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In this study, a ratiometric fluorescence nanoprobe is developed for the analysis of hydrogen peroxide (H2O2). Silver nanoclusters (AgNCs) were synthesized by chemical reduction method using sodium borohydride (NaBH4) as reducing agent, and were coupled with CdSe/ZnS quantum dots (QDs) to form the ratiometric fluorescence nanoprobe silver nanoclusters-quantum dots (AgNCs-QDs). The effect of the volume ratio of CdSe/ZnS QDs to AgNCs on the fluorescence ratio of AgNCs-QDs was investigated. The fluorescence characterization results show that two emission peaks of AgNCs-QDs are located at 473 nm and 661 nm, respectively. Transmission electron microscope (TEM) and X-ray photoelectron spectroscopy (XPS) results show that H2O2 can cause the fluorescence probe to aggregate, while etching AgNCs to produce silver ions, which together cause the fluorescence of the QDs in the ratiometric fluorescent probe to be quenched. Based on this strategy, the fluorescence intensity ratio of the two emission peaks F473/F661 exhibits a strong linear correlation with the concentration of H2O2. The detection range is 3.32 µM ~ 2.65 mM with a detection limit of 3.32 µM. In addition, the ratiometric fluorescence probe can specifically recognize H2O2 and has excellent anti-interference performance and good fluorescence stability. Importantly, the probe was utilized for the detection of H2O2 in serum, showing the possibility of the probe in clinical detection applications.
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BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that results from widespread immune complex deposition and secondary tissue injury. Hydroxychloroquine (HCQ) has been used clinically to treat SLE, while its exact mechanism has still remained elusive. Some studies have shown that myeloid-derived suppressor cells (MDSCs) play a vital role in the regulation of SLE. In this study, we aimed to explore the effects of HCQ on the apoptosis of MDSCs in lupus mice and its possible molecular regulatory mechanism. METHODS: We constructed the imiquimod (IMQ)-induced lupus model in mice. The proportion and apoptosis of MDSCs were measured by flow cytometry. CD81-overexpressed adeno-associated virus was intraperitoneally injected into the lupus mice. We also transfected the CD81 siRNA into bone marrow-derived MDSCs, and employed qRT-PCR and Western blotting to quantify the level of CD81. RESULTS: The results showed that HCQ ameliorated IMQ-induced lupus symptoms, and simultaneously inhibited the expansion of MDSCs. In particular, HCQ induced the apoptosis of MDSCs, and also up-regulated the expression level of CD81 in MDSCs, which might indicate the relationship between the expression level of CD81 and the apoptosis of MDSCs. CD81 was further confirmed to participate in the apoptosis of MDSCs and lupus disease progression by overexpressing CD81 in vivo. Molecular docking experiment further proved the targeting effect of HCQ on CD81. And then we interfered CD81 in bone marrow derived MDSCs in vitro, and it was revealed that HCQ rescued the decreased expression level of CD81 and relieved the immune imbalance of Th17/Treg cells. CONCLUSION: In summary, HCQ promoted the apoptosis of MDSCs by up-regulating the expression level of CD81 in MDSCs, and ultimately alleviated lupus symptoms. Our results may assist scholars to develop further effective therapies for SLE.
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Antirreumáticos , Lúpus Eritematoso Sistêmico , Células Supressoras Mieloides , Animais , Antirreumáticos/uso terapêutico , Apoptose , Hidroxicloroquina/metabolismo , Hidroxicloroquina/farmacologia , Hidroxicloroquina/uso terapêutico , Camundongos , Simulação de Acoplamento Molecular , Células Supressoras Mieloides/metabolismo , Regulação para CimaRESUMO
A multimodal deep learning model, DeepNCI, is proposed for improving noncovalent interactions (NCIs) calculated via density functional theory (DFT). DeepNCI is composed of a three-dimensional convolutional neural network (3D CNN) for abstracting critical and comprehensive features from 3D electron density, and a neural network for modeling one-dimensional quantum chemical properties. By merging features from two networks, DeepNCI is able to reduce the root-mean-square error of DFT-calculated NCI from 1.19 kcal/mol to â¼0.2 kcal/mol for a NCI molecular database (>1000 molecules). The representativeness of the joint features can be visualized by t-distributed stochastic neighbor embedding (t-SNE), where they can distinguish categorized NCI systems quite well. Therefore, the fused model performs better than its component networks. In addition, the 3D CNN takes electron density as inputs that are in the same range, despite the size of molecular systems, so it can promote model applicability and transferability. To clarify the applicability of DeepNCI, an application domain (AD) has been defined with merged features using the K-nearest-neighbor method. The calculations for external test sets are shown that AD can properly monitor the reliability for a prediction. The model transferability is tested with a small database of homolysis bond dissociation energy including only dozens of samples. With NCI database pretrained parameters, the same or better performance than the reported results is achieved by transfer learning. This suggests that the DeepNCI model is transferable and it may transfer to other relative tasks, which possibly can resolve some small sampling problems. The source code of DeepNCI can be freely accessed at https://github.com/wenzelee/DeepNCI.
