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Preliminary pharmacological studies revealed that the EtOAc fraction (BGEA) might be the main active fraction with anti-inflammatory and antinociceptive effects in Beaumontia grandiflora Wall. Further assays on BGEA at doses of 200, 400, and 800 mg/kg using four animal models showed that it could inhibit the xylene-induced ear edema, carrageenan-induced paw edema, and acetic acid-induced writhing and prolong the latency time in the hot-plate test. ELISA analysis revealed that the anti-inflammatory activity of BGEA might be associated with the decrease of TNF-α, IL-1ß, and IL-6 levels and the increase of the IL-10 level. The acute toxicity test showed that except for the n-BuOH fraction, the LD50 values of the extract and other three fractions were higher than 2000 mg/kg bw. Finally, 14 compounds were identified from BGEA by LC-MS. This research provides some basis for the folk use of B. grandiflora in the treatment of inflammation and pain-related diseases.
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Deep venous thrombosis (DVT) has a significant negative impact on surgical and tumor patient's safety and quality of life. There was no specific report on the incidence and risk factors of postoperative lower extremity DVT in cervical cancer patients. Analysis of the risk factors of postoperative DVT in patients with cervical cancer is of great clinical significance for prevention and treatment. We retrospectively analyzed 309 cervical cancer patients treated by the Hubei Cervical Cancer Prevention Center and used a logistic regression model to test the risk variables of postoperative lower extremity deep venous thrombosis in cervical cancer patients. By univariate analyses, the results of the study showed that the incidence of postoperative DVT was significantly increased in cervical cancer patients complicated with old age, obesity, high preoperative plasma D-dimer level, increased preoperative triglyceride level, chronic diseases (hypertension, diabetes, and cardiovascular disease), open surgery, long operation time, intraoperative blood transfusion, advanced tumor stage, and preoperative chemotherapy/radiotherapy. Advanced age, obesity, elevated preoperative D-dimer level, high preoperative triglyceride level, and open surgery were independent risk factors for postoperative lower extremity DVT in patients with cervical cancer by multivariate regression analyses (all P < .05). In gynecologic patients with cervical cancer, there is a high incidence of postoperative lower extremity DVT. Clinicians should develop systematic and comprehensive prevention and treatment measures for the risk factors to lower this morbidity and improve patient prognosis.
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Neoplasias do Colo do Útero , Trombose Venosa , Humanos , Feminino , Neoplasias do Colo do Útero/complicações , Neoplasias do Colo do Útero/cirurgia , Estudos Retrospectivos , Qualidade de Vida , Trombose Venosa/epidemiologia , Fatores de Risco , Obesidade/complicações , Incidência , Complicações Pós-Operatórias/prevenção & controle , Extremidade Inferior/irrigação sanguínea , TriglicerídeosRESUMO
Background: Ginseng (Panax ginseng Mayer) is an important natural medicine. However, a long culture period and challenging quality control requirements limit its further use. Although artificial cultivation can yield a sustainable medicinal supply, research on the association between the transplantation and chaining of metabolic networks, especially the regulation of ginsenoside biosynthetic pathways, is limited. Methods: Herein, we performed Liquid chromatography tandem mass spectrometry based metabolomic measurements to evaluate ginsenoside accumulation and categorise differentially abundant metabolites (DAMs). Transcriptome measurements using an Illumina Platform were then conducted to probe the landscape of genetic alterations in ginseng at various ages in transplantation mode. Using pathway data and crosstalk DAMs obtained by MapMan, we constructed a metabolic profile of transplantation Ginseng. Results: Accumulation of active ingredients was not obvious during the first 4 years (in the field), but following transplantation, the ginsenoside content increased significantly from 6-8 years (in the wild). Glycerolipid metabolism and Glycerophospholipid metabolism were the most significant metabolic pathways, as Lipids and lipid-like molecule affected the yield of ginsenosides. Starch and sucrose were the most active metabolic pathways during transplantation Ginseng growth. Conclusion: This study expands our understanding of metabolic network features and the accumulation of specific compounds during different growth stages of this perennial herbaceous plant when growing in transplantation mode. The findings provide a basis for selecting the optimal transplanting time.
