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Objectives: We investigate the impact of wildfire disasters on cognitive health (i.e., thinking and language skills) in individuals aged 10 years and older using 2014 and 2018 wildfire and cognitive ability survey data from China. Methods: We distinguished wildfires in each county at different wind directions each day by exogenous wind direction changes, and analyzed the effects of wildfires on cognitive abilities through upwind and non-upwind wildfires. Results: Our analysis shows that for every 10-unit increase in upwind wildfires compared to non-upwind wildfires, respondents' scores on word and math tests decrease by 0.235 and 0.236 standard deviations, respectively. Furthermore, we find that the impact of wildfire on cognitive ability is more pronounced in younger individuals, and those with lower defensive expenditures experience more severe impacts. Additionally, wildfires negatively affect individuals' cognitive abilities by generating air pollution. Conclusion: Wildfires significantly reduce individuals' cognitive abilities. Two recommendations are as follows: 1) governments should follow the principle of green development, introduce relevant regulations, and increase investment in adaptive technologies. 2) Individuals should raise awareness of climate hazards preparedness and strengthen defensive protection.
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Cognición , Incendios Forestales , Humanos , China , Masculino , Femenino , Adulto , Persona de Mediana Edad , Adolescente , Niño , Adulto Joven , Desastres , Anciano , Encuestas y Cuestionarios , Cambio ClimáticoRESUMEN
BACKGROUND: The objective of this study was to investigate the value of mismatch negativity (MMN) and P300 event-related potentials for discriminating the consciousness state and predicting improvement of consciousness at 6 months in patients with coma and other disorders of consciousness (DOC). METHODS: We performed MMN and P300 on 42 patients with DOC with a mean onset time of 40.21 ± 19.43 days. These patients with DOC were categorized into coma, unresponsive wakefulness syndrome (UWS), minimal consciousness minus (MCS-), and minimal consciousness plus (MCS +) groups according to neurobehavioral assessment and the Coma Recovery Scale-Revised score. The primary outcome was the improvement of consciousness at 6 months in patients with DOC. We assessed the efficacy of MMN and P300 in quantitatively predicting the prognosis at 6 months and the capability of MMN and P300 parameters to differentiate between DOC. RESULTS: At least one significant difference in either MMN or P300 parameters was displayed among the DOC groups, but not between the MCS- and MCS+ groups (significance level: 0.05). Both MMN and P300 amplitudes showed desirable predictive accuracy at 6 months, with areas under the curve (AUCs) of 0.859 and 0.856, respectively. The optimal thresholds for MMN and P300 amplitudes were 2.044 and 1.095 µV. However, the combined MMN-P300 amplitude showed better 6-month predictive accuracy (AUC 0.934, 95% confidence interval 0.860-1.000), with a sensitivity of 85% and a specificity of 90.9%. CONCLUSIONS: MMN and P300 may help discriminate among coma, UWS, and MCS, but not between patients with MCS- and patients with MCS+ . The MMN amplitude, P300 amplitude, and especially combined MMN-P300 amplitude at 6 months may be interesting predictors of consciousness improvement at 6 months in patients with DOC. TRIAL REGISTRATION: Chinese Clinical Trial Registry identifier ChiCTR2400083798.
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Passive radiative cooling technology without electric consumption is an emerging sustainability technology that plays a key role in advancing sustainable development. However, most radiative cooling materials are vulnerable to outdoor contamination and thermal/UV exposure, which leads to decreased performance. Herein, we report a hierarchically structured polyimide/zinc oxide (PINF/ZnO) composite membrane that integrates sunlight reflectance of 91.4% in the main thermal effect of the solar spectrum (0.78-1.1 µm), the mid-infrared emissivity of 90.0% (8-13 µm), UV shielding performance, thermal resistance, and ideal hydrophobicity. The comprehensive performance enables the composite membrane to yield a temperature drop of â¼9.3 °C, compared to the air temperature, under the peak solar irradiance of â¼800 W m-2. In addition, the temperature drop of as-obtained composite membranes after heating at 200 °C for 6 h in a nitrogen/air atmosphere can be well maintained at â¼9.0 °C, demonstrating their ideal radiative cooling effect in a high-temperature environment. Additionally, the PINF/ZnO composite membrane shows excellent chemical durability after exposure to the outdoor environment. This work provides a new strategy to integrate chemical durability and thermal resistance with radiative cooling, presenting great potential for passive radiative cooling materials toward practical applications in harsh environments.
