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Nonradicals are effective in selectively degrading electron-rich organic contaminants, which unfortunately suffer from unsatisfactory yield and uncontrollable composition due to the competitive generation of radicals. Herein, we precisely construct a local microenvironment of the carbon nitride-supported high-loading (~9 wt.%) Fe single-atom catalyst (Fe SAC) with sulfur via a facile supermolecular self-assembly strategy. Short-distance S coordination boosts the peroxymonosulfate (PMS) activation and selectively generates high-valent iron-oxo species (FeIV=O) along with singlet oxygen (1O2), significantly increasing the 1O2 yield, PMS utilization, and p-chlorophenol reactivity by 6.0, 3.0, and 8.4 times, respectively. The composition of nonradicals is controllable by simply changing the S content. In contrast, long-distance S coordination generates both radicals and nonradicals, and could not promote reactivity. Experimental and theoretical analyses suggest that the short-distance S upshifts the d-band center of the Fe atom, i.e., being close to the Fermi level, which changes the binding mode between the Fe atom and O site of PMS to selectively generate 1O2 and FeIV=O with a high yield. The short-distance S-coordinated Fe SAC exhibits excellent application potential in various water matrices. These findings can guide the rational design of robust SACs toward a selective and controllable generation of nonradicals with high yield and PMS utilization.
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Idiopathic pulmonary fibrosis (IPF) poses significant challenges due to limited treatment options despite its complex pathogenesis involving cellular and molecular mechanisms. This study investigated the role of transient receptor potential ankyrin 1 (TRPA1) channels in regulating M2 macrophage polarization in IPF progression, potentially offering novel therapeutic targets. Using a bleomycin-induced pulmonary fibrosis model in C57BL/6J mice, we assessed the therapeutic potential of the TRPA1 inhibitor HC-030031. TRPA1 upregulation was observed in fibrotic lungs, correlating with worsened lung function and reduced survival. TRPA1 inhibition mitigated fibrosis severity, evidenced by decreased collagen deposition and restored lung tissue stiffness. Furthermore, TRPA1 blockade reversed aberrant M2 macrophage polarization induced by bleomycin, associated with reduced Smad2 phosphorylation in the TGF-ß1-Smad2 pathway. In vitro studies with THP-1 cells treated with bleomycin and HC-030031 corroborated these findings, highlighting TRPA1's involvement in fibrotic modulation and macrophage polarization control. Overall, targeting TRPA1 channels presents promising therapeutic potential in managing pulmonary fibrosis by reducing pro-fibrotic marker expression, inhibiting M2 macrophage polarization, and diminishing collagen deposition. This study sheds light on a novel avenue for therapeutic intervention in IPF, addressing a critical need in the management of this challenging disease.
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Fibrose Pulmonar Idiopática , Macrófagos , Canal de Cátion TRPA1 , Animais , Camundongos , Acetanilidas , Bleomicina , Colágeno , Proteínas do Citoesqueleto , Camundongos Endogâmicos C57BL , Purinas , Canal de Cátion TRPA1/metabolismoRESUMO
The DNA methylation is gradually acquired during oogenesis, a process sustained by successful follicle development. However, the functional roles of methyl-CpG-binding protein 2 (MeCP2), an epigenetic regulator displaying specifical binding with methylated DNA, remains unknown in oogenesis. In this study, we found MeCP2 protein was highly expressed in primordial and primary follicle, but was almost undetectable in secondary follicles. However, in aged ovary, MeCP2 protein is significantly increased in both oocyte and granulosa cells. Overexpression of MeCP2 in growing oocyte caused transcription dysregulation, DNA hypermethylation, and genome instability, ultimately leading to follicle growth arrest and apoptosis. MeCP2 is targeted by DCAF13, a substrate recognition adaptor of the Cullin 4-RING (CRL4) E3 ligase, and polyubiquitinated for degradation in both cells and oocytes. Dcaf13-null oocyte exhibited an accumulation of MeCP2 protein, and the partial rescue of follicle growth arrest induced by Dcaf13 deletion was observed following MeCP2 knockdown. The RNA-seq results revealed that large amounts of genes were regulated by the DCAF13-MeCP2 axis in growing oocytes. Our study demonstrated that CRL4DCAF13 E3 ubiquitin ligase targets MeCP2 for degradation to ensure normal DNA methylome and transcription in growing oocytes. Moreover, in aged ovarian follicles, deceased DCAF13 and DDB1 protein were observed, indicating a potential novel mechanism that regulates ovary aging.
