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Very preterm (VPT) infants (born at less than 32 weeks gestational age) are at high risk for various adverse neurodevelopmental deficits. Unfortunately, most of these deficits cannot be accurately diagnosed until the age of 2-5 years old. Given the benefits of early interventions, accurate diagnosis and prediction soon after birth are urgently needed for VPT infants. Previous studies have applied deep learning models to learn the brain structural connectome (SC) to predict neurodevelopmental deficits in the preterm population. However, none of these models are specifically designed for graph-structured data, and thus may potentially miss certain topological information conveyed in the brain SC. In this study, we aim to develop deep learning models to learn the SC acquired at term-equivalent age for early prediction of neurodevelopmental deficits at 2 years corrected age in VPT infants. We directly treated the brain SC as a graph, and applied graph convolutional network (GCN) models to capture complex topological information of the SC. In addition, we applied the supervised contrastive learning (SCL) technique to mitigate the effects of the data scarcity problem, and enable robust training of GCN models. We hypothesize that SCL will enhance GCN models for early prediction of neurodevelopmental deficits in VPT infants using the SC. We used a regional prospective cohort of â¼280 VPT infants who underwent MRI examinations at term-equivalent age from the Cincinnati Infant Neurodevelopment Early Prediction Study (CINEPS). These VPT infants completed neurodevelopmental assessment at 2 years corrected age to evaluate cognition, language, and motor skills. Using the SCL technique, the GCN model achieved mean areas under the receiver operating characteristic curve (AUCs) in the range of 0.72â¼0.75 for predicting three neurodevelopmental deficits, outperforming several competing models. Our results support our hypothesis that the SCL technique is able to enhance the GCN model in our prediction tasks.
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Conectoma , Recien Nacido Prematuro , Lactante , Recién Nacido , Humanos , Preescolar , Estudios Prospectivos , Encéfalo/diagnóstico por imagen , Recién Nacido de muy Bajo PesoRESUMEN
The ultrasensitive DNA methyltransferase (Dam MTase) assay is of high significance for biomedical research and clinical diagnosis because of its profound effect on gene regulation. However, detection sensitivity is still limited by shortcomings, including photobleaching and weak signal intensities of conventional fluorophores at low concentrations. Plasmonic nanostructures with ultrastrong electromagnetic fields and fluorescence enhancement capability that can overcome these intrinsic defects hold great potential for ultrasensitive bioanalysis. Herein, a silica-coated gold nanostars (Au NSTs@SiO2)-based plasmon-enhanced fluorescence (PEF) probe with 20 "hot spots" was developed for ultrasensitive detection of Dam MTase. Here, the Dam Mtase assay was achieved by detecting the byproduct PPi of the rolling circle amplification reaction. It is worth noting that, benefiting from the excellent fluorescence enhancement capability of Au NSTs originating from their 20 "hot spots", the detection limit of Dam Mtase was reduced by nearly 105 times. Moreover, the proposed Au NST-based PEF probe enabled versatile evaluation of Dam MTase inhibitors as well as endogenous Dam MTase detection in GW5100 and JM110 Escherichia coli cell lysates, demonstrating its potential in biomedical analysis.
