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BACKGROUND: Previous investigations identified a connection between air pollution and kidney diseases. Nevertheless, there is a lack of comprehensive evidence on the long-term risks posed by air pollution with respect to acute kidney injury (AKI) and AKI-related death. METHODS: This prospective cohort analysis included 414,885 UK Biobank (UKB) participants who did not exhibit AKI at the study's outset. AKI was defined based on ICD-10 codes recorded for hospitalized patients. Cox proportional hazards models were used to assess the association between prolonged exposure to air pollutants (particulate matter with diameters of 2.5 micrometers or less (PM2.5), between 2.5 and 10 micrometers (PM2.5-10), and 10 micrometers or less (PM10), along with nitrogen dioxide (NO2) and nitrogen oxides (NOx)) and the risk of AKI and AKI-related death, adjusting for potential confounders including sex, age, ethnicity, education, income, lifestyle factors, and relevant clinical covariates. Restricted cubic splines were applied to evaluate non-linear dose-response relationships, and stratified analyses were performed to explore potential effect modification across subgroups. RESULTS: Over an average follow-up duration of 11.7 years, 14,983 cases of AKI and 326 cases of AKI-related death were diagnosed. Quartile analysis showed individuals exposed to higher levels of these air pollutants had a significantly higher risk of developing AKI and AKI-related death compared to those in the lowest quartile (all P < 0.05). The RCS curves depicting the relationship between PM2.5, PM2.5-10, PM10, NO2, NOx, and the risk of AKI showed a significant departure from linearity (P for non-linearity < 0.05), while the relationships between PM2.5, NO2, NOx, and the risk of AKI-related death did not exhibit a significant departure from linearity (P for non-linearity > 0.05). Sensitivity analyses confirmed the robustness of our findings. CONCLUSION: Our study reveals a direct association between prolonged air pollution exposure and elevated risks of both AKI and AKI-related death. These findings offer scientific validation for the adoption of environmental and public health measures directed towards the reduction of air pollution. Such initiatives could potentially ease the impact associated with AKI and AKI-related death.
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Lesión Renal Aguda , Contaminación del Aire , Exposición a Riesgos Ambientales , Material Particulado , Humanos , Masculino , Lesión Renal Aguda/mortalidad , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Femenino , Estudios Prospectivos , Persona de Mediana Edad , Reino Unido/epidemiología , Contaminación del Aire/efectos adversos , Contaminación del Aire/análisis , Anciano , Exposición a Riesgos Ambientales/efectos adversos , Material Particulado/análisis , Material Particulado/efectos adversos , Hospitalización/estadística & datos numéricos , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Adulto , Bancos de Muestras Biológicas , Factores de Riesgo , Estudios de Casos y Controles , Modelos de Riesgos Proporcionales , Biobanco del Reino UnidoRESUMEN
Background: Gut microbiota have been previously reported to be related to a variety of immune diseases. However, the causal connection between Sjögren's syndrome (SS) and gut microbiota has yet to be clarified. Methods: We employed a two-sample Mendelian randomization (MR) analysis to evaluate the causal connection between gut microbiota and SS, utilizing summary statistics from genome-wide association studies (GWASs) obtained from the MiBioGen and FinnGen consortia. The inverse variance weighted (IVW) approach represents the primary method of Mendelian randomization (MR) analysis. Sensitivity analysis was used to eliminate instrumental variables heterogeneity and horizontal pleiotropy. In addition, we performed an analysis using independent GWAS summary statistics for SS from the European Bioinformatics Institute (EBI) dataset for further verify our results. Results: IVW results demonstrated that the phylum Lentisphaerae (OR = 0.79, 95% CI: 0.63-0.99, p = 0.037), class Deltaproteobacteria (OR = 0.67, 95% CI: 0.47-0.96, p = 0.030), family Porphyromonadaceae (OR = 0.60, 95% CI: 0.38-0.94, p = 0.026), genus Eubacterium coprostanoligenes group (OR = 0.61, 95% CI: 0.4-0.93, p = 0.021), genus Blautia (OR = 0.62, 95% CI: 0.43-0.90, p = 0.012), genus Butyricicoccus (OR = 0.61, 95% CI: 0.42-0.90, p = 0.012), genus Escherichia.Shigella (OR = 0.7, 95% CI: 0.49-0.99, p = 0.045) and genus Subdoligranulum (OR = 0.61, 95% CI: 0.44-0.86, p = 0.005) exhibited protective effects on SS. Relevant heterogeneity of horizontal pleiotropy or instrumental variables was not detected. Furthermore, repeating our results with an independent cohort provided by the EBI dataset, only the genus Eubacterium coprostanoligenes group remained significantly associated with the protective effect on SS (OR = 0.41, 95% CI: 0.18-0.91, p = 0.029). Two-step MR analysis further revealed that genus Eubacterium coprostanoligenes group exerts its protective effect by reducing CXCL6 levels in SS (OR, 0.87; 95% CI = 0.76-0.99, p = 0.033). Conclusions: Our study using two-sample MR analysis identified a causal association between multiple genera and SS. A two-step MR result calculated that genus Eubacterium coprostanoligenes group mediated its protective effect by reducing CXCL6 levels in SS. However, the datasets available from the MiBioGen and FinnGen consortia do not provide sufficient information or comprehensive demographic data for subgroup analyses. Additional validation using various omics technologies is necessary to comprehend the development of SS in the intricate interplay between genes and the environment over a period of time.
