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BACKGROUND: The clinical profile of cluster headache may differ among different regions of the world, warranting interest in the data obtained from the initial Chinese Cluster Headache Register Individual Study (CHRIS) for better understanding. METHODS: We conducted a multicenter, prospective, longitudinal cohort study on cluster headache across all 31 provinces of China, aiming to gather clinical characteristics, treatment approaches, imaging, electrophysiological and biological samples. RESULTS: In total 816 patients were enrolled with a male-to-female ratio of 4.33:1. The mean age at consultation was 34.98 ± 9.91 years, and 24.89 ± 9.77 years at onset. Only 2.33% were diagnosed with chronic cluster headache, and 6.99% had a family history of the condition. The most common bout was one to two times per year (45.96%), lasting two weeks to one month (44.00%), and occurring frequently in spring (76.23%) and winter (73.04%). Of these, 68.50% experienced one to two attacks per day, with the majority lasting one to two hours (45.59%). The most common time for attacks was between 9 am and 12 pm (75.86%), followed by 1 am and 3 am (43.48%). Lacrimation (78.80%) was the most predominant autonomic symptom reported. Furthermore, 39.22% of patients experienced a delay of 10 years or more in receiving a correct diagnosis. Only 35.67% and 24.26% of patients received common acute and preventive treatments, respectively. CONCLUSION: Due to differences in ethnicity, genetics and lifestyle conditions, CHRIS has provided valuable baseline data from China. By establishing a dynamic cohort with comprehensive multidimensional data, it aims to advance the management system for cluster headache in China.
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Cefaleia Histamínica , Feminino , Humanos , Masculino , China/epidemiologia , Cefaleia Histamínica/diagnóstico , Cefaleia Histamínica/epidemiologia , Cefaleia Histamínica/terapia , Estudos Longitudinais , Estudos Prospectivos , AdultoRESUMO
BACKGROUND: Gut microbiota disturbance is increasingly suggested to be involved in the pathogenesis of migraine but this connection remains unsubstantiated. This study aimed to investigate whether the gut microbiome influences migraine-related hyperalgesia. METHODS: Nitroglycerin-induced hyperalgesia was evaluated in mice with different gut microbiota statuses as follows: Specific pathogen-free mice; germ-free mice; specific pathogen-free mice treated with antibiotics to deplete the gut microbiome (ABX mice); and germ-free mice transplanted with the gut microbial profile from specific pathogen-free mice (GFC mice). Moreover, nitroglycerin-induced hyperalgesia was compared between recipient mice transplanted with gut microbiota from a patient with migraine and those that received gut microbiota from a sex- and age-matched healthy control. RESULTS: In specific pathogen-free mice, a decreased mechanical threshold in the hind paw, increased grooming time, increased c-Fos expression level and decreased calcitonin gene-related peptide expression level as well as increased tumor necrosis factor-α concentration in the trigeminal nucleus caudalis were observed after nitroglycerin administration compared with saline treatment. However, increased basal sensitivity and higher basal concentrations of TNF-α in the trigeminal nucleus caudalis were observed in germ-free and ABX mice, while no significant difference in hyperalgesia was observed between the nitroglycerin group and saline group in germ-free and ABX mice. Moreover, significant hyperalgesia was induced by nitroglycerin administration in GFC mice. The mice transplanted with the gut microbial profile from a patient with migraine had more severe nitroglycerin-induced hyperalgesia than the mice receiving microbiota from a matched healthy control. CONCLUSION: Our findings highlight the involvement of the gut microbiome in normal mechanical pain sensation and pathogenesis of migraine.