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Proteína 2 de Ligação a Metil-CpG , Ubiquitina-Proteína Ligases , Feminino , Humanos , Proteínas Culina/genética , Proteínas Culina/metabolismo , DNA/metabolismo , Metilação de DNA , Proteína 2 de Ligação a Metil-CpG/genética , Proteína 2 de Ligação a Metil-CpG/metabolismo , Oócitos/metabolismo , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Inspired by enzymatic catalysis, it is crucial to construct hydrogen-bonding-rich microenvironment around catalytic sites; unfortunately, its precise construction and understanding how the distance between such microenvironment and catalytic sites affects the catalysis remain significantly challenging. In this work, a series of metal-organic framework (MOF)-based single-atom Ru1 catalysts, namely, Ru1/UiO-67-X (X = -H, -m-(NH2)2, -o-(NH2)2), have been synthesized, where the distance between the hydrogen-bonding microenvironment and Ru1 sites is modulated by altering the location of amino groups. The -NH2 group can form hydrogen bonds with H2O, constituting a unique microenvironment that causes an increased water concentration around the Ru1 sites. Remarkably, Ru1/UiO-67-o-(NH2)2 displays a superior photocatalytic hydrogen production rate, â¼4.6 and â¼146.6 times of Ru1/UiO-67-m-(NH2)2 and Ru1/UiO-67, respectively. Both experimental and computational results suggest that the close proximity of amino groups to the Ru1 sites in Ru1/UiO-67-o-(NH2)2 improves charge transfer and H2O dissociation, accounting for the promoted photocatalytic hydrogen production.
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BACKGROUND: Stroke is a globally dangerous disease capable of causing irreversible neuronal damage with limited therapeutic options. Meldonium, an inhibitor of carnitine-dependent metabolism, is considered an anti-ischemic drug. However, the mechanisms through which meldonium improves ischemic injury and its potential to protect neurons remain largely unknown. METHODS: A rat model with middle cerebral artery occlusion (MCAO) was used to investigate meldonium's neuroprotective efficacy in vivo. Infarct volume, neurological deficit score, histopathology, neuronal apoptosis, motor function, morphological alteration and antioxidant capacity were explored via 2,3,5-Triphenyltetrazolium chloride staining, Longa scoring method, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, rotarod test, transmission electron microscopy and Oxidative stress index related kit. A primary rat hippocampal neuron model subjected to oxygen-glucose deprivation reperfusion was used to study meldonium's protective ability in vitro. Neuronal viability, mitochondrial membrane potential, mitochondrial morphology, respiratory function, ATP production, and its potential mechanism were assayed by MTT cell proliferation and cytotoxicity assay kit, cell-permeant MitoTracker® probes, mitochondrial stress, real-time ATP rate and western blotting. RESULTS: Meldonium markedly reduced the infarct size, improved neurological function and motor ability, and inhibited neuronal apoptosis in vivo. Meldonium enhanced the morphology, antioxidant capacity, and ATP production of mitochondria and inhibited the opening of the mitochondrial permeability transition pore in the cerebral cortex and hippocampus during cerebral ischemia-reperfusion injury (CIRI) in rats. Additionally, meldonium improved the damaged fusion process and respiratory function of neuronal mitochondria in vitro. Further investigation revealed that meldonium activated the Akt/GSK-3ß signaling pathway to inhibit mitochondria-dependent neuronal apoptosis. CONCLUSION: Our study demonstrated that meldonium shows a neuroprotective function during CIRI by preserving the mitochondrial function, thus prevented neurons from apoptosis.
