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Defect engineering is an effective strategy to enhance the enzyme-like activity of nanozymes. However, previous efforts have primarily focused on introducing defects via de novo synthesis and post-synthetic treatment, overlooking the dynamic evolution of defects during the catalytic process involving highly reactive oxygen species. Herein, a defect-engineered metal-organic framework (MOF) nanozyme with mixed linkers is reported. Over twofold peroxidase (POD)-like activity enhancement compared with unmodified nanozyme highlights the critical role of in situ defect formation in enhancing the catalytic performance of nanozyme. Experimental results reveal that highly active hydroxyl radical (â¢OH) generated in the catalytic process etches the 2,5-dihydroxyterephthalic acid ligands, contributing to electronic structure modulation of metal sites and enlarged pore sizes in the framework. The self-enhanced POD-like activity induced by in situ defect engineering promotes the generation of â¢OH, holding promise in colorimetric sensing for detecting dichlorvos. Utilizing smartphone photography for RGB value extraction, the resultant sensing platform achieves the detection for dichlorvos ranging from 5 to 300 ng mL-1 with a low detection limit of 2.06 ng mL-1. This pioneering work in creating in situ defects in MOFs to improve catalytic activity offers a novel perspective on traditional defect engineering.
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Korla pear has a unique taste and aroma and is a breeding parent of numerous pear varieties. It is susceptible to Valsa mali var. pyri, which invades bark wounded by freezing injury. Its genetic relationships have not been fully defined and could offer insight into the mechanism for freezing tolerance and disease resistance. We generated a high-quality, chromosome-level genome assembly for Korla pear via the Illumina and PacBio circular consensus sequencing (CCS) platforms and high-throughput chromosome conformation capture (Hi-C). The Korla pear genome is ~ 496.63 Mb, and 99.18% of it is assembled to 17 chromosomes. Collinearity and phylogenetic analyses indicated that Korla might be derived from Pyrus pyrifolia and that it diverged ~ 3.9-4.6 Mya. During domestication, seven late embryogenesis abundant (LEA), two dehydrin (DHN), and 54 disease resistance genes were lost from Korla pear compared with P. betulifolia. Moreover, 21 LEA and 31 disease resistance genes were common to the Korla pear and P. betulifolia genomes but were upregulated under overwintering only in P. betulifolia because key cis elements were missing in Korla pear. Gene deletion and downregulation during domestication reduced freezing tolerance and disease resistance in Korla pear. These results could facilitate the breeding of novel pear varieties with high biotic and abiotic stress resistance.
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Cromosomas de las Plantas , Genoma de Planta , Pyrus , Pyrus/genética , Pyrus/fisiología , Cromosomas de las Plantas/genética , Filogenia , Estaciones del Año , Resistencia a la Enfermedad/genética , CongelaciónRESUMEN
OBJECTIVE: Ischemic stroke is a leading cause of death and disability in individuals worldwide. Cerebral ischemia-reperfusion injury (CIRI) typically results in severe secondary injury and complications following reperfusion therapy. Microglia play critical roles in the inflammatory reaction of CIRI. However, less attention has been given to microglial death in this process. Our study aims to explore microglial death in CIRI and the effects and mechanism of minocycline treatment on microglia. METHODS: A middle cerebral artery occlusion (MCAO) model was applied to induce CIRI in rats. At 0 h, 24 h and 48 h post-operation, rats were intraperitoneally injected with 45 mg/kg minocycline. Neurological deficit scoring, 2,3,5-triphenyltetrazolium chloride (TTC) staining, assessment of activated microglia and examination of mitochondrial structure were conducted and checked at 72 h after reperfusion. Additionally, an in vitro model of oxygen-glucose deprivation/reperfusion (OGD/R) model was established. BV-2 cells were treated with various pharmacological inhibitors of cell death or minocycline. Cell viability, lipid peroxidation, mitochondrial structure and function, and labile Fe2+ and ferroptosis-associated gene/protein levels were measured. Hemin was used for further validation after transcriptome analysis. RESULTS: In the MCAO and OGD/R models, ferroptosis was identified as a major form of microglial death. Minocycline inhibited microglia ferroptosis by reducing HO-1 expression. In addition, minocycline improved mitochondrial membrane potential, mitochondrial structures and microglial survival in vivo. Minocycline also decreased labile Fe2+ levels, lipid peroxidation, and expression of ferritin heavy chain (FTH) and it improved mitochondrial structure and function in vitro. Upregulation of HO-1 counteracted the protective effect of minocycline. CONCLUSION: Ferroptosis is a major form of microglial death in CIRI. The protective mechanism of minocycline in CIRI partially hinges on its ability to effectively ameliorate microglia ferroptosis by downregulating HO-1 expression. Consequently, targeting microglia ferroptosis is a promising treatment for CIRI.