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It is well documented that diabetes mellitus (DM) is strongly associated with cognitive decline and structural damage to the brain. Cognitive deficits appear early in DM and continue to worsen as the disease progresses, possibly due to different underlying mechanisms. Normal iron metabolism is necessary to maintain normal physiological functions of the brain, but iron deposition is one of the causes of some neurodegenerative diseases. Increasing evidence shows that iron overload not only increases the risk of DM, but also contributes to the development of cognitive impairment. The current review highlights the role of iron overload in diabetic cognitive impairment (DCI), including the specific location and regulation mechanism of iron deposition in the diabetic brain, the factors that trigger iron deposition, and the consequences of iron deposition. Finally, we also discuss possible therapies to improve DCI and brain iron deposition.
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Objective: To explore and evaluate the clinical therapeutic effect of laparoscopic uterine artery pre-ligation combined with hysteroscopic curettage in the treatment of type II cesarean scar pregnancy. Methods: This study analyzed the clinical data of patients with cesarean scar pregnancy (CSP) in the Maternal and Child Health Hospital of Hubei Province from 2018 to 2022. A total of 134 patients with type II cesarean section were enrolled, out of which 78 patients were included in the final analysis. Treatment included either uterine artery embolization (UAE) combined with hysteroscopic curettage (n = 37 patients) or laparoscopic uterine artery pre-ligation (LUAP) combined with hysteroscopic curettage (n = 41 patients). The demographic and clinical characteristics of these two groups were recorded, and their short- and long-term complications on follow-up were compared. For patients with subsequent fertility requirements, we followed up these patients for 2 years after surgery, then collected and analyzed the compared subsequent pregnancy outcome. Results: We found no significant discrepancies in the success rate of operation, length of hospital stay, and intraoperative blood loss between the two different operation modes. The cost of LUAP was significantly lower than that of UAE. Furthermore, the incidence of short-term postoperative complications such as fever and pelvic pain was lower in patients treated with LUAP than in those treated with UAE. In terms of long-term postoperative complications, the recovery time for menstruation in the LUAP group (49.81 ± 11.47) was earlier than that in the UAE group (34.90 ± 7.41) (p < 0.05). Additionally, 4.9% of patients in the LUAP group had decreased menstrual flow, while 59% of patients in the UAE group had a marked decrease in menstrual flow, and the incidence and severity of intrauterine adhesions were significantly lower in the LUAP group than in the UAE group(p < 0.05). Consistent with the aforementioned observations, patients treated with LUAP had better postoperative re-pregnancy outcomes than those treated with UAE. Conclusions: Based on the findings, LUAP combined with hysteroscopic curettage is a safe and effective surgical scheme for the treatment of type II CSPs. In addition, compared with UAE, LUAP is associated with a lower surgical cost, fewer short and long-term complications, and better postoperative pregnancy outcomes. Thus, it should be widely applied in patients with type II CSPs.
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Free fatty acid receptor 1 (FFAR1) is a potential therapeutic target for the treatment of type 2 diabetes (T2D). It has been validated that agonists targeting FFAR1 can achieve the initial therapeutic endpoints of T2D, and the epimer agonists (R,S) AM-8596 can activate FFAR1 differently, with one acting as a partial agonist and the other as a full agonist. Up to now, the origin of the stereoselectivity of FFAR1 agonists remains elusive. In this work, we used molecular simulation methods to elucidate the mechanism of the stereoselectivity of the FFAR1 agonists (R)-AM-8596 and (S)-AM-8596. We found that the full agonist (R)-AM-8596 disrupts the residue interaction network around the receptor binding pocket and promotes the opening of the binding site for the G-protein, thereby resulting in the full activation of FFAR1. In contrast, the partial agonist (S)-AM-8596 forms stable electrostatic interactions with FFAR1, which stabilizes the residue network and hinders the conformational transition of the receptor. Our work thus clarifies the selectivity and underlying molecular activation mechanism of FFAR1 agonists.
