ABSTRACT
BACKGROUND: Aortic aneurysm and aortic dissection (AAD) are life-threatening vascular diseases, with endothelium being the primary target for AAD treatment. Protein S-sulfhydration is a newly discovered posttranslational modification whose role in AAD has not yet been defined. This study aims to investigate whether protein S-sulfhydration in the endothelium regulates AAD and its underlying mechanism. METHODS: Protein S-sulfhydration in endothelial cells (ECs) during AAD was detected and hub genes regulating homeostasis of the endothelium were identified. Clinical data of patients with AAD and healthy controls were collected, and the level of the cystathionine γ lyase (CSE)/hydrogen sulfide (H2S) system in plasma and aortic tissue were determined. Mice with EC-specific CSE deletion or overexpression were generated, and the progression of AAD was determined. Unbiased proteomics and coimmunoprecipitation combined with mass spectrometry analysis were conducted to determine the upstream regulators of the CSE/H2S system and the findings were confirmed in transgenic mice. RESULTS: Higher plasma H2S levels were associated with a lower risk of AAD, after adjustment for common risk factors. CSE was reduced in the endothelium of AAD mouse and aorta of patients with AAD. Protein S-sulfhydration was reduced in the endothelium during AAD and protein disulfide isomerase (PDI) was the main target. S-sulfhydration of PDI at Cys343 and Cys400 enhanced PDI activity and mitigated endoplasmic reticulum stress. EC-specific CSE deletion was exacerbated, and EC-specific overexpression of CSE alleviated the progression of AAD through regulating the S-sulfhydration of PDI. ZEB2 (zinc finger E-box binding homeobox 2) recruited the HDAC1-NuRD complex (histone deacetylase 1-nucleosome remodeling and deacetylase) to repress the transcription of CTH, the gene encoding CSE, and inhibited PDI S-sulfhydration. EC-specific HDAC1 deletion increased PDI S-sulfhydration and alleviated AAD. Increasing PDI S-sulfhydration with the H2S donor GYY4137 or pharmacologically inhibiting HDAC1 activity with entinostat alleviated the progression of AAD. CONCLUSIONS: Decreased plasma H2S levels are associated with an increased risk of aortic dissection. The endothelial ZEB2-HDAC1-NuRD complex transcriptionally represses CTH, impairs PDI S-sulfhydration, and drives AAD. The regulation of this pathway effectively prevents AAD progression.
Subject(s)
Aortic Aneurysm , Aortic Dissection , Animals , Mice , Cystathionine gamma-Lyase/genetics , Endothelial Cells/metabolism , Endothelium/metabolism , Histone Deacetylase 1 , Hydrogen Sulfide/metabolism , Mi-2 Nucleosome Remodeling and Deacetylase Complex , Protein S , Zinc Finger E-box Binding Homeobox 2ABSTRACT
The complexity of the multielement interaction in high-entropy alloys (HEAs) may provide more active sites to adapt different catalytic reaction steps in oxygen evolution reaction (OER). Investigating the correlation between structure and performance of HEAs electrocatalysts is both essential and challenging. In this work, FeCoNiCrMox HEA nanoparticles are successfully fabricated utilizing a unique nanofabrication method called inert gas condensation. With the increase of high-valence metal component Mo, the atomic structure amorphization and electronic structure reconstruction are unveiled. According to the X-ray photoelectron spectroscopy valence spectra, the d-band center of FeCoNiCrMox is ascending, and thus enhancing the adsorption energy. Synchrotron pair distribution function analysis reflects the degree of structural disorder and reveals a robust correlation with the intrinsic OER activities of the electrocatalysts. FeCoNiCrMo1.0 high-entropy metallic glass nanoparticles exhibit an outstanding OER performance with an ultralow overpotential of 294.5 mV at a high current density of 100 mA cm-2. This work brings fundamental and practical insights into the modulation mechanism of metal components of HEAs catalysts for developing OER.
ABSTRACT
The unique catalytic activities of high-entropy alloys (HEAs) emerge from the complex interaction among different elements in a single-phase solid solution. As a "green" nanofabrication technique, inert gas condensation (IGC) combined with laser source opens up a highly efficient avenue to develop HEA nanoparticles (NPs) for catalysis and energy storage. In this work, the novel N-doped non-noble HEA NPs are designed and successfully prepared by IGC. The N-doping effects of HEA NPs on oxygen evolution reaction (OER) and hydrogen evolution reaction (HER) are systematically investigated. The results show that N-doping is conducive to improving the OER, but unfavorable for HER activity. The FeCoNiCrN NPs achieve an overpotential of 269.7 mV for OER at a current density of 10 mA cm-2 in 1.0 M KOH solution, which is among the best reported values for non-noble HEA catalysts. The effects of the differences in electronegativity, ionization energy and electron affinity energy among mixed elements in N-doped HEAs are discussed as inducing electron transfer efficiency. Combined with X-ray photoelectron spectroscopy and the extended X-ray absorption fine structure analysis, an element-design strategy in N-doped HEAs electrocatalysts is proposed to improve the intrinsic activity and ameliorate water splitting performance.
