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PURPOSE: To explore the impact of microRNA 146a (miR-146a) and the underlying mechanisms in profibrotic changes following glaucoma filtering surgery (GFS) in rats and stimulation by transforming growth factor (TGF)-ß1 in rat Tenon's capsule fibroblasts. METHODS: Cultured rat Tenon's capsule fibroblasts were treated with TGF-ß1 and analyzed with microarrays for mRNA profiling to validate miR-146a as the target. The Tenon's capsule fibroblasts were then respectively treated with lentivirus-mediated transfection of miR-146a mimic or inhibitor following TGF-ß1 stimulation in vitro, while GFS was performed in rat eyes with respective intraoperative administration of miR-146a, mitomycin C (MMC), or 5-fluorouracil (5-FU) in vivo. Profibrotic genes expression levels (fibronectin, collagen Iα, NF-KB, IL-1ß, TNF-α, SMAD4, and α-smooth muscle actin) were determined through qPCR, Western blotting, immunofluorescence staining and/or histochemical analysis in vitro and in vivo. SMAD4 targeting siRNA was further used to treat the fibroblasts in combination with miR-146a intervention to confirm its role in underlying mechanisms. RESULTS: Upregulation of miR-146a reduced the proliferation rate and profibrotic changes of rat Tenon's capsule fibroblasts induced by TGF-ß1 in vitro, and mitigated subconjunctival fibrosis to extend filtering blebs survival after GFS in vivo, where miR-146a decreased expression levels of NF-KB-SMAD4-related genes, such as fibronectin, collagen Iα, NF-KB, IL-1ß, TNF-α, SMAD4, and α-smooth muscle actin(α-SMA). Additionally, SMAD4 is a key target gene in the process of miR-146a inhibiting fibrosis. CONCLUSIONS: MiR-146a effectively reduced TGF-ß1-induced fibrosis in rat Tenon's capsule fibroblasts in vitro and in vivo, potentially through the NF-KB-SMAD4 signaling pathway. MiR-146a shows promise as a novel therapeutic target for preventing fibrosis and improving the success rate of GFS.
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Fibroblastos , Fibrosis , Cirugía Filtrante , Glaucoma , MicroARNs , Ratas Sprague-Dawley , Animales , MicroARNs/metabolismo , MicroARNs/genética , Glaucoma/patología , Glaucoma/genética , Cirugía Filtrante/efectos adversos , Fibroblastos/metabolismo , Masculino , Cápsula de Tenon/metabolismo , Cápsula de Tenon/patología , Proliferación Celular/efectos de los fármacos , Factor de Crecimiento Transformador beta1/metabolismo , Ratas , Proteína Smad4/metabolismo , Proteína Smad4/genética , FN-kappa B/metabolismo , Mitomicina/farmacología , Mitomicina/uso terapéutico , Regulación de la Expresión GénicaRESUMEN
As a prototypical member of the IL-17 family, interleukin-17A (IL-17A) has received increasing attentions for its potent proinflammatory role as well as potential to be a key therapeutic target in human autoimmune inflammatory diseases; however, its roles in other pathological scenarios like neuroinflammations are not fully elucidated yet but appear essentially correlating and promising. Glaucoma is the leading cause of irreversible blindness with complicated pathogenesis still to be understood, where neuroinflammation was reported to be critically involved in its both initiation and progression. Whether IL-17A takes part in the pathogenesis of glaucoma through interfering neuroinflammation due to its potent proinflammatory effect is still unknown. In the present study, we investigated the role of IL-17A in the pathological process of glaucoma neuropathy as well as its relationship with the predominant immune inflammation mediator microglia in retina, trying to elucidate the underlying mechanisms from the view of inflammation modulation. In our study, RNA sequencing was performed for the retinas of chronic ocular hypertension (COH) and control mice. Western blot, RT-PCR, immunofluorescence, and ELISA were used to evaluate the microglial activation and proinflammatory cytokines release at conditioned levels of IL-17A, along with assessment of optic nerve integrity including retinal ganglion cells (RGCs) counting, axonal neurofilament quantification, and flash visual-evoked potential (F-VEP) examination. And the possibly involved