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OBJECTIVE: Language is one of the most celebrated hallmarks of human cognition. With the continuous improvement of medical technology, functional MRI (fMRI) has been used in aphasia. Although many related studies have been carried out, most studies have not extensively focused on brain regions with reduced activation in aphasic patients. The aim of this study was to identify brain regions normally activated in healthy controls but with reduced activation in aphasic patients during fMRI language tasks. METHODS: We collected all previous task-state fMRI studies of secondary aphasia. The brain regions showed normal activation in healthy controls and reduced activation in aphasic patients were conducted activation likelihood estimation (ALE) meta-analysis to obtain the brain regions with consistently reduced activation in aphasic patients. RESULTS: The ALE meta-analysis revealed that the left inferior frontal gyrus, left middle temporal gyrus, left superior temporal gyrus, left fusiform gyrus, left lentiform nucleus and the culmen of the cerebellum were the brain regions with reduced activation in aphasic patients. DISCUSSION: These findings from the ALE meta-analysis have significant implications for understanding the language network and the potential for recovery of language functions in individuals with aphasia.
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Ovarian cancer (OC) remains the primary cause of mortality among gynecological malignancies, and the identification of reliable molecular biomarkers to prognosticate OC outcomes is yet to be achieved. The gene palmitoyl protein thioesterase 2 (PPT2), which has been sparsely studied in OC, was closely associated with metabolism. This study aimed to determine the association between PPT2 expression, prognosis, immune infiltration, and potential molecular mechanisms in OC. We obtained the RNA-seq and clinical data from The Cancer Genome Atlas (TCGA), The Genotype-Tissue Expression (GTEx) and Gene Expression Omnibus (GEO) databases, then Kaplan-Meier analysis, univariate Cox regression, multivariate Cox regression, nomogram, and calibration were conducted to assess and verify the role of PPT2. Gene set enrichment analysis (GSEA) was used to figure out the closely correlated pathways with PPT2. Overexpression experiment was performed to explore the function of PPT2. Our findings showed that PPT2 mRNA expression was apparent down-regulation in OC tissue compared to normal ovarian tissues in TCGA, GTEx datasets, and GEO datasets. This differential expression was also confirmed in our in-house datasets at both the mRNA and protein levels. Decreased PPT2 expression correlated with lower survival rates in TCGA, several GEO datasets, and our in-house datasets. Multivariate analysis revealed that PPT2 was an independent factor in predicting better outcomes for OC patients in TCGA and GEO. A negative correlation was revealed between immune infiltration and PPT2 expression through Single-sample GSEA (ssGSEA). Additionally, PPT2 was negatively correlated with an up-regulated immune score, stromal score, and estimate score, suggesting that patients with low PPT2 expression might benefit more from immunotherapy. Numerous chemical agents showed lower IC50 in patients with high PPT2 expression. In single-cell RNA sequencing (scRNA-seq) analysis of several OC datasets, we found PPT2 was mainly expressed in endothelial cells. Furthermore, we found that PPT2 inhibited OC cell proliferation in vitro. Our results demonstrated that PPT2 was considered a favorable prognostic biomarker for OC and may be vital in predicting response to immunotherapy and chemotherapy. Further research was needed to fully understand the relationship between PPT2 and immunotherapy efficacy in OC patients.
