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Mosaic loss of the X chromosome (mLOX) is the most common clonal somatic alteration in leukocytes of female individuals1,2, but little is known about its genetic determinants or phenotypic consequences. Here, to address this, we used data from 883,574 female participants across 8 biobanks; 12% of participants exhibited detectable mLOX in approximately 2% of leukocytes. Female participants with mLOX had an increased risk of myeloid and lymphoid leukaemias. Genetic analyses identified 56 common variants associated with mLOX, implicating genes with roles in chromosomal missegregation, cancer predisposition and autoimmune diseases. Exome-sequence analyses identified rare missense variants in FBXO10 that confer a twofold increased risk of mLOX. Only a small fraction of associations was shared with mosaic Y chromosome loss, suggesting that distinct biological processes drive formation and clonal expansion of sex chromosome missegregation. Allelic shift analyses identified X chromosome alleles that are preferentially retained in mLOX, demonstrating variation at many loci under cellular selection. A polygenic score including 44 allelic shift loci correctly inferred the retained X chromosomes in 80.7% of mLOX cases in the top decile. Our results support a model in which germline variants predispose female individuals to acquiring mLOX, with the allelic content of the X chromosome possibly shaping the magnitude of clonal expansion.
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Aneuploidia , Cromossomos Humanos X , Células Clonais , Leucócitos , Mosaicismo , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Alelos , Doenças Autoimunes/genética , Bancos de Espécimes Biológicos , Segregação de Cromossomos/genética , Cromossomos Humanos X/genética , Cromossomos Humanos Y/genética , Células Clonais/metabolismo , Células Clonais/patologia , Exoma/genética , Proteínas F-Box/genética , Predisposição Genética para Doença/genética , Mutação em Linhagem Germinativa , Leucemia/genética , Leucócitos/metabolismo , Modelos Genéticos , Herança Multifatorial/genética , Mutação de Sentido Incorreto/genéticaRESUMO
The electrochemical nitrogen oxidation reaction (NOR) holds significant potential to revolutionize the traditional nitrate synthesis processes. However, the progression in NOR has been notably stymied due to the sluggish kinetics of initial N2 adsorption and activation processes. Herein, the research embarks on the development of a CeO2-Co3O4 heterostructure, strategically engineered to facilitate the electron transfer from CeO2 to Co3O4. This orchestrated transfer operates to amplify the d-band center of the Co active sites, thereby enhancing N2 adsorption and activation dynamics by strengthening the CoâN bond and diminishing the resilience of the N≡N bond. The synthesized CeO2-Co3O4 manifests promising prospects, showcasing a significant HNO3 yield of 37.96 µg h-1 mgcat -1 and an elevated Faradaic efficiency (FE) of 29.30% in a 0.1 m Na2SO4 solution at 1.81 V versus RHE. Further substantiating these findings, an array of in situ methodologies coupled with DFT calculations vividly illustrate the augmented adsorption and activation of N2 on the surface of CeO2-Co3O4 heterostructure, resulting in a substantial reduction in the energy barrier pertinent to the rate-determining step within the NOR pathway. This research carves a promising pathway to amplify N2 adsorption throughout the electrochemical NOR operations and delineates a blueprint for crafting highly efficient NOR electrocatalysts.
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Manganese-based oxides (MnOx) suffer from sluggish charge diffusion kinetics and poor cycling stability in sodium ion storage. Herein, an interfacial electric field (IEF) in CeO2/MnOx is constructed to obtain high electronic/ionic conductivity and structural stability of MnOx. The as-designed CeO2/MnOx exhibits a remarkable capacity of 397 F g-1 and favorable cyclic stability with 92.13% capacity retention after 10,000 cycles. Soft X-ray absorption spectroscopy and partial density of states results reveal that the electrons are substantially injected into the Mn t2g orbitals driven by the formed IEF. Correspondingly, the MnO6 units in MnOx are effectively activated, endowing the CeO2/MnOx with fast charge transfer kinetics and high sodium ion storage capacity. Moreover, In situRaman verifies a remarkably increased structural stability of CeO2/MnOx, which is attributed to the enhanced MnâO bond strength and efficiently stabilized MnO6 units. Mechanism studies show that the downshift of Mn 3d-band center dramatically increases the Mn 3d-O 2p orbitals overlap, thus inhibiting the Jahn-Teller (J-T) distortion of MnOx during sodium ion insertion/extraction. This work develops an advanced strategy to achieve both fast and sustainable sodium ion storage in metal oxides-based energy materials.