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Apoptose , Sobrevivência Celular , Metilidrazinas , Mitocôndrias , Neurônios , Fármacos Neuroprotetores , Ratos Sprague-Dawley , Traumatismo por Reperfusão , Animais , Fármacos Neuroprotetores/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/tratamento farmacológico , Masculino , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Metilidrazinas/farmacologia , Metilidrazinas/uso terapêutico , Isquemia Encefálica/patologia , Isquemia Encefálica/tratamento farmacológico , Infarto da Artéria Cerebral Média/complicações , Infarto da Artéria Cerebral Média/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RatosRESUMO
BACKGROUND: Acute hypobaric hypoxia-induced brain injury has been a challenge in the health management of mountaineers; therefore, new neuroprotective agents are urgently required. Meldonium, a well-known cardioprotective drug, has been reported to have neuroprotective effects. However, the relevant mechanisms have not been elucidated. We hypothesized that meldonium may play a potentially novel role in hypobaric hypoxia cerebral injury. METHODS: We initially evaluated the neuroprotection efficacy of meldonium against acute hypoxia in mice and primary hippocampal neurons. The potential molecular targets of meldonium were screened using drug-target binding Huprot™ microarray chip and mass spectrometry analyses after which they were validated with surface plasmon resonance (SPR), molecular docking, and pull-down assay. The functional effects of such binding were explored through gene knockdown and overexpression. RESULTS: The study clearly shows that pretreatment with meldonium rapidly attenuates neuronal pathological damage, cerebral blood flow changes, and mitochondrial damage and its cascade response to oxidative stress injury, thereby improving survival rates in mice brain and primary hippocampal neurons, revealing the remarkable pharmacological efficacy of meldonium in acute high-altitude brain injury. On the one hand, we confirmed that meldonium directly interacts with phosphoglycerate kinase 1 (PGK1) to promote its activity, which improved glycolysis and pyruvate metabolism to promote ATP production. On the other hand, meldonium also ameliorates mitochondrial damage by PGK1 translocating to mitochondria under acute hypoxia to regulate the activity of TNF receptor-associated protein 1 (TRAP1) molecular chaperones. CONCLUSION: These results further explain the mechanism of meldonium as an energy optimizer and provide a strategy for preventing acute hypobaric hypoxia brain injury at high altitudes.
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Lesões Encefálicas , Fosfoglicerato Quinase , Animais , Fosfoglicerato Quinase/metabolismo , Fosfoglicerato Quinase/genética , Camundongos , Lesões Encefálicas/tratamento farmacológico , Lesões Encefálicas/metabolismo , Lesões Encefálicas/patologia , Masculino , Hipocampo/efeitos dos fármacos , Hipocampo/patologia , Hipocampo/metabolismo , Hipóxia/tratamento farmacológico , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismoRESUMO
The thermal stability of MAPbI3 poses a challenge for the industry. To overcome this limitation, a thorough investigation of MAPbI3 is necessary. In this work, thermal gravimetric analysis (TGA) and Fourier transform infrared (FTIR) spectroscopy were conducted to identify the thermal decomposition products of MAPbI3, which were found to be CH3I, NH3, and PbI2. In situ X-ray diffraction (XRD) measurements were then performed in the temperature range from 300 to 700 K, which revealed the significant decomposition of the (110), (220), and (310) surfaces of MAPbI3 between 550 and 600 K. Density functional theory (DFT) calculations demonstrated that the (220) surface exhibited the highest stability. Additionally, the transition states of thermal decomposition showed that the energy barrier for the decomposition of the (110) surface was 2.07 eV. Our combined experimental and theoretical results provide a better understanding of the thermal decomposition mechanism of MAPbI3, providing valuable theoretical support for the design of long-term stable devices.
