. Therefore, the target can be measured visually and quantitatively through colorimetric analysis and the measurement of total dissolved solids (TDS) using a pressure-triggered liquid flow device integrated into the platform. The designed platform is distinguished by its simplicity, specificity, cost-effectiveness, and remarkable sensitivity. It allows for the visual detection of PSA within concentration ranges of 0.5-100 ng/L (colorimetric) and 3-100 ng/L (TDS reading), boasting detection limits as low as 0.15 ng/L (colorimetric) and 0.57 ng/L (TDS reading). The strategy of target-triggered nanoenzyme release significantly enhances sensitivity and provides a guiding approach for visual biomarker detection.
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Aptámeros de Nucleótidos , Colorimetría , ADN Catalítico , Oro , Nanopartículas del Metal , Pruebas en el Punto de Atención , Antígeno Prostático Específico , Antígeno Prostático Específico/análisis , Humanos , Oro/química , ADN Catalítico/química , ADN Catalítico/metabolismo , Nanopartículas del Metal/química , Aptámeros de Nucleótidos/química , Platino (Metal)/química , Hidrogeles/química , Técnicas Biosensibles , Plata/química , Límite de DetecciónRESUMEN
DOT1L mediates the methylation of histone H3 at lysine 79 and, in turn, the transcriptional activation or repression in a context-dependent manner, yet the regulatory mechanisms and functions of DOT1L/H3K79me remain to be fully explored. Following peptide affinity purification and proteomic analysis, we identified that DCAF1-a component of the E3 ligase complex involved in HIV regulation-is associated with H3K79me2 and DOT1L. Interestingly, blocking the expression or catalytic activity of DOT1L or repressing the expression of DCAF1 significantly enhances the tumor necrosis factor alpha (TNF-α)/nuclear factor κB (NF-κB)-induced reactivation of the latent HIV-1 genome. Mechanistically, upon TNF-α/NF-κB activation, DCAF1 is recruited to the HIV-1 long terminal repeat (LTR) by DOT1L and H3K79me2. Recruited DCAF1 subsequently induces the ubiquitination of NF-κB and restricts its accumulation at the HIV-1 LTR. Altogether, our findings reveal a feedback modulation of HIV reactivation by DOT1L-mediated histone modification regulation and highlight the potential of targeting the DOT1L/DCAF1 axis as a therapeutic strategy for HIV treatment.
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VIH-1 , N-Metiltransferasa de Histona-Lisina , Histonas , FN-kappa B , Ubiquitina-Proteína Ligasas , Humanos , VIH-1/fisiología , VIH-1/metabolismo , N-Metiltransferasa de Histona-Lisina/metabolismo , N-Metiltransferasa de Histona-Lisina/genética , Histonas/metabolismo , FN-kappa B/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Ubiquitinación , Duplicado del Terminal Largo de VIH/genética , Células HEK293 , Activación Viral , Metilación , Factor de Necrosis Tumoral alfa/metabolismo , Infecciones por VIH/virología , Infecciones por VIH/metabolismo , Lisina/metabolismo , Proteínas Serina-Treonina QuinasasRESUMEN
OBJECTIVE: Research on factors contributing to depressive symptoms in cancer patients at a national level, encompassing a comprehensive set of variables was limited. This study aimed to address this gap by identifying the factors associated with depressive symptoms among cancer patients through a nationwide cross-sectional analysis. METHODS: Various factors, including demographic, socioeconomic, behavioral patterns, general and self-rated health status, chronic conditions, dietary habits, and cancer-related factors, were examined. Data was from the National Health and Nutrition Examination Survey. Univariate and multivariate logistic regression analyses were performed to identify associated factors. The receiver-operating characteristic (ROC) curve was used to evaluate the performance of the logistic model. RESULTS: The findings showed that five sociodemographic factors, two behavioral styles, self-rated health status, comorbid arthritis, two dietary factors and two cancer-related factors were strongly associated with depressive symptoms. Compared with those aged 20-39 years, cancer individuals aged 40-59 years (OR = 0.48, P < 0.05) and those 60 years or older (OR = 0.18, P < 0.05) had lower odds of depression. Positive factors included being never married (OR = 1.98, P < 0.05), widowed, divorced or separated (OR = 1.75, P < 0.05), unemployment (OR = 1.87, P < 0.05), current smoking (OR = 1.84, P < 0.05), inadequate sleep (OR = 1.96, P < 0.05), comorbid arthritis (OR = 1.79, P < 0.05), and poor self-rated health status (OR = 3.53, P < 0.05). No significant association was identified between the Healthy Eating Index 2015 and the Dietary Inflammatory Index with depression (P > 0.05). Shorter cancer diagnosis duration was associated with reduced odds of depression (P < 0.05). The logistic model had an area under the curve of 0.870 (95% CI: 0.846-0.894, P < 0.05). CONCLUSIONS: Cancer patients should receive enhanced family and social support while cultivating a healthy lifestyle and diet. Incorporating plenty of fruits, greens, and beans is highly recommended, along with establishing a comprehensive health management framework.
