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Ionic liquids (ILs) offer a wide range of promising applications due to their unique and designable properties compared to conventional solvents. Further development and application of ILs require correlating/predicting their pressure-viscosity-temperature behavior. In this review, we firstly introduce methods for calculation of thermodynamic inputs of viscosity models. Next, we introduce theories, theoretical and semi-empirical models coupling various theories with EoSs or activity coefficient models, and empirical and phenomenological models for viscosity of pure ILs and IL-related mixtures. Our modelling description is followed immediately by model application and performance. Then, we propose simple predictive equations for viscosity of IL-related mixtures and systematically compare performances of the above-mentioned theories and models. In concluding remarks, we recommend robust predictive models for viscosity at atmospheric pressure as well as proper and consistent theories and models for P-η-T behavior. The work that still remains to be done to obtain the desired theories and models for viscosity of ILs and IL-related mixtures is also presented. The present review is structured from pure ILs to IL-related mixtures and aims to summarize and quantitatively discuss the recent advances in theoretical and empirical modelling of viscosity of ILs and IL-related mixtures.
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Zinc-iodine batteries are one of the most intriguing types of batteries that offer high energy density and low toxicity. However, the low intrinsic conductivity of iodine, together with high polyiodide solubility in aqueous electrolytes limits the development of high-areal-capacity zinc-iodine batteries with high stability, especially at low current densities. Herein, we proposed a hydrophobic polyiodide ionic liquid as a zinc-ion battery cathode, which successfully activates the iodine redox process by offering 4 orders of magnitude higher intrinsic electrical conductivity and remarkably lower solubility that suppressed the polyiodide shuttle in a dual-plating zinc-iodine cell. By the molecular engineering of the chemical structure of the polyiodide ionic liquid, the electronic conductivity can reach 3.4 × 10-3 S cm-1 with a high Coulombic efficiency of 98.2%. The areal capacity of the zinc-iodine battery can achieve 5.04 mAh cm-2 and stably operate at 3.12 mAh cm-2 for over 990 h. Besides, a laser-scribing designed flexible dual-plating-type microbattery based on a polyiodide ionic liquid cathode also exhibits stable cycling in both a single cell and 4 × 4 integrated cell, which can operate with the polarity-switching model with high stability.
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The gut microbiota has been demonstrated to be correlated with the clinical phenotypes of diseases, including cancers. However, there are few studies on clinical subtyping based on the gut microbiota, especially in breast cancer (BC) patients. Here, using machine learning methods, we analysed the gut microbiota of BC, colorectal cancer (CRC), and gastric cancer (GC) patients to identify their shared metabolic pathways and the importance of these pathways in cancer development. Based on the gut microbiota-related metabolic pathways, human gene expression profile and patient prognosis, we established a novel BC subtyping system and identified a subtype called "challenging BC". Tumours with this subtype have more genetic mutations and a more complex immune environment than those of other subtypes. A score index was proposed for in-depth analysis and showed a significant negative correlation with patient prognosis. Notably, activation of the TPK1-FOXP3-mediated Hedgehog signalling pathway and TPK1-ITGAE-mediated mTOR signalling pathway was linked to poor prognosis in "challenging BC" patients with high scores, as validated in a patient-derived xenograft (PDX) model. Furthermore, our subtyping system and score index are effective predictors of the response to current neoadjuvant therapy regimens, with the score index significantly negatively correlated with both treatment efficacy and the number of immune cells. Therefore, our findings provide valuable insights into predicting molecular characteristics and treatment responses in "challenging BC" patients.
