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It has remained unclear whether individuals with psychiatric disorders involving altered visual processing employ similar neuronal mechanisms during perceptual learning of a visual task. We investigated this question by training patients with body dysmorphic disorder, a psychiatric disorder characterized by distressing or impairing preoccupation with nonexistent or slight defects in one's physical appearance, and healthy controls on a visual detection task for human faces with low spatial frequency components. Brain activation during task performance was measured with functional magnetic resonance imaging before the beginning and after the end of behavioral training. Both groups of participants improved performance on the trained task to a similar extent. However, neuronal changes in the fusiform face area were substantially different between groups such that activation for low spatial frequency faces in the right fusiform face area increased after training in body dysmorphic disorder patients but decreased in controls. Moreover, functional connectivity between left and right fusiform face area decreased after training in patients but increased in controls. Our results indicate that neuronal mechanisms involved in perceptual learning of a face detection task differ fundamentally between body dysmorphic disorder patients and controls. Such different neuronal mechanisms in body dysmorphic disorder patients might reflect the brain's adaptations to altered functions imposed by the psychiatric disorder.
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Transtornos Dismórficos Corporais , Aprendizagem , Imageamento por Ressonância Magnética , Humanos , Transtornos Dismórficos Corporais/fisiopatologia , Transtornos Dismórficos Corporais/psicologia , Transtornos Dismórficos Corporais/diagnóstico por imagem , Feminino , Adulto , Adulto Jovem , Masculino , Aprendizagem/fisiologia , Encéfalo/fisiopatologia , Encéfalo/diagnóstico por imagem , Mapeamento Encefálico , Estimulação Luminosa/métodosRESUMO
Drought is one of the natural stresses that greatly impact plants. Castor bean (Ricinus communis L.) is an oil crop with high economic value. Drought is one of the factors limiting castor bean growth. The drought resistance mechanisms of castor bean have become a research focus. In this study, we used castor germinating embryos as experimental materials, and screened genes related to drought resistance through physiological measurements, proteomics and metabolomics joint analysis; castor drought-related genes were subjected to transient silencing expression analysis in castor leaves to validate their drought-resistant functions, and heterologous overexpression and backward complementary expression in Arabidopsis thaliana, and analysed the mechanism of the genes' response to the participation of Arabidopsis thaliana in drought-resistance.Three drought tolerance-related genes, RcECP 63, RcDDX 31 and RcA/HD1, were obtained by screening and analysis, and transient silencing of expression in castor leaves further verified that these three genes corresponded to drought stress, and heterologous overexpression and back-complementary expression of the three genes in Arabidopsis thaliana revealed that the function of these three genes in drought stress response.In this study, three drought tolerance related genes, RcECP 63, RcDDX 31 and RcA/HD1, were screened and analysed for gene function, which were found to be responsive to drought stress and to function in drought stress, laying the foundation for the study of drought tolerance mechanism in castor bean.
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Arabidopsis , Secas , Ricinus communis , Sementes , Ricinus communis/genética , Ricinus communis/fisiologia , Sementes/genética , Sementes/fisiologia , Sementes/crescimento & desenvolvimento , Arabidopsis/genética , Arabidopsis/fisiologia , Genes de Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Regulação da Expressão Gênica de Plantas , Estresse Fisiológico/genética , Resistência à SecaRESUMO
BACKGROUND: Effects of intensive blood pressure (BP) control on cognitive outcomes in patients with excess orthostatic BP changes are unclear. We aimed to evaluate whether orthostatic BP changes modified the effects of BP intervention on cognitive impairment. METHODS: We analyzed 8547 participants from the Systolic Blood Pressure Intervention Trial Memory and cognition IN Decreased Hypertension. Associations between orthostatic BP changes and incident cognitive outcomes were evaluated by restricted cubic spline curves based on Cox models. The interactions between orthostatic BP changes and intensive BP intervention were assessed. RESULTS: The U-shaped associations were observed between baseline orthostatic systolic BP changes and cognitive outcomes. However, there were insignificant interactions between either change in orthostatic systolic BP (P for interaction = 0.81) or diastolic BP (P for interaction = 0.32) and intensive BP intervention for the composite outcome of probable dementia or mild cognitive impairment (MCI). The hazard ratio of intensive versus standard target for the composite cognitive outcome was 0.82 (95% CI 0.50-1.35) in those with an orthostatic systolic BP reduction of >20 mmHg and 0.41 (95% CI 0.21-0.80) in those with an orthostatic systolic BP increase of >20 mmHg. Results were similar for probable dementia and MCI. The annual changes in global cerebral blood flow (P for interaction = 0.86) consistently favored intensive BP treatment across orthostatic systolic BP changes. CONCLUSION: Intensive BP control did not have a deteriorating effect on cognitive outcomes among hypertensive patients experiencing significant postural BP changes.