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Microbioma Gastrointestinal , Transtornos de Enxaqueca , Animais , Humanos , Hiperalgesia/induzido quimicamente , Camundongos , Transtornos de Enxaqueca/induzido quimicamente , Transtornos de Enxaqueca/metabolismo , Nitroglicerina/efeitos adversos , DorRESUMO
The transition from the fetal to the neonatal circulation includes dilatation of the pulmonary arteries (PA) and closure of the Ductus Arteriosus Botalli (DAB). The resting membrane potential and various potassium channel activities in smooth muscle cells (SMC) from fetal and neonatal PA and DAB obtained from the same species has not been systematically analyzed. The key issue addressed in this paper is how the resting membrane potential and the whole-cell potassium current (IK) change when PASMC or DABSMC are transitioned from hypoxia, reflecting the fetal state, to normoxia, reflecting the post-partal state. Patch-clamp measurements were employed to characterize whole-cell K+ channel activity in fetal and post-partal (newborn) PASMC and DABSMC. The main finding of this paper is that the SMC from both tissues use a similar set of K+ channels (voltage-dependent (Kv), calcium-sensitive (KCa), TASK-1 and probably also TASK-2 channels); however, their activity level depends on the cell type and the oxygen level. Furthermore, we provide the first evidence for pH-sensitive non-inactivating K+ current in newborn DABSMC and PASMC, suggesting physiologically relevant TASK-1 and TASK-2 channel activity, the latter particularly in the Ductus Arteriosus Botalli.
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Canal Arterial , Canais de Potássio , Circulação Pulmonar , Animais , Canal Arterial/metabolismo , Desenvolvimento Fetal/fisiologia , Humanos , Recém-Nascido , Músculo Liso Vascular/metabolismo , Canais de Potássio/metabolismo , Artéria Pulmonar/metabolismo , Circulação Pulmonar/fisiologia , RatosRESUMO
BACKGROUND: Astrocytic activation might play a significant role in the central sensitization of chronic migraine (CM). However, the temporal characteristics of the astrocytic activation in the trigeminal nucleus caudalis (TNC) and the molecular mechanism under the process remain not fully understood. Therefore, this study aims to investigate the duration and levels change of astrocytic activation and to explore the correlation between astrocytic activation and the levels change of cytokines release. METHODS: We used a mice model induced by recurrent dural infusion of inflammatory soup (IS). The variation with time of IS-induced mechanical thresholds in the periorbital and hind paw plantar regions were evaluated using the von Frey filaments test. We detected the expression profile of glial fibrillary acidic protein (GFAP) in the TNC through immunofluorescence staining and western blot assay. We also investigated the variation with time of the transcriptional levels of GFAP and ionized calcium binding adapter molecule 1 (Iba1) through RNAscope in situ hybridization analysis. Then, we detected the variation with time of cytokines levels in the TNC tissue extraction and serum, including c-c motif chemokine ligand 2 (CCL2), c-c motif chemokine ligand 5 (CCL5), c-c motif chemokine ligand 7 (CCL7), c-c motif chemokine ligand 12 (CCL12), c-x-c motif chemokine ligand 1 (CXCL1), c-x-c motif chemokine ligand 13 (CXCL13), interferon gamma (IFN-γ), tumor necrosis factor alpha (TNF-α), macrophage colony-stimulating factor (M-CSF), interleukin 1beta (IL-1ß), interleukin 6 (IL-6), interleukin 10 (IL-10), interleukin 17A (IL-17A). RESULTS: Recurrent IS infusion resulted in cutaneous allodynia in both the periorbital region and hind paw plantar, ranging from 5 d (after the second IS infusion) to 47 d (28 d after the last infusion) and 5 d to 26 d (7 d after the last infusion), respectively. The protein levels of GFAP and messenger ribonucleic acid (mRNA) levels of GFAP and Iba1 significantly increased and sustained from 20 d to 47 d (1 d to 28 d after the last infusion), which was associated with the temporal characteristics of astrocytic activation in the TNC. The CCL7 levels in the TNC decreased from 20 d to 47 d. But the CCL7 levels in serum only decreased on 20 d (1 d after the last infusion). The CCL12 levels in the TNC decreased on 22 d (3 d after the last infusion) and 33 d (14 d after the last infusion). In serum, the CCL12 levels only decreased on 22 d. The IL-10 levels in the TNC increased on 20 d. CONCLUSIONS: Our results indicate that the astrocytic activation generated and sustained in the IS-induced mice model from 1 d to 28 d after the last infusion and may contribute to the pathology through modulating CCL7, CCL12, and IL-10 release.