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Neoplasias da Mama , Microbioma Gastrointestinal , Humanos , Neoplasias da Mama/genética , Neoplasias da Mama/microbiologia , Neoplasias da Mama/metabolismo , Feminino , Prognóstico , Animais , Camundongos , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica , Transdução de Sinais , Perfilação da Expressão Gênica , Ensaios Antitumorais Modelo de Xenoenxerto , MultiômicaRESUMO
BACKGROUND & AIMS: HBsAg loss is only observed in a small proportion of patients with chronic hepatitis B (CHB) who undergo interferon treatment. Investigating the host factors crucial for functional cure of CHB can aid in identifying individuals who would benefit from peginterferon-α (Peg-IFNα) therapy. METHODS: We conducted a genome-wide association study (GWAS) by enrolling 48 patients with CHB who achieved HBsAg loss after Peg-IFNα treatment and 47 patients who didn't. In the validation stage, we included 224 patients, of whom 90 had achieved HBsAg loss, to validate the identified significant single nucleotide polymorphisms. To verify the functional involvement of the candidate genes identified, we performed a series of in vitro and in vivo experiments. RESULTS: GWAS results indicated a significant association between the rs7519753 C allele and serum HBsAg loss in patients with CHB after Peg-IFNα treatment (p = 4.85 × 10-8, odds ratio = 14.47). This association was also observed in two independent validation cohorts. Expression quantitative trait locus analysis revealed higher hepatic TP53BP2 expression in individuals carrying the rs7519753 C allele (p = 2.90 × 10-6). RNA-sequencing of liver biopsies from patients with CHB after Peg-IFNα treatment revealed that hepatic TP53BP2 levels were significantly higher in the HBsAg loss group compared to the HBsAg persistence group (p = 0.035). In vitro and in vivo experiments demonstrated that loss of TP53BP2 decreased interferon-stimulated gene levels and the anti-HBV effect of IFN-α. Mechanistically, TP53BP2 was found to downregulate SOCS2, thereby facilitating JAK/STAT signaling. CONCLUSION: The rs7519753 C allele is associated with elevated hepatic TP53BP2 expression and an increased probability of serum HBsAg loss post-Peg-IFNα treatment in patients with CHB. TP53BP2 enhances the response of the hepatocyte to IFN-α by suppressing SOCS2 expression. IMPACT AND IMPLICATIONS: Chronic hepatitis B (CHB) remains a global public health issue. Although current antiviral therapies are more effective in halting disease progression, only a few patients achieve functional cure for hepatitis B with HBsAg loss, highlighting the urgent need for a cure for CHB. This study revealed that the rs7519753 C allele, which is associated with high expression of hepatic TP53BP2, significantly increases the likelihood of serum HBsAg loss in patients with CHB undergoing Peg-IFNα treatment. This finding not only provides a promising predictor for HBsAg loss but identifies a potential therapeutic target for Peg-IFNα treatment. We believe our results are of great interest to a wide range of stakeholders based on their potential clinical implications.
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Antivirais , Hepatite B Crônica , Humanos , Antivirais/uso terapêutico , Antígenos de Superfície da Hepatite B/genética , Hepatite B Crônica/tratamento farmacológico , Hepatite B Crônica/genética , Estudo de Associação Genômica Ampla , Quimioterapia Combinada , Interferon-alfa/farmacologia , Interferon-alfa/uso terapêutico , Polietilenoglicóis/uso terapêutico , Antígenos E da Hepatite B , Proteínas Recombinantes/uso terapêutico , Resultado do Tratamento , DNA Viral/genética , Proteínas Reguladoras de ApoptoseRESUMO
Research on the local hippocampal atrophy for early detection of dementia has gained considerable attention. However, accurately quantifying subtle atrophy remains challenging in existing morphological methods due to the lack of consistent biological correspondence with the complex curving regions like the hippocampal head. Thereby, this article presents an innovative axis-referenced morphometric model (ARMM) that follows the anatomical lamellar organization of the hippocampus, which capture its precise and consistent longitudinal curving trajectory. Specifically, we establish an "axis-referenced coordinate system" based on a 7 T ex vivo hippocampal atlas following its entire curving longitudinal axis and orthogonal distributed lamellae. We then align individual hippocampi by deforming this template coordinate system to target spaces using boundary-guided diffeomorphic transformation, while ensuring that the lamellar vectors adhere to the constraint of medial-axis geometry. Finally, we measure local thickness and curvatures based on the coordinate system and boundary surface reconstructed from vector tips. The morphometric accuracy is evaluated by comparing reconstructed surfaces with those directly extracted from 7 T and 3 T MRI hippocampi. The results demonstrate that ARMM achieves the best performance, particularly in the curving head, surpassing the state-of-the-art morphological models. Additionally, morphological measurements from ARMM exhibit higher discriminatory power in distinguishing early Alzheimer's disease from mild cognitive impairment compared to volume-based measurements. Overall, the ARMM offers a precise morphometric assessment of hippocampal morphology on MR images, and sheds light on discovering potential image markers for neurodegeneration associated with hippocampal impairment.