signaling pathways were screened out to go through further validation in scenarios with conditioned IL-17A. Subsequently, IL-17A was found to be significantly upregulated in COH retina. Furthermore, suppression of IL-17A effectively diminished the loss of RGCs, improved axonal quality, and F-VEP performance in COH mice. Mechanistically, IL-17A promoted microglial activation and proinflammatory cytokines release along with enhanced phenotypic conversion of activated microglia to M2-type in early stage and to M1-type in late stage in glaucomatous retinas. Microglia elimination decreased the proinflammatory factors secretion, enhanced the RGCs survival and axonal quality mediated by IL-17A. Furthermore, IL-17A-induced the overactivation of microglia in glaucomatous condition was alleviated after blocking the p38 MAPK pathway. Taken together, IL-17A is involved in the regulation of retinal immune response and RGCs cell death in experimental glaucoma by essentially promoting retinal microglial activation via p38 MAPK signaling pathway. IL-17A dynamically regulates the phenotypic conversion of retinal microglia in experimental glaucoma partly depending on the duration of elevated intraocular pressure. Suppression of IL-17A contributes to alleviate glaucoma neuropathy and exhibits promising potential as an innovative target for therapeutic strategy in glaucoma.
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Glaucoma , Hipertensión Ocular , Ratones , Humanos , Animales , Interleucina-17/metabolismo , Microglía/metabolismo , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Enfermedades Neuroinflamatorias , Glaucoma/metabolismo , Retina/metabolismo , Hipertensión Ocular/etiología , Inflamación/metabolismo , Citocinas/metabolismo , Modelos Animales de EnfermedadRESUMEN
Toxic ginkgolic acids (GAs) are a challenge for Ginkgo biloba-related food. Although a detection method for GAs is available, bulky instruments limit the field testing of GAs. Herein, by assembling gold nanoclusters with copper tannic acid (CuTA), CuAuTA nanocomposites were designed as peroxidase mimics for the colorimetric determination of GAs. Compared with single CuTA, the obtained CuAuTA nanocomposites possessed enhanced peroxidase-like properties. Based on the inhibitory effect of GAs for the catalytic activity of CuAuTA nanozymes, CuAuTA could be utilized for the colorimetric sensing of GAs with a low limit of quantitation of 0.17 µg mL-1. Using a smartphone and the ImageJ software in conjunction, a nanozyme-based intelligent detection platform was developed with a detection limit of 0.86 µg mL-1. This sensing system exhibited good selectivity against other potential interferents. Experimental data demonstrated that GAs might bind to the surface of CuAuTA, blocking the catalytically active sites and resulting in decreased catalytic activity. Our CuAuTA nanozyme-based system could also be applied to detect real ginkgo nut and ginkgo powder samples with recoveries of 93.12-111.6% and relative standard deviations less than 0.3%. Our work may offer a feasible strategy for the determination of GAs and expand the application of nanozymes in food safety detection.
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Barbecue smoke, car exhaust, cigarette smoke, and other waste gases contain toxic reactive oxygen species (ROS) and polycyclic aromatic hydrocarbons (PAHs). Herein, CeO2-based porous carbonaceous frameworks (CeO2 PCFs) were explored as antioxidant nanozymes to scavenge ROS and absorb benzo[a]pyrene (B[a]P). Using cerium-based frameworks as the precursors, CeO2 PCFs were constructed by high-temperature calcination. Due to excellent superoxide dismutase-like and catalase-like activity, CeO2 PCFs could effectively eliminate superoxide radical, hydroxyl radical, and hydrogen peroxide. The 2,2'-azino-bis (3-ethylbenzthiazoline-6-sulfonic acid) free radical scavenging assay had substantiated free radical scavenging ability of CeO2 PCFs. In addition, with a large surface area and porous structure, CeO2 PCFs could adsorb B[a]P efficiently. The designed CeO2 PCFs may provide a new opportunity as scavengers of ROS and absorbents of PAHs in some harmful gases.