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This study aimed to investigate the expression and significance of insulin-like growth factor binding protein 5 (IGFBP5) and extracellular matrix (ECM) related proteins in anterior vaginal wall tissues among aged pelvic organ prolapse (POP) patients. Tissues from the anterior vaginal wall were collected from 28 patients with POP and 20 patients without POP. The expression of protein and mRNA levels of IGFBP5 and ECM related proteins were evaluated in the vaginal wall tissues using immunohistochemistry, western blotting, and RT-qPCR techniques. The expression levels were then compared with clinical parameters. The expression levels of protein and mRNA of IGFBP5, collagen I, and collagen III were significantly lower in the POP group. Protein and mRNA expression levels of MMP2 were significantly higher in the POP group. IGFBP5 protein and mRNA expression levels were negatively correlated with age and significantly lower in older POP patients (≥ 65 years old) compared to younger POP patients (< 65 years old). IGFBP5 protein and mRNA expression levels were also significantly lower in POP-Q stage IV patients compared to POP-Q stage III patients. IGFBP5 expression level is negatively correlated with the age and severity of prolapse. The significant decrease in IGFBP5 expression may play a crucial part in the aging process and the occurrence of POP.
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Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina , Prolapso de Órgano Pélvico , Vagina , Humanos , Femenino , Prolapso de Órgano Pélvico/metabolismo , Prolapso de Órgano Pélvico/genética , Prolapso de Órgano Pélvico/patología , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/genética , Proteína 5 de Unión a Factor de Crecimiento Similar a la Insulina/metabolismo , Vagina/metabolismo , Vagina/patología , Anciano , Persona de Mediana Edad , ARN Mensajero/genética , ARN Mensajero/metabolismo , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 2 de la Matriz/genética , Factores de EdadRESUMEN
BACKGROUND: Compost-bedded pack barns (CBP) are getting huge attention as an alternative housing system for dairy cows due to their beneficial impact on animal welfare. Effective microorganisms (EM) inoculums are believed to enhance compost quality, improve soil structure and benefit the environment. However, little information is available on the impact of incubation with external EM combinations on the barn environment, compost quality and microbial diversity in CBP. This experiment was carried out to investigate the effect of inoculating different combinations of EM [Lactobacillus plantarum (L), Compound Bacillus (B) and Saccharomyces cerevisiae (S)] on compost quality and microbial communities of CBP products, as well as the relationship with the heifers' barn environment. CBP barns were subjected to the following four treatments: CON with no EM inoculum, LB/LS/LBS were Incubated with weight ratios of 1:2 (L: B), 1:2 (L: S), 1:1:1 (L: B: S), respectively. RESULTS: The EM inoculation (LB, LS, LBS) reduced the concentration of respirable particulate matter (PM10 and PM2.5) in the CBP, and decreased the serum total protein and total cholesterol levels in heifers. Notably, LBS achieved the highest content of high-density lipoprotein compared to other treatments. Microbiome results revealed that EM inoculation reduced the bacterial abundance (Chao1 index) and fungal diversity (Shannon & Simpson indexes), while increasing the relative abundance of various bacterial genera (Pseudomonas, Paracoccus, Aequorivita) and fungi (Pestalotiopsis), which are associated with cellulose decomposition that ultimately resulted in accelerating organic matter degradation and humification. Furthermore, high nutrient elements (TK&TP) and low mycotoxin content were obtained with EM inoculation, with LBS showing a particularly pronounced effect. Meanwhile, LBS contributed to a decline in the proportion of fungal pathogen categories but also led to an increase in fungal saprotroph categories. CONCLUSION: Generally, EM inoculation positively impacted compost product quality as organic fertilizer and barn environment by modifying the abundance of cellulolytic bacteria and fungi, while inhibiting the reproduction of pathogenic microbes, especially co-supplementing with L, B and S achieved an amplifying effect.
