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Ten new drimane meroterpenoids talarines A-J (1-10), along with six known analogues (11-16), were isolated from desert soil-derived fungus Talaromyces pinophilus LD-7. Their 2D structures were elucidated by comprehensive interpretation of NMR and HRESIMS data. Electronic circular dichroism calculation was used to establish their absolute configurations. Compounds 2, 10, and 11 showed antiviral activities toward vesicular stomatitis virus with IC50 values of 18, 15, and 23 nM, respectively. The structure-bioactivity relationship indicated that chlorine substitution at C-5 contributed greatly to their antiviral activities. Finally, we identified a new halogenase outside the biosynthetic gene cluster, which was responsible for C-5 halogenation of the precursor isocoumarin 17 as a tailoring step in chlorinated meroterpenoids assembly.
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Antivirales , Talaromyces , Antivirales/farmacología , Antivirales/química , Antivirales/aislamiento & purificación , Vías Biosintéticas , Halogenación , Estructura Molecular , Sesquiterpenos Policíclicos/farmacología , Relación Estructura-Actividad , Talaromyces/química , Terpenos/farmacología , Terpenos/química , Terpenos/aislamiento & purificaciónRESUMEN
Steel fiber reinforced high-strength concrete (SFRHSC) is a composite material composed of cement, coarse aggregate, and randomly distributed short steel fibers. The excellent tensile strength of steel fiber can significantly improve the crack resistance and ductility of high-strength concrete (HSC). In this study, experimental and numerical investigations were performed to study the cyclic behavior of the HSC beam-column joint. Three SFRHSC and one HSC beam-column joint were prepared and tested under cyclic load. Two different volume ratios of steel fibers and three stirrups ratios in the joint core area were experimentally studied. After verification of the experimental results, numerical simulations were further carried out to investigate the influence of steel fibers volume ratio and stirrups ratio in the joint core area on the seismic performance. Evaluation of the hysteretic response, ductility, energy dissipation, stiffness, and strength degradation were the main aims of this study. Results indicate that the optimal volume fraction of steel fibers is 1.5%, and the optimal stirrups ratio in the joint core area is 0.9% in terms of the enhancement of the seismic performance of the SFRHSC beam-column joint.
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Instance segmentation of biological cells is important in medical image analysis for identifying and segmenting individual cells, and quantitative measurement of subcellular structures requires further cell-level subcellular part segmentation. Subcellular structure measurements are critical for cell phenotyping and quality analysis. For these purposes, instance-aware part segmentation network is first introduced to distinguish individual cells and segment subcellular structures for each detected cell. This approach is demonstrated on human sperm cells since the World Health Organization has established quantitative standards for sperm quality assessment. Specifically, a novel Cell Parsing Net (CP-Net) is proposed for accurate instance-level cell parsing. An attention-based feature fusion module is designed to alleviate contour misalignments for cells with an irregular shape by using instance masks as spatial cues instead of as strict constraints to differentiate various instances. A coarse-to-fine segmentation module is developed to effectively segment tiny subcellular structures within a cell through hierarchical segmentation from whole to part instead of directly segmenting each cell part. Moreover, a sperm parsing dataset is built including 320 annotated sperm images with five semantic subcellular part labels. Extensive experiments on the collected dataset demonstrate that the proposed CP-Net outperforms state-of-the-art instance-aware part segmentation networks.