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AIMS: Whether changes in endothelial tight junctions (TJs) lead to the formation of thoracic aortic aneurysm and dissection (TAAD) and serve as an early indicator and therapeutic target remains elusive. METHODS AND RESULTS: Single-cell RNA sequencing analysis showed aberrant endothelial TJ expressions in the thoracic aortas of patients with TAAD. In a ß-aminopropionitrile (BAPN)-induced TAAD mouse model, endothelial TJ function was disrupted in the thoracic aortas at an early stage (5 and 10 days) as observed by a vascular permeability assay, while the intercellular distribution of crucial TJ components was significantly decreased by en face staining. For the non-invasive detection of endothelial TJ function, two dextrans of molecular weights 4 and 70 kDa were conjugated with the magnetic resonance imaging (MRI) contrast agent Gd-DOTA to synthesize FITC-dextran-DOTA-Gd and rhodamine B-dextran-DOTA-Gd. MRI images showed that both probes accumulated in the thoracic aortas of the BAPN-fed mice. Particularly, the mice with increased accumulated signals from 5 to 10 days developed TAAD at 14 days, whereas the mice with similar signals between the two time points did not. Furthermore, the protease-activated receptor 2 inhibitor AT-1001, which seals TJs, alleviated the BAPN-induced impairment of endothelial TJ function and expression and subsequently reduced TAAD incidence. Notably, endothelial-targeted ZO-1 conditional knockout increased TAAD incidence. Mechanistically, vascular inflammation and edema were observed in the thoracic aortas of the BAPN-fed mice, whereas these phenomena were attenuated by AT-1001. CONCLUSION: The disruption of endothelial TJ function is an early event prior to TAAD formation, herein serving as a potential indicator and a promising target for TAAD.
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Aneurisma da Aorta Torácica , Dissecção Aórtica , Camundongos , Animais , Aminopropionitrilo/efeitos adversos , Junções Íntimas/metabolismo , Junções Íntimas/patologia , Transdução de Sinais , Aneurisma da Aorta Torácica/prevenção & controleRESUMO
PURPOSE: We aimed to evaluate the safety and effectiveness of three-dimensional (3D)-printed guide plates for assisting in the positioning of the rotation axis of an elbow-hinged external fixator. METHODS: Terrible triad (TT) patients, who were screened using the predefined inclusion and exclusion criteria, underwent installation of a hinged external fixator on the basis of internal fixation; 3D-printed guide plates, generated from the patient's imaging data, assisted in positioning the rotation axis. All patients received the same peri-operative management and were followed up at six, 12, 24, and 48 weeks postoperatively. The duration of positioning pin placement, the number of fluoroscopies, pin placement success rate, types and incidence of post-operative complications, and the Mayo elbow performance score (MEPS) of the diseased elbow and range of motion (ROM) of both elbows were assessed. RESULTS: In 25 patients who completed the follow-up, the average time required for positioning pin placement was 329.32 ± 42.38 s (263-443 s), the average number of fluoroscopies was 2.32 ± 0.48 times (2-3 times), and the pin placement success rate was 100%. At the last follow-up, the mean MEPS of the diseased elbow was 97.50 ± 6.92 (75-100), with an excellent and good rate of 100%, and all patients demonstrated stable concentric reduction. The average range of flexion and extension was 135.08° ± 17.10° (77-146°), while the average range of rotation was 169.21° ± 18.14° (108-180°). No significant difference was observed in the average ROM between the both elbows (P > 0.05). Eight (32%) patients developed post-operative complications, including elbow stiffness due to heterotopic ossification in three (12%) patients, all of whom did not require secondary intervention. CONCLUSION: Utilizing 3D-printed guide plates for positioning the rotation axis of an elbow-hinged external fixator significantly reduced intra-operative positioning pin placement time and the number of fluoroscopies with excellent positioning results. Satisfactory results were also obtained in terms of post-operative complications, elbow ROM, and functional scores.