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Diabetes Mellitus Tipo 2 , Sítios de Ligação , Diabetes Mellitus Tipo 2/tratamento farmacológico , Humanos , Receptores Acoplados a Proteínas G/químicaRESUMO
In recent years, drug-induced nephrotoxicity has been one of the main reasons for the failure of drug development. Early prediction of the nephrotoxicity for drug candidates is critical to the success of clinical trials. Therefore, it is very important to construct an effective model that can predict the potential nephrotoxicity of compounds. Machine learning methods have been widely used to predict the physicochemical properties, biological activities, and safety assessment of compounds. In this study, we manually collected 777 valid drug data and constructed a total of 72 classification models using nine types of molecular fingerprints combined with different machine learning algorithms. From experimental literature and the US FDA Drugs Database, some marketed drugs were screened for external validation of the models. Finally, three models exhibited good performance in the prediction of nephrotoxicity of both chemical drugs and Chinese herbal medicines. The best model was the support vector machine algorithm combined with CDK graph only fingerprint. Furthermore, the applicability domain of the models was analyzed according to the OECD principles, and we also used the SARpy and information gain methods to find eight substructures that might cause nephrotoxicity, so as to attract attention in the future drug discovery.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Aprendizado de Máquina , Algoritmos , Simulação por Computador , Descoberta de Drogas , Humanos , Máquina de Vetores de SuporteRESUMO
Estrogen-related receptor α (ERRα), a member of nuclear receptors (NRs), plays a role in the regulation of cellular energy metabolism and is reported to be a novel potential target for type 2 diabetes therapy. To date, only a few agonists of ERRα have been identified to improve insulin sensitivity and decrease blood glucose levels. Herein, the discovery of novel potent agonists of ERRα determined using a combined virtual screening approach is described. Molecular dynamics (MD) simulations were used to obtain structural ensembles that can consider receptor flexibility. Then, an efficient virtual screening strategy with a combination of similarity search and ensemble docking was performed against the Enamine, SPECS, and Drugbank databases to identify potent ERRα agonists. Finally, a total of 66 compounds were purchased for experimental testing. Biological investigation of promising candidates identified seven compounds that have activity against ERRα with EC50 values ranging from 1.11 to 21.70 µM, with novel scaffolds different from known ERRα agonists until now. Additionally, the molecule GX66 showed micromolar inverse activity against ERRα with an IC50 of 0.82 µM. The predicted binding modes showed that these compounds were anchored in ERRα-LBP via interactions with several residues of ERRα. Overall, this study not only identified the novel potent ERRα agonists or an inverse agonist that would be the promising starting point for further exploration but also demonstrated a successful molecular dynamics-guided approach applicable in virtual screening for ERRα agonists.
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Diabetes Mellitus Tipo 2 , Humanos , Simulação de Dinâmica Molecular , Receptores de Estrogênio/metabolismo , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
Type 2 diabetes mellitus (T2DM) is a heterogeneous disorder, so achieving the desired therapeutic efficacy through monotherapy is tricky. Drug combinations play a vital role in treating multiple complex diseases by providing increased efficacy and reduced toxicity. Here, we adopted a computational framework to discover potential drugs and drug pairs for T2DM. Firstly, we collected T2DM-associated genes and constructed the disease module for T2DM. Then, by quantifying the proximity between drugs and the disease module, we found out potential drugs. Based on the drug-induced gene expression profiles, we further performed Gene Set Enrichment Analysis (GSEA) on these drugs and identified several potential candidates. In addition, through network-based separation, potential drug combinations for T2DM were predicted. Results from this study could provide insights for anti-T2DM drug discovery and rational drug use of existing agents. As a useful computational framework, our approach could also be applied in drug research for other complex diseases.