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Inmunoterapia , Neoplasias Ováricas , Tioléster Hidrolasas , Humanos , Femenino , Neoplasias Ováricas/genética , Neoplasias Ováricas/inmunología , Neoplasias Ováricas/mortalidad , Neoplasias Ováricas/terapia , Pronóstico , Inmunoterapia/métodos , Tioléster Hidrolasas/genética , Tioléster Hidrolasas/metabolismo , Biomarcadores de Tumor/genética , Regulación Neoplásica de la Expresión GénicaRESUMEN
Polyurethane foam (PUF) pads are widely used in semiconductor manufacturing, particularly for chemical mechanical polishing (CMP). This study prepares PUF composites with microcrystalline cellulose (MCC) and nanocrystalline cellulose (NCC) to improve CMP performance. MCC and NCC were characterized using scanning electron microscopy (SEM) and X-ray diffraction (XRD), showing average diameters of 129.7 ± 30.9 nm for MCC and 22.2 ± 6.7 nm for NCC, both with high crystallinity (ca. 89%). Prior to preparing composites, the study on the influence of the postbaked step on the PUF was monitored through Fourier-transform infrared spectroscopy (FTIR). After that, PUF was incorporated with MCC/NCC to afford two catalogs of polyurethane foam composites (i.e., PUFC-M and PUFC-N). These PUFCs were examined for their thermal and surface properties using a differential scanning calorimeter (DSC), thermogravimetric analysis (TGA), dynamic mechanical analyzer (DMA), and water contact angle (WCA) measurements. Tgs showed only slight changes but a notable increase in the 10% weight loss temperature (Td10%) for PUFCs, rising from 277 °C for PUF to about 298 °C for PUFCs. The value of Tan δ dropped by up to 11%, indicating improved elasticity. Afterward, tensile and abrasion tests were conducted, and we acquired significant enhancements in the abrasion performance (e.g., from 1.04 mm/h for the PUF to 0.76 mm/h for a PUFC-N) of the PUFCs. Eventually, we prepared high-performance PUFCs and demonstrated their capability toward the practical CMP process.
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Migraine is a chronic, recurrent neurovascular disorder characterized by episodes closely associated with neurovascular hypersensitivity. Oxidative stress can worsen the hypersensitive state of the central nervous system, which in turn can trigger pro-inflammatory factors that result in neurogenic inflammation. Topiramate is frequently used as a preventative measure for migraines, but there is currently little empirical data to support its efficacy through pathways related to neurogenic inflammation and oxidative stress. This review provides an overview of current knowledge regarding the etiology, inducements, pathophysiology, and available treatments for migraine, with a focus on the clinical and experimental evidence of neurogenic inflammation and oxidative stress in migraine. It also delves into the antioxidant and anti-inflammatory qualities of topiramate, clarifying the possible ways in which topiramate affects these pathways to lessen migraine symptoms.
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Diurnal gene expression is a pervasive phenomenon occurring across all kingdoms of life, orchestrating adaptive responses to daily environmental fluctuations and thus enhancing organismal fitness. Our understanding of the plant circadian clock is primarily derived from studies in Arabidopsis and direct comparisons are difficult due to differences in gene family sizes. To this end, the identification of functional orthologs based on diurnal and tissue expression is necessary. The diurnal.plant.tools database constitutes a repository of gene expression profiles from 17 members of the Archaeplastida lineage, with built-in tools facilitating cross-species comparisons. In this database update, we expand the dataset with diurnal gene expression from 4 agriculturally significant crop species and Marchantia, a plant of evolutionary significance. Notably, the inclusion of diurnal gene expression data for Marchantia enables researchers to glean insights into the evolutionary trajectories of the circadian clock and other biological processes spanning from algae to angiosperms. Moreover, integrating diurnal gene expression data with datasets from related gene co-expression databases, such as CoNekt-Plants and CoNekt-Stress, which contain gene expression data for tissue and perturbation experiments, provides a comprehensive overview of gene functions across diverse biological contexts. This expanded database serves as a valuable resource for elucidating the intricacies of diurnal gene regulation and its evolutionary underpinnings in plant biology.