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Microglia activation and release of pro-inflammatory cytokines have been closely linked to glaucoma. However, the mechanisms that initiate these pathways remain unclear. Here, we investigated the role of a pro-inflammatory cytokine--osteopontin (OPN), in retinal microglia activation process along with the underlying mechanisms in glaucoma. A rat chronic ocular hypertension (COH) model was established presenting an increase in retinal OPN level and activation of microglia. Primary microglia cells were isolated and cultured under a pressure culture system showing heightened expressions of microglia-derived OPN with changes in inflammatory factors (TNF-α, IL-1ß, and IL-6). OPN and OPN neutralizing antibody (Anti-OPN) interventions were both applied systems for comparison, and cross-referenced with OPN knockdown in vitro. JAK/STAT, NF-κB, ERK1/2, and p38 MAPK, recognized as the primary signaling pathways related to microglia activation, were then screened on whether they can facilitate OPN to act on microglia and their impact on specific inhibitors. Thereafter, retrograde labeling of retinal ganglion cells (RGCs) and flash visual evoked potentials (F-VEP) were used to investigate neuron protection in context of each blockade. Results suggest that OPN is able to enhance the proliferation and activation of retinal microglia in experimental glaucoma which may play a role in the glaucomatous optic neuropathy, and contribute to the eventual RGCs loss and vision function impairment. Such effect may be mediated through the regulation of p38 MAPK signaling pathway.
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Glaucoma/tratamiento farmacológico , Hipertensión Ocular/etiología , Osteopontina/farmacología , Células Ganglionares de la Retina/efectos de los fármacos , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Citocinas/metabolismo , Modelos Animales de Enfermedad , Potenciales Evocados Visuales/efectos de los fármacos , Potenciales Evocados Visuales/fisiología , Glaucoma/metabolismo , Masculino , Microglía/efectos de los fármacos , Microglía/metabolismo , Hipertensión Ocular/metabolismo , Osteopontina/metabolismo , Ratas Sprague-Dawley , Retina/metabolismo , Células Ganglionares de la Retina/metabolismo , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
Detailed information on spatial distribution of croplands and grain yields is crucial for agricultural management and food security, but is often limited by a lack of geospatial data. By integrating satellite observation and statistical data, this study produced new geospatial data of cropland areas and grain yields in China during 2000-2020. We found that the decrease of relatively high-yielding croplands in southern China mainly caused by the expansion of constructed land. Yet, the increase of croplands largely occurred in temperature/water-limited regions of Northern Arid and Semiarid Region (NASR) and Northeast China Plain (NCP). Croplands' decrease in southern China and expansion in NCP and NASR jointly led to the continuous northward shift of the centre of gravity of croplands and grain yields. This spatial transfer of croplands resulted in relatively lower-than- average grain yield per unit area (AGYA) croplands decreasing from 38.96% (2000) to 35.75% (2020), but also relatively higher-than-AGYA croplands decreasing from 38.41% (2000) to 35.01% (2020), implying spatial challenges of grain production. Generally, every 1 km2 of cropland loss in traditional high-yield zones required nearly 1-3 times expansion in area in NASR and NCP to balance grain yield losses. The new geospatial data and these findings from this study could provide valuable information for regional agriculture development and policy marking.
