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Parkinson's disease (PD) is a degenerative disorder of the nervous system characterized by the loss of dopaminergic neurons and damage of neurons in the substantia nigra (SN) and striatum, resulting in impaired motor functions. This study aims to investigate how extracellular vesicles (EVs) derived from human umbilical cord mesenchymal stem cells (HucMSC) regulate Special AT-rich sequence-binding protein-1 (SATB 1) and influence Wnt/ß-catenin pathway and autophagy in PD model. The PD model was induced by damaging SH-SY5Y cells and mice using 6-OHDA. According to the study, administering EVs every other day for 14 days improved the motor behavior of 6-OHDA-induced PD mice and reduced neuronal damage, including dopaminergic neurons. Treatment with EVs for 12 hours increased the viability of 6-OHDA-induced SH-SY5Y cells. The upregulation of SATB 1 expression with EV treatment resulted in the activation of the Wnt/ß-catenin pathway in PD model and led to overexpression of ß-catenin. Meanwhile, the expression of LC3 II was decreased, indicating alterations in autophagy. In conclusion, EVs could mitigate neuronal damage in the 6-OHDA-induced PD model by upregulating SATB 1 and activating Wnt/ß-catenin pathway while also regulating autophagy. Further studies on the potential therapeutic applications of EVs for PD could offer new insights and strategies.
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The Ordos Basin is characterized by abundant natural gas resources, and the marine-continental transitional shale gas of the Permian Shanxi Formation has great exploration and development potential. However, few systematic studies have focused on the burial history, thermal maturity, and hydrocarbon generation of the shale, which limits the understanding of shale gas enrichment and resource evaluation. To reveal the shale gas resource potential, we focused on the Shanxi Formation shale in the southeastern Ordos Basin. Net erosion was estimated, and then one-dimensional (1D) and three-dimensional (3D) geological models were constructed using PetroMod to simulate the burial-thermal history and hydrocarbons generated in the Shanxi Formation shale, and finally, the gas generation intensity was evaluated. The results show that four periods of uplift and erosion events have occurred in the study area since the Mesozoic, of which the erosion in the Late Cretaceous was the most severe. The burial center gradually shifted from east to northwest in the study area, and the basin reached the maximum burial depth in the Late Cretaceous and then gradually changed to a monoclinal tilted east to west after uplift and erosion. The Shanxi Formation shale reached the hydrocarbon generation threshold at 233 Ma (Ro = 0.5%), reached the oil generation peak at 200 Ma (Ro = 1.0%), and entered the high maturity stage rapidly (Ro = 1.3%). Currently, the average maturity is approximately 2.48%, which is in the overmature stage. The center of shale maturity was in the southern part of the study area before the Late Jurassic and shifted northeast in the late Early Cretaceous. Cumulative gas generated to date is 44.0 × 1012 m3, and the center of gas generation was in the middle-eastern region of the study area before the Early-Middle Jurassic and shifted northwest in the Early Cretaceous. This study provides a theoretical basis and guidance for the exploration and development of marine-continental transitional shale in the Ordos Basin.
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BACKGROUND: Acrylamide (ACR) is a widely used compound that is known to be neurotoxic to both experimental animals and humans, causing nerve damage. The widespread presence of ACR in the environment and food means that the toxic risk to human health can no longer be ignored. Rosmarinic acid (RA), a natural polyphenolic compound extracted from the perilla plant, exhibits anti-inflammatory, antioxidant, and other properties. It has also been demon strated to possess promising potential in neuroprotection. However, its role and potential mechanism in treating ACR induced neurotoxicity are still elusive. PURPOSE: This study explores whether RA can improve ACR induced neurotoxicity and its possible mechanism. METHODS: The behavioral method was used to study RA effect on ACR exposed mice's neurological function. We studied its potential mechanism through metabolomics, Nissl staining, HE staining, immunohistochemical analysis, and Western blot. RESULTS: RA pretreatment reversed the increase in mouse landing foot splay and decrease in spontaneous activity caused by 3 weeks of exposure to 50 mg/kg/d ACR. Further experiments demonstrated that RA could prevent ACR induced neuronal apoptosis, significantly downregulate nuclear factor-κB and tumor necrosis factor-α expression, and inhibit NOD-like receptor protein 3 inflammasome activation, thereby reducing inflammation as confirmed by metabolomics results. Additionally, RA treatment prevented endoplasmic reticulum stress (ERS) caused by ACR exposure, as evidenced by the reversal of significant P-IRE1α,TRAF2,CHOP expression increase. CONCLUSION: RA alleviates ACR induced neurotoxicity by inhibiting ERS and inflammation. These results provide a deeper understanding of the mechanism of ACR induced neurotoxicity and propose a potential new treatment method.