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Bacterias , Compostaje , Hongos , Animales , Bovinos , Compostaje/métodos , Hongos/clasificación , Bacterias/clasificación , Bacterias/aislamiento & purificación , Vivienda para Animales , Interacciones Microbianas , Femenino , Microbiología del Suelo , MicrobiotaRESUMEN
Motor adaptation - the process of reducing motor errors through feedback and practice - is an essential feature of human competence, allowing us to move accurately in dynamic and novel environments. Adaptation typically results from sensory feedback, with most learning driven by visual and proprioceptive feedback that arises with the movement. In humans, motor adaptation can also be driven by symbolic feedback. In the present study, we examine how implicit and explicit components of motor adaptation are modulated by symbolic feedback. We conducted three reaching experiments involving over 400 human participants to compare sensory and symbolic feedback using a task in which both types of learning processes could be operative (Experiment 1) or tasks in which learning was expected to be limited to only an explicit process (Experiments 2 and 3). Adaptation with symbolic feedback was dominated by explicit strategy use, with minimal evidence of implicit recalibration. Even when matched in terms of information content, adaptation to rotational and mirror reversal perturbations was slower in response to symbolic feedback compared to sensory feedback. Our results suggest that the abstract and indirect nature of symbolic feedback disrupts strategic reasoning and/or refinement, deepening our understanding of how feedback type influences the mechanisms of sensorimotor learning.
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With the aging population in China, health issues among the elderly are becoming increasingly prominent, leading to a rapidly growing demand for health interventions for the elderly. Exergames are one of the important emerging methods in the field of health interventions for the elderly, widely used and yielding positive results. While research on exergames is well-established abroad, it is still in its infancy in China, lacking reports on the types, interaction forms, intervention content, application status, and effectiveness of exergames. Exergames are suitable for widespread use among the elderly in China, and there is a need to accelerate the development and application of exergames in the field of health interventions for the elderly in China.
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Juegos de Video , Humanos , Anciano , China , Ejercicio Físico , Terapia por Ejercicio/métodosRESUMEN
This article reports on a study that examined the impact of a flipped English as a Foreign Language (EFL) course on college students' second language (L2) development. Specifically, an 18-week quasi-experiment was administered in a general English course at a Chinese university, with a total of 612 first-year students randomly assigned to the treatment (n = 137) and control (n = 475) groups. Using the propensity score matching and difference-in-differences (PSM-DID) model, we analyzed norm scores on high-stakes assessments administered on the entry and completion of the intervention. The results revealed a causal link between flipped learning (FL) and improved L2 language performance though the impact of FL had substantial heterogeneity as greater gains were found in reading than in writing and listening. Quantile regression analysis suggested the effectiveness of FL varied greatly by proficiency level in that students in the lowest quantiles achieved high improvement in reading and listening but moderate improvement in writing. We discuss the pedagogical implications of these findings to college L2 flipped instruction and recommend that future research be conducted in a more rigorous experimental design to obtain robust and accurate estimates of the effectiveness of FL.
