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This study constructed an electrochemiluminescence (ECL) biosensor for ultrasensitive detection of Pb2+ in a ternary system by employing DNAzyme. The ternary system is composed of a potassium-neutralized perylene derivative (K4PTC) as the ECL emitter, K2S2O8 as the coreactant, and neodymium metal-organic frameworks (Nd-MOFs) as the coreaction accelerators. Nd-MOFs immobilize DNAzymes and enhance the luminescence intensity of the K4PTC/K2S2O8 system. As part of this system, K4PTC enhances the ECL signal in solution and supports Pb2+ detection. The sequence of ferrocene (Fc)-linked DNA (DNA-Fc) is catalytically cleaved by DNAzymes in the presence of Pb2+. This causes the removal of DNA1-Fc from the electrode surface to recover the ECL signal. As a result, the as-prepared ECL biosensor can quantify Pb2+ with a detection limit (LOD) of 4.1 fM in the range of 1 µM to 10 fM. The ECL biosensor displays high specificity, good stability, excellent reproducibility, and desirable practicality for Pb2+ detection in tap water. Moreover, by simply changing the sequence of the DNAzyme, new biosensors can be designed for ultrasensitive detection of different heavy metal ions, offering an excellent approach for monitoring water quality safety.
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Técnicas Biosensibles , ADN Catalítico , Técnicas Electroquímicas , Plomo , Mediciones Luminiscentes , Plomo/análisis , Plomo/química , Técnicas Biosensibles/métodos , ADN Catalítico/química , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , Estructuras Metalorgánicas/química , Límite de Detección , Contaminantes Químicos del Agua/análisis , Perileno/química , Perileno/análogos & derivados , Metalocenos/química , Compuestos FerrososRESUMEN
The pressing demand for large-scale energy storage solutions has propelled the development of advanced battery technologies, among which zinc-ion batteries (ZIBs) are prominent due to their resource abundance, high capacity, and safety in aqueous environments. However, the use of manganese oxide cathodes in ZIBs is challenged by their poor electrical conductivity and structural stability, stemming from the intrinsic properties of MnO2 and the destabilizing effects of ion intercalation. To overcome these limitations, our research delves into atomic-level engineering, emphasizing quantum spin exchange interactions (QSEI). These essential for modifying electronic characteristics, can significantly influence material efficiency and functionality. We demonstrate through density functional theory (DFT) calculations that enhanced QSEI in manganese oxides broadens the Oâ p band, narrows the band gap, and optimizes both proton adsorption and electron transport. Empirical evidence is provided through the synthesis of Ru-MnO2 nanosheets, which display a marked increase in energy storage capacity, achieving 314.4â mAh g-1 at 0.2â A g-1 and maintaining high capacity after 2000â cycles. Our findings underscore the potential of QSEI to enhance the performance of TMO cathodes in ZIBs, pointing to new avenues for advancing battery technology.
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Malignant tumors of the hematologic system have a high degree of malignancy and high mortality rates. Chimeric antigen receptor T cell (CAR-T) therapy has become an important option for patients with relapsed/refractory tumors, showing astonishing therapeutic effects and thus, it has brought new hope to the treatment of malignant tumors of the hematologic system. Despite the significant therapeutic effects of CAR-T, its toxic reactions, such as Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS), cannot be ignored since they can cause damage to multiple systems, including the cardiovascular system. We summarize biomarkers related to prediction, diagnosis, therapeutic efficacy, and prognosis, further exploring potential monitoring indicators for toxicity prevention. This review aims to summarize the effects of CAR-T therapy on the cardiovascular, hematologic, and nervous systems, as well as potential biomarkers, and to explore potential monitoring indicators for preventing toxicity, thereby providing references for clinical regulation and assessment of therapeutic effects.