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BACKGROUND: The epidemiological evidence regarding the correlation between air pollution, residential greenspace, and the risk of kidney stone disease (KSD) is limited, with no large-scale prospective studies conducted on this relationship. OBJECTIVE: We conducted a large-scale prospective study from the UK Biobank to explore the correlation between air pollution, residential greenspace, and the risk of KSD. METHODS: This study included 419,835 UK Biobank participants who did not have KSD at baseline. An air pollution score was derived through the summation of concentrations for five air pollutants, including particulate matter (PM) with aerodynamic diameter ≤2.5 µm (PM2.5), ranging from 2.5 to 10 µm (PM2.5-10), ≤10 µm (PM10), nitrogen dioxide (NO2), and nitrogen oxides (NOx). Various covariates were adjusted for in Cox proportional hazard regression to evaluate the risk of KSD associated with air pollution score, single air pollutant, and residential greenspace. RESULTS: During a follow-up period of 12.7 years, 4503 cases of KSD were diagnosed. Significant associations were found between KSD risk and air pollution score (HR: 1.08, 95% CI: 1.03-1.13), PM2.5 (1.06, 1.02-1.11), PM10 (1.04, 1.01-1.07), NO2 (1.09, 1.02-1.16), NOx (1.08, 1.02-1.11), greenspace buffered at 300 m (0.95, 0.91-0.99), and greenspace buffered at 1000 m (0.92, 0.86-0.98) increase per interquartile range (IQR). PM2.5 and NO2 reductions may be a key mechanism for the protective impact of residential greenspace on KSD (P for indirect path < 0.05). IMPACT: Prolonged exposure to air pollution was correlated with a higher risk of KSD, while residential greenspace exhibits an inverse association with KSD risk, partially mediated by the reduction in air pollutants concentrations. These findings emphasize the significance of mitigating air pollution and maintaining substantial greenspace exposure as preventive measures against KSD.
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The utilization of electroporation for delivering CRISPR/Cas9 system components has enabled efficient gene editing in mammalian zygotes, facilitating the development of genome-edited animals. In this study, our research focused on targeting the ACTG1 and MSTN genes in sheep, revealing a threshold phenomenon in electroporation with a voltage tolerance in sheep in vitro fertilization (IVF) zygotes. Various poring voltages near 40 V and pulse durations were examined for electroporating sheep zygotes. The study concluded that stronger electric fields required shorter pulse durations to achieve the optimal conditions for high gene mutation rates and reasonable blastocyst development. This investigation also assessed the quality of Cas9/sgRNA ribonucleoprotein complexes (Cas9 RNPs) and their influence on genome editing efficiency in sheep early embryos. It was highlighted that pre-complexation of Cas9 proteins with single-guide RNA (sgRNA) before electroporation was essential for achieving a high mutation rate. The use of suitable electroporation parameters for sheep IVF zygotes led to significantly high mutation rates and heterozygote ratios. By delivering Cas9 RNPs and single-stranded oligodeoxynucleotides (ssODNs) to zygotes through electroporation, targeting the MSTN (Myostatin) gene, a knock-in efficiency of 26% was achieved. The successful generation of MSTN-modified lambs was demonstrated by delivering Cas9 RNPs into IVF zygotes via electroporation.