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Nasal administration is a non-invasive method of drug delivery that offers several advantages, including rapid onset of action, ease of use, no first-pass effect, and fewer side effects. On this basis, nose-to-brain delivery technology offers a new method for drug delivery to the brain and central nervous system, which has attracted widespread attention. In this paper, the development status and trends of nasal drug delivery and nose-to-brain delivery technology are deeply analyzed through multiple dimensions: literature research, questionnaire surveys, and patent analysis. First, FDA-approved nasal formulations for nose-to-brain delivery were combed. Second, we collected a large amount of relevant information about nasal drug delivery through a questionnaire survey of 165 pharmaceutical industry practitioners in 28 provinces and 161 different organizations in China. Third, and most importantly, we conducted a patent analysis of approximately 700+ patents related to nose-to-brain delivery, both domestically and internationally. This analysis was conducted in terms of patent application trends, technology life cycle, technology composition, and technology evolution. The LDA topic model was employed to identify technological topics in each time window (1990-2023), and the five key major evolution paths were extracted. The research results in this paper will provide useful references for relevant researchers and enterprises in the pharmaceutical industry, promoting the further development and application of nasal drug delivery and nose-to-brain delivery technology.
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The non-coding RNA LINC00894 modulates tumor proliferation and drug resistance. However, its role in brain is still unclear. Using RNA-pull down combined with mass spectrometry and RNA binding protein immunoprecipitation, EIF5 was identified to interact with LINC00894. Furthermore, LINC00894 knockdown decreased EIF5 protein expression, whereas LINC00894 overexpression increased EIF5 protein expression in SH-SY5Y and BE(2)-M17 (M17) neuroblastoma cells. Additionally, LINC00894 affected the ubiquitination modification of EIF5. Adeno-associated virus (AAV) mediated LINC00894 overexpression in the brain inhibited the expression of activated Caspase-3, while increased EIF5 protein level in rats and mice subjected to transient middle cerebral artery occlusion reperfusion (MCAO/R). Meanwhile, LINC00894 knockdown increased the number of apoptotic cells and expression of activated Caspase-3, and its overexpression decreased them in the oxygen-glucose deprivation and reoxygenation (OGD/R) in vitro models. Further, LINC00894 was revealed to regulated ATF4 protein expression in condition of OGD/R and normoxia. LINC00894 knockdown also decreased the expression of glutamate-cysteine ligase catalytic subunit (GCLC) and ATF4, downregulated glutathione (GSH), and the ratio of GSH to oxidized GSH (GSH: GSSG) in vitro. By using RNA-seq combined with qRT-PCR and immunoblot, we identified that fibroblast growth factor 21 (FGF21) and aconitate decarboxylase 1 (ACOD1), as the ATF4 target genes were regulated by LINC00894 in the MCAO/R model. Finally, we revealed that ATF4 transcriptionally regulated FGF21 and ACOD1 expression; ectopic overexpression of FGF21 or ACOD1 in LINC00894 knockdown cells decreased activated Caspase-3 expression in the OGD/R model. Our results demonstrated that LINC00894 regulated cerebral ischemia injury by stabilizing EIF5 and facilitating EIF5-ATF4-dependent induction of FGF21 and ACOD1.
