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Metal-insulator-metal (MIM) configurations based on Fabry-Pérot resonators have advanced the development of color filtering through interactions between light and matter. However, dynamic color changes without breaking the structure of the MIM resonator upon environmental stimuli are still challenging. Here, we report monolithic metal-organic framework (MOF)-based MIM resonators with tunable bandwidth that can boost both dynamic optical filtering and active chemical sensing by laser-processing microwell arrays on the top metal layer. Programmable tuning of the reflection color of the MOF-based MIM resonator is achieved by controlling the MOF layer thicknesses, which is demonstrated by simulation of light-matter interactions on subwavelength scales. Laser-processed microwell arrays are used to boost sensing performance by extending the pathway for diffusion of external chemicals into nanopores of the MOFs. Both experiments and molecular dynamics simulations demonstrate that tailoring the period and height of the microwell array on the MIM resonator can advance the high detection sensitivity of chemicals.
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This study demonstrates the hybridization of polyelectrolyte brushes with anti-inflammatory drug-loaded nanoMOFs that can achieve highly efficient aqueous lubrication and sustained drug release for the synergistic therapy of osteoarthritis (OA). Poly(3-sulfopropyl methacrylate potassium salt) (PSPMK) brushes are grown on the surface of the UiO-66-NH2 via one-pot grafting polymerization, which served as a general surface modification method of NH2 -MOFs to grow the polymer brushes. The growth of the PSPMK brushes greatly enhance the stability, dispersity, and swollen property of the AS-UiO-66-NH2@PSPMK in aqueous media. Using as lubricating additives, the UiO-66-NH2 @PSPMK achieves not only reductions in both coefficient of friction and wear volume over 70% and 99% but also supports high load-carrying capacity and long-term durability. The PSPMK brushes can be served as an universal interfacial modification soft layer that can significantly improve the aqueous lubricating performance of other types of NH2 -MOFs. After encapsulating the anti-inflammatory aspirin (AS), the AS-UiO-66-NH2 @PSPMK shows both sustained drug release and good biocompatibility toward the human normal chondrocytes. This work establishes anti-inflammatory drug-loaded UiO-66-NH2 @PSPMK as a potential multifunctional joint lubricant for OA treatment.
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Estruturas Metalorgânicas , Compostos Organometálicos , Humanos , Polieletrólitos , Lubrificação , Liberação Controlada de Fármacos , AspirinaRESUMO
The habenula, an ancient small brain area in the epithalamus, densely expresses nicotinic acetylcholine receptors and is critical for nicotine intake and aversion. As such, identification of strategies to manipulate habenular activity may yield approaches to treat nicotine addiction. Here we show that GPR151, an orphan G-protein-coupled receptor (GPCR) highly enriched in the habenula of humans and rodents, is expressed at presynaptic membranes and synaptic vesicles and associates with synaptic components controlling vesicle release and ion transport. Deletion of Gpr151 inhibits evoked neurotransmission but enhances spontaneous miniature synaptic currents and eliminates short-term plasticity induced by nicotine. We find that GPR151 couples to the G-alpha inhibitory protein Gαo1 to reduce cyclic adenosine monophosphate (cAMP) levels in mice and in GPR151-expressing cell lines that are amenable to ligand screens. Gpr151- knockout (KO) mice show diminished behavioral responses to nicotine and self-administer greater quantities of the drug, phenotypes rescued by viral reexpression of Gpr151 in the habenula. These data identify GPR151 as a critical modulator of habenular function that controls nicotine addiction vulnerability.