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Transtornos de Enxaqueca , Núcleos do Trigêmeo , Animais , Sensibilização do Sistema Nervoso Central , Hiperalgesia/induzido quimicamente , Camundongos , DorRESUMO
BACKGROUND: The aim of the study was to investigate whether MwoA and MwA are different manifestations of a single disease, distinct clinical entities, or located at two poles of a spectrum. METHODS: In this cross-sectional study, 5438 patients from 10 hospitals in China were included: 4651 were diagnosed with migraine without aura (MwoA) and 787 with migraine with aura (MwA). We used a validated standardized electronic survey to collect multidimensional data on headache characteristics and evaluated the similarities and differences between migraine subtypes. To distinguish migraine subtypes, we employed correlational analysis, factor analysis of mixed data (FAMD), and decision tree analysis. RESULTS: Compared to MwA, MwoA had more severe headaches, predominantly affected females, were more easily produced by external factors, and were more likely to have accompanying symptoms and premonitory neck stiffness. Patients with MwA are heterogeneous, according to correlation analysis; FAMD divided the subjects into three clear clusters. The majority of the differences between MwoA and MwA were likewise seen when typical aura with migraine headache (AWM) and typical aura with non-migraine headache (AWNM) were compared. Furthermore, decision trees analysis revealed that the chaotic MwA data reduced the decision tree's accuracy in distinguishing MwoA from MwA, which was significantly increased by splitting MwA into AWM and AWNM. CONCLUSIONS: The clinical phenomics of headache phenotype varies gradually from MwoA to AWM and AWNM, and AWM is a mid-state between MwoA and AWNM. We tend to regard migraine as a spectrum disorder, and speculate that different migraine subtypes have different "predominant regions" that generate attacks.
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Epilepsia , Enxaqueca com Aura , Enxaqueca sem Aura , Estudos Transversais , Epilepsia/complicações , Feminino , Cefaleia/complicações , Humanos , Enxaqueca com Aura/complicações , Enxaqueca com Aura/diagnóstico , Enxaqueca com Aura/genética , Enxaqueca sem Aura/diagnóstico , FenômicaRESUMO
BACKGROUND: Mutations in ATP1A2, the gene encoding the α2 subunit of Na+/K+-ATPase, are the main cause of familial hemiplegic migraine type 2 (FHM2). The clinical presentation of FHM2 with mutations in the same gene varies from pure FHM to severe forms with epilepsy and intellectual disability, but the correlation of these symptoms with different ATP1A2 mutations is still unclear. METHODS: Ten ATP1A2 missense mutations were selected according to different phenotypes of FHM patients. They caused pure FHM (FHM: R65W, R202Q, R593W, G762S), FHM with epilepsy (FHME: R548C, E825K, R938P), or FHM with epilepsy and intellectual disability (FHMEI: T378N, G615R, D718N). After ouabain resistance and fluorescence modification, plasmids carrying those mutations were transiently transfected into HEK293T and HeLa cells. The biochemical functions were studied including cell survival assays, membrane protein extraction, western blotting, and Na+/K+-ATPase activity tests. The electrophysiological functions of G762S, R938P, and G615R mutations were investigated in HEK293T cells using whole-cell patch-clamp. Homology modeling was performed to determine the locational distribution of ATP1A2 mutations. RESULTS: Compared with wild-type pumps, all mutations showed a similar level of protein expression and decreased cell viability in the presence of 1 µM ouabain, and there was no significant difference among the mutant groups. The changes in Na+/K+-ATPase activity were correlated with the severity of FHM phenotypes. In the presence of 100 µM ouabain, the Na+/K+-ATPase activity was FHM > FHME > FHMEI. The ouabain-sensitive Na+/K+-ATPase activity of each mutant was significantly lower than that of the wild-type protein, and there was no significant difference among all mutant groups. Whole-cell voltage-clamp recordings in HEK293T cells showed that the ouabain-sensitive pump currents of G615R were significantly reduced, while those of G762S and R938P were comparable to those of the wild-type strain. CONCLUSIONS: ATP1A2 mutations cause phenotypes ranging from pure FHM to FHM with epilepsy and intellectual disability due to varying degrees of deficits in biochemical and electrophysiological properties of Na+/K+-ATPase. Mutations associated with intellectual disability presented with severe impairment of Na+/K+-ATPase. Whether epilepsy is accompanied, or the type of epilepsy did not seem to affect the degree of impairment of pump function.