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Técnicas Biosensibles , Metiltransferasa de ADN de Sitio Específico (Adenina Especifica) , Metiltransferasa de ADN de Sitio Específico (Adenina Especifica)/análisis , Dióxido de Silicio , Oro/química , Metilasas de Modificación del ADN , Escherichia coli , Colorantes Fluorescentes/química , ADN , Sondas de ADN/químicaRESUMEN
BACKGROUND: Cancer stem cells (CSCs) in triple-negative breast cancer (TNBC) are recognized as a highly challenging subset of cells, renowned for their heightened propensity for relapse and unfavorable prognosis. Monensin, an ionophoric antibiotic, has been reported to exhibit significant therapeutic efficacy against various cancers, especially CSCs. Erlotinib is classified as one of the EGFR-TKIs and has been previously identified as a promising therapeutic target for TNBC. Our research aims to assess the effectiveness of combination of monensin and erlotinib as a potential treatment strategy for TNBC. METHODS: The combination of monensin and erlotinib was assessed for its potential anticancer activity through various in vitro assays, including cytotoxicity assay, colony formation assay, wound healing assay, transwell assay, mammosphere formation assay, and proportion of CSCs assay. Additionally, an in vivo study using tumor-bearing nude mice was conducted to evaluate the inhibitory effect of the monensin and erlotinib combination on tumor growth. RESULTS: The results indicated that combination of monensin with erlotinib synergistically inhibited cell proliferation, the migration rate, the invasion ability and decreased the CSCs proportion, and CSC markers SOX2 and CD133 in vivo and in vitro. Furthermore, the primary proteins involved in the signaling pathways of the EGFR/ERK and PI3K/AKT are simultaneously inhibited by the combination treatment of monensin and erlotinib in vivo and in vitro. CONCLUSIONS: The simultaneous inhibition of the EGFR/ERK and PI3K/AKT/mTOR signaling pathways by the combination of monensin and erlotinib exhibited a synergistic effect on suppressing tumor proliferation and cancer cell stemness in TNBC.
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Proliferación Celular , Sinergismo Farmacológico , Receptores ErbB , Clorhidrato de Erlotinib , Monensina , Células Madre Neoplásicas , Transducción de Señal , Neoplasias de la Mama Triple Negativas , Ensayos Antitumor por Modelo de Xenoinjerto , Clorhidrato de Erlotinib/farmacología , Clorhidrato de Erlotinib/administración & dosificación , Neoplasias de la Mama Triple Negativas/tratamiento farmacológico , Neoplasias de la Mama Triple Negativas/patología , Neoplasias de la Mama Triple Negativas/metabolismo , Humanos , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/metabolismo , Animales , Receptores ErbB/metabolismo , Receptores ErbB/antagonistas & inhibidores , Femenino , Ratones , Transducción de Señal/efectos de los fármacos , Monensina/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/metabolismo , Movimiento Celular/efectos de los fármacos , Protocolos de Quimioterapia Combinada Antineoplásica/farmacología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Ratones DesnudosRESUMEN
Hepatocellular carcinoma (HCC) stands as one of the most malignant tumors characterized by poor prognosis and high mortality rates. Emerging evidence underscores the crucial role of the B7 protein family in various cancers, including HCC. However, the involvement of the human endogenous retrovirus H long-terminal repeat-associated protein 2 (HHLA2, or B7-H5) in HCC remains unclear. Immunohistochemistry was employed to assess the differential expression of HHLA2 between HCC and normal liver tissues. A battery of assays, including CCK8, EdU, tablet clone-forming, Transwell, and wound healing assays, were conducted to elucidate the function and potential mechanisms of HHLA2 in the malignant biological behaviors of HCC. Additionally, a xenograft mouse model was established to evaluate the tumorigenicity of hepatoma cell lines exhibiting different HHLA2 expression levels in vivo. Western blot analysis was used to analyze HHLA2, secretory phosphoprotein 1 (SPP1), and PI3K/AKT/mTOR levels. HHLA2 exhibited elevated expression in HCC tissues, correlating with poor tumor differentiation and shortened overall survival in HCC patients. In vitro experiments demonstrated that HHLA2 overexpression (OE) promoted the proliferation, migration, and invasion of hepatoma cells, while in vivo experiments revealed that HHLA2 OE enhanced HCC tumor growth. Conversely, inhibition of HHLA2 expression yielded the opposite effect. Downregulation of SPP1 inhibited the proliferation, migration, and invasion induced by HHLA2 OE, and this effect was linked to the PI3K/AKT/mTOR signaling pathway. Our findings indicate that HHLA2 promotes the proliferation, migration, and invasion of hepatoma cells via the SPP1/PI3K/AKT signaling pathway, establishing it as a potential therapeutic target for HCC.