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Atrofia , Demência , Hipocampo , Imageamento por Ressonância Magnética , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/normas , Atrofia/patologia , Demência/diagnóstico por imagem , Demência/patologia , Masculino , Idoso , Feminino , Processamento de Imagem Assistida por Computador/métodos , Idoso de 80 Anos ou mais , Pessoa de Meia-IdadeRESUMO
This study aimed to elucidate the opioid mechanisms underlying dexamethasone-induced pain antihypersensitive effects in neuropathic rats. Dexamethasone (subcutaneous and intrathecal) and membrane-impermeable Dex-BSA (intrathecal) administration dose-dependently inhibited mechanical allodynia and thermal hyperalgesia in neuropathic rats. Dexamethasone and Dex-BSA treatments increased expression of dynorphin A in the spinal cords and primary cultured microglia. Dexamethasone specifically enhanced dynorphin A expression in microglia but not astrocytes or neurons. Intrathecal injection of the microglial metabolic inhibitor minocycline blocked dexamethasone-stimulated spinal dynorphin A expression; intrathecal minocycline, the glucocorticoid receptor antagonist Dex-21-mesylate, dynorphin A antiserum, and κ-opioid receptor antagonist GNTI completely blocked dexamethasone-induced mechanical antiallodynia and thermal antihyperalgesia. Additionally, dexamethasone elevated spinal intracellular cAMP levels, leading to enhanced phosphorylation of PKA, p38 MAPK and CREB. The specific adenylate cyclase inhibitor DDA, PKA inhibitor H89, p38 MAPK inhibitor SB203580 and CREB inhibitor KG-501 completely blocked dexamethasone-induced anti-neuropathic pain and increased microglial dynorphin A exprression. In conclusion, this study reveal that dexamethasone mitigateds neuropathic pain through upregulation of dynorphin A in spinal microglia, likely involving the membrane glucocorticoid receptor/cAMP/PKA/p38 MAPK/CREB signaling pathway.
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Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico , Proteínas Quinases Dependentes de AMP Cíclico , AMP Cíclico , Dexametasona , Dinorfinas , Microglia , Neuralgia , Ratos Sprague-Dawley , Transdução de Sinais , Medula Espinal , Proteínas Quinases p38 Ativadas por Mitógeno , Animais , Microglia/metabolismo , Microglia/efeitos dos fármacos , AMP Cíclico/metabolismo , Medula Espinal/metabolismo , Medula Espinal/efeitos dos fármacos , Masculino , Neuralgia/metabolismo , Neuralgia/tratamento farmacológico , Dinorfinas/metabolismo , Ratos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Dexametasona/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/metabolismo , Hiperalgesia/metabolismo , Hiperalgesia/tratamento farmacológicoRESUMO
White matter dysplasia (WMD) in preterm infants due to intrauterine inflammation is caused by excessive apoptosis of oligodendrocyte precursor cells (OPCs). In recent years, studies have found that excessive autophagy and apoptosis are highly interconnected and important in infection and inflammatory diseases in general. Therefore, in this study, we aimed to confirm whether regulation of autophagy by using the Akt phosphorylation agonist SC79 can inhibit abnormal apoptosis of OPCs and promote myelin maturation and white matter development in neonatal rats with WMD. We investigated the effect of inflammation on oligodendrocyte development in P0 neonatal rats by intracerebellar injection of LPS, and collected brain tissue at P2 and P5. Immunohistochemical and immunofluorescence staining were used to evaluate white matter damage, while immunofluorescence staining, terminal deoxynucleotidyl transferase dUTP nick end labeling analysis (TUNEL), and western blotting were used to evaluate autophagy and apoptosis. First, we observed that white matter development was arrested and white matter fiber maturation was impaired in LPS-inflicted pups compared with those in the sham-operated group. Second, treatment with SC79 reduced the levels of LC3II, caspase 3, caspase 9, and Bax/Bcl-2 and increased the levels of p62, p-Akt, and p-mTOR in the brain tissue of neonatal rats. Finally, SC79 treatment inhibited OPC apoptosis by increasing the binding of Beclin 1 to Bcl-2, which promoted OPC differentiation and maturation. However, the opposite results were observed after rapamycin administration. Taken together, our results suggest that SC79 can inhibit the abnormal apoptosis of OPCs caused by excessive autophagy through the Akt/mTOR pathway and that SC79 is a potential therapeutic agent for WMD in preterm infants.
