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Preclinical and human studies on the relationship between obesity/metabolic syndrome (MetS) and lower urinary tract dysfunction (LUTD) are inconsistent. We compared the temporal effects of feeding four different diets used to induce obesity/MetS, including 60% fructose, 2% cholesterol +10% lard, 30% fructose + 20% lard, or 32.5% lard diet, up to 42 wk, on metabolic parameters and bladder function in male Sprague-Dawley rats. Rats fed a 30% fructose + 20% lard or 32.5% lard diet consumed less food (grams), but only the 32.5% lard diet group took in more calories. Feeding rats a 60% fructose or 30% fructose + 20% lard diet led to glucose intolerance and increased blood pressure. Higher body weight and increased cholesterol levels were observed in the rats maintained on a 2% cholesterol +10% lard diet, whereas exposure to a 32.5% lard diet affected most of the above parameters. Voiding behavior measurement showed that voiding frequency and the total voided volume were lower in the experimental diet groups except for the 30% fructose + 20% lard group. The mean voided volume was lower in the 30% fructose + 20% lard and 32.5% lard groups compared with the control group. Cystometric analysis revealed a decreased bladder capacity, mean voided volume, intermicturition interval, and compliance in the 32.5% lard diet group. In conclusion, experimental diets including 60% fructose, 30% fructose + 20% lard, or 2% cholesterol + 10% lard diet differently affected physiological and metabolic parameters and bladder function to a limited extent, while exposure to a 32.5% lard diet had a greater impact.
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Síndrome Metabólica , Humanos , Ratos , Masculino , Animais , Síndrome Metabólica/etiologia , Ratos Sprague-Dawley , Triglicerídeos , Bexiga Urinária/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Dieta , Colesterol , Frutose/efeitos adversosRESUMO
Intensive and lasting stress may induce severe damage to a human's physical and mental health. Successful stress management depends on the effective monitoring of people's everyday activities, in particular, their sedentary behaviors. Here, we propose an unobtrusive office sedentary behavior monitoring system that combines Bluetooth signals and ballistocardiogram (BCG) signals to classify an individual's sitting modes into four categories: off-seat, sedate, working, and in-motion. The proposed monitoring system simultaneously reads received signal strength indicators (RSSI) from several fixed Bluetooth Low Energy (BLE) beacons and BCG data from the piezoelectric sensor placed underneath the chair cushion, with distinct sampling frequencies. The raw signals are first denoised with local subspace projection. Then we extract the local spectral features from the reconstructed signal and the signal differences for a two-stage stacking learning algorithm. The temporally classified results establish a desk-based worker's sedentary profile and make possible the timely intervention of physical inactivity. We tested the prototype system for 15 subjects, and the preliminary results achieved 95% accuracy, demonstrating its potential in a real-world application.
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Comportamento Sedentário , Humanos , Algoritmos , Monitorização FisiológicaRESUMO
This cross-sectional study aimed to analyse the relationship between Tai Chi exercise habits and depression tendency and sleep quality in people practicing Tai Chi in Chengdu, China. A total of 1352 Tai Chi practitioners aged 50-79 years old were divided into six groups according to age and gender for Tai Chi exercise habits, depression tendency and sleep quality. The frequency of weekly Tai Chi practice and duration of single Tai Chi practice have a significant positive correlation with the exercise years. For female subjects who had long-term Tai Chi exercise, depression decreased with the duration and weekly frequency of a single exercise. Tai Chi exercise habits reduced sleep disturbance scores (in the male group aged 60-69 years old, exercise years, r = -0.242, p = 0.004) and sleep duration (in the male and female group aged 70-79 years old, duration of single Tai Chi practice, r = -0.334, p = 0.035; r = -0.235, p = 0.029), suggesting that long-term Tai Chi exercise may reduce the trend of poor sleep quality due to increased ageing.
