RESUMO
Thermogenesis in brown and beige adipose tissue has important roles in maintaining body temperature and countering the development of metabolic disorders such as obesity and type 2 diabetes1,2. Although much is known about commitment and activation of brown and beige adipose tissue, its multiple and abundant immunological factors have not been well characterized3-6. Here we define a critical role of IL-27-IL-27Rα signalling in improving thermogenesis, protecting against diet-induced obesity and ameliorating insulin resistance. Mechanistic studies demonstrate that IL-27 directly targets adipocytes, activating p38 MAPK-PGC-1α signalling and stimulating the production of UCP1. Notably, therapeutic administration of IL-27 ameliorated metabolic morbidities in well-established mouse models of obesity. Consistently, individuals with obesity show significantly decreased levels of serum IL-27, which can be restored after bariatric surgery. Collectively, these findings show that IL-27 has an important role in orchestrating metabolic programs, and is a highly promising target for anti-obesity immunotherapy.
Assuntos
Adipócitos/metabolismo , Metabolismo Energético , Interleucina-27/metabolismo , Termogênese , Animais , Cirurgia Bariátrica , Modelos Animais de Doenças , Feminino , Humanos , Resistência à Insulina , Interleucina-27/sangue , Interleucina-27/uso terapêutico , Masculino , Camundongos , Obesidade/sangue , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Obesidade/prevenção & controle , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Receptores de Interleucina/metabolismo , Transdução de Sinais , Proteína Desacopladora 1/biossíntese , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
Inflammation resolution is an essential process for preventing the development of chronic inflammatory diseases. However, the mechanisms that regulate inflammation resolution in psoriasis are not well understood. Here, we report that ANKRD22 is an endogenous negative orchestrator of psoriasiform inflammation because ANKRD22-deficient mice are more susceptible to IMQ-induced psoriasiform inflammation. Mechanistically, ANKRD22 deficiency leads to excessive activation of the TNFRII-NIK-mediated noncanonical NF-κB signaling pathway, resulting in the hyperproduction of IL-23 in DCs. This is due to ANKRD22 being a negative feedback regulator for NIK because it physically binds to and assists in the degradation of accumulated NIK. Clinically, ANKRD22 is negatively associated with IL-23A expression and psoriasis severity. Of greater significance, subcutaneous administration of an AAV carrying ANKRD22-overexpression vector effectively hastens the resolution of psoriasiform skin inflammation. Our findings suggest ANKRD22, an endogenous supervisor of NIK, is responsible for inflammation resolution in psoriasis, and may be explored in the context of psoriasis therapy.
Assuntos
Modelos Animais de Doenças , Interleucina-23 , Psoríase , Transdução de Sinais , Psoríase/metabolismo , Psoríase/patologia , Psoríase/terapia , Psoríase/etiologia , Psoríase/imunologia , Psoríase/genética , Psoríase/induzido quimicamente , Animais , Camundongos , Interleucina-23/metabolismo , Interleucina-23/genética , Humanos , Inflamação/metabolismo , Inflamação/patologia , Camundongos Knockout , Pele/patologia , Pele/metabolismo , Quinase Induzida por NF-kappaB , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , NF-kappa B/metabolismoRESUMO
Microglial polarization and associated inflammatory activity are the key mediators of depression pathogenesis. The natural Smilax glabra rhizomilax derivative engeletin has been reported to exhibit robust anti-inflammatory activity, but no studies to date have examined the mechanisms through which it can treat depressive symptoms. We showed that treatment for 21 days with engeletin significantly alleviated depressive-like behaviours in chronic stress social defeat stress (CSDS) model mice. T1-weighted imaging (T1WI), T2-weighted imaging (T2WI) imaging revealed no significant differences between groups, but the bilateral prefrontal cortex of CSDS mice exhibited significant increases in apparent diffusion coefficient and T2 values relative to normal control mice, with a corresponding reduction in fractional anisotropy, while engeletin reversed all of these changes. CSDS resulted in higher levels of IL-1ß, IL-6, and TNF-a production, enhanced microglial activation, and greater M1 polarization with a concomitant decrease in M2 polarization in the mPFC, whereas engeletin treatment effectively abrogated these CSDS-related pathological changes. Engeletin was further found to suppress the LCN2/C-X-C motif chemokine ligand 10 (CXCL10) signalling axis such that adeno-associated virus-induced LCN2 overexpression ablated the antidepressant effects of engeletin and reversed its beneficial effects on the M1/M2 polarization of microglia. In conclusion, engeletin can alleviate CSDS-induced depressive-like behaviours by regulating the LCN2/CXCL10 pathway and thereby altering the polarization of microglia. These data suggest that the antidepressant effects of engeletin are correlated with the polarization of microglia, highlighting a potential avenue for future design of antidepressant strategies that specifically target the microglia.
