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irGSEA is an R package designed to assess the outcomes of various gene set scoring methods when applied to single-cell RNA sequencing data. This package incorporates six distinct scoring methods that rely on the expression ranks of genes, emphasizing relative expression levels over absolute values. The implemented methods include AUCell, UCell, singscore, ssGSEA, JASMINE and Viper. Previous studies have demonstrated the robustness of these methods to variations in dataset size and composition, generating enrichment scores based solely on the relative gene expression of individual cells. By employing the robust rank aggregation algorithm, irGSEA amalgamates results from all six methods to ascertain the statistical significance of target gene sets across diverse scoring methods. The package prioritizes user-friendliness, allowing direct input of expression matrices or seamless interaction with Seurat objects. Furthermore, it facilitates a comprehensive visualization of results. The irGSEA package and its accompanying documentation are accessible on GitHub (https://github.com/chuiqin/irGSEA).
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Algoritmos , Análise de Célula Única , Software , Análise de Célula Única/métodos , Humanos , Biologia Computacional/métodos , Perfilação da Expressão Gênica/métodos , Análise de Sequência de RNA/métodosRESUMO
Takotsubo syndrome (TTS), commonly referred to as "broken heart syndrome," is a distinctive form of acute and reversible heart failure that primarily affects young to middle-aged individuals, particularly women. While emotional or physical stressors often trigger TTS, rare cases have been linked to interventional procedures for congenital heart disease (CHD). Despite its recognition, the exact causes of TTS remain elusive. Research indicates that dysregulation in autonomic nerve function, involving sympathetic and parasympathetic activities, plays a pivotal role. Genetic factors, hormonal influences like estrogen, and inflammatory processes also contribute, unveiling potential gender-specific differences in its occurrence. Understanding these multifaceted aspects of TTS is crucial for refining clinical approaches and therapies. Continued research efforts will not only deepen our understanding of this syndrome but also pave the way for more targeted and effective diagnostic and treatment strategies. In this report, we conduct an in-depth analysis of a case involving a TTS patient, examining the illness progression and treatment procedures. The aim of this analysis is to enhance the understanding of TTS among primary care physicians. By delving into this case, we aspire to prevent misdiagnosis of typical TTS cases that patients may present, thereby ensuring a more accurate diagnosis and appropriate treatment.
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Permeabilidade do Canal Arterial , Insuficiência Cardíaca , Cardiomiopatia de Takotsubo , Pessoa de Meia-Idade , Humanos , Feminino , Cardiomiopatia de Takotsubo/diagnóstico por imagem , Cardiomiopatia de Takotsubo/etiologia , Permeabilidade do Canal Arterial/complicações , Insuficiência Cardíaca/complicações , Emoções , SíndromeRESUMO
PURPOSE: Metabolic-associated fatty liver disease (MAFLD) is an aging-related disease. Obstructive sleep apnea (OSA) may cause MAFLD. This study aimed to explore whether or not intermittent hypoxia (IH), the hallmark of OSA, induces liver aging through oxidative stress. METHODS: C57BL/6J male mice were administered normal air (control), IH, or antioxidant tempol + IH daily for 6 weeks before the collection of serum and liver tissue samples. A histological examination was conducted to assess liver aging. ELISA was performed to measure liver function indicator levels in the serum and oxidative stress indicator activities in the liver. Western blot analysis was carried out to determine the protein expression of the markers related to oxidative stress, inflammation, and senescence. RESULTS: Compared with control, IH resulted in significant increases in serum ALT, AST, and TG levels in mice (all P < 0.001), along with lobular inflammation and accumulation of collagen and fat in the liver. The protein levels of inflammatory factors and senescent markers were significantly increased in the IH mouse liver compared with those in the control mouse liver. Meanwhile, IH significantly reduced SOD and CAT activities while enhancing p22phox and Nrf2 protein expression in mouse liver compared with control. Importantly, antioxidant therapy with tempol effectively abrogated the effects of IH on oxidative stress response and aging-related liver injury. CONCLUSIONS: Our findings suggest that IH induces liver inflammation and aging through oxidative stress. OSA may exacerbate target organ aging and participate in target organ damage. Strategies targeting oxidative stress may prevent and treat OSA-related MAFLD.