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Carcinoma Hepatocelular , Movimiento Celular , Proliferación Celular , Neoplasias Hepáticas , Invasividad Neoplásica , Osteopontina , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Humanos , Carcinoma Hepatocelular/patología , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/patología , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Animales , Fosfatidilinositol 3-Quinasas/metabolismo , Ratones , Masculino , Femenino , Osteopontina/metabolismo , Osteopontina/genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Persona de Mediana Edad , Ratones Desnudos , Pronóstico , Ensayos Antitumor por Modelo de Xenoinjerto , Ratones Endogámicos BALB C , InmunoglobulinasRESUMEN
The primary cell wall is a fundamental plant constituent that is flexible but sufficiently rigid to support the plant cell shape. Although many studies have demonstrated that reactive oxygen species (ROS) serve as important signaling messengers to modify the cell wall structure and affect cellular growth, the regulatory mechanism underlying the spatial-temporal regulation of ROS activity for cell wall maintenance remains largely unclear. Here, we demonstrate the role of the Arabidopsis (Arabidopsis thaliana) multicopper oxidase-like protein skewed 5 (SKU5) and its homolog SKU5-similar 1 (SKS1) in root cell wall formation through modulating ROS homeostasis. Loss of SKU5 and SKS1 function resulted in aberrant division planes, protruding cell walls, ectopic deposition of iron, and reduced nicotinamide adeninedinucleotide phosphate (NADPH) oxidase-dependent ROS overproduction in the root epidermis-cortex and cortex-endodermis junctions. A decrease in ROS level or inhibition of NADPH oxidase activity rescued the cell wall defects of sku5 sks1 double mutants. SKU5 and SKS1 proteins were activated by iron treatment, and iron over-accumulated in the walls between the root epidermis and cortex cell layers of sku5 sks1. The glycosylphosphatidylinositol-anchored motif was crucial for membrane association and functionality of SKU5 and SKS1. Overall, our results identified SKU5 and SKS1 as regulators of ROS at the cell surface for regulation of cell wall structure and root cell growth.
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Proteínas de Arabidopsis , Arabidopsis , Pared Celular , Raíces de Plantas , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Pared Celular/metabolismo , Hierro/metabolismo , NADPH Oxidasas/genética , NADPH Oxidasas/metabolismo , Oxidación-Reducción , Oxidorreductasas/genética , Oxidorreductasas/metabolismo , Especies Reactivas de Oxígeno/metabolismoRESUMEN
Central precocious puberty (CPP) refers to a syndrome of early puberty initiation with a characteristic increase in the release of gonadotropin-releasing hormone (GnRH); therefore, it is also called GnRH-related precocious puberty. About a quarter of idiopathic central precocious puberty (ICPP) may be familial. Studies suggest that mutations of makorin ring finger protein 3 (MKRN3) can cause familial central precocious puberty (FCPP). In this report, we describe a Chinese female patient carrying a novel MKRN3 variant (c.980G>A/p.Arg327His) and presenting the CPP phenotype. This novel variant attenuated its own ubiquitination, degradation, and inhibition on the transcriptional and translational activity of GNRH1, which was verified through functional tests. We can consider this variant as a loss-of-function mutation, which subsides the inhibition of GnRH1-related signaling and gives rise to GnRH-related precocious puberty.
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Pubertad Precoz , Humanos , Femenino , Pubertad Precoz/genética , Mutación Missense/genética , Ubiquitina-Proteína Ligasas/genética , Hormona Liberadora de Gonadotropina/genética , Mutación , PubertadRESUMEN
We herein present a study on the Ag(I)-mediated semipinacol rearrangement of iododifluorohomoallyl alcohols, the resulting allylic difluoromethyl ketones underwent oxidative allylic C-H esterification under palladium catalysis in the absence of external ligand. This process yielded a range of difluoromethyl ketones derived from allyl esters in a single operation. The reaction features broad scope of o-nitrobenzoic acids and homoallylic iododifluoroalcohols affording the targeted molecules in synthetically useful yields. Control experiments illustrated that the silver salt acted as not only a Lewis acid to promote the cleavage of a C-I bond and furnish the semipinacol rearrangement but also a co-oxidant in the catalytic cycle for the allylic C-H esterification.