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Sistemas CRISPR-Cas , Electroporación , Fertilización In Vitro , Edición Génica , ARN Guía de Sistemas CRISPR-Cas , Ribonucleoproteínas , Cigoto , Animales , Edición Génica/métodos , Electroporación/métodos , Cigoto/metabolismo , Fertilización In Vitro/métodos , Ribonucleoproteínas/genética , Ribonucleoproteínas/metabolismo , ARN Guía de Sistemas CRISPR-Cas/genética , Ovinos , Proteína 9 Asociada a CRISPR/metabolismo , Proteína 9 Asociada a CRISPR/genética , Miostatina/genética , Femenino , Animales Modificados GenéticamenteRESUMEN
Background: Prematurity presents a significant life crisis for families, often exceeding their expectations. Fathers of premature infants face the burden of multiple caregiving roles and undergo psychological changes. When confronted with such crises, individuals often engage in self-evaluation and may experience positive transformations. This study aims to employ a qualitative research methodology to explore the experiences of fathers of preterm infants. Materials and methods: A phenomenological approach design will be utilized, drawing upon semi-structured in-depth interviews informed by existing literature. Thematic analysis will be employed, adhering to the Consolidated Criteria for Reporting Qualitative Research (COREQ) guidelines. In-depth individual interviews, lasting 40-60 minutes, will be conducted with fathers of preterm infants to understand their experiences. The thematic analysis process will facilitate a comprehensive understanding of the factors contributing to post-traumatic growth among these fathers. This methodology provides a structured approach to investigating the experiences and influences on post-traumatic growth in fathers of preterm infants. Results: This study will highlight changes in post-traumatic growth among fathers of preterm infants. Discussion: Research on the post-traumatic growth (PTG) of fathers of preterm infants is crucial to understanding the unique challenges and psychological transformations they experience. This study aims to explore the factors contributing to PTG in these fathers and how cultural contexts in China influence this process. By elucidating these aspects, the findings can inform targeted interventions and support systems tailored to the needs of fathers of preterm infants. The results may also contribute to developing guidelines and policies to promote psychological well-being and resilience among this population in the healthcare system. Ethics and dissemination: This study adheres to the International Ethical Guidelines for Biomedical Research and the Declaration of Helsinki. Approval has been obtained from the People's Hospital of Deyang Human Research Ethics Committee (No: 2019-04-150-K01). The research follows the principles of open science, and the findings will be published while ensuring participants' confidentiality.
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Osimertinib is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (EGFR-TKI) approved for patients with EGFR T790M resistance mutations as first- or second-line treatment of EGFR-positive patients. Resistance to Osimertinib will inevitably develop, and the underlying mechanisms are largely unknown. In this study, we discovered that acquired resistance to Osimertinib is associated with abnormal DNA damage response (DDR) in lung adenocarcinoma cells. We discovered that the polycomb protein Lethal(3) Malignant Brain Tumor-Like Protein 1 (L3MBTL1) regulates chromatin structure, thereby contributing to DDR and Osimertinib resistance. EGFR oncogene inhibition reduced L3MBTL1 ubiquitination while stabilizing its expression in Osimertinib-resistant cells. L3MBTL1 reduction and treatment with Osimertinib significantly inhibited DDR and proliferation of Osimertinib-resistant lung cancer cells in vitro and in vivo. L3MBTL1 binds throughout the genome and plays an important role in EGFR-TKI resistance. It also competes with 53BP1 for H4K20Me2 and inhibits the development of drug resistance in Osimertinib-resistant lung cancer cells in vitro and in vivo. Our findings suggest that L3MBTL1 inhibition is a novel approach to overcoming EGFR-TKI-acquired resistance.
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Acrilamidas , Adenocarcinoma del Pulmón , Compuestos de Anilina , Daño del ADN , Resistencia a Antineoplásicos , Epigénesis Genética , Receptores ErbB , Neoplasias Pulmonares , Humanos , Acrilamidas/farmacología , Resistencia a Antineoplásicos/genética , Resistencia a Antineoplásicos/efectos de los fármacos , Compuestos de Anilina/farmacología , Compuestos de Anilina/uso terapéutico , Adenocarcinoma del Pulmón/genética , Adenocarcinoma del Pulmón/tratamiento farmacológico , Adenocarcinoma del Pulmón/patología , Adenocarcinoma del Pulmón/metabolismo , Daño del ADN/efectos de los fármacos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/metabolismo , Epigénesis Genética/efectos de los fármacos , Animales , Línea Celular Tumoral , Receptores ErbB/metabolismo , Receptores ErbB/genética , Ratones , Proteínas del Grupo Polycomb/metabolismo , Proteínas del Grupo Polycomb/genética , Ratones Desnudos , Proteína 1 de Unión al Supresor Tumoral P53/metabolismo , Proteína 1 de Unión al Supresor Tumoral P53/genética , Inhibidores de Proteínas Quinasas/farmacología , Proliferación Celular/efectos de los fármacos , Ubiquitinación/efectos de los fármacos , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Indoles , PirimidinasRESUMEN
Calcium oxalate (CaOx) kidney stones are common and recurrent, lacking pharmacological prevention. Randall's plaques (RPs), calcium deposits in renal papillae, serve as niduses for some CaOx stones. This study explores the role of osteogenic-like cells in RP formation resembling ossification. CaP crystals deposit around renal tubules, interstitium, and blood vessels in RP tissues. Human renal interstitial fibroblasts (hRIFs) exhibit the highest osteogenic-like differentiation potential compared to chloride voltage-gated channel Ka positive tubular epithelial cells, aquaporin 2 positive collecting duct cells, and vascular endothelial cells, echoing the upregulated osteogenic markers primarily in hRIFs within RP tissues. Utilizing RNA-seq, osteomodulin (OMD) is found to be upregulated in hRIFs within RP tissues and hRIFs following osteogenic induction. Furthermore, OMD colocalizes with CaP crystals and calcium vesicles within RP tissues. OMD can enhance osteogenic-like differentiation of hRIFs in vitro and in vivo. Additionally, crystal deposits are attenuated in mice with Omd deletion in renal interstitial fibroblasts following CaOx nephrocalcinosis induction. Mechanically, a positive feedback loop of OMD/BMP2/BMPR1A/RUNX2/OMD drives hRIFs to adopt osteogenic-like fates, by which OMD induces osteogenic-like microenvironment of renal interstitium to participate in RP formation. We identify OMD upregulation as a pathological feature of RP, paving the way for preventing CaOx stones.