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Enxaqueca com Aura , Células HEK293 , Células HeLa , Hemiplegia , Humanos , Enxaqueca com Aura/genética , Mutação , Fenótipo , ATPase Trocadora de Sódio-Potássio/genéticaRESUMO
BACKGROUND: ATP1A2 has been identified as the genetic cause of familial hemiplegic migraine type 2. Over 80 ATP1A2 mutations have been reported, but no data from Chinese family studies has been included. Here, we report the first familial hemiplegic migraine type 2 Chinese family with a novel missense mutation. METHODS: Clinical manifestations in the family were recorded. Blood samples from patients and the unaffected members were collected for whole-exome sequencing to identify the pathogenic mutation. Seven online softwares (SIFT, PolyPhen-2, PROVEAN, PANTHER, MutationTaster2, MutationAssessor and PMut) were used for predicting the pathogenic potential of the mutation. PredictProtein, Jpred 4 and PyMOL were used to analyze structural changes of the protein. The mutation function was further tested by Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay. RESULTS: All patients in the family had typical hemiplegic migraine attacks. Co-segregation of the mutation with the migraine phenotype in four generations, with 10 patients, was completed. The identified novel mutation, G762S in ATP1A2, exhibited the disease-causing feature by all the predictive softwares. The mutation impaired the local structure of the protein and decreased cell viability. CONCLUSION: G762S in ATP1A2 is a novel pathogenic mutation identified in a Chinese family with familial hemiplegic migraine, which causes loss of function by changing the protein structure of the Na+/K+-ATPase α2 subunit.
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Enxaqueca com Aura/genética , ATPase Trocadora de Sódio-Potássio/genética , Povo Asiático/genética , Feminino , Humanos , Masculino , Mutação de Sentido Incorreto , Linhagem , Adulto JovemRESUMO
The present study investigated the effects of diesel exhaust (DE) on an experimental model of bleomycin (BLM)-induced lung injury and fibrosis in mice. BLM was intravenously administered to both Nrf2+/+ and Nrf2-/- C57BL/6J mice on day 0. The mice were exposed to DE for 56 days from 28 days before the BLM injection to 28 days after the BLM injection. Inhalation of DE induced significant inhibition of airway clearance function and the proinflammatory cytokine secretion in macrophages, an increase in neutrophils, and severe lung inflammatory injury, which were greater in Nrf2-/- mice than in Nrf2+/+ mice. In contrast, inhalation of DE was observed to induce a greater increase of hydroxyproline content in the lung tissues and significantly higher pulmonary antioxidant enzyme mRNA expression in the Nrf2+/+ mice than in Nrf2-/- mice. DE is an important risk factor, and Nrf2 regulates the risk of a DE inhalation induced immune response during BLM lung injury and fibrosis in mice.
