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The maintenance and expansion of human neural stem cells (hNSCs) in 3D tissue scaffolds is a promising strategy in producing cost-effective hNSCs with quality and quantity applicable for clinical applications. A few biopolymers have been extensively used to fabricate 3D scaffolds, including hyaluronic acid, collagen, alginate, and chitosan, due to their bioactive nature and availability. However, these polymers are usually applied in combination with other biomolecules, leading to their responses difficult to ascribe to. Here, scaffolds made of chitosan, alginate, hyaluronic acid, or collagen, are explored for hNSC expansion under xeno-free and chemically defined conditions and compared for hNSC multipotency maintenance. This study shows that the scaffolds made of pure chitosan support the highest adhesion and growth of hNSCs, yielding the most viable cells with NSC marker protein expression. In contrast, the presence of alginate, hyaluronic acid, or collagen induces differentiation toward immature neurons and astrocytes even in the maintenance medium and absence of differentiation factors. The cells in pure chitosan scaffolds preserve the level of transmembrane protein profile similar to that of standard culture. These findings point to the potential of using pure chitosan scaffolds as a base scaffolding material for hNSC expansion in 3D.
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Stimulator of Interferon Genes (STING) is essential for the inflammatory response to cytosolic DNA. Despite that aberrant activation of STING is linked to an increasing number of inflammatory diseases, the development of inhibitors has been challenging, with no compounds in the pipeline beyond the preclinical stage. We previously identified endogenous nitrated fatty acids as novel reversible STING inhibitors. With the aim of improving the specificity and efficacy of these compounds, we developed and tested a library of nitroalkene-based compounds for in vitro and in vivo STING inhibition. The structure-activity relationship study revealed a robustly improved electrophilicity and reduced degrees of freedom of nitroalkenes by conjugation with an aromatic moiety. The lead compounds CP-36 and CP-45, featuring a ß-nitrostyrene moiety, potently inhibited STING activity in vitro and relieved STING-dependent inflammation in vivo. This validates the potential for nitroalkene compounds as drug candidates for STING modulation to treat STING-driven inflammatory diseases, providing new robust leads for preclinical development.
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Alcenos , Inflamação , Proteínas de Membrana , Nitrocompostos , Proteínas de Membrana/antagonistas & inibidores , Proteínas de Membrana/metabolismo , Animais , Inflamação/tratamento farmacológico , Humanos , Camundongos , Alcenos/química , Alcenos/farmacologia , Nitrocompostos/química , Nitrocompostos/farmacologia , Relação Estrutura-AtividadeRESUMO
The Asian citrus psyllid (ACP) Diaphorina citri Kuwayama is the leading vector of Candidatus Liberibacter asiaticus (CLas), the causative agent of citrus Huanglongbing (HLB) disease. The distribution and dynamics of CLas within ACP are critical to understanding how the transmission, spread and infection of CLas occurs within its host vector in nature. In this study, the distribution and titer changes of CLas in various tissues of ACP 5th instar nymphs and adults were examined by fluorescence in situ hybridization (FISH) and real-time quantitative PCR (qPCR) techniques. Results demonstrated that 100% of ACP 5th instar nymphs and adults were infected with CLas following feeding on infected plants, and that CLas had widespread distribution in most of the tissues of ACP. The titers of CLas within the midgut, salivary glands and hemolymph tissues were the highest in both 5th instar nymphs and adults. When compared with adults, the titers of CLas in these three tissues of 5th instar nymphs were significantly higher, while in the mycetome, ovary and testes they were significantly lower than those of adults. FISH visualization further confirmed these findings. Dynamic analysis of CLas demonstrated that it was present across all the developmental ages of ACP adults. There was a discernible upward trend in the presence of CLas with advancing age in most tissues of ACP adults, including the midgut, hemolymph, salivary glands, foot, head, cuticula and muscle. Our findings have significant implications for the comprehensive understanding of the transmission, dissemination and infestation of CLas, which is of much importance for developing novel strategies to halt the spread of CLas, and therefore contribute to the efficient prevention and control of HLB.