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BACKGROUND: In the era of combination therapy, there has been limited research on body composition. Specific body composition, such as sarcopenia, possesses the potential to serve as a predictive biomarker for toxic effects and clinical response in patients with urothelial carcinoma (UC) undergoing tislelizumab combined with gemcitabine and cisplatin (T + GC). MATERIALS AND METHODS: A total of 112 UC patients who received T + GC were selected at the Affiliated Hospital of Xuzhou Medical University from April 2020 to January 2023. Baseline patient characteristics and detailed hematological parameters were collected using the electronic medical system and laboratory examinations. The computed tomography images of patients were analyzed to calculate psoas muscle mass index (PMI). We evaluated the association between sarcopenia (PMI < 4.5 cm2/m2 in men; PMI < 3.3 cm2/m2 in women) and both hematological toxicity and tumor response. RESULTS: Overall, of the 112 patients (65.2% male, median age 56 years), 43 (38.4%) were defined as sarcopenia. Patients with sarcopenia were notably older (p = 0.037), more likely to have hypertension (p = 0.009), and had poorer ECOG-PS (p = 0.027). Patients with sarcopenia were more likely to develop leukopenia (OR 2.969, 95% CI 1.028-8.575, p = 0.044) after receiving at least two cycles of T + GC. However, these significant differences were not observed in thrombocytopenia and anemia. There were no significant differences in the tumor response and grade 3-4 hematological toxicity between patients with sarcopenia and those without sarcopenia. CONCLUSIONS: Patients with sarcopenia were more likely to develop leukopenia after receiving T + GC. There were no notable alterations observed in relation to anemia or thrombocytopenia. No significant difference was found between the sarcopenia group and non-sarcopenia group in terms of tumor response and grade 3-4 hematological toxicity.
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Anticuerpos Monoclonales Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Desoxicitidina , Gemcitabina , Leucopenia , Sarcopenia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Sarcopenia/inducido químicamente , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Cisplatino/uso terapéutico , Leucopenia/inducido químicamente , Desoxicitidina/análogos & derivados , Desoxicitidina/administración & dosificación , Desoxicitidina/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Anciano , Anticuerpos Monoclonales Humanizados/efectos adversos , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Estudios Retrospectivos , Carcinoma de Células Transicionales/tratamiento farmacológico , Carcinoma de Células Transicionales/complicaciones , Neoplasias de la Vejiga Urinaria/tratamiento farmacológico , Neoplasias de la Vejiga Urinaria/patología , Neoplasias de la Vejiga Urinaria/complicaciones , Adulto , Neoplasias Urológicas/tratamiento farmacológico , Neoplasias Urológicas/complicaciones , Neoplasias Urológicas/patologíaRESUMEN
Acute lung injury (ALI) is a respiratory failure disease associated with high mortality rates in patients. The primary pathological damage is attributed to the excessive release of pro-inflammatory mediators in pulmonary tissue. However, specific therapy for ALI has not been developed. In this study, a series of novel ferulic acid-parthenolide (FA-PTL) and ferulic acid-micheliolide (FA-MCL) hybrid derivatives were designed, synthesized, and evaluated for their anti-inflammatory activities in vitro. Compounds 2, 4, and 6 showed pronounced anti-inflammatory activity against LPS-induced expression of pro-inflammatory cytokines in vitro. Importantly, compound 6 displayed good water solubility, and treatment of mice with compound 6 (10 mg/kg) significantly prevented weight loss and ameliorated inflammatory cell infiltration and edema in lung tissue, as well as improving the alveolar structure. These results suggest that compound 6 (((1aR,7aS,8R,10aS,10bS,E)-8-((dimethylamino)methyl)-1a-methyl-9-oxo-1a,2,3,6,7,7a,8,9,10a,10b-decahydrooxireno[2',3':9,10]cyclodeca[1,2-b]furan-5-yl)methyl (E)-3-(4-hydroxy-3-methoxyphenyl)acrylate 2-hydroxypropane-1,2,3-tricarboxylate) might be considered as a lead compound for further evaluation as a potential anti-ALI agent.
