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Cognitive impairment affects 29-67% of patients with neuromyelitis optica spectrum disorder. Previous studies have reported glutamate homeostasis disruptions in astrocytes, leading to imbalances in gamma-aminobutyric acid levels. However, the association between these neurotransmitter changes and cognitive deficits remains inadequately elucidated. Point RESolved Spectroscopy and Hadamard Encoding and Reconstruction of MEGA-Edited Spectroscopy techniques were utilized to evaluate gamma-aminobutyric acid, glutamate, glutathione levels, and excitation/inhibition balance in the anterior cingulate cortex, posterior cingulate cortex, and occipital cortex of 39 neuromyelitis optica spectrum disorder patients and 41 healthy controls. Cognitive function was assessed using neurocognitive scales. Results showed decreased gamma-aminobutyric acid levels alongside increased glutamate, glutathione, and excitation/inhibition ratio in the anterior cingulate cortex and posterior cingulate cortex of neuromyelitis optica spectrum disorder patients. Specifically, within the posterior cingulate cortex of neuromyelitis optica spectrum disorder patients, decreased gamma-aminobutyric acid levels and increased excitation/inhibition ratio correlated significantly with anxiety scores, whereas glutathione levels predicted diminished executive function. The results suggest that neuromyelitis optica spectrum disorder patients exhibit dysregulation in the GABAergic and glutamatergic systems in their brains, where the excitation/inhibition imbalance potentially acts as a neuronal metabolic factor contributing to emotional disorders. Additionally, glutathione levels in the posterior cingulate cortex region may serve as predictors of cognitive decline, highlighting the potential benefits of reducing oxidative stress to safeguard cognitive function in neuromyelitis optica spectrum disorder patients.
Assuntos
Ácido Glutâmico , Giro do Cíngulo , Espectroscopia de Ressonância Magnética , Neuromielite Óptica , Ácido gama-Aminobutírico , Humanos , Giro do Cíngulo/metabolismo , Giro do Cíngulo/diagnóstico por imagem , Feminino , Adulto , Neuromielite Óptica/metabolismo , Neuromielite Óptica/diagnóstico por imagem , Masculino , Ácido Glutâmico/metabolismo , Espectroscopia de Ressonância Magnética/métodos , Pessoa de Meia-Idade , Ácido gama-Aminobutírico/metabolismo , Glutationa/metabolismo , Adulto Jovem , Neurotransmissores/metabolismo , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/diagnóstico por imagemRESUMO
Co-loading of sonosensitizers and chemotherapeutic drugs into nanocarriers can improve the biocompatibilities, stabilities, and targeting of drugs and reduce the adverse reactions of drugs, providing a robust platform to orchestrate the synergistic interplay between chemotherapy and sonodynamic therapy (SDT) in cancer treatment. In this regard, biodegradable manganese dioxide (MnO2) has attracted widespread attention because of its unique properties in the tumor microenvironment (TME). Accordingly, herein, MnO2 nanoshells with hollow mesoporous structures (H-MnO2) were etched to co-load hematoporphyrin monomethyl ether (HMME) and doxorubicin (DOX), and DOX/HMME-HMnO2@bovine serum albumin (BSA) obtained after simple BSA modification of DOX/HMME-HMnO2 exhibited excellent hydrophilicity and dispersibility. H-MnO2 rapidly degraded in the weakly acidic TME, releasing loaded HMME and DOX, and catalysed the decomposition of H2O2 abundantly present in TME, producing oxygen (O2) in situ, significantly increasing O2 concentration and downregulating the hypoxia-inducible factor 1α (HIF-1α). After irradiation of the tumor area with low-frequency ultrasound, the drug delivery efficiency of DOX/HMME-HMnO2@BSA substantially increased, and the excited HMME generated a large amount of reactive oxygen species (ROS), which caused irreversible damage to tumor cells. Moreover, the cell death rate exceeded 60% after synergistic SDT-chemotherapy. Therefore, the pH-responsive nanoshells designed in this study can realize drug accumulation in tumor regions by responding to TME and augment SDT-chemotherapy potency for breast cancer treatment by improving hypoxia in tumors. Thus, this study provides theoretical support for the development of multifunctional nanocarriers and scientific evidence for further exploration of safer and more efficient breast cancer treatments.