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Elucidating the genetic architecture of DNA methylation (DNAm) is crucial for decoding the etiology of complex diseases. However, current epigenomic studies often suffer from incomplete coverage of methylation sites and the use of tissues containing heterogeneous cell populations. To address these challenges, we present a comprehensive human methylome atlas based on deep whole-genome bisulfite sequencing (WGBS) and whole-genome sequencing (WGS) of purified monocytes from 298 European Americans (EA) and 160 African Americans (AA) in the Louisiana Osteoporosis Study. Our atlas enables the analysis of over 25 million DNAm sites. We identified 1,383,250 and 1,721,167 methylation quantitative trait loci (meQTLs) in cis -regions for EA and AA populations, respectively, with 880,108 sites shared between ancestries. While cis -meQTLs exhibited population-specific patterns, primarily due to differences in minor allele frequencies, shared cis -meQTLs showed high concordance across ancestries. Notably, cis -heritability estimates revealed significantly higher mean values in the AA population (0.09) compared to the EA population (0.04). Furthermore, we developed population-specific DNAm imputation models using Elastic Net, enabling methylome-wide association studies (MWAS) for 1,976,046 and 2,657,581 methylation sites in EA and AA, respectively. The performance of our MWAS models was validated through a systematic multi-ancestry analysis of 41 complex traits from the Million Veteran Program. Our findings bridge the gap between genomics and the monocyte methylome, uncovering novel methylation-phenotype associations and their transferability across diverse ancestries. The identified meQTLs, MWAS models, and data resources are freely available at www.gcbhub.org and https://osf.io/gct57/ .
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The rapid transport kinetics of divalent magnesium ions are crucial for achieving distinguished performance in aqueous magnesium-ion battery-based energy storage capacitors. However, the strong electrostatic interaction between Mg2+ with double charges and the host material significantly restricts Mg2+ diffusivity. In this study, a new composite material, EDA-Mn2O3, with double-energy storage mechanisms comprising an organic phase (ethylenediamine, EDA) and an inorganic phase (manganese sesquioxide) was successfully synthesized via an organic-inorganic coupling strategy. Inorganic-phase Mn2O3 serves as a scaffold structure, enabling the stable and reversible intercalation/deintercalation of magnesium ions. The organic phase EDA adsorbed onto the surface of Mn2O3 as an elastic matrix, works synergistically with Mn2O3, and utilizes bidentate chelating ligands to capture Mg2+. The robust coordination effect of terminal biprotonic amine in EDA enhances the structural diversity and specific capacity characteristics of the composite material, as further corroborated by density functional theory (DFT) calculations, ex situ XRD, XPS, and Raman spectroscopy. As expected, the EDA-Mn2O3 composite achieved an outstanding specific discharge capacity of 188.97â mAh/g at 0.1â A/g. Additionally, an aqueous magnesium ion capacitor with EDA-Mn2O3 serving as the cathode can reach 110.17â Wh/kg, which stands out among the aqueous magnesium ion capacitors that have been reported thus far. The abundant reversible redox sites are ensured by the strategic design concept based on the synergistic structure and composition advantages of organic and inorganic phases. This study aimed to explore the practical application value of organic-inorganic composite electrodes with double-energy storage mechanisms.