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The biomarker 5-chlorocytosine (5ClC) appears in the DNA of inflamed tissues. Replication of a site-specific 5ClC in a viral DNA genome results in C â T mutations, which is consistent with 5ClC acting as a thymine mimic in vivo. Direct damage of nucleic acids by immune-cell-derived hypochlorous acid is one mechanism by which 5ClC could appear in the genome. A second, nonmutually exclusive mechanism involves damage of cytosine nucleosides or nucleotides in the DNA precursor pool, with subsequent utilization of the 5ClC deoxynucleotide triphosphate as a precursor for DNA synthesis. The present work characterized the mutagenic properties of 5ClC in the nucleotide pool by exposing cells to the nucleoside 5-chloro-2'-deoxycytidine (5CldC). In both Escherichia coli and mouse embryonic fibroblasts (MEFs), 5CldC in the growth media was potently mutagenic, indicating that 5CldC enters cells and likely is erroneously incorporated into the genome from the nucleotide pool. High-resolution sequencing of DNA from MEFs derived from the gptΔ C57BL/6J mouse allowed qualitative and quantitative characterization of 5CldC-induced mutations; CG â TA transitions in 5'-GC(Y)-3' contexts (Y = a pyrimidine) were dominant, while TA â CG transitions appeared at a much lower frequency. The high-resolution mutational spectrum of 5CldC revealed a notable similarity to the Catalogue of Somatic Mutations in Cancer mutational signatures SBS84 and SBS42, which appear in human lymphoid tumors and in occupationally induced cholangiocarcinomas, respectively. SBS84 is associated with the expression of activation-induced cytidine deaminase (AID), a cytosine deaminase associated with inflammation, as well as immunoglobulin gene diversification during antibody maturation. The similarity between the spectra of AID activation and 5CldC could be coincidental; however, the administration of 5CldC did induce some AID expression in MEFs, which have no inherent expression of its gene. In summary, this work shows that 5CldC induces a distinct pattern of mutations in cells. Moreover, that pattern resembles human mutational signatures induced by inflammatory processes, such as those triggered in certain malignancies.
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Desoxicitidina/análogos & derivados , Fibroblastos , Neoplasias , Animais , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Fibroblastos/metabolismo , Mutação , Neoplasias/genética , DNA/metabolismo , Mutagênicos , NucleotídeosRESUMO
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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Introduction: Clinical studies have shown that endodontically-treated nonvital teeth exhibit less root resorption during orthodontic tooth movement. The purpose of this study was to explore whether hypoxic dental pulp stem cells (DPSCs) can promote osteoclastogenesis in orthodontically induced inflammatory root resorption (OIIRR). Methods: Succinate in the supernatant of DPSCs under normal and hypoxic conditions was measured by a succinic acid assay kit. The culture supernatant of hypoxia-treated DPSCs was used as conditioned medium (Hypo-CM). Bone marrow-derived macrophages (BMDMs) from succinate receptor 1 (SUCNR1)-knockout or wild-type mice were cultured with conditioned medium (CM), exogenous succinate or a specific inhibitor of SUCNR1 (4c). Tartrate-resistant acid phosphatase (TRAP) staining, Transwell assays, qPCR, Western blotting, and resorption assays were used to evaluate osteoclastogenesis-related changes. Results: The concentration of succinate reached a maximal concentration at 6 h in the supernatant of hypoxia-treated DPSCs. Hypo-CM-treated macrophages were polarized to M1 proinflammatory macrophages. Hypo-CM treatment significantly increased the formation and differentiation of osteoclasts and increased the expression of osteoclastogenesis-related genes, and this effect was inhibited by the specific succinate inhibitor 4c. Succinate promoted chemotaxis and polarization of M1-type macrophages with increased expression of osteoclast generation-related genes. SUCNR1 knockout decreased macrophage migration, M1 macrophage polarization, differentiation and maturation of osteoclasts, as shown by TRAP and NFATc1 expression and cementum resorption. Conclusions: Hypoxic DPSC-derived succinate may promote osteoclast differentiation and root resorption. The regulation of the succinate-SUCNR1 axis may contribute to the reduction in the OIIRR.