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Articulação do Cotovelo , Fixadores Externos , Impressão Tridimensional , Amplitude de Movimento Articular , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Articulação do Cotovelo/cirurgia , Articulação do Cotovelo/fisiopatologia , Adulto , Amplitude de Movimento Articular/fisiologia , Placas Ósseas , Rotação , Idoso , Resultado do Tratamento , Lesões no Cotovelo , Fixação de Fratura/métodos , Fixação de Fratura/instrumentaçãoRESUMO
Developing solid-state hydrogen storage materials is as pressing as ever, which requires a comprehensive understanding of the dehydrogenation chemistry of a solid-state hydride. Transition state search and kinetics calculations are essential to understanding and designing high-performance solid-state hydrogen storage materials by filling in the knowledge gap that current experimental techniques cannot measure. However, the ab initio analysis of these processes is computationally expensive and time-consuming. Searching for descriptors to accurately predict the energy barrier is urgently needed, to accelerate the prediction of hydrogen storage material properties and identify the opportunities and challenges in this field. Herein, we develop a data-driven model to describe and predict the dehydrogenation barriers of a typical solid-state hydrogen storage material, magnesium hydride (MgH2), based on the combination of the crystal Hamilton population orbital of Mg-H bond and the distance between atomic hydrogen. By deriving the distance energy ratio, this model elucidates the key chemistry of the reaction kinetics. All the parameters in this model can be directly calculated with significantly less computational cost than conventional transition state search, so that the dehydrogenation performance of hydrogen storage materials can be predicted efficiently. Finally, we found that this model leads to excellent agreement with typical experimental measurements reported to date and provides clear design guidelines on how to propel the performance of MgH2 closer to the target set by the United States Department of Energy (US-DOE).
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Buffalo meat is gaining popularity for its nutritional properties, such as its low fat and cholesterol content. However, it is often unsatisfactory to consumers due to its dark color and low tenderness. There is currently limited research on the regulatory mechanisms of buffalo meat quality. Xinglong buffalo are raised in the tropical Hainan region and are undergoing genetic improvement from draught to meat production. For the first time, we evaluated the meat quality traits of Xinglong buffalo using the longissimus dorsi muscle and compared them to Hainan cattle. Furthermore, we utilized a multi-omics approach combining transcriptomics and metabolomics to explore the underlying molecular mechanism regulating meat quality traits. We found that the Xinglong buffalo had significantly higher meat color redness but lower amino acid content and higher shear force compared to Hainan cattle. Differentially expressed genes (DEGs) and differentially accumulated metabolites (DAMs) were identified, with them being significantly enriched in nicotinic acid and nicotinamide metabolic and glycine, serine, and threonine metabolic pathways. The correlation analysis revealed that those genes and metabolites (such as: GAMT, GCSH, PNP, L-aspartic acid, NADP+, and glutathione) are significantly associated with meat color, tenderness, and amino acid content, indicating their potential as candidate genes and biological indicators associated with meat quality. This study contributes to the breed genetic improvement and enhancement of buffalo meat quality.
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Owing to the ultralong afterglow, room temperature decay phosphorescence nanomaterials have aroused enough attention. In the work, by simple one-pot solid-state thermal decomposition reaction, aggregate carbon dots (CDs) was prepared from trimesic and boric acid. Based on the intermolecular hydrogen bonds and intramolecular π-π stacking weak interaction from precursors, CDs was encapsulated in boron oxide matrix and formed aggregation. The aggregate state of CDs facilitated the triplet excited states (Tn), which could induce the room temperature decay phosphorescence properties. By careful investigation, under different excitation wavelengths at 254 and 365 nm, the aggregate CDs showed > 15 s and > 3 s room temperature phosphorescence emission in the naked eye, which was associated with 1516.12 ms and 718.62 ms lifetime respectively. And the aggregate CDs exhibited widespread application in encoding encryption, optical anti-counterfeiting and fingerprint identification etc. The interesting aggregate CDs revealed unexpected ultralong-afterglow room temperature decay phosphorescence properties and the work opened a window for constructing ultralong-afterglow room temperature decay phosphorescence aggregate CDs nanomaterials.