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Espermatozoides , Humanos , Masculino , Procesamiento de Imagen Asistido por Computador/métodos , Algoritmos , Redes Neurales de la ComputaciónRESUMEN
BACKGROUND: To improve diagnostic precision in pediatric vertigo, particularly in Vestibular Migraine of Childhood (VMC), probable VMC (pVMC), Recurrent Vertigo of Childhood (RVC), and unspecified categories, by delineating clinical characteristics and prevalence to refine diagnostics and treatments. METHODS: Retrospective analysis of 102 pediatric patients (five to 18 years; 46 females, 56 males) at the Dizziness Center of the Otolaryngology Department in a tertiary-level hospital from January 2019 to December 2023. Patients were classified into VMC, pVMC, RVC, and indeterminate groups. Evaluations included audiometry and vestibular tests (video head impulse test [vHIT] or caloric testing), conducted in the audiology unit and vestibular testing laboratory. Data were analyzed using IBM SPSS 20.0. RESULTS: Diagnoses were 8.8% VMC, 31.4% pVMC, 51.0% RVC, and 8.8% indeterminate. Nausea and vomiting were common in VMC and pVMC; cochlear symptoms like tinnitus and hearing loss predominated in VMC. Although vestibular testing showed no significant group differences, VMC had more vHIT abnormalities and RVC had more caloric test anomalies. CONCLUSIONS: This study highlights the need for comprehensive diagnostics in pediatric vestibular disorders, revealing unique and overlapping traits across VMC, pVMC, and RVC. Insights call for further research to refine diagnostic criteria and improve treatment methods.
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Trastornos Migrañosos , Centros de Atención Terciaria , Vértigo , Humanos , Femenino , Masculino , Niño , Adolescente , Vértigo/diagnóstico , Vértigo/etiología , Trastornos Migrañosos/diagnóstico , Trastornos Migrañosos/complicaciones , Estudios Retrospectivos , Preescolar , Enfermedades Vestibulares/diagnóstico , Recurrencia , Pruebas de Función Vestibular , Prueba de Impulso Cefálico , Pruebas CalóricasRESUMEN
Oxidative stress plays a crucial role in increasing the risk of developing diabetic retinopathy (DR). The oxidative balance score (OBS) and the composite dietary antioxidant index (CDAI) are two tools for assessing the effects of diet and lifestyle on oxidative stress. The aim of this study was to investigate the association between OBS, CDAI and the occurrence of DR. After controlling for potential confounders, OBS was negatively associated with DR with an odds ratio (OR) of 0.976 and a 95% confidence interval (CI) of 0.956-0.996, suggesting that for every unit increase in OBS, the risk of DR was reduced by 2.4%. In contrast, the relationship between OBS and CDAI was not significant (P > 0.05), suggesting that it was OBS, not CDAI, that contributed to the reduced risk of diabetic retinopathy. After adjusting for potential confounders, OBS was negatively associated with DR (OR: 0.976; 95% CI 0.956-0.996), but this association was not found in CDAI (P > 0.05), suggesting that for every one-unit increase in OBS, there was a 2.4% reduction in the risk of developing DR. This study suggests that a diet and lifestyle high in OBS reduces the risk of developing DR, which provides a rationale for nutritional interventions to prevent DR.
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Antioxidantes , Retinopatía Diabética , Dieta , Estilo de Vida , Humanos , Retinopatía Diabética/etiología , Retinopatía Diabética/epidemiología , Retinopatía Diabética/prevención & control , Masculino , Femenino , Estudios Transversales , Antioxidantes/metabolismo , Persona de Mediana Edad , Estrés Oxidativo , Encuestas Nutricionales , Adulto , Anciano , Factores de Riesgo , Oportunidad RelativaRESUMEN
BACKGROUND: Organoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch-to-batch variations, lack of the native microenvironment and clinical applicability. MAIN BODY: The concept of organoids has derived patient-derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, 'tumour assembloids' inspired by cell-coculture technology have attracted attention to complement the current PDTO technology. High-quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour-infiltrating lymphocyte, T cell receptor-engineered T cell and chimeric antigen receptor-T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank. CONCLUSION: Fundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre-clinical immunotherapy screening using PDTOs will be beneficial to cancer patients. KEY POINTS: The current PDTO models have not yet constructed key cellular and non-cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.