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Agricultura , Grano Comestible , Agricultura/métodos , China , Agua , Recursos HídricosRESUMEN
So far, few animals with the ability of lignin degradation have been reported except termite and longicorn. In this study, it was found that the crude fiber and acid detergent lignin (ADL) of rice straw can be degraded dramatically higher by buffalo than those by cattle. In order to further study this ability of buffalo, the digestion of roughages in buffalo rumen was studied using rumen nylon bag experiment, scanning electron microscopy (SEM), and Van Soest fiber analysis. The SEM results showed that the degradation degree of rice straw was dramatically higher in buffalo than that in cattle. The digestibility of crude fiber was significantly higher in buffalo than that in cattle (P < 0.01). The digestibility of ADL, cellulose, hemicellulose, acid detergent, fiber, and neutral detergent fiber of rice straw in buffalo rumen was significantly higher than that in cattle (P < 0.05). The ADL degradation rate of rice straw in buffalo rumen was significantly higher than that in cattle rumen, indicating that buffalo was capable of utilizing lignin and had superior utilizing capability than cattle. It was observed that various roughages can be dramatically digested by buffalo rumen with the ranking of ADL degradation rate: peanut vine (15.04%) > rice silage > maize silage > rice straw > corn stover > wheat stalk > bract leaf > potato vine (7.22%), verifying that buffalo rumen possessed the ability to digest universal roughages. In conclusion, this study revealed that buffalo was more efficient in ADL degradation compared with cattle.
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Búfalos , Lignina , Alimentación Animal/análisis , Animales , Bovinos , Fibras de la Dieta/metabolismo , Digestión , Fermentación , Lignina/metabolismo , Rumen/metabolismo , Ensilaje/análisis , Zea maysRESUMEN
Notch receptors have large extracellular domains containing up to 36 tandem epidermal growth factor-like (EGF) repeats, which facilitate cell signaling by binding ligands on neighboring cells. Notch receptors play major roles in a variety of developmental processes by controlling cell fate decisions. Each EGF repeat consists of about 40 amino acids with 3 conserved disulfide bonds. Many of the EGF repeats are modified by O-linked fucose glycans, and more than half have calcium-binding sites, but the sequences of the EGF repeats vary giving distinct roles to each repeat. EGF repeat 27 (EGF27) from mouse NOTCH1 is modified with O-fucose and is 1 of 7 repeats that is differentially modified by specific Fringe enzymes, which are known to regulate NOTCH1 activation and ligand binding. To better understand the role of EGF27 in NOTCH1 function and regulation, the 3-dimensional structures of EGF27 and its glycoforms are being pursued. E. coli cells were used to produce EGF27 in sufficient quantities for nuclear magnetic resonance analysis. Previous attempts to express the repeat alone and refold the repeat under a steady redox environment were unsuccessful due to low yields and extensive mixed-disulfide bond cross-linking. A new strategy using a cleavable maltose binding protein fusion tag increased the solubility and yield of EGF27. With the fusion tag, EGF27 was refolded to produce the correct disulfide bond arrangement, which was verified enzymatically with the glycosyltransferases, Protein O-fucosyltransferase 1 (POFUT1) and Lunatic Fringe (LFNG).
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Fucosa , Biosíntesis de Péptidos , Péptidos , Receptor Notch1 , Animales , Fucosa/química , Fucosa/metabolismo , Glicosilación , Ratones , Péptidos/química , Péptidos/genética , Receptor Notch1/biosíntesis , Receptor Notch1/química , Receptor Notch1/genética , Proteínas Recombinantes/biosíntesis , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Secuencias Repetitivas de AminoácidoRESUMEN
BACKGROUND Chronic ocular hypertension (COH) models mostly focus on changes in intraocular pressure (IOP) and loss of retinal ganglion cells (RGCs). The present study evaluated important glaucoma-related changes in visual function, response to common ocular hypotensive drugs, and safety for our previously developed rat model. MATERIAL AND METHODS The model was established through a single injection of hydrogel into the anterior chambers. Efficacy was assessed through F-VEP by measuring latency and amplitude of P1. We evenly divided 112 rats into 4 groups: control and COH at 2, 4, and 8 weeks. Response to 5 common drugs (brimonidine, timolol, benzamide, pilocarpine, and bimatoprost) were each tested on 6 rats and assessed using difference in IOP. Safety assessment was conducted through histological analysis of 24 rats evenly divided into 4 groups of control and COH at 2, 4, and 8 weeks. Corneal endothelial cells (CECs) of 24 additional rats were used to determine toxic effects through TUNEL and CCK-8 assays. RESULTS P1 latency and amplitude of VEP demonstrated the model is effective in inducing optic nerve function impairment. Only the drug pilocarpine failed to have an obvious hypotensive effect, while the other 4 were effective. CECs at 2, 4, and 8 weeks showed no significant differences from control groups in results of histological analysis, TUNEL, and CCK-8 assays. CONCLUSIONS A single injection of hydrogel into the anterior chamber is effective for modeling COH, can respond to most commonly used hypotensive drugs, and is non-toxic to the eyes.