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Citocinas/metabolismo , Lesão Pulmonar/genética , Fator 2 Relacionado a NF-E2/metabolismo , Emissões de Veículos/toxicidade , Animais , Bleomicina/toxicidade , Fibrose , Hidroxiprolina/metabolismo , Lesão Pulmonar/etiologia , Lesão Pulmonar/imunologia , Lesão Pulmonar/patologia , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Estresse OxidativoRESUMO
Epithelial-mesenchymal transition (EMT) is critical for embryonic development, and this process is recapitulated in adults during wound healing, tissue regeneration, fibrosis and cancer progression. Cell migration is believed to play a key role in both normal wound repair and in abnormal tissue remodeling. Prostaglandin E2 (PGE2) inhibits fibroblast chemotaxis, but stimulates chemotaxis in airway epithelial cells. The current study was designed to explore the role of PGE2 and its four receptors on airway epithelial cell migration following EMT using both the Boyden blindwell chamber chemotaxis assay and the wound closure assay. EMT in human bronchial epithelial cells (HBECs) was induced by TGF-ß1 and a mixture of cytokines (IL-1ß, TNF-α, and IFN-γ). PGE2 and selective agonists for all four EP receptors stimulated chemotaxis and wound closure in HBECs. Following EMT, the EP1 and EP3 agonists were without effect, while the EP2 and EP4 agonists inhibited chemotaxis as did PGE2. The effects of the EP2 and EP4 receptors on HBEC and EMT cell migration were further confirmed by blocking the expected signaling pathways. Taken together, these results demonstrate that PGE2 switches from a stimulator to an inhibitor of cell migration following EMT of airway epithelial cells and that this inhibition is mediated by an altered effect of EP2 and EP4 signaling and an apparent loss of the stimulatory effects of EP1 and EP3. Change in the PGE2 modulation of chemotaxis may play a role in repair following injury.
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Movimento Celular/efeitos dos fármacos , Dinoprostona/farmacologia , Células Epiteliais/metabolismo , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Receptores de Prostaglandina E Subtipo EP2/metabolismo , Receptores de Prostaglandina E Subtipo EP4/metabolismo , Linhagem Celular , Citocinas/metabolismo , Células Epiteliais/citologia , HumanosRESUMO
This study assessed the effect of extended exposure to cigarette smoke extract (CSE) on tissue repair functions in lung fibroblasts. Human fetal (HFL-1) and adult lung fibroblasts were exposed to CSE for 14 days. Senescence-associated ß-galactosidase (SA ß-gal) expression, cell proliferation, and tissue repair functions including chemotaxis and gel contraction were assessed. HFL-1 proliferation was inhibited by CSE and nearly half of the CSE-exposed cells were SA ß-gal positive after 14 days exposure, whereas 33% of adult lung fibroblasts were SA ß-gal positive in response to 10% CSE exposure. The SA ß-gal-positive cells did not proliferate as indicated by bromodeoxyuridine incorporation. In contrast, cells negative for SA ß-gal after CSE exposure proliferated faster than cells never exposed to CSE. These nonsenescent cells migrated more and contracted collagen gels more than control cells. CSE exposure stimulated TGF-ß1 production, and both inhibition of TGF-ß receptor kinase and TGF-ß1 siRNA blocked CSE modulation of fibroblast function. Extended exposure to CSE might induce two different fibroblast phenotypes, a senescent and a profibrotic phenotype. The fibroblasts that resist CSE-induced cellular senescence may contribute to the pathogenesis of idiopathic pulmonary fibrosis and could contribute to fibrotic lesions in chronic obstructive pulmonary disease acting through a TGF-ß1-mediated pathway. In contrast, the senescent cells may contribute to the pathogenesis of emphysema.