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Citrus , Hemípteros , Hibridização in Situ Fluorescente , Insetos Vetores , Ninfa , Doenças das Plantas , Animais , Hemípteros/microbiologia , Insetos Vetores/microbiologia , Doenças das Plantas/microbiologia , Ninfa/microbiologia , Citrus/microbiologia , Rhizobiaceae/genética , Rhizobiaceae/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Glândulas Salivares/microbiologia , Hemolinfa/microbiologiaRESUMO
BACKGROUND: As a significant bridge between perforasomes, choke vessels are the key structure of blood supply expansion, also a prerequisite for preventing distal ischemic necrosis of the multiterritory perforator flap, where the remodeling of choke vessels after flap elevation plays an essential role. This systematic review highlights the underlying mechanisms and clinical ways to promote remodeling of choke vessels, as well as experimental observation approaches to further guide researchers. METHODS: A systematic review was conducted from 1975 to 2023 through PubMed, EMBASE, Web of Science, and Cochrane database with the key words "choke vessels" and "perforator flap" to investigate the mechanisms and ways to promote remodeling of choke vessels as well as observation approaches. The inclusion criteria and exclusion criteria were set to screen the literature. RESULTS: A total of 94 literatures were obtained through database retrieval. After removing the duplicate literature, reading the title and abstract, and reviewing the full text finally, 33 articles were included in the final study. CONCLUSIONS: The underlying remodeling of choke vessels may be related to fluid shear stress, hypoxia, and inflammation. The clinical ways to promote remodeling of choke vessels include surgical delay, arterial supercharge, venous superdrainage, drugs, and stem cells. Various experimental methods of observing microvascular morphology allow for a comprehensive research of choke vessels.
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Retalho Perfurante , Remodelação Vascular , Humanos , Remodelação Vascular/fisiologia , Retalho Perfurante/irrigação sanguínea , Retalho Perfurante/transplante , Procedimentos de Cirurgia Plástica/métodosRESUMO
In the existing work of tensor product (TP) model transformation, the TP model transformation-based work on the quadrotor's control system design is scarce, the direct TP model transformation control strategy that applied to the quadrotor fails due to the calculation complexity, infeasibility of the huge amount of linear matrix inequalities, and the complexity of solving the linear matrix inequalities. To solve this problem, a partial TP model transformation-based double loop fuzzy controller has been studied in this work, the double-loop hybrid control scheme combines the fully actuated control method and the TP model transformation, while the fully actuated control method is used to the position subsystem control loop, and the TP model transformation based fuzzy controller is applied to the attitude control of the quadrotor. Moreover, for comparison purpose, a varying-input method based on TP model transformation is extended to the quadrotor's system control. The double-loop hybrid control scheme could also be extended with other TP model transformation based tensor sampling methods, such as, uniform sampling method and varying-input method. At last, the proposed algorithms are evaluated and compared on Parrot Mambo Minidrone, MFP450 and CUAV V5+ based hexarotor.