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Polpa Dentária , Camundongos Knockout , Osteoclastos , Osteogênese , Reabsorção da Raiz , Células-Tronco , Ácido Succínico , Animais , Camundongos , Polpa Dentária/citologia , Polpa Dentária/efeitos dos fármacos , Polpa Dentária/metabolismo , Osteoclastos/efeitos dos fármacos , Osteoclastos/metabolismo , Reabsorção da Raiz/patologia , Reabsorção da Raiz/metabolismo , Humanos , Ácido Succínico/metabolismo , Osteogênese/efeitos dos fármacos , Células-Tronco/metabolismo , Células-Tronco/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Hipóxia Celular/efeitos dos fármacos , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Meios de Cultivo Condicionados/farmacologia , Células CultivadasRESUMO
In the present investigation, a series of dimethoxy or methylenedioxy substituted-cinnamamide derivatives containing tertiary amine moiety (N. N-Dimethyl, N, N-diethyl, Pyrrolidine, Piperidine, Morpholine) were synthesized and evaluated for cholinesterase inhibition and blood-brain barrier (BBB) permeability. Although their chemical structures are similar, their biological activities exhibit diversity. The results showed that all compounds except for those containing morpholine group exhibited moderate to potent acetylcholinesterase inhibition. Preliminary screening of BBB permeability shows that methylenedioxy substituted compounds have better brain permeability than the others. Compound 10c, containing methylenedioxy and pyrrolidine side chain, showed a better acetylcholinesterase inhibition (IC50: 1.52±0.19â µmol/L) and good blood-brain barrier permeability. Further pharmacokinetic investigation of compound 10c using ultra high performance liquid chromatography-mass/mass spectrometry (UPLC-MS/MS) in mice showed that compound 10c in brain tissue reached its peak concentration (857.72±93.56â ng/g) after dosing 30â min. Its half-life in the serum is 331â min (5.52â h), and the CBrain/CSerum at various sampling points is ranged from 1.65 to 4.71(Mean: 2.76) within 24â hours. This investigation provides valuable information on the chemistry and pharmacological diversity of cinnamic acid derivatives and may be beneficial for the discovery of central nervous system drugs.
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Barreira Hematoencefálica , Inibidores da Colinesterase , Cinamatos , Animais , Humanos , Masculino , Camundongos , Acetilcolinesterase/metabolismo , Aminas/química , Aminas/farmacologia , Barreira Hematoencefálica/metabolismo , Inibidores da Colinesterase/química , Inibidores da Colinesterase/farmacologia , Inibidores da Colinesterase/síntese química , Inibidores da Colinesterase/farmacocinética , Inibidores da Colinesterase/metabolismo , Cinamatos/química , Cinamatos/farmacologia , Cinamatos/farmacocinética , Descoberta de Drogas , Estrutura Molecular , Relação Estrutura-Atividade , Pirrolidinas/química , Pirrolidinas/farmacologia , Morfolinas/química , Morfolinas/farmacologia , Piperidinas/química , Piperidinas/farmacologiaRESUMO
PURPOSE: The Xsight lung tracking system (XLTS) utilizes an advanced image processing algorithm to precisely identify the position of a tumor and determine its location in orthogonal x-ray images, instead of finding fiducials, thereby minimizing the risk of fiducial insertion-related side effects. To assess and gauge the effectiveness of CyberKnife Synchrony in treating liver tumors located in close proximity to or within the diaphragm, we employed the Xsight diaphragm tracking system (XDTS), which was based on the XLTS. METHODS: We looked back at the treatment logs of 11 patients (8/11 [XDTS], 3/11 [Fiducial-based Target Tracking System-FTTS]) who had liver tumors in close proximity to or within the diaphragm. And the results are compared with the patients who undergo the treatment of FTTS. The breathing data information was calculated as a rolling average to reduce the effect of irregular breathing. We tested the tracking accuracy with a dynamic phantom (18023-A) on the basis of patient-specific respiratory curve. RESULTS: The average values for the XDTS and FTTS correlation errors were 1.38 ± 0.65 versus 1.50 ± 0.26 mm (superior-inferior), 1.28 ± 0.48 versus 0.40 ± 0.09 mm (left-right), and 0.96 ± 0.32 versus 0.47 ± 0.10 mm(anterior-posterior), respectively. The prediction errors for two methods of 0.65 ± 0.16 versus 5.48 ± 3.33 mm in the S-I direction, 0.34 ± 0.10 versus 1.41 ± 0.76 mm in the A-P direction, and 0.22 ± 0.072 versus 1.22 ± 0.48 mm in the L-R direction. The coverage rate of FTTS slightly less than that of XDTS, such as 96.53 ± 8.19% (FTTS) versus 98.03 ± 1.54 (XDTS). The prediction error, the motion amplitude, and the variation of the respiratory center phase were strongly related to each other. Especially, the higher the amplitude and the variation, the higher the prediction error. CONCLUSION: The diaphragm has the potential to serve as an alternative to gold fiducial markers for detecting liver tumors in close proximity or within it. We also found that we needed to reduce the motion amplitude and train the respiration of the patients during liver radiotherapy, as well as control and evaluate their breathing.