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Graphene has been extensively applied in composite materials due to its high thermal conductivity. Multi-layered graphene has great potential in the construction of a continuous filler network but is restricted by the high interfacial thermal resistance between adjacent graphene layers. This paper investigates the effects of the overlapping area and interlayer sp3 bonding of partially overlapped bilayer graphene on the interfacial thermal resistance using molecular dynamic simulations. The results show the linear relationship between the interfacial thermal resistance and the overlapping area. Then, identical vacancy defects of the same plane coordinates were added to each of the two graphene sheets, and it was found that the presence of an armchair edge restricted the formation of interface sp3 bonding to some extent, while the zigzag edge did not. However, their similar bond length and the phonon density of state of bonded atoms in the models with different edges indicated their similar effects on the heat transfer. Therefore, the thermal resistance of all single sp3 bonds in different models could be approximated to 14.3 × 10-9 m2 KW-1. A formula is proposed to describe the inverse relationship between the number of sp3 bonds and the interfacial thermal resistance. Finally, the vacancy defect on the upper graphene sheet was moved to stagger the two vacancies. The length of sp3 bonds was changed slightly due to the staggered arrangement, and the interfacial thermal resistance was found to be positively correlated with the bond length. This allows valuable interfacial heat-transfer properties of the partially overlapped bilayer graphene to contribute to the thermal management of the 3D filler network.
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Previously compound I showed great anti-glioblastoma activity without toxicity in a mouse xenograft study. In this study, a sensitive and rapid high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was developed and validated to investigate the pharmacokinetics and brain distribution of compound I in mice. The protein precipitation method was applied to extract the compound from mouse plasma and brain homogenates, and it was then separated using a Kinetex C18 column with a mobile phase consisting of acetonitrile-0.1% formic acid water (50:50, v/v). The analytes were detected with multiple reaction monitoring for the quantitative response of the compounds. The inter- and intra-day precisions were <8.29 and 3.85%, respectively, and the accuracy range was within ±7.33%. The method was successfully applied to evaluate the pharmacokinetics of compound I in mouse plasma and brain tissue. The peak concentration in plasma was achieved within 1 h. The apparent elimination half-life was 4.06 h. The peak concentration of compound I in brain tissue was 0.88 µg/g. The results indicated that compound I was rapidly distributed and could cross the blood-brain barrier. The pharmacokinetic profile summarized provides valuable information for the further investigation of compound I as a potential anti-glioblastoma agent.
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Barreira Hematoencefálica , Espectrometria de Massas em Tandem , Administração Oral , Animais , Cromatografia Líquida de Alta Pressão/métodos , Humanos , Camundongos , Reprodutibilidade dos Testes , Espectrometria de Massas em Tandem/métodosRESUMO
The Eph receptor tyrosine kinases and their ephrin ligands direct axon pathfinding and neuronal cell migration, as well as mediate many other cell-cell communication events. Their dysfunctional signaling has been shown to lead to various diseases, including cancer. The Ephs and ephrins both localize to the plasma membrane and, upon cell-cell contact, form extensive signaling assemblies at the contact sites. The Ephs and the ephrins are divided into A and B subclasses based on their sequence conservation and affinities for each other. The molecular details of Eph-ephrin recognition have been previously revealed and it has been documented that ephrin binding induces higher-order Eph assemblies, which are essential for full biological activity, via multiple, distinct Eph-Eph interfaces. One Eph-Eph interface type is characterized by a homotypic, head-to-tail interaction between the ligand-binding and the fibronectin domains of two adjacent Eph molecules. While the previous Eph ectodomain structural studies were focused on A class receptors, we now report the crystal structure of the full ectodomain of EphB2, revealing distinct and unique head-to-tail receptor-receptor interactions. The EphB2 structure and structure-based mutagenesis document that EphB2 uses the head-to-tail interactions as a novel autoinhibitory control mechanism for regulating downstream signaling and that these interactions can be modulated by posttranslational modifications.
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Receptor EphB2/química , Receptor EphB2/metabolismo , Transdução de Sinais , Animais , Células HEK293 , Humanos , Camundongos , Domínios Proteicos , Receptor EphB2/genética , Relação Estrutura-AtividadeRESUMO
EphA2 receptor kinase could become a novel target for anti-glioblastoma treatment. Doxazosin previously identified acts like the endogenous ligand of EphA2 and induces cell apoptosis. Through lead structure modification a derivative of Doxazosin possessing unique dimeric structure showed an improvement in the activity. In the current study, we expanded the dimeric scaffold by lead optimization to explore the chemical space of the conjoining moieties and a slight variation to the core structure. 27 new derivatives were synthesized and examined with EphA2 overexpressed and wild type glioblastoma cell lines for cell proliferation and EphA2 activation. Three new compounds 3d, 3e, and 7bg showed potent and selective activities against the growth of EphA2 overexpressed glioblastoma cells. Dimer 3d modification replaces the long alkyl chain with a short polyethylene glycol chain. Dimer 7bg has a relatively longer polyethylene glycol chain in comparison to compound 3d and the length is more similar to the lead compound. Whereas dimer 3e has a rigid aromatic linker exploring the chemical space. The diversity of the linkers in the active suggest additional hydrogen binding sites has a positive correlation to the activity. All three dimers showed selective activity in EphA2 overexpressed cells, indicating the activity is correlated to the EphA2 targeting effect.