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Cyclodextrin (CD) is an important guest material owing to the water solubility and biocompatibility. In the paper, an organic small molecule was synthesized. According to supramolecular self-assembly, the organic molecule was bounded to the cavity of Poly ß-cyclodextrin, which was characterized by IR, SEM and TEM et al. After self-assembly interaction, the morphology has changed obviously comparing with precursors. Simultaneously, the supramolecular self-assembly complex exhibited good water solubility. Moreover, By Gaussian calculation, the high binding activity between organic molecule and cyclodextrin was confirmed. By fluorescence investigation, the supramolecular system showed high fluorescence sensing activity for Zn2+ in pure water environment, which could track the dynamic change of Zn2+ in organisms. In addition, the supramolecular system exhibited low cytotoxicity. The work provided an interesting pathway for constructing water-soluble and low cytotoxic fluorescence sensor for Zn2+.
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OBJECTIVE: Subjective cognitive decline (SCD) is highlighted in patients with major depressive disorder (MDD), which impairs objective cognitive performance and worsens the clinical outcomes. Immune dysregulation is supposed to be the potential mechanism of cognitive impairment. However, the peripheral immune biomarkers in patients troubled with MDD and SCD are not conventionally described. METHODS: A prospective-observational study was conducted for 8 weeks. Subjective cognitive function was measured using the Chinese version of the 20-item perceived deficits questionnaire-depression (PDQ-D) and depression symptoms were evaluated with Hamilton Depression Rating Scale-17 (HDRS-17). Luminex assays were used to measure 48 immune cytokines in plasma at baseline. Integrating these results and clinicopathological features, a logistic regression model was used to develop a prognostic prediction. RESULTS: Totally, 114 patients were enrolled in this study. Among the patients who completed follow-up, 56% (N = 50) had residual subjective cognitive decline, and 44% (N = 50) did not. The plasma levels of FGF basic, INF-γ, IL-1ß, MCP-1, M-CSF and SCF were increased and the levels of IL-9, RANTES and PDGF-BB were decreased in the SCD group. Additionally, Basic FGF, IFN-γ, IL-1ß, and SCF were positively correlated and IL-9, RANTES, and PDGF-BB were negatively correlated with the PDQ-D scores after treatment. Notably, combinations of cytokines (SCF and PDGF-BB) and PDQ-D scores at baseline showed good performance (The area under the receiver operating characteristic curve = 0.818) in the prediction of subjective cognitive decline. CONCLUSION: A prognostic model based on protein concentrations of SCF, PDGF-BB, and scores of PDQ-D showed considerable accuracy in predicting residual subjective cognitive decline in depression.
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Disfunção Cognitiva , Transtorno Depressivo Maior , Humanos , Transtorno Depressivo Maior/complicações , Transtorno Depressivo Maior/diagnóstico , Transtorno Depressivo Maior/psicologia , Estudos Prospectivos , Prognóstico , Becaplermina , Interleucina-9 , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Biomarcadores , CitocinasRESUMO
The selectivity control of Pd nanoparticles (NPs) in the direct CO esterification with methyl nitrite toward dimethyl oxalate (DMO) or dimethyl carbonate (DMC) remains a grand challenge. Herein, Pd NPs are incorporated into isoreticular metal-organic frameworks (MOFs), namely UiO-66-X (X=-H, -NO2 , -NH2 ), affording Pd@UiO-66-X, which unexpectedly exhibit high selectivity (up to 99 %) to DMC and regulated activity in the direct CO esterification. In sharp contrast, the Pd NPs supported on the MOF, yielding Pd/UiO-66, displays high selectivity (89 %) to DMO as always reported with Pd NPs. Both experimental and DFT calculation results prove that the Pd location relative to UiO-66 gives rise to discriminated microenvironment of different amounts of interface between Zr-oxo clusters and Pd NPs in Pd@UiO-66 and Pd/UiO-66, resulting in their distinctly different selectivity. This is an unprecedented finding on the production of DMC by Pd NPs, which was previously achieved by Pd(II) only, in the direct CO esterification.