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BACKGROUND: With the rapid escalation of global urbanization, the role of blue-green spaces in urban ecology, public health, and planning has become increasingly prominent. Although their contributions to ecological preservation, public health, and urban design are widely acknowledged, research into public engagement and willingness to participate in the management and planning of these spaces is still in its early stages. OBJECTIVE: This study aims to identify key factors influencing public willingness to participate in blue-green space management, focusing specifically on people's perceptions of blue-green spaces (including perceived quality and accessibility), their usage behaviors (i.e., frequency of usage of blue-green spaces), and their self-assessed physical and mental health. METHODS: We interviewed local residents through random sampling to obtain sample data, and used a representative sample (n = 815, 510 women; 305 men, age 18-85 years, lived in Chengdu for an extensive time) of residents living in Chengdu City, China. Employing a quantitative approach, we examined the relationships between factors such as gender, regular occupation, income, behavior, and health status in relation to the willingness to participate. Additionally, we explored how perceptions and behaviors impacted health statuses and, consequently, inclinations to participate. RESULTS: The findings indicate that individuals with steady occupations and higher incomes are more inclined to engage in the management and planning of blue-green spaces. Notably, men exhibited a greater tendency to participate than women. Furthermore, access to blue-green spaces emerged as a crucial mechanism for addressing health disparities, offering significant implications for urban planning and public health. CONCLUSION: Successful blue-green space planning and understanding of willingness to participate necessitates the holistic consideration of people's perceptions of blue-green spaces, their usage behaviour and their self-rate health. For a tangible impact on health equity and global urban development, it's essential to prioritize blue-green spaces in planning, especially in lower-income regions. This not only promotes environmental perception but can also be a strategic approach to address health disparities. Our findings offer vital insights for tailoring international urban planning and management practices towards these goals.
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Saúde Pública , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Adolescente , China , Adulto Jovem , Idoso de 80 Anos ou mais , Urbanização , Cidades , Participação da Comunidade , Planejamento de CidadesRESUMO
Animal experiments are important in trauma-related studies because they simulate in vivo effects. Rodents are a good choice for preparing trauma models; however, contractile healing in rodents results in a healing pattern that differs considerably from that in humans. Therefore, this study developed a new rodent model that avoids contractile healing of the skin around the wound using an anticontraction ring, and the skin in the wound's center remains intact and acts as a source for epithelialized diffusion healing. Cell proliferation, migration, revascularization, and collagen secretion did not differ between the novel and conventional full-skin defect trauma models. However, the healing rate at various stages significantly differed between the 2 groups owing to differences in the healing patterns. And without effective treatment, the experimental group cannot heal. The stabilities of the novel and conventional methods were good regardless of operator or batch. In summary, this new animal trauma model provides a stable experimental environment similar to that in humans, which may promote trauma-related research.
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Modelos Animais de Doenças , Cicatrização , Animais , Cicatrização/fisiologia , Ratos , Reepitelização , Masculino , Ratos Sprague-Dawley , Proliferação de Células , Pele/lesõesRESUMO
OBJECTIVE: To compare the serum levels of brain-derived neurotrophic factor (BDNF) in type 2 diabetes mellitus (T2DM) patients with healthy controls (HC) and evaluate the BDNF levels in T2DM patients with/without cognitive impairment. METHODS: PubMed, EMBASE, and the Cochrane Library databases were searched for the published English literature on BDNF in T2DM patients from inception to December 2022. The BDNF data in the T2DM and HC groups were extracted, and the study quality was evaluated using the Agency for Healthcare Research and Quality. A meta-analysis of the pooled data was conducted using Review Manager 5.3 and Stata 12.0 software. RESULTS: A total of 18 English articles fulfilled with inclusion criteria. The standard mean difference of the serum BDNF level was significantly lower in T2DM than that in the HC group (SMD: -2.04, z = 11.19, P <0.001). Besides, T2DM cognitive impairment group had a slightly lower serum BDNF level compared to the non-cognitive impairment group (SMD: -2.59, z = 1.87, P = 0.06). CONCLUSION: BDNF might be involved in the neuropathophysiology of cerebral damage in T2DM, especially cognitive impairment in T2DM.