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Topological materials carrying topological surface states (TSSs) have extraordinary carrier mobility and robustness, which provide a new platform for searching for efficient hydrogen evolution reaction (HER) electrocatalysts. However, the majority of these TSSs originate from the sp band of topological quantum catalysts rather than the d band. Here, based on the density functional theory calculation, it is reported a topological semimetal Pd3Sn carrying TSSs mainly derived from d orbital and proposed that optimizing surface state electrons of Pd3Sn by introduction heteroatoms (Ni) can promote hybridization between hydrogen atoms and electrons, thereby reducing the Gibbs free energy (ΔGH) of adsorbed hydrogen and improving its HER performance. Moreover, this is well verified by electrocatalytic experiment results, the Ni-doped Pd3Sn (Ni0.1Pd2.9Sn) show much lower overpotential (-29 mV vs RHE) and Tafel slope (17 mV dec-1) than Pd3Sn (-39 mV vs RHE, 25 mV dec-1) at a current density of 10 mA cm-2. Significantly, the Ni0.1Pd2.9Sn nanoparticles exhibit excellent stability for HER. The electrocatalytic activity of Ni0.1Pd2.9Sn nanoparticles is superior to that of commercial Pt. This work provides an accurate guide for manipulating surface state electrons to improve the HER performance of catalysts.
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Sepsis-induced cardiomyopathy (SIC) leads to high mortality and has no effective treatment strategy. Atractylenolide â (AT-I) is a sesquiterpene lactone compound and possesses various biological activities such as anti-inflammatory and organ protection. This study was designed to explore the role and the mechanism of AT-I in SIC. CCK-8 assay was used to assess the viability of AT-I-treated RAW 264.7 cells and immunofluorescence assay was used to detect M1 marker CD86. The expressions of M1 markers Cox2, iNOS and CD11b and PARP1/NLRP3 signaling pathway-related proteins were detected using western blot. The transfection efficiency of oe-PARP1 was examined with RT-qPCR and western blot. The ROS activity in H9c2 cells was detected using DCFH-DA assay and western blot was used to detect the expressions of inflammation- and oxidative stress-related proteins. The apoptosis of H9c2 cells was detected using flow cytometry and western blot. The present study found that AT-I inhibited LPS-induced M1 polarization in RAW 264.7 cells through the downregulation of PARP1/NLRP3 signaling pathway, thereby inhibiting the oxidative stress and apoptosis of H9c2 cells. In conclusion, AT-I might be a promising therapeutic agent for SIC by suppressing macrophage polarization through the modulation of PARP1/NLRP3 signaling pathway.
Assuntos
Lactonas , Macrófagos , Miócitos Cardíacos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Poli(ADP-Ribose) Polimerase-1 , Sepse , Sesquiterpenos , Transdução de Sinais , Animais , Camundongos , Transdução de Sinais/efeitos dos fármacos , Sepse/complicações , Sepse/metabolismo , Sepse/tratamento farmacológico , Sesquiterpenos/farmacologia , Células RAW 264.7 , Lactonas/farmacologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Macrófagos/metabolismo , Macrófagos/efeitos dos fármacos , Poli(ADP-Ribose) Polimerase-1/metabolismo , Miócitos Cardíacos/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/patologia , Apoptose/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Polaridade Celular/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , RatosRESUMO
To investigate the role of Peg13 in modulating the inflammatory response in sepsis, we established Lipopolysaccharide (LPS)-induced 293T cells and mouse models. Peg13 expression was assessed at various time points after infection using RT-qPCR. The levels of high mobility group box 1 (HMGB1) and interleukin-6 (IL-6) were quantified through ELISA. A total of 44 septic patients and 36 healthy participants were recruited to measure Peg13 and HMGB1 levels in the blood. Peg13 demonstrated significant down-regulation in the supernatant of LPS-induced 293T cells and in the blood of LPS-induced mice. Moreover, the levels of proinflammatory cytokines HMGB1 and IL-6 were elevated in both the supernatant of LPS-induced cell models and blood specimens from LPS-induced murine models, and this elevation could be notably reduced by Peg13 suppression. In a clinical context, Peg13 and HMGB1 levels were higher in septic patients compared to healthy subjects. Peg13 exhibited a negative correlation with HMGB1, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) among septic patients. Peg13 mitigates the inflammatory response by reducing the release of proinflammatory cytokines HMGB1 and IL-6 in sepsis, presenting a potential therapeutic target for alleviating inflammation in sepsis treatment.