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Inmunoterapia , Neoplasias , Organoides , Humanos , Inmunoterapia/métodos , Neoplasias/terapia , Neoplasias/tratamiento farmacológico , Neoplasias/inmunología , Organoides/efectos de los fármacos , Medicina de Precisión/métodosRESUMEN
Incrementing thermal conductivity in polymer composites through the incorporation of inorganic thermally conductive fillers is typically constrained by the requirement of high filler content. This necessity often complicates processing and adversely affects mechanical properties. This study presents the fabrication of a polystyrene (PS)/boron nitride (BN) composite exhibiting elevated thermal conductivity with a modest 10 wt% BN content, achieved through optimized compression molding. Adjustments to molding parameters, including molding-cycle numbers, temperature, and pressure, were explored. The molding process, conducted above the glass transition temperature of PS, facilitated orientational alignment of BN within the PS matrix predominantly in the in-plane direction. This orientation, achieved at low filler loading, resulted in a threefold enhancement of thermal conductivity following a single molding time. Furthermore, the in-plane alignment of BN within the PS matrix was found to intensify with increased molding time and pressure, markedly boosting the in-plane thermal conductivity of the PS/BN molded composites. Within the range of molding parameters examined, the highest thermal conductivity (1.6 W/m·K) was observed in PS/BN composites subjected to five molding cycles at 140 °C and 10 MPa, without compromising mechanical properties. This study suggests that compression molding, which allows low filler content and straightforward operation, offers a viable approach for the mass production of polymer composites with superior thermal conductivity.
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Purpose: COVID-19 is rampant throughout the world, which has caused great damage to human lives and seriously hindered the development of the global economy. Aiming at the treatment of SARS-CoV-2, in this study, we proposed a novel fenobody strategy based on ferritin (Fe) self-assembly technology. Methods: The neutralizing nanobody H11-D4 of SARS-CoV-2 fused to the C-terminus of end-modified human ferritin was expressed in E. coli and silkworm baculovirus expression systems. A large number of nanoparticles were successfully self-assembled in silkworms, while relatively few nanoparticles can be observed in the treated products from E. coli by electron microscopy. Subsequently, the fenobody's expression level and neutralizing activity were then evaluated. Results: The results showed that the IC50 of H11-D4 and fenobody Fe-H11-D4 expressed in E. coli were 171.1 nmol L-1 and 20.87 nmol L-1, respectively. However, the IC50 of Fe-HD11-D4 expressed in silkworms was 1.46 nmol L-1 showing better neutralization activity. Conclusion: Therefore, fenobodies can be well self-assembled in silkworm baculovirus expression system, and ferritin self-assembly technology can effectively improve nanobody neutralization activity.
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COVID-19 , SARS-CoV-2 , Humanos , Ferritinas , Escherichia coli , Anticuerpos Neutralizantes , Anticuerpos AntiviralesRESUMEN
The spike protein of SARS-CoV-2 as well as its receptor binding domain (RBD) has been demonstrated to be capable of activating the release of pro-inflammatory mediators in endothelial cells and immune cells such as monocytes. However, the effects of spike protein or its RBD on airway epithelial cells and mechanisms underlying these effects have not been adequately characterized. Here, we show that the RBD of spike protein alone can induce bronchial epithelial inflammation in a manner of ATP/P2Y2 dependence. Incubation of human bronchial epithelia with RBD induced IL-6 and IL-8 release, which could be inhibited by antibody. The incubation of RBD also up-regulated the expression of inflammatory indicators such as ho-1 and mkp-1. Furthermore, ATP secretion was observed after RBD treatment, P2Y2 receptor knock down by siRNA significantly suppressed the IL-6 and IL-8 release evoked by RBD. Additionally, S-RBD elevated the phosphorylation level of ERK1/2, and the effect that PD98059 can inhibit the pro-inflammatory cytokine release suggested the participation of ERK1/2. These novel findings provide new evidence of SARS-CoV-2 on airway inflammation and introduce purinergic signaling as promising treatment target.