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The fruits of Alpinia oxyphylla (Alpiniae Oxyphyllae Fructus, AOF) are one of the "Four Famous South Medicines" in China. In this study, beta-site amyloid protein precursor cleaving enzyme 1 (BACE1) was applied to explore the active components in AOF responsible for type 2 diabetes mellitus (T2DM)-related cognitive disorder. As a result, 24 compounds including three unreported ones (1, 3, 4) were isolated from AOF. Compound 1 is an unusual carboncarbon linked diarylheptanoid dimer, and compound 4 is the first case of 3,4-seco-eudesmane sesquiterpenoid with a 5/6-bicyclic skeleton. Four diarylheptanoids (3, 5-7), one flavonoid (9) and two sesquiterpenoids (14 and 20) showed BACE1 inhibitory activity, of which the most active 6 was revealed to be a non-competitive and anti-competitive mixed inhibitor. Docking simulation suggested that OH-4' of 6 played important roles in maintaining activity by forming hydrogen bonds with Ser36 and Ile126 residues. Compounds 3, 5, 9 and 20 displayed neuroprotective effects against amyloid ß (Aß)-induced damage in BV2 cells. Mechanism study revealed that compounds 5 and 20 downregulated the expression of BACE1 and upregulated the expression of Lamp2 to exert effects. Thus, the characteristic diarylheptanoids and sesquiterpenoids in AOF had the efficacy to alleviate T2DM-related cognitive disorder by inhibiting BACE1 activity and reversing Aß-induced neuronal damage.
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Alpinia , Secretasas de la Proteína Precursora del Amiloide , Ácido Aspártico Endopeptidasas , Diabetes Mellitus Tipo 2 , Frutas , Sesquiterpenos , Alpinia/química , Ácido Aspártico Endopeptidasas/antagonistas & inhibidores , Ácido Aspártico Endopeptidasas/metabolismo , Secretasas de la Proteína Precursora del Amiloide/antagonistas & inhibidores , Frutas/química , Estructura Molecular , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Sesquiterpenos/farmacología , Sesquiterpenos/aislamiento & purificación , Simulación del Acoplamiento Molecular , Diarilheptanoides/farmacología , Diarilheptanoides/aislamiento & purificación , Diarilheptanoides/química , Fitoquímicos/farmacología , Fitoquímicos/aislamiento & purificación , Humanos , Animales , China , Flavonoides/farmacología , Flavonoides/aislamiento & purificación , Flavonoides/química , Trastornos del Conocimiento/tratamiento farmacológico , Ratones , Extractos VegetalesRESUMEN
OBJECTIVE: To investigate the effect of chrysophanol, a phytochemical derived from Radix et Rhizoma Rhei on HepG2 liver cancer cells. METHODS: HepG2 cell line was treated with different concentrations chrysophanol (0-100 µmol/L) for 24 h. The cell counting kit 8 assay was employed to assess cell viability. Intracellular calcium levels were examined using Fluo-4 AM and Mag-fluo-4 AM staining, followed by flow cytometry analysis. Mitochondrial membrane potential was measured with JC-1 assay kit. Additionally, the expressions of key proteins such as p-JNK, Bax, cytochrome c (Cyt C), cleaved caspase-3 (cCaspase-3), and caspase-8 were analyzed by Western blot. The inhibitory effects of chrysophanol on the invasion of cells were determined using a Transwell assay. Analysis of invasiveness was conducted by wound healing assay. RESULTS: Chrysophanol significantly reduced the proliferation of HepG2 liver cancer cells by affecting intracellular calcium distribution, diminishing mitochondrial membrane potential, and enhancing the expressions of p-JNK, Bax, Cyt C, cCaspase-3, and caspase-8 in the groups treated with 75 or 100 µmol/L chrysophanol compared to the control group (P<0.05). Additionally, 75 and 100 µmol/L chrysophanol exhibited inhibitory effects on cell migration and wound healing. CONCLUSION: Chrysophanol demonstrates potential against HepG2 liver cancer cells, suggesting its potential use as a therapeutic agent for liver cancer treatment.
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Hyperglycemia accelerates calcification of atherosclerotic plaques in diabetic patients, and the accumulation of advanced glycation end products (AGEs) is closely related to the atherosclerotic calcification. Here, we show that hyperglycemia-mediated AGEs markedly increase vascular smooth muscle cells (VSMCs) NF90/110 activation in male diabetic patients with atherosclerotic calcified samples. VSMC-specific NF90/110 knockout in male mice decreases obviously AGEs-induced atherosclerotic calcification, along with the inhibitions of VSMC phenotypic changes to osteoblast-like cells, apoptosis, and matrix vesicle release. Mechanistically, AGEs increase the activity of NF90, which then enhances ubiquitination and degradation of AGE receptor 1 (AGER1) by stabilizing the mRNA of E3 ubiquitin ligase FBXW7, thus causing the accumulation of more AGEs and atherosclerotic calcification. Collectively, our study demonstrates the effects of VSMC NF90 in mediating the metabolic imbalance of AGEs to accelerate diabetic atherosclerotic calcification. Therefore, inhibition of VSMC NF90 may be a potential therapeutic target for diabetic atherosclerotic calcification.