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Habenula/fisiologia , Plasticidade Neuronal/fisiologia , Nicotina/metabolismo , Agonistas Nicotínicos/metabolismo , Receptores Acoplados a Proteínas G/fisiologia , Transtornos Relacionados ao Uso de Substâncias/metabolismo , Animais , Células CHO , Cricetulus , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Habenula/metabolismo , Humanos , Camundongos Knockout , Plasticidade Neuronal/efeitos dos fármacos , Plasticidade Neuronal/genética , Nicotina/administração & dosagem , Agonistas Nicotínicos/administração & dosagem , Receptores Acoplados a Proteínas G/genética , Transmissão Sináptica/genética , Transmissão Sináptica/fisiologiaRESUMO
Paraquat (PQ) is an environmental poison that causes clinical symptoms similar to those of Parkinson's disease (PD) in vitro and in rodents. It can lead to the activation of microglia and apoptosis of dopaminergic neurons. However, the exact role and mechanism of microglial activation in PQ-induced neuronal degeneration remain unknown. Here, we isolated the microglia-derived exosomes exposed with 0 and 40 µM PQ, which were subsequently co-incubated with PQ-exposed neuronal cells to simulate intercellular communication. First, we found that exosomes released from microglia caused a change in neuronal cell vitality and reversed PQ-induced neuronal apoptosis. RNA sequencing data showed that these activated microglia-derived exosomes carried large amounts of circZNRF1. Moreover, a bioinformatics method was used to study the underlying mechanism of circZNRF1 in regulating PD, and miR-17-5p was predicted to be its target. Second, an increased Bcl2/Bax ratio could play an anti-apoptotic role. Bcl2 was predicted to be a downstream target of miR-17-5p. Our results showed that circZNRF1 plays an anti-apoptotic role by absorbing miR-17-5p and regulating the binding of Bcl2 after exosomes are internalized by dopaminergic neurons. In conclusion, we demonstrated a new intercellular communication mechanism between microglia and neurons, in which circZNRF1 plays a key role in protecting against PQ-induced neuronal apoptosis through miR-17-5p to regulate the biological process of PD. These findings may offer a novel approach to preventing and treating PD.
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MicroRNAs , Microglia , Paraquat/toxicidade , Neurônios Dopaminérgicos , Proteínas Proto-Oncogênicas c-bcl-2 , MicroRNAs/genéticaRESUMO
The construction of porous nanocarriers with good lubricating performance and stimuli-responsive drug release is significant for the synergetic therapy of osteoarthritis (OA). Although metal-organic framework nanoparticles (nanoMOFs) as carriers can support drug delivery, achieving the synergy of aqueous lubrication and stimuli-responsive drug release is challenging. In this work, a core-shell nanoMOFs@poly(N-isopropylacrylamide) (PNIPAm) microgel hybrid via one-pot soap-free emulsion polymerization is developed. Programmable growth of the PNIPAm microgel layer on the surface of nanoMOFs is achieved by tuning the concentration of the monomer and the crosslinker in the reaction. Reversible swelling-collapsing behaviors of the hybrid are realized by tuning the temperature below and above the lower critical solution temperature. When used as water lubrication additives, the hybrid enables reductions in both the coefficient of friction and wear volume. In vitro thermal-responsive drug release is demonstrated on the diclofenac sodium-loaded hybrid by controlling the swelling and collapsing states of the PNIPAm nanolayer. Moreover, the good biocompatibility of the hybrid is verified by culturing toward HeLa and BEAS-2B cells. These results establish a nanoMOFs@microgel hybrid that can achieve friction and wear reduction and thermal-responsive drug release.
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Microgéis , Nanopartículas , Liberação Controlada de Fármacos , Lubrificação , ÁguaRESUMO
This paper describes how metal-organic frameworks (MOFs) conformally coated on plasmonic nanoparticle arrays can support exciton-plasmon modes with features resembling strong coupling but that are better understood by a weak coupling model. Thin films of Zn-porphyrin MOFs were assembled by dip coating on arrays of silver nanoparticles (NP@MOF) that sustain surface lattice resonances (SLRs). Coupling of excitons with these lattice plasmons led to an SLR-like mixed mode in both transmission and transient absorption spectra. The spectral position of the mixed mode could be tailored by detuning the SLR in different refractive index environments and by changing the periodicity of the nanoparticle array. Photoluminescence showed mode splitting that can be interpreted as modulation of the exciton line shape by the Fano profile of the surface lattice mode, without requiring Rabi splitting. Compared with pristine Zn-porphyrin, hybrid NP@MOF structures achieved a 16-fold enhancement in emission intensity. Our results establish MOFs as a crystalline molecular emitter material that can couple with plasmonic structures for energy exchange and transfer.