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Antihipertensivos/farmacología , Hidrogeles/efectos adversos , Presión Intraocular/efectos de los fármacos , Hipertensión Ocular , Animales , Enfermedad Crónica , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Hidrogeles/farmacología , Masculino , Hipertensión Ocular/inducido químicamente , Hipertensión Ocular/tratamiento farmacológico , Hipertensión Ocular/fisiopatología , Ratas , Ratas Sprague-DawleyRESUMEN
Phytochemical investigation of whole plants of Euphorbia pilosa led to the isolation and identification of two new daphnane-diterpenoid glucosides, euphopilosides A and B (1 and 2, resp.), and a new ent-abietane, euphopilolide (3), together with eight known compounds. Compounds 1 and 2 are the first daphnane-type diterpenoid glycosides. Their structures were elucidated by a combination of 1D- and 2D-NMR, and MS analyses, and acid hydrolysis. Compounds 1-9 were evaluated for their in vitro cytotoxicities against five human tumor cell lines, HL-60, SMMC-7721, A-549, MCF-7, and SW-480. Compound 7 showed moderate inhibitory activity against all five cell lines.
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Antineoplásicos Fitogénicos/química , Diterpenos/química , Euphorbia/química , Glucósidos/química , Antineoplásicos Fitogénicos/aislamiento & purificación , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Diterpenos/aislamiento & purificación , Diterpenos/farmacología , Glucósidos/aislamiento & purificación , Glucósidos/farmacología , Humanos , Neoplasias/tratamiento farmacológicoRESUMEN
Three new phenolic compounds (1-3) were isolated from the heartwood of Dalbergia odorifera T. Chen. (Leguminosae). Their structures were established based on spectroscopic methods including 1D and 2D NMR (HSQC, COSY, HMBC and ROESY). Compound 2 exhibited cytotoxicity against BEL-7402 tumor cell lines.
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Antineoplásicos Fitogénicos/aislamiento & purificación , Benzofuranos/aislamiento & purificación , Cromonas/aislamiento & purificación , Dalbergia/química , Medicamentos Herbarios Chinos/aislamiento & purificación , Flavonoides/aislamiento & purificación , Compuestos Heterocíclicos de 4 o más Anillos/aislamiento & purificación , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Benzofuranos/química , Benzofuranos/farmacología , Cromonas/química , Cromonas/farmacología , Ensayos de Selección de Medicamentos Antitumorales , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Flavonoides/química , Flavonoides/farmacología , Compuestos Heterocíclicos de 4 o más Anillos/química , Compuestos Heterocíclicos de 4 o más Anillos/farmacología , Humanos , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Fenoles/químicaRESUMEN
Fourteen compounds were isolated from Dalbergia odoriferae and purified by repeated column chromatography on silica and sephadex LH-20 gel and structurally identified by spectral analysis. These compounds were identified as 4, 9-dimethoxy-3-hydroxypterocarpan (1), medicarpin (2), 2', 4', 5-trihydroxy-7-methoxyisoflavone (3), 2', 3', 7-trihydroxy-4'-methoxyisoflavan (4), formononetin (5), 3, 8-dihydroxy-9-methoxypterocarpan (6), koparin (7), 3-hydroxy-9-methoxypterocarp-6a-ene (8), 2'-hydroxyformononetin (9), stevenin (10), 2', 7-dihydroxy-4', 5'-dimethoxyisoflavone (11), lyoniresinol (12), 2, 4-dihydroxy-5-methoxy-benzophenone (13) and neokhriol A (14). Compounds 1, 3, 4, 6, 8, 12 and 14 were isolated from this plant for the first time. Antibacterial activity assay showed that compound 4 had inhibitory effect on Ralstonia solanacearum.