ABSTRACT
Cardiac fibrosis (CF) is an irreversible pathological process that occurs in almost all kinds of cardiovascular diseases. Phosphorylation-dependent activation of c-Jun N-terminal kinase (JNK) induces cardiac fibrosis. However, whether S-nitrosylation of JNK mediates cardiac fibrosis remains an open question. A biotin-switch assay confirmed that S-nitrosylation of JNK (SNO-JNK) increased significantly in the heart tissues of hypertrophic patients, transverse aortic constriction (TAC) mice, spontaneously hypertensive rats (SHRs), and neonatal rat cardiac fibroblasts (NRCFs) stimulated with angiotensin II (Ang II). Site to site substitution of alanine for cysteine in JNK was applied to determine the S-nitrosylated site. S-Nitrosylation occurred at both Cys116 and Cys163 and substitution of alanine for cysteine 116 and cysteine 163 (C116/163A) inhibited Ang II-induced myofibroblast transformation. We further confirmed that the source of S-nitrosylation was inducible nitric oxide synthase (iNOS). 1400 W, an inhibitor of iNOS, abrogated the profibrotic effects of Ang II in NRCFs. Mechanistically, SNO-JNK facilitated the nuclear translocation of JNK, increased the phosphorylation of c-Jun, and induced the transcriptional activity of AP-1 as determined by chromatin immunoprecipitation and EMSA. Finally, WT and iNOS-/- mice were subjected to TAC and iNOS knockout reduced SNO-JNK and alleviated cardiac fibrosis. Our findings demonstrate an alternative mechanism by which iNOS-induced SNO-JNK increases JNK pathway activity and accelerates cardiac fibrosis. Targeting SNO-JNK might be a novel therapeutic strategy against cardiac fibrosis.
Subject(s)
Fibrosis/pathology , Heart Diseases/pathology , JNK Mitogen-Activated Protein Kinases/metabolism , Angiotensin II/pharmacology , Animals , Aorta/drug effects , Fibroblasts/drug effects , Humans , Imines/pharmacology , Mice , Mice, Inbred C57BL , Mice, Knockout , Nitric Oxide Synthase Type II/drug effects , Rats , Rats, Inbred SHR , Signal Transduction/drug effectsABSTRACT
Distant metastasis frequently occurs in oral squamous cell carcinoma (OSCC) and contributes to the adverse prognosis for patients with OSCC. However, the potential mechanisms behind the metastasis have not yet been clarified. This study investigated the role of miR-378 in the migration and invasiveness of OSCC in vitro and in vivo. According to our results, the migration and invasiveness of OSCC cells were increased in cells overexpressing miR-378, and reduced in cells where miR-378-3p/5p was silenced. In addition, overexpression of miR-378 suppressed the expressions and activities of matrix metalloproteinase 9 (MMP-9) and MMP-2. Epithelial-mesenchymal transition (EMT) was restrained by overexpression of miR-378, as evidenced by an increase in E-cadherin expression and decrease in N-cadherin and uPA expression. However, knockdown of miR-378-3p/5p produced the opposite results. Moreover, kallikrein-related peptidase 4 (KLK4) was confirmed to be a target gene of miR-378. Overexpression of KLK4 reversed the induced decrease in migration and invasiveness of cells overexpressing miR-378 by upregulating the levels of MMP-9, MMP-2, and N-cadherin, and downregulating the level of E-cadhrin. Finally, the number of metastasis nodules in the lung tissues of nude mice was reduced by overexpression of miR-378, whereas the number of metastases increased with knockdown of miR-378. Taken together, our results suggest that the miR-378-KLK4 axis is involved in the mechanisms behind the migration and invasiveness of OSCC cells. Targeting the miR-378-KLK4 axis may be an effective measure for treating OSCC.