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Introduction: Human cytomegalovirus (HCMV) is the most common viral infection seen in newborns. The major route of transmission for acquired human cytomegalovirus infection is breast milk from mothers who are HCMV seropositive to the infants. Thus, a rapid, economical, and simple method to perform HCMV test in breast milk is crucial and necessary for preventing acquired HCMV infection, especially in underdeveloped regions with limited laboratory resources. Methods: In this study, an effective technique for the detection of HCMV was constructed by combining multienzyme isothermal rapid amplification (MIRA) and lateral flow chromatography strip (LFD). Primers for the conserved HCMV sequence UL83 were utilized for MIRA-LFD testing. Results: Our results showed that the entire MIRA reaction could be completed in 12 minutes at 37°C, and LFD outcomes could be observed visibly after 10 minutes. The detection sensitivity of this method reached 50 copy/µl. Samples of breast milk were examined to compare MIRA-LFD and conventional qPCR. The accuracy of MIRA-LFD was 100%. Discussion: The straightforward, rapid, economic features of the test can provide the significant advantages for the prevention of breast milk-acquired cytomegalovirus infection, particularly in resource-limited locations with high seroprevalence of cytomegalovirus.
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Infecciones por Citomegalovirus , Citomegalovirus , Leche Humana , Técnicas de Diagnóstico Molecular , Técnicas de Amplificación de Ácido Nucleico , Sensibilidad y Especificidad , Humanos , Citomegalovirus/genética , Citomegalovirus/aislamiento & purificación , Leche Humana/virología , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/virología , Técnicas de Amplificación de Ácido Nucleico/métodos , Técnicas de Diagnóstico Molecular/métodos , Femenino , Recién Nacido , Factores de TiempoRESUMEN
The ability of Deinococcus bacteria to survive in harsh environments, such as high radiation, extreme temperature, and dryness, is mainly attributed to the generation of unique pigments, especially carotenoids. Although the limited number of natural pigments produced by these bacteria restricts their industrial potential, metabolic engineering and synthetic biology can significantly increase pigment yield and expand their application prospects. In this study, we review the properties, biosynthetic pathways, and functions of key enzymes and genes related to these pigments and explore strategies for improving pigment production through gene editing and optimization of culture conditions. Additionally, studies have highlighted the unique role of these pigments in antioxidant activity and radiation resistance, particularly emphasizing the critical functions of deinoxanthin in D. radiodurans. In the future, Deinococcus bacterial pigments will have broad application prospects in the food industry, drug production, and space exploration, where they can serve as radiation indicators and natural antioxidants to protect astronauts' health during long-term space flights.
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Randall's plaques (RP) serve as anchoring sites for calcium oxalate (CaOx) stones, but the underlying mechanism remains unclear. Renal interstitium with a high-calcium environment is identified as pathogenesis of RP formation where the role of human renal interstitial fibroblasts (hRIFs) was highlighted. Our study aims to elucidate the potential mechanism by which a high-calcium environment drives ectopic calcification of hRIFs to participate in RP formation. Alizarin Red staining demonstrated calcium nodules in hRIFs treated with high-calcium medium. Utilizing transcriptome sequencing, tissue factor pathway inhibitor-2 (TFPI-2) was found to be upregulated in high-calcium-induced hRIFs and RP tissues, and TFPI-2 promoted high-calcium-induced calcification of hRIFs. Subsequently, the downstream regulator of TFPI2 was screened by transcriptome sequencing analysis of hRIFs with TFPI-2 knockdown or overexpressed. Dachsous Cadherin Related 1 (DCHS1) knockdown was identified to suppress the calcification of hRIFs enhanced by TFPI-2. Further investigation revealed that TFPI-2/DCHS1 axis promoted high-calcium-induced calcification of hRIFs via disturbing the balance of ENPP1/ALP activities, but without effect on the canonical osteogenic markers, such as osteopontin (OPN), osteogenic factors runt-related transcription factor 2 (RUNX2), bone morphogenetic protein 2 (BMP2). In summary, our study mimicked the high-calcium environment observed in CaOx stone patients with hypercalciuria, and discovered that the high-calcium drove ectopic calcification of hRIFs via a novel TFPI-2-DCHS1-ALP/ENPP1 pathway rather than adaption of osteogenic phenotypes to participate in RP formation.