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Antineoplásicos/síntese química , Proliferação de Células/efeitos dos fármacos , Doxazossina/síntese química , Glioblastoma/tratamento farmacológico , Quinazolinas/química , Receptor EphA2/agonistas , Antineoplásicos/farmacologia , Sítios de Ligação , Linhagem Celular Tumoral , Dimerização , Doxazossina/farmacologia , Ensaios de Seleção de Medicamentos Antitumorais , Humanos , Hidrocarbonetos Aromáticos/química , Estrutura Molecular , Polietilenoglicóis/química , Polietilenoglicóis/metabolismo , Ligação Proteica , Relação Estrutura-Atividade , Especificidade por SubstratoRESUMO
Compound 27 {1, 12-bis[4-(4-amino-6,7-dimethoxyquinazolin-2-yl)piperazin-1-yl]dodecane-1,12-dione} is a novel small molecule agonist of EphA2 receptor tyrosine kinase. It showed much improved activity for the activation of EphA2 receptor compared with the parental compound doxazosin. To support further pharmacological and toxicological studies of the compound, a method using liquid chromatography and electrospray ionization tandem mass spectrometry (LC-MS/MS) has been developed for the quantification of this compound. Liquid-liquid extraction was used to extract the compound from mouse plasma and brain tissue homogenate. Reverse-phase chromatography with gradient elution was performed to separate compound 27 from the endogenous molecules in the matrix, followed by MS detection using positive ion multiple reaction monitoring mode. Multiple reaction monitoring transitions m/z 387.3 â 290.1 and m/z 384.1 â 247.1 were selected for monitoring compound 27 and internal standard prazosin, respectively. The linear calibration range was 2-200 ng/mL with the intra- and inter-day precision and accuracy within the acceptable range. This method was successfully applied to the quantitative analysis of compound 27 in mouse plasma and brain tissue with different drug administration routes.
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Cromatografia Líquida/métodos , Piperazinas/análise , Piperazinas/farmacocinética , Quinazolinas/análise , Quinazolinas/farmacocinética , Receptor EphA2/agonistas , Espectrometria de Massas em Tandem/métodos , Animais , Química Encefálica , Feminino , Modelos Lineares , Camundongos , Piperazinas/química , Quinazolinas/química , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: Glioblastoma (GBM) is the most common and aggressive brain tumors. It has poor prognosis even with optimal radio- and chemo-therapies. Since GBM is highly heterogeneous, drugs that target on specific molecular profiles of individual tumors may achieve maximized efficacy. Currently, the Cancer Genome Atlas (TCGA) projects have identified hundreds of GBM-associated genes. We develop a drug repositioning approach combining disease genomics and mouse phenotype data towards predicting targeted therapies for GBM. METHODS: We first identified disease specific mouse phenotypes using the most recently discovered GBM genes. Then we systematically searched all FDA-approved drugs for candidates that share similar mouse phenotype profiles with GBM. We evaluated the ranks for approved and novel GBM drugs, and compared with an existing approach, which also use the mouse phenotype data but not the disease genomics data. RESULTS: We achieved significantly higher ranks for the approved and novel GBM drugs than the earlier approach. For all positive examples of GBM drugs, we achieved a median rank of 9.2 45.6 of the top predictions have been demonstrated effective in inhibiting the growth of human GBM cells. CONCLUSION: We developed a computational drug repositioning approach based on both genomic and phenotypic data. Our approach prioritized existing GBM drugs and outperformed a recent approach. Overall, our approach shows potential in discovering new targeted therapies for GBM.