Assuntos
Antidepressivos , Flavonóis , Glicosídeos , Microglia , Camundongos , Animais , Microglia/metabolismo , Antidepressivos/farmacologia , Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Depressão/etiologia , Transdução de SinaisRESUMO
Polarization, as an important characterization of the symmetry breaking systems, has attracted tremendous attention in two-dimensional (2D) materials. Due to their significant symmetry breaking, Janus 2D ferrovalley materials provide a desirable platform to investigate the charge, spin, and valley polarization, as well as their coupling effects. Herein, using first-principles calculations, the polarization properties of charge, spin, and valley in Janus VSiGeZ4 (Z = N, P, and As) monolayers are systematically studied. The mirror symmetry breaking leads to a non-zero dipole moment and surface work function difference, indicating the presence of out-of-plane charge polarization. Magnetic properties calculations demonstrate that VSiGeN4 is a 2D-XY magnet with a Berezinskii-Kosterlitz-Thouless temperature of 342 K, while VSiGeP4 and VSiGeAs4 have an out-of-plane magnetization with a Curie temperature below room temperature. The magnetization can be rotated by applying biaxial strain, allowing manipulation of the spin polarization via nonmagnetic means. The spontaneous valley polarization is predicted to be 46, 49, and 70 meV for VSiGeN4, VSiGeP4, and VSiGeAs4, respectively, whose physical origin can be elucidated by employing the model analysis. In particular, the biaxial strain can induce the valley polarization switching from the valence (conduction) band to conduction (valence) band, but it hardly changes the valley polarization strength. Meanwhile, the valley extremum is transformed from the K' (K) to K (K') points. The present work not only provides an underlying insight into the polarization properties of Janus VSiGeZ4 but also offers a class of promising materials for spintronic and valleytronic devices.
RESUMO
Intracerebral hemorrhage (ICH) remains a significant cause of morbidity and mortality around the world, and surgery is still the most direct and effective way to remove ICH. However, the potential risks brought by surgery, such as normal brain tissue damage, post-operative infection, and difficulty in removing deep hematoma, are still the main problems in the surgical treatment of ICH. Activation of the peroxisome proliferator-activated receptor gamma (PPARγ) is reported to show a good therapeutic effect in hematoma clearance. Herein, a magnetic targeting nanocarrier loaded with a PPARγ agonist (15d-PGJ2-MNPs) is synthesized, which could be magnetically targeted and enriched in the area of the hematoma after intravenous injection. Subsequent application of focusing ultrasound (FUS) could enhance drug diffusion, which activates the PPARγ receptors on macrophages around the hematoma for better hematoma clearance. The 15d-PGJ2-MNP treatment alleviates brain injury, accelerates hematoma clearance, attenuates neuroinflammation, reduces brain edema and significantly improves the deficits in sensory and motor function and spatial learning ability in the ICH mouse model. This work proposes an effective magnetic targeting plus FUS method to treat ICH, highlighting its great potential in the treatment of hemorrhagic stroke.