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Algoritmos , Diafragma , Processamento de Imagem Assistida por Computador , Neoplasias Hepáticas , Imagens de Fantasmas , Radiocirurgia , Dosagem Radioterapêutica , Planejamento da Radioterapia Assistida por Computador , Radioterapia de Intensidade Modulada , Respiração , Humanos , Radiocirurgia/métodos , Diafragma/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/radioterapia , Planejamento da Radioterapia Assistida por Computador/métodos , Radioterapia de Intensidade Modulada/métodos , Processamento de Imagem Assistida por Computador/métodos , Marcadores Fiduciais , Masculino , Feminino , Movimento , Pessoa de Meia-Idade , Prognóstico , Idoso , Radioterapia Guiada por Imagem/métodos , Órgãos em Risco/efeitos da radiaçãoRESUMO
Cracks inside urban underground comprehensive pipe galleries are small and their characteristics are not obvious. Due to low lighting and large shadow areas, the differentiation between the cracks and background in an image is low. Most current semantic segmentation methods focus on overall segmentation and have a large perceptual range. However, for urban underground comprehensive pipe gallery crack segmentation tasks, it is difficult to pay attention to the detailed features of local edges to obtain accurate segmentation results. A Global Attention Segmentation Network (GA-SegNet) is proposed in this paper. The GA-SegNet is designed to perform semantic segmentation by incorporating global attention mechanisms. In order to perform precise pixel classification in the image, a residual separable convolution attention model is employed in an encoder to extract features at multiple scales. A global attention upsample model (GAM) is utilized in a decoder to enhance the connection between shallow-level features and deep abstract features, which could increase the attention of the network towards small cracks. By employing a balanced loss function, the contribution of crack pixels is increased while reducing the focus on background pixels in the overall loss. This approach aims to improve the segmentation accuracy of cracks. The comparative experimental results with other classic models show that the GA SegNet model proposed in this study has better segmentation performance and multiple evaluation indicators, and has advantages in segmentation accuracy and efficiency.
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Transition metal oxides (TMOs) are key in electrochemical energy storage, offering cost-effectiveness and a broad potential window. However, their full potential is limited by poor understanding of their slow reaction kinetics and stability issues. This study diverges from conventional complex nano-structuring, concentrating instead on spin-related charge transfer and orbital interactions to enhance the reaction dynamics and stability of TMOs during energy storage processes. We successfully reconfigured the orbital degeneracy and spin-dependent electronic occupancy by disrupting the symmetry of magnetic cobalt (Co) sites through straightforward strain stimuli. The key to this approach lies in the unfilled Co 3d shell, which serves as a spin-dependent regulator for carrier transfer and orbital interactions within the reaction. We observed that the opening of these 'spin gates' occurs during a transition from a symmetric low-spin state to an asymmetric high-spin state, resulting in enhanced reaction kinetics and maintained structural stability. Specifically, the spin-rearranged Al-Co3O4 exhibited a specific capacitance of 1371â F g-1, which is 38 % higher than that of unaltered Co3O4. These results not only shed light on the spin effects in magnetic TMOs but also establish a new paradigm for designing electrochemical energy storage materials with improved efficiency.