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Biologia Computacional/métodos , Genômica , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Animais , Perfilação da Expressão Gênica/métodos , Regulação Neoplásica da Expressão Gênica , Genoma Humano , Glioblastoma/patologia , Humanos , Camundongos , MicroRNAs , Medicina de Precisão , PrognósticoRESUMO
The sterile α motif (SAM) domain of the ephrin receptor tyrosine kinase, EphA2, undergoes tyrosine phosphorylation, but the effect of phosphorylation on the structure and interactions of the receptor is unknown. Studies to address these questions have been hindered by the difficulty of obtaining site-specifically phosphorylated proteins in adequate amounts. Here, we describe the use of chemically synthesized and specifically modified domain-length peptides to study the behavior of phosphorylated EphA2 SAM domains. We show that tyrosine phosphorylation of any of the three tyrosines, Tyr(921), Tyr(930), and Tyr(960), has a surprisingly small effect on the EphA2 SAM structure and stability. However, phosphorylation at Tyr(921) and Tyr(930) enables differential binding to the Src homology 2 domain of the adaptor protein Grb7, which we propose will lead to distinct functional outcomes. Setting up different signaling platforms defined by selective interactions with adaptor proteins thus adds another level of regulation to EphA2 signaling.
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Proteína Adaptadora GRB7/química , Fosfotirosina/química , Receptor EphA2/química , Motivos de Aminoácidos , Proteína Adaptadora GRB7/genética , Proteína Adaptadora GRB7/metabolismo , Humanos , Fosfotirosina/genética , Fosfotirosina/metabolismo , Estrutura Terciária de Proteína , Receptor EphA2/genética , Receptor EphA2/metabolismo , Transdução de Sinais/fisiologiaRESUMO
The impact of Eph and ephrin signaling on cell behavior is complex and highly context dependent. Forward signaling initiated by Eph receptor activation and reverse signaling initiated by ephrin activation often mediate opposite effects. The apparent ligand-independent functions of Eph receptors recognized recently add another layer of complexity. This review will attempt to sort out the information generated recently on signaling by the A subfamily of Eph receptors and ephrin ligands. We will focus on EphA/ephrin-A signaling in the context of several physiological and disease processes, where new progresses have been made lately and unifying themes are emerging amid previous confusions. For more comprehensive survey of literature on Eph/ephrin signaling pathways and networks, readers are referred to outstanding reviews both in this volume and in other recent publications.
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Receptores da Família Eph/metabolismo , Transdução de Sinais , Animais , Adesão Celular , Movimento Celular , Efrinas/metabolismo , Efrinas/fisiologia , Humanos , Neoplasias/metabolismo , Neoplasias/patologia , Receptor Cross-TalkRESUMO
Eph receptor tyrosine kinases mediate cell-cell communication by interacting with ephrin ligands residing on adjacent cell surfaces. In doing so, these juxtamembrane signaling complexes provide important contextual information about the cellular microenvironment that helps orchestrate tissue morphogenesis and maintain homeostasis. Eph/ephrin signaling has been implicated in various aspects of mammalian skin physiology, with several members of this large family of receptor tyrosine kinases and their ligands present in the epidermis, hair follicles, sebaceous glands, and underlying dermis. This review focuses on the emerging role of Eph receptors and ephrins in epidermal keratinocytes where they can modulate proliferation, migration, differentiation, and death. The activation of Eph receptors by ephrins at sites of cell-cell contact also appears to play a key role in the maturation of intercellular junctional complexes as keratinocytes move out of the basal layer and differentiate in the suprabasal layers of this stratified, squamous epithelium. Furthermore, alterations in the epidermal Eph/ephrin axis have been associated with cutaneous malignancy, wound healing defects and inflammatory skin conditions. These collective observations suggest that the Eph/ephrin cell-cell communication pathway may be amenable to therapeutic intervention for the purpose of restoring epidermal tissue homeostasis and integrity in dermatological disorders.
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Diferenciação Celular , Efrinas/fisiologia , Epiderme/metabolismo , Receptores da Família Eph/fisiologia , Transdução de Sinais , Animais , Adesão Celular , Proliferação de Células , Efrinas/metabolismo , Epiderme/patologia , Humanos , Queratinócitos/metabolismo , Queratinócitos/fisiologia , Receptores da Família Eph/metabolismo , Neoplasias Cutâneas/metabolismo , Neoplasias Cutâneas/patologia , CicatrizaçãoRESUMO
(1) Background: Identifying acute aortic syndrome (AAS) and thoracic aortic aneurysm (TAA) in busy emergency departments (EDs) is crucial due to their life-threatening nature, necessitating timely and accurate diagnosis. (2) Methods: This retrospective case-control study was conducted in the ED of three hospitals. Adult patients visiting the ED between 1 January 2010 and 1 January 2020 with a chief complaint of chest or back pain were enrolled in the study. The collected chest radiography (CXRs) data were divided into training (80%) and testing (20%) datasets. The training dataset was trained by four different convolutional neural network (CNN) models. (3) Results: A total of 1625 patients were enrolled in this study. The InceptionV3 model achieved the highest F1 score of 0.76. (4) Conclusions: Analysis of CXRs using a CNN-based model provides a novel tool for clinicians to interpret ED patients with chest pain and suspected AAS and TAA. The integration of such imaging tools into ED could be considered in the future to enhance the diagnostic workflow for clinically fatal diseases.