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COVID-19 , Glicoproteína de la Espiga del Coronavirus , Humanos , Glicoproteína de la Espiga del Coronavirus/metabolismo , Sistema de Señalización de MAP Quinasas , Interleucina-6/metabolismo , Interleucina-8/metabolismo , Células Endoteliales/metabolismo , SARS-CoV-2/metabolismo , COVID-19/metabolismo , Transducción de Señal , Mucosa Respiratoria/metabolismo , Inflamación/metabolismo , Adenosina Trifosfato/farmacología , Adenosina Trifosfato/metabolismo , Unión ProteicaRESUMEN
The tumor microenvironment (TME) is critical for tumor growth and metastasis. The TME contains cancer-associated cells, tumor matrix, and tumor secretory factors. The fabrication of artificial tumors, so-called tumoroids, is of great significance for the understanding of tumorigenesis and clinical cancer therapy. The assembly of multiple tumor cells and matrix components through interdisciplinary techniques is necessary for the preparation of various tumoroids. This article discusses current methods for constructing tumoroids (tumor tissue slices and tumor cell co-culture) for pre-clinical use. This article focuses on the artificial matrix materials (natural and synthetic materials) and biofabrication techniques (cell assembly, bioengineered tools, bioprinting, and microfluidic devices) used in tumoroids. This article also points out the shortcomings of current tumoroids and potential solutions. This article aims to promotes the next-generation tumoroids and the potential of them in basic research and clinical application.
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Neoplasias , Humanos , Neoplasias/terapia , Técnicas de Cocultivo , Microambiente TumoralRESUMEN
BACKGROUND: Spodoptera litura is a harmful pest that feeds on more than 80 species of plants, and can be infected and killed by Spodoptera litura nucleopolyhedrovirus (SpltNPV). SpltNPV-C3 is a type C SpltNPV clone, that was observed and collected in Japan. Compared with type A or type B SpltNPVs, SpltNPV-C3 can cause the rapid mortality of S. litura larvae. METHODS: In this study, occlusion bodies (OBs) and occlusion-derived viruses (ODVs) of SpltNPV-C3 were purified, and OBs were observed by scanning electron microscopy (SEM). ODVs were observed under a transmission electron microscope (TEM). RESULTS: Both OBs and ODVs exhibit morphological characteristics typical of nucleopolyhedroviruses (NPVs).The genome of SpltNPV-C3 was sequenced and analyzed; the total length was 148,634 bp (GenBank accession 780,426,which was submitted as SpltNPV-II), with a G + C content of 45%. A total of 149 predicted ORFs were found. A phylogenetic tree of 90 baculoviruses was constructed based on core baculovirus genes. LCâMS/MS was used to analyze the proteins of SpltNPV-C3; 34 proteins were found in the purified ODVs, 15 of which were core proteins. The structure of the complexes formed by per os infectivity factors 1, 2, 3 and 4 (PIF-1, PIF-2, PIF-3 and PIF-4) was predicted with the help of the AlphaFold multimer tool and predicted conserved sequences in PIF-3. SpltNPV-C3 is a valuable species because of its virulence, and the analysis of its genome and proteins in this research will be beneficial for pest control efforts.
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Nucleopoliedrovirus , Proteoma , Animales , Nucleopoliedrovirus/genética , Spodoptera , Cromatografía Liquida , Filogenia , Espectrometría de Masas en Tándem , BaculoviridaeRESUMEN
Rhododendron, the largest genus of Ericaceae, consists of approximately 1000 species that are widely distributed in Europe, Asia, and North America but mainly exist in Asia. Rhododendron plants have not only good ornamental and economic value but also significant medicinal potential. In China, many Rhododendron plants are used as traditional Chinese medicine or ethnic medicine for the treatment of respiratory diseases, pain, bleeding and inflammation. Rhododendron is known for its abundant metabolites, especially diterpenoids. In the past 13 years, a total of 610 chemical constituents were reported from Rhododendron plants, including 222 diterpenoids, 122 triterpenoids, 103 meroterpenoids, 71 flavonoids and 92 other constituents (lignans, phenylpropanoids, phenolic acids, monoterpenoids, sesquiterpenoids, coumarins, steroids, fatty acids). Moreover, the bioactivities of various extracts and isolates, both in vitro and in vivo, were also investigated. Our review summarized the research progress of Rhododendron regarding traditional uses, phytochemistry and pharmacology in the past 13 years (2010 to December 2022), which will provide new insight for prompting further research on Rhododendron application and drug development.