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Aterosclerosis , Proteína 7 que Contiene Repeticiones F-Box-WD , Productos Finales de Glicación Avanzada , Ratones Noqueados , Músculo Liso Vascular , Miocitos del Músculo Liso , Proteínas del Factor Nuclear 90 , Receptor para Productos Finales de Glicación Avanzada , Animales , Masculino , Ratones , Productos Finales de Glicación Avanzada/metabolismo , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patología , Aterosclerosis/metabolismo , Aterosclerosis/genética , Aterosclerosis/patología , Humanos , Proteína 7 que Contiene Repeticiones F-Box-WD/metabolismo , Proteína 7 que Contiene Repeticiones F-Box-WD/genética , Miocitos del Músculo Liso/metabolismo , Miocitos del Músculo Liso/patología , Proteínas del Factor Nuclear 90/metabolismo , Proteínas del Factor Nuclear 90/genética , Receptor para Productos Finales de Glicación Avanzada/metabolismo , Receptor para Productos Finales de Glicación Avanzada/genética , Calcificación Vascular/metabolismo , Calcificación Vascular/patología , Calcificación Vascular/genética , Ratones Endogámicos C57BL , Ubiquitinación , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/patología , Hiperglucemia/metabolismo , Hiperglucemia/genética , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Placa Aterosclerótica/genética , ApoptosisRESUMEN
Porcine Epidemic Diarrhea Virus (PEDV) is a highly contagious virus that causes Porcine Epidemic Diarrhea (PED). This enteric disease results in high mortality rates in piglets, leading to significant financial losses in the pig industry. However, vaccines cannot provide sufficient protection against epidemic strains. Spike (S) protein exposed on the surface of virion mediates PEDV entry into cells. Our findings imply that matrine (MT), a naturally occurring alkaloid, inhibits PEDV infection targeting S protein of virions and biological process of cells. The GLY434 residue in the autodocking site of the S protein and MT conserved based on sequence comparison. This study provides a comprehensive analysis of viral attachment, entry, and virucidal effects to investigate how that MT inhibits virus replication. MT inhibits PEDV attachment and entry by targeting S protein. MT was added to cells before, during, or after infection, it exhibits anti-PEDV activities and viricidal effects. Network pharmacology focuses on addressing causal mechanisms rather than just treating symptoms. We identified the key genes and screened the cell apoptosis involved in the inhibition of MT on PEDV infection in network pharmacology. MT significantly promotes cell apoptosis in PEDV-infected cells to inhibit PEDV infection by activating the MAPK signaling pathway. Collectively, we provide the biological foundations for the development of single components of traditional Chinese medicine to inhibit PEDV infection and spread.