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Disfunção Cognitiva , Demência , Hipertensão , Hipotensão Ortostática , Humanos , Pressão Sanguínea , Cognição , Hipertensão/tratamento farmacológico , Hipotensão Ortostática/psicologiaRESUMO
Soilborne diseases cause significant economic losses in agricultural production around the world. They are difficult to control because a host plant is invaded by multiple pathogens, and chemical control often does not work well. In this study, we isolated and identified an endophytic Streptomyces sp. NEAU-DD186 from moss, which showed broad-spectrum antifungal activity against 17 soilborne phytopathogenic fungi, with Bipolaris sorokiniana being the most prominent. The strain also exhibited strong antibacterial activity against soilborne phytopathogenic bacteria Ralstonia solanacearum. To evaluate its biocontrol potential, the strain was prepared into biofertilizer by solid-state fermentation. Response surface methodology was employed to optimize the fermentation conditions for maximizing spore production and revealed that the 1:1 ratio of vermicompost to wheat bran, a temperature of 28°C, and 50% water content with an inoculation amount of 15% represented the optimal parameters. Pot experiments showed that the application of biofertilizer with a spore concentration of 108 CFU/g soil could effectively suppress the occurrence of tomato bacterial wilt caused by R. solanacearum and wheat root rot caused by B. sorokiniana, and the biocontrol efficacy was 81.2 and 72.2%, respectively. Chemical analysis of strain NEAU-DD186 extracts using nuclear magnetic resonance spectrometry and mass analysis indicated that 25-O-malonylguanidylfungin A and 23-O-malonylguanidylfungin A were the main active constituents, which showed high activity against R. solanacearum (EC50 of 2.46 and 2.58 µg ml-1) and B. sorokiniana (EC50 of 3.92 and 3.95 µg ml-1). In conclusion, this study demonstrates that Streptomyces sp. NEAU-DD186 can be developed as biofertilizer to control soilborne diseases.
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Doenças das Plantas , Streptomyces , Doenças das Plantas/prevenção & controle , Agricultura , Antibacterianos , AntifúngicosRESUMO
The Xuanfei Baidu (XFBD) prescription, a traditional Chinese medicine prescription, has demonstrated significant anti-inflammatory activities; however, the number of its reported constituents is limited, and its anti-inflammatory constituents are unclear. In this study, the constituents of XFBD granule, a granule dosage of XFBD prescription, were thoroughly examined in vitro and in vivo using liquid chromatography-quadruple-time-of-flight-mass spectrometry, and the anti-inflammatory constituents were screened. A total of 214 constituents were identified from the XFBD granule, 62 of which were confirmed via comparison with reference standards. After intragastric administration of XFBD granule, 63 and 28 constituents were absorbed into the rat sera and lungs in prototype form, respectively. XFBD granule and XFBD-containing serum were found to significantly reduce nitric oxide (NO) and interleukin-6 (IL-6) secretion in lipopolysaccharide-induced RAW264.7 cells. Five anti-inflammatory constituents (verbasoside, scutellarin, luteolin, apigenin, and pogostone) were found to reduce the concentration of NO and IL-6 in a dose-dependent manner. Moreover, the combination of these five constituents could significantly reduce NO secretion even when the concentration of each constituent was two to three orders of magnitude lower than their individual minimum effective concentrations. Overall, this study provides a valuable reference for the discovery of effective constituents from the XFBD granule.