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Bases de Dados de Compostos Químicos , Redes Neurais de Computação , Reprodutibilidade dos Testes , Análise por Conglomerados , Bases de Dados FactuaisRESUMO
Na metal anode is one of most promising anode materials for next-generation secondary batteries. However, the practical application of Na anode is limited by dendritic growth, rapid volume change, and serious interface problems in the process of Na electroplating/stripping, resulting in low coulombic efficiency, short life, and safety issues of sodium metal batteries (SMBs). Herein, the cyclic instability mechanisms of the Na anode and the corresponding advanced protection strategies including in situ solid-electrolyte-interphase (SEI), artificial SEI, and three-dimensional conductive frame, are systematically reviewed. Notably, this review summarizes the latest research progress on interface modification and electrode modification of all-solid-state SMBs. Finally, the outlooks of anode interphase in SMBs are summarized and prospected, providing a promising way for high-energy and safe SMBs.
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BACKGROUND: The impact of different pouch phenotypes on long-term functional outcomes and quality of life (QoL) remains unclear. Our aim is to investigate the association between endoscopic pouchitis phenotypes and patients' long-term prognosis by assessing pouch function and QoL. METHODS: Pouchitis was classified into distinct phenotypes according to the Chicago Classification. Pouch function was assessed using the Pouch Functional Score (PFS), and QoL was evaluated using the Cleveland Global Quality of Life (CGQL) score. RESULTS: A total of 252 patients were enrolled in the study, with 78 patients diagnosed with pouchitis. According to the Chicago classification, 42 of these pouchitis patients exhibited an endoscopic phenotype characterized by a combination of diffuse inflammation of the pouch body, inlet involvement, and cuffitis, referred to as the Diffuse-Inlet-Cuffitis phenotype. Patients with pouchitis of the Diffuse-Inlet-Cuffitis phenotype showed significantly higher PFS (11.5 vs 5.5, p = 0.013) and lower CGQL scores (0.67 vs 0.7, p = 0.029) compared to those with other pouch phenotypes. Independent risk factors for this severe phenotype were identified as preoperative disease duration (OR = 1.062, 95% CI: 1.006-1.122, p = 0.030) and disease extent E3 (OR = 2.836, 95% CI: 1.052-7.644, p = 0.036). CONCLUSIONS: Our study suggested that pouchitis with the Diffuse-Inlet-Cuffitis endoscopic phenotype is common and seriously impairs the long-term prognosis in patients with UC after IPAA. The finding will be beneficial to the stratified management of patients with pouchitis.