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Depresión , Neoplasias , Humanos , Estudios Transversales , Masculino , Femenino , Persona de Mediana Edad , Depresión/epidemiología , Adulto , Neoplasias/psicología , Neoplasias/epidemiología , Adulto Joven , Factores de Riesgo , Anciano , República de Corea/epidemiología , Encuestas Nutricionales , Estado de Salud , Factores Socioeconómicos , Factores SociodemográficosRESUMEN
Following spinal cord injury, the inflammatory environment at the injury site causes local microglia and astrocytes to activate, which worsens the nerve damage in the affected area. Quercetin, an anti-inflammatory agent, has been limited in spinal cord injury due to its poor water solubility and easy degradation. Stem cell-derived extracellular vesicles can go through the blood-brain barrier and are an ideal drug delivery system. In this study, umbilical cord mesenchymal stem cell-derived extracellular vesicles were used to load quercetin to prevent its degradation and allow it to accumulate at the site of spinal cord injury. Our results showed that quercetin-loaded extracellular vesicles could inhibit the activation of microglia to M1 phenotype through the TLR4/NF-κB pathway, and the activation of astrocytes to A1 phenotype through the JAK2/STAT3 pathway. This reduced the production of inflammatory factors, mitigated neuronal damage, and inhibited the growth of astroglial scar, but promoted the recovery of motor function in rats with spinal cord injury.
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Vesículas Extracelulares , Células Madre Mesenquimatosas , Quercetina , Ratas Sprague-Dawley , Recuperación de la Función , Traumatismos de la Médula Espinal , Cordón Umbilical , Traumatismos de la Médula Espinal/metabolismo , Traumatismos de la Médula Espinal/tratamiento farmacológico , Traumatismos de la Médula Espinal/patología , Quercetina/farmacología , Quercetina/administración & dosificación , Animales , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Recuperación de la Función/efectos de los fármacos , Recuperación de la Función/fisiología , Humanos , Vesículas Extracelulares/metabolismo , Vesículas Extracelulares/efectos de los fármacos , Cordón Umbilical/citología , Ratas , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Microglía/efectos de los fármacos , Microglía/metabolismo , Femenino , Trasplante de Células Madre Mesenquimatosas/métodosRESUMEN
Biodegradable plastics, hailed for their environmental friendliness, may pose unforeseen risks as they undergo gastrointestinal degradation, forming oligomer nanoplastics. Despite this, the influence of gastrointestinal degradation on the potential human toxicity of biodegradable plastics remains poorly understood. To this end, the impact of the murine in vivo digestive system is investigated on the biotransformation, biodistribution, and toxicity of PLA polymer and PLA oligomer MPs. Through a 28-day repeated oral gavage study in mice, it is revealed that PLA polymer and oligomer microplastics undergo incomplete and complete degradation, respectively, in the gastrointestinal tract. Incompletely degraded PLA polymer microplastics transform into oligomer nanoplastics, heightening bioavailability and toxicity, thereby exacerbating overall toxic effects. Conversely, complete degradation of PLA oligomer microplastics reduces bioavailability and mitigates toxicity, offering a potential avenue for toxicity reduction. Additionally, the study illuminates shared targets and toxicity mechanisms in Parkinson's disease-like neurotoxicity induced by both PLA polymer and PLA oligomer microplastics. This involves the upregulation of MICU3 in midbrains, leading to neuronal mitochondrial calcium overload. Notably, neurotoxicity is mitigated by inhibiting mitochondrial calcium influx with MCU-i4 or facilitating mitochondrial calcium efflux with DBcAMP in mice. These findings enhance the understanding of the toxicological implications of biodegradable microplastics on human health.
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Microplásticos , Poliésteres , Animales , Microplásticos/toxicidad , Ratones , Tracto Gastrointestinal/efectos de los fármacos , Tracto Gastrointestinal/metabolismo , Plásticos Biodegradables , Masculino , Distribución Tisular , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/metabolismoRESUMEN
Toward the challenges of signaling transduction amplified in enantioselective recognition, we herein devised an innovative strategy for highly selective recognition of amino acids and their derivatives, leveraging photothermal effects. In this approach, bifunctional l-ascorbic acid is employed to reduce silver ions in situ on Au nanostars. Simultaneously, its oxidate (l-dehydroascorbic acid) is bonded to the silver shell as a chiral selector to prepare chiral nanoparticles (C-AuNS@Ag NPs) with the ability to recognize stereoisomers and sensitively modulate the photothermal effect. l-Dehydroascorbic acid can selectively capture one of the enantiomers of the two forms through hydrogen bonding and drive aggregation of the nanoparticles, which sharply enhances the photothermal effect. Consequently, the two forms of the system exhibit a significant temperature difference, which enables the discrimination and quantification of enantiomers. Our strategy verifies that six chiral amino acids and their derivatives can be discriminated with enantioselective response values of up to 79. Additionally, the chiral recognition mechanism was revealed through density functional theory (DFT) calculations, providing a paradigm shift in the development of enantiomeric recognition strategies.
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Acute mesenteric ischemia (AMI) is a clinically significant vascular and gastrointestinal condition, which is closely related to the blood supply of the small intestine. Unfortunately, it is still challenging to properly discriminate small intestinal tissues with different degrees of ischemia. In this study, hyperspectral imaging (HSI) was used to construct pseudo-color images of oxygen saturation about small intestinal tissues and to discriminate different degrees of ischemia. First, several small intestine tissue models of New Zealand white rabbits were prepared and collected their hyperspectral data. Then, a set of isosbestic points were used to linearly transform the measurement data twice to match the reference spectra of oxyhemoglobin and deoxyhemoglobin, respectively. The oxygen saturation was measured at the characteristic peak band of oxyhemoglobin (560 nm). Ultimately, using the oxygenated hemoglobin reflectance spectrum as the benchmark, we obtained the relative amount of median oxygen saturation in normal tissues was 70.0 %, the IQR was 10.1 %, the relative amount of median oxygen saturation in ischemic tissues was 49.6 %, and the IQR was 14.6 %. The results demonstrate that HSI combined with the oxygen saturation computation method can efficiently differentiate between normal and ischemic regions of the small intestinal tissues. This technique provides a powerful support for internist to discriminate small bowel tissues with different degrees of ischemia, and also provides a new way of thinking for the diagnosis of AMI.