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Anti-Inflamatórios , Medicamentos de Ervas Chinesas , Lipopolissacarídeos , Animais , Camundongos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Células RAW 264.7 , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Ratos , Cromatografia Líquida/métodos , Masculino , Óxido Nítrico/metabolismo , Espectrometria de Massas/métodos , Ratos Sprague-Dawley , Interleucina-6/sangueRESUMO
BACKGROUND: Standardized and reliable medical photographs are crucial for preoperative and postoperative comparisons and academic communication in the medical field. There is limited research on photographic techniques in patients with cleft lip. Deformities of the lip and nose in patients with cleft lip are not only associated with morphological abnormalities but also with abnormalities of muscle function. METHODS: Considering the morphology and function of the lips and nose in cleft lip patients, the study captured the deformity of cleft lip patients in 6 positions: frontal view, 45 degrees left-right tilted side view, 90 degrees left-right tilted side view, and basal view, and in 5 facial expressions: tightly closed lips, slightly open mouth, smiling, teeth bared, and pout. RESULTS: In 6 different positions and 5 different expressions, we took pictures of lip and nasal deformities covering most of the common deformities in patients with cleft lip, such as white lip scarring, interruption of continuity of vermillion border, lip prolapse, asymmetric corners of the mouth, collapsed ala nasi, loss of the nasal base and deviated nasal septum. CONCLUSIONS: This paper suggests a set of effective, easy-to-follow, and precise photographic protocols to assist cleft lip surgeons in capturing suitable and informative, high-quality 2D digital photographs. LEVEL OF EVIDENCE: Level-V.
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Cell fate is precisely modulated by complex but well-tuned molecular signaling networks, whose spatial and temporal dysregulation commonly leads to hazardous diseases. Biomolecular condensates (BCs), as a newly emerging type of biophysical assemblies, decipher the molecular codes bridging molecular behaviors, signaling axes, and clinical prognosis. Particularly, physical traits of BCs play an important role; however, a panoramic view from this perspective toward clinical practices remains lacking. In this review, we describe the most typical five physical traits of BCs, and comprehensively summarize their roles in molecular signaling axes and corresponding major determinants. Moreover, establishing the recent observed contribution of condensate physics on clinical therapeutics, we illustrate next-generation medical strategies by targeting condensate physics. Finally, the challenges and opportunities for future medical development along with the rapid scientific and technological advances are highlighted.
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Condensados Biomoleculares , Transdução de Sinais , Biofísica , Diferenciação Celular , FenótipoRESUMO
China leads the world in freshwater pearl production, an industry in which the triangle sail mussel (Sinohyriopsis cumingii) plays a pivotal role. In this paper, we report a high-quality chromosome-level genome assembly of S. cumingii with a size of 2.90 Gb-the largest yet reported among bivalves-and 89.92% anchorage onto 19 linkage groups. The assembled genome has 37,696 protein-coding genes and 50.86% repeat elements. A comparative genomic analysis revealed expansions of 752 gene families, mostly associated with biomineralization, and 237 genes under strong positive selection. Notably, the fibrillin gene family exhibited gene family expansion and positive selection simultaneously, and it also exhibited multiple high expressions after mantle implantation by transcriptome analysis. Furthermore, RNA silencing and an in vitro calcium carbonate crystallization assay highlighted the pivotal role played by one fibrillin gene in calcium carbonate deposition and aragonite transformation. This study provides a valuable genomic resource and offers new insights into the mechanism of pearl biomineralization.
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Bivalves , Unionidae , Animais , Biomineralização/genética , Bivalves/genética , Bivalves/química , Unionidae/genética , Unionidae/metabolismo , Carbonato de Cálcio , Água Doce , Fibrilinas/metabolismoRESUMO
Osteoarthritis (OA) is a joint disease characterized by articular cartilage loss, which afflicts many people worldwide. Knowing the disease severity can improve the recovery rate of OA. Antibody array technology was utilized for protein expression profiling of synovial fluid from eight mild knee OA patients, eight severe knee OA patients and 16 healthy persons. Subsequently, 48 mild OA patients, 56 severe OA patients and 24 healthy controls were utilized for validation by ELISA. In the protein expression profiling, inducible costimulator (ICOS) levels were markedly higher in OA patients compared with those in the healthy population, and were significantly higher in severe OA than those in mild OA. Furthermore, ICOS levels were shown to be significantly correlated with WOMAC, MRI-MOAKS and MRI-UTE-T2* scores. The multivariate logistic regression analysis indicated that higher levels of ICOS could significantly increase the risk of severe OA. Synovial ICOS levels were positively correlated with the radiographic severity of OA. ICOS may represent a biomarker for predicting the OA severity and may be involved in the development and progression of knee OA.