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Boronate affinity materials have been successfully used for the selective recognition of glycoproteins. However, by such materials, the large-scale glycoproteins enrichment from human plasma under physiological conditions is rarely reported. In this work, 3-carboxybenzoboroxole (CBX) functionalized polyethylenimine (PEI) modified magnetic graphene oxide nanocomposites were synthesized. Benefitting from the low pKa value of CBX (â¼6.9) and PEI dendrimer-assisted multivalent binding, the Freundlich constant (KF) for the adsorption of horseradish peroxidase (HRP) was 3.0-7.3 times higher than that obtained by previous work, displaying the high enrichment capacity. Moreover, PEI could improve the hydrophilicity of nanocomposites and reduce nonglycoprotein adsorption. Therefore, such nanocomposites were successfully applied to the analysis of human plasma glycoproteome under physiological conditions, and the identified glycoproteins number and recognition selectivity was increased when compared to the results obtained by previous boronic acid-functionalized particles (Sil@Poly(APBA-co-MBAAm)) under common alkaline condition (137 vs 78 and 67.8% vs 57.8%, respectively). In addition, thrombin (F2), an important plasma glycoprotein, labile under alkaline conditions, was specifically identified by our method, demonstrating the great promise of such nanocomposites in the deep-coverage glycoproteome analysis.
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Compostos de Boro/química , Glicoproteínas/química , Grafite/química , Compostos Heterocíclicos com 2 Anéis/química , Nanocompostos/química , Polietilenoimina/química , Adsorção , Glicoproteínas/sangue , Peroxidase do Rábano Silvestre/química , Peroxidase do Rábano Silvestre/metabolismo , Humanos , Fenômenos Magnéticos , Modelos Moleculares , Estrutura MolecularRESUMO
Three-dimensional branched copolymer, with N,N'-methylene bisacrylamide as the crosslinker and 3-allyloxy-2-hydroxy-1-propane sulfonic acid sodium salt as the monomer, was grafted from silica particles by thiol-ene click reaction. The obtained hydrophilic material with sulfonic acid groups was successfully applied for chromatography separation and glycopeptide enrichment. The separation mechanism was proven as the mixed mode of hydrophilic interaction and cation-exchange by investigating the effect of various chromatographic factors on the retention of polar analytes. By such mixed-mode chromatography, nucleosides, nucleobases, and acidic compounds were successfully separated. The column efficiency was up to 136,000 theoretical plates m-1 for cytidine, which was much higher than those of previous reports. Furthermore, benefitting from the large amount of hydrophilic groups provided by the branched copolymer, the material was used for the selective enrichment of glycopeptides. Results demonstrated the great potential of such material for chromatography separation and glycoproteome analysis. Graphical abstract The branched copolymer modified HILIC/cation-exchange particles Sil@Poly(AHPS-co-MBAAm) were prepared via thiol-ene click copolymerization reaction. Such Sil@Poly(AHPS-co-MBAAm) particles showed great performance in the separation of polar compounds and the enrichment of glycopeptides.