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Diterpenos , Rhododendron , Fitoterapia , Etnofarmacología , Medicina Tradicional , Fitoquímicos/farmacología , Fitoquímicos/uso terapéutico , Extractos Vegetales/farmacologíaRESUMEN
Background: Vertigo and hearing loss are both prevalent in the elderly. This study retrospectively analyzed hearing test results from elderly patients experiencing vertigo and dizziness at ENT outpatient over a 10-year period, in order to study the patterns of hearing loss in this patient population. Methods: Nine thousand three hundred eighty four patients over 50 years old underwent retrospective collection and screening of outpatient diagnosis, pure tone audiometry, acoustic immittance measurement (tympanogram) and auditory brainstem response (ABR) test. The patient's audiograms are divided into 7 subtypes according to a set of fixed criteria. Meanwhile, K-Means clustering analysis method was used to classify the audiogram. Results: The Jerger classification of tympanogram in elderly patients with vertigo and dizziness showed the majority falling under type A. The leading audiogram shapes were flat (27.81% in right ear and 26.89% in left ear), high-frequency gently sloping (25.97% in right ear and 27.34% in left ear), and high-frequency steeply sloping (21.60% in right ear and 22.53% in left ear). Meniere's disease (MD; 30.87%), benign recurrent vertigo (BRV; 19.07%), and benign paroxysmal positional vertigo (BPPV; 15.66%) were the most common etiologies in elderly vestibular diseases. We observed statistically significant differences in hearing thresholds among these vestibular diseases (P < 0.001). K-Means clustering analysis suggested that the optimal number of clusters was three, with sample sizes for the three clusters being 2,747, 2,413, and 4,139, respectively. The ANOVA statistical results of each characteristic value showed P < 0.001. Conclusion: The elderly patients often have mild to moderate hearing loss as a concomitant symptom with vertigo. Female patients have better hearing thresholds than males. The dominant audiometric shapes in this patient population were flat, high-frequency gently sloping, and high-frequency steeply sloping according to a set of fixed criteria. This study highlights the need for tailored strategies in managing hearing loss in elderly patients with vertigo and dizziness.
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Cell death is a fundamental physiological process in all living organisms. Processes such as embryonic development, organ formation, tissue growth, organismal immunity, and drug response are accompanied by cell death. In recent years with the development of electron microscopy as well as biological techniques, especially the discovery of novel death modes such as ferroptosis, cuprotosis, alkaliptosis, oxeiptosis, and disulfidptosis, researchers have been promoted to have a deeper understanding of cell death modes. In this systematic review, we examined the current understanding of modes of cell death, including the recently discovered novel death modes. Our analysis highlights the common and unique pathways of these death modes, as well as their impact on surrounding cells and the organism as a whole. Our aim was to provide a comprehensive overview of the current state of research on cell death, with a focus on identifying gaps in our knowledge and opportunities for future investigation. We also presented a new insight for macroscopic intracellular survival patterns, namely that intracellular molecular homeostasis is central to the balance of different cell death modes, and this viewpoint can be well justified by the signaling crosstalk of different death modes. These concepts can facilitate the future research about cell death in clinical diagnosis, drug development, and therapeutic modalities.
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As an epizootic causative agent, the Getah virus (GETV) can cause moderate illness in horses, lethal disease in foxes, and reproductive disorders and fetal death in pigs. Due to the wide range of hosts and multiple routes of transmission, GETV has become a growing potential threat to the global livestock industry, and even to public health. More attention and research on GETV are urgently needed. In this study, we successfully isolated a novel GETV strain, named BJ0304, from a commercial live vaccine against porcine reproductive and respiratory syndrome virus (PRRSV) and determined its growth kinetics. Then, genetic and phylogenetic analyses were performed. The results revealed that BJ0304 was clustered into Group III, and it was most related to the GETV-V1 strain based on the complete genome sequence. Furthermore, the pathogenicity of the isolate was assessed and found to be a low virulent strain in mice relative to its closest homolog GETV-V1. Finally, mutation and glycosylation analysis showed that a unique mutation (171 T > I) at one amino acid of E2, which affected the glycosylation of E2, may be associated with viral pathogenicity. In summary, the general characteristic of a novel Group III-classified GETV-BJ0304 isolated from commercial live PRRSV vaccine was defined and then mutation/glycosylation-related potential virulence factor was discussed. This study highlights the complexity of GETV transmission routes in swine and the need for more surveillance on commercial animal vaccines, contributes to the understanding of genetic characterization of clinical isolates, provides possible virulence factors in favor of unveiling the viral pathogenesis, and eventually lays the foundation for the prevention and control of GETV.