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Antioxidantes , Óxidos N-Cíclicos , Apneia Obstrutiva do Sono , Marcadores de Spin , Camundongos , Masculino , Animais , Antioxidantes/farmacologia , Camundongos Endogâmicos C57BL , Estresse Oxidativo/fisiologia , Fígado/patologia , Hipóxia , Inflamação/complicaçõesRESUMO
BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is a leading cause of chronic liver disease worldwide. Autophagy plays a pivotal role in lipid metabolism; however, the mechanism underlying the reduced autophagic activity in MAFLD remains elusive. METHODS: Autophagy was monitored by TUNEL assay and immunofluorescence staining of LC3. The expression of autophagy-related proteins, PPARα, HDAC2, and HRD1 was detected by Western blot. The association between HDAC2 and PPARα promoter was assessed by chromatin immunoprecipitation (ChIP) and dual-luciferase assays, and the HRD1-mediated ubiquitin-proteasomal degradation of HDAC2 was detected by co-immunoprecipitation (co-IP). The in vitro findings were validated in a hypoxia-induced MAFLD mouse model. Histological changes, fibrosis, and apoptosis in liver tissues were detected by hematoxylin and eosin staining, Masson's trichrome staining, and TUNEL assay. The immunoreactivities of key molecules were examined by IHC analysis. RESULTS: Hypoxia-suppressed autophagy in hepatocytes. Hypoxic exposure downregulated HRD1 and PPARα, while upregulating HDAC2 in hepatocytes. Overexpression of PPARα promoted hepatic autophagy, while knocking down HDAC2 or overexpressing HRD1 reduced hypoxia-suppressed autophagy in hepatocytes. Mechanistically, HDAC2 acted as a transcriptional repressor of PPARα, and HRD1 mediated the degradation of HDAC2 through the ubiquitin-proteasome pathway. Functional studies further showed that hypoxia-suppressed hepatic autophagy via the HRD1/HDAC2/PPARα axis in vitro and in vivo. CONCLUSION: HRD1-mediated ubiquitination of HDAC2 regulates PPARα-mediated autophagy and ameliorates hypoxia-induced MAFLD.
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OBJECTIVES: Growing evidence appears to intimate a profound connection between periodontitis and coronary atherosclerosis (CA), yet the existence of a causal relationship remains unclear. Through the implementation of Mendelian randomization analysis, we further evaluated the potential causal link between chronic/acute periodontitis (CP/AP) and CA. METHODS: Utilizing genome-wide association study (GWAS) summary statistics, we incorporated periodontitis data derived from European samples (n1 = 198,441; n2 = 195,762) and CA data from 61,194 cases. We conducted a 2 sample, bidirectional Mendelian randomization (MR) analysis using the inverse-variance weighted (IVW) method as the main analytical approach. Supplementary analyses were executed through MR Egger, Weighted median (WM), IVW, Simple mode, and Weighted mode approaches. RESULTS: The IVW analysis revealed no significant causal relationship between CA and periodontitis (CA-CP: OR = 2.110, 95% CI = 0.208-21.317, P = .527; CA-AP: OR = 0.414, 95% CI = 0.051-3.384, P = .644). Similarly, the bidirectional analysis did not identify impact of periodontitis on CA (OR = 1.000, 95% CI = 0.999-1.001, P = .953). The supplementary analyses corroborated these findings. CONCLUSIONS: While studies highlighting a correlation between periodontitis and CA, our comprehensive analysis does not corroborate a causal association between periodontitis and CA. Further research is needed to elucidate other potential shared mechanisms and causal evidence between periodontitis and CA.
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Doença da Artéria Coronariana , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Periodontite , Humanos , Doença da Artéria Coronariana/genética , Periodontite/genética , Periodontite/complicações , Polimorfismo de Nucleotídeo ÚnicoRESUMO
BACKGROUND: Nocturnal hypoxemia is an established factor in the pathogenesis and exacerbation of term metabolic (dysfunction) associated fatty liver disease (MAFLD). Kupffer cells (KCs) are resident macrophages in the liver, and their activity is closely related to the progress of MAFLD. KC insufficient autophagy is involved in MAFLD pathogenesis. Herein, the regulatory mechanism of KC autophagy under chronic intermittent hypoxia (CIH) condition was investigated. METHODS: Primary KCs and hepatic stellate cells (HSCs) were isolated from mouse liver. Immunofluorescence was employed to detect immunofluorescence intensity of LC3 protein and HDAC4 distribution. KC apoptosis was measured by TUNEL staining. Dual-luciferase reporter and ChIP assays were performed to analyze the interactions between HDAC4, MEF2C and RUBCN. RESULTS: Herein, our results revealed that CIH-induced increased CX3CL1 in HSCs inhibited KC autophagy and promoted cell apoptosis by interacting with CX3CR1. Meanwhile, CX3CL1 treatment inhibited KC autophagy (p < 0.001, fold change: 0.059) and promoted cell apoptosis (p < 0.001, fold change: 8.18). Rubicon knockdown promoted KC autophagy (p < 0.001, fold change: 2.90) and inhibited cell apoptosis (p < 0.05, fold change: 0.23), while these effects were reversed by CX3CL1 treatment (p < 0.01, fold change: 6.59; p < 0.001, fold change: 0.35). Our mechanistic experiments demonstrated that HDAC4 overexpression transcriptionally inhibited RUBCN expression by interacting with MEF2C, thereby promoting KC autophagy and inhibiting cell apoptosis. Moreover, CaMKIIδ inhibition promoted the translocation of HDAC4 from the cytosol to the nucleus to promote KC autophagy and inhibit the apoptosis. CONCLUSION: Taken together, CIH-induced increased CX3CL1 expression in HSCs inhibited KC autophagy and promoted apoptosis by regulating the CX3CR1/ CaMKIIδ/HDAC4/Rubicon axis.