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Fator Neurotrófico Derivado do Encéfalo , Disfunção Cognitiva , Diabetes Mellitus Tipo 2 , Fator Neurotrófico Derivado do Encéfalo/sangue , Humanos , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Disfunção Cognitiva/sangue , Estudos de Casos e ControlesRESUMO
This paper presents a novel and efficient method for certifying primary organs involved in secondary metabolite synthesis. As the most important secondary metabolite in Parispolyphylla var. yunnanensis (Franch.) Hand. -Mzt. (PPY), Paris saponin (PS) has a variety of pharmacological activities and PPY is in increasing demand. This study established leaf, rhizome, and stem-vascular-bundle 13C6-Glucose feeding and non-feeding four treatments to precisely certify the primary organs involved in Paris saponins VII (PS VII) synthesis. By combining liquid chromatography-mass spectrometry (LC-MS), the 13C/12C ratios of leaf, rhizome, stem, and root in different treatments were quickly and accurately calculated, and four types of PS isotopic ion peak(M-) ratios were found: (M+1) -/M-, (M+2) -/M-, (M+3) -/M- and (M+4) -/M-. The results showed that the ratio of 13C/12C in the rhizomes of the stem-vascular-bundle and rhizome feeding treatments was significantly higher than that in the non-feeding treatment. Compared to the non-feeding treatment, the ratio of PS VII molecules (M+2) -/M- in the leaves increased significantly under leaf and stem-vascular-bundle feeding treatments. Simultaneously, compared to the non-feeding treatment, the ratio of PS VII molecules (M+2) -/M- in the leaves under rhizome treatment showed no significant difference. Furthermore, the ratio of PS VII molecules (M+2) -/M- in the stem, root, and rhizome showed no differences among the four treatments. Compared to the non-feeding treatment, the ratio of the Paris saponin II (PS II) molecule (M+2) -/M- in leaves under leaf feeding treatment showed no significant difference, and the (M+3) -/M- ratio of PS II molecules in leaves under leaf feeding treatment were lower. The data confirmed that the primary organ for the synthesizing of PS VII is the leaves. It lays the foundation for future identification of the primary organs and pathways involved in the synthesis of secondary metabolites in medicinal plants.
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Espectrometria de Massa com Cromatografia Líquida , Espectrometria de Massas em Tandem , Espectrometria de Massas em Tandem/métodos , Cromatografia Líquida , Folhas de PlantaAssuntos
Endosperma , Oryza , Tiamina , Oryza/metabolismo , Oryza/genética , Endosperma/metabolismo , Tiamina/metabolismoRESUMO
Rheumatoid arthritis (RA) is a systemic autoimmune disease characterized by chronic inflammation of the joints and bone destruction. Because of systemic administration and poor targeting, traditional anti-rheumatic drugs have unsatisfactory treatment efficacy and strong side effects, including myelosuppression, liver or kidney function damage, and malignant tumors. Consequently, mesenchymal stem cells (MSCs)-involved therapy is proposed for RA therapy as a benefit of their immunosuppressive and tissue-repairing effects. This review summarizes the progress of MSCs-involved RA therapy through suppressing inflammation and promoting tissue regeneration and predicts their potential clinical application.
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Artrite Reumatoide , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Artrite Reumatoide/terapia , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , AnimaisRESUMO
This editorial discusses the article written by Zheng et al that was published in the latest edition of the World Journal of Gastrointestinal Surgery. Our primary focus is on the causes, location, diagnosis, histological classification, and therapy of ectopic pancreas. Ectopic pancreas refers to the presence of pancreatic tissue that is situated in a location outside its usual anatomical placement, and is not connected to the normal pancreas in terms of blood supply or anatomical structure. Currently, the embryological origin of ectopic pancreas remains uncertain. The most prevalent form of ectopic pancreatic is gastric ectopic pancreas. Endoscopic ultrasonography examination can visualize the morphological characteristics of the ectopic pancreatic lesion and pinpoint its anatomical location. The histological categorization of ectopic pancreas evolves. Endoscopic treatment has been widely advocated in ectopic pancreas.