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Cartilagem Articular , Osteoartrite do Joelho , Humanos , Anticorpos , Ensaio de Imunoadsorção Enzimática , Osteoartrite do Joelho/diagnóstico por imagem , Líquido SinovialRESUMO
Methamphetamine abuse results in a host of social and medical issues. Methamphetamine use disorder (MUD) can hinder the brain and impair cognitive functions and mental health. Transcranial magnetic stimulation (TMS) is a non-invasive approach in the treatment of MUD. Recent studies have demonstrated encouraging and positive effects of TMS on the craving, affective symptoms, sleep quality, and cognitive functions in individuals with MUD. The regulation of specific brain activities through TMS has also been found to be a contributing factor to these positive outcomes. It is essential to employ more techniques, participants, and stimulation parameters and targets in the future.
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Individuals experience difficulty falling asleep in a new environment, termed the first night effect (FNE). However, the impact of the FNE on sleep-induced brain plasticity remains unclear. Here, using a within-subject design, we found that the FNE significantly reduces visual plasticity during sleep in young adults. Sleep-onset latency (SOL), an indicator of the FNE, was significantly longer during the first sleep session than the second session, confirming the FNE. We assessed performance gains in visual perceptual learning after sleep and increases in the excitatory-to-inhibitory neurotransmitter (E/I) ratio in early visual areas during sleep using magnetic resonance spectroscopy and polysomnography. These parameters were significantly smaller in sleep with the FNE than in sleep without the FNE; however, these parameters were not correlated with SOL. These results suggest that while the neural mechanisms of the FNE and brain plasticity are independent, sleep disturbances temporarily block the neurochemical process fundamental for brain plasticity.
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Plasticidade Neuronal , Sono , Humanos , Masculino , Sono/fisiologia , Feminino , Adulto Jovem , Adulto , Polissonografia , Percepção Visual/fisiologia , Espectroscopia de Ressonância Magnética , Aprendizagem/fisiologia , Encéfalo/fisiologiaRESUMO
Individuals experience difficulty falling asleep in a new environment, termed the first night effect (FNE). However, the impact of the FNE on sleep-induced brain plasticity remains unclear. Here, using a within-subject design, we found that the FNE significantly reduces visual plasticity during sleep in young adults. Sleep-onset latency (SOL), an indicator of the FNE, was significantly longer during the first sleep session than the second session, confirming the FNE. We assessed performance gains in visual perceptual learning after sleep and increases in the excitatory-to-inhibitory neurotransmitter (E/I) ratio in early visual areas during sleep using magnetic resonance spectroscopy and polysomnography. These parameters were significantly smaller in sleep with the FNE than in sleep without the FNE; however, these parameters were not correlated with SOL. These results suggest that while the neural mechanisms of the FNE and brain plasticity are independent, sleep disturbances temporarily block the neurochemical process fundamental for brain plasticity.
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The pervasive use of information technologies (IT) has tremendously benefited our daily lives. However, unpredicted technical breakdowns and errors can lead to the experience of stress, which has been termed technostress. It remains poorly understood how people dynamically respond to unpredicted system runtime errors occurring while interacting with the IT systems on a behavioral and neuronal level. To elucidate the mechanisms underlying such processes, we conducted a functional magnetic resonance imaging (fMRI) study in which 15 young adults solved arithmetic problems of three difficulty levels (easy, medium and hard) while two types of system runtime errors (problem errors and feedback errors) occurred in an unexpected manner. The problem error condition consisted of apparently defective displays of the arithmetic problem and the feedback error condition involved erroneous feedback. We found that the problem errors positively influenced participants' problem-solving performance at the high difficulty level (i.e., hard tasks) at the initial stage of the session, while feedback errors disturbed their performance. These dynamic behavioral changes are mainly associated with brain activation changes in the posterior cingulate and the default mode network, including the posterior cingulate cortex, the mPFC, the retrosplenial cortex and the parahippocampal gyrus. Our study illustrates the regulatory role of the posterior cingulate in coping with unpredicted errors as well as with dynamic changes in the environment.