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Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3's role in CKD's narrative and position it as a promising therapeutic contender.
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Progresión de la Enfermedad , Fibrosis , Perfilación de la Expresión Génica , Insuficiencia Renal Crónica , Análisis de la Célula Individual , Animales , Ratones , Fibrosis/patología , Fibrosis/metabolismo , Fibrosis/genética , Insuficiencia Renal Crónica/genética , Insuficiencia Renal Crónica/patología , Insuficiencia Renal Crónica/metabolismo , Ratones Noqueados , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Riñón/patología , Riñón/metabolismo , Transcriptoma , Especies Reactivas de Oxígeno/metabolismo , Transición Epitelial-Mesenquimal/genética , Modelos Animales de Enfermedad , Mitocondrias/metabolismo , Mitocondrias/patología , Mitocondrias/genéticaRESUMEN
Under the influence of multiple uncertain factors at home and abroad, urban amenities, as the underlying support for urban renewal activities, are of great significance in enhancing urban economic resilience. The panel data of Chinese cities from 2011 to 2019 is used in this study. Urban amenity is measured from artificial amenities and climate amenities, respectively. By using a two-way fixed effects model, we empirically test the impact of urban amenities on urban economic resilience. The key findings of this study are as follows. (1) Urban amenities can significantly enhance urban economic resilience. (2) Heterogeneity analysis shows that there are regional differences in the role of urban amenities in promoting urban economic resilience, with cities in the eastern region, strong environmental regulations, and high urbanization rates benefiting more. (3) We further find that urban amenities mainly enhance economic resilience by promoting population agglomeration, attracting labor migration, improving the quality of human capital, and stimulating urban innovation. Our conclusions recommend to rationally allocate and optimize urban amenity resources, strengthen urban planning and construction management, and create a more livable urban environment, thereby enhancing urban economic resilience.
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Ciudades , Planificación de Ciudades , Urbanización , China , Humanos , Planificación de Ciudades/economía , Población Urbana/estadística & datos numéricos , Remodelación Urbana/economíaRESUMEN
Abnormal secretion and dysrhythmias of cortisol (CORT) are associated with various diseases such as sleep disorders, depression, and chronic fatigue. Wearable devices are a cutting-edge technology for point-of-care detection and dynamic monitoring of CORT with inspiring convenience. Herein, we developed a minimally invasive skin-worn device with the advanced integration of both interstitial fluid (ISF) sampling and target molecule sensing for simultaneous detection of CORT via a microneedle-based sensor with high sensitivity, excellent efficiency, and outstanding reproducibility. In the microneedle patch, swellable hydrogel was employed as the adsorption matrix for ISF extraction. Meanwhile, europium metal-organic frameworks (Eu-MOF) wrapped in the matrix played a vital role in CORT recognition and quantitative analysis. The wearable and label-free Eu-MOF-loaded microneedle patch exhibited high sensitivity in CORT detection with the detection limit reaching 10-9 M and excellent selectivity. Molecular dynamics simulation-driven mechanism exploration revealed that the strong interface interaction promoted fluorescence quenching of Eu-MOF. Moreover, in vitro and in vivo investigation confirmed the feasibility and reliability of the sensing method, and excellent biocompatibility was validated. Overall, a sensitive approach based on the wearable Eu-MOF microneedle (MN) patch was established for the simultaneous detection of CORT via visible fluorescence quenching with exciting clinical-translational ability.