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Transition metal oxides (TMOs) are promising cathode materials for aqueous zinc ion batteries (ZIBs), however, their performance is hindered by a substantial Hubbard gap, which limits electron transfer and battery cyclability. Addressing this, we introduce a heteroatom coordination approach, using triethanolamine to induce axial N coordination on Mn centers in MnO2, yielding N-coordinated MnO2 (TEAMO). This approach leverages the change of electronegativity disparity between Mn and ligands (O and N) to disrupt spin symmetry and augment spin polarization. This enhancement leads to the closure of the Hubbard gap, primarily driven by the intensified occupancy of the Mn eg orbitals. The resultant TEAMO exhibit a significant increase in storage capacity, reaching 351â mAh g-1 at 0.1â A g-1. Our findings suggest a viable strategy for optimizing the electronic structure of TMO cathodes, enhancing the potential of ZIBs in energy storage technology.
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Demência , Manejo da Dor , Humanos , Demência/enfermagem , Manejo da Dor/métodos , Dor/psicologiaRESUMO
Chiral active particles (CAPs) are self-propelling particles that break time-reversal symmetry by orbiting or spinning, leading to intriguing behaviors. Here, we examined the dynamics of CAPs moving in 2D lattices of disk obstacles through active Brownian dynamics simulations and granular experiments with grass seeds. We find that the effective diffusivity of the CAPs is sensitive to the structure of the obstacle lattice, a feature absent in achiral active particles. We further studied the transport of CAPs in obstacle arrays under an external field and found a reentrant directional locking effect, which can be used to sort CAPs with different activities. Finally, we demonstrated that parallelogram lattices of obstacles without mirror symmetry can separate clockwise and counter-clockwise CAPs. The mechanisms of the above three novel phenomena are qualitatively explained. As such, our work provides a basis for designing chirality-based tools for single-cell diagnosis and separation, and active particle-based environmental sensors.
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This study addresses the critical challenge in alkaline direct formate fuel cells (DFFCs) of slow formate oxidation reaction (FOR) kinetics as a result of strong hydrogen intermediate (Had) adsorption on Pd catalysts. We developed WO3-supported Pd nanoparticles (EG-Pd/WO3) via an organic reduction method using ethylene glycol (EG), aiming to modulate the d-band center of Pd and alter Had adsorption dynamics. Cyclic voltammetry demonstrated significantly improved Had desorption kinetics in EG-Pd/WO3 catalysts. Density functional theory (DFT) calculations revealed that the presence of EG reduces the d-band center of Pd, leading to weaker Pd-H bonds and enhanced Had desorption during the FOR. This research provides a new approach to optimize catalyst efficiency in DFFCs, highlighting the potential for more effective and sustainable energy solutions through advanced material engineering.
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OBJECTIVE: The primary objective of this study was to assess the diagnostic potential of galectin-3 (Gal-3), fractalkine (FKN), interleukin (IL)-6, microRNA(miR)-21, and cardiac troponin I (cTnI) in patients with ischemic cardiomyopathy (ICM). METHOD: A total of 78 ICM patients (Case group) and 80 healthy volunteers (Control group) admitted to our hospital for treatment or physical examination from Aug. 2018 to Feb. 2020 were included in the current study. The serum concentration of Gal-3, FKN, IL-6, miR-21, and plasma expression of cTnI of both groups were determined. The severity of ICM was classified using New York Heart Association (NYHA) scale. RESULTS: When compared with the control group, the case group had a significantly high blood concentration of Gal-3, FKN, IL-6, miR-21, and cTnI (P < 0.001). NYHA class II patients had lower blood levels of Gal-3, FKN, IL-6, miR-21, and cTnI than that in patients of NYHA class III and IV without statistical significance (P > 0.05). However, statistical significance could be achieved when comparing the above-analyzed markers in patients classified between class III and IV. Correlation analysis also revealed that serum levels of Gal-3, FKN, IL-6, miR-21, and cTnI were positively correlated with NYHA classification (R = 0.564, 0.621, 0.792, 0.981, P < 0.05). CONCLUSION: Our study revealed that up-regulated serum Gal-3, FKN, IL-6, miR-21, and cTnI levels were closely related to the progression of ICM. This association implies that these biomarkers have diagnostic potential, offering a promising avenue for early detection and monitoring of ICM progression.