Assuntos
Hemorragia Cerebral , PPAR gama , Camundongos , Animais , PPAR gama/agonistas , PPAR gama/metabolismo , Hemorragia Cerebral/diagnóstico por imagem , Hemorragia Cerebral/terapia , Hemorragia Cerebral/complicações , Encéfalo/metabolismo , Hematoma/terapia , Hematoma/tratamento farmacológico , Modelos Animais de Doenças , Fenômenos MagnéticosRESUMO
Hypoxia-inducible factor 2α (HIF2α) plays a pivotal role in breast tumor growth and metastasis. However, the regulatory mechanisms of HIF2α protein stability remain poorly understood. The precise role of the deubiquitinase (DUB) ubiquitin-specific peptidase 5 (USP5) in breast cancer and the underlying mechanism remains largely unknown. Here, we identified USP5 as a novel DUB for HIF2α. Physically, USP5 interacts with HIF2α and protects HIF2α from ubiquitin-proteasome degradation, thereby promoting the transcription of HIF2α target genes, such as SLC2A1, PLOD2, P4HA1, and VEGFA. USP5 ablation impairs breast cancer cells proliferation, colony formation, migration, and invasion. Moreover, USP5 is highly expressed in breast cancer, and the protein levels of USP5 are positively correlated with HIF2α protein levels in human breast cancer tissues. Importantly, high levels of USP5 leads to poor clinical outcome in patients with breast cancer. Collectively, USP5 stabilizes HIF2α through its DUB activity and provides a potential therapeutic target for breast cancer.
Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Neoplasias da Mama , Endopeptidases/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/química , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células , Feminino , Humanos , Proteólise , Ubiquitina/metabolismoRESUMO
Mu oil tree (Vernicia montana) is an economically important woody oil plant, which is widely distributed in southern China. In mid-May 2020, a leaf spot disease was observed on the leaves of mu oil tree in Taihe County in Jiangxi Province, China (26°55'25.55â³N, 114°49'5.85â³E). The disease incidence was estimated to be above 40%. Initial symptoms were circular red-brown spots which were 1-2 mm in diameter, then enlarged with red-brown center. In later stages, the spots coalesced and formed large patches, and subsequently red-brown centers of lesions gradually dried and fell out, forming a "shot hole" appearance. To identify the pathogen, diseased leaves were collected from Taihe County. Leaf tissues (5 × 5 mm) were cut from the margins of typical symptomatic lesions, surface- sterilized in 75% ethanol for 30 seconds and 3% sodium hypochlorite for 60 seconds, then rinsed with sterile distilled water three times. Leaf pieces were placed on potato dextrose agar (PDA; 1.5%, Difco-BD Diagnostics) and incubated at 25 °C in the dark. Pure cultures were obtained from individual conidia by recovering single spores. On PDA, colonies were initially white and cottony. The mycelia then became pinkish to deep-pink with time at the center on the front side and pink on the reverse side. Colonies produced pale orange conidial masses after 9 days. Conidia were fusiform with acute ends, smooth-walled, hyaline, and measured 3.6-5.5 × 8.1-14.5 µm (4.5 ± 0.5 × 10.6 ± 1.0 µm, n = 100). The morphological characteristics of the isolate matched the descriptions of Colletotrichum acutatum complex (Damm et al. 2012). For molecular identification, the internal transcribed spacer (ITS) region, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), chitin synthase (CHS-1), beta-tubulin 2 (TUB2), and actin (ACT) were sequenced using the primers ITS1/ITS4, GDF/GDR, CHS-79F/CHS-345R, T1/Bt2b, ACT-512F/ACT-783R, respectively (Weir et al. 2012). The obtained sequences were deposited into the GenBank [accession nos. MW584317 (ITS); MW656269 (GAPDH); MW656270 (TUB2); MW656268 (CHS-1); MW656267 (ACT)]. All the sequences showed 94 to 100% similarity with those of C. fioriniae. A neighbor-joining phylogenetic tree was generated by combining all the sequenced loci using MEGA7.0 (Kumar et al. 2016). The isolate TH-M4 clustered with C. fioriniae, having 