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Giro do Cíngulo , Imageamento por Ressonância Magnética , Humanos , Giro do Cíngulo/fisiologia , Giro do Cíngulo/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Masculino , Feminino , Adulto Jovem , Adulto , Resolução de Problemas/fisiologia , Rede de Modo Padrão/fisiologia , Rede de Modo Padrão/diagnóstico por imagem , Mapeamento Encefálico/métodosRESUMO
Objective: The main purpose of this study was to explore the mechanical properties of the anterior cruciate ligament and its attachments following reconstruction with the all-inside technique after anterior cruciate ligament injury. Methods: Knee joint computed tomography data were collected from healthy volunteers, and knee joint models were created using Mimics software. A normal knee joint model, an all-inside reconstructed anterior cruciate ligament model, and a traditional reconstructed anterior cruciate ligament model were established. A tensile force of 134 N and a bending moment of 5 N/m were applied at the anterior aspect of the proximal tibia in these three models. The knee joint was subjected to external rotation, internal rotation, varus, valgus, flexion, and extension under this bending moment. The magnitude and distribution of stress on the ligament or graft and the magnitude and distribution of stress on the graft attachments were observed under different loading conditions. Results: Under different external forces, the maximum stress on the ligament in the normal model fluctuated from 1.949 to 18.302 MPa, with an uncertain distribution of maximum stress. The maximum stress on the graft in the all-inside reconstructed anterior cruciate ligament model fluctuated from 0.705 to 3.465 MPa and was mainly distributed at the junction of the graft and the tibial footprint. In the traditional reconstructed anterior cruciate ligament model, the maximum stress on the graft fluctuated from 5.012 to 59.269 MPa and was primarily distributed at the junction of the interference screw and the graft. The concentration of stress on the loop and plate in the all-inside reconstructed anterior cruciate ligament model fluctuated from 70.461 to 346.363 MPa, with maximum stress distributed at the junction of the loop and the tibial surface. The maximum stress on the interference screw in the traditional reconstructed anterior cruciate ligament model fluctuated from 10.184 to 92.298 MPa, with maximum stress primarily distributed at the end of the interference screw. Conclusion: Under different external forces, the graft used in all-inside anterior cruciate ligament reconstruction is subjected to fewer external forces than that used in traditional anterior cruciate ligament reconstruction, which may indicate a relatively stable mechanical environment. The strength of the loop and plate can theoretically tolerate daily knee joint movements of patients without injury.
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Osteosarcomas are malignant bone tumors that typically originate in the epiphyses of the long bones of the extremities in adolescents. Asiatic acid has been reported to possess antiinflammatory, neuroprotective, antidiabetic, antitumor and antimicrobial activities. The present study used a combination of network pharmacological prediction and in vitro experimental validation to explore the potential pharmacological mechanism of asiatic acid against osteosarcoma. A total of 78 potential asiatic acid targets in osteosarcoma were identified using databases. Kyoto Encyclopedia of Genes and Genomes analysis indicated that the PI3K/AKT and MAPK signaling pathways are essential in the treatment of osteosarcoma with asiatic acid. Molecular docking revealed binding of asiatic acid to EGFR, Caspase3, ESR1, HSP90AA1, IL6 and SRC proteins. asiatic acid inhibited proliferation through G2/M cell cycle arrest in osteosarcoma cells. In addition, asiatic acid induced mitochondriadependent apoptosis as demonstrated by increases in Bax and VDAC1 expression, and a decrease in Bcl2 protein expression. The increased autophagosomes, increased LC3II/I ratios and decreased p62 expression in the treatment group indicated that asiatic acid triggered autophagy. In addition, asiatic acid decreased the levels of phosphorylated (p)PI3K/PI3K and pAKT/AKT, increased reactive oxygen species (ROS) and upregulated the levels of pERK1/2/ERK1/2, pp38/p38 and pJNK/JNK in osteosarcoma cells. These results demonstrated that asiatic acid inhibited osteosarcoma cells proliferation by inhibiting PI3K/AKT and activating ROS/MAPK signaling pathways, suggesting asiatic acid is a potential agent against osteosarcoma.