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Senescência Celular/efeitos dos fármacos , Fibroblastos/patologia , Pulmão/patologia , Enfisema Pulmonar/patologia , Fibrose Pulmonar/patologia , Fumaça/efeitos adversos , Adulto , Idoso , Apoptose/efeitos dos fármacos , Western Blotting , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Quimiotaxia , Ensaio de Imunoadsorção Enzimática , Feminino , Feto , Fibroblastos/efeitos dos fármacos , Fibroblastos/metabolismo , Humanos , Pulmão/efeitos dos fármacos , Pulmão/metabolismo , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Fenótipo , Enfisema Pulmonar/induzido quimicamente , Enfisema Pulmonar/metabolismo , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/metabolismo , Fator de Crescimento Transformador beta1/antagonistas & inibidores , Fator de Crescimento Transformador beta1/genética , Fator de Crescimento Transformador beta1/metabolismo , beta-Galactosidase/metabolismoRESUMO
Social media platforms provide the public with a forum for interaction and communication with tourism destinations, playing a significant role in the shaping and dissemination of destination images. Similarly, social media plays a vital role in the construction and propagation of online images for higher education institutions. For instance, indicators such as likes, shares, and visits on Weibo can serve as measures of public engagement with university social media. To reveal the triggering rules of social media engagement by projected images of destinations and related factors, this paper builds a Bayesian model using data from posts and interactions on the official Sina Weibo account of a Chinese university from 2018 to 2023. This model simulates to infer the optimal decisions that trigger university social media engagement.
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Mídias Sociais , Humanos , Universidades , Teorema de Bayes , Comunicação , Emoções , ChinaRESUMO
Alzheimer's disease is the predominant form of dementia, and disulfidptosis is the latest reported mode of cell death that impacts various disease processes. This study used bioinformatics to analyze genes associated with disulfidptosis in Alzheimer's disease comprehensively. Based on the public datasets, the differentially expressed genes associated with disulfidptosis were identified, and immune cell infiltration was investigated through correlation analysis. Subsequently, hub genes were determined by a randomforest model. A prediction model was constructed using logistic regression. In addition, the drug-target affinity was predicted by a graph neural network model, and the results were validated by molecular docking. Five hub genes (PPEF1, NEUROD6, VIP, NUPR1, and GEM) were identified. The gene set showed significant enrichment for AD-related pathways. The logistic regression model demonstrated an AUC of 0.952, with AUC values of 0.916 and 0.864 in validated datasets. The immune infiltration analysis revealed significant heterogeneity between the Alzheimer's disease and control groups. High-affinity drugs for hub genes were identified. Through our study, a disease prediction model was constructed using potential biomarkers, and drugs targeting the genes were predicted. These results contribute to further understanding of the molecular mechanisms underlying Alzheimer's disease.
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Doença de Alzheimer , Biomarcadores , Doença de Alzheimer/genética , Doença de Alzheimer/metabolismo , Humanos , Biologia Computacional/métodos , Simulação de Acoplamento Molecular , Apoptose , Perfilação da Expressão Gênica , Redes Reguladoras de GenesRESUMO
BACKGROUND: This study used optical coherence tomography (OCT) to observe real-time internal gap formation in both bulk-fill and conventional resin composites. It aimed to provide a quantitative analysis of variations, addressing the inconclusive nature of microleakage assessment caused by differences in testing methods. METHODS: Fifty extracted third molars prepared with Class I cavities, were divided into five groups (n = 10). Conventional resin Filtek Z350 XT (FZX) was applied with a double-layer filling of 2 mm per layer. Bulk-fill resins X-tra fil (XTF), Filtek Bulk Fill Posterior Restorative (FBP), Surefil SDR Flow + (SDR), and Filtek Flowable Restorative (FFR) were applied with a single-layer filling of 4 mm. Real-time OCT imaging was conducted during light curing. Post-curing, the entire sample was OCT-scanned. Following this, ImageJ software was used to measure the gap (G1 %). Subsequently, thermal cycling (TC) (5000 times, 5 °C-55 °C) was applied, followed by OCT scanning to calculate the gap (G2 %) and ΔG%. Data were analyzed using two-way repeated measures ANOVA, Kruskal-Wallis test, and Duncan's test (α=0.05). RESULTS: There was no significant difference in G1 % among the groups (p > 0.05). Following TC, FZX exhibited the highest G2 %, succeeded by FFR, FBP, XTF, and SDR, with SDR demonstrating the lowest G2 % (p < 0.05). FZX showed the highest ΔG% (p < 0.05), while SDR exhibited the lowest ΔG% (p < 0.05). CONCLUSION: OCT proves to be a promising tool for detecting microleakage. TC exerted a more significant negative impact on conventional resin. Surefil SDR Flow + displayed the least microleakage, both before and after TC.