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Dalbergia/química , Extractos Vegetales/química , Extractos Vegetales/aislamiento & purificación , Anisoles/química , Anisoles/aislamiento & purificación , Anisoles/farmacología , Antibacterianos/química , Antibacterianos/aislamiento & purificación , Antibacterianos/farmacología , Benzofenonas/química , Benzofenonas/aislamiento & purificación , Benzofenonas/farmacología , Cromatografía/métodos , Dextranos , Geles , Isoflavonas/química , Isoflavonas/aislamiento & purificación , Isoflavonas/farmacología , Pruebas de Sensibilidad Microbiana , Naftalenos/química , Naftalenos/aislamiento & purificación , Naftalenos/farmacología , Extractos Vegetales/farmacología , Pterocarpanos/química , Pterocarpanos/aislamiento & purificación , Pterocarpanos/farmacología , Ralstonia solanacearum/efectos de los fármacos , Ralstonia solanacearum/crecimiento & desarrollo , Gel de SíliceRESUMEN
To develop functional, sustainable and eco-friendly active packaging materials as alternatives to plastic films, we successfully prepared Ginkgo biloba leaf polysaccharide-stabilized selenium nanomaterials (Se-GBLP). Se-GBLP with glutathione peroxidase-like activity could efficiently remove harmful reactive oxygen species. As a functional additive, Se-GBLP was incorporated into degradable chitosan (CS) to fabricate CS/Se-GBLP films. The addition of Se-GBLP improved the mechanical properties, UV-visible light barrier performance, water vapor permeability, and antioxidant activity of the films. Preservation experiments demonstrated CS/Se-GBLP film could maintain quality and prolong the storage time of bananas and cherry tomatoes. It was the first time to use selenium-based nanozyme for fruit preservation. This work offered a cost-effective solution to reduce post-harvest losses, increasing sustainability and profitability. Future research should focus on more factors affecting freshness such as variety, maturity, harvest and storage conditions to improve preservation, as well as on the material's safety concern and environmental impact.
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Embalaje de Alimentos , Conservación de Alimentos , Ginkgo biloba , Glutatión Peroxidasa , Polisacáridos , Selenio , Antioxidantes/química , Antioxidantes/metabolismo , Embalaje de Alimentos/instrumentación , Conservación de Alimentos/instrumentación , Conservación de Alimentos/métodos , Frutas/química , Ginkgo biloba/química , Glutatión Peroxidasa/metabolismo , Glutatión Peroxidasa/química , Musa/química , Nanoestructuras/química , Extractos Vegetales/química , Hojas de la Planta/química , Polisacáridos/química , Polisacáridos/metabolismo , Selenio/química , Solanum lycopersicum/químicaRESUMEN
PURPOSE: To assess the quantity and quality of global research on uveitis, visualize the research hotspots, and reveal the study trends in uveitis. METHODS: This bibliometric analysis was performed with the data obtained from the Web of Science core collection (WoSCC) database and Scopus. Bibliometrix and VOSviewer were used to analyze and visualize study trends and hotspots. Citespace was used to conduct the cooperation and co-citation network analysis. RESULTS: A total of 5837 and 7195 documents were exported for further analysis in WoSCC and Scopus, respectively. The USA has published the most articles related to uveitis (1627, 27.87%, WoS; 1979, 27.51%, Scopus) and accounted for the most frequency of total citations (42345 times total citations 35 900 times without self-citations in WoSCC database). Most of the papers focusing on uveitis were published in Ocular Immunology and Inflammation (761, 13.04% within WoS; 793, 11.02% within Scopus). Additionally, novel biotherapy is the hotspot of uveitis research which also may be a sustained research interest in the future. CONCLUSIONS: An increasing trend of publications was found in uveitis research. The USA was the leading contributor in this field, and it was the center of cooperation network. Our study provided an overview of uveitis research, which may serve as a valuable reference and guide for stakeholders interested in uveitis.