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Neoplasias Ósseas , Osteossarcoma , Humanos , Adolescente , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt , Espécies Reativas de Oxigênio , Osteossarcoma/tratamento farmacológico , Neoplasias Ósseas/tratamento farmacológicoRESUMO
The further commercialization of layer-structured Ni-rich LiNi0.83Co0.11Mn0.06O2 (NCM83) cathode for high-energy lithium-ion batteries (LIBs) has been challenged by severe capacity decay and thermal instability owing to the microcracks and harmful phase transitions. Herein, Ti4+-doped NCM83 cathode materials are rationally designed via a simple and low-cost in-situ modification method to improve the crystal structure and electrode-electrolyte interface stability by inhibiting irreversible polarizations and harmful phase transitions of the NCM83 cathode materials due to Ti4+-doped forms stronger metal-O bonds and a stable bulk structural. In addition, the optimal doping amount of the composite cathode material is also determined through the results of physical characterization and electrochemical performance testing. The optimized Ti4+-doped NCM83 cathode material presents wider Li+ ions diffusion channels (c = 14.1687 Å), lower Li+/Ni2+ mixing degree (2.68 %), and compact bulk structure. The cell assembled with the optimized Ti4+-doped NCM83 cathode material exhibits remarkable capacity retention ratio of 95.4 % after 100cycles at 2.0C and room temperature, and outstanding reversible discharge specific capacity of 148.2 mAh g-1 at 5.0C. Even under elevated temperature of 60 °C, it delivers excellent capacity retention ratio of 92.2 % after 100cycles at 2.0C, which is significantly superior to the 47.9 % of the unmodified cathode material. Thus, the in-situ Ti4+-doped strategy presents superior advantages in enhancing the structural stability of Ni-rich cathode materials for LIBs.
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AIMS: Relationship between body mass index (BMI), frailty, and clinical adverse events remains unclear in patients with heart failure (HF) with preserved ejection fraction (HFpEF) in different patient populations. We aimed to compare the association of BMI, frailty, and clinical adverse events between a US cohort from the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) study and a Chinese cohort from the Heart Failure Registry of Patient Outcomes (HERO) study. METHODS AND RESULTS: We used data of 1715 participants enrolled from America in the TOPCAT study and 1487 patients with HFpEF in the Chinese registry study, the HERO. We evaluated the relationship between BMI and frailty using multivariate restricted cubic spline logistic regression. Association between frailty and BMI categories and primary outcomes including HF hospitalization, aborted sudden death, and cardiovascular death, all-cause mortality, and HF hospitalization were analysed by Cox proportional hazards models. The patients' mean age was 72 ± 11 years for both study populations, with 50% and 46% female for the TOPCAT study and the HERO study, respectively. Patients in the TOPCAT study had a higher mean BMI (33.9 vs. 24 kg/m2), with 72.3% vs. 52.9% defined as moderately to severely frail (frailty index > 0.3). In the TOPCAT study, risk of frailty rose as BMI increased, but not in the HERO study. Patients with frailty were at significant higher risk for the primary composite outcomes [hazard ratio (HR) 1.84 (95% confidence interval: 1.46-2.32)], all-cause mortality [HR 1.73 (1.34-2.25)], and HF hospitalization [HR 1.83 (1.40-2.40)] in the TOPCAT study. The corresponding numbers in the HERO study were 1.26 (1.01-1.57), 2.21 (1.45-3.35), and 1.15 (0.81-1.37), respectively. The association of frailty with clinical outcomes did not vary with BMI categories in the two studies. CONCLUSIONS: BMI distribution and association between BMI and frailty risk were different between the two study populations. Frailty was associated with clinical adverse events and this association was consistent across different BMI categories in both studies.