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Síndrome de Liberación de Citoquinas , Inmunoterapia Adoptiva , Humanos , Inmunoterapia Adoptiva/efectos adversos , Inmunoterapia Adoptiva/métodos , Síndrome de Liberación de Citoquinas/prevención & control , Síndrome de Liberación de Citoquinas/etiología , Síndromes de Neurotoxicidad/etiología , Síndromes de Neurotoxicidad/prevención & control , Biomarcadores , Animales , Receptores Quiméricos de Antígenos/inmunología , Neoplasias Hematológicas/terapia , Neoplasias Hematológicas/inmunología , Neoplasias/terapia , Neoplasias/inmunologíaRESUMEN
The strategic enhancement of manganese-oxygen (MnâO) covalency is a promising approach to improve the intercalation kinetics of sodium ions (Naâº) in manganese dioxide (MnO2). In this study, an augmenting MnâO covalency in MnO2 by strategically incorporating cobalt at oxygen edge-sharing Co octahedral sites is focused on. Both experimental results and density functional theory (DFT) calculations reveal an increased electron polarization from oxygen to manganese, surpassing that directed toward cobalt, thereby facilitating enhanced electron transfer and strengthening covalency. The synthesized Co-MnO2 material exhibits outstanding electrochemical performance, demonstrating a superior specific capacitance of 388 F g-1 at 1 A g-1 and maintaining 97.21% capacity retention after 12000 cycles. Additionally, an asymmetric supercapacitor constructed using Co-MnO2 achieved a high energy density of 35 Wh kg-1 at a power density of 1000 W kg-1, underscoring the efficacy of this material in practical applications. This work highlights the critical role of transition metal-oxygen interactions in optimizing electrode materials and introduces a robust approach to enhance the functional properties of manganese oxides, thereby advancing high-performance energy storage technologies.
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An ultrasensitive self-powered biosensor is constructed for miRNA-21 detection based on Au nanoparticles @ Pd nanorings (Au NPs@Pd NRs) and catalytic hairpin assembly (CHA). The Au NPs@Pd NRs possess excellent electrical conductivity to improve the electron transfer rate and show good elimination of byproduct H2O2 to assist glucose oxidase (GOD) to catalyze glucose; CHA is used as an amplification strategy to effectively enhance the sensitivity of the biosensor. To further amplify the output signal, a capacitor is integrated into the self-powered biosensor. With multiple signal amplification strategies, the self-powered biosensor possesses a linear range of 0.1-10-4 fM and a lower limit of detection (LOD) of 0.032 fM (S/N = 3). In addition, the as-prepared self-powered biosensor displays potential applicability in the assay toward miRNA-21 in human serum samples.
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Técnicas Biosensibles , Glucosa Oxidasa , Oro , Nanopartículas del Metal , MicroARNs , Paladio , MicroARNs/análisis , MicroARNs/sangre , Técnicas Biosensibles/métodos , Oro/química , Nanopartículas del Metal/química , Humanos , Catálisis , Paladio/química , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Límite de Detección , Técnicas Electroquímicas , Glucosa/análisis , Peróxido de Hidrógeno/químicaRESUMEN
A triple signal amplification strategy was integrated with a built-in double electrode and external energy storage device to fabricate a novel self-powered biosensor for ultrasensitive detection of miRNA-21. Specifically, DNA tetrahedra and haripin2-glucose oxidase are modified on the surface of the biocathode and bioanode by catalytic hairpin assembly (CHA) to achieve dual signal amplification. Moreover, triple signal amplification is realized by including an external capacitor. Consequently, the as-constructed self-powered biosensor demonstrates a low detection limit of 0.06 fM toward the miRNA-21 assay within the range of 0.1 fM to 10 pM. This study presents a practical and sensitive approach to timely cancer detection.
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Técnicas Biosensibles , Glucosa Oxidasa , MicroARNs , MicroARNs/análisis , Técnicas Biosensibles/métodos , Humanos , Glucosa Oxidasa/química , Glucosa Oxidasa/metabolismo , Técnicas Electroquímicas/métodos , Límite de Detección , Electrodos , ADN/química , ADN/genética , Técnicas de Amplificación de Ácido NucleicoRESUMEN
BACKGROUND: To develop and evaluate a nomogram for predicting impacted ureteral stones using some simple and easily available clinical features. METHODS: From June 2019 to July 2022, 480 patients who underwent ureteroscopic lithotripsy (URSL) for ureteral calculi were enrolled in the study. From the eligible study population between June 2019 and December 2020, a training and validation set was randomly generated in a 7:3 ratio. To further evaluate the generalization performance of the nomogram, we performed an additional validation using the data from January 2021 to July 2022. Lasso regression analysis was used to identify the most useful predictive features. Subsequently, a multivariate logistic regression algorithm was applied to select independent predictive features. The predictive performance of the nomogram was assessed using Receiver Operating Characteristic (ROC) curves, calibration curves and decision Curve Analysis (DCA). The Hosmer-Lemeshow Test was utilized to evaluate the overall goodness of fit of the nomogram. RESULTS: Multivariate logistic regression analysis showed that flank pain, hydronephrosis, stone length/width, HU below (Hounsfield unit density of the ureter center below the stone), HU above/below (HU above divided by HU below) and UWT (ureteral wall thickness) were ascertained as independent predictors of impacted ureteral stones. The nomogram showed outstanding performance within the training dataset, with the area under the curve (AUC) of 0.907. Moreover, the AUC was 0.874 in the validation dataset. The ROC curve, calibration curve, DCA curve and Hosmer-Lemeshow Test suggested that the nomogram maintains excellent clinical applicability and demonstrates commendable performance. Similar results were achieved in the test dataset as well. CONCLUSIONS: We established a nomogram that can be effectively used for preoperative diagnosis of impacted ureteral stones, which is of great significance for the treatment of this disease.