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Metal nanoclusters (NCs) with atomically precise structures have sparked interest in catalysis. Unfortunately, their high aggregation tendency and the spatial resistance of surface ligands pose significant challenges. Herein, Au25 NCs are encapsulated into isoreticular metal-organic frameworks (MOFs), namely UiO-66-X (X = H, NH2, OH, and NO2), followed by the removal of surface ligands on Au25 NCs. The resulting surface-clean Au25 NCs, protected by the MOF spatial confinement, exhibit much superior activity and stability with respect to pristine Au25 NCs in the oxidative esterification of furfural. Remarkably, experimental and theoretical results jointly demonstrate that diverse functional groups on UiO-66-X modulate the Au25 electronic state, giving rise to the discriminated substrate adsorption energy of Au25@UiO-66-X. As a result, the high electron density and suitable substrate adsorption ability dominate the activity trend: Au25@UiO-66-NH2 > Au25@UiO-66-OH > Au25@UiO-66 > Au25@UiO-66-NO2. This work develops a new strategy for the stabilization of surface-clean metal NCs in pore wall-engineered MOFs for enhanced catalysis.
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BACKGROUND: Neuroinflammation-induced injury is intimately associated with poor prognosis in patients with cerebral venous sinus thrombosis (CVST). The cyclic GMP-AMP synthase-stimulator of interferon gene (cGAS-STING) axis is a cytoplasmic double-stranded DNA (dsDNA) sensing pathway has recently emerged as a crucial mediator of neuroinflammation in ischemic stroke. However, the role of the cGAS-STING pathway in modulating post-CVST inflammation and the underlying mechanisms involved remain unclear. METHODS: A CVST model was induced by ferric chloride in male C57BL/6J mice. The selective cGAS inhibitor RU.521, STING agonist 2'3'-cGAMP, and STING siRNA were delivered by intranasal administration or intraventricular injection. Post-CVST assessments included rotarod test, TUNEL staining, Fluoro-Jade C staining, dihydroethidium staining, western blotting, qPCR, immunofluorescence, immunohistochemistry, ELISA and flow cytometry. RESULTS: cGAS, STING, NLRP3 and GSDMD were significantly upregulated after CVST and mostly in the microglia of the mouse brain. CVST triggered the release of dsDNA into the cytoplasm and elicited an inflammatory response via activating the cGAS-STING axis. RU.521 decreased the levels of 2'3'-cGAMP, STING and downstream inflammatory cytokines, and suppressed the expressions of NLRP3 inflammasome and pyroptosis-pertinent components containing cleaved caspase-1, GSDMD, GSDMD-C, pro- and cleaved IL-1ß, and cleaved IL-1ß/pro-IL-1ß. Besides, RU.521 treatment also reduced oxidative stress, lessened the numbers of microglia and neutrophils, and ameliorated neuronal apoptosis, degeneration along with neurological deficits post-CVST. 2'3'-cGAMP delivery enhanced the expressions of STING and related inflammatory mediators, NLRP3 inflammasome and pyroptosis-relevant proteins, whereas these alterations were significantly abrogated by the silencing of STING by siRNA. CONCLUSIONS: Our data demonstrate that repression of the cGAS-STING pathway diminishes the neuroinflammatory burden of CVST and highlight this approach as a potential therapeutic tactic in CVST-mediated pathologies.