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Resinas Compostas , Tomografia de Coerência Óptica , Resinas Compostas/química , Tomografia de Coerência Óptica/métodos , Humanos , Teste de Materiais , Dente Serotino/diagnóstico por imagem , MetacrilatosRESUMO
OBJECTIVE: Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. METHODS: First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. RESULTS: We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset. CONCLUSION: Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.
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One of the early changes upon tuber induction is the switch from apoplastic to symplastic unloading. Whether and how this change in unloading mode contributes to sink strength has remained unclear. In addition, developing tubers also change from energy to storage-based sucrose metabolism. Here, we investigated the coordination between changes in unloading mode and sucrose metabolism and their relative role in tuber sink strength by looking into callose and sucrose metabolism gene expression combined with a model of apoplastic and symplastic unloading. Gene expression analysis suggests that callose deposition in tubers is decreased by lower callose synthase expression. Furthermore, changes in callose and sucrose metabolism are strongly correlated, indicating a well-coordinated developmental switch. Modelling indicates that symplastic unloading is not the most efficient unloading mode per se. Instead, it is the concurrent metabolic switch that provides the physiological conditions necessary to potentiate symplastic transport and thereby enhance tuber sink strength .
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The imperfect charge behavior at the interfaces of perovskite/electron-transport layer (ETL)/transparent conducting oxide (TCO) limits the further performance improvement of perovskite/silicon tandem solar cells. Herein, an indium tin oxide interlayer is deposited between ETL and TCO to address this issue. Specifically, the interlayer is prepared using an all-physical and H2O-free method, electron-beam evaporation, which can avoid any potential damage to the underlying perovskite and ETL layers. Moreover, the interlayer's composition can be readily tuned by changing the evaporator component, enabling authors to regulate the contact resistance and energy-level alignment of the ETL/TCO interface. Consequently, the resultant perovskite/silicon tandem solar cells exhibit an impressive power conversion efficiency (PCE) of 30.8% (certified 30.3%). Moreover, the device retains 98% of its initial PCE after continuous operation under ambient conditions for 1078 h, representing one of the most stable and efficient perovskite/silicon tandem solar cells.
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Diesel exhaust particle (DEP) is the major components of PM2.5, and much attention has focused on PM2.5 in relation to adverse health effects, and many pulmonary diseases. In the present study, we used a human bronchial epithelial cell (HBEC) line to investigate the anti-inflammatory effects of erythromycin (EM) and EM703 - a new derivative of erythromycin without antibacterial effects on the expressions of IL-8 caused by DEP exposure. DEP showed a dose-dependent stimulatory effect on IL-8 product in HBEC. Increases of IL-8 expression by DEP stimulation were significantly blocked by both EM and EM703 pretreatment. Furthermore, NF-κB and Nrf2 activation, the antioxidant enzymes such as HO-1, NQO-1 mRNA expression were increased by DEP exposure and these increases were blocked by both of EM and EM703 pretreatment. Our results suggest that, EM and EM703 may have an inhibitory effect on expression inflammatory cytokines in HBEC induced by DEP not only as an anti-inflammation but also an antioxidant drug. EM and EM703 might contribute to chemical prevention of the risk of pulmonary diseases induced by oxidative stress from environmental pollutant, such as DEP.