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Wolbachia, one of the most ubiquitous heritable symbionts in lepidopteran insects, can cause mitochondrial introgression in related host species. We recently found mito-nuclear discordance in the Lepidopteran tribe Tagiadini Mabille 1878 from which Wolbachia has not been reported. In this study, we found that 13 of the 46 species of Tagiadini species tested were positive for Wolbachia. Overall, 14% (15/110) of Tagiadini specimens were infected with Wolbachia and nine new STs were found from 15 isolates. A co-phylogenetic comparison, divergence time estimation and Wolbachia recombination analysis revealed that mito-nuclear discordance in Tagiadini species is not mediated by Wolbachia, but Wolbachia acquisition in Tagiadini appears to have occurred mainly through horizontal transmission rather than codivergence.
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Nowadays, nanozymes have not only been used as biosensors in the detection field, but also their application prospects in disease treatment have been explored. Numerous nanomaterials have similar catalytic activities such as peroxidase, oxidase, catalase and superoxide dismutase, and they can be used for antibacterial, anticancer and antioxidant therapy. Although there have been many studies on the application of nanozymes in the therapeutic field, the current nanozyme-based systems often lack targeting and ignore the harm to the surrounding normal tissues. Although promising, the biosafety of nanomaterials has always been the concern of researchers. To improve the treatment effect and reduce toxic and side effects, precision treatment has become the key. At present, a few studies have modified targeted molecules on nanozymes to achieve precise targeting through specific interaction with surface overexpression factors of bacteria or cells. Combined with the catalysis of nanozymes, the targeted treatment of diseases can be achieved. This review summarizes the current research of nanozyme systems in targeted antibacterial, anticancer and antioxidant applications. At the same time, the challenges and development prospects of nanozyme-based targeted therapy system are summarized. It is expected that this work will provide new ideas and new directions for the precise treatment of nanozymes.
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Conventional nanozyme-based pesticide detection often requires the assistance of acetylcholinesterase. In this work, a CuCeTA nanozyme was successfully designed for the direct colorimetric detection of glyphosate. Direct detection can effectively avoid the problems caused by cascading with natural enzymes such as acetylcholinesterase. By assembling tannic acid, copper sulfate pentahydrate and cerium(III) nitrate hexahydrate, CuCeTA nanoflowers were prepared. The obtained CuCeTA possessed excellent peroxidase-like activity that could catalyze the oxidation of 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB in the presence of hydrogen peroxide. Glyphosate could effectively inhibit the peroxidase-like activity of CuCeTA while other pesticides (fenthion, chlorpyrifos, profenofos, phosmet, bromoxynil and dichlorophen) did not show significant inhibitory effects on the catalytic activity of CuCeTA. In this way, CuCeTA could be used for the colorimetric detection of glyphosate with a low detection limit of 0.025 ppm. Combined with a smartphone and imageJ software, a glyphosate test paper was designed with a detection limit of 3.09 ppm. Fourier transform infrared spectroscopy demonstrated that glyphosate and CuCeTA might be bound by coordination, which could affect the catalytic activity of CuCeTA. Our CuCeTA-based nanozyme system exhibited unique selectivity and sensitivity for glyphosate detection and this work may provide a new strategy for rapid and convenient detection of pesticides.