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Apoptose , Células de Kupffer , Animais , Camundongos , Autofagia , Células Estreladas do Fígado , HipóxiaRESUMO
Orthorhombic niobium pentoxide (T-Nb2O5) is regarded as a potential anode material for lithium-ion batteries (LIBs) due to ultrafast charge/discharge and high safety. However, the poor electronic conductivity and low mass loading of nanostructured T-Nb2O5 limit its practical application in LIBs. Herein, we design and construct dense microspheres consisting of nanostructured T-Nb2O5 embedded in amorphous N-doped carbon (Nb2O5@NC) via a facile method to achieve fast ionic and electronic transport as well as a high mass loading. The dense micro-sized particles with an interconnected carbon network avoid the low mass loading and volumetric energy density of conventional nanostructures. Interconnected pores in the range of a few nanometers are also formed in the Nb2O5@NC microspheres. Notably, at a high mass loading of 12.8 mg cm-2, Nb2O5@NC can achieve a high specific capacity of 171.5 mAh g-1 and an areal capacity of 2.05 mAh cm-2, showing its high lithium storage capacity. The intercalation reaction mechanism with a small volume change during cycling at both crystal lattice and microsphere levels is confirmed by in situ X-ray diffraction and in situ high-resolution transmission electron microscopy. The elegant structure and the electrochemical reaction mechanism disclosed in the work is important for designing ultrafast-(dis)charge electrode materials.
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RATIONALE: Idiopathic hypereosinophilic syndrome (IHES) is a rare disease in which patients which present with eosinophilia-associated damage. Previous studies focused on organ damage from increased eosinophilic granulocytosis. We report IHES in a patient who presented with multiple organ damage (MOD). PATIENT CONCERNS: A 52-year-old male presented with MOD, including myocardial damage suggestive of myocardial infarction, cardiac tamponade, respiratory failure, skin damage, and gastrointestinal damage. DIAGNOSES: The absolute eosinophil count was 12,920/mm, much higher than occurs in other diseases associated with eosinophilia (1500/mm), and suggesting a diagnosis of IHES. INTERVENTIONS: Prednisone combined with hydroxyurea. OUTCOMES: At 6 months after completion of drug treatment, the patient had no chest pain or dyspnea, and the results of a blood panel, chest computed tomography, and gastroscopy were normal. LESSONS: MOD is very rare in patients with IHES. Patients receiving prompt diagnosis and treatment have very good prognoses.
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Síndrome Hipereosinofílica/diagnóstico , Diagnóstico Diferencial , Humanos , Síndrome Hipereosinofílica/tratamento farmacológico , Síndrome Hipereosinofílica/patologia , Masculino , Pessoa de Meia-Idade , Insuficiência de Múltiplos Órgãos/diagnóstico , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Insuficiência de Múltiplos Órgãos/etiologiaRESUMO
The study with completely randomized design on Loess Plateau showed that soil water storage, water consumption, and water profit and loss had a positive correlation with the amount of irrigation. Managed with light, moderate and excessive pruning, soil water storage was increased by 0.2%, 0.5% and 0.9%, soil water consumption was reduced by 0.5%, 2.0% and 2.5%, while soil water profit and loss was increased by 150%, 190% and 210%, respectively. Under treatments with irrigation, covering with grass, mulching with plastic film, and pruning, soil water storage was increased by 4.4%, 1.2%, 1.6% and 0.5%, respectively. Irrigation, moderate pruning, covering with grass, and mulching with plastic film could increase leaf water potential and the angle between little leaf and stem, and excessive pruning could increase the chlorophyll content at most extent (0.27 mg x dm(-2)). The angle between little leaf and stem had a positive correlation with leaf water potential, which could be a reliable, direct and punctual index in evaluating the water condition of walnut and soil, and applied extensively in practice.