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Pot experiments were conducted using Chinese fir (Cunninghamia lanceolata (Lamb.) Hook.) and Phoebe bournei (Hemsl.) Yang) to investigate whether soil microplastics adversely affect the nurturing and renewal of plantations. Microplastics composed of polyethylene and polypropylene with a size of 48 µm were used. The treatments included a control group (without microplastics) and groups treated with microplastic concentrations of 1% and 2% (w/w). The effects of microplastics on the growth, photosynthetic pigments in leaves, antioxidant systems, and osmotic regulation substances of the seedlings were analysed by measuring the seedling height, ground-line diameter growth, chlorophyll (chlorophyll a, chlorophyll b, and total chlorophyll) contents, antioxidant enzyme (superoxide dismutase, peroxidase, catalase) activities, and malondialdehyde, soluble sugar, and soluble protein levels. The results indicated that treatment with 1% polyethylene microplastics increased the chlorophyll a, total chlorophyll, and soluble protein contents in the leaves of both types of seedlings while inhibiting superoxide dismutase and peroxidase activities in P. bournei seedlings. Treatment with 2% polyethylene or polypropylene microplastics suppressed the chlorophyll a, chlorophyll b, and total chlorophyll contents; superoxide dismutase, peroxidase, and catalase activities; and soluble sugar and soluble protein levels in the leaves of both types of seedlings, resulting in reduced growth in terms of height and ground-line diameter. The physiological effects of polyethylene microplastics were more evident than those of polypropylene at the same concentration. The results demonstrated that microplastics can affect photosynthesis, the antioxidant system, and osmotic regulation in Chinese fir and P. bournei seedlings, thereby inhibiting their normal growth and development. Exposure to 1% (w/w) microplastics triggered stress responses in seedlings, whereas 2% (w/w) microplastics impeded seedling growth.
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Cerebral ischemia/reperfusion injury (CIRI) is a common feature of ischemic stroke leading to a poor prognosis. Effective treatments targeting I/R injury are still insufficient. The study aimed to investigate the mechanisms, by which glycyrrhizic acid (18ß-GA) in ameliorates CIRI. Our results showed that 18ß-GA significantly decreased the infarct volume, neurological deficit scores, and pathological changes in the brain tissue of rats after middle cerebral artery occlusion. Western blotting showed that 18ß-GA inhibited the expression levels of phosphorylated JAK2 and phosphorylated STAT3. Meanwhile, 18ß-GA increased LC3-II protein levels in a reperfusion duration-dependent manner, which was accompanied by an increase in the Bcl-2/Bax ratio. Inhibition of 18ß-GA-induced autophagy by 3-methyladenine (3-MA) enhanced apoptotic cell death. In addition, 18ß-GA inhibited the JAK2/STAT3 pathway, which was largely activated in response to oxygen-glucose deprivation/reoxygenation. However, the JAK2/STAT3 activator colivelin TFA abolished the inhibitory effect of 18ß-GA, suppressed autophagy, and significantly decreased the Bcl-2/Bax ratio. Taken together, these findings suggested that 18ß-GA pretreatment ameliorated CIRI partly by triggering a protective autophagy via the JAK2/STAT3 pathway. Therefore might be a potential drug candidate for treating ischemic stroke.
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Autofagia , Infarto de la Arteria Cerebral Media , Janus Quinasa 2 , Fármacos Neuroprotectores , Ratas Sprague-Dawley , Daño por Reperfusión , Factor de Transcripción STAT3 , Transducción de Señal , Animales , Janus Quinasa 2/metabolismo , Janus Quinasa 2/antagonistas & inhibidores , Factor de Transcripción STAT3/metabolismo , Daño por Reperfusión/metabolismo , Daño por Reperfusión/tratamiento farmacológico , Autofagia/efectos de los fármacos , Autofagia/fisiología , Masculino , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Fármacos Neuroprotectores/farmacología , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/metabolismo , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Isquemia Encefálica/patología , Ácido Glicirrínico/farmacología , Ratas , Apoptosis/efectos de los fármacos , Encéfalo/efectos de los fármacos , Encéfalo/metabolismo , Encéfalo/patologíaRESUMEN
To optimize the imbalance between the interfacial bonding and porosity properties of carbon paper (CP) caused by phenol formaldehyde resin (PF) impregnation, and therefore improve the performance of proton exchange membrane fuel cells (PEMFCs), a new approach through cellulose nanofibers grafted with methyl methacrylate (CNFM) as a modified reinforcement and pore-forming agent for PF is investigated. Through suppressing the methylene backbone fracture of CNFM-modified PF during its thermal depolymerization, the interfacial bonding between PF matrix carbon and carbon fibers is enhanced. Compared with unmodified CP, the in-plane resistivity of CNFM-modified CP is reduced by 35.78 %, while the connected porosity increases to 82.26 %, and more homogeneous pore size distribution (PSD) in the range of 20-40 µm is obtained for CNFM-modified CP. Besides, the tensile strength, flexural strength, and air permeability of CNFM-modified CP increase by 72.78 %, 298.4 %, and 103.97 %, respectively. In addition, CNFM-modified CP achieves the peak power density of PEMFCs to 701.81 mW·cm-2, exhibiting 10.98 % improvement compared with commercial CP (632.39 mW·cm-2), evidently achieving an integral promotion of CP and comprehensive performance.