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Hidrocortisona , Estructuras Metalorgánicas , Agujas , Dispositivos Electrónicos Vestibles , Estructuras Metalorgánicas/química , Humanos , Hidrocortisona/análisis , Animales , Europio/química , Técnicas Biosensibles/instrumentación , RatonesRESUMEN
OBJECTIVE: This study presents a detailed analysis of the clinical and genetic characteristics of uterine leiomyoma associated with Hereditary Leiomyomatosis and Renal Cell Cancer (HLRCC), combined with exploration of family history, pathology, and management procedures, supported by thorough evidence collection. METHODS: Blood samples were collected from the proband, and the pathogenic variant was verified using Sanger sequencing. A comprehensive review of family history, FH deficiency pathology, FH and 2SC immunohistochemistry staining was conducted. Functional evidence was derived from clinical and genetic information, supplemented by a literature collection and mutation was reclassified based on ACMG/AMP guidelines. RESULTS: The study successfully identifies a novel missense mutation (c.1240A>G; p.Lys414Glu) in exon 9 of FH, with no prior reports in existing databases. The patient's phenotype and family history, coupled with evidence collected from the literature, contribute to the preliminary determination of the variant as likely pathogenic. We also emphasize that the importance of combining FH-deficient morphology and immunohistochemical staining with 2SC for enhanced sensitivity. CONCLUSION: This research adds a novel missense mutation to the repertoire of FH gene variants, emphasizing its likely pathogenic nature based on a multidimensional analysis of phenotype, family history, and literature evidence. The findings enhance our understanding of the genetic landscape associated with FH and underscore the importance of thorough characterization for accurate variant classification.
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BACKGROUND: Chronic kidney disease (CKD) patients have been found to be at risk of concurrent cognitive dysfunction in previous studies, which has now become an important public health issue of widespread concern. AIM: To investigate the risk factors for concurrent cognitive dysfunction in patients with CKD. METHODS: This is a prospective cohort study conducted among patients with CKD between October 2021 and March 2023. A questionnaire was formulated by literature review and expert consultation and included questions about age, sex, education level, per capita monthly household income, marital status, living condition, payment method, and hypertension. RESULTS: Logistic regression analysis showed that patients aged 60-79 years [odds ratio (OR) = 1.561, P = 0.015] and ≥ 80 years (OR = 1.760, P = 0.013), participants with middle to high school education (OR = 0.820, P = 0.027), divorced or widowed individuals (OR = 1.37, P = 0.032), self-funded patients (OR = 2.368, P = 0.008), and patients with hypertension (OR = 2.011, P = 0.041) had a higher risk of cognitive impairment. The risk of cognitive impairment was lower for those with a college degree (OR = 0.435, P = 0.034) and married individuals. CONCLUSION: The risk factors affecting cognitive dysfunction are age, 60-79 years and ≥ 80 years; education, primary school education or less; marital status, divorced or widowed; payment method, self-funded; hypertension; and CKD.
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Acute myocardial infarction (AMI) is one of the critical health conditions often caused by the rupture of unstable coronary artery plaque, triggering a series of events, such as platelet activation, thrombus formation, coronary artery blockage, lasted severe ischemia, and hypoxia in cardiomyocytes, and culminating in cell death. Platelet-derived microvesicles (PMVs) act as intermediates for cellular communication. Nevertheless, the role of PMVs in myocardial infarction remains unclear. Initially, AMI-related messenger ribose nucleic acid (mRNA) and micro RNA (miRNA) datasets from the Gene Expression Omnibus (GEO) database were analyzed, specifically focusing on the expressed genes associated with Ferroptosis. Further, a miRNA-mRNA regulatory network specific to AMI was constructed. Then, the effect of PMVs on cardiomyocyte survival was further confirmed through in vitro experiments. High ACSL1 expression was observed in the platelets of AMI patients. The gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses revealed that ACSL1, located in the mitochondria, played a key role in the PPAR signaling pathway. The elevated ACSL1 expression in a co-culture model of PMVs and AC16 cardiomyocytes significantly increased the AC16 cell Ferroptosis. Further, we validated that the platelet ACSL1 expression could be regulated by hsa-miR-449a. Together, these findings suggested that platelet ACSL1 could trigger myocardial cell death via PMV transport. In addition, this research provided a theoretical framework for attenuating myocardial cell Ferroptosis in patients with acute myocardial infarction.
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Exploring anticorrosion electromagnetic wave (EMW) absorbing materials in harsh conditions remains a challenge. Herein, S-NiSe/HG nanocomposites encapsulated in room-temperature self-healing polyurethane (S-NiSe/HG/SPU) were exploited as superior anticorrosion EMW absorbing materials. A dual-defect engineering collaborative Schottky interface construction endows S-NiSe/HG with a high vacancy concentration, abundant defects, and moderate conductivity. These structural merits synergistically balance dielectric loss by enhancing dipole-interface polarization loss and optimizing conduction loss. As a result, S-NiSe/HG demonstrates the optimal EMW absorption performance with a minimum reflection loss (RLmin) of -54.8 dB and an adequate absorption bandwidth (EAB) of 7.1 GHz. Besides, S-NiSe/HG/SPU combines the maze effect of S-NiSe/HG with the active repair capability of SPU, thereby providing long-term corrosion resistance for the Mg alloy. Even under corrosion for 10 days, S-NiSe/HG/SPU affords a low corrosion current density (1.3 × 10-5 A) and high charge transfer resistance (3796 Ω cm2). Overall, this work provides valuable insights for in-depth exploration of dielectric loss and development of multifunctional EMW-absorbing materials.