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Alcaloides , Antivirales , Apoptosis , Sistema de Señalización de MAP Quinasas , Matrinas , Virus de la Diarrea Epidémica Porcina , Quinolizinas , Glicoproteína de la Espiga del Coronavirus , Quinolizinas/farmacología , Quinolizinas/química , Alcaloides/farmacología , Alcaloides/química , Animales , Virus de la Diarrea Epidémica Porcina/efectos de los fármacos , Apoptosis/efectos de los fármacos , Glicoproteína de la Espiga del Coronavirus/metabolismo , Antivirales/farmacología , Antivirales/química , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Chlorocebus aethiops , Células Vero , Porcinos , Replicación Viral/efectos de los fármacos , Internalización del Virus/efectos de los fármacosRESUMEN
Resistant starch (RS) is important in controlling diabetes. The primary objective of this study is to examine the impact of molecular conformation on the enzymatic hydrolysis efficiency of starch by α-amylase. And the interactions between starch molecules with different conformations and α-amylase were analysed by using molecule dynamics simulation and molecular docking. It was found, the natural conformational starch molecule was hydrolysed from the middle of the starch chain by α-amylase, producing polysaccharides. The bent PS-conformational starch molecules with multiple O2-O3 intramolecular hydrogen bonds produced by high-pressure was hydrolysed from the head of the starch chain to produce glucose, which is not conducive to RS formation. The stretched H-conformation without intramolecular hydrogen bonds produced by heat treatment was not hydrolysed by α-amylase. However, it occupied the active groove and formed strong interactions with α-amylase, which prevented other starch molecules from binding to α-amylase, thus reducing hydrolysis efficiency. Moreover, the total interaction energies between the three starch molecules and α-amylase were approximately 78 kJ/mol. And several hydrogen bonds were formed between the starch molecules and α-amylase, which provides evidence for the continuous sliding hydrolysis hypothesis of α-amylase. Moreover, these results provide an important reference for elucidating the mechanism of RS formation.
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Enlace de Hidrógeno , Simulación del Acoplamiento Molecular , Almidón , alfa-Amilasas , Almidón/química , Almidón/metabolismo , Hidrólisis , alfa-Amilasas/química , alfa-Amilasas/metabolismo , Simulación de Dinámica Molecular , Conformación MolecularRESUMEN
Primary Sjögren's syndrome (pSS) is a chronic inflammatory autoimmune disease with an unclear pathogenesis, and there is currently no approved drug for the treatment of this disease. Iguratimod, as a novel clinical anti-rheumatic drug in China and Japan, has shown remarkable efficacy in improving the symptoms of patients with pSS in clinical studies. In this study we investigated the mechanisms underlying the therapeutic effect of iguratimod in the treatment of pSS. Experimental Sjögren's syndrome (ESS) model was established in female mice by immunizing with salivary gland protein. After immunization, ESS mice were orally treated with iguratimod (10, 30, 100 mg·kg-1·d-1) or hydroxychloroquine (50 mg·kg-1·d-1) for 70 days. We showed that iguratimod administration dose-dependently increased saliva secretion, and ameliorated ESS development by predominantly inhibiting B cells activation and plasma cell differentiation. Iguratimod (30 and 100 mg·kg-1·d-1) was more effective than hydroxychloroquine (50 mg·kg-1·d-1). When the potential target of iguratimod was searched, we found that iguratimod bound to TEC kinase and promoted its degradation through the autophagy-lysosome pathway in BAFF-activated B cells, thereby directly inhibiting TEC-regulated B cells function, suggesting that the action mode of iguratimod on TEC was different from that of conventional kinase inhibitors. In addition, we found a crucial role of TEC overexpression in plasma cells of patients with pSS. Together, we demonstrate that iguratimod effectively ameliorates ESS via its unique suppression of TEC function, which will be helpful for its clinical application. Targeting TEC kinase, a new regulatory factor for B cells, may be a promising therapeutic option.
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Diferenciación Celular , Cromonas , Células Plasmáticas , Proteínas Tirosina Quinasas , Síndrome de Sjögren , Sulfonamidas , Animales , Síndrome de Sjögren/tratamiento farmacológico , Femenino , Diferenciación Celular/efectos de los fármacos , Ratones , Proteínas Tirosina Quinasas/antagonistas & inhibidores , Proteínas Tirosina Quinasas/metabolismo , Células Plasmáticas/efectos de los fármacos , Cromonas/farmacología , Cromonas/uso terapéutico , Sulfonamidas/farmacología , Sulfonamidas/uso terapéutico , Benzofuranos/farmacología , Benzofuranos/uso terapéutico , Hidroxicloroquina/farmacología , Hidroxicloroquina/uso terapéutico , Modelos Animales de Enfermedad , Humanos , Linfocitos B/efectos de los fármacos , Linfocitos B/metabolismo , Antirreumáticos/farmacología , Antirreumáticos/uso terapéuticoRESUMEN
As the next generation of in-vehicle intelligent platforms, the augmented reality heads-up display (AR-HUD) has a huge information interaction capacity, can provide drivers with auxiliary driving information, avoid the distractions caused by the lower head during the driving process, and greatly improve driving safety. However, AR-HUD systems still face great challenges in the realization of multi-plane full-color display, and they cannot truly achieve the integration of virtual information and real road conditions. To overcome these problems, many new devices and materials have been applied to AR-HUDs, and many novel systems have been developed. This study first reviews some key metrics of HUDs, investigates the structures of various picture generation units (PGUs), and finally focuses on the development status of AR-HUDs, analyzes the advantages and disadvantages of existing technologies, and points out the future research directions for AR-HUDs.