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Alphavirus , Síndrome Respiratorio y de la Reproducción Porcina , Virus del Síndrome Respiratorio y Reproductivo Porcino , Vacunas , Animales , Porcinos , Caballos , Ratones , Virus del Síndrome Respiratorio y Reproductivo Porcino/genética , Alphavirus/genética , Filogenia , Síndrome Respiratorio y de la Reproducción Porcina/prevención & controlRESUMEN
Introduction: Getah virus (GETV) has become a growing potential threat to the global livestock industry and public health. However, little is known about the viral pathogenesis and immune escape mechanisms, leading to ineffective control measures. Methods: In this study, the antiviral activity of exogenous interferons (IFNs) was assessed by using western blotting (WB), real-time quantitative PCR (RT-qPCR) and indirect immunofluorescence assay (IFA). The comparative transcriptomics among mock- and GETV-infected (MOI = 0.1) ST cells with or without IFN-γ was performed by RNA-seq, and then the transcriptome profiling of GETV-infected ST cells and key pathways and putative factors involved in inhibitory effect of IFN-γ on GETV replication were analyzed by bioinformatics methods and RT-qPCR. Results: The results showed that treatment with IFN-γ could suppress GETV replication, and the inhibitory effect lasted for at least 48 h, while the exogenous IFN-α/ω and IFN-λ3 treatments failed to inhibit the viral infection and early replication in vitro. Furthermore, the blueprint of virus-host interaction was plotted by RNA-seq and RT-qPCR, showing systemic activation of inflammatory, apoptotic, and antiviral pathways in response to GETV infection, indicating viral hijacking and inhibition of innate host immunity such as IFN-I/III responses. Last and most importantly, activation of the JAK-STAT signaling pathway and complement and coagulation cascades may be a primary driver for IFN-γ-mediated inhibition of GETV replication. Discussion: These findings revealed that GETV possessed the capability of viral immune escape and indicated that IFN-γ aided in the prevention and control of GETV, implying the potential molecular mechanism of suppression of GETV by IFN-γ, all of which warrant emphasis or further clarification.
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Despite the wide usage of ß2-adrenoceptor agonists in asthma treatment, they do have side effects such as aggravating inflammation. We previously reported that isoprenaline induced Cl- secretion and IL-6 release via cAMP-dependent pathways in human bronchial epithelia, but the mechanisms underlying the inflammation-aggravation effects of ß2-adrenoceptor agonists remain pooly understood. In this study, we investigated formoterol, a more specific ß2-adrenoceptor agonist, -mediated signaling pathways involved in the production of IL-6 and IL-8 in 16HBE14o- human bronchial epithelia. The effects of formoterol were detected in the presence of PKA, exchange protein directly activated by cAMP (EPAC), cystic fibrosis transmembrane conductance regulator (CFTR), extracellular signal-regulated protein kinase (ERK)1/2 and Src inhibitors. The involvement of ß-arrestin2 was determined using siRNA knockdown. Our results indicate that formoterol can induce IL-6 and IL-8 secretion in concentration-dependent manner. The PKA-specific inhibitor, H89, partially inhibited IL-6 release, but not IL-8. Another intracellular cAMP receptor, EPAC, was not involved in either IL-6 or IL-8 release. PD98059 and U0126, two ERK1/2 inhibitors, blocked IL-8 while attenuated IL-6 secretion induced by formoterol. Furthermore, formoterol-induced IL-6 and IL-8 release was attenuated by Src inhibitors, namely dasatinib and PP1, and CFTRinh172, a CFTR inhibitor. In addition, knockdown of ß-arrestin2 by siRNA only suppressed IL-8 release when a high concentration of formoterol (1 µM) was used. Taken together, our results suggest that formoterol stimulates IL-6 and IL-8 release which involves PKA/Src/ERK1/2 and/or ß-arrestin2 signaling pathways.