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Células Precursoras de Oligodendrócitos , Substância Branca , Humanos , Recém-Nascido , Ratos , Animais , Substância Branca/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Precursoras de Oligodendrócitos/metabolismo , Lipopolissacarídeos/farmacologia , Recém-Nascido Prematuro , Apoptose , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Inflamação , Proteínas Proto-Oncogênicas c-bcl-2/metabolismoRESUMO
BACKGROUND: Inappropriate activation and aggregation of platelets can lead to arterial thrombosis. Thrombin is the most potent platelet agonist that activates human platelets via two PARs (proteinase-activated receptors), PAR1 and PAR4. The aim is to study the activity and mechanism of an oligosaccharide HS-11 (the undecasaccharide, derived from sea cucumber Holothuria fuscopunctata) in inhibiting thrombin-mediated platelet activation and aggregation and to evaluate its antithrombotic activity. METHODS: Platelet activation was analyzed by detecting CD62P/P-selectin expression using flow cytometry. The HS-11-thrombin interaction and the binding site were studied by biolayer interferometry. Intracellular Ca2+ mobilization of platelets was measured by FLIPR Tetra System using Fluo-4 AM (Fluo-4 acetoxymethyl). Platelet aggregation, thrombus formation, and bleeding Assay were assessed. RESULTS: An oligosaccharide HS-11, depolymerized from fucosylated glycosaminoglycan from sea cucumber Holothuria fuscopunctata blocks the interaction of thrombin with PAR1 and PAR4 complex by directly binding to thrombin exosite II, and completely inhibits platelet signal transduction, including intracellular Ca2+ mobilization and protein phosphorylation. Furthermore, HS-11 potently inhibits thrombin-PARs-mediated platelet aggregation and reduces thrombus formation in a model of ex vivo thrombosis. CONCLUSIONS: The study firstly report that the fucosylated glycosaminoglycan oligosaccharide has antiplatelet activity by binding to thrombin exosite II, and demonstrates that thrombin exosite II plays an important role in the simultaneous activation of PAR1 and PAR4, which may be a potential antithrombotic target for effective treatment of arterial thrombosis.
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Receptor PAR-1 , Trombose , Humanos , Plaquetas/metabolismo , Fibrinolíticos/farmacologia , Glicosaminoglicanos/metabolismo , Oligossacarídeos/farmacologia , Ativação Plaquetária , Agregação Plaquetária , Receptores de Trombina , Trombina/metabolismo , Trombose/prevenção & controle , Trombose/metabolismoRESUMO
OBJECTIVES: Coronary artery calcification (CAC) is frequently observed in Takayasu's arteritis (TAK). Our objective is to calculate the prevalence and severity of CAC in TAK, while evaluating the influence of traditional cardiovascular risk factors, glucocorticoid exposure, and disease activity on CAC. METHODS: This retrospective study involved 155 TAK patients. We measured the Agatston score by coronary computed tomography angiography (CCTA) and categorised all patients into groups with or without CAC (41 vs. 114) to compare clinical characteristics and ancillary findings between the two groups. RESULTS: Among the TAK patients, a total of 41 TAK patients (26.45%) exhibited CAC. Age of onset, disease duration, history of hypertension, history of hyperlipidaemia, Numano V and glucocorticoid use emerged as the independent risk factors for developing CAC in TAK (OR [95% CI] 1.084[1.028-1.142], p=0.003; 1.005 [1.001-1.010], p=0.020; 4.792 [1.713-13.411], p=0.003; 4.199 [1.087-16.219], p=0.037; 3.287 [1.070-10.100], p=0.038; 3.558[1.269-9.977], p=0.016). Nonetheless, CAC was not associated with disease activity. Moreover, the extent of calcification score in TAK showed a positive correlation with the number of traditional cardiovascular risk factors. CONCLUSIONS: We recommend CCTA screening for Numano V classified TAK patients. Glucocorticoid usage significantly escalates the risk of CAC. Therefore, in cases of effectively controlled disease, the inclusion of immunosuppressants aimed at reducing glucocorticoid dosage is advisable.
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Angiografia por Tomografia Computadorizada , Angiografia Coronária , Doença da Artéria Coronariana , Arterite de Takayasu , Calcificação Vascular , Humanos , Arterite de Takayasu/diagnóstico por imagem , Arterite de Takayasu/epidemiologia , Arterite de Takayasu/tratamento farmacológico , Arterite de Takayasu/complicações , Feminino , Masculino , Estudos Retrospectivos , Adulto , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/epidemiologia , Doença da Artéria Coronariana/etiologia , Calcificação Vascular/diagnóstico por imagem , Calcificação Vascular/epidemiologia , Pessoa de Meia-Idade , Fatores de Risco , Prevalência , Índice de Gravidade de Doença , Glucocorticoides/uso terapêutico , Glucocorticoides/efeitos adversos , Adulto Jovem , Fatores de Risco de Doenças CardíacasRESUMO
At present, the mechanism of varietal differences in cadmium (Cd) accumulation in rice is not well understood. Two rice cultivars, ZZY (high translocation-high grain Cd) and SJ18 (low translocation-low grain Cd), were used to analyze transcriptome differences in the spike-neck tissue in field trials. The results showed that, compared with ZZY, 22,367 differentially expressed genes (DEGs) were identified in SJ18, including 2941 upregulated and 19,426 downregulated genes. GO analysis enriched 59 downregulated terms, concerning 24 terms enriched for more than 1000 DEGs, including cellular and metabolic processes, biological regulation, localization, catalytic activity, transporter activity, signaling, etc. KEGG enrichment identified 21 significant downregulated pathways, regarding the ribosome, metabolic pathways, biosynthesis of secondary metabolism, signaling transduction, cell membrane and cytoskeleton synthesis, genetic information transfer, amino acid synthesis, etc. Weighted gene co-expression network analysis (WGCNA) revealed that these DEGs could be clustered into five modules. Among them, the yellow module was significantly related to SJ18 with hub genes related to OsHMA and OsActin, whereas the brown module was significantly related to ZZY with hub genes related to mitogen-activated protein kinase (MAPK), CBS, and glutaredoxin. This suggests that different mechanisms are involved in the process of spike-neck-grain Cd translocation among varieties. This study provides new insights into the mechanisms underlying differences in Cd transport among rice varieties.