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OBJECTIVE: The efficacy of sirolimus in treating severe or refractory systemic lupus erythematosus (SLE) has been confirmed by small-scale clinical trials. However, few studies focused on mild or moderate SLE. Therefore, in this study we elucidated clinical efficacy of add-on sirolimus in patients with mild or moderate SLE. METHODS: Data of 17 consecutive patients with SLE were retrospectively collected. SLE Disease Activity Index-2000 (SLEDAI-2K), clinical manifestation, laboratory data and peripheral T lymphocyte subsets with cytokines were collected before and 6 months after sirolimus add-on treatment. T cell subsets were detected by flow cytometry and cytokines were determined by multiplex bead-based flow fluorescent immunoassay simultaneously. Twenty healthy controls matched with age and sex were also included in our study. RESULTS: (1) The numbers of peripheral blood lymphocytes, T cells, T helper (Th) cells, regulatory T (Treg) cells, Th1 cells, Th2 cells and Treg/Th17 ratios in patients with SLE were significantly lower, while the numbers of Th17 cells were evidently higher than those of healthy control (p<0.05). (2) After 6 months of sirolimus add-on treatment, urinary protein, pancytopenia, immunological indicators and SLEDAI-2K in patients with SLE were distinctively improved compared with those before sirolimus treatment (p<0.05). (3) The numbers of peripheral blood lymphocytes, T cells, Th cells, Treg cells, Th2 cells and the ratios of Treg/Th17 in patients with SLE after treatment were clearly higher than those before (p<0.05). (4) The levels of plasma interleukin (IL)-5, IL-6 and IL-10 in patients with SLE decreased notably, conversely the IL-4 levels increased remarkably compared with pretreatment (p<0.05). CONCLUSIONS: (1) Patients with SLE presented imbalanced T cell subsets, especially the decreased ratio of Treg/Th17. (2) Sirolimus add-on treatment ameliorated clinical involvement, serological abnormalities and disease activity without adverse reactions in patients with SLE. (3) The multi-target therapy facilitates the enhanced numbers of Treg cells, Treg/Th17 imbalance and anti-inflammatory cytokines, simultaneously, reducing inflammatory cytokines.
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Lúpus Eritematoso Sistêmico , Sirolimo , Humanos , Sirolimo/efeitos adversos , Estudos Retrospectivos , Subpopulações de Linfócitos T/metabolismo , CitocinasRESUMO
Anti-HER2 (human epidermal growth factor receptor 2) therapies significantly increase the overall survival of patients with HER2-positive breast cancer. Unfortunately, a large fraction of patients may develop primary or acquired resistance. Further, a multidrug combination used to prevent this in the clinic places a significant burden on patients. To address this issue, this work develops a nanotherapeutic platform that incorporates bimetallic gold-silver hollow nanoshells (AuAg HNSs) with exceptional near-infrared (NIR) absorption capability, the small-molecule tyrosine kinase inhibitor pyrotinib (PYR), and Herceptin (HCT). This platform realizes targeted delivery of multiple therapeutic effects, including chemo-and photothermal activities, oxidative stress, and immune response. In vitro assays reveal that the HCT-modified nanoparticles exhibit specific recognition ability and effective internalization by cells. The released PYR inhibit cell proliferation by downregulating HER2 and its associated pathways. NIR laser application induces a photothermal effect and tumor cell apoptosis, whereas an intracellular reactive oxygen species burst amplifies oxidative stress and triggers cancer cell ferroptosis. Importantly, this multimodal therapy also promotes the upregulation of genes related to TNF and NF-κB signaling pathways, enhancing immune activation and immunogenic cell death. In vivo studies confirm a significant reduction in tumor volume after treatment, substantiating the potential effectiveness of these nanocarriers.