99% bootstrap support. Base on the morphology and multi-gene phylogeny, isolate TH-M4 was identified as C. fioriniae (Damm et al. 2012). To confirm pathogenicity, 20 healthy leaves of 10 mu oil trees (3-year-old) grown outdoors were inoculated with a drop of spore suspension (106 conidia per mL) of the isolate TH-M4 in September 2020. Another 10 plants were inoculated with sterile water as the control. The leaves were wounded with a sterile toothpick. All the inoculated leaves were covered with black plastic bags to maintain humidity for 2 days. The pathogenicity test was repeated twice. The resulting symptoms were similar to those on the original infected plants, whereas the control leaves remained asymptomatic. The same fungus was re-isolated from the lesions on the inoculated plant, fulfilling Koch's postulates. C. fioriniae has been recorded as anthracnose pathogen on Mahonia aquifolium (Garibaldi et al. 2020), Paeonia lactiflora (Park et al. 2020), Solanum melongena (Xu et al. 2020), and Juglans regia (Varjas et al. 2020). To our knowledge, this is the first report of C. fioriniae associated with leaf spot disease on mu oil tree in China. This study provided crucial information for epidemiologic studies and appropriate control strategies for this oil plant disease.
RESUMO
Spent lead paste is the main component in lead-acid batteries reaching end of life. It contains about 55% lead sulphate and 35% lead dioxide, as well as minor amounts of lead oxide. It is necessary to recycle spent lead paste with minimal pollution and low energy consumption instead of the conventional smelting method. In this study, a novel approach involving hydrometallurgical desulphurisation and thermal degradation is developed to recover lead as PbO products from spent lead acid batteries. First, the desulphurisation effects and phase compositions of products with different transforming agents were compared, and the optimum conditions using (NH4)2CO3 as a transforming agent were determined. And then, the thermal degradation processes of both precursors lead carbonate and lead dioxide were investigated to prepare α-PbO, Pb3O4, and ß-PbO products in argon and air atmospheres, respectively. Both the desulphurisation precursors and the calcination products were characterised by thermogravimetry and differential scanning calorimetry, X-ray diffraction, and scanning electron microscopy. The results showed that the lead oxide products were prepared, including α-PbO at 450°C in argon, Pb3O4 and ß-PbO at 480°C and 620°C in air, respectively.
Assuntos
Fontes de Energia Elétrica , Reciclagem , Poluição Ambiental , Termogravimetria , Difração de Raios XRESUMO
The unique physical property of negative thermal expansion (NTE) is not only interesting for scientific research but also important for practical applications. Chemical modification generally tends to weaken NTE. It remains a challenge to obtain enhanced NTE from currently available materials. Herein, we successfully achieve enhanced NTE in Pb(Ti1-xVx)O3 by improving its ferroelectricity. With the chemical substitution of vanadium, lattice tetragonality (c/a) is highly promoted, which is attributed to strong spontaneous polarization, evidenced by the enhanced covalent interaction in the V/Ti-O and Pb-O2 bonds from first-principles calculations. As a consequence, Pb(Ti0.9V0.1)O3 exhibits a nonlinear and much stronger NTE over a wide temperature range with a volumetric coefficient of thermal expansion αV = -3.76 × 10-5/°C (25-550 °C). Interestingly, an intrinsic giant volume contraction (â¼3.7%) was obtained at the composition of Pb(Ti0.7V0.3)O3 during the ferroelectric-to-paraelectric phase transition, which represents the highest value ever reported. Such volume contraction is well correlated to the effect of spontaneous volume ferroelectrostriction. The present study extends the scope of the NTE family and provides an effective approach to explore new materials with large NTE, such as through adjusting the NTE-related ferroelectric property in the family of ferroelectrics.