Subject(s)
Carcinoma, Squamous Cell/metabolism , Kallikreins/metabolism , MicroRNAs/metabolism , Mouth Neoplasms/metabolism , Animals , Antigens, CD/metabolism , Cadherins/metabolism , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Movement , Epithelial-Mesenchymal Transition , Gene Silencing , Humans , Lung/metabolism , Matrix Metalloproteinase 2/metabolism , Matrix Metalloproteinase 9/metabolism , Mice , Mice, Nude , Mouth Neoplasms/pathology , Neoplasm Invasiveness , Neoplasm MetastasisABSTRACT
OBJECTIVE: To investigate the protective effect of Wuziyanzong Pills (WYP) in the rat model of oligoasthenospermia (OAS) and its action mechanism. METHODS: Sixty male SD rats were equally randomized into six groups: normal control, OAS model, Shengjing Capsules (1.6 g per kg of the body weight), low-dose WYP (1 g per kg of the body weight), medium-dose WYP (2 g per kg of the body weight), and high-dose WYP (4 g per kg of the body weight). The OAS model was established by intragastric administration of Tripterygium glucoside at 30 mg per g per d for 6 weeks. From the 3rd week of modeling, the rats of the medication groups were treated intragastrically with corresponding drugs for 4 weeks. Then all the rats were sacrificed for measurement of the testicular and epididymal organ coefficients, examination of epididymal sperm quality and apoptosis, and detection of the openness of the sperm mitochondrial permeability transition pore (MPTP). Histopathological changes in the testis were observed by HE staining and the apoptosis of spermatogenic cells determined by Hochest staining. RESULTS: WYP obviously improved the organ coefficients of the testis and epididymis, increased sperm concentration, motility and viability, decreased the apoptosis of spermatogenic cells, and inhibited the abnormal openness of MPTP in the OAS model rats. HE staining showed that the number and levels of spermatogenic cells were significantly increased while Hochest staining manifested that the apoptosis of spermatogenic cells was remarkably inhibited in the seminiferous tubules of the testis in the WYP-treated rats. CONCLUSIONS: WYP can improve sperm quality and reduce the apoptosis of spermatogenic cells (including sperm) in OAS model rats, which may be related with its inhibitory effect on the abnormal openness of MPTP.
Subject(s)
Asthenozoospermia/drug therapy , Drugs, Chinese Herbal/pharmacology , Epididymis/drug effects , Oligospermia/drug therapy , Spermatozoa/drug effects , Testis/drug effects , Animals , Apoptosis/drug effects , Asthenozoospermia/chemically induced , Male , Mitochondrial Membrane Transport Proteins/drug effects , Mitochondrial Permeability Transition Pore , Random Allocation , Rats , Rats, Sprague-Dawley , Sperm Count , Sperm Motility/drug effects , Spermatozoa/cytology , TripterygiumABSTRACT
In recent years, antibiotic-based carbon nanodots have been extensively developed and studied, because of their excellent synergistic fluorescence and antibacterial properties. These antibacterial carbon nanodots have also been developed with various new applications, such as heavy iron detection, pH sensitivity, temperature response, and bacterial count detection in various environments. In this article, using vancomycin hydrochloride as the only precursor, vancomycin hydrochloride carbon nanodots were rapidly synthesized by a one-step microwave method. The diameter of the vancomycin hydrochloride carbon nanodots was concentrated at 0.899 ± 0.40 nm with a uniform size and excitation-dependent fluorescence. Vancomycin hydrochloride carbon nanodots showed better antibacterial activity than the original vancomycin hydrochloride with low biological toxicity and good stability. In the pH range of approximately 7-13, there was a good linear relationship between the fluorescence intensity of the carbon nanodots and the pH value (R2 = 0.98516). Moreover, vancomycin hydrochloride carbon nanodots could quickly and specifically detect poisonous Sn4+ through changes in their fluorescence intensity, with a detection limit of approximately 5.2 µM. Multifunctional vancomycin hydrochloride carbon nanodots have good application prospects in the fields of antibacterial, toxic Sn4+ detection, and pH-sensitive aspects.
ABSTRACT
This study examined the accuracy of the Behavior Assessment System for Children-3 for Autism Spectrum Disorder (ASD) diagnosis using parent (PRS) and teaching rating (TRS) scales. The accuracy of three PRS and TRS derived scores with strong theoretical relationships to ASD (Developmental Social Disorders [DSD], Atypicality [ATP], and Withdrawal [WIT]) and the Autism Probability Index (AUI) was examined. The T scores of 149 children with ASD were compared with typically developing children within similar demographics to assess diagnostic accuracy (i.e., differential validity). The results revealed statistically significant differences for all scales between the group with ASD and the matched group of typically developing children. Sensitivity and specificity were maximized for both the PRS and TRS when DSD, ATP, and WIT scales were greater than 60 and a cut score of on the AUI was set at 55. Overall, sensitivity and specificity indexes associated with these cut scores demonstrated strong diagnostic utility for differentiating the two groups.
Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Adenosine Triphosphate , Adolescent , Autism Spectrum Disorder/diagnosis , Child , Humans , Parents , Sensitivity and SpecificityABSTRACT
Developing carbon-based catalysts for advanced oxidation processes, owing to their abundant reserves, metal-free properties, superior biocompatibility as well as great resistance to acids and alkalis, presents an enticing prospect for environmental remediation. The thermally reduced graphene with diverse surface functional groups from vacuum-promoting thermal expansion of graphene oxide was fabricated by the progressive carbonization from 250 °C to 1000 °C (denoted as G250, G600, and G1000 according to temperature). Among them, G1000 possessed highest defective degrees, the largest specific surface area, and the most abundant, highly active oxygen-containing functional groups such as ketones and quinones. 0.10 g L-1 of G1000 could almost completely eliminate bisphenol A (19 mg L-1) within 15 min under the synergistic effect of adsorption and degradation. The structural evolution of graphene during the thermal-reduction process was systematically characterized and analyzed to understand the peroxymonosulfate-activated mechanism. The technological means included active species quenching experiments, electron paramagnetic resonance tests, and electrochemical analyses. This work presents some solid evidence to support the origin of active sites for catalytic degradation and provides new insights into the design of non-metallic catalysts in advanced oxidation processes.
Subject(s)
Graphite , Graphite/chemistry , Oxygen/chemistry , Peroxides/chemistry , Oxidation-ReductionABSTRACT
Novel hierarchical CuNiAl layered double hydroxide (CuNiAl LDH) nanotubes were prepared with in situ transformation of Al2O3 produced using the atomic layer deposition (ALD) method. Based on the characterizations using X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), FT-IR spectrometry, scanning electron microscopy (SEM) and transmission electron microscopy (TEM), CuNiAl LDH displays a typical nanotube-like structure consisting of uniform ultrathin nanoflakes. It is also confirmed that nitrate precursors play a crucial role in the formation of the LDH hierarchical structure. The unique hierarchical tube-like structure for CuNiAl LDH can supply more active sites and higher surface areas, leading to outstanding peroxidase mimicking property. The kinetic analyses indicate that the catalytic behavior of CuNiAl LDH follows classic Michaelis-Menten models and the affinity of CuNiAl LDH to the substrate is significantly higher than horseradish peroxidase. A simple and label-free method was developed for the colorimetric detection of glucose. As low as 2.9 µM of glucose can be detected with a broad linear range from 10 to 200 µM. The established method is also proved to be suitable for glucose detection in juice samples.
Subject(s)
Aluminum/chemistry , Copper/chemistry , Glucose/analysis , Hydroxides/chemistry , Nanotubes/chemistry , Nickel/chemistry , Benzidines/chemistry , Catalysis , Colorimetry , Fruit and Vegetable Juices/analysis , Glucose Oxidase/chemistry , Hydrogen Peroxide/analysis , PeroxidaseABSTRACT
High-performance microwave absorbers with special features are desired to meet the requirements of more complex modern service environments, especially corrosive environments. Therefore, high-efficiency microwave absorbers with corrosion resistance should be developed urgently. Herein, a 3D NiAl-layered double hydroxide/graphene (NiAl-LDH/G) composite synthesized by atomic-layer-deposition-assisted in situ growth is presented as an anticorrosive microwave absorber. The content of NiAl-LDH in the composite is optimized to achieve impedance matching. Furthermore, under the cooperative effects of the interface polarization loss, conduction loss, and 3D porous sandwich-like structure, the optimal NiAl-LDH/G shows excellent microwave absorption performance with a minimum reflection loss of -41.5 dB and a maximum effective absorption bandwidth of 4.4 GHz at a loading of only 7 wt% in epoxy. Remarkably, the encapsulation effect of NiAl-LDH can restrain the galvanic corrosion owing to graphene. The epoxy coating with the NiAl-LDH/G microwave absorber on carbon steel exhibits long-term corrosion resistance, owing to the synergetic effect of the superior impermeability of graphene and the chloridion-capture capacity of the NiAl-LDH. The NiAl-LDH/G composite is a promising anticorrosive microwave absorber, and the findings of this study may motivate the development of functional microwave absorbers that meet the demands of anticorrosive performance of coatings.