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Neoplasias da Mama , Ouro , Hipertermia Induzida , Receptor ErbB-2 , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/terapia , Neoplasias da Mama/metabolismo , Neoplasias da Mama/genética , Feminino , Humanos , Camundongos , Animais , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Hipertermia Induzida/métodos , Ouro/química , Trastuzumab/farmacologia , Trastuzumab/uso terapêutico , Prata/química , Linhagem Celular Tumoral , Modelos Animais de Doenças , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Terapia Combinada/métodos , Nanopartículas Metálicas/uso terapêutico , Nanopartículas Metálicas/química , Proliferação de Células/efeitos dos fármacosRESUMO
BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) has a fibrotic stroma that has both tumor-promoting and tumor-restraining properties. Different types of cancer-associated fibroblasts (CAFs) have been described. Here, we investigated whether CAFs within the same subtype exhibit heterogeneous functions. METHODS: We evaluated the gene and protein expression differences in two myofibroblastic CAF (myCAF) lines using single-cell and bulk RNA-sequencing. We utilized proliferation and migration assays to determine the effect of different CAF lines on a tumor cell line. RESULTS: We found that myCAF lines express an activated stroma subtype gene signature, which is associated with a shorter survival in patients. Although both myCAF lines expressed α-smooth muscle actin (α-SMA), platelet-derived growth factor-α (PDGFR-α), fibroblast-activated protein (FAP), and vimentin, we observed heterogeneity between the two lines. Similarly, despite being consistent with myCAF gene expression overall, heterogeneity within specific genes was observed. We found that these differences extended to the functional level where the two myCAF lines had different effects on the same tumor cell line. The myCAF216 line, which had slightly increased inflammatory CAF-like gene expression and higher protein expression of α-SMA, PDGFR-α, and FAP was found to restrain migration of tumor cells. CONCLUSIONS: We found that two myCAF lines with globally similar expression characteristics had different effects on the same tumor cell line, one promoting and the other restraining migration. Our study highlights that there may be unappreciated heterogeneity within CAF subtypes. Further investigation and attention to specific genes or proteins that may drive this heterogeneity will be important.
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Fibroblastos Associados a Câncer , Carcinoma Ductal Pancreático , Neoplasias Pancreáticas , Humanos , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Neoplasias Pancreáticas/patologia , Carcinoma Ductal Pancreático/patologia , Fibroblastos/metabolismo , Linhagem Celular Tumoral , Microambiente TumoralRESUMO
Fluid hydrogel is proper to be incorporated with rigid porous prosthesis interface, acting as a soft carrier to support cells and therapeutic factors, to enhance osseointegration. In the previous study, we innovatively utilized self-healing supramolecular hydrogel as 3D cell culture platform to incorporate with 3D printed porous titanium alloy scaffold, constructing a novel bioactive interface. However, the concrete relationship and mechanism of hydrogel stiffness influencing cellular behaviors of bone marrow mesenchymal stem cells (BMSCs) within the interface are still inconclusive. Herein, we synthesized a series of supramolecular hydrogels with variable stiffness as extracellular matrix (ECM) to enhance the osseointegration of 3D printed prosthesis interface. BMSCs exposed to stiff hydrogel received massive environmental mechanical stimulations, subsequently transducing biophysical cues into biochemical signal through mechanotransduction process. The mRNA-sequencing analysis revealed that the activated FAK-MAPK pathway played significant roles in promoting osteogenic differentiation, thus contributing to a strong osseointegration. Our work preliminarily demonstrated the relationship of ECM stiffness and osteogenic differentiation trend of BMSCs, and optimized stiffness of hydrogel within a certain range benefitting for osteogenic differentiation and prosthesis interface osseointegration, providing a valuable insight into the development of orthopaedic implants equipped with osteogenic mechanotransduction ability.
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Hidrogéis , Células-Tronco Mesenquimais , Hidrogéis/química , Osteogênese , Osseointegração , Mecanotransdução Celular , Próteses e Implantes , Diferenciação CelularRESUMO
Oxyfluoride transparent glass-ceramics (GC) are widely used as the matrix for rare-earth (RE) ions due to their unique properties such as low phonon energy, high transmittance, and high solubility for RE ions. Tb3+ doped oxyfluoride glasses exhibit a large absorption cross section for ultraviolet (UV) excitation, high stability, high photoluminescence quantum efficiency, and sensitive spectral conversion characteristics, making them promising candidate materials for use as the spectral converter in UV photodetectors. Herein, a Tb3+ doped oxyfluoride GC is developed by using the melt-quenching method, and the microstructure and optical properties of the GC sample are carefully investigated. By combining with a Si-based photo-resistor,a solar-blind UV detector is fabricated, which exhibits a significant photoelectric response with a broad detection range from 188 to 400 nm. The results indicate that the designed UV photodetector is of great significance for the development of solar-blind UV detectors.