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Diabetes Mellitus Tipo 2/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Diabetes Mellitus Tipo 2/genética , Combinação de Medicamentos , Descoberta de Drogas , Perfilação da Expressão Gênica , Humanos , Modelos Moleculares , Estrutura Molecular , TranscriptomaRESUMO
Despite extensive research, the exact mechanisms involved in colorectal cancer (CRC) etiology and pathogenesis remain unclear. This study aimed to examine the correlation between tumor-associated alternative splicing (AS) events and tumor immune infiltration (TII) in CRC. We analyzed transcriptome profiling and clinical CRC data from The Cancer Genome Atlas (TCGA) database and lists of AS-related and immune-related signatures from the SpliceSeq and Innate databases, respectively to develop and validate a risk model of differential AS events and subsequently a TII risk model. We then conducted a two-factor survival analysis to study the association between TII and AS risk and evaluated the associations between immune signatures and six types of immune cells based on the TIMER database. Subsequently, we studied the distribution of six types of TII cells in high- and low-risk groups for seven AS events and in total. We obtained the profiles of AS events/genes for 484 patients, which included 473 CRC tumor samples and 41 corresponding normal samples, and detected 22581 AS events in 8122 genes. Exon Skip (ES) (8446) and Mutually Exclusive Exons (ME) (74) exhibited the most and fewest AS events, respectively. We then classified the 433 patients with CRC into low-risk (n = 217) and high-risk (n = 216) groups based on the median risk score in different AS events. Compared with patients with low-risk scores (mortality = 11.8%), patients with high-risk scores were associated with poor overall survival (mortality = 27.6%). The risk score, cancer stage, and pathological stage (T, M, and N) were closely correlated with prognosis in patients with CRC (P < 0.001). We identified 6479 differentially expressed genes from the transcriptome profiles of CRC and intersected 468 differential immune-related signatures. High-AS-risk and high-TII-risk predicted a poor prognosis in CRC. Different AS types were associated with different TII risk characteristics. Alternate Acceptor site (AA) and Alternate Promoter (AP) events directly affected the concentration of CD4T cells, and the level of CD8T cells was closely correlated with Alternate Terminator (AT) and Exon Skip (ES) events. Thus, the concentration of CD4T and CD8T cells in the CRC immune microenvironment was not specifically modulated by AS. However, B cell, dendritic cell, macrophage, and neutrophilic cell levels were strongly correlated with AS events. These results indicate adverse associations between AS event risk levels and immune cell infiltration density. Taken together, our findings show a clear association between tumor-associated alternative splicing and immune cell infiltration events and patient outcome and could form a basis for the identification of novel markers and therapeutic targets for CRC and other cancers in the future.
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Ionic liquid (IL) technology provides a useful platform to enhance the oral absorption of therapeutic agents. In the present work, gliclazide (GLI), a second-generation sulfonylurea drug was transformed into an IL with tetrabutylphosphonium. The physicochemical properties of this IL were systematically characterized by DSC, TGA, FT-IR, NMR, and HPLC. For the further preparation development, a solution stability test was conducted. GLI-based IL could improve the solution stability in a neutral environment. To assess oral potential, the solubility characteristics including equilibrium solubility, 24 h kinetic saturation solubilities and supersaturation profiles were first explored. Significant enhancement of solubilities, supersaturation ratio and duration of supersaturation was found for the synthesized IL. Computational methodology was utilized to better understand the improved solubility results. From the simulated results, [TBP][GLI] showed a longer time period when the distance between cation and anion was far above the baseline and a higher deviation degree, indicating less stable ion pairs of [TBP][GLI] in an aqueous environment and it being easy for the cation and anion to tear apart and form interactions with water molecules. The prepared [TBP][GLI] exhibited intestinal transportation ability and safety as evidenced by the in vitro gastrointestinal tract artificial membrane permeability assays (GIT-PAMPA) and cytotoxicity experiments with Caco-2 cells. A mesoporous carrier, AEROPERL® 300 Pharma, was chosen to load the IL and then encapsuled into enteric capsules. The prepared oral capsules containing GLI-based IL loaded mesoporous silica particles released fast and could realize 100% release within 60 min.