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In this Letter, we explore the intersection of chirality and recently discovered toroidal spatiotemporal optical vortices (STOVs). We introduce "photonic conchs" theoretically as a new type of toroidal-like state exhibiting geometrical chirality, and experimentally observe these wave packets with controllable topological charges. Unlike toroidal STOVs, photonic conchs exhibit unique chirality-related dynamical evolution in free space and possess an orbital angular momentum correlated with all the dimensions of space-time. This research deepens our understanding of toroidal light states and potentially advances various fields by unveiling similar wave phenomena in a broader scope of physics systems, including acoustics and electronics.
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The current study aimed to investigate the potential role of astragaloside IV (AS-IV) in improving cellular lipid deposition and its underlying mechanism. A fatty liver cell model was established by treating hepatoma cells with palmitic acid. AS-IV and SC79 were used for treatment. Oil Red O staining was applied to detect intracellular lipid deposition, and transmission electron microscopy was utilized to assess autophagosome formation. Immunofluorescence double staining was applied to determine microtubule-associated proteins 1A/1B light chain 3 (LC3) expression. Western blot analysis was performed to detect the expression of LC3, prostacyclin, Beclin-1, V-akt murine thymoma viral oncogene homolog (Akt), phosphorylated Akt, mTOR, and phosphorylated mTOR. Oil Red O staining revealed that AS-IV reduced intracellular lipid accumulation. Further, it increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in the cells. It also reduced the phosphorylation levels of Akt and mTOR and the levels of prostacyclin. However, the effects of AS-IV decreased with SC79 treatment. In addition, LC3Bâ +â BODIPY493/503 fluorescence double staining showed that AS-IV reduced intracellular lipid deposition levels by enhancing autophagy. AS-IV can reduce lipid aggregation in fatty liver cells, which can be related to enhanced hepatocyte autophagy by inhibiting the Akt/mTOR signaling pathway.
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Autofagia , Hígado Graso , Metabolismo de los Lípidos , Saponinas , Triterpenos , Animales , Humanos , Ratones , Autofagia/efectos de los fármacos , Compuestos Azo , Beclina-1/metabolismo , Hígado Graso/tratamiento farmacológico , Lípidos , Prostaglandinas I , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/metabolismo , Saponinas/farmacología , Serina-Treonina Quinasas TOR/efectos de los fármacos , Serina-Treonina Quinasas TOR/metabolismo , Triterpenos/farmacología , Metabolismo de los Lípidos/efectos de los fármacosRESUMEN
Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.