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Liver fibrosis is a significant health burden, marked by the consistent deposition of collagen. Unfortunately, the currently available treatment approaches for this condition are far from optimal. Lysyl oxidase-like protein 2 (LOXL2) secreted by hepatic stellate cells (HSCs) is a crucial player in the cross-linking of matrix collagen and is a significant target for treating liver fibrosis. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) have been proposed as a potential treatment option for chronic liver disorders. Previous studies have found that MSC-sEV can be used for microRNA delivery into target cells or tissues. It is currently unclear whether microRNA-4465 (miR-4465) can target LOXL2 and inhibit HSC activation. Additionally, it is uncertain whether MSC-sEV can be utilized as a gene therapy vector to carry miR-4465 and effectively inhibit the progression of liver fibrosis. This study explored the effect of miR-4465-modified MSC-sEV (MSC-sEVmiR-4465) on LOXL2 expression and liver fibrosis development. The results showed that miR-4465 can bind specifically to the promoter of the LOXL2 gene in HSC. Moreover, MSC-sEVmiR-4465 inhibited HSC activation and collagen expression by downregulating LOXL2 expression in vitro. MSC-sEVmiR-4465 injection could reduce HSC activation and collagen deposition in the CCl4-induced mouse model. MSC-sEVmiR-4465 mediating via LOXL2 also hindered the migration and invasion of HepG2 cells. In conclusion, we found that MSC-sEV can deliver miR-4465 into HSC to alleviate liver fibrosis via altering LOXL2, which might provide a promising therapeutic strategy for liver diseases.
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Aminoácido Oxidorreductasas , Vesículas Extracelulares , Células Estrelladas Hepáticas , Cirrosis Hepática , Células Madre Mesenquimatosas , MicroARNs , Animales , Humanos , Masculino , Ratones , Aminoácido Oxidorreductasas/genética , Aminoácido Oxidorreductasas/metabolismo , Vesículas Extracelulares/metabolismo , Células Estrelladas Hepáticas/metabolismo , Cirrosis Hepática/terapia , Cirrosis Hepática/metabolismo , Cirrosis Hepática/genética , Células Madre Mesenquimatosas/metabolismo , Ratones Endogámicos C57BL , MicroARNs/genética , MicroARNs/metabolismoRESUMEN
In recent years, flexible and stretchable strain sensors have emerged as a prominent area of research, primarily due to their remarkable stretchability and extremely low strain detection threshold. Nevertheless, the advancement of sensors is currently constrained by issues such as complexity, high costs, and limited durability. To tackle the aforementioned issues, this study introduces a lepidophyte-inspired flexible, stretchable strain sensor (LIFSSS). The stretchable bioelectronics composites were composed of multiwalled carbon nanotubes, graphene, neodymium iron boron, and polydimethylsiloxane. Unique biolepidophyted microstructures and magnetic conductive nanocomposites interact with each other through synergistic interactions, resulting in the effective detection of tensile strain and magnetic excitation. The LIFSSS exhibits a 170% tensile range, a linearity of 0.99 in 50-170% strain (0.96 for full-scale range), and a fine durability of 7000 cycles at 110% tensile range. The sensor accurately detects variations in linear tensile force, human movement, and microexpressions. Moreover, LIFSSS demonstrates enhanced efficacy in sign language recognition for individuals with hearing impairments and magnetic grasping for robotic manipulators. Hence, the LIFSSS proposed in this study shows potential applications in various fields, including bioelectronics, electronic skin, and physiological activity monitoring.