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OBJECTIVE: This study explores LncRNA TM1-3P effects on the proliferation, apoptosis, and inflammatory response of fibroblasts in osteoarthritis (OA) and its underlying mechanism. METHODS: Bioinformatics was performed to analyze OA disease-related genes, miRNA profiles, and function. The targeted regulation of LncRNA TM1-3P and miR-144-3p, ONECUT2 and miR-144-3p were analyzed by dual luciferase reporter gene assay, RNA Binding Protein Immunoprecipitation (RIP), and RNA pull down. Histopathological morphology of the knee joint was observed by hematoxylin-eosin (HE) and Annona Red O/Fast Green. The expressions of mRNAs and proteins were detected by RT-qPCR, Western blot, and immunohistochemistry. Unpaired T test was used between groups, and the one-way analysis of variance of repeated measurement data was applied for multi-group comparison, following Tukey's post-test. RESULTS: ONECUT2 and Smurf2 genes were significantly elevated in the osteoarthritis group compared with the normal group (P < 0.001, P < 0.001). Expressions of ONECUT2 and LncRNA TM1-3P were increased, and expression of miR-144-3p was decreased in interleukin (IL)-1ß-induced human fibroblast synovial cells (hFSCs) (mRNA: 1.06 ± 0.24 vs. 3.29 ± 0.73, proteins: 0.22 ± 0.03 vs. 0.46 ± 0.22, 1.23 ± 0.22 vs. 3.76 ± 0.73, 1.06 ± 0.25 vs. 0.37 ± 0.13, P < 0.01, P < 0.001, P < 0.01, P < 0.05). Overexpression of miR-144-3p down-regulated the ONECUT2 expression, reduced cell proliferation, promoted apoptosis in hFSCs induced by IL-1ß (mRNA: 0.89 ± 0.14 vs. 0.15 ± 0.01, P < 0.05; proteins: 0.46 ± 0.01 vs. 0.23 ± 0.01, P < 0.001; CCK8: 1.88 ± 0.07 vs. 1.65 ± 0.07; P < 0.05; EDU: 55.82 ± 1.44 vs 40.57 ± 2.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.0001). Overexpression of LncRNA TM1-3P up-regulated the expression of ONECUT2, promoted cell proliferation, and inhibited apoptosis (mRNA: 0.9 ± 0.09 vs 1.94 ± 0.12, P < 0.05; proteins: 0.61 ± 0.05 vs 0.76 ± 0.03, P > 0.05; CCK8: 2.07 ± 0.05 vs 2.47 ± 0.06; P < 0.01; EDU: 52.67 ± 1.17 vs 60.06 ± 3.24, P < 0.05; apoptosis: 10.57 ± 0.79 vs 16.36 ± 0.35, P < 0.001), which were reversed by the overexpression of miR-144-3p treatment (mRNA: 1.82 ± 0.07 vs 0.31 ± 0.07, P < 0.0001; proteins: 0.74 ± 0.02 vs 0.35 ± 0.01, P < 0.01; CCK8: 2.41 ± 0.01 vs 1.67 ± 0.02; P < 0.0001; EDU: 66.85 ± 2.86 vs 44.68 ± 1.97, P < 0.0001; apoptosis: 7.19 ± 0.19 vs 13.36 ± 0.53, P < 0.0001). Silencing LncRNA TM1-3P attenuated the injury of knee joint tissue, down-regulated the expression of ONECUT2, Smurf2, IL-1ß, IL-6, TNF-α, and improved the expression of Rap1 in rats (0.71 ± 0.04 vs 0.48 ± 0.02, 0.68 ± 0.06 vs 0.36 ± 0.02, 0.74 ± 0.03 vs 0.49 ± 0.04, 0.78 ± 0.01 vs 0.54 ± 0.03, 0.68 ± 0.02 vs 0.4 ± 0.04, 0.24 ± 0.01 vs 0.4 ± 0.03, P < 0.05, P < 0.05, P < 0.05, P < 0.01, P < 0.01, P < 0.05). CONCLUSION: LncRNA TM1-3P improved inflammation and damage of knee joints in OA rats through miR-144-3p/ONECUT2 axis, providing a new theoretical basis for gene therapy of OA.