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Lesión Pulmonar Aguda , Ácidos Cumáricos , Sesquiterpenos , Humanos , Animales , Ratones , Lipopolisacáridos/efectos adversos , Antiinflamatorios/farmacología , Pulmón/metabolismo , Lesión Pulmonar Aguda/tratamiento farmacológico , Citocinas/metabolismo , Sesquiterpenos/farmacología , Lactonas/farmacologíaRESUMEN
In plants, thousands of nucleus-encoded proteins translated in the cytosol are sorted to chloroplasts and mitochondria by binding to specific receptors of the TOC (translocon on the outer chloroplast membrane) and the TOM (translocon on the outer mitochondrial membrane) complexes for import into those organelles. The degradation pathways for these receptors are unclear. Here, we discovered a converged ubiquitin-proteasome pathway for the degradation of Arabidopsis thaliana TOC and TOM tail-anchored receptors. The receptors are ubiquitinated by E3 ligase(s) and pulled from the outer membranes by the AAA+ adenosine triphosphatase CDC48, after which a previously uncharacterized cytosolic protein, transmembrane domain (TMD)-binding protein for tail-anchored outer membrane proteins (TTOP), binds to the exposed TMDs at the C termini of the receptors and CDC48, and delivers these complexes to the 26S proteasome.
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Proteínas de Arabidopsis , Arabidopsis , Complejo de la Endopetidasa Proteasomal , Ubiquitina , Complejo de la Endopetidasa Proteasomal/metabolismo , Proteínas de Arabidopsis/metabolismo , Arabidopsis/metabolismo , Ubiquitina/metabolismo , Proteolisis , Proteína que Contiene Valosina/metabolismoRESUMEN
BACKGROUND: Massa Medicata Fermentata (MMF) is one of the most commonly used traditional fermented Chinese medicines. MMF is widely used for the treatment of digestive diseases such as dyspepsia and flatulence in traditional Chinese medicine (TCM). However, the therapeutic mechanism of MMF is not well understood. METHOD: In this study, SD rats received 0.1% iodoacetamide either alone or in combination with water platform sleep deprivation to induce functional dyspepsia and were administered MMF (1 or 3 g/kg/d, ig), mosapride citrate (Mosa., 2 mg/kg/d, ig) or saline for 21 days. After treatment, the sucrose preferences and gastric emptying rates of the rats were assessed; HE staining was used to detect the pathological changes in the rat duodenum; ELISA kits were used to detect motilin (MTL) in the rat duodenum and the serum contents of Interferon-λ (IFN-λ), Interleukin 6 (IL-6), and Tumor Necrosis Factor-α (TNF-α). An approach based on 16S rDNA amplicon sequencing was utilized to explore the intestinal microflora in the colon contents of rats and the metabolism of the microflora to assess the potential mechanisms of MMF in ameliorating functional dyspepsia (FD). In addition, gas chromatography-mass spectrometry (GC/MS) was used to detect changes in short fatty acids (SCFAs) in the colon contents of rats. RESULTS: MMF reduced the serum levels of TNF-α, and IFN-λ, improved the morphology of duodenal intestinal villi and ameliorated intestinal mucosal lamina propria injury in FD rats, and the sucrose preference increased and the gastric emptying rate decreased in FD rats. MMF alleviated intestinal microflora disturbance and exerted a regulatory effect on Bacteroidetes, Proteobacteria, and Firmicutes, reduced total SCAFs, Butyric Acid, Propionic acid-2-methyl, Butanoic Acid-3-methyl, and Hexanoic acid. CONCLUSIONS: These results showed that the effect of MMF on the intestinal flora and its metabolites may provide a new treatment strategy for FD.