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Fresnel incoherent correlation holography (FINCH) can achieve high-precision and non-scanning 3D imaging. However, as a holographic imaging technology, the huge bandwidth requirements and the amount of holographic data transmitted have always been one of the important factors limiting its application. In addition, the hardware cost of pixel array-based CCD or CMOS imaging is very high under high resolution or specific wavelength conditions. Accordingly, a single-pixel Fresnel incoherent correlation holography (SP-FINCH) compressed imaging method is proposed, which replaces pixel array detector with single-pixel detector and designs a Trumpet network to achieve low-cost and high-resolution imaging. Firstly, a modified FINCH imaging system is constructed and data acquisition is carried out using a single-pixel detector. Secondly, a Trumpet network is constructed to directly map the relationship between one-dimensional sampled data and two-dimensional image in an end-to-end manner. Moreover, by comparing the reconstructed images using neural network with that using commonly used single-pixel reconstruction methods, the results indicate that the proposed SP-FINCH compressed imaging method can significantly improve the quality of image reconstruction at lower sampling rate and achieve imaging without phase-shifting operation. The proposed method has been shown to be feasible and advantageous through numerical simulations and optical experiment results.
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BACKGROUND: Glioblastoma are highly malignant type of primary brain tumors. Treatment for glioblastoma multiforme (GBM) generally involves surgery combined with chemotherapy and radiotherapy. However, the development of tumoral chemo- and radioresistance induces complexities in clinical practice. Multiple signaling pathways are known to be involved in radiation-induced cell survival. However, the role of alpha-thalassemia X-linked mutant retardation syndrome (ATRX), a chromatin remodeling protein, in GBM radioresistance remains unclear. METHODS: In the present study, the ATRX mutation rate in patients with glioma was obtained from The Cancer Genome Atlas, while its expression analyzed using bioinformatics. Datasets were also obtained from the Gene Expression Omnibus, and ATRX expression levels following irradiation of GBM were determined. The effects of ATRX on radiosensitivity were investigated using a knockdown assays. RESULTS: The present study demonstrated that the ATRX mutation rate in patients with GBM was significantly lower than that in patients with low-grade glioma, and that patients harboring an ATRX mutation exhibited a prolonged survival, compared with to those harboring the wild-type gene. Single-cell RNA sequencing demonstrated that ATRX counts increased 2 days after irradiation, with ATRX expression levels also increasing in U-251MG radioresistant cells. Moreover, the results of in vitro irradiation assays revealed that ATRX expression was increased in U-251MG cells, while ATRX knockdown was associated with increased levels of radiosensitivity. CONCLUSIONS: High ATRX expression levels in primary GBM may contribute to high levels of radioresistance. Thus ATRX is a potential target for overcoming the radioresistance in GBM.
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Glutamine (Gln), known as the most abundant free amino acid, is widely spread in human body. In this study, we demonstrated the protective effects of glutamine against mouse abdominal aortic aneurysm (AAA) induced by both angiotensin II (AngII) and calcium phosphate (Ca3(PO4)2) in vivo, which was characterized with lower incidence of mouse AAA. Moreover, histomorphological staining visually presented more intact elastic fiber and less collagen deposition in abdominal aortas of mice treated by glutamine. Further, we found glutamine inhibited the excessive production of reactive oxide species (ROS), activity of matrix metalloproteinase (MMP), M1 macrophage activation, and apoptosis of vascular smooth muscle cells (VSMCs) in suprarenal abdominal aortas of mice, what's more, the high expressions of MMP-2 protein, MMP-9 protein, pro-apoptotic proteins, and IL-6 as well as TNF-α in protein and mRNA levels in cells treated by AngII were down-regulated by glutamine. Collectively, these results revealed that glutamine protected against mouse AAA through inhibiting apoptosis of VSMCs, M1 macrophage activation, oxidative stress, and extracellular matrix degradation.