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Cromatografia por Troca Iônica/métodos , Glicopeptídeos/análise , Dióxido de Silício/química , Compostos de Sulfidrila/química , Acrilamidas/química , Resinas de Troca de Cátion/química , Cátions/química , Química Click , Glicopeptídeos/isolamento & purificação , Interações Hidrofóbicas e HidrofílicasRESUMO
To achieve the simultaneous capture of various target proteins, the multiepitope templates imprinted particles were developed by phase inversion-based poly(ether sulfone) (PES) self-assembly. Herein, with the top three high-abundance proteins in the human plasma, serum albumin, immunoglobulin G, and transferrin, as the target proteins, their N-terminal peptides were synthesized as the epitope templates. After the preorganization of three epitopes and PES in dimethylacetamide, the multiepitope templates imprinted particles were formed in water through self-assembly, by which the simultaneous recognition of three target proteins in human plasma was achieved with high selectivity. Furthermore, the binding kinetics study proved that the adsorption mechanism in this imprinting system toward three epitope templates was the same as that on the single-epitope imprinting polymer. These results demonstrate that our proposed multiepitope templates imprinting strategy might open a new era of artificial antibodies to achieve the recognition of various targets simultaneously.
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Imunoglobulina G/sangue , Impressão Molecular , Albumina Sérica Humana/análise , Transferrina/análise , Epitopos , Humanos , Cinética , Tamanho da Partícula , Polímeros/síntese química , Polímeros/química , Sulfonas/síntese química , Sulfonas/químicaRESUMO
Calcium/voltage-gated, large conductance potassium (BK) channels control numerous physiological processes, including myogenic tone. BK channel regulation by direct interaction between lipid and channel protein sites has received increasing attention. Leukotrienes (LTA4, LTB4, LTC4, LTD4, and LTE4) are inflammatory lipid mediators. We performed patch clamp studies in Xenopus oocytes that co-expressed BK channel-forming (cbv1) and accessory ß1 subunits cloned from rat cerebral artery myocytes. Leukotrienes were applied at 0.1 nm-10 µm to either leaflet of cell-free membranes at a wide range of [Ca(2+)]i and voltages. Only LTB4 reversibly increased BK steady-state activity (EC50 = 1 nm; Emax reached at 10 nm), with physiological [Ca(2+)]i and voltages favoring this activation. Homomeric cbv1 or cbv1-ß2 channels were LTB4-resistant. Computational modeling predicted that LTB4 docked onto the cholane steroid-sensing site in the BK ß1 transmembrane domain 2 (TM2). Co-application of LTB4 and cholane steroid did not further increase LTB4-induced activation. LTB4 failed to activate ß1 subunit-containing channels when ß1 carried T169A, A176S, or K179I within the docking site. Co-application of LTB4 with LTA4, LTC4, LTD4, or LTE4 suppressed LTB4-induced activation. Inactive leukotrienes docked onto a portion of the site, probably preventing tight docking of LTB4. In summary, we document the ability of two endogenous lipids from different chemical families to share their site of action on a channel accessory subunit. Thus, cross-talk between leukotrienes and cholane steroids might converge on regulation of smooth muscle contractility via BK ß1. Moreover, the identification of LTB4 as a highly potent ligand for BK channels is critical for the future development of ß1-specific BK channel activators.
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Ativação do Canal Iônico/fisiologia , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/metabolismo , Leucotrieno B4/metabolismo , Animais , Cálcio/metabolismo , Artérias Cerebrais/citologia , Feminino , Ativação do Canal Iônico/efeitos dos fármacos , Ativação do Canal Iônico/genética , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/química , Subunidades alfa do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/química , Subunidades beta do Canal de Potássio Ativado por Cálcio de Condutância Alta/genética , Leucotrieno A4/química , Leucotrieno A4/metabolismo , Leucotrieno A4/farmacologia , Leucotrieno B4/química , Leucotrieno B4/farmacologia , Leucotrieno C4/química , Leucotrieno C4/metabolismo , Leucotrieno C4/farmacologia , Leucotrieno D4/química , Leucotrieno D4/metabolismo , Leucotrieno D4/farmacologia , Leucotrieno E4/química , Leucotrieno E4/metabolismo , Leucotrieno E4/farmacologia , Potenciais da Membrana/efeitos dos fármacos , Microinjeções , Modelos Moleculares , Estrutura Molecular , Células Musculares/citologia , Células Musculares/metabolismo , Oócitos/efeitos dos fármacos , Oócitos/metabolismo , Oócitos/fisiologia , Técnicas de Patch-Clamp , Ligação Proteica , Estrutura Terciária de Proteína , RNA Complementar/administração & dosagem , RNA Complementar/genética , Ratos , Xenopus laevisRESUMO
The specific recognition of biomolecules by artificial antibodies has inspired fascination among chemists and biologists. Herein, we propose a new method to prepare epitope-oriented surface-imprinted nanoparticles with high template utilization efficiency. Using a His-tag as the anchor to facilitate the epitope immobilization/removal and the self-polymerization of dopamine to control the imprinted shell thickness, the prepared epitope-imprinted nanoparticles show specific recognition of the target protein. Moreover, with improved hydrophilicity of the His-tag-anchored epitope, this method opens up a universal route for imprinting epitopes with various polarities.