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Estrés Oxidativo , Ácido Rosmarínico , Ratones , Humanos , Animales , Acrilamida/toxicidad , Endorribonucleasas , Proteínas Serina-Treonina Quinasas , Hipocampo , Inflamación/tratamiento farmacológico , Estrés del Retículo EndoplásmicoRESUMEN
Currently, there is no effective treatment for Parkinson's disease (PD), and the regenerative treatment of neural stem cells (NSCs) is considered the most promising method. This study aimed to investigate the protective effect and mechanism of NSCs on neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced cynomolgus monkey (Macaca fascicularis) model of PD. We first found that injecting NSCs into the subarachnoid space relieved motor dysfunction in PD cynomolgus monkeys, as well as reduced dopaminergic neuron loss and neuronal damage in the substantia nigra (SN) and striatum. Besides, NSCs decreased 17-estradiol (E2) level, an estrogen, in the cerebrospinal fluid (CSF) of PD cynomolgus monkeys, which shows NSCs may provide neuro-protection by controlling estrogen levels in the CSF. Furthermore, NSCs elevated proliferator-activated receptor gamma coactivator-1 alpha (PGC-1a), mitofusin 2 (MFN2), and optic atrophy 1 (OPA1) expression, three genes mediating mitochondrial biogenesis, in the SN and striatum of PD monkeys. In addition, NSCs suppress reactive oxygen species (ROS) production caused by MPTP, as well as mitochondrial autophagy, therefore preserving dopaminergic neurons. In summary, our findings show that NSCs may preserve dopaminergic and neuronal cells in an MPTP-induced PD cynomolgus monkey model. These protective benefits might be attributed to NSCs' ability of modulating estrogen balance, increasing mitochondrial biogenesis, and limiting oxidative stress and mitochondrial autophagy. These findings add to our understanding of the mechanism of NSC treatment and shed light on further clinical treatment options.
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Intoxicación por MPTP , Células-Madre Neurales , Enfermedad de Parkinson , Animales , Humanos , Macaca fascicularis/metabolismo , Intoxicación por MPTP/terapia , Intoxicación por MPTP/metabolismo , Células-Madre Neurales/metabolismo , Enfermedad de Parkinson/metabolismo , Neuronas Dopaminérgicas , Dopamina/metabolismo , Estrógenos/farmacologíaRESUMEN
Atrazine is a widely used herbicide in agricultural production. Previous studies have shown that atrazine affects hormone secretion and oocyte maturation in female reproduction. However, the specific mechanism by which atrazine affects ovarian function remains unclear. In this study, using a mouse gastric lavage model, we report that four weeks of atrazine exposure affects body growth, interferes with the estrous cycle, and increases the number of atretic follicles in mice. The expression levels of follicle development related factors StAR, BMP15, and AMH decreased. Metabolomic analysis revealed that atrazine activates an inflammatory response in ovarian tissue. Further studies confirmed that the expression levels of TNF-α, IL-6, and NF-κB increased in the ovaries of mice exposed to atrazine. Additionally, α-smooth muscle actin (α-SMA) accumulated in ovarian tissue, and transforming growth factor-ß (TGF-ß) signaling was activated, indicating the occurrence of tissue fibrosis. Moreover, mice exposed to atrazine produced fewer oocytes and exhibited reduced embryonic development. Furthermore, mice exposed to atrazine exhibited altered gut microbiota abundance and a disrupted colon barrier. Collectively, these findings suggest that atrazine exposure induces ovarian inflammation and fibrosis, disrupts ovarian homeostasis, and impairs follicle maturation, ultimately reducing oocyte quality.
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Porous silicon oxycarbide (SiOC) ceramics with tailorable microstructure and porosity were fabricated using phenyl-substituted cyclosiloxane (C-Ph) as a molecular-scale porogen are analyzed in this study. A gelated precursor was synthesized via the hydrosilylation of hydrogenated and vinyl-functionalized cyclosiloxanes (CSOs), followed by pyrolysis at 800-1400 °C in flowing N2 gas. Tailored morphologies, such as closed-pore and particle-packing structures, with porosities in the range 20.2-68.2% were achieved by utilizing the high boiling point of C-Ph and the molecular aggregation in the precursor gel induced by the conjugation force of phenyl. Moreover, some of the C-Ph participated in pyrolysis as a carbon source, which was confirmed by the carbon content and thermogravimetric analysis (TGA) data. This was further confirmed by the presence of graphite crystals derived from C-Ph, as determined by high-resolution transmission electron microscopy (HRTEM). In addition, the proportion of C-Ph involved in the ceramic process and its mechanism were investigated. The molecular aggregation strategy for phase separation was demonstrated to be facile and efficient, which may promote further research on porous materials. Moreover, the obtained low thermal conductivity of 27.4 mW m-1 K-1 may contribute to the development of thermal insulation materials.