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Calcinosis , Fibroblastos , Glicoproteínas , Humanos , Calcinosis/patología , Calcinosis/metabolismo , Fibroblastos/metabolismo , Fibroblastos/patología , Glicoproteínas/metabolismo , Glicoproteínas/genética , Calcio/metabolismo , Riñón/patología , Riñón/metabolismo , Fosfatasa Alcalina/metabolismo , Cálculos Renales/metabolismo , Cálculos Renales/patología , Cálculos Renales/etiología , Cálculos Renales/genética , Células CultivadasRESUMEN
Diagnosing liver lesions is crucial for treatment choices and patient outcomes. This study develops an automatic diagnosis system for liver lesions using multiphase enhanced computed tomography (CT). A total of 4039 patients from six data centers are enrolled to develop Liver Lesion Network (LiLNet). LiLNet identifies focal liver lesions, including hepatocellular carcinoma (HCC), intrahepatic cholangiocarcinoma (ICC), metastatic tumors (MET), focal nodular hyperplasia (FNH), hemangioma (HEM), and cysts (CYST). Validated in four external centers and clinically verified in two hospitals, LiLNet achieves an accuracy (ACC) of 94.7% and an area under the curve (AUC) of 97.2% for benign and malignant tumors. For HCC, ICC, and MET, the ACC is 88.7% with an AUC of 95.6%. For FNH, HEM, and CYST, the ACC is 88.6% with an AUC of 95.9%. LiLNet can aid in clinical diagnosis, especially in regions with a shortage of radiologists.
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Carcinoma Hepatocelular , Colangiocarcinoma , Aprendizaje Profundo , Hemangioma , Neoplasias Hepáticas , Tomografía Computarizada por Rayos X , Humanos , Neoplasias Hepáticas/diagnóstico por imagen , Carcinoma Hepatocelular/diagnóstico por imagen , Tomografía Computarizada por Rayos X/métodos , Masculino , Hemangioma/diagnóstico por imagen , Colangiocarcinoma/diagnóstico por imagen , Colangiocarcinoma/patología , Femenino , Hígado/diagnóstico por imagen , Hígado/patología , Persona de Mediana Edad , Hiperplasia Nodular Focal/diagnóstico por imagen , Adulto , Anciano , Área Bajo la Curva , Quistes/diagnóstico por imagenRESUMEN
Deoxynivalenol-3-glucoside (D3G), the masked form of the important mycotoxin deoxynivalenol (DON), displays potential toxicity but is difficult to control owing to the lack of rapid detection methods. Herein, an innovative molecularly imprinted polymer (MIP)-based electrochemical sensor was developed for the rapid detection of D3G. MIP, an efficient recognition element for D3G, was electropolymerized using o-phenylenediamine based on a surface functional monomer-directing strategy for the first time. CeO2, which contains both Ce3+ and Ce4+ oxidation states, was introduced as a nanozyme to catalyze H2O2 reduction, while Mn doping generated more oxygen vacancies and considerably improved the catalytic activity. Mn-CeO2 also served as a promising substrate material because of its large surface area and excellent conductivity. Under optimal conditions, a good linear relationship was observed for D3G detection over the concentration range of 0.01-50 ng/mL. The proposed sensor could detect D3G down to 0.003 ng/mL with excellent selectivity, even distinguishing its precursor DON in complex samples. The sensor exhibited acceptable stability with high reproducibility and accuracy, and could successfully determine D3G in grain samples. To the best of our knowledge, this is the first electrochemical sensing platform for rapid D3G detection that can easily be expanded to other masked mycotoxins.
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Cerio , Técnicas Electroquímicas , Manganeso , Tricotecenos , Tricotecenos/análisis , Tricotecenos/química , Cerio/química , Manganeso/química , Polímeros Impresos Molecularmente/química , Impresión Molecular , Polímeros/química , Reproducibilidad de los Resultados , Grano Comestible/química , Límite de Detección , Glucósidos/química , Glucósidos/análisis , Contaminación de Alimentos/análisis , Peróxido de Hidrógeno/química , Peróxido de Hidrógeno/análisisRESUMEN
BACKGROUND: Previous studies have linked kidney stone disease (KSD) with depression, but there are no reports on the relationship between anxiety and KSD, and the mechanism underlying the potential relationship remains unclear. METHODS: Associations of anxiety and incident KSD were assessed in the National Health and Nutrition Examination Survey (NHENES) using multivariate logistic regression. Two-sample bidirectional Mendelian randomization studies and a two-step two-sample MR was used to estimate the mediating factors that influence KSD risk. RESULTS: Examinations of NHANES data revealed that a rise in the frequency and intensity of anxiety were independently associated with incident KSD. In MR analysis, anxiety (uk-a-51 and uk-b-6519) were from the UK Biobank, with sample sizes of 328,717 and 450,765 respectively. KSD data were from the FinnGen, including 8597 cases and 333,128 controls. In the IVW analysis, genetically predicted anxieties (ukb-a-51 and ukb-b-6519) were found to be causally associated with a higher risk of KSD, with odds ratios of 6.18 (95 % CI 2.54-15.04) and 3.44 (95 % CI 1.67-7.08), respectively. There were no reverse causal effects. Further mediation analysis indicated that anxiety increases the risk of KSD by raising eGFR, through which 11.8 % of the effect of anxiety on KSD risk was mediated. LIMITATIONS: The research was confined to individuals of European heritage, and there could be specific genetic variances among diverse ethnicities. CONCLUSION: The current study suggests anxiety as an independent causal risk factor for KSD and unveils a new pathogenic mechanism, showing that anxiety raises eGFR, thereby increasing the risk of KSD.