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The traditional Chinese medicines (TCMs) have been used to treat diseases over a long history, but it is still a great challenge to uncover the underlying mechanisms for their therapeutic effects due to the complexity of their ingredients. Based on a novel network pharmacology-based approach, we explored in this study the potential therapeutic targets of Liuwei Dihuang (LWDH) decoction in its neuroendocrine immunomodulation (NIM) function. We not only collected the known targets of the compounds in LWDH but also predicted the targets for these compounds using the balanced substructure-drug-target network-based inference (bSDTNBI), which is a target prediction method based on network inferring developed by our laboratory. A "target-(pathway)-target" (TPT) network, in which targets of LWDH were connected by relevant pathways, was constructed and divided into several separate modules with strong internal connections. Then the target module that contributes the most to NIM function was determined through a contribution scoring algorithm. Finally, the targets with the highest contribution score to NIM-related diseases in this target module were recommended as potential therapeutic targets of LWDH.
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Medicamentos de Ervas Chinesas/análise , Algoritmos , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Medicina Tradicional ChinesaRESUMO
The typical electron-deficiency of the boron element renders fascinating architectures and chemical bonding to boron-based nanoclusters. We theoretically predict two di-Ca-doped boron clusters, B6Ca2 (D2h, 1Ag) and B8Ca2 (D8h, 1A1g), and both adopt interesting inverse sandwich geometries, showing an elongated D2h B6 or perfectly planar D8h B8 ring being sandwiched by two Ca atoms only, respectively. Natural atomic charge analyses indicate that the Ca atoms donate nearly all the 4s electrons to the B6 (or B8) ring, forming [Ca]2+[B6]4-[Ca]2+ and [Ca]2+[B8]4-[Ca]2+ charge transfer complexes. The interaction between the two Ca atoms and the boron rings is governed by robust electrostatics albeit by weaker B-Ca covalent interaction. Chemical bonding analyses show that B6Ca2 has 4σ and 6π delocalized electrons on the elongated B6 ring, leading to a conflicting aromatic system. B8Ca2, possessing 6σ and 6π delocalized electrons on the B8 ring, is doubly aromatic. Additionally, the B6Ca2 and B8Ca2 clusters show noticeable structural and electronic transmutation relative to their equivalent electronic B6Be2 and B8Mg2 clusters, respectively. The intrinsic reasons behind the transmutations are elucidated via in-depth bonding analyses.
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Free fatty acid receptor 1 (FFAR1), a member of class A in G-protein-coupled receptors (GPCRs), is a promising antidiabetic target. The crystal structure of FFAR1 revealed that one agonist (MK-8666) binds to the extracellular vestibule of this receptor, while another (AP8) occupies the surface pocket between transmembrane (TM) helices TM4 and TM5. In this study, we performed 1 µs unbiased molecular dynamics (MD) simulation on each of five systems, to uncover why two ligands in completely different sites both serve as agonists and how they exert a positive synergistic effect together. They are two agonist-bound systems (FFAR1_MK-8666 and FFAR1_AP8), a ternary complex system FFAR1_MK-8666_AP8, an antagonist-bound system (FFAR1_15i), and an unliganded (apo) system, among which the antagonist 15i-bound and apo systems were used as controls. The results showed that Y913.37 played a pivotal role in the activation process of FFAR1. The agonist could disrupt the Y913.37-centered residue interaction network within protein, whereas the antagonist could stabilize the network. Furthermore, our simulations revealed that the hydrophobic layer amino acid residues next to the transmission switch (CWXP) formed a gate and could open only upon agonist activation, which might exert an important role in the formation of water pathway. These results would be helpful for elucidating the molecular activation mechanism of FFAR1 and provide insights into the design and discovery of novel allosteric agonists of FFAR1 for the treatment of type 2 diabetes mellitus (T2DM).