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Movimiento Celular , Dinaminas , Células Endoteliales de la Vena Umbilical Humana , Subunidad alfa del Factor 1 Inducible por Hipoxia , Ratones Endogámicos C57BL , Dinámicas Mitocondriales , Quinazolinonas , Especies Reactivas de Oxígeno , Neovascularización Retiniana , Factor A de Crecimiento Endotelial Vascular , Dinámicas Mitocondriales/efectos de los fármacos , Animales , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Humanos , Especies Reactivas de Oxígeno/metabolismo , Dinaminas/metabolismo , Dinaminas/antagonistas & inhibidores , Factor A de Crecimiento Endotelial Vascular/metabolismo , Quinazolinonas/farmacología , Neovascularización Retiniana/metabolismo , Neovascularización Retiniana/patología , Neovascularización Retiniana/tratamiento farmacológico , Movimiento Celular/efectos de los fármacos , Ratones , Proliferación Celular/efectos de los fármacos , Mitocondrias/metabolismo , Mitocondrias/efectos de los fármacos , AngiogénesisRESUMEN
Tetrachloroethylene ï¼PCEï¼ and trichloroethylene ï¼TCEï¼ are typical volatile halogenated organic compounds in groundwater that pose serious threats to the ecological environment and human health. To obtain an anaerobic microbial consortium capable of efficiently dechlorinating PCE and TCE to a non-toxic end product and to explore its potential in treating contaminated groundwaterï¼ an anaerobic microbial consortium W-1 that completely dechlorinated PCE and TCE to ethylene was obtained by repeatedly feeding PCE or TCE into the contaminated groundwater collected from an industrial site. The dechlorination rates of PCE and TCE were ï¼120.1 ±4.9ï¼ µmol·ï¼L·dï¼-1 and ï¼172.4 ±21.8ï¼ µmol·ï¼L·dï¼-1 in W-1ï¼ respectively. 16S rRNA gene amplicon sequencing and quantitative PCR ï¼qPCRï¼ showed that the relative abundance of Dehalobacter increased from 1.9% to 57.1%ï¼ with the gene copy number increasing by 1.7×107 copies per 1 µmol Cl- released when 98.3 µmol of PCE was dechlorinated to cis-1ï¼2-dichloroethylene ï¼cis-1ï¼2-DCEï¼. The relative abundance of Dehalococcoides increased from 1.1% to 53.8% when cis-1ï¼2-DCE was reductively dechlorinated to ethylene. The growth yield of Dehalococcoides gene copy number increased by 1.7×108 copies per 1 µmol Cl- released for the complete reductive dechlorination of PCE to ethylene. The results indicated that Dehalobacter and Dehalococcoides cooperated to completely detoxify PCE. When TCE was used as the only electron acceptorï¼ the relative abundance of Dehalococcoides increased from ï¼29.1 ±2.4ï¼% to ï¼7.7 ±0.2ï¼%ï¼ and gene copy number increased by ï¼1.9 ±0.4ï¼×108 copies per 1 µmol Cl- releasedï¼ after dechlorinating 222.8 µmol of TCE to ethylene. The 16S rRNA gene sequence of Dehalococcoides LWT1ï¼ the main functional dehalogenating bacterium in enrichment culture W-1ï¼ was obtained using PCR and Sanger sequencingï¼ and it showed 100% similarity with the 16S rRNA gene sequence of D. mccartyi strain 195. The anaerobic microbial consortium W-1 was also bioaugmented into the groundwater contaminated by TCE at a concentration of 418.7 µmol·L-1. The results showed that ï¼69.2 ±9.8ï¼% of TCE could be completely detoxified to ethylene within 28 days with a dechlorination rate of ï¼10.3 ±1.5ï¼ µmol·ï¼L·dï¼-1. This study can provide the microbial resource and theoretical guidance for the anaerobic microbial remediation in PCE or TCE-contaminated groundwater.