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Ansiedad , Receptores ErbB , Cálculos Renales , Análisis de la Aleatorización Mendeliana , Humanos , Cálculos Renales/genética , Cálculos Renales/epidemiología , Masculino , Femenino , Ansiedad/epidemiología , Persona de Mediana Edad , Receptores ErbB/genética , Adulto , Factores de Riesgo , Encuestas Nutricionales , AncianoRESUMEN
A hydrophobic Cu2O cathode (CuxO-L) was designed to solve the challenge of low oxidation ability in electro-Fenton (EF) for treating emerging pollutants. This fabrication process involved forming Cu(OH)2 nanorods by oxidizing copper foam (Cu-F) with (NH4)2S2O8, followed by coating them with glucose via hydrothermal treatment. Finally, a self-assembled monolayer of 1-octadecanethiol was introduced to create a low-surface-energy, functionalized CuxO-L cathode. Results exhibited an approximately 7.9-fold increase in hydroxyl radical (·OH) generation compared to the initial Cu-F. This enhancement was attributed to two key factors: (â ) the superior O2-capturing ability of CuxO-L cathode, which led to high H2O2 production due to a 2 nm thick hydrophobic gas layer facilitated O2-capturing; (â ¡) a relative high concentration of Cu+ at the CuxO-L cathode promoted the activation of H2O2 into·OH. In addition, the performance of EF with the CuxO-L cathode using sulfathiazole (STZ) as a model pollutant was evaluated. This study offers valuable insights into the design of O2-capturing cathodes in EF processes, particularly for treating emerging organic pollutants.
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The dehydrocoupling reaction between alcohols and hydrosilanes is considered to be one of the most atom-economical ways to produce Si-O coupling compounds because its byproduct is only hydrogen (H2), which make it extremely environmentally friendly. In past decades, various kinds of homogeneous catalysts for the dehydrocoupling of alcohols and hydrosilanes, such as transition metal complexes, alkaline earth metals, alkali metals, and noble metal complexes, have been reported for their good activity and selectivity. Nevertheless, the practical applications of these catalysts still remain unsatisfactory, which is mainly restricted by environmental impact and non-reusability. A facile and recyclable heterogeneous catalyst, ultra-small Ag nanoparticles supported on porous carbon (Ag/C) for the etherification of silanes, has been developed. It has high catalytic activity for the Si-O coupling reaction, and the apparent activation energy of the reaction is about 30 kJ/mol. The ultra-small Ag nanoparticles dispersed in the catalyst through the carrier C have an enrichment effect on all reactants, which makes the reactants reach the adsorption saturation state on the surface of Ag nanoparticles, thus accelerating the coupling reaction process and verifying that the kinetics of the reaction of the catalyst indicate a zero-grade reaction.
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Chitosan and its derivatives are ideal nasal vaccine adjuvant to deliver antigens to immune cells. Previously, we successfully used a chitosan derivative, O-(2-Hydroxyl) propyl-3-trimethyl ammonium chitosan chloride (O-HTCC), and a ß-glucan derivative, curdlan sulfate (CS), to prepare a nanoparticle adjuvant CS/O-HTCC which could deliver ovalbumin to antigen presenting cells (APCs) through nasal inhalation. In this article, we used SARS-CoV-2 spike receptor binding domain (S-RBD) as the antigen and CS/O-HTCC nanoparticles as the adjuvant to develop a nasal mucosal protein subunit vaccine, CS/S-RBD/O-HTCC. The humoral immunity, cell-mediated immunity and mucosal immunity induced by vaccines were evaluated. The results showed that CS/S-RBD/O-HTCC could induce desirable immunization with single or bivalent antigen through nasal inoculation, giving one booster vaccination with mutated S-RBD (beta) could bring about a broad cross reaction with ancestral and different mutated S-RBD, and vaccination of the BALB/c mice with CS/S-RBD/O-HTCC containing S-RBD mix antigens (ancestral and omicron) could induce the production of binding and neutralizing antibodies against both of the two antigens. Our results indicate that CS/O-HTCC is a promising nasal mucosal adjuvant to prepare protein subunit vaccine for both primary and booster immunization, and the adjuvant is suitable for loading more than one antigen for preparing multivalent vaccines.