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Inflamassomos , Proteínas de Membrana/metabolismo , Piroptose , Animais , Modelos Animais de Doenças , Humanos , Inflamassomos/metabolismo , Interferons , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Doenças Neuroinflamatórias , Nucleotidiltransferases/metabolismo , RNA Interferente Pequeno/genética , Transdução de Sinais/fisiologiaRESUMO
Metal oxide nanomaterials directly grown on conductive substrates are optimal electrode materials because their structures allow for rapid ion and electron transport and thereby reduce internal resistance in the electrode. The development of such binder-free, self-supporting electrodes is of great significance for applications in electrocatalysis. In this work, a simple hydrothermal inâ situ self-assembly reaction and annealing process was developed to prepare three kinds of nickel oxide @ carbon felt (NiO@CF) nanocomposites with different morphologies. The influence of different precipitators (strong or weak bases) on the morphology of the resulting nano-sized nickel oxide nanocomposites was investigated. The microstructures of the NiO@CF samples were characterized with field emission scanning electron microscopy (FESEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), and X-ray photoelectron spectroscopy (XPS). When ammonia was used as the precipitator, NiO grew vertically on the surface of the carbon felt and formed a mesoporous nanosheet-like structure (NiO NSs@CF). As an electrocatalytic nitrogen reduction reaction (e-NRR) electrode, the NiO NSs@CF sample showed an excellent NH3 yield (71.3â µg h-1 â mg-1 cat. ) and Faradaic efficiency (17.9 % at -0.5â V vs. RHE) in 0.1â M Na2 SO4 . The good performance was attributed to the vertical interleaved mesoporous sheet-like structure (with the pore size of 15â nm and the thickness of â¼30â nm) and the relatively high concentration of oxygen vacancies. First-principles calculations with strong on-site Coulomb interactions demonstrated that the presence of oxygen vacancy on NiO sample leads to a significantly stronger N binding over the surface, benefiting for the nitrogen gas adsorption and reduction. The e-NRR performance of this binder-free, flexible electrode material is superior to that of other reported nickel-based nanomaterials. This study highlights the potential of such binder-free carbon felt electrodes for use in e-NRR that could meet the needs of industrial production.
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Inorganic metal halide perovskites, such as CsPbI3 , have recently drawn extensive attention due to their excellent optical properties and high photoelectric efficiencies. However, the structural instability originating from inherent ionic defects leads to a sharp drop in the photoelectric efficiency, which significantly limits their applications in solar cells. The instability induced by ionic defects remains unresolved due to its complicated reaction process. Herein, to explore the effects of ionic defects on stability, we develop a deep learning potential for a CsPbI3 ternary system based upon density functional theory (DFT) calculated data for large-scale molecular dynamics (MD) simulations. By exploring 2.4 million configurations, of which 7,730 structures are used for the training set, the deep learning potential shows an accuracy approaching DFT-level. Furthermore, MD simulations with a 5,000-atom system and a one nanosecond timeframe are performed to explore the effects of bulk and surface defects on the stability of CsPbI3 . This deep learning potential based MD simulation provides solid evidence together with the derived radial distribution functions, simulated diffraction of X-rays, instability temperature, molecular trajectory, and coordination number for revealing the instability mechanism of CsPbI3 . Among bulk defects, Cs defects have the most significant influence on the stability of CsPbI3 with a defect tolerance concentration of 0.32 %, followed by Pb and I defects. With regards to surface defects, Cs defects have the largest impact on the stability of CsPbI3 when the defect concentration is less than 15 %, whereas Pb defects act play a dominant role for defect concentrations exceeding 20 %. Most importantly, this machine-learning-based MD simulation strategy provides a new avenue to explore the ionic defect effects on the stability of perovskite-like materials, laying a theoretical foundation for the design of stable perovskite materials.
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Aprendizado Profundo , Luz SolarRESUMO
Polynuclear silver clusters have attracted intensive attention in the academic community owing to their rich physicochemical properties. The development of thione-protected silver clusters has been lagging behind the well-explored thiolate-protected silver-sulfide clusters. Herein, we report two N-heterocyclic thione-protected silver clusters: [Ag4(2-TBI)6(SO4)3]2- (Ag4) and [Br@Ag8(2-TBI)12(SO4)2]3+ (Ag8) (2-TBI = 2-thiobenzimidazol), which cocrystallize to form cluster-based molecular crystals with a CaF2-type structure. The cocrystal shows high thermal stability in air. Notably, the two cluster-based layers are alternately assembled to exhibit a unique k-vector-differential crystallographic arrangement. This work may lay a foundation for synthesis of atomically precise and stable silver clusters using readily available N-heterocyclic thione ligands.