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Fragilidade , Insuficiência Cardíaca , Humanos , Feminino , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Masculino , Índice de Massa Corporal , Fragilidade/complicações , Volume Sistólico , Antagonistas de Receptores de Mineralocorticoides/uso terapêuticoRESUMO
Alginate lyase Aly448, a potential new member of the polysaccharide lyase (PL) 7 family, which was cloned and identified from the macroalgae-associated bacterial metagenomic library, showed bifunctionality. The molecular docking results revealed that Aly448 has two completely different binding sites for alginate (polyMG), poly-α-l-guluronic acid (polyG), and poly-ß-d-mannuronic acid (polyM) substrates, respectively, which might be the molecular basis for the enzyme's bifunctionality. Truncational results confirmed that predicted key residues affected the bifunctionality of Aly448, but did not wholly explain. Besides, Aly448 presented excellent biochemical characteristics, such as higher thermal stability and pH tolerance. Degradation of polyMG, polyM, and polyG substrates by Aly448 produced tetrasaccharide (DP4), disaccharide (DP2), and galactose (DP1), which exhibited excellent antioxidant activity. These findings provide novel insights into the substrate recognition mechanism of bifunctional alginate lyases and pave a new path for the exploitation of natural antioxidant agents.
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Antioxidantes , Proteínas de Bactérias , Proteínas de Bactérias/metabolismo , Simulação de Acoplamento Molecular , Polissacarídeo-Liases/química , Alginatos/química , Especificidade por Substrato , Concentração de Íons de HidrogênioRESUMO
AIMS: To predict the vagus nerve stimulation (VNS) efficacy for pediatric drug-resistant epilepsy (DRE) patients, we aim to identify preimplantation biomarkers through clinical features and electroencephalogram (EEG) signals and thus establish a predictive model from a multi-modal feature set with high prediction accuracy. METHODS: Sixty-five pediatric DRE patients implanted with VNS were included and followed up. We explored the topological network and entropy features of preimplantation EEG signals to identify the biomarkers for VNS efficacy. A Support Vector Machine (SVM) integrated these biomarkers to distinguish the efficacy groups. RESULTS: The proportion of VNS responders was 58.5% (38/65) at the last follow-up. In the analysis of parieto-occipital α band activity, higher synchronization level and nodal efficiency were found in responders. The central-frontal θ band activity showed significantly lower entropy in responders. The prediction model reached an accuracy of 81.5%, a precision of 80.1%, and an AUC (area under the receiver operating characteristic curve) of 0.838. CONCLUSION: Our results revealed that, compared to nonresponders, VNS responders had a more efficient α band brain network, especially in the parieto-occipital region, and less spectral complexity of θ brain activities in the central-frontal region. We established a predictive model integrating both preimplantation clinical and EEG features and exhibited great potential for discriminating the VNS responders. This study contributed to the understanding of the VNS mechanism and improved the performance of the current predictive model.
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Conectoma , Epilepsia Resistente a Medicamentos , Eletroencefalografia , Entropia , Estimulação do Nervo Vago , Humanos , Estimulação do Nervo Vago/métodos , Feminino , Epilepsia Resistente a Medicamentos/terapia , Epilepsia Resistente a Medicamentos/fisiopatologia , Masculino , Criança , Eletroencefalografia/métodos , Pré-Escolar , Conectoma/métodos , Resultado do Tratamento , Adolescente , Máquina de Vetores de Suporte , Biomarcadores , SeguimentosRESUMO
As a crucial sink of metal-containing nanoparticles (MNPs), road dust can record their spatiotemporal variations in urban environments. In this study, taking Shanghai as a representative megacity in China, a total of 272 dust samples were collected in the winter and summer of 2013 and 2021/2022 to understand the spatiotemporal variations and driving factors of MNPs. The number concentrations of Fe-, Ti-, and Zn-containing NPs were 3.8 × 106 - 8.4 × 108, 2.3 × 106-1.4 × 108, and 6.0 × 105-2.3 × 108 particles/mg, respectively, according to single particle (sp)ICP-MS analysis. These MNPs showed significantly higher number concentrations in summer than in winter. Hotspots of Fe-containing NPs were more concentrated in industrial and traffic areas, Zn-containing NPs were mainly distributed in the central urban areas, while Ti-containing NPs were abundant in areas receiving high rainfall. The structural equation model results indicates that substantial rainfall in summer can help remove MNPs from atmospheric PM2.5 into dust, while in winter industrial and traffic activities were the primary contributors for MNPs. Moreover, the contribution of traffic emissions to MNPs has surpassed industrial one over the last decade, highlighting the urgency to control traffic-sourced MNPs, especially those from non-exhaust emissions by electric vehicles.