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Chloroflexi , Dicloruros de Etileno , Tetracloroetileno , Tricloroetileno , Humanos , Anaerobiosis , ARN Ribosómico 16S/genética , Etilenos , Dicloroetilenos , Biodegradación Ambiental , Chloroflexi/genéticaRESUMEN
Introduction: The World Health Organization (WHO) recommends vaccination against hepatitis B as soon as possible following birth for all infants, regardless of prematurity. Hepatitis B vaccination at birth is clearly justified, represents a crucial step in the global control of perinatally acquired hepatitis B and there are no safety concerns in infants born at term. However, there is limited information on the safety of the hepatitis B vaccine in preterm infants, whose immune responses and morbidity risk differ from those in infants born at term. Objectives: The objectives of this paper are to systematically review the literature regarding the safety and risk of adverse events following immunisation (AEFIs) associated with the administration of the hepatitis B vaccine (monovalent or as part of a combination vaccine) to preterm infants. Methods: We performed a search for relevant papers published between 1 January 2002 and 30 March 2023 in the Ovid MEDLINE, Ovid Embase, Cochrane Central Register of Controlled Trials and CINAHL Plus databases. Two authors independently reviewed and analysed each article to include in the systematic review. Narrative synthesis is presented. Results: Twenty-one relevant papers were identified and included in this systematic review. The vast majority of data pertained to multi-antigen (combination) vaccine preparations and vaccination episodes from 6 weeks of age onwards. We found no publications investigating the timing of the birth dose of the hepatitis B vaccine, and AEFI reporting was exclusively short-term (hours to days following administration). There was substantial variability in the reported rate of AEFIs between studies, ranging from 0% to 96%. Regardless of frequency, AEFIs were mostly minor and included injection site reactions, temperature instability and self-limiting cardiorespiratory events. Six studies reported serious adverse events (SAEs) such as the requirement for escalation of respiratory support. However, these occurred predominantly in high-risk infant populations and were rare (~1%). Using the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach, the certainty of evidence was assessed as very low. Conclusions: Despite substantial variability between the relatively small number of published studies in terms of cohort selection, definitions, vaccine preparations and reporting, hepatitis B-containing vaccines (mostly as combination vaccines) appear to be relatively well tolerated in preterm infants from 6 weeks of age. Research focusing on the safety of hepatitis B vaccine in preterm infants specifically within 7 days of birth is lacking, particularly regarding long-term morbidity risk. Further research in this area is required.
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Over the past decades, many forests have been converted to monoculture plantations, which might affect the soil microbial communities that are responsible for governing the soil biogeochemical processes. Understanding how reforestation efforts alter soil prokaryotic microbial communities will therefore inform forest management. In this study, the prokaryotic communities were comparatively investigated in a secondary Chinese fir forest (original) and a reforested Chinese fir plantation (reforested from a secondary Chinese fir forest) in Southern China. The results showed that reforestation changed the structure of the prokaryotic community: the relative abundances of important prokaryotic families in soil. This might be caused by the altered soil pH and organic matter content after reforestation. Soil profile layer depth was an important factor as the upper layers had a higher diversity of prokaryotes than the lower ones (p < 0.05). The composition of the prokaryotic community presented a seasonality characteristic. In addition, the results showed that the dominant phylum was Acidobacteria (58.86%) with Koribacteraceae (15.38%) as the dominant family in the secondary Chinese fir forest and the reforested plantation. Furthermore, soil organic matter, total N, hydrolyzable N, and NH4+-N were positively correlated with prokaryotic diversity (p < 0.05). Also, organic matter and NO3--N were positively correlated to prokaryotic abundance (p < 0.05). This study demonstrated that re-forest transformation altered soil properties, which lead to the changes in microbial composition. The changes in microbial community might in turn influence biogeochemical processes and the environmental variables. The study could contribute to forest management and policy-making.
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Tumor microenvironment (TME)-induced nanocatalytic therapy is a promising strategy for cancer treatment, but the low catalytic efficiency limits its therapeutic efficacy. Single-atom catalysts (SACs) are a new type of nanozyme with incredible catalytic efficiency. Here, a single-atom manganese (Mn)-N/C nanozyme is constructed. Mn-N/C catalyzes the conversion of cellular H2O2 to âOH through a Fenton-like reaction and enables the sufficient generation of reactive oxygen species (ROS), which induces immunogenic cell death (ICD) of tumor cells and significantly promotes CD8+T anti-tumor immunity. Moreover, RNA sequencing analysis reveals that Mn-N/C treatment activates type I interferon (IFN) signaling, which is critical for Mn-N/C-mediated anti-tumor immune response. Mechanistically, the release of cytosolic DNA and Mn2+ triggered by Mn-N/C collectively activates the cGAS-STING pathway, subsequently stimulating type I IFN induction. A highly efficient single-atom nanozyme, Mn-N/C, which enhances anti-tumor immune response and exhibits synergistic therapeutic effects when combined with the anti-PD-L1 blockade, is proposed.