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Presbycusis has been reported as related to cognitive decline, but its underlying neurophysiological mechanism is still unclear. This study aimed to investigate the relationship between metabolite levels, cognitive function, and node characteristics in presbycusis based on graph theory methods. Eighty-four elderly individuals with presbycusis and 63 age-matched normal hearing controls underwent magnetic resonance spectroscopy, functional magnetic resonance imaging scans, audiological assessment, and cognitive assessment. Compared with the normal hearing group, presbycusis patients exhibited reduced gamma-aminobutyric acid and glutamate levels in the auditory region, increased nodal characteristics in the temporal lobe and precuneus, as well as decreased nodal characteristics in the superior occipital gyrus and medial orbital. The right gamma-aminobutyric acid levels were negatively correlated with the degree centrality in the right precuneus and the executive function. Degree centrality in the right precuneus exhibited significant correlations with information processing speed and executive function, while degree centrality in the left medial orbital demonstrated a negative association with speech recognition ability. The degree centrality and node efficiency in the superior occipital gyrus exhibited a negative association with hearing loss and speech recognition ability, respectively. These observed changes indicate alterations in metabolite levels and reorganization patterns at the brain network level after auditory deprivation.
Assuntos
Disfunção Cognitiva , Imageamento por Ressonância Magnética , Presbiacusia , Humanos , Masculino , Feminino , Presbiacusia/diagnóstico por imagem , Presbiacusia/metabolismo , Presbiacusia/fisiopatologia , Idoso , Disfunção Cognitiva/diagnóstico por imagem , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Espectroscopia de Ressonância Magnética , Ácido Glutâmico/metabolismo , Ácido gama-Aminobutírico/metabolismo , Pessoa de Meia-Idade , Encéfalo/diagnóstico por imagem , Encéfalo/metabolismoRESUMO
The exploitation of high-performance supercapacitors is crucial to promote energy storage technologies. Benefiting from the three-dimensional conductive micronanostructures and high specific capacity of the PPy@CuCo2S4@NF (polypyrrole/copper cobalt sulfide/nickel foam) composite electrode, this electrode exhibits a high specific capacity of 1403.21 C g-1 at 1 A g-1 and a capacitance retention of 85.79% after 10,000 cycles at 10 A g-1. The assembled PPy@CuCo2S4@NF//AC aqueous hybrid supercapacitor (AHSC) reveals a wide operating potential window of 1.5 V and achieves a high specific capacity of 322.52 C g-1 at 1 A g-1 and a capacitance retention of 86.84% after 15,000 cycles at 10 A g-1. The AHSC also exhibits a high power density of 733.69 W kg-1 at an energy density of 67.19 W h kg-1, surpassing those of previously reported spinel-based supercapacitors. Ex situ X-ray diffraction and X-ray photoelectron spectroscopy results show that the CuCo2S4 spinel structure changes to CuS2 and CoS2 cube structures, and the oxidation states of Cu and Co increase during charging and discharging processes. Density functional theory calculations suggest a superior conductivity for CuCo2S4 compared to that for CuCo2O4, demonstrating that CuCo2S4 has superior electrochemical performance. These findings attest to the considerable potential of the spinel materials for advanced energy storage applications.