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Epitopos/química , Histidina/química , Impressão Molecular , Nanopartículas/química , Dopamina/química , Interações Hidrofóbicas e Hidrofílicas , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Monolithic, crystalline and highly oriented coordination network compound (CNC) Prussian blue (PB) thin films have been deposited though different routes on conductive substrates. Characterization of the monolithic thin films reveals a long-term stability, even after many redox cycles the crystallinity as well as the high orientation remain intact during the electrochromic switching process.
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For inorganic semiconductors crystalline order leads to a band structure which gives rise to drastic differences to the disordered material. An example is the presence of an indirect band gap. For organic semiconductors such effects are typically not considered, since the bands are normally flat, and the band-gap therefore is direct. Herein we show results from electronic structure calculations demonstrating that ordered arrays of porphyrins reveal a small dispersion of occupied and unoccupied bands leading to the formation of a small indirect band gap. We demonstrate herein that such ordered structures can be fabricated by liquid-phase epitaxy and that the corresponding crystalline organic semiconductors exhibit superior photophysical properties, including large charge-carrier mobility and an unusually large charge-carrier generation efficiency. We have fabricated a prototype organic photovoltaic device based on this novel material exhibiting a remarkable efficiency.
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Proteome scale absolute quantification is fundamental for the quantitative understanding of an organism. The unsatisfactory accuracy for protein abundance estimation of current algorithms has been partially improved by the Absolute Protein EXpression profiling (APEX) algorithm, which implements the prior expectations of peptides' appearances in the calculation of protein abundances. However, the abundance feature (AF) in APEX is the spectral count (SC); an AF suffers from a narrow dynamic range, thus, unsatisfactory accuracy. Therefore, we adopted another tandem mass spectrometric (MS/MS) level AF called Summed MS/MS Total ion current (SMT), which cumulates the MS/MS fragment intensities rather than simply counting the MS/MS spectra, to surmount this particular deficiency. The combination of APEX and SMT (abbreviated as APEX-SMT) is capable of improving the accuracy of absolute quantification by reducing the average relative deviation by ~55-85% compared to that of APEX, through a series of tests on the Universal Proteomics Standard sample with a dynamic range of 5 orders of magnitude (UPS2). The algorithm could also be used for relative quantification. When applied to the relative quantification of a publicly available benchmark dataset, APEX-SMT could provide comparable accuracy to APEX. All these results suggest that APEX-SMT is a promising alternative to APEX for proteome quantification.
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Algoritmos , Bases de Dados de Ácidos Nucleicos/normas , Perfilação da Expressão Gênica/normas , Proteoma/análise , Espectrometria de Massas em Tandem/normas , Animais , Perfilação da Expressão Gênica/métodos , Íons , Proteoma/genética , Ratos , Espectrometria de Massas em Tandem/métodos , LevedurasRESUMO
Crystalline, highly orientated surface-anchored MOF thin films, grown on Au substrates, were prepared using liquid-phase epitaxy (LPE). The successful loading of La(3+) ions into the Cu3(BTC)2 (HKUST-1) SURMOFs (surface-mounted metal-organic frameworks) was monitored using X-ray diffraction (XRD). Theoretical calculations using classical force-field based Monte Carlo simulations yield a structure with two La(3+) ions within the large Cu3(BTC)2 pores, in full agreement with experimental results on the composition of these films and the relative intensities of the XRD peaks. Implications of these findings for using MOF thin films for electronic applications are briefly discussed.