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Oryza , Oryza/genética , Transcriptoma , Cádmio/toxicidade , Perfilação da Expressão Gênica , Metabolismo Secundário , Grão ComestívelRESUMO
Ridge-furrow with full ï¬lm mulching has been widely applied to increase crop yield and water productivity on the Loess Plateau, but it may stimulate carbon (C) mineralization. How to integrate other technological benefits based on this technology for long-term maintenance of high yield and soil fertility is a pressing issue. With the local farmers' practice (FP) as a control, three integrated soil-crop system management (ISSM) practices integrating fertilizer rates, fertilizer types and planting densities (ISSM-N1, ISSM-N2 and ISSM-MN) were established to improve maize yield and soil quality. Compared with the FP, the maize yield increased by 13.34%, 21.83% and 30.24%, and the soil quality index (SQI) increased by 9.66%, 14.91% and 38.38% for ISSM-N1, ISSM-N2 and ISSM-MN, respectively. However, ISSM-N1 did not significantly increase yield, and ISSM-N2 increased residual soil nitrate and decreased nitrogen (N) partial factor productivity significantly. Compared to the FP, ISSM practices increased soil organic carbon (SOC), labile organic C fractions (LOCFs) and potassium permanganate organic C fractions in the topsoil to varying degrees, but only ISSM-MN reached significant levels for most C fractions. The sensitivity index indicated very easily oxidizable C (24.6%), easily oxidizable C (24.7%), hot-water extractable C (30.8%), labile organic C (24.7%) and particulate organic C (57.3%) were more sensitive than SOC (22.7%). ISSM-MN sequestered significantly higher C than the other treatments. The results of the relative importance analysis and the structural equation model indicated that LOCFs were the direct contributors to yield, while recalcitrant C (CO) was the indirect contributor, revealing the underlying mechanism that CO decomposed to replenish LOCFs and the total N pool with the water soluble C pool as the transit station. Overall, ISSM-MN is the most promising strategy to improve crop yield and soil fertility in the long term on the Loess Plateau.
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Agricultura , Solo , Solo/química , Agricultura/métodos , Carbono/análise , Fertilizantes/análise , Zea mays , Nitrogênio/análise , Água/análise , ChinaRESUMO
INTRODUCTION: This study aimed to evaluate the prevalence and psychometric properties of vertigo and dizziness in an obstructive sleep apnoea (OSA) population. METHODS: Five hundred and twelve OSA patients and 53 controls were enroled. All eligible subjects were asked to complete the basic information questionnaire, the Chinese version of Vestibular Disorders Activities of Daily Living (VADL-C), the Dizziness Handicap Inventory (DHI) and the Activities-Specific Balance Confidence (ABC) scale. RESULTS: Among 512 enroled OSA patients, a 22.46% (115) prevalence of vertigo and dizziness was found. The scores of the VADL-C, DHI and ABC of the study group were significantly worse (p < .001) than those of the control group, while the abnormal rates of the three scales in the study group were higher than those of the control group. In the study group, the results of the VADL-C were correlated with those of the DHI (r = .55, p < .001) and inversely correlated with those of the ABC (r = -.50, p < .001), and the results of the DHI were inversely correlated with those of the ABC (r = -.60, p < .001). CONCLUSIONS: A high prevalence of vertigo and dizziness in the OSA population was detected. Psychometric results showed that vertigo and dizziness in OSA patients led to changes in activities of daily living, increased frequency of somatic symptoms, and reduced balance confidence. In the diagnosis and treatment of OSA patients, the occurrence of vertigo and dizziness is worth clinicians' attention.