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Multitarget assay has always been a hot topic in electrochemiluminescence (ECL) methods. Herein, a "on-off-on" ECL aptasensor was developed for the ultrasensitive and sequential detection of possible biological warfare agents, deoxynivalenol (DON) and abrin (ABR). As a luminophore, polymer dots (Pdots) with aggregation-induced emission exhibit high ECL efficiency in the aptasensor, i.e., the signal "on" state. The DON assays mainly depend on ECL quenching due to the efficient quenching effect between ferrocene-H2-ferrocene (Fc-H2-Fc) and Pdots, i.e., the signal "off" state. When the aptasensor is incubated with the oligonucleotide sequence S2 to replace Fc-H2-Fc, obvious ECL recovery occurs, i.e., the signal "on" state, which can be used to sequentially detect ABR. The limit of detection (LOD) for DON is 0.73 fg·mL-1 in the range of 5.0 to 50 ng·mL-1; and the LOD for ABR is â¼0.38 pg·mL-1 in the range of 1.25 pg·mL-1 to 1.25 µg·mL-1. The as-designed ECL aptasensor exhibits good stability and reproducibility, high specificity, and favorable practicality. Therefore, this work provides a new approach for assays of DON and ABR in food safety and can be used as a model to design an ultrasensitive ECL biosensor for multitarget detection.
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Técnicas Biosensibles , Técnicas Electroquímicas , Mediciones Luminiscentes , Polímeros , Puntos Cuánticos , Tricotecenos , Técnicas Biosensibles/métodos , Mediciones Luminiscentes/métodos , Técnicas Electroquímicas/métodos , Polímeros/química , Tricotecenos/análisis , Puntos Cuánticos/química , Abrina/análisis , Límite de Detección , Aptámeros de Nucleótidos/químicaRESUMEN
A macroscopic perspective is indispensable for understanding the intricate relationship between deubiquitinases and tumorigenesis. Proteomics has been proposed as a viable approach for elucidating the complex role of deubiquitylation in cellular progression. Instead of studying the function of a single ubiquitinase, research on a deubiquitinase family with similar catalytic core(s) may provide a new perspective for the pathological understanding of cancer. The Ubiquitin C-terminal hydrolase L (UCHL) family consists of four members: UCHL1, UCHL3, UCHL5, and BRAC1 associated protein-1 (BAP1), and they have been implicated in tumorigenesis and metastasis. Some members are considered hallmarks of intracranial lesions, colon cancer, chromatin remodeling, and histone stability. The present study uncovered an unknown correlation between the UCHL family and renal cancer. We discovered that UCHLs exhibit diverse regulatory effects in renal cancer, establishing connections between the renal cancer and truncated gene mutations, mitochondrial energetic metastasis, immune cell infiltration, and chromosomal stability of UCHLs family. Notably, we found that the increase of UCHL5 expression in renal cancer cells decreases the antigen processing and presentation of RCC tumor-infiltrating B cells. Further research identified that the expression of UCHL5 in RCC tumors is correlated with transport proteins, which led us to find that the abundance of UCHL5 in the blood of late-stage renal cell cancer patients is upregulated from 18 ng/L to 500 ng/L. Therefore, we propose that the abundance of UCHL5 in patients' blood can be a possible indicator of poor prognosis for renal cell cancer.