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Purpose: The effects of the combination of strength training and acupuncture on chronic ankle instability have not been studied. This study examined effects of strength training combined with acupuncture on balance ability, ankle motion perception, and muscle strength in chronic ankle instability among college students. Methods: Forty-six chronic ankle instability college students were randomly categorized into the experimental group (n = 24, strength training + acupuncture) and the control group (n = 22, strength training) for an 8-week intervention. Results: For the results at 8 weeks, compared with the baseline, in the experimental group, the chronic Ankle Instability Tool (CAIT) score, ankle dorsiflexion, plantar flex, eversion peak torque (60°/s), and plantar flex peak torque (180°/s) increased by 13.7%, 39.4%, 13.7%, 14.2%, and 12.3%, respectively. Dorsiflexion, plantar flexion, inversion, and eversion kinesthetic sensation test angles decreased by 17.4%, 20.6%, 15.0%, and 17.2%, respectively. Anterior-posterior and medial-lateral displacement, and anterior-posterior and medial-lateral velocity decreased by 28.9%, 31.6%, 33.3%, and 12.4%, respectively. Anterior-posterior and medial-lateral displacement, and anterior-posterior and medial-lateral mean velocity decreased by 28.9%, 31.6%, 33.3%, and 12.4%, respectively. In the control group, the Cumberland Ankle Instability Tool score and the ankle dorsiflexion peak torque (60°/s) increased by 13.8% and 17.9%, respectively. The inversion kinesthetic sensation test angle decreased by 15.2%, whereas anterior-posterior and medial-lateral displacement, and anterior-posterior and medial-lateral mean velocity decreased by 17.1%, 29.4%, 12.3%, and 16.8%, respectively. 2) For the comparison between the groups after 8 weeks, the values of ankle dorsiflexion and plantar flex peak torque (60°/s) in the experimental group were greater than those in the control group. The values of ankle plantar flex kinesthetic sensation test angle, the anterior-posterior displacement, and anterior-posterior mean velocity in the experimental group were lower than those in the control group. Conclusion: Acupuncture treatment in conjunction with muscle strength training can further improve the balance ability of anterior-posterior, ankle dorsiflexion, and plantar flex strength and plantar flex motion perception in chronic ankle instability participants.
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Gravitational forces can induce deviations in body posture from desired configurations in multi-legged arboreal robot locomotion with low leg stiffness, affecting the contact angle between the swing leg's end-effector and the climbing surface during the gait cycle. The relationship between desired and actual foot positions is investigated here in a leg-stiffness-enhanced model under external forces, focusing on the challenge of unreliable end-effector attachment on climbing surfaces in such robots. Inspired by the difference in ceiling attachment postures of dead and living geckos, feedforward compensation of the stance phase legs is the key to solving this problem. A feedforward gravity compensation (FGC) strategy, complemented by leg coordination, is proposed to correct gravity-influenced body posture and improve adhesion stability by reducing body inclination. The efficacy of this strategy is validated using a quadrupedal climbing robot, EF-I, as the experimental platform. Experimental validation on an inverted surface (ceiling walking) highlights the benefits of the FGC strategy, demonstrating its role in enhancing stability and ensuring reliable end-effector attachment without external assistance. In the experiment, robots without FGC only completed 3 out of 10 trials, while robots with FGC achieved a 100% success rate in the same trials. The speed was substantially greater with FGC, achieving 9.2 mm s-1in the trot gait. This underscores the proposed potential of the FGC strategy in overcoming the challenges associated with inconsistent end-effector attachment in robots with low leg stiffness, thereby facilitating stable locomotion even at an inverted body attitude.