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Adyuvantes Inmunológicos , Administración Intranasal , COVID-19 , Quitosano , Ratones Endogámicos BALB C , Nanopartículas , SARS-CoV-2 , Glicoproteína de la Espiga del Coronavirus , Vacunas de Subunidad , beta-Glucanos , Quitosano/química , Animales , Nanopartículas/química , beta-Glucanos/química , beta-Glucanos/inmunología , SARS-CoV-2/inmunología , Vacunas de Subunidad/inmunología , Ratones , Glicoproteína de la Espiga del Coronavirus/inmunología , Glicoproteína de la Espiga del Coronavirus/química , Glicoproteína de la Espiga del Coronavirus/genética , Adyuvantes Inmunológicos/farmacología , COVID-19/prevención & control , COVID-19/inmunología , Femenino , Vacunas contra la COVID-19/inmunología , Vacunas contra la COVID-19/química , Anticuerpos Antivirales/inmunología , Inmunidad Mucosa/efectos de los fármacos , Mutación , Anticuerpos Neutralizantes/inmunología , Portadores de Fármacos/química , Adyuvantes de Vacunas/química , HumanosRESUMEN
Network neuroscience, especially causal brain network, has facilitated drug-resistant epilepsy (DRE) studies, while surgical success rate in patients with DRE is still limited, varying from 30% â¼ 70 %. Predicting surgical outcomes can provide additional guidance to adjust treatment plans in time for poorly predicted curative effects. In this retrospective study, we aim to systematically explore biomarkers for surgical outcomes by causal brain network methods and multicenter datasets. Electrocorticogram (ECoG) recordings from 17 DRE patients with 58 seizures were included. Ictal ECoG within clinically annotated epileptogenic zone (EZ) and non-epileptogenic zone (NEZ) were separately computed using six different algorithms to construct causal brain networks. All the brain network results were divided into two groups, successful and failed surgeries. Statistical results based on the Mann-Whitney-U-test show that: causal connectivity of α -frequency band ( 8 â¼ 13 Hz) in EZ calculated by convergent cross mapping (CCM) gains the most significant differences between the surgical success and failure groups, with a P value of 7.85e-08 and Cohen's d effect size of 0.77. CCM-defined EZ brain network can also distinguish the successful and failed surgeries considering clinical covariates (clinical centers, DRE types) with [Formula: see text]. Based on the brain network features, machine learning models were developed to predict the surgical outcomes. Among them, the SVM classifier with Gaussian kernel function and Bayesian optimization demonstrates the highest average accuracy of 84.48% by 5-fold cross-validation, further indicating that the CCM-defined EZ brain network is a reliable biomarker for predicting DRE surgical outcomes.
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Algoritmos , Epilepsia Refractaria , Electrocorticografía , Red Nerviosa , Humanos , Epilepsia Refractaria/cirugía , Epilepsia Refractaria/fisiopatología , Epilepsia Refractaria/diagnóstico por imagen , Estudios Retrospectivos , Masculino , Femenino , Electrocorticografía/métodos , Resultado del Tratamiento , Adulto , Adulto Joven , Adolescente , Red Nerviosa/fisiopatología , Encéfalo/fisiopatología , Encéfalo/diagnóstico por imagen , Niño , Aprendizaje AutomáticoRESUMEN
BACKGROUND: Differential diagnosis between benign ascites and malignant ascites remains challenging in clinical practice, the aim of our study is to determine the differential value of the ratio of ascitic-serum tumor markers between benign ascites and malignant ascites. METHODS: 418 patients with new-onset ascites were retrospectively enrolled in this study. The pertinent data of patients enrolled were collected; diagnostic value of tumor markers, ascites-serum tumor marker ratio, and diagnostic algorithm based on ascitic tumor markers and ascites-serum tumor marker ratio in patients with ascites were investigated. RESULTS: 81.25% of the patients with benign ascites had low (<1) ratio of ascites-serum tumor markers (Max [A/S CEA, A/S CA15-3, A/S CA19-9]); and 91.88% of patients with benign ascites had the ratio of ascites-serum tumor marker less than 1.5. On the other hand, 94.96% of the patients with malignant ascites had high (≥1) ratio of ascites-serum tumor markers; and 97.29% of patients with malignant ascites had the ratio of ascites-serum tumor markers more than 0.67. Finally, diagnostic algorithm based on ascitic tumor markers and ascites-serum tumor marker ratio showed 96.37% of the sensitivity, and 94.37% of the accuracy in the diagnosis of malignant ascites, while ascitic tumor markers with a sensitivity of 78.29%, and an accuracy of 84.93%. CONCLUSIONS: Diagnostic algorithm based on ascitic tumor markers and ascites-serum tumor marker ratio exhibited an excellent performance in distinguishing benign and malignant ascites, which should be recommended in patients with new-onset ascites in clinical practice.