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Biomarcadores , Quimiocina CX3CL1 , Galectina 3 , Interleucina-6 , MicroRNAs , Isquemia Miocárdica , Troponina I , Humanos , Feminino , Masculino , Troponina I/sangue , Interleucina-6/sangue , MicroRNAs/sangue , Quimiocina CX3CL1/sangue , Quimiocina CX3CL1/genética , Pessoa de Meia-Idade , Galectina 3/sangue , Galectina 3/genética , Biomarcadores/sangue , Idoso , Isquemia Miocárdica/sangue , Isquemia Miocárdica/diagnóstico , Cardiomiopatias/sangue , Cardiomiopatias/diagnóstico , Estudos de Casos e Controles , Galectinas/sangue , Proteínas Sanguíneas/análiseRESUMO
OBJECTIVES: Instance-level tooth segmentation extracts abundant localization and shape information from panoramic radiographs (PRs). The aim of this study was to evaluate the performance of a mask refinement network that extracts precise tooth edges. METHODS: A public dataset which consists of 543 PRs and 16211 labelled teeth was utilized. The structure of a typical Mask Region-based Convolutional Neural Network (Mask RCNN) was used as the baseline. A novel loss function was designed focus on producing accurate mask edges. In addition to our proposed method, 3 existing tooth segmentation methods were also implemented on the dataset for comparative analysis. The average precisions (APs), mean intersection over union (mIoU), and mean Hausdorff distance (mHAU) were exploited to evaluate the performance of the network. RESULTS: A novel mask refinement region-based convolutional neural network was designed based on Mask RCNN architecture to extract refined masks for individual tooth on PRs. A total of 3311 teeth were correctly detected from 3382 tested teeth in 111 PRs. The AP, precision, and recall were 0.686, 0.979, and 0.952, respectively. Moreover, the mIoU and mHAU achieved 0.941 and 9.7, respectively, which are significantly better than the other existing segmentation methods. CONCLUSIONS: This study proposed an efficient deep learning algorithm for accurately extracting the mask of any individual tooth from PRs. Precise tooth masks can provide valuable reference for clinical diagnosis and treatment. This algorithm is a fundamental basis for further automated processing applications.
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Algoritmos , Dente , Humanos , Radiografia Panorâmica , Redes Neurais de Computação , Dente/diagnóstico por imagemRESUMO
BACKGROUND AND AIMS: Therapeutic arteriogenesis is a promising direction for the treatment of ischemic disease caused by atherosclerosis. However, pharmacological or biological approaches to stimulate functional collateral vessels are not yet available. Identifying new drug targets to promote and explore the underlying mechanisms for therapeutic arteriogenesis is necessary. METHODS: Peptide OM-LV20 (20 ng/kg) was administered for 7 consecutive days on rat hindlimb ischemia model, collateral vessel growth was assessed by H&E staining, liquid latex perfusion, and specific immunofluorescence. In vitro, we detected the effect of OM-LV20 on human umbilical vein endothelial cells (HUVEC) proliferation and migration. After transfection, we performed quantitative real-time polymerase chain reaction, in situ-hybridization and dual luciferase reporters to assessed effective miRNAs and target genes. The proteins related to downstream signaling pathways were detected by Western blot. RESULTS: OM-LV20 significantly increased visible collateral vessels and endothelial nitric oxide synthase (eNOS), together with enhanced inflammation cytokine and monocytes/macrophage infiltration in collateral vessels. In vitro, we defined a novel microRNA (miR-29b-3p), and its inhibition enhanced proliferation and migration of HUVEC, as well as the expression of vascular endothelial growth factor A (VEGFA). OM-LV20 also promoted migration and proliferation of HUVEC, and VEGFA expression was mediated via inhibition of miR-29b-3p. Furthermore, OM-LV20 influenced the protein levels of VEGFR2 and phosphatidylinositol3-kinase (PI3K)/AKT and eNOS in vitro and invivo. CONCLUSIONS: Our data indicated that OM-LV20 enhanced arteriogenesis via the miR-29b-3p/VEGFA/VEGFR2-PI3K/AKT/eNOS axis, and highlighte the application potential of exogenous peptide molecular probes through miRNA, which could promote effective therapeutic arteriogenesis in ischemic conditions.