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Dispepsia , Microbioma Gastrointestinal , Ratas , Animales , Dispepsia/tratamiento farmacológico , Dispepsia/microbiología , Microbioma Gastrointestinal/genética , Factor de Necrosis Tumoral alfa/metabolismo , Ratas Sprague-DawleyRESUMEN
In response to the problem of complex interaction between oil and water in the oil-water interface, especially heavy oil and water, this study investigated the effects of complex surfactants on the interaction of two phases and their aggregation characteristics by molecular dynamics simulation. The results showed that increasing the content of sodium lauryl polyether carboxylate (AEC-9Na) was beneficial to the coordination between it and alkyl glycoside (APG-10), improved the interfacial activity, and enhanced the interfacial stability of the composite system, and the best effect was achieved when AEC-9Na:APG-10 = 8:2. The thickness of the oil and water film on the oil-water interface was irregular. When the concentration of AEC-9Na was lower than that of APG-10, the total thickness of the interfacial film (ttotal) first increased. When the content of AEC-9Na is higher, a large number of sodium ions were adsorbed near the -COO- group of AEC-9Na, which will polarize out of the hydration layer structure and attract water molecules from the second hydration layer on the heavy oil surface to the first hydration layer through electrostatic interaction. Then, the thickness of the interface film was compressed, and the interface film was reduced. When the ratio increased to 10:0, the oil and water phase competed to adsorb surfactant molecules, and the headgroup tended to lay on the interface. Moreover, the hydrophilicity of the surfactant layer was weakened, and the thickness of the water film decreased. The distribution of surfactant was looser than 8:2, the light components of heavy oil molecules (saturated and aromatic hydrocarbons) entered the gap between surfactants in large quantities, and the hydrophobic tail chain tended to be laid on the oil-water interface. The oleophilicity of the surfactant layer increased, and the thickness of the oil film remarkably increased, so the total thickness of the interface film increased again.
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Anlotinib have shown certain therapeutic effects of renal cell carcinoma (RCC), but drug resistance during treatment leads to the fact that the therapeutic effect is unsatisfactory. Herein, we investigated the tumor immune microenvironment about resistance mechanisms when application of Anlotinib and further improved its therapeutic effect. Our results showed that Anlotinib suppressed cell proliferation and promoted cell apoptosis in RCC cells. Meanwhile, the significantly up-regulated expression of PD-L1 was observed in Anlotinib-treated RCC cells by the concentration and time-dependent manner. Further study showed that Anlotinib-induced PD-L1 expression was regulated by autocrine IL-6 mediated JAK2/STAT3 signaling pathways. Interestingly, Anlotinib combined with PD-L1 blockade increased the infiltration of IFN-γ+CD8+ T cells and natural killer (NK) cells, also decreased the quantity of Treg cells and MDSCs in vivo. Likewise, the therapy above showed significantly synergistic therapeutic effect as demonstrated by reduced tumor volume and weight. These results indicated that the drug resistance might be attributed to the Anlotinib induced-PD-L1 mediated immunosuppression in renal cancer treatment. Anlotinib combined anti-PDL-1 treatment exerts the potential anti-tumor effect by promoting the induction and activation of immune killer cells. The therapeutic strategy of Anlotinib combined anti-PDL-1 could be a potential and promising approach for the therapy of renal cancer or other malignant tumors.
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Carcinoma de Células Renales , Neoplasias Renales , Antígeno B7-H1/metabolismo , Linfocitos T CD8-positivos , Carcinoma de Células Renales/tratamiento farmacológico , Línea Celular Tumoral , Humanos , Indoles , Neoplasias Renales/tratamiento farmacológico , Quinolinas , Microambiente TumoralRESUMEN
INTRODUCTION: As a folk herbal medicine, Trillium tschonoskii has been used for thousands of years. However, due to the complexity of the chemical constituents of this herb, few investigations have acquired a comprehensive understanding of its quality markers. OBJECTIVE: This study was conducted to characterise the chemical composition of T. tschonoskii and identify its potential quality markers. MATERIAL AND METHODS: A systematic analytical method based on ultra-high-performance liquid chromatography coupled with mass spectrometry (UHPLC-MS) was used to characterise the constituents of T. tschonoskii. Multivariate statistical analysis was performed to investigate the chemical differences between different tissues, as well as the relationship between chemical compositions and habitats. The potential quality markers were predicted via network pharmacology and molecular docking, then confirmed by cellular assays. RESULTS: A total of 77 compounds were co-isolated and identified, and among them, 26 were discovered from the genus Trillium for the first time. Ten batches of roots/rhizomes were explicitly clustered into five groups according to the climate types of the habitats, and the clusters of the fruits and roots/rhizomes from the same plants were independent due to the significant difference in chemical composition. Diosgenin had a good docking affinity with the relevant targets within the IL-17 pathway and cytokine pathway and could significantly inhibit TNF-α expression in hypoxic brain microvascular endothelial cells (BMECs). CONCLUSION: This is the first study to establish the chemical composition profile of T. tschonoskii by UHPLC-MS systematically, and diosgenin was confirmed to be a potential quality marker of T. tschonoskii for the treatment of headaches.