RESUMO
Due to their novel spin and valley properties, two-dimensional (2D) ferrovalley materials are expected to be promising candidates for next-generation spintronic and valleytronic devices. However, they are subject to various defects in practical applications. Therefore, the electronic, valley, and magnetic properties may be modified in the presence of the defects. In this work, utilizing first-principles calculations, we systematically studied the effects of defects on the electronic, valley, and magnetic properties of the 2D ferrovalley material VSi2N4. It has been found that C doping, O doping, and N vacancies result in the half-metallic feature, Si vacancies result in the metallic feature, and V vacancies result in a bipolar gapless semiconductor. These defect-induced electronic properties can be effectively tuned by changing defect concentration and layer thickness. Since the impurity bands do not affect the K and K' valleys, valley polarization is well maintained in O-doped and N-defective systems. Importantly, these defects play a crucial role in modifying the magnetic properties of the pristine VSi2N4, especially the magnitude of local magnetic moments and the magnetic anisotropy energy. Detailed analysis of the density of states demonstrates that the variations of the total magnetic moment and magnetic anisotropy energy with biaxial strain are determined by the electronic states near the Fermi level rather than the type of defect, which provides a new understanding of the effects of defects on the magnetic properties of 2D materials. Moreover, the layer thickness can affect the magnetic coupling between defects and surrounding V atoms. Our results offer insight into the electronic, valley, and magnetic properties of VSi2N4 in the presence of various point defects.
RESUMO
Music-oriented auditory attention detection (AAD) aims at determining which instrument in polyphonic music a listener is paying attention to by analyzing the listener's electroencephalogram (EEG). However, the existing linear models cannot effectively mimic the nonlinearity of the human brain, resulting in limited performance. Thus, a nonlinear music-oriented AAD model is proposed in this paper. Firstly, an auditory feature and a musical feature are fused to represent musical sources precisely and comprehensively. Secondly, the EEG is enhanced if music stimuli are presented in stereo. Thirdly, a neural network architecture is constructed to capture nonlinear and dynamic interactions between the EEG and auditory stimuli. Finally, the musical source most similar to the EEG in the common embedding space is identified as the attended one. Experimental results demonstrate that the proposed model outperforms all baseline models. On 1-s decision windows, it reaches accuracies of 92.6% and 81.7% under mono duo and trio stimuli, respectively. Additionally, it can be easily extended to speech-oriented AAD. This work can open up new possibilities for studies on both brain neural activity decoding and music information retrieval.
Assuntos
Música , Humanos , Percepção Auditiva , Eletroencefalografia , Encéfalo , Redes Neurais de Computação , Estimulação Acústica/métodosRESUMO
SLMO2 is a lipid transporter that transports phosphatidylserine to the interior of mitochondria, also known as PRELID3B, which plays an important role in lipid metabolism. It has also been reported to be involved in the growth process of breast and lung tumors. However, its functions and underlying mechanisms in cancer progress remain elusive, and the potential as pan-cancer biomarker and therapeutic target remains unexplored. Using the TCGA project and GEO database, we performed pan-cancer analysis of SLMO2, which including the expression pattern, prognostic value, mutation landscape, methylation modification, protein-protein interaction network and the relationship between SLMO2 expression and immune infiltration. KEGG enrichment analysis was also performed to predict function and relevant cellular pathways of SLMO2. In addition, proliferation and migration assays were performed to detect the proliferation and metastasis capacity of breast cancer and lung cancer cells. In our study, we found that SLMO2 was overexpressed in pan-cancer and the elevated expression of SLMO2 was correlated with poorer prognosis. SLMO2 mutations were distributed in a variety of tumors and correlated with prognosis. Promoter methylation analysis showed that SLMO2 methylation levels were lower in most tumors compared with normal tissues, while a few tumors showed increased methylation levels of SLMO2. SLMO2 expression was also positively correlated with immune infiltration of MDSCs. Further pathway enrichment analysis indicated that SLMO2 was involved in regulating of cytoplasmic transport and other oncogenic processes. In vitro experiments have shown that SLMO2 promotes the proliferation and migration of breast cancer and lung cancer cells. In conclusion, our findings suggested that SLMO2 was a potential prognostic and immunological marker in pan-cancer. This study suggested a potential strategy for targeting SLMO2 to treat tumors, including manipulating tumor growth or the tumor microenvironment, especially the infiltration of MDSC.
Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Humanos , Feminino , Prognóstico , Neoplasias da Mama/genética , Neoplasias Pulmonares/genética , Biomarcadores Tumorais/genética , Transporte Biológico , Microambiente TumoralRESUMO
Objective. The instability of the EEG acquisition devices may lead to information loss in the channels or frequency bands of the collected EEG. This phenomenon may be ignored in available models, which leads to the overfitting and low generalization of the model.Approach. Multiple self-supervised learning tasks are introduced in the proposed model to enhance the generalization of EEG emotion recognition and reduce the overfitting problem to some extent. Firstly, channel masking and frequency masking are introduced to simulate the information loss in certain channels and frequency bands resulting from the instability of EEG, and two self-supervised learning-based feature reconstruction tasks combining masked graph autoencoders (GAE) are constructed to enhance the generalization of the shared encoder. Secondly, to take full advantage of the complementary information contained in these two self-supervised learning tasks to ensure the reliability of feature reconstruction, a weight sharing (WS) mechanism is introduced between the two graph decoders. Thirdly, an adaptive weight multi-task loss (AWML) strategy based on homoscedastic uncertainty is adopted to combine the supervised learning loss and the two self-supervised learning losses to enhance the performance further.Main results. Experimental results on SEED, SEED-V, and DEAP datasets demonstrate that: (i) Generally, the proposed model achieves higher averaged emotion classification accuracy than various baselines included in both subject-dependent and subject-independent scenarios. (ii) Each key module contributes to the performance enhancement of the proposed model. (iii) It achieves higher training efficiency, and significantly lower model size and computational complexity than the state-of-the-art (SOTA) multi-task-based model. (iv) The performances of the proposed model are less influenced by the key parameters.Significance. The introduction of the self-supervised learning task helps to enhance the generalization of the EEG emotion recognition model and eliminate overfitting to some extent, which can be modified to be applied in other EEG-based classification tasks.
Assuntos
Eletroencefalografia , Emoções , Aprendizado de Máquina Supervisionado , Aprendizado de Máquina Supervisionado/normas , Conjuntos de Dados como Assunto , HumanosRESUMO
Lithium supply risk is increasing and driving rapid progress in lithium recovery schemes from spent lithium-ion batteries (LIBs). In this study, a facile recycling process consisting mainly of reduction roasting and NaHCO3 leaching was adopted to improve lithium recovery. The Li of spent LiNixCoyMn1-x-yO2 powder were converted to Li2CO3 and LiAlO2 with the reduction effect of C and residual Al in the roasting process. NaHCO3 leaching was utilized to selectively dissolve lithium from Li2CO3 and water-insoluble LiAlO2. The activation energy of NaHCO3 leaching was 9.31 kJâmol-1 and the leaching of lithium was a diffusion control reaction. More than 95.19 % lithium was leached and recovered as a Li2CO3 product with a purity of 99.80 %. Thus, this approach provides a green path to selective recovery of lithium with good economics.