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Proteínas de Homeodomínio , MicroRNAs , Osteoartrite , RNA Longo não Codificante , Animais , Humanos , Ratos , Apoptose , Proliferação de Células , Condrócitos/metabolismo , Fibroblastos/metabolismo , Proteínas de Homeodomínio/metabolismo , Inflamação/metabolismo , MicroRNAs/metabolismo , Osteoartrite/genética , RNA Longo não Codificante/metabolismo , RNA Mensageiro/metabolismo , Fatores de Transcrição/metabolismo , Ubiquitina-Proteína Ligases/metabolismoRESUMO
Adeno-associated virus (AAV) is a leading vector for virus-based gene therapy. The receptor for AAV (AAVR; also named KIAA0319L) was recently identified, and the precise characterization of AAV-AAVR recognition is in immediate demand. Taking advantage of a particle-filtering algorithm, we report here the cryo-electron microscopy structure of the AAV2-AAVR complex at 2.8 Å resolution. This structure reveals that of the five Ig-like polycystic kidney disease (PKD) domains in AAVR, PKD2 binds directly to the spike region of the AAV2 capsid adjacent to the icosahedral three-fold axis. Residues in strands B and E, and the BC loop of AAVR PKD2 interact directly with the AAV2 capsid. The interacting residues in the AAV2 capsid are mainly in AAV-featured variable regions. Mutagenesis of the amino acids at the AAV2-AAVR interface reduces binding activity and viral infectivity. Our findings provide insights into the biology of AAV entry with high-resolution details, providing opportunities for the development of new AAV vectors for gene therapy.
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Capsídeo/metabolismo , Infecções por Parvoviridae/virologia , Parvovirinae/metabolismo , Receptores de Superfície Celular/metabolismo , Capsídeo/ultraestrutura , Proteínas do Capsídeo/genética , Proteínas do Capsídeo/metabolismo , Linhagem Celular , Microscopia Crioeletrônica , Dependovirus , Interações Hospedeiro-Parasita , Humanos , Parvovirinae/genética , Parvovirinae/ultraestrutura , Ligação Proteica , Domínios Proteicos , Receptores de Superfície Celular/química , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/ultraestruturaRESUMO
A total of 14 samples were collected in May 2016(dry season)and August 2016 (wet season) in the downstream area of the Taizi River. â³15 N-NO3- and â³18 O-NO3- were determined using the azide method, and â³18 O-H2O was determined using a CO2-H2O equilibration technique. To identify NO3- sources and transformations in the downstream area of Taizi River Basin, ion chromatography, Nessler's reagent spectrophotometry, the azide method, and CO2-H2O equilibration methods were utilized to determine the concentrations of NO3-, Cl-, NH4+-N, and isotopic compositions (â³15 N and â³18 O) of NO3- and the â³18 O-H2O in surface water. The results showed that the NO3- was mainly derived from mixed sources. During the dry season, the nitrate in the surface water was derived from soil nitrogen, manure, and sewage in the upper reaches, and mainly derived from synthetic fertilizer, manure, and sewage in the middle and lower reaches of the Beisha River. The nitrate was mainly derived from manure and sewage in the Nansha River. The nitrate was mainly derived from soil nitrogen in the upper reaches, mainly derived from synthetic fertilizer, manure, and sewage in the middle reaches, and mainly derived from manure and sewage in the lower reaches of the Haicheng River. During the wet season, the nitrate sources in surface water were soil nitrogen, synthetic fertilizer, manure, and sewage in the Beisha River; synthetic fertilizer, manure, and sewage in the middle and lower reaches of the Haicheng River and the Nansha River; and soil nitrogen and synthetic fertilizer in the upper reaches of the Haicheng River. NO3- and NH4+-N concentrations decreased with increasing â³15 N-NO3- from the dry season to the wet season, indicating that volatilization of NH4+-N and denitrification of NO3- might occur during the wet season. There is a slightly positive relationship between the reciprocal of the concentration of 1/ρ(NO3-) and â³15 N-NO3- during the wet season, indicating that mixing processes occurred in surface water. The results will provide information on nitrate sources during seasonal variations in the plain areas.