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Diosgenina , Medicamentos Herbarios Chinos , Trillium , Trillium/química , Cromatografía Líquida de Alta Presión , Farmacología en Red , Células Endoteliales , Simulación del Acoplamiento Molecular , Espectrometría de MasasRESUMEN
Obtaining solutions to optimal transportation (OT) problems is typically intractable when marginal spaces are continuous. Recent research has focused on approximating continuous solutions with discretization methods based on i.i.d. sampling, and this has shown convergence as the sample size increases. However, obtaining OT solutions with large sample sizes requires intensive computation effort, which can be prohibitive in practice. In this paper, we propose an algorithm for calculating discretizations with a given number of weighted points for marginal distributions by minimizing the (entropy-regularized) Wasserstein distance and providing bounds on the performance. The results suggest that our plans are comparable to those obtained with much larger numbers of i.i.d. samples and are more efficient than existing alternatives. Moreover, we propose a local, parallelizable version of such discretizations for applications, which we demonstrate by approximating adorable images.
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Headache is a common clinical complication of ischemic stroke. As a precursor of stroke, headache occurs repeatedly in the convalescent period of ischemic stroke, leading to secondary stroke and seriously hindering patients' rehabilitation. Currently, it is believed that the pathogenesis of ischemic stroke-related headache is associated with the abnormal release of vasoactive substances, high platelet aggregation, and stimulation of intracranial pain-sensitive structures. The active ingredients in traditional Chinese medicines(TCM) with the effects of activating blood to resolve stasis and clearing heat to release exterior can protect brain tissue and relieve headache by reducing the release of inflammatory cytokines, alleviating antioxidant stress, inhibiting neuronal apoptosis and so on. This paper introduces the research progress in the potential mechanism and TCM treatment of ischemic stroke-related headache, aiming to provide reference for further research and drug development of this complication.
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Isquemia Encefálica , Medicamentos Herbarios Chinos , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Isquemia Encefálica/complicaciones , Isquemia Encefálica/tratamiento farmacológico , Medicina Tradicional China , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Cefalea/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
Isoprene is the most abundant precursor of global secondary organic aerosol (SOA). The epoxide pathway plays a critical role in isoprene SOA (iSOA) formation, in which isoprene epoxydiols (IEPOX) and/or hydroxymethyl-methyl-α-lactone (HMML) can react with nucleophilic sulfate and water producing isoprene-derived organosulfates (iOSs) and oxygen-containing tracers (iOTs), respectively. This process is complicated and highly influenced by anthropogenic emissions, especially in the polluted urban atmospheres. In this study, we took a 1-year measurement of the paired iOSs and iOTs formed through the IEPOX and HMML pathways at the three urban sites from northern to southern China. The annual average concentrations of iSOA products at the three sites ranged from 14.6 to 36.5 ng m-3. We found that the nucleophilic-addition reaction of isoprene epoxides with water dominated over that with sulfate in the polluted urban air. A simple set of reaction rate constant could not fully describe iOS and iOT formation everywhere. We also found that the IEPOX pathway was dominant over the HMML pathway over urban regions. Using the kinetic data of IEPOX to estimate the reaction parameters of HMML will cause significant underestimation in the importance of HMML pathway. All these findings provide insights into iSOA formation over polluted areas.