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Tracking nitrogen pollution sources is crucial for the effective management of water quality; however, it is a challenging task due to the complex contaminative scenarios in the freshwater systems. The contaminative pattern variations can induce quick responses of aquatic microorganisms, making them sensitive indicators of pollution origins. In this study, the soil and water assessment tool, accompanied by a detailed pollution source database, was used to detect the main nitrogen pollution sources in each sub-basin of the Liuyang River watershed. Thus, each sub-basin was assigned to a known class according to SWAT outputs, including point source pollution-dominated area, crop cultivation pollution-dominated area, and the septic tank pollution-dominated area. Based on these outputs, the random forest (RF) model was developed to predict the main pollution sources from different river ecosystems using a series of input variable groups (e.g., natural macroscopic characteristics, river physicochemical properties, 16S rRNA microbial taxonomic composition, microbial metagenomic data containing taxonomic and functional information, and their combination). The accuracy and the Kappa coefficient were used as the performance metrics for the RF model. Compared with the prediction performance among all the input variable groups, the prediction performance of the RF model was significantly improved using metagenomic indices as inputs. Among the metagenomic data-based models, the combination of the taxonomic information with functional information of all the species achieved the highest accuracy (0.84) and increased median Kappa coefficient (0.70). Feature importance analysis was used to identify key features that could serve as indicators for sudden pollution accidents and contribute to the overall function of the river system. The bacteria Rhabdochromatium marinum, Frankia, Actinomycetia, and Competibacteraceae were the most important species, whose mean decrease Gini indices were 0.0023, 0.0021, 0.0019, and 0.0018, respectively, although their relative abundances ranged only from 0.0004 to 0.1 %. Among the top 30 important variables, functional variables constituted more than half, demonstrating the remarkable variation in the microbial functions among sites with distinct pollution sources and the key role of functionality in predicting pollution sources. Many functional indicators related to the metabolism of Mycobacterium tuberculosis, such as K24693, K25621, K16048, and K14952, emerged as significant important factors in distinguishing nitrogen pollution origins. With the shortage of pollution source data in developing regions, this suggested approach offers an economical, quick, and accurate solution to locate the origins of water nitrogen pollution using the metagenomic data of microbial communities.
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Microbiota , Contaminantes Químicos del Agua , Nitrógeno/análisis , Ríos/química , ARN Ribosómico 16S , Contaminación del Agua/análisis , Monitoreo del Ambiente , China , Contaminantes Químicos del Agua/análisisRESUMEN
Reticulum 3 (RTN3) is an endoplasmic reticulum (ER) protein that has been reported to act in neurodegenerative diseases and lipid metabolism. However, the role of RTN3 in acute kidney injury (AKI) has not been explored. Here, we employed public datasets, patient data, and animal models to explore the role of RTN3 in AKI. The underlying mechanisms were studied in primary renal tubular epithelial cells and in the HK2 cell line. We found reduced expression of RTN3 in AKI patients, cisplatin-induced mice, and cisplatin-treated HK2 cells. RTN3-null mice exhibit more severe AKI symptoms and kidney fibrosis after cisplatin treatment. Mitochondrial dysfunction was also found in cells with RTN3 knockdown or knockout. A mechanistic study revealed that RTN3 can interact with HSPA9 in kidney cells. RTN3 deficiency may disrupt the RTN3-HSPA9-VDAC2 complex and affect MAMs during ER-mitochondrion contact, which further leads to mitochondrial dysfunction and exacerbates cisplatin-induced AKI. Our study indicated that RTN3 was important in the kidney and that a decrease in RTN3 in the kidney might be a risk factor for the aggravation of AKI.