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Diabetes Mellitus Tipo 2 , Humanos , Hipoglicemiantes , Ligantes , Simulação de Dinâmica Molecular , Receptores Acoplados a Proteínas GRESUMO
Estrogen-related receptor alpha (ERRα), a member of nuclear receptors (NRs), participates in energy metabolism. Recent experiments identified that several agonists to increase the activity of ERRα, which have a therapeutic effect in improving insulin sensitivity and lowering blood glucose levels. However, the detailed molecular mechanism about how the ligands affect the structure of ERRα remains elusive. To better understand the conformational change of ERRα complexed with agonists and inverse agonists, unbiased molecular dynamics (MD) simulations were performed on the ligand binding domain of ERRα (ERRα-LBD) bound with different ligands. According to the results, the ERRα-agonist interactions were more stable in the presence of the peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α). More importantly, we observed that the binding of inverse agonists would decrease the stability of helix 12 (H12) of ERRα. Moreover, we suggested that Phe232 and Phe414 should be key residues in the interaction pathway from ligands to H12, which provided a possible explanation about how ligands impact the structure of ERRα. These results would provide insights into the design of novel and efficient agonists of ERRα to treat metabolic diabetes.Communicated by Ramaswamy H. Sarma.
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Simulação de Dinâmica Molecular , Receptores de Estrogênio , Metabolismo Energético , Ligantes , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
Estrogen-related receptor alpha (ERRα) has attracted increasing concerns. ERRα, orphan nuclear receptor, plays important roles in energy metabolism. Therefore, small molecule agonists of ERRα could be a potential therapeutic strategy in the treatment of metabolic diseases such as diabetes. Recently, Wei et al. identified cholesterol as the endogenous agonist of ERRα. However, the detailed molecular mechanism of cholesterol bound with ERRα remains ambiguous. Thus, in this study molecular docking and molecular dynamics (MD) simulations were performed to characterize how cholesterol affects the behavior of ERRα. Based on the results, we found that a proven residue Phe232 and others including Leu228, Glu235, Arg276, and Phe399 were key residues to ligand binding. A hydrogen-bonding interaction between cholesterol and Glu235 ensured the orientation of the ligand in the binding pocket, while hydrophobic interactions between cholesterol and the above-mentioned residues promoted the stability of ERRα-cholesterol complex. In the presence of the proliferator-activated receptor γ coactivator 1α (PGC-1α), the cholesterol-ERRα interaction became more stable. Interestingly, we observed that cholesterol facilitated the binding of ERRα with its coactivator PGC-1α via stabilizing the conformation of helix 12 and the interaction surface of ERRα/PGC-1α. Overall, these findings would be valuable for the future rational design of novel ERRα agonists.
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Colesterol/química , Receptores de Estrogênio/metabolismo , Sítios de Ligação , Colesterol/metabolismo , Humanos , Ligação de Hidrogênio , Interações Hidrofóbicas e Hidrofílicas , Ligantes , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Ligação Proteica , Estrutura Terciária de Proteína , Proteínas de Ligação a RNA/química , Proteínas de Ligação a RNA/metabolismo , Receptores de Estrogênio/química , Termodinâmica , Receptor ERRalfa Relacionado ao EstrogênioRESUMO
Blindwalking to replicate an instructed distance requires various sensory signals. Recent evidence in movement science across many organisms suggests that multifractal organization of connective tissue supports the use of these signals. Multifractal structure is a multiplicity of power laws defining distribution of proportion across many time scales that helps predict judgments of the objects' length. Present work tests whether the multifractal structure in postural accelerometry during blindwalking predicts blindwalking distance replications. Ten undergraduate student participants each completed 20 trials of distance-perception each comprising two laps. On each Lap 1, experimenters led participants to walk on any of five prescribed distances, randomly assigning half to walk Lap 1 with eyes open and another half to walked Lap 1 with eyes closed. On Lap 2, all participants walked with eyes closed to replicate instructed distances from Lap 1. We collected postural accelerometry from the torso during each lap. Regression modeling showed that multifractality of postural accelerometry on both Lap 1 and Lap 2 contributed significantly to Lap-2 blindwalking responses. According to this model, more accurate Lap-2 replications of Lap-1 distance came from eyes-closed participants whose posture had comparable multifractality on both laps. Multifractality provides insights into the sequence of exploratory behaviors for blindwalking responses to distance perception.