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Tontura , Psicometria , Apneia Obstrutiva do Sono , Vertigem , Humanos , Masculino , Tontura/epidemiologia , Feminino , Apneia Obstrutiva do Sono/epidemiologia , Apneia Obstrutiva do Sono/complicações , Apneia Obstrutiva do Sono/diagnóstico , Vertigem/epidemiologia , Vertigem/diagnóstico , Estudos Transversais , Pessoa de Meia-Idade , Prevalência , Inquéritos e Questionários , Adulto , Atividades Cotidianas , IdosoRESUMO
BACKGROUND: Previous studies show that spinal cord ischemia and hypoxia is an important cause of spinal cord necrosis and neurological loss. Therefore, the study aimed to identify genes related to ischemia and hypoxia after spinal cord injury (SCI) and analyze their functions, regulatory mechanism, and potential in regulating immune infiltration. METHODS: The expression profiles of GSE5296, GSE47681, and GSE217797 were downloaded from the Gene Expression Omnibus database. Gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to determine the function and pathway enrichment of ischemia- and hypoxia-related differentially expressed genes (IAHRDEGs) in SCI. LASSO model was constructed, and support vector machine analysis was used to identify key genes. The diagnostic values of key genes were evaluated using decision curve analysis and receiver operating characteristic curve analysis. The interaction networks of miRNAs-IAHRDEGs and IAHRDEGs-transcription factors were predicted and constructed with the ENCORI database and Cytoscape software. CIBERSORT algorithm was utilized to analyze the correlation between key gene expression and immune cell infiltration. RESULTS: There were 27 IAHRDEGs identified to be significantly expressed in SCI at first. These genes were mostly significantly enriched in wound healing function and the pathway associated with lipid and atherosclerosis. Next, five key IAHRDEGs (Abca1, Casp1, Lpl, Procr, Tnfrsf1a) were identified and predicted to have diagnostic value. Moreover, the five key genes are closely related to immune cell infiltration. CONCLUSION: Abca1, Casp1, Lpl, Procr, and Tnfrsf1a may promote the pathogenesis of ischemic or hypoxic SCI by regulating vascular damage, inflammation, and immune infiltration.
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Traumatismos da Medula Espinal , Fatores de Transcrição , Humanos , Receptor de Proteína C Endotelial , Traumatismos da Medula Espinal/genética , Isquemia , Biologia ComputacionalRESUMO
Increasing evidence has shown a higher sensitivity of Alzheimer's disease (AD) progression by local hippocampal atrophy rather than the whole volume. However, existing morphological methods based on subfield-volume or surface in imaging studies are not capable to describe the comprehensive process of hippocampal atrophy as sensitive as histological findings. To map histological distinctive measurements onto medical magnetic resonance (MR) images, we propose a multiscale skeletal representation (m-s-rep) to quantify focal hippocampal atrophy during AD progression in longitudinal cohorts from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The m-s-rep captures large-to-small-scale hippocampal morphology by spoke interpolation over label projection on skeletal models. To enhance morphological correspondence within subjects, we align the longitudinal m-s-reps by surface-based transformations from baseline to subsequent timepoints. Cross-sectional and longitudinal measurements derived from m-s-rep are statistically analyzed to comprehensively evaluate the bilateral hippocampal atrophy. Our findings reveal that during the early AD progression, atrophy primarily affects the lateral-medial extent of the hippocampus, with a difference of 1.8 mm in lateral-medial width in 2 years preceding conversion (p < .001), and the medial head exhibits a maximum difference of 3.05%/year in local atrophy rate (p = .011) compared to controls. Moreover, progressive mild cognitive impairment (pMCI) exhibits more severe and widespread atrophy in the head and body compared to stable mild cognitive impairment (sMCI), with a maximum difference of 1.21 mm in thickness in the medial head 1 year preceding conversion (p = .012). In summary, our proposed method can quantitatively measure the hippocampal morphological changes on 3T MR images, potentially assisting the pre-diagnosis and prognosis of AD.
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Doença de Alzheimer , Hipocampo , Doença de Alzheimer/diagnóstico por imagem , Doença de Alzheimer/patologia , Anisotropia , Atrofia , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Conjuntos de Dados como Assunto , Imageamento por Ressonância Magnética , Neuroimagem , Progressão da DoençaRESUMO
The relationship between alcohol dehydrogenase (ADH) and liver fibrosis has been studied, but the mechanism of ADH involvement in liver fibrosis remains unclear. The aim of the present study was to explore the role of ADHI, the classical liver ADH, in hepatic stellate cell (HSC) activation and the effect of 4-methylpyrazole (4-MP), an ADH inhibitor, on liver fibrosis induced by carbon tetrachloride (CCl4) in mice. The results showed that overexpression of ADHI significantly increases proliferation, migration, adhesion and invasion rates of HSC-T6 cells as compared with controls. When HSC-T6 cells were activated by ethanol, TGF-ß1 or LPS, the expression of ADHI was elevated significantly (P < 0.05). Overexpression of ADHI significantly increased the levels of COL1A1 and α-SMA, markers of HSC activation. Moreover, the expression of COL1A1 and α-SMA was decreased significantly by transfection of ADHI siRNA (P < 0.01). In a liver fibrosis mouse model ADH activity increased significantly and was highest in the 3rd week. The activity of ADH in the liver was correlated with its activity in the serum (P < 0.05). 4-MP significantly decreased ADH activity and ameliorated liver injury, and ADH activity was positively correlated with the Ishak score of liver fibrosis. In conclusion, ADHI plays an important role in the activation of HSC, and inhibition of ADH ameliorates liver fibrosis in mice.