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Lesión Renal Aguda , Enfermedades Mitocondriales , Humanos , Ratones , Animales , Cisplatino/efectos adversos , Apoptosis , Lesión Renal Aguda/inducido químicamente , Riñón/metabolismo , Mitocondrias/metabolismo , Enfermedades Mitocondriales/metabolismo , Proteínas Portadoras , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismoRESUMEN
Paclitaxel is a well known anticancer compound. Its biosynthesis involves the formation of a highly functionalized diterpenoid core skeleton (baccatin III) and the subsequent assembly of a phenylisoserinoyl side chain. Despite intensive investigation for half a century, the complete biosynthetic pathway of baccatin III remains unknown. In this work, we identified a bifunctional cytochrome P450 enzyme [taxane oxetanase 1 (TOT1)] in Taxus mairei that catalyzes an oxidative rearrangement in paclitaxel oxetane formation, which represents a previously unknown enzyme mechanism for oxetane ring formation. We created a screening strategy based on the taxusin biosynthesis pathway and uncovered the enzyme responsible for the taxane oxidation of the C9 position (T9αH1). Finally, we artificially reconstituted a biosynthetic pathway for the production of baccatin III in tobacco.
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Alcaloides , Sistema Enzimático del Citocromo P-450 , Ingeniería Metabólica , Paclitaxel , Proteínas de Plantas , Taxoides , Taxus , Alcaloides/biosíntesis , Alcaloides/genética , Hidrocarburos Aromáticos con Puentes/química , Hidrocarburos Aromáticos con Puentes/metabolismo , Éteres Cíclicos/química , Éteres Cíclicos/metabolismo , Paclitaxel/biosíntesis , Taxoides/metabolismo , Taxus/enzimología , Taxus/genética , Sistema Enzimático del Citocromo P-450/química , Sistema Enzimático del Citocromo P-450/genética , Proteínas de Plantas/química , Proteínas de Plantas/genéticaRESUMEN
OBJECTIVE: To study the influence of the initial partial pressure of carbon dioxide (PaCO2) and frequency of blood gas analyses on the positivity rate and safety of apnea testing (AT). DESIGN: A prospective multicenter cohort study. SETTING: Seven teaching hospitals. PARTICIPANTS: A total of 55 patients who underwent AT. INTERVENTIONS: Patients were divided into 2 groups according to their initial PaCO2-the experimental group (≥40 mmHg, 27 patients) and the control group (<40 mmHg, 28 patients). Blood gas analysis was performed at 3, 5, and 8 minutes, and vital signs were taken. AT results and complications were compared between the groups. RESULTS: The initial PaCO2 of the experimental group was 42.8 ± 2.2 mmHg v 36.4 ± 2.9 mmHg in the controls. The AT positivity rate was 100%. The experimental group needed less time to reach the target PaCO2 than the control group (4.07 ± 1.27 minutes v 5.68 ± 2.06 minutes; p = 0.001). Twenty-six patients (96.3%) in the experimental group reached the target PaCO2 in 5 minutes v 17 in the control group (60.7%) (p = 0.001). Seven patients (12.7%) were unable to complete 8-minute disconnection due to hypotension. The experimental group had a slightly lower incidence of hypotension than the control group, but there was no statistical difference (7.4% v 17.9%, p = 0.245). CONCLUSION: Increasing the baseline PaCO2 and doing more blood gas analyses can significantly shorten the time needed for AT and improve the AT positivity rate.