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Contaminantes Atmosféricos , Compuestos Epoxi , Aerosoles/análisis , Butadienos , Hemiterpenos , Pentanos , Sulfatos , AguaRESUMEN
Ectodysplasin A (EDA), a ligand of the TNF family, plays an important role in maintaining the homeostasis of the ocular surface. EDA is necessary for the development of the meibomian gland, the lacrimal gland, as well as the proliferation and barrier function of the corneal epithelium. The mutation of EDA can induce the destruction of the ocular surface resulting in keratopathy, abnormality of the meibomian gland and maturation of the lacrimal gland. Experimental animal studies showed that a prenatal ultrasound-guided intra-amniotic injection or postnatal intravenous administration of soluble recombinant EDA protein can efficiently prevent the development of ocular surface abnormalities in EDA mutant animals. Furthermore, local application of EDA could restore the damaged ocular surface to some extent. Hence, a recombinant EDA-based therapy may serve as a novel paradigm to treat ocular surface disorders, such as meibomian gland dysfunction and corneal epithelium abnormalities.
Asunto(s)
Enfermedades de la Córnea , Epitelio Corneal , Aparato Lagrimal , Femenino , Animales , Embarazo , Ectodisplasinas/genética , Epitelio Corneal/metabolismo , Aparato Lagrimal/metabolismo , Enfermedades de la Córnea/metabolismo , HomeostasisRESUMEN
Subway carriages are enclosed for extended periods of time, with a high density of passengers. Providing a safe, healthy, and comfortable cabin environment is a great challenge, particularly during the COVID-19 pandemic. An increase in ventilation rate can potentially reduce infection probability, which may result in worsening environmental quality (e.g., thermal comfort) and larger energy consumption. Thus, exploring the trade-off among infection risk, environmental quality (with regard to ventilation, thermal comfort, and air quality), and energy consumption is important to optimize ventilation systems for carriages. The effect of different supply air parameters (e.g., velocity and temperature) and ventilation modes of mixing ventilation (MV) & Supply air from the Floor and Return air from the Ceiling (SFRC) was studied. The questionnaires were analyzed to explore passenger dissatisfaction with the carriage environment using a MV system. Simulations were performed to predict the velocity, temperature, and CO2 concentration fields. In addition, the comprehensive benefit was evaluated by analytic hierarchy process (AHP), based on infection probability from the revisited Wells-Riley equation, Air Diffusion Performance Index (ADPI), Predicted Mean Vote (PMV), Pollutant Removal Effectiveness (PRE) and energy consumption estimated by cooling load (Lcool). Compared with MV, the optimized SFRC provided softer draft sensation and decreased CO2 concentration by 42%. The SFRC achieved better comprehensive benefits, with an infection risk reduced to 0.4%, ADPI of 80%, PMV approaching zero, PRE up to 16, and energy efficiency increased by 30%. This work contributes to the optimal design of subway carriage ventilation systems in the post-epidemic era.
RESUMEN
Although most dramatic structural changes occur in the perinatal period, a growing body of evidences demonstrates that adolescence and early adulthood are also important for substantial neurodevelopment. We were thus motivated to explore brain development during puberty by evaluating functional connectivity network (FCN) differences between childhood and young adulthood using multi-paradigm task-based functional magnetic resonance imaging (fMRI) measurements. Different from conventional multigraph based FCN construction methods where the graph network was built independently for each modality/paradigm, we proposed a multigraph learning model in this work. It promises a better fitting to FCN construction by jointly estimating brain network from multi-paradigm fMRI time series, which may share common graph structures. To investigate the hub regions of the brain, we further conducted graph Fourier transform (GFT) to divide the fMRI BOLD time series of a node within the brain network into a range of frequencies. Then we identified the hub regions characterizing brain maturity through eigen-analysis of the low frequency components, which were believed to represent the organized structures shared by a large population. The proposed method was evaluated using both synthetic and real data, which demonstrated its effectiveness in extracting informative brain connectivity patterns. We detected 14 hub regions from the child group and 12 hub regions from the young adult group. We show the significance of these findings with a discussion of their functions and activation patterns as a function of age. In summary, our proposed method can extract brain connectivity network more accurately by considering the latent common structures between different fMRI paradigms, which are significant for both understanding brain development and recognizing population groups of different ages.