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Percepção de Distância/fisiologia , Postura/fisiologia , Tronco/fisiologia , Caminhada/fisiologia , Adolescente , Adulto , Feminino , Humanos , Masculino , Adulto JovemRESUMO
Research on reading comprehension of connected text emphasizes reliance on single-word features that organize a stable, mental lexicon of words and that speed or slow the recognition of each new word. However, the time needed to recognize a word might not actually be as fixed as previous research indicates, and the stability of the mental lexicon may change with task demands. The present study explores the effects of narrative coherence in self-paced story reading to single-word feature effects in lexical decision. We presented single strings of letters to 24 participants, in both lexical decision and self-paced story reading. Both tasks included the same words composing a set of adjective-noun pairs. Reading times revealed that the tasks, and the order of the presentation of the tasks, changed and/or eliminated familiar effects of single-word features. Specifically, experiencing the lexical-decision task first gradually emphasized the role of single-word features, and experiencing the self-paced story-reading task afterwards counteracted the effect of single-word features. We discuss the implications that task-dependence and narrative coherence might have for the organization of the mental lexicon. Future work will need to consider what architectures suit the apparent flexibility with which task can accentuate or diminish effects of single-word features.
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Psicolinguística/métodos , Desempenho Psicomotor/fisiologia , Leitura , Adolescente , Adulto , Tomada de Decisões , Humanos , Adulto JovemRESUMO
In order to evaluate the pollution degree of the dust in Hangzhou City, the indoor dust samples of 19 offices, families and students' dormitories were collected from August to March in 2013 at Hangzhou for evaluating the pollution level of polybrominated diphenyl ethers (PBDEs), to analyze concentrations of 14 PBDEs congeners and congener distribution as well as the possible influencing factors, and to estimate the PBDEs exposure levels of adults and children through the dust intake. The results showed that the average ∑14PBDEs of office was 9.28×102 ng·g-1, and the median was 1.03×103 ng·g-1; the average ∑14PBDEs of family was 7.83×102 ng·g-1, and the median was 9.11×102 ng·g-1; the average ∑14PBDEs of student dormitory was 4.07×102 ng·g-1, and the median was 4.03×102 ng·g-1. The pollution level of the office was higher than that of the living environment. BDE-209 was the largest monomer, and its contribution was 75.48%, followed by BDE-190, BDE-154 and BDE-71.PBDEs exposure levels of adults and children by dust intake were 13.12-32.63 ng·d-1 and 32.40-54.54 ng·d-1, respectively. Children's PBDEs exposure in the dust was higher than that of the adults, mainly because the average dust intake of children was higher than that of adults. The analysis showed that the PBDEs from indoor dust intake was a potential health hazard, and the biggest potential harm to children.
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Poluição do Ar em Ambientes Fechados/análise , Poeira/análise , Exposição Ambiental/análise , Éteres Difenil Halogenados/análise , Adulto , Criança , China , Cidades , Monitoramento Ambiental , Habitação , HumanosRESUMO
OBJECTIVE: To observe the protection of total flavones of Hippophae Rhamnoides (TFH) on vascular endothelial cells (VECs). METHODS: Human umbilical VECs (ECV304) were used. The vascular endothelial injured cell model was prepared using hydrogen dioxide (H2O2). The cell apoptosis rate and changes of mean fluorescence intensity were detected using flow cytometry (FCM). The Caspase-3 activity in VECs was detected by Western blot. RESULTS: VEC apoptosis was induced by 200 micromol/L H2O2. TFH in different concentrations (400, 200, and 100 microg/mL) could significantly lower the cell apoptosis rate induced by H2O2 respectively (all P < 0.05), and obviously inhibit Caspase-3 activities (all P < 0.01). CONCLUSIONS: TFH could fight against H2O2 injured VECs apoptosis. Lowering the Caspase-3 expression was one of its mechanisms in protecting VECs.