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Apnea , Hipotensión , Humanos , Apnea/diagnóstico , Apnea/epidemiología , Estudios Prospectivos , Estudios de Cohortes , Análisis de los Gases de la Sangre , Dióxido de CarbonoRESUMEN
Importance: High myopia is a global concern due to its escalating prevalence and the potential risk of severe visual impairment caused by pathologic myopia. Using artificial intelligence to estimate future visual acuity (VA) could help clinicians to identify and monitor patients with a high risk of vision reduction in advance. Objective: To develop machine learning models to predict VA at 3 and 5 years in patients with high myopia. Design, Setting, and Participants: This retrospective, single-center, cohort study was performed on patients whose best-corrected VA (BCVA) at 3 and 5 years was known. The ophthalmic examinations of these patients were performed between October 2011 and May 2021. Thirty-four variables, including general information, basic ophthalmic information, and categories of myopic maculopathy based on fundus and optical coherence tomography images, were collected from the medical records for analysis. Main Outcomes and Measures: Regression models were developed to predict BCVA at 3 and 5 years, and a binary classification model was developed to predict the risk of developing visual impairment at 5 years. The performance of models was evaluated by discrimination metrics, calibration belts, and decision curve analysis. The importance of relative variables was assessed by explainable artificial intelligence techniques. Results: A total of 1616 eyes from 967 patients (mean [SD] age, 58.5 [14.0] years; 678 female [70.1%]) were included in this analysis. Findings showed that support vector machines presented the best prediction of BCVA at 3 years (R2 = 0.682; 95% CI, 0.625-0.733) and random forest at 5 years (R2 = 0.660; 95% CI, 0.604-0.710). To predict the risk of visual impairment at 5 years, logistic regression presented the best performance (area under the receiver operating characteristic curve = 0.870; 95% CI, 0.816-0.912). The baseline BCVA (logMAR odds ratio [OR], 0.298; 95% CI, 0.235-0.378; P < .001), prior myopic macular neovascularization (OR, 3.290; 95% CI, 2.209-4.899; P < .001), age (OR, 1.578; 95% CI, 1.227-2.028; P < .001), and category 4 myopic maculopathy (OR, 4.899; 95% CI, 1.431-16.769; P = .01) were the 4 most important predicting variables and associated with increased risk of visual impairment at 5 years. Conclusions and Relevance: Study results suggest that developing models for accurate prediction of the long-term VA for highly myopic eyes based on clinical and imaging information is feasible. Such models could be used for the clinical assessments of future visual acuity.
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Degeneración Macular , Miopía Degenerativa , Miopía , Enfermedades de la Retina , Baja Visión , Humanos , Femenino , Persona de Mediana Edad , Estudios de Cohortes , Estudios Retrospectivos , Inteligencia Artificial , Miopía/epidemiología , Agudeza Visual , Enfermedades de la Retina/etiología , Degeneración Macular/complicaciones , Baja Visión/etiología , Trastornos de la Visión/diagnóstico , Trastornos de la Visión/complicaciones , Tomografía de Coherencia Óptica/efectos adversos , Aprendizaje Automático , Miopía Degenerativa/complicaciones , Miopía Degenerativa/diagnósticoRESUMEN
Intestinal metabolism-related diseases, such as constipation, inflammatory bowel disease, irritable bowel syndrome, and colorectal cancer, could be associated with the dysfunction of intestinal mitochondria. The mitochondria of intestinal epithelial cells are of great significance for promoting intestinal motility and maintaining intestinal metabolism. It is necessary for the prophylaxis and therapy of intestinal metabolism-related diseases to improve mitochondrial function. We investigated the effect of 4,6-diamino-2-pyrimidinethiol-modified gold nanoparticles (D-Au NPs) on intestinal mitochondria and studied the regulatory role of D-Au NPs on mitochondria metabolism-related disease. D-Au NPs improved the antioxidation capability of mitochondria, regulated the mitochondrial metabolism, and maintained intestinal cellular homeostasis via the activation of AMPK and regulation of PGC-1α with its downstream signaling (UCP2 and DRP1), enhancing the intestinal mechanical barrier. D-Au NPs improved the intestinal mitochondrial function to intervene in the emergence of constipation, which could help develop drugs to treat and prevent mitochondrial metabolism-related diseases. Our findings provided an in-depth understanding of the mitochondrial effects of Au NPs for improving human intestinal barriers.