Assuntos
Fontes de Energia Elétrica , Lítio , Reciclagem , Lítio/química , Reciclagem/métodos , Bicarbonato de Sódio/químicaRESUMO
Purpose: Psoriasis is a systemic inflammatory disease, and the mechanism that links psoriasis to depression is still elusive. Hence, this study aimed to elucidate the potential pathogenesis of psoriasis and depression comorbidity. Methods: The gene expression profiles of psoriasis (GSE34248, GSE78097 and GSE161683) and depression (GSE39653) were downloaded from the Gene Expression Omnibus (GEO) DataSets. Functional annotation, protein-protein interaction (PPI) network and module construction, and hub gene identification and co-expression analysis were performed, following identification of the common differentially expressed genes (DEGs) of psoriasis and depression. Results: A total of 115 common DEGs (55 up-regulated and 60 down-regulated) were identified between psoriasis and depression. Functional analysis indicated that T cell activation and differentiation were predominantly implicated in the potential pathogenesis of these two diseases. In addition, Th17 cell differentiation and cytokines is closely related to both. Finally, 17 hub genes were screened, including CTLA4, LCK, ITK, IL7R, CD3D, SOCS1, IL4R, PRKCQ, SOCS3, IL23A, PDGFB, PAG1, TGFA, FGFR1, RELN, ITGB5 and TNXB, which re-emphasized the importance of the immune system in psoriasis and depression. Conclusion: Our study reveals the common pathogenesis of psoriasis and depression. These common pathways and hub genes may apply to a molecular screening tool for depression in psoriasis patients, which could help dermatologists optimize patient management in routine care.
RESUMO
Hydrazine (N2H4) can cause serious damage to human health, while intracellular viscosity is highly associated with many diseases and cellular dysfunctions. Herein, we report the synthesis of a dual-responsive organic molecule-based fluorescent probe with excellent water solubility being capable of detection of N2H4 and viscosity through dual-fluorescence channels in "turn on" manner for both. Besides sensitive detection of N2H4 in aqueous solution with detection limit of 0.135 µM, this probe could be used for vapor N2H4 detection in colorimetric and fluorescent manners. In addition, the probe demonstrated viscosity-dependent fluorescence enhancement behavior, and as high as 150-fold enhancement could be obtained at 95% glycerol aqueous solution. Cell imaging experiment revealed that the probe could be used for the discriminating of living and dead cells.
Assuntos
Sondas Moleculares , Água , Humanos , Viscosidade , Espectrometria de Fluorescência/métodos , Corantes Fluorescentes , Hidrazinas , Células HeLaRESUMO
Transplantation of neural stem cells (NSCs) has been proved to promote functional rehabilitation of brain lesions including ischemic stroke. However, the therapeutic effects of NSC transplantation are limited by the low survival and differentiation rates of NSCs due to the harsh environment in the brain after ischemic stroke. Here, we employed NSCs derived from human induced pluripotent stem cells together with exosomes extracted from NSCs to treat cerebral ischemia induced by middle cerebral artery occlusion/reperfusion in mice. The results showed that NSC-derived exosomes significantly reduced the inflammatory response, alleviated oxidative stress after NSC transplantation, and facilitated NSCs differentiation in vivo. The combination of NSCs with exosomes ameliorated the injury of brain tissue including cerebral infarction, neuronal death, and glial scarring, and promoted the recovery of motor function. To explore the underlying mechanisms, we analyzed the miRNA profiles of NSC-derived exosomes and the potential downstream genes. Our study provided the rationale for the clinical application of NSC-derived exosomes as a supportive adjuvant for NSC transplantation after stroke.
Assuntos
Isquemia Encefálica , Exossomos , Células-Tronco Pluripotentes Induzidas , AVC Isquêmico , Camundongos , Humanos , Animais , Isquemia Encefálica/terapia , Infarto Cerebral , Diferenciação Celular/fisiologiaRESUMO
Amino acid (aa) metabolism is closely correlated with the pathogenesis of psoriasis; however, details on aa transportation during this process are barely known. Here, we find that SLC38A5, a sodium-dependent neutral aa transporter that counter-transports protons, is markedly upregulated in the psoriatic skin of both human patients and mouse models. SLC38A5 deficiency significantly ameliorates the pathogenesis of psoriasis, indicating a pathogenic role of SLC38A5. Surprisingly, SLC38A5 is almost exclusively expressed in dendritic cells (DCs) when analyzing the psoriatic lesion and mainly locates on the lysosome. Mechanistically, SLC38A5 potentiates lysosomal acidification, which dictates the cleavage and activation of TLR7 with ensuing production of pro-inflammatory cytokines such as interleukin-23 (IL-23) and IL-1ß from DCs and eventually aggravates psoriatic inflammation. In summary, this work uncovers an auxiliary mechanism in driving lysosomal acidification, provides inspiring insights for DC biology and psoriasis etiology, and reveals SLC38A5 as a promising therapeutic target for treating psoriasis.