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Células Estreladas do Fígado , Cirrose Hepática , Animais , Camundongos , Tetracloreto de Carbono/toxicidade , Modelos Animais de Doenças , Células Estreladas do Fígado/metabolismo , Fígado/metabolismo , Cirrose Hepática/patologia , Fator de Crescimento Transformador beta1/metabolismo , Álcool Desidrogenase/metabolismoRESUMO
Homeostasis of intestinal stem cells (ISCs) is maintained by the orchestration of niche factors and intrinsic signaling networks. Here, we have found that deletion of Erk1 and Erk2 (Erk1/2) in intestinal epithelial cells at embryonic stages resulted in an unexpected increase in cell proliferation and migration, expansion of ISCs, and formation of polyp-like structures, leading to postnatal death. Deficiency of epithelial Erk1/2 results in defects in secretory cell differentiation as well as impaired mesenchymal cell proliferation and maturation. Deletion of Erk1/2 strongly activated Wnt signaling through both cell-autonomous and non-autonomous mechanisms. In epithelial cells, Erk1/2 depletion resulted in loss of feedback regulation, leading to Ras/Raf cascade activation that transactivated Akt activity to stimulate the mTor and Wnt/ß-catenin pathways. Moreover, Erk1/2 deficiency reduced the levels of Indian hedgehog and the expression of downstream pathway components, including mesenchymal Bmp4 - a Wnt suppressor in intestines. Inhibition of mTor signaling by rapamycin partially rescued Erk1/2 depletion-induced intestinal defects and significantly prolonged the lifespan of mutant mice. These data demonstrate that Erk/Mapk signaling functions as a key modulator of Wnt signaling through coordination of epithelial-mesenchymal interactions during intestinal development.
Assuntos
Intestinos/embriologia , Sistema de Sinalização das MAP Quinases , Via de Sinalização Wnt , Animais , Proteína Morfogenética Óssea 4/genética , Proteína Morfogenética Óssea 4/metabolismo , Camundongos , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/genética , Serina-Treonina Quinases TOR/metabolismo , Quinases raf/genética , Quinases raf/metabolismoRESUMO
Zika virus (ZIKV) belongs to mosquito-borne flaviviruses. Unlike other members in the family, ZIKV can be sexually transmitted, and the female genital tracts are susceptible to ZIKV. However, the impact of ZIKV infection on nonpregnant female reproductive health is not understood. In this study, we investigated the effects of ZIKV infection on the ovary by using nonpregnant female interferon α/ß receptor-deficient (Ifnar1-/-) mice. The results showed that the ovary supported ZIKV replication, and the granulosa and theca cells of antral follicles were susceptible. ZIKV replication in situ significantly reduced the numbers of antral follicles, aggravated follicular atresia, and disrupted folliculogenesis. Notably, ZIKV replication in the ovary caused disordered ovarian steroidogenesis manifested by decreased expression of key enzymes linked to sex hormone synthesis, including the cytochrome P450 17A1 (CYP17A1) and aromatase (CYP19A1). Further, we observed that ZIKV infection disrupted the estrous cycle and thus prolonged the time to conceive. More importantly, although ZIKV RNA could not be detected at 3 months postinfection, damaged ovarian structure and dysfunction were also observed. Taken together, our study demonstrates that ZIKV infection in nonpregnant female mice cause ovarian damage and dysfunction, even long after ZIKV clearance. These data provide important information to understand the effects of ZIKV infection in female reproductive tissues and basic evidence for further studies. IMPORTANCE Zika virus (ZIKV), a flavivirus, is primarily transmitted by mosquito bites. But it can also be transmitted vertically and sexually. Although ZIKV-associated Guillain-Barré syndrome and microcephaly have drawn great attention, there have been few studies on the potential effects of ZIKV on the genital tract of nonpregnant females. This study investigated the effects of ZIKV on the ovaries in mice. We found that ZIKV replicated in the ovary and the granulosa and theca cells of antral follicles were susceptible. ZIKV replication in situ significantly damaged ovarian structure and function and disrupted folliculogenesis. Notably, ZIKV infection further disrupted the estrous cycle and prolonged the time to conceive in mice by causing disordered ovarian steroidogenesis. These effects were observed in both the acute phase and the recovery phase after viral elimination. Overall, the new findings provide important additions to make out the potential adverse impacts of ZIKV on reproductive health in females.