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Oro , Nanopartículas del Metal , Humanos , Oro/metabolismo , Nanopartículas del Metal/uso terapéutico , Ligandos , Mitocondrias , Estreñimiento/inducido químicamente , Estreñimiento/tratamiento farmacológico , Estreñimiento/metabolismoRESUMEN
The efficiency of de novo synthesis of hyaluronic acid (HA) using Pasteurella multocida hyaluronate synthase (PmHAS) is limited by its low catalytic activity during the initial reaction steps when monosaccharides are the acceptor substrates. In this study, we identified and characterized a ß-1,4-N-acetylglucosaminyl-transferase (EcGnT) derived from the O-antigen gene synthesis cluster of Escherichia coli O8:K48:H9. Recombinant ß1,4 EcGnT effectively catalyzed the production of HA disaccharides when the glucuronic acid monosaccharide derivative 4-nitrophenyl-ß-D-glucuronide (GlcA-pNP) was used as the acceptor. Compared with PmHAS, ß1,4 EcGnT exhibited superior N-acetylglucosamine transfer activity (~ 12-fold) with GlcA-pNP as the acceptor, making it a better option for the initial step of de novo HA oligosaccharide synthesis. We then developed a biocatalytic approach for size-controlled HA oligosaccharide synthesis using the disaccharide produced by ß1,4 EcGnT as a starting material, followed by stepwise PmHAS-catalyzed synthesis of longer oligosaccharides. Using this approach, we produced a series of HA chains of up to 10 sugar monomers. Overall, our study identifies a novel bacterial ß1,4 N-acetylglucosaminyltransferase and establishes a more efficient process for HA oligosaccharide synthesis that enables size-controlled production of HA oligosaccharides. KEY POINTS: ⢠A novel ß-1,4-N-acetylglucosaminyl-transferase (EcGnT) from E. coli O8:K48:H9. ⢠EcGnT is superior to PmHAS for enabling de novo HA oligosaccharide synthesis. ⢠Size-controlled HA oligosaccharide synthesis relay using EcGnT and PmHAS.
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Ácido Hialurónico , Pasteurella multocida , N-Acetilglucosaminiltransferasas/genética , Escherichia coli/genética , Oligosacáridos/química , Hialuronano Sintasas , Transferasas , Pasteurella multocida/genéticaRESUMEN
Tumor-associated macrophages (TAMs) are key components of tumor immune microenvironment and play a dual role in promoting tumor growth and anti-tumor immunity. Therefore, regulating TAMs has become a promising method in cancer immunotherapy. NF- κB pathway is the key regulatory pathway of TAMs. Targeting this pathway has shown the potential to improve tumor immune microenvironment. At present, there are still some controversies and the idea of combined therapy in this field. This article reviews the progress in the field of immunotherapy in improving tumor immune microenvironment by exploring the mechanism of regulating TAMs (including promoting M1 polarization, inhibiting M2 polarization and regulating TAMs infiltration).
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FN-kappa B , Neoplasias , Humanos , FN-kappa B/metabolismo , Macrófagos Asociados a Tumores/metabolismo , Macrófagos/metabolismo , Neoplasias/patología , Transducción de Señal , Microambiente TumoralRESUMEN
Based on 2010-2019 Chinese logistics listed companies as research samples, the paper used the binary Logit model measuring degree of financing constraints. The Kernel density function and Markov chain model are used to forecast China listed companies financing logistics dynamic constraints and business performance growth. Furthermore the stock of knowledge was chosen as a threshold variable to explore the impact of financing constraints on corporate performance growth of listed logistics enterprises. We find that the degree of financing constraints of logistics enterprises in our country has not been significantly eased. Corporate performance has not changed significantly and there are no obvious spatial gap and polarization with the passage of time. The impact of financing constraints on the corporate performance growth of logistics enterprises in China has a double threshold effect of knowledge stock, and has an inhibitory effect that first increases and then decreases. This is because in the short term, the investment of knowledge stock by enterprises can crowd out more corporate liquidity, and in the long run, it is related to the conversion rate of the knowledge stock itself. Because of the uneven regional distribution of resources and differences in the degree of economic development, there is a growing disincentive effect in central China as the stock of knowledge accumulates.
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Metal aerogels (MAs) are emerging porous materials displaying unprecedented potential in catalysis, sensing, plasmonic technologies, etc. However, the lack of efficient regulation of their nano-building blocks (NBBs) remains a big hurdle that hampers the in-depth investigation and performance enhancement. Here, by harmonizing composition and ligand effects, Pt- and Bi-based single- and bimetallic aerogels bearing NBBs of controlled dimensions and shapes are obtained by facilely tuning the metal precursors and the applied ligands. Particularly, by further modulating the electronic and optic properties of the aerogels via adjusting the content of the catalytically active Pt component and the semiconducting Bi component, both the electrocatalytic and photoelectrocatalytic performance of the Pt-Bi aerogels can be manipulated. In this light, an impressive catalytic performance for electro-oxidation of methanol is acquired, marking a mass activity of 6.4-fold higher under UV irradiation than that for commercial Pt/C. This study not only sheds light on in situ manipulating NBBs of MAs, but also puts forward guidelines for crafting high-performance MAs-based electrocatalysts and photoelectrocatalysts toward energy-related electrochemical processes.