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Biomarcadores de Tumor , Carcinoma de Células Renales , Neoplasias Renales , Ubiquitina Tiolesterasa , Humanos , Ubiquitina Tiolesterasa/genética , Ubiquitina Tiolesterasa/metabolismo , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/patología , Pronóstico , Neoplasias Renales/genética , Neoplasias Renales/patología , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Regulación Neoplásica de la Expresión Génica , Línea Celular TumoralRESUMEN
The purpose of present work was to study the effects of permeation enhancers' two kinetic behaviors of simultaneous lateral diffusion and vertical penetration in the skin on its enhancing effect. The skin diffusion kinetics of isopropyl ester permeation enhancers were characterized by the innovative concentric tape peeling study and Raman imaging, which were quantitatively assessed through innovative parameters, namely, lateral-to-vertical penetration amount (CL-V) and lateral-to-vertical penetration distance (DL-V). The enhancement effect of permeation enhancers on drug flurbiprofen (FLU) was assessed by in vitro skin permeation tests, which were confirmed by transdermal water loss and skin resistance study. The relationship between kinetic parameters of permeation enhancers and permeation parameters of FLU was carried out by correlation analysis. The molecular mechanisms of effect of skin diffusion kinetics of permeation enhancers on drug permeation were characterized by molecular docking, modulated-temperature differential scanning calorimetry (MTDSC), Raman spectra, solid-state NMR and molecular dynamic simulation. The results indicated skin diffusion kinetics of short-chain (C8-C12) isopropyl ester permeation enhancers were governed by vertical penetration, while long-chain (C14-C18) ones were characterized by lateral spread. Quadratic correlation between CL-V and enhancement ratio of permeation-retention ratio of FLU (ERQ/R) (R2 = 0.95), DL-V and enhancement ratio of permeation area (ERA) of FLU (R2 = 0.98) indicating that varied skin diffusion kinetics of permeation enhancers directly influenced the barrier function of stratum corneum (SC) and further enhancing drug permeation. In terms of molecular mechanism, long-chain isopropyl ester enhancers had good miscibility with SC, leading to their high CL-V and DL-V, and causing strong interaction strength with SC and resulting in weaker skin barrier function for drug permeation. In summary, in comparison to short-chain isopropyl ester enhancers that relied on penetration, long-chain ones that depended on lateral spread exhibited greater enhancement efficacy, which guided the application of enhancers in transdermal formulations.
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Administración Cutánea , Ésteres , Flurbiprofeno , Permeabilidad , Absorción Cutánea , Piel , Absorción Cutánea/efectos de los fármacos , Flurbiprofeno/farmacocinética , Flurbiprofeno/administración & dosificación , Flurbiprofeno/química , Animales , Piel/metabolismo , Difusión , Ésteres/química , Cinética , Simulación del Acoplamiento Molecular , Porcinos , Masculino , Espectrometría Raman , Simulación de Dinámica MolecularRESUMEN
Novel hollow AuAg nanoboxes (AuAg NBs) were designed for an innovative electrochemiluminescence (ECL) sensor to ultrasensitively detect Pb2+ and Hg2+ with the aid of DNAzyme and "thymine-Hg2+-thymine" ("T-Hg2+-T") structure. AuAg NBs are employed as an excellent surface plasma resonance (SPR) source, as well as an effective coreaction accelerator for the CoNi NFs/S2O82- system to greatly improve ECL performance. To detect Pb2+, the DNAzyme catalyzes the cleavage of ribonucleic acid targets into numerous small nucleic acid fragments, leading to an ECL signal. When Hg2+ is added, the thymine-thymine (T-T) mismatches of the Hg2+ aptamer bind Hg2+ to form the "T-Hg2+-T" structure, which not only inhibits the SPR process but also produces a large steric hindrance, thus quenching the ECL signal and allowing quantification of Hg2+. The novel ECL sensor quantifies Pb2+ in the range of 0.1 fM to 0.1 µM with a limit of detection of 0.07 fM and Hg2+ in the range of 10 pM to 1 µM with a LOD of 4.07 pM.