Assuntos
Fertilização , Ovário/virologia , Progesterona/sangue , Zika virus/patogenicidade , Animais , Modelos Animais de Doenças , Ciclo Estral , Feminino , Atresia Folicular , Camundongos , Ovário/patologia , Ovário/fisiopatologia , Receptor de Interferon alfa e beta/deficiência , Especificidade da Espécie , Replicação Viral , Zika virus/fisiologia , Infecção por Zika virus/sangue , Infecção por Zika virus/virologiaRESUMO
BACKGROUND: The floc is a characteristic of microbial aggregate growth, displaying cloudy suspensions in water. Floc formation has been demonstrated in a series of bacteria and the floc-forming bacteria play a crucial role in activated sludge (AS) process widely used for municipal sewage and industrial wastewater treatment over a century. It has been demonstrated that some exopolysaccharide biosynthesis genes and the sigma factor (sigma54 or rpoN) were required for floc forming in some bacteria. However, the mechanism underlying the floc formation stills need to be elucidated. RESULTS: In this study, we demonstrate that a TPR (Tetratricopeptide repeats) protein-encoding gene prsT is required for floc formation of Aquincola tertiaricarbonis RN12 and an upstream PEP-CTERM gene (designated pepA), regulated by RpoN1, is involved in its floc formation but not swarming motility and biofilm formation. Overexpression of PepA could rescue the floc-forming phenotype of the rpoN1 mutant by decreasing the released soluble exopolysaccharides and increasing the bound polymers. CONCLUSION: Our results indicate that the wide-spread PEP-CTERM proteins play an important role in the self-flocculation of bacterial cells and may be a component of extracellular polymeric substances required for floc-formation.
Assuntos
Burkholderiales , Esgotos , Esgotos/microbiologia , Bactérias/genética , Proteínas , FloculaçãoRESUMO
Hand, foot, and mouth disease (HFMD) is a common pediatric infectious illness caused by enteroviruses (EVs). EV-A serotypes are the main pathogens associated with HFMD. In this study, 213 stool samples from 213 children with severe HFMD in Yunnan, China in 2013, 2015, and 2016 were further analyzed retrospectively for EV-B infection. A total of 70.0% of the specimens tested positive for EV.20 EV serotypes were detected. The predominant serotype was enterovirus A71 (EV-A71, 27.7%), followed by coxsackievirus B4 (CV-B4, 16.4%), CV-A16 (9.9%), CV-B5 (6.6%), and Echovirus 9 (E-9,4.7%). EV-A and EV-B accounted for 45.1% and 41.3%, respectively. Among the positive specimens, 28.6% were CV-Bs. Co-infection was present in 19.3% of these cases. In the study, CV-B5 and the majority of CV-B4 isolates belonged to genotypes VI and C3, respectively. This result indicates that EV-B, especially CV-Bs, might be the important agents associated with HFMD and this knowledge will contribute to the prevention and treatment of the disease.
Assuntos
Enterovirus Humano A , Infecções por Enterovirus , Enterovirus , Doença de Mão, Pé e Boca , Criança , Humanos , Lactente , Doença de Mão, Pé e Boca/epidemiologia , Doença de Mão, Pé e Boca/complicações , Estudos Retrospectivos , China/epidemiologia , Enterovirus Humano B/genética , Infecções por Enterovirus/complicaçõesRESUMO
Green micro-light emitting diodes (micro-LEDs) is one of the three primary color light sources as full-color display, which serves as a key research object in the field of micro-LED display. As the micro-LED size decreases, the surface-area-to-volume ratio of the device increases, leading to more serious damage on the sidewall by inductively coupled plasma (ICP) etching. The passivation process of SiO2 provides an effective method to reduce sidewall damage caused by ICP etching. In this work, green rectangular micro-LEDs with passivation layer thickness of 0â¼600â nm was designed using the finite-difference time-domain (FDTD) simulation. In order to verify the simulation results, the micro-LED array was fabricated by parallel laser micro-lens array (MLA) lithography in high speed and large area. The effect of the SiO2 passivation layer thickness on the performance of the green micro-LED was analyzed, which shows that the passivation layer thickness-light extraction efficiency curve fluctuates periodically. For the sample with 90â nm thickness of SiO2 passivation layer, there exists a small leakage current and higher operating current density, and the maximum external quantum efficiency (EQE) is 2.8 times higher than micro-LED without SiO2 passivation layer.