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Objective: This study aimed to investigate the prevalence, molecular types, and virulence genes of methicillin-resistant Staphylococcus aureus (MRSA) causing skin and soft tissue infections (SSTIs) in the Shaoxing region. Methods: MRSA strains were collected from patients with SSTIs in Shaoxing People's Hospital from January 2019 to December 2019. We conducted SCCmec typing, Staphylococcus protein A (SPA) typing, multilocus sequence typing (MLST), and virulence gene analysis using whole-genome sequencing on all MRSA strains. Results: The detection rate of community-acquired MRSA (CA-MRSA) isolated from SSTI patients in our hospital was 33.3% (6/18). The primary SCCmec types of CA-MRSA strains were IV and V, with IVg(2B) and V(5C2&5) accounting for 16.7% each. Hospital-acquired MRSA (HA-MRSA) strains primarily exhibited SCCmec types IVa(2B) (25.0%), followed by II(2A) (16.7%), V(5C2) (16.7%), and V(5C2&5) (8.3%). SPA typing indicated that CA-MRSA strains causing SSTIs were predominantly t437 (14.3%), t034 (14.3%), t309 (14.3%), t4549 (14.3%), and t7637 (14.3%). The primary SPA type of HA-MRSA strains was t311 (16.7%). MLST typing revealed that the main sequence types (STs) of CA-MRSA strains causing SSTIs were ST22 (33.3%), followed by ST398, ST59, ST88, and ST630, each accounting for 16.7%. The principal STs of HA-MRSA strains were ST398 (16.7%), ST59 (16.7%), ST88 (16.7%), and ST5 (16.7%), followed by ST22, ST630, ST6, and ST188, each at 8.3%. The primary clones of CA-MRSA strains causing SSTIs were ST59-t437-IVg(2B) (16.7%) and ST630-t4549-V(5C2&5) (16.7%), while the primary clones of HA-MRSA strains were ST59-t437-IVa(2B), ST630-t4549-V(5C2&5), ST6-t304-IVa(2B), ST5-t311-II(2A), ST59-t172-IVa(2B), ST398-t571-V(5C2), ST398-t034-V(5C2), and ST5-t311-II(2A), each accounting for 8.3%. The detection rate of the lukSF-PV virulence gene was higher in CA-MRSA strains (50.0%) than in HA-MRSA strains (16.7%). Conclusions: The isolation rate of CA-MRSA strains causing SSTIs was high in Shaoxing People's Hospital, with ST59-t437-IVg(2B) and ST630-t4549-V(5C2&5) being the predominant clones. MRSA strains exhibited multiple virulence genes, with the lukSF-PV gene having a higher detection rate in CA-MRSA strains, signifying its importance as a virulence factor in CA-MRSA.
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Staphylococcus aureus Resistente à Meticilina , Infecções dos Tecidos Moles , Infecções Estafilocócicas , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Virulência/genética , Infecções dos Tecidos Moles/epidemiologia , Tipagem de Sequências Multilocus , Infecções Estafilocócicas/epidemiologia , Epidemiologia Molecular , Testes de Sensibilidade Microbiana , AntibacterianosRESUMO
The van der Waals (vdW) gaps in layered transition-metal dichalcogenides (TMDs) with an interlayer poor charge transport are considered the bottleneck for higher hydrogen evolution reaction (HER) performance of TMDs. Filling the vdW gap of TMDs materials with intercalants is considered a good way to generate new interesting properties. However, postsynthesis intercalation with foreign atoms may bring extra crystalline imperfections and low yields. In this work, to overcome the interlayer potential barriers of TMDs, CrS2-Cr1/3-CrS2 is produced by naturally self-intercalating native Cr1/3 atom plane into the vdW layered CrS2. The CrS2-Cr1/3-CrS2 exhibits strong chemical bonds and high electrical conductivity, which can provide excellent HER electrocatalytic performance. Moreover, based on the first-principles calculations and experimental verification, the intercalated Cr atoms exhibit a Gibbs free energy of the adsorbed hydrogen close to zero and could further improve the electrocatalytic HER performance. Our work provides a new view in self-intercalation for electrocatalysis applications.
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The high recombination rate of photoinduced electron-hole pairs limits the hydrogen production efficiency of the MoS2 catalyst in photoelectrochemical (PEC) water splitting. The strategy of prolonging the lifetime of photoinduced carriers is of great significance to the promotion of photoelectrocatalytic hydrogen production. An ideal approach is to utilize edge defects, which can capture photoinduced electrons and thus slow down the recombination rate. However, for two-dimensional MoS2, most of the surface areas are inert basal planes. Here, a simple method for preparing one-dimensional MoS2 nanoribbons with abundant inherent edges is proposed. The MoS2 nanoribbon-based device has a good spectral response in the range of 400-500 nm and has a longer lifetime of photoinduced carriers than other MoS2 nanostructure-based photodetectors. An improved PEC catalytic performance of these MoS2 nanoribbons is also experimentally verified under the illumination of 405 nm by using the electrochemical microcell technique. This work provides a new strategy to prolong the lifetime of photoinduced carriers for further improvement of PEC activity, and the evaluation of photoelectric performance provides a feasible way for transition-metal dichalcogenides to be widely used in the energy field.