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Técnicas Biosensibles , ADN Catalítico , Oro , Plomo , Mediciones Luminiscentes , Mercurio , Plata , Mercurio/análisis , Oro/química , Técnicas Biosensibles/métodos , Plomo/análisis , Plomo/química , ADN Catalítico/química , ADN Catalítico/metabolismo , Plata/química , Técnicas Electroquímicas/métodos , Resonancia por Plasmón de Superficie , Nanopartículas del Metal/química , Límite de Detección , Timina/químicaRESUMEN
Renal cell carcinoma (RCC) is one of the most prevalent types of urological cancer. Exosomes are vesicles derived from cells and have been found to promote the development of RCC, but the potential biomarker and molecular mechanism of exosomes on RCC remain ambiguous. Here, we first screened differentially expressed exosome-related genes (ERGs) by analyzing The Cancer Genome Atlas (TCGA) database and exoRBase 2.0 database. We then determined prognosis-related ERGs (PRERGs) by univariate Cox regression analysis. Gene Dependency Score (gDS), target development level, and pathway correlation analysis were utilized to examine the importance of PRERGs. Machine learning and lasso-cox regression were utilized to screen and construct a 5-gene risk model. The risk model showed high predictive accuracy for the prognosis of patients and proved to be an independent prognostic factor in three RCC datasets, including TCGA-KIRC, E-MTAB-1980, and TCGA-KIRP datasets. Patients with high-risk scores showed worse outcomes in different clinical subgroups, revealing that the risk score is robust. In addition, we found that immune-related pathways are highly enriched in the high-risk group. Activities of immune cells were distinct in high-/low-risk groups. In independent immune therapeutic cohorts, high-risk patients show worse immune therapy responses. In summary, we identified several exosome-derived genes that might play essential roles in RCC and constructed a 5-gene risk signature to predict the prognosis of RCC and immune therapy response.
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Carcinoma de Células Renales , Exosomas , Neoplasias Renales , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/inmunología , Carcinoma de Células Renales/terapia , Humanos , Exosomas/genética , Exosomas/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/inmunología , Neoplasias Renales/terapia , Pronóstico , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión Génica , Inmunoterapia , Femenino , Bases de Datos Genéticas , Masculino , Medición de Riesgo , Factores de RiesgoRESUMEN
PdPt nanosheets decorated on SnS2 nanosheets (i.e., PdPt@SnS2 NSs) were fabricated for a novel electrochemiluminescence (ECL) biosensor for ultrasensitive detection of miRNA-21 based on catalytic hairpin assembly (CHA) cycles. The PdPt@SnS2 NSs serve as both the main luminophore and a highly effective coreaction accelerator in the ECL biosensor. In the CHA cycles, more miRNA-21 is captured, and the performance of the ECL biosensor is improved. When miRNA-21 is present, the hairpin chain DNA1 (i.e., H1) is opened, and the ferrocene (Fc)-modified hairpin chain DNA2 (i.e., Fc-H2) hybridizes with as-opened H1 by replacing miRNA-21 to stimulate CHA cycles of miRNA-21. During the CHA cycles, Fc-H2 quenches the ECL signal to monitor miRNA-21. As a result, the ECL biosensor shows ultrasensitive and highly selective detection of miRNA-21 from 1 aM to 1 nM with a detection limit (LOD) of 0.02 aM. In addition, the ECL biosensor exhibits excellent practicality for miRNA-21 detection in human serum samples.
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Técnicas Biosensibles , Técnicas Electroquímicas , Mediciones Luminiscentes , MicroARNs , Paladio , Platino (Metal) , Platino (Metal)/química , Humanos , MicroARNs/sangre , MicroARNs/análisis , Técnicas Biosensibles/métodos , Paladio/química , Límite de Detección , Compuestos de Estaño/química , Sulfuros/química , Nanoestructuras/químicaRESUMEN
BACKGROUND: Cancer-associated fibroblasts (CAFs) are found in primary and advanced tumours. They are primarily involved in tumour progression through complex mechanisms with other types of cells in the tumour microenvironment. However, essential fibroblasts-related genes (FRG) in bladder cancer still need to be explored, and there is a shortage of an ideal predictive model or molecular subtype for the progression and immune therapeutic assessment for bladder cancer, especially muscular-invasive bladder cancer based on the FRG. MATERIALS AND METHODS: CAF-related genes of bladder cancer were identified by analysing single-cell RNA sequence datasets, and bulk transcriptome datasets and gene signatures were used to characterize them. Then, 10 types of machine learning algorithms were utilised to determine the hallmark FRG and construct the FRG index (FRGI) and subtypes. Further molecular subtypes combined with CD8+ T-cells were established to predict the prognosis and immune therapy response. RESULTS: Fifty-four BLCA-related FRG were screened by large-scale scRNA-sequence datasets. The machine learning algorithm established a 3-genes FRGI. High FRGI represented a worse outcome. Then, FRGI combined clinical variables to construct a nomogram, which shows high predictive performance for the prognosis of bladder cancer. Furthermore, the BLCA datasets were separated into two subtypes - fibroblast hot and cold types. In five independent BLCA cohorts, the fibroblast hot type showed worse outcomes than the cold type. Multiple cancer-related hallmark pathways are distinctively enriched in these two types. In addition, high FRGI or fibroblast hot type shows a worse immune therapeutic response. Then, four subtypes called CD8-FRG subtypes were established under the combination of FRG signature and activity of CD8+ T-cells, which turned out to be effective in predicting the prognosis and immune therapeutic response of bladder cancer in multiple independent datasets. Pathway enrichment analysis, multiple gene signatures, and epigenetic alteration characterize the CD8-FRG subtypes and provide a potential combination strategy method against bladder cancer. CONCLUSIONS: In summary, the authors established a novel FRGI and CD8-FRG subtype by large-scale datasets and organised analyses, which could accurately predict clinical outcomes and immune therapeutic response of BLCA after surgery.