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The exponential stabilization of stochastic neural networks in mean square sense with saturated impulsive input is investigated in this paper. Firstly, the saturated term is handled by polyhedral representation method. When the impulsive sequence is determined by average impulsive interval, impulsive density and mode-dependent impulsive density, the sufficient conditions for stability are proposed, respectively. Then, the ellipsoid and the polyhedron are used to estimate the attractive domain, respectively. By transforming the estimation of the attractive domain into a convex optimization problem, a relatively optimum domain of attraction is obtained. Finally, a three-dimensional continuous time Hopfield neural network example is provided to illustrate the effectiveness and rationality of our proposed theoretical results.
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Algoritmos , Redes Neurais de Computação , Processos Estocásticos , Fatores de Tempo , Fenômenos FísicosRESUMO
Nitrated fatty acids are important anti-inflammatory and protective lipids formed in the gastric compartment, with conjugated linoleic acid (rumenic acid, RA, 9Z,11E-18:2) being the primary substrate for lipid nitration. The recently reported identification of nitrated rumelenic acid (NO2-RLA) in human urine has led to hypothesize that rumelenic acid (RLA, 9Z,11E,15Z-18:3) from dairy fat is responsible for the formation of NO2-RLA. To evaluate the source and mechanism of NO2-RLA formation, 15N labeled standards of NO2-RLA were synthesized and characterized. Afterward, milk fat with different RA and RLA levels was administered to mice in the presence of nitrite, and the appearance of nitrated fatty acids in plasma and urine followed. We confirmed the formation of NO2-RLA and defined the main metabolites in plasma, urine, and tissues. In conclusion, RLA obtained from dairy products is the main substrate for forming this novel electrophilic lipid reported to be present in human urine.
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Ácidos Linoleicos Conjugados , Nitratos , Camundongos , Humanos , Animais , Nitratos/química , Nitritos/metabolismo , Dióxido de Nitrogênio , Ácidos Graxos/química , Laticínios , Ácidos LinolênicosRESUMO
Mechanical stimuli regulate the chondrogenic differentiation of mesenchymal stem cells and the homeostasis of chondrocytes, thus affecting implant success in cartilage tissue engineering. The mechanical microenvironment plays fundamental roles in the maturation and maintenance of natural articular cartilage, and the progression of osteoarthritis Hence, cartilage tissue engineering attempts to mimic this environment in vivo to obtain implants that enable a superior regeneration process. However, the specific type of mechanical loading, its optimal regime, and the underlying molecular mechanisms are still under investigation. First, this review delineates the composition and structure of articular cartilage, indicating that the morphology of chondrocytes and components of the extracellular matrix differ from each other to resist forces in three top-to-bottom overlapping zones. Moreover, results from research experiments and clinical trials focusing on the effect of compression, fluid shear stress, hydrostatic pressure, and osmotic pressure are presented and critically evaluated. As a key direction, the latest advances in mechanisms involved in the transduction of external mechanical signals into biological signals are discussed. These mechanical signals are sensed by receptors in the cell membrane, such as primary cilia, integrins, and ion channels, which next activate downstream pathways. Finally, biomaterials with various modifications to mimic the mechanical properties of natural cartilage and the self-designed bioreactors for experiment in vitro are outlined. An improved understanding of biomechanically driven cartilage tissue engineering and the underlying mechanisms is expected to lead to efficient articular cartilage repair for cartilage degeneration and disease.