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Regulador de Conductancia de Transmembrana de Fibrosis Quística , Interleucina-8 , Humanos , Fumarato de Formoterol/farmacología , Regulador de Conductancia de Transmembrana de Fibrosis Quística/metabolismo , Interleucina-8/metabolismo , Interleucina-6/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismo , Inflamación , ARN Interferente Pequeño , Receptores Adrenérgicos/metabolismoRESUMEN
The carbon stocks (Corg stocks) in mangrove sediments and the distribution and source changes of sedimented organic matter in Qinglan Bay are not understood as the mangrove forests decrease. In this paper, we collected two sediment cores in the interior mangrove and 37 surface sediment samples from mangrove-fringe, tidal flat and subtidal habitats and then analysed the total organic carbon (TOC), total nitrogen (TN), and the stable organic carbon isotope (δ13C) and nitrogen isotope (δ15N) in the sediment samples to obtain the organic matter sources and carbon stocks in two different mangrove sediment cores from Qinglan Bay. The δ13C and TOC/TN values showed that mangrove plants and algae were the main sources of organic matter. Relatively high contributions of mangrove plants (>50 %) were distributed in the mangrove areas in Wenchang estuary, the northern region of Bamen Bay and the eastern side of the Qinglan tidal inlet. The enriched δ15N values might be related to anthropogenic nutrient inputs, including increased aquaculture wastewater, human sewage and ship wastewater. The Corg stocks in cores Z02 and Z03 were 357.79 Mg C ha-1 and 265.78 Mg C ha-1, respectively. This Corg stock difference might have been related to the salinity and the benthos activities. The high Corg stock values measured in Qinglan Bay were caused by the mangrove maturity and stand age. The total Corg storage of the mangrove ecosystem in Qinglan Bay was estimated to be approximately 263.93 Gg C. This study contributes to organic carbon stocks and sources of sedimented organic matter in global mangroves.
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Background: Saccades are often observed on video head impulse tests (vHIT) in patients with Meniere's Disease (MD) and Vestibular Migraine (VM). However, their saccadic features are not fully described. Objective: This study aims to identify the saccades characteristics of MD and VM. Methods: 75 VM patients and 103 definite unilateral MD patients were enrolled in this study. First raw saccades were exported and analyzed. The VM patients were divided into left and right based on their ears, while the MD patients were separated into affected and unaffected subgroups based on their audiograms and symptoms. Results: The MD patients have more saccades on the affected side (85% vs. 69%), and saccade velocity is more consistent than the contralateral side (shown by the coefficient of variation). The saccades occurrence rates on both sides are similar in VM (77% vs. 76%), as are other saccadic parameters. The MD patients have more significant inter-aural differences than the VM patients, manifested in higher velocity (p-value 0.000), earlier arriving (p-value 0.010), and more time-domain gathered (p-value 0.003) on the affected side. Conclusions: Bilateral saccades are commonly observed in MD and VM. In contrast to MD, saccades on VM are subtle, scattered, and late-arrived. Furthermore, the MD patients showed inconsistent saccadic distribution with more velocity-uniform saccades on the affected side.
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Spike (S) protein, a homotrimeric glycoprotein, is the most important antigen target for SARS-CoV-2 vaccines. A complete simulation of the advanced structure of this homotrimer during subunit vaccine development is the most likely method to improve its immunoprotective effects. In this study, preparation strategies for the S protein receptor-binding domain, S1 region, and ectodomain trimer nanoparticles were designed using ferritin nanoparticle self-assembly technology. The Bombyx mori baculovirus expression system was used to prepare three nanoparticle vaccines with high expression levels recorded in silkworms. The results in mice showed that the nanoparticle vaccine prepared using this strategy could induce immune responses when administered via both the subcutaneous administration and oral routes. Given the stability of these ferritin-based nanoparticle vaccines, an easy-to-use and low-cost oral immunization strategy can be employed in vaccine blind areas attributed to shortages of ultralow-temperature equipment and medical resources in underdeveloped areas. Oral vaccines are also promising candidates for limiting the spread of SARS-CoV-2 in domestic and farmed animals, especially in stray and wild animals.