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Pé , Gravitação , Lagartos , Locomoção , Robótica , Robótica/instrumentação , Robótica/métodos , Animais , Locomoção/fisiologia , Lagartos/fisiologia , Pé/fisiologia , Marcha/fisiologia , Fenômenos Biomecânicos , Biomimética/instrumentação , Biomimética/métodos , Desenho de Equipamento , Dedos do Pé/fisiologia , Modelos BiológicosRESUMO
Tripartite-motif 56 (TRIM56) is a member of the TRIM family, and was shown to be an interferon-inducible E3 ubiquitin ligase that can be overexpressed upon stimulation with double-stranded DNA to regulate stimulator of interferon genes (STING) to produce type I interferon and thus mediate innate immune responses. Its role in tumors remains unclear. In this study, we investigated the relationship between the expression of the TRIM56 gene and its prognostic value in pan-cancer, identifying TRIM56 expression as an adverse prognostic factor in glioma patients. Therefore, glioma was selected as the primary focus of our investigation. We explored the differential expression of TRIM56 in various glioma subtypes and verified its role as an independent prognostic factor in gliomas. Our research revealed that TRIM56 is associated with malignant biological behaviors in gliomas, such as proliferation, migration, and invasion. Additionally, it can mediate M2 polarization of macrophages in gliomas. The results were validated in vitro and in vivo. Furthermore, we utilized single-cell analysis to investigate the impact of TRIM56 expression on cell communication between glioma cells and non-tumor cells. We constructed a multi-gene signature based on cell markers of tumor cells with high TRIM56 expression to enhance the prediction of cancer patient prognosis. In conclusion, our study demonstrates that TRIM56 serves as a reliable immune-related prognostic biomarker in glioma.
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Glioma , Interferons , Humanos , Prognóstico , Glioma/genética , Biomarcadores , Análise de Célula Única , Proteínas com Motivo Tripartido/genética , Proteínas com Motivo Tripartido/metabolismo , Ubiquitina-Proteína LigasesRESUMO
A precise measurement of animal behavior and reaction forces from their surroundings can help elucidate the fundamental principle of animal locomotion, such as landing and takeoff. Compared with stiff substrates, compliant substrates, like leaves, readily yield to loads, presenting grand challenges in measuring the reaction forces on the substrates involving compliance. To gain insight into the kinematic mechanisms and structural-functional evolution associated with arboreal animal locomotion, this study introduces an innovative device that facilitates the quantification of the reaction forces on compliant substrates, like leaves. By utilizing the stiffness-damping characteristics of servomotors and the adjustable length of a cantilever structure, the substrate compliance of the device can be accurately controlled. The substrate was further connected to a force sensor and an acceleration sensor. With the cooperation of these sensors, the measured interaction force between the animal and the compliant substrate prevented the effects of inertial force coupling. The device was calibrated under preset conditions, and its force measurement accuracy was validated, with the error between the actual measured and theoretical values being no greater than 10%. Force curves were measured, and frictional adhesion coefficients were calculated from comparative experiments on the landing/takeoff of adherent animals (tree frogs and geckos) on this device. Analysis revealed that the adhesion force limits were significantly lower than previously reported values (0.2~0.4 times those estimated in previous research). This apparatus provides mechanical evidence for elucidating structural-functional relationships exhibited by animals during locomotion and can serve as an experimental platform for optimizing the locomotion of bioinspired robots on compliant substrates.