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Linfocitos T CD8-positivos , Biología Computacional , Aprendizaje Automático , Neoplasias de la Vejiga Urinaria , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/inmunología , Neoplasias de la Vejiga Urinaria/patología , Humanos , Linfocitos T CD8-positivos/inmunología , Pronóstico , Fibroblastos Asociados al Cáncer/inmunología , Fibroblastos Asociados al Cáncer/metabolismo , Análisis de la Célula Individual , Masculino , Microambiente Tumoral/inmunología , Microambiente Tumoral/genética , Femenino , Inmunoterapia/métodos , Análisis de Secuencia de ARN , Transcriptoma , MultiómicaRESUMEN
Background: The decline in muscle strength and function with aging is well recognized, but remains poorly characterized at the molecular level. Here, we report the epigenetic relationship between genome-wide DNA methylation and handgrip strength (HGS) among Chinese monozygotic (MZ) twins. Methods: DNA methylation (DNAm) profiling was conducted in whole blood samples through Reduced Representation Bisulfite Sequencing method. Generalized estimating equation was applied to regress the DNAm of each CpG with HGS. The Genomic Regions Enrichment of Annotations Tool was used to perform enrichment analysis. Differentially methylated regions (DMRs) were detected using comb-p. Causal inference was performed using Inference about Causation through Examination of Familial Confounding method. Finally, we validated candidate CpGs in community residents. Results: We identified 25 CpGs reaching genome-wide significance level. These CpGs located in 9 genes, especially FBLN1, RXRA, and ABHD14B. Many enriched terms highlighted calcium channels, neuromuscular junctions, and skeletal muscle organ development. We identified 21 DMRs of HGS, with several DMRs within FBLN1, SLC30A8, CST3, and SOCS3. Causal inference indicated that the DNAm of 16 top CpGs within FBLN1, RXRA, ABHD14B, MFSD6, and TYW1B might influence HGS, while HGS influenced DNAm at two CpGs within FBLN1 and RXRA. In validation analysis, methylation levels of six CpGs mapped to FLBN1 and one CpG mapped to ABHD14B were negatively associated with HGS weakness in community population. Conclusion: Our study identified multiple DNAm variants potentially related to HGS, especially CpGs within FBLN1 and ABHD14B. These findings provide new clues to the epigenetic modification underlying muscle strength decline.
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In the quest for proficient electrocatalysts for ammonia's electrocatalytic nitrogen reduction, cobalt oxides, endowed with a rich d-electron reservoir, have emerged as frontrunners. Despite the previously evidenced prowess of CoO in this realm, its ammonia yield witnesses a pronounced decline as the reaction unfolds, a phenomenon linked to the electron attrition from its Co2+ active sites during electrocatalytic nitrogen reduction reaction (ENRR). To counteract this vulnerability, we harnessed electron-laden phosphorus (P) elements as dopants, aiming to recalibrate the electronic equilibrium of the pivotal Co active site, thereby bolstering both its catalytic performance and stability. Our empirical endeavors showcased the doped P-CoO's superior credentials: it delivered an impressive ammonia yield of 49.6 and, notably, a Faradaic efficiency (FE) of 9.6% at -0.2 V versus RHE, markedly eclipsing its undoped counterpart. Probing deeper, a suite of ex-situ techniques, complemented by rigorous theoretical evaluations, was deployed. This dual-pronged analysis unequivocally revealed CoO's propensity for an electron-driven valence metamorphosis to Co3+ post-ENRR. In stark contrast, P-CoO, fortified by P doping, exhibits a discernibly augmented ammonia yield. Crucially, P's intrinsic ability to staunch electron leakage from the active locus during ENRR ensures the preservation of the valence state, culminating in enhanced catalytic dynamism and fortitude. This investigation not only illuminates the intricacies of active site electronic modulation in ENRR but also charts a navigational beacon for further enhancements in this domain.