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Homeodomain-leucine zipper class I (HD-Zip I) transcription factors have been functionally characterized in plant responses to abiotic stresses, but their roles in plant immunity are poorly understood. Here, a HD-Zip I gene, CaHZ27, was isolated from pepper (Capsicum annum) and characterized for its role in pepper immunity. Quantitative real-time polymerase chain reaction showed that CaHDZ27 was transcriptionally induced by Ralstonia solanacearum inoculation and exogenous application of methyl jasmonate, salicylic acid, or ethephon. The CaHDZ27-green fluorescent protein fused protein was targeted exclusively to the nucleus. Chromatin immunoprecipitation demonstrated that CaHDZ27 bound to the 9-bp pseudopalindromic element (CAATAATTG) and triggered ß-glucuronidase expression in a CAATAATTG-dependent manner. Virus-induced gene silencing of CaHDZ27 significantly attenuated the resistance of pepper plants against R. solanacearum and downregulated defense-related marker genes, including CaHIR1, CaACO1, CaPR1, CaPR4, CaPO2, and CaBPR1. By contrast, transient overexpression of CaHDZ27 triggered strong cell death mediated by the hypersensitive response and upregulated the tested immunity-associated marker genes. Ectopic CaHDZ27 expression in tobacco enhances its resistance against R. solanacearum. These results collectively suggest that CaHDZ27 functions as a positive regulator in pepper resistance against R. solanacearum. Bimolecular fluorescence complementation and coimmunoprecipitation assays indicate that CaHDZ27 monomers bind with each other, and this binding is enhanced significantly by R. solanacearum inoculation. We speculate that homodimerization of CaHZ27 might play a role in pepper response to R. solanacearum, further direct evidence is required to confirm it.
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Capsicum/imunologia , Capsicum/microbiologia , Resistência à Doença , Proteínas de Homeodomínio/metabolismo , Zíper de Leucina , Proteínas de Plantas/metabolismo , Ralstonia solanacearum/fisiologia , Acetatos/farmacologia , Sequência de Aminoácidos , Capsicum/efeitos dos fármacos , Capsicum/genética , Morte Celular/efeitos dos fármacos , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Ciclopentanos/farmacologia , DNA de Plantas/metabolismo , Resistência à Doença/efeitos dos fármacos , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Inativação Gênica/efeitos dos fármacos , Luminescência , Compostos Organofosforados/farmacologia , Oxilipinas/farmacologia , Doenças das Plantas/genética , Doenças das Plantas/imunologia , Doenças das Plantas/microbiologia , Imunidade Vegetal/efeitos dos fármacos , Folhas de Planta/efeitos dos fármacos , Folhas de Planta/genética , Proteínas de Plantas/química , Plantas Geneticamente Modificadas , Ligação Proteica/efeitos dos fármacos , Multimerização Proteica , Transporte Proteico/efeitos dos fármacos , Ralstonia solanacearum/efeitos dos fármacos , Ácido Salicílico/farmacologia , Nicotiana/genética , Ativação Transcricional/genética , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
OBJECTIVE: To explore the effect and mechanism of electroacupuncture (EA) for Z syndrome without organic lesion (metabolic syndrome combined with obstructive sleep apnea hypopnea syndrome). METHODS: Fifty-eight patients with Z syndrome were divided into three groups according to mild,moderate and severe degree. Acupuncture and EA were used at Daimai (GB 26), Zhongwan (CV 12), Xiawan (CV 10), Zusanli ST 36), Qihai (CV 6) and Huaroumen (ST 24), etc., once a day and five times a week. The treatment of ten times was a course, and two courses were acquired continuously. Sleep respiration monitoring (PSG) was done before EA and in one week after treatment respectively. Triacylglycerol (TG) fasting blood glucose (FBG) fasting insulin (INS) and serum leptin (Lep) were tested before and after treatment in the three groups. RESULTS: After treatment apnea hypopnea index (AHI) and the percentage of the time of arterial oxygen saturation (SaO2) less than 90% taken in the total sleep time (SLT 90%) were improved apparently than those before treatment in the three groups (all P < 0.05). The levels of TG, FPG, INS and Lep were decreased after treatment in all groups (all P < 0.05). CONCLUSION: EA can improve AHI and nocturnal hypoxia of Z syndrome, and the mechanism may be related to decreasing the indices of metabolism syndrome and leptin.