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Peroxidasa , Plaguicidas , Peroxidasa/química , Acetilcolinesterasa , Colorimetría/métodos , Peroxidasas , Colorantes , GlifosatoRESUMEN
This study aimed to isolate and identify a ligninolytic bacterium from the rumen of buffalo (Bubalus bubalis) and investigate its effects as a silage additive for whole-plant rape. Three lignin-degradation strains were isolated from the buffalo rumen, with AH7-7 being chosen for further experiments. Strain AH7-7, with acid tolerance and a 51.4% survival rate at pH 4, was identified as Bacillus cereus. It exhibited a lignin-degradation rate of 20.5% after being inoculated in a lignin-degrading medium for 8 days. We divided the rape into four groups according to the various additive compositions to examine the fermentation quality, nutritional value, and bacterial community after ensiling: Bc group (inoculated with B. cereus AH7-7 3.0 × 106 CFU g FW-1), Blac group (inoculated with B. cereus AH7-7 1.0 × 106 CFU g FW-1, L. plantarum 1.0 × 106 CFU g FW-1, and L. buchneri 1.0 × 106 CFU g FW-1), Lac group (inoculated with L. plantarum 1.5 × 106 CFU g FW-1 and L. buchneri 1.5 × 106 CFU g FW-1), and Ctrl group (no additives). After 60 days of fermentation, the application of B. cereus AH7-7 was potent in modulating the fermentation quality of silage, especially when combined with L. plantarum and L. buchneri, as indicated by lower dry matter loss and higher contents of crude protein, water-soluble carbohydrate, and lactic acid. Furthermore, treatments with the B. cereus AH7-7 additive decreased the contents of acid detergent lignin, cellulose, and hemicellulose. The B. cereus AH7-7 additive treatments reduced the bacterial diversity and optimized the bacterial community compositions of silage, with an increase in the relative abundance of beneficial Lactobacillus and a decrease in the relative abundance of undesirable Pantoea and Erwinia. Functional prediction revealed that inoculation with B. cereus AH7-7 could increase the cofactors and vitamins metabolism, amino acid metabolism, translation, replication and repair, and nucleotide metabolism, while decreasing the carbohydrate metabolism, membrane transport, and energy metabolism. In brief, B. cereus AH7-7 improved the microbial community, fermentation activity, and ultimately the quality of silage. The ensiling with B. cereus AH7-7, L. plantarum, and L. buchneri combination is an effective and practical strategy to improve the fermentation and nutrition preservation of rape silage.
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Interactions between microglia and macroglia play important roles in the neurodegeneration of the central nervous system and so is the situation between microglia and Müller cells in retina neurodegenerations like glaucoma. This study focuses on the roles of microglia-derived osteopontin (OPN) in impacting Müller cells and retinal ganglion cells (RGCs). Rat model and cell pressurization culture were used to simulate glaucoma scenarios. Animals were differently treated with anti-OPN, suppressors of OPN receptors (Itgαvß3/CD44) or microglia inhibitor minocycline, while isolated retinal Müller cells were accordingly treated with conditioned media from microglia culture pretreated with pressuring, overexpression-OPN, SiR-OPN, or minocycline. SB203580 was introduced to explore the role of p38 MAPK signaling pathway. Results revealed microglia may secret OPN to impact Müller cells' autophagy and RGCs survival via binding to Itgαvß3/CD44 receptors in glaucomatous neurodegeneration with involvement of p38 MAPK pathway. This discovery may benefit understanding neurodegenerative disorders and exploring therapeutics.
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Two new meroterpenes, guignardone D (1) and guignardone E (2), were isolated from endophytic fungus A1 of Scyphiphora hydrophyllacea Gaertn. F. Their structures were established based on spectroscopic methods including 1D and 2D NMR (HMQC, (1)H-(1)H COSY, HMBC, and ROESY).