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Nanobodies have emerged as promising tools in biomedicine due to their single-chain structure and inherent stability. They generally have convex paratopes, which potentially prefer different epitope sites in an antigen compared to traditional antibodies. In this study, a synthetic phage display nanobody library was constructed and used to identify nanobodies targeting a tumor-associated antigen, the human B7-H3 protein. Combining next-generation sequencing and single-clone validation, two nanobodies were identified to specifically bind B7-H3 with medium nanomolar affinities. Further characterization revealed that these two clones targeted a different epitope compared to known B7-H3-specific antibodies, which have been explored in clinical trials. Furthermore, one of the clones, dubbed as A6, exhibited potent antibody-dependent cell-mediated cytotoxicity (ADCC) against a colorectal cancer cell line with an EC50 of 0.67 nM, upon conversion to an Fc-enhanced IgG format. These findings underscore a cost-effective strategy that bypasses the lengthy immunization process, offering potential rapid access to nanobodies targeting unexplored antigenic sites.
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Restrictive cardiomyopathy (RCM) is a rare cardiomyopathy characterized by diastolic dysfunction, which affects cardiac systolic function. We successfully established human induced pluripotent stem cells (hiPSCs) from peripheral blood mononuclear cells of 24-year-old male with restrictive cardiomyopathy (RCM). The patient-derived hiPSCs carried heterozygous mutation of CRYAB gene (c.326A > G, p.D109G), which was consistent with clinical whole exon sequencing results. We confirmed the pluripotency, multipotential differentiation and karyotype of hiPSCs. The hiPSCs will be useful for studying the pathogenesis of RCM caused by CRYAB (c.326A > G) mutation.
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Cardiomiopatías , Cardiomiopatía Restrictiva , Células Madre Pluripotentes Inducidas , Humanos , Masculino , Adulto Joven , Cardiomiopatías/genética , Cardiomiopatía Restrictiva/genética , Leucocitos Mononucleares , Mutación/genéticaRESUMEN
The oxygen diffusion rate in hafnia (HfO2)-based resistive memory plays a pivotal role in enabling nonvolatile data retention. However, the information retention times obtained in HfO2 resistive memory devices are many times higher than the expected values obtained from oxygen diffusion measurements in HfO2 materials. In this study, we resolve this discrepancy by conducting oxygen isotope tracer diffusion measurements in amorphous hafnia (a-HfO2) thin films. Our results show that the oxygen tracer diffusion in amorphous HfO2 films is orders of magnitude lower than that of previous measurements on monoclinic hafnia (m-HfO2) pellets. Moreover, oxygen tracer diffusion is much lower in denser a-HfO2 films deposited by atomic layer deposition (ALD) than in less dense a-HfO2 films deposited by sputtering. The ALD films yield similar oxygen diffusion times as experimentally measured device retention times, reconciling this discrepancy between oxygen diffusion and retention time measurements. More broadly, our work shows how processing conditions can be used to control oxygen transport characteristics in amorphous materials without long-range crystal order.
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Research has indicated that mindfulness is a protective factor against suicidal ideation. However, the dynamic reciprocal relation between them has been understudied. In this study, 110 female college students with suicidal ideation completed a measure of trait mindfulness and a 28-day diary of suicidal ideation and three-dimensional state mindfulness, including acting with awareness, present-moment attention, and nonjudgmental acceptance. Dynamic structural equation modeling was used to examine the dynamic and bidirectional effects between dimensions of state mindfulness and suicidal ideation and the moderating effect of trait mindfulness. Results showed that suicidal ideation predicted lower levels of present-moment attention the next day. More importantly, there was a dynamic and bidirectional relation between nonjudgmental acceptance and suicidal ideation for people with trait mindfulness higher than the average level (i.e., M + 0.15SD). Our findings suggested that studies and interventions on suicide should pay more attention to specific dimensions of state mindfulness and trait mindfulness.