ABSTRACT
Atherosclerosis-associated cardiovascular disease is one of the main causes of death and disability among patients with diabetes mellitus. However, little is known about the impact of S-nitrosylation in diabetes-accelerated atherosclerosis. Here, we show increased levels of S-nitrosylation of guanine nucleotide-binding protein G(i) subunit alpha-2 (SNO-GNAI2) at Cysteine 66 in coronary artery samples from diabetic patients with atherosclerosis, consistently with results from mice. Mechanistically, SNO-GNAI2 acted by coupling with CXCR5 to dephosphorylate the Hippo pathway kinase LATS1, thereby leading to nuclear translocation of YAP and promoting an inflammatory response in endothelial cells. Furthermore, Cys-mutant GNAI2 refractory to S-nitrosylation abrogated GNAI2-CXCR5 coupling, alleviated atherosclerosis in diabetic mice, restored Hippo activity, and reduced endothelial inflammation. In addition, we showed that melatonin treatment restored endothelial function and protected against diabetes-accelerated atherosclerosis by preventing GNAI2 S-nitrosylation. In conclusion, SNO-GNAI2 drives diabetes-accelerated atherosclerosis by coupling with CXCR5 and activating YAP-dependent endothelial inflammation, and reducing SNO-GNAI2 is an efficient strategy for alleviating diabetes-accelerated atherosclerosis.
Subject(s)
Atherosclerosis/etiology , Atherosclerosis/metabolism , Diabetic Angiopathies/etiology , Diabetic Angiopathies/metabolism , GTP-Binding Protein alpha Subunit, Gi2/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Animals , Cells, Cultured , Cysteine/chemistry , Diabetes Mellitus, Experimental/complications , Diabetes Mellitus, Experimental/metabolism , GTP-Binding Protein alpha Subunit, Gi2/chemistry , GTP-Binding Protein alpha Subunit, Gi2/genetics , Hippo Signaling Pathway , Human Umbilical Vein Endothelial Cells , Humans , Male , Melatonin/pharmacology , Mice , Mice, Knockout , Mutagenesis, Site-Directed , Nitric Oxide Synthase Type II/metabolism , Nitroso Compounds/chemistry , Nitroso Compounds/metabolism , Protein Serine-Threonine Kinases/metabolism , Receptors, CXCR5/deficiency , Receptors, CXCR5/genetics , Receptors, CXCR5/metabolism , Transcription Factors/metabolism , YAP-Signaling ProteinsABSTRACT
ß-FeOOH is utilized as a new cathode material for rechargeable chloride ion batteries for the first time. ß-FeOOH has superior rate capabilities and a high reversible capacity of 122 mA h g-1 after 100 cycles. This work opens up new possibilities for the development of anion batteries.
ABSTRACT
The exploration of flexible supercapacitors with high energy density is a matter of considerable interest to meet the demand of wearable electronic devices. In this work, with carbon nanotubes (CNTs) grown on carbon cloth (CC) as flexible substrate, NiCoP nanoflake-surrounded CNT nanoarrays (NiCoP/CNT) and N-doped carbon coated CNT nanoarrays (CNT@N-C) were synthesized on CC and utilized as cathode and anode materials for constructing flexible all-solid-state hybrid supercapacitor. Both them exhibit excellent electrochemical performance. NiCoP/CNT/CC composites can deliver a specific capacitance of 261.4 mAh g-1, and CNT@N-C/CC exhibits a high capacitance of 256 F g-1 at the current density of 0.5 A g-1. The hybrid supercapacitor built from the two well designed electrodes can provide a specific capacitance of 123.3 mAh g-1 at current density 1 mA g-1 within a potential window of 0-1.5 V and retain almost 85% of its initial capacitance after 5000 cycles. Furthermore, the flexible devices show the maximum energy density of 138.7 Wh kg-1 and a power density of 6.25 kW kg-1, obviously superior to some recent reported supercapacitor devices, indicating its potential in practical application.
ABSTRACT
This study illustrates the accuracy and efficiency of using an evidence-based assessment (EBA) strategy for diagnosis of attention-deficit/hyperactivity disorder (ADHD) by integrating the scale scores obtained on BASC-3 teacher and parent rating scales. The examined process used empirical diagnostic likelihood ratios (DLRs) derived from a sample of children with ADHD (N = 339) matched on demographic characteristics from the normative sample. The results show that behavioral scales of executive functioning and functional communication provided incremental utility in ADHD diagnosis. With a revised probability of .80 or higher as the diagnostic criterion, teachers, and parents positively diagnosed 70% and 94% of the ADHD cases respectively. The EBA approach was efficient, with four scales on average used to reach the proposed posterior probability for final diagnosis. Finally, teachers and parents demonstrated a high agreement with respect to the diagnosis results and scales used for the diagnosis.