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This study analyzed the nitrate (NO3-), ammonia nitrogen (NH4+-N), chloride (Cl-), δ15 N-NO3-, δ18O-NO3-, and δ18O-H2O in the surface water to identify the nitrate sources and transformation processes in midstream areas of the Taizi River basin in May and August 2016, corresponding to the dry season and wet season, respectively. The results indicated that the NO3-, Cl-, and NH4+-N concentrations and the δ18O-NO3- in the dry season were greater than those in the wet season, and the δ15 N-NO3- did not show significant seasonal variations based on the Man-Whitney U test. The NO3- was derived mainly from the mixed sources according to the ranges of NO3-/Cl-, δ15 N-NO3-, and δ18O-NO3-. The nitrate sources in the surface water were synthetic fertilizer, soil nitrogen, manure, and sewage in the Xihe River (XR), Lanhe River (LR), and Xiada River (XDR) and soil nitrogen and synthetic fertilizer in the Er dao River (EDR) during the wet season. The sources were synthetic fertilizer and soil nitrogen in the XDR and soil nitrogen, manure, and sewage in the XR, LR, and EDR during the dry season. The significant negative relationship between NO3- and NH4+ and the significant positive relationship between NO3- and δ15 N-NO3- in the wet season indicated that the volatilization and nitrification of soil N might be related to NO3- sources in the wet season. NH4+-N and δ15 N-NO3- increased with decreasing NO3- and Cl- in EDR and LR during the wet season, which indicated denitrification processes occurred. There was a significant relationship between NO3- and Cl-, indicating that mixing processes occurred in the surface water during the two sampling periods. This study will provide a better understanding for nitrate sources related to seasonal variations and transformation processes in hilly areas.
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The nitrate (NO3-) pollution of aquatic systems in Northeast China is a severe problem. To identify NO3- sources and transformations in different zones with different land uses in the Taizi River Basin, ion-exchange methods were utilized to determine the concentrations and isotopic compositions (δ15N and δ18O) of NO3- and chloride (Cl-). Results showed that Cl- concentrations ranged from 2.7 to 73.4 mg/L. Cl- concentrations were the highest in zone 8 and the lowest in zone 1. NO3- concentrations ranged from 0.3 to 27.4 mg/L and were the highest in zone 1 and the lowest in zone 8. During the sampling period, δ15N-NO3- values varied from 3.8 to 37.2, and δ18O-NO3- values ranged from -0.5 to 10.4. δ15N-NO3- values were the highest in zone 9 and the lowest in zone 1. The differences in physicochemical parameters and NO3- isotopes may be affected by land use and biogeochemical nitrogen processes in different zones. The combined analysis of dual isotopes (δ15N-NO3- and δ18O-NO3-) and NO3-/Cl- versus Cl- showed that different sources contributed NO3- to different zones during the sampling period. Soil N, manure, and sewage were the main NO3- sources in the Taizi River Basin. In zones 1 to 6, the δ15N-NO3- values of almost all samples were more than 10, NO3-/Cl- values were high, and Cl- molar concentration was low during the sampling period. These findings suggested that the volatilization and nitrification of soil NH4+ might be related to NO3- sources in zones 1 to 6. A 1:1 to 2:1 linear relationship between δ15N-NO3- and δ18O-NO3- combined with the significantly negative relationship between ln (NO3-) and δ18O-NO3- indicated that denitrification affected NO3- distribution in zones 8 to 9 during the sampling period. These results can provide useful information to control NO3- concentrations in different zones in Taizi River Basin.
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Cloretos/análise , Nitratos/análise , Isótopos de Nitrogênio/análise , Isótopos de Oxigênio/análise , Poluentes Químicos da Água/análise , China , Monitoramento Ambiental , RiosRESUMO
Carbon material containing nickel, nitrogen and sulfur (Ni-NSC) has been synthesized using metal-organic frameworks (MOFs) as precursor by annealing treatment with a size from 200 to 300 nm. Pd nanoparticles supported on the Ni-NSC (Pd/Ni-NSC) are used as electrocatalysts for ethanol oxidation in alkaline media. Due to the synergistic effect between Pd and Ni, S, N, free OH radicals can form on the surface of Ni, N and S atoms at lower potentials, which react with CH3CO intermediate species on the Pd surface to produce CH3COO- and release the active sites. On the other hand, the stronger binding force between Pd and co-doped N and S is responsible for enhancing dispersion and preventing agglomeration of the Pd nanoparticles. The Pd(20 wt%)/Ni-NSC shows better electrochemical performance of ethanol oxidation than the traditional commercial Pd(20 wt%)/C catalyst. Onset potential on the Pd(20 wt%)/Ni-NSC electrode is 36 mV more negative compared with that on the commercial Pd(20 wt%)/C electrode. The Pd(20 wt%)/Ni-NSC in this paper demonstrates to have excellent electrocatalytic properties and is considered as a promising catalyst in alkaline direct ethanol fuel cells.