Assuntos
Sistemas de Transporte de Aminoácidos Neutros , Psoríase , Animais , Camundongos , Humanos , Células Dendríticas/metabolismo , Pele/patologia , Psoríase/patologia , Inflamação/patologia , Modelos Animais de Doenças , Lisossomos/patologia , Concentração de Íons de HidrogênioRESUMO
Objective. To take full advantage of both labeled data and unlabeled ones, the Graph Convolutional Network (GCN) was introduced in electroencephalography (EEG) based emotion recognition to achieve feature propagation. However, a single feature cannot represent the emotional state entirely and precisely due to the instability of the EEG signal and the complexity of the emotional state. In addition, the noise existing in the graph may affect the performance greatly. To solve these problems, it was necessary to introduce feature/similarity fusion and noise reduction strategies.Approach. A semi-supervised EEG emotion recognition model combining graph fusion, network enhancement, and feature fusion was proposed. Firstly, different features were extracted from EEG and then compacted by Principal Component Analysis (PCA), respectively. Secondly, a Sample-by-sample Similarity Matrix (SSM) was constructed based on each feature, and similarity network fusion (SNF) was adopted to fuse the graphs corresponding to different SSMs to take advantage of their complementarity. Then, Network Enhancement (NE) was performed on the fused graph to reduce the noise in it. Finally, GCN was performed on the concatenated features and the enhanced fused graph to achieve feature propagation.Main results. Experimental results demonstrated that: (a) When 5.30%of SEED and 7.20%of SEED-IV samples were chosen as the labeled samples, respectively, the minimum classification accuracy improvement achieved by the proposed scheme over state-of-the-art schemes were 1.52%on SEED and 13.14%on SEED-IV, respectively. (b) When 8.00%of SEED and 9.60%of SEED-IV samples were chosen as the labeled samples, respectively, the minimum training time reduction achieved by the proposed scheme over state-of-the-art schemes were 46.75 s and 22.55 s, respectively. (c) Graph fusion, network enhancement, and feature fusion all contributed to the performance enhancement. (d) The key hyperparameters that affect the performance were relatively few and easy to set to obtain outstanding performance.Significance. This paper demonstrated that the combination of graph fusion, network enhancement, and feature fusion help to enhance GCN-based EEG emotion recognition.
Assuntos
Eletroencefalografia , Emoções , Análise de Componente PrincipalRESUMO
A transient three-dimensional comprehensive numerical model was established to study ion transport caused by diffusion, convection, and electro-migration in the electro-refining process for scrap-metal recycling. The Poisson-Nernst-Planck equations were used to define ion transport within the electrolyte, while the Naiver-Stokes equations and the energy equation were employed to describe fluid flow and heat transfer. In addition, the Butler-Volmer formulation was used to represent the kinetics of the electrochemical reaction. The comparison between the measured and simulated data indicates the reliability of the model. Under the action of diffusion and electro-migration, the positive copper ion moves from the anode to the cathode, while the negative sulfate ion migrates in the opposite direction. The distribution of the ion concentration, however, greatly changes if the fluid flow is taken into account. The ion concentration around the anode and the rate of the electrochemical reaction that occurs at the anode surface are reduced by the fluid flow. The proposed computational framework offers a valuable basis for future research and development in the field of scrap-metal recycling technology.