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BACKGROUND AND OBJECTIVE: Research on body composition phenotypes and bone health in adolescents is limited. Hence, this study aimed to analyze the relationship between different body composition phenotypes, bone mineral content, and bone metabolism markers in Chinese adolescents. METHODS: In this cross-sectional study, 1852 adolescents aged 12 to 18 years were selected from six schools in Yinchuan City between 2017 and 2020 using stratified cluster random sampling. The participant's body composition and bone mineral content (BMC) were measured using bioelectrical impedance analysis (BIA). Serum bone metabolic markers (OC, CTX, and Ca) were measured. Based on their FMI and LMI, individuals were categorized into four body composition phenotypes: low fat mass-low lean mass (LFMI-LLMI), low fat mass-high lean mass (LFMI-HLMI), high fat mass-high lean mass (HFMI-HLMI), high fat mass-low lean mass (HFMI-LLMI). RESULTS: There was a statistically significant difference between the four different body composition phenotypes with BMC, CTX and Ca in boys (all P < 0.05), similar conclusions were found in girls, except the OC and CTX. After adjusting for age, gender, smoking, drinking, and others, compared with the LFMI-HLMI reference group, the two high FMI groups (HFMI-LLMI and HFMI-HLMI) had a greater negative correlation with BMC, while the low BMC risk of the HFMI-LLMI group was the highest (OR = 33.28; 95%CI: 11.12-99.63; P < 0.001). The correlation between BMC of different body composition phenotypes in boys was greater than that in girls. HFMI-HLMI is a risk phenotype negatively associated with Ca content (ß = -0.12; 95%CI: -0.19 to -0.04; P < 0.05). Regardless of body composition level, BMC was always negatively correlated with fat mass (LLMI: ß = -0.27; 95%CI: -0.32-0.21; HLMI: ß = -0.52, 95%CI: -0.65-0.40) and positively correlated with lean mass (LFMI: ß =0.24; 95%CI: 0.20-0.28; HFMI: ß =0.23, 95%CI:0.13-0.33) (all P < 0.001). The fat mass showed different correlations with OC and CTX in girls and boys based on LLMI or HLMI (all P < 0.05). CONCLUSION: HFMI-LLMI is a risk phenotype of low BMC in Chinese adolescents, and the relationship between fat mass and bone metabolism markers is affected by lean body mass and gender.
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Composição Corporal , Densidade Óssea , Fenótipo , Adolescente , Criança , Feminino , Humanos , Masculino , Tecido Adiposo/metabolismo , Composição Corporal/fisiologia , Densidade Óssea/fisiologia , China , Estudos Transversais , População do Leste Asiático , Impedância ElétricaRESUMO
For the first time, a novel donor-acceptor structured COF with excellent photothermal conversion and mono-dispersity in various oils without any further modification is reported; it realized responsive friction reduction, excellent antiwear and long-time lubrication.