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MicroRNAs , Peptídeos , Fator A de Crescimento do Endotélio Vascular , Humanos , Ratos , Animais , Artéria Femoral/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Isquemia/genética , Proliferação de CélulasRESUMO
Direct formate fuel cells have gained traction due to their eco-friendly credentials and inherent safety. However, their potential is hampered by the kinetic challenges of the formate oxidation reaction (FOR) on Pd-based catalysts, chiefly due to the unfavorable adsorption of hydrogen species (Had). These species clog the active sites, hindering efficient catalysis. Here, we introduce a straightforward strategy to remedy this bottleneck by incorporating Pd with Cu to expedite the removal of Pd-Had in alkaline media. Notably, Cu plays a pivotal role in bolstering the concentration of hydroxyl adsorbates (OHad) on the surface of catalyst. These OHad species can react with Had, effectively unblocking the active sites for FOR. The as-synthesized catalyst of PdCu/C exhibits a superior FOR performance, boasting a remarkable mass activity of 3.62 A mg-1. Through CO-stripping voltammetry, we discern that the presence of Cu in Pd markedly speeds up the formation of adsorbed hydroxyl species (OHad) at diminished potentials. This, in turn, aids the oxidative removal of Pd-Had, leveraging a synergistic mechanism during FOR. Density functional theory computations further reveal intensified interactions between adsorbed oxygen species and intermediates, underscoring that the Cu-Pd interface exhibits greater oxyphilicity compared to pristine Pd. In this study, we present both experimental and theoretical corroborations, unequivocally highlighting that the integrated copper species markedly amplify the generation of OHad, ensuring efficient removal of Had. This work paves the way, shedding light on the strategic design of high-performing FOR catalysts.
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The electrocatalytic conversion of formate in alkaline solutions is of paramount significance in the realm of fuel cell applications. Nonetheless, the adsorptive affinity of adsorbed hydrogen (Had) on the catalyst surface has traditionally impeded the catalytic efficiency of formate in such alkaline environments. To circumvent this challenge, our approach introduces an interfacial push-pull effect on the catalyst surface. This mechanism involves two primary actions: First, the anchoring of palladium (Pd) nanoparticles on a phosphorus-doped TiO2 substrate (Pd/TiO2-P) promotes the formation of electron-rich Pd with a downshifted d band center, thereby "pushing" the desorption of Had from the Pd active sites. Second, the TiO2-P support diminishes the energy barrier for Had transfer from the Pd sites to the support itself, "pulling" Had to effectively relocate from the Pd active sites to the support. The resultant Pd/TiO2-P catalyst showcases a remarkable mass activity of 4.38 A mgPd-1 and outperforms the Pd/TiO2 catalyst (2.39 A mgPd-1) by a factor of 1.83. This advancement not only surmounts a critical barrier in catalysis but also delineates a scalable pathway to bolster the efficacy of Pd-based catalysts in alkaline media.
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Although there is a body of research indicating the potential impact of polycyclic aromatic hydrocarbons (PAHs) exposure on male infertility, the understanding of how PAH might affect female infertility is still limited. This study aimed to evaluate associations of PAHs, both individually and as a mixture, with female infertility using multiple logistic regression, Bayesian kernel machine regression (BKMR), and quantile g-computation (QGC) models based on data from the National Health and Nutrition Examination Survey (NHANES) 2013-2016. The study included 729 female participants. Multiple logistic regression results indicated that there was a significant association between the third tertile of 2-hydroxy fluorene (2-OHFLU) and female infertility, and the OR was 2.84 (95% CI: 1.24-6.53, P value = 0.015) compared with the first tertile after adjusting for the potential covariates. The BKMR model revealed a positive overall trend between mixed PAH exposure and female infertility, particularly when the mixture was at or above the 55th percentile, where 2-hydroxynaphthalene (2-OHNAP) and 1-hydroxypyrene (1-OHPYR) were the primary influences of the mixture. The univariate exposure-response function indicated positive associations between individual PAH exposure, specifically 2-OHNAP, 2-OHFLU, and 1-OHPYR, and female infertility. The QGC model also indicated a positive trend between exposure to a mixture of PAHs and female infertility, although it did not reach statistical significance (ORâ¯=â¯1.33, 95%CI: 0.86-2.07), with 1-OHPYR having the greatest positive effect on the outcome. This study suggested that exposure to PAHs may be associated with female infertility and further research is needed to consolidate and confirm these findings.