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Flexible dielectric capacitors have been widely studied recently on account of their fast charge-discharge speed, high power density, and superior wearable characteristics. Inorganic ferroelectric fillers/polymer matrix composites combining large maximum electric displacement (Dmax) of ferroelectric materials with good flexibility and high electric breakdown strength (Eb) of the polymer are regarded as the most promising materials for preparing flexible dielectric capacitors with superior energy storage properties. However, simultaneously achieving large discharge energy density (Wd) and high energy efficiency (η) in these composites remains challenging on account of a large remnant electric displacement (Dr) and low Dmax - Dr values of ferroelectric fillers. In contrast, antiferroelectrics (AFEs) exhibit near zero Dr and larger Dmax - Dr values and are thus attractive composite fillers to simultaneously achieve large Wd and high η. On the basis of these factors, in this report, we design and prepare Pb0.97La0.02(Zr0.5SnxTi0.5-x)O3 (PLZST) AFE nanoparticles (NPs)/poly(vinylidene fluoride-co-hexafluoropropylene) (P(VDF-HFP)) nanocomposites and investigate the effects of the Sn and AFE NPs contents on the energy storage capacity of the nanocomposites. Through reasonable adjustment of the Sn content and the PLZST AFE fillers content, because of the large Dmax - Dr value of 7.75 µC/cm2 and small Dr value of 0.26 µC/cm2 at the Eb as high as 3162 kV/cm, the Pb0.97La0.02(Zr0.5Sn0.38Ti0.12)O3 AFE NPs/P(VDF-HFP) polymer nanocomposite with 7 wt % fillers exhibits the most superior energy storage properties with an ultrahigh η of 93.4% and a large Wd of 12.5 J/cm3. These values are superior to those of the recently reported dielectric nanocomposites with a single-layer structure containing ferroelectric nanowires, nanofibers, nanobelts, nanotubes, and nanosheets or core-shell structure fillers, which are prepared via a very complicated method. This work not only shows that, in principle, the polarization characteristics of the composites depend mainly on those of the inorganic fillers but also demonstrates a convenient, effective, and scalable way to fabricate dielectric capacitors with superior flexibility and energy storage capacities.
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We report the formation of multi-layer nylon-6 (PA-6) nanofibrous membranes by electrostatic spinning coupled with a hot pressing process. The structure and porosity of multi-layer PA-6 nanofibrous membranes were characterized using a scanning electron microscope and the N2 nitrogen adsorption and desorption isotherms. We show that multi-layer PA-6 nanofibrous membranes can be used for efficient and continuous indigo dye filtration. Under the condition of constant pressure at the 0.1 MPa dead end filtration, continuous filter for a period of time, the filtration efficiency for indigo dye increases with the increase of the number of layers in PA-6 nanofibrous membranes. The 10 layer PA-6 nanofiber membrane can completely remove the indigo dye, and early filtration flux was high, with extended time, the filtration flux decline and gradually stabilized.
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The amount of adsorbed shale gas is a key parameter used in shale gas resource evaluation and target area selection, and it is also an important standard for evaluating the mining value of shale gas. Currently, studies on the correlation between particle size and methane adsorption are controversial. In this study, an isothermal adsorption apparatus, the gravimetric sorption analyzer, is used to test the adsorption capacity of different particle sizes in shale to determine the relationship between the particle size and the adsorption capacity of shale. Thegravimetric method requires fewer parameters and produces better results in terms of accuracy and consistency than methods like the volumetric method. Gravimetric measurements are performed in four steps: a blank measurement, preprocessing, a buoyancy measurement, and adsorption and desorption measurements. Gravimetric measurement is presently considered to be a more scientific and accurate method of measuring the amount of adsorption; however, it is time-consuming and requires a strict measuring technique. A Magnetic Suspension Balance (MSB) is the key to verify the accuracy and consistency of this method. Our results show that adsorption capacity and particle size are correlated, but not a linear correlation, and the adsorptions in particles sieved into 40 - 60 and 60 - 80 meshes tend to be larger. We propose that the maximum adsorption corresponding to the particle size is approximately 250 µm (60 mesh) in the shale gas fracturing.
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Metano/química , Gas Natural/análisis , Tamaño de la Partícula , Adsorción , Metano/análisisRESUMEN
In this paper, we present the design and simulation of a p-n junction betavoltaic battery based on large-grain polysilicon. By the Monte Carlo simulation, the average penetration depth were obtained, according to which the optimal depletion region width was designed. The carriers transport model of large-grain polysilicon is used to determine the diffusion length of minority carrier. By optimizing the doping concentration, the maximum power conversion efficiency can be achieved to be 0.90% with a 10 mCi/cm(2) Ni-63 source radiation.