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Failure of articular cartilage lubrication and inflammation are the main causes of osteoarthritis (OA), and integrated treatment realizing joint lubrication and anti-inflammation is becoming the most effective treat model. Inspired by low friction of human synovial fluid and adhesive chemical effect of mussels, our work reports a biomimetic lubricating system that realizes long-time lubrication, photothermal responsiveness and anti-inflammation property. To build the system, a dopamine-mediated strategy is developed to controllably graft hyaluronic acid on the surface of metal organic framework. The design constructs a biomimetic core-shell structure that has good dispersity and stability in water with a high drug loading ratio of 99%. Temperature of the solution rapidly increases to 55 °C under near-infrared light, and the hard-soft lubricating system well adheres to wear surfaces, and greatly reduces frictional coefficient by 75% for more than 7200 times without failure. Cell experiments show that the nanosystem enters cells by endocytosis, and releases medication in a sustained manner. The anti-inflammatory outcomes validate that the nanosystem prevents the progression of OA by down-regulating catabolic proteases and pain-related genes and up-regulating genes that are anabolic in cartilage. The study provides a bioinspired strategy to employ metal organic framework with controlled surface and structure for friction reduction and anti-inflammation, and develops a new concept of OA synergistic therapy model for practical applications.
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Materiais Biomiméticos , Ácido Hialurônico , Osteoartrite , Osteoartrite/tratamento farmacológico , Osteoartrite/patologia , Osteoartrite/metabolismo , Humanos , Materiais Biomiméticos/química , Materiais Biomiméticos/farmacologia , Ácido Hialurônico/química , Ácido Hialurônico/farmacologia , Animais , Estruturas Metalorgânicas/química , Estruturas Metalorgânicas/farmacologia , Propriedades de Superfície , Lubrificação , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Tamanho da Partícula , Dopamina/química , Dopamina/farmacologia , Liberação Controlada de FármacosRESUMO
OBJECTIVE: This study mainly explores (2R,6R; 2S,6S)-HNK and its compounds whether there are antidepressant effects. METHODS: Four HNK compounds were obtained from 2-(Chlorophenyl) Cyclopentylmethanone. Forced swimming test, locomotor sensitization test, and conditioned location preference test were used to screen the antidepressant activity of the synthesized target compounds. RESULTS: In the case of 10 mg HNK treatment, compared with saline, the immobile time of mice in the HNK group, I5 group and I6 group at 1 h and 7 days had statistical significance. In the case of 10 mg HNK treatment, compared with saline, the immobile time of compound C and D groups in the glass cylinder area was significantly different. In the locomotor sensitization test, the movement distance of compound C and D groups on day 15 and day 7 mice increased significantly compared with the first day. In the conditioned place preference experiment, compound C and compound D induced conditioned place preference in mice compared with the Veh group. CONCLUSION: The results of the forced swimming test, locomotor sensitization test, and conditioned location preference test showed that compounds C and D may have certain anti-depressant activity. However, HNK exerts a rapid and significant antidepressant effect within 1 week, but the duration is short.
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Antidepressivos , Ketamina , Atividade Motora , Natação , Animais , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Camundongos , Masculino , Ketamina/farmacologia , Ketamina/análogos & derivados , Atividade Motora/efeitos dos fármacos , Fatores de Tempo , Comportamento Animal/efeitos dos fármacos , Depressão/tratamento farmacológico , Modelos Animais de Doenças , Reprodutibilidade dos TestesRESUMO
With the accumulation of plastic waste in the environment, the toxicity of micro- and nano-plastics (MNPs) to microalgae has attracted increasing attention. However, the underlying toxic mechanisms of MNPs remain to be elucidated. In this study, we synthesized micro- and nano-scale of polystyrene MNPs (PS MNPs) to investigate their toxicity and toxic mechanisms in Chlamydomonas reinhardtii. We found that PS MNPs significantly inhibit the production of photosynthetic pigments and increase soluble protein content. The detailed analysis of results shows that both materials affect photosynthetic efficiency by damaging the donor side, reaction center, and electron transfer of photosystem II. Moreover, compared to PS MPs, PS NPs have a greater negative impact on algal cells. Analyzing the transcriptome of cells suggests that the most sensitive metabolic pathways in response to PS MNPs involve oxidative phosphorylation, biosynthesis of secondary metabolites, and photosynthesis. Especially, genes related to photosynthesis and oxidative phosphorylation showed significant changes in expression after exposure to PS MNPs. This study provided molecular-level insights into the toxic mechanisms of PS MNPs on microalgae.