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Anti-Inflamatórios/farmacologia , Eritromicina/análogos & derivados , Eritromicina/farmacologia , Material Particulado/farmacologia , Emissões de Veículos/toxicidade , Linhagem Celular , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Células Epiteliais/efeitos dos fármacos , Humanos , Mediadores da Inflamação/metabolismo , Interleucina-8/biossíntese , Fator 2 Relacionado a NF-E2 , NF-kappa B/antagonistas & inibidores , Estresse Oxidativo/efeitos dos fármacos , Estresse Oxidativo/fisiologiaRESUMO
Purpose: Although the motives of philanthropy vary from country to country around the world, it is still conducive to building a harmonious society to a certain extent. Methods: It uses partial least squares (PLS) to verify the stability of the model and test the model's hypotheses to analyze the mechanism of action between perceived class mobility and behavioral intention to give online. Results: It was found that perceived class mobility, philanthropic sentiment, and philanthropic cognition affected online giving intention; perceived class mobility had a significant effect on philanthropic cognition and philanthropic sentiment; philanthropic sentiment and philanthropic cognition mediated the relationship between perceived class mobility and giving behavior intention. Conclusion: The study suggests that nonprofit organizations should stimulate behavioral intentions to give by creating an atmosphere of upward class mobility.
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Significance: Previous studies have demonstrated that the biomechanical properties of the optic nerve head (ONH) are associated with a variety of ophthalmic diseases; however, they have not been adequately studied. Aim: We aimed to obtain a two-dimensional (2D) velocity distribution image based on the one-to-one correspondence between velocity values and position using the acoustic radiation force optical coherence elastography (ARF-OCE) technique combined with a 2D phase velocity algorithm. Approach: An ARF-OCE system has the advantages of non-invasive detection, high resolution, high sensitivity, and high-speed imaging for quantifying the biomechanical properties of the ONH at different intraocular pressures (IOPs) and detection directions. The 2D phase velocity algorithm is used to calculate the phase velocity values at each position within the imaging region, and then the 2D velocity distribution image is realized by mapping the velocity values to the corresponding structure based on the one-to-one relationship between velocity and position. The elasticity changes can be read directly according to the quantitative relationship between Lamb wave velocity and Young's modulus. Results: Our quantitative results show that the phase velocity and Young's modulus of the ONH increase by 32.50% and 129.44%, respectively, with increasing IOP, which is in general agreement with the results of previous studies, but they did not produce large fluctuations with the constant change of the ONH direction. These results are consistent with the changes of elastic information in the 2D velocity distribution image. Conclusions: The results suggest that the ARF-OCE technology has great potential in detecting the biomechanical properties of the ONH at different IOPs and directions, and thus may offer the possibility of clinical applications.
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As powerful vasodilators, prostacyclin analogues are presently the mainstay in the treatment of severe pulmonary arterial hypertension. Although the hemodynamic effects of prostacyclin analogues are well known, the molecular mechanism of their acute effects on pulmonary vascular tone and systemic vascular tone remains poorly understood. Peroxisome proliferator-activated receptor-ß/δ (PPARß/δ) was previously identified as a putative receptor responsible for the modulation of target gene expression in response to prostacyclin analogues. The present study investigated the signaling pathway of prostacyclin in human pulmonary arterial smooth muscle cells (PASMCs), and sought to define the role of PPARß/δ in the acute vasodilating effect. In human PASMCs, prostacyclin rapidly activated TWIK-related acid-sensitive K channel 1 (TASK-1) and calcium-dependent potassium channels (K(Ca)). This pathway was mediated via the prostanoid I receptor-protein kinase A pathway. The silencing of PPARß/δ demonstrated that the downstream K(Ca) activation was exclusively dependent on PPARß/δ signaling, whereas the activation of TASK-1 was not. In addition, the PPARß/δ-induced activation of K(Ca) was independent of NO. The acute prostacyclin-induced K(Ca) activation is critically dependent on PPARß/δ as a rapid signaling factor. This accounts in part for the vasodilating effect of prostacyclin in pulmonary arteries, and provides insights into a new molecular explanation for the effects of prostanoids.