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To analyze the metabolites (blood, urine and feces) in normal rats after intragastric administration of the decoction of Phellodendri Amurensis Cortex (PAC) and to map the metabolic profile of PAC in vivo of rat; meanwhile, to evaluate the anti-rheumatoid arthritis (RA) effect of PAC by blood metabolomics technique and to explore its mechanism. Performing on UPLC-Q-TOF-MS technology with a Waters ACQUITY UPLC BEH-C18 column (100â¯mm × 2.1â¯mm, 1.7 µm), the mobile phase was acetonitrile-0.1% formic acid aqueous solution (gradient elution). Prior to and following the administration of the decoction of PAC, the samples of blood, urine, and fecal were collected from the rats, in the positive ion mode, pharmacogenic metabolites in each biological sample were identified according to the accurate mass, fragment ions, retention time, metabolic reaction type, comparison of reference substance and retrieval of Pub Med database; The adjuvant-type arthritis (AA) rat model was established, and blood metabonomics method was used to study the improvement effect of rheumatoid arthritis after drug intervention with PAC, and its mechanism was preliminarily explored through analysis of metabolic pathway. A total of 72 exogenous components were identified, including 17 prototype components and 55 metabolites; 14 biomarkers were screened by blood metabolomics techniques combined with multivariate statistical analysis, and PAC significantly improved symptoms of rheumatoid arthritis in rats, and the metabolic pathway analysis mainly involves 5 metabolic pathways. The components in the aqueous decoction of PAC mainly undergo phase I metabolic reactions in rats, such as oxidation, reduction, dehydrogenation, demethylation, and phase II metabolic reactions, such as acetylation, glucuronidation, methylation; PAC has anti-rheumatoid arthritis effects, and its mechanism of action may be related to biosynthesis of aminoacyl-tRNA, metabolism of phenylalanine, metabolism of tryptophan, degradation of valine, leucine and isoleucine and biosynthesis of pantothenic acid and coenzyme A, providing a scientific basis for the study of the pharmacodynamic substances and the action mechanism of PAC against RA.
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Artrite Reumatoide , Medicamentos de Ervas Chinesas , Phellodendron , Ratos , Animais , Phellodendron/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/farmacologia , Metabolômica , Metaboloma , Artrite Reumatoide/tratamento farmacológicoRESUMO
Animals have evolved highly effective locomotion capabilities in terrestrial, aerial, and aquatic environments. Over life's history, mass extinctions have wiped out unique animal species with specialized adaptations, leaving paleontologists to reconstruct their locomotion through fossil analysis. Despite advancements, little is known about how extinct megafauna, such as the Ichthyosauria one of the most successful lineages of marine reptiles, utilized their varied morphologies for swimming. Traditional robotics struggle to mimic extinct locomotion effectively, but the emerging soft robotics field offers a promising alternative to overcome this challenge. This paper aims to bridge this gap by studyingMixosauruslocomotion with soft robotics, combining material modeling and biomechanics in physical experimental validation. Combining a soft body with soft pneumatic actuators, the soft robotic platform described in this study investigates the correlation between asymmetrical fins and buoyancy by recreating the pitch torque generated by extinct swimming animals. We performed a comparative analysis of thrust and torque generated byCarthorhyncus,Utatsusaurus,Mixosaurus,Guizhouichthyosaurus, andOphthalmosaurustail fins in a flow tank. Experimental results suggest that the pitch torque on the torso generated by hypocercal fin shapes such as found in model systems ofGuizhouichthyosaurus,MixosaurusandUtatsusaurusproduce distinct ventral body pitch effects able to mitigate the animal's non-neutral buoyancy. This body pitch control effect is particularly pronounced inGuizhouichthyosaurus, which results suggest would have been able to generate high ventral pitch torque on the torso to compensate for its positive buoyancy. By contrast, homocercal fin shapes may not have been conducive for such buoyancy compensation, leaving torso pitch control to pectoral fins, for example. Across the range of the actuation frequencies of the caudal fins tested, resulted in oscillatory modes arising, which in turn can affect the for-aft thrust generated.
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Nadadeiras de Animais , Modelos Biológicos , Robótica , Natação , Animais , Natação/fisiologia , Nadadeiras de Animais/fisiologia , Nadadeiras de Animais/anatomia & histologia , Robótica/instrumentação , Fenômenos Biomecânicos , Répteis/fisiologia , Répteis/anatomia & histologia , Fósseis , Simulação por Computador , Biomimética/métodosRESUMO
Objective: This study aimed to investigate the effects of regular isokinetic muscle strength training on knee muscle strength, proprioception, and balance ability in athletes after anterior cruciate ligament (ACL) reconstruction. Methods: Forty-one athletes who underwent ACL reconstruction were randomly divided into the experimental (n = 21) and control (n = 20) groups. The experimental group used an isokinetic muscle strength tester for 4 weeks (five times/ week) of knee flexion and extension isokinetic muscle strength training. The control group used the knee joint trainer (pneumatic resistance) for the same exercise regimen as the experimental group. Results: 1) Four weeks when compared with the baseline. Experimental group: the knee flexion and extension PT (60°/s and 240°/s) increased by 31.7%, 40.3%, 23.4%, and 42.9% (p < 0.01), and the flexion muscular endurance increased by 21.4% and 19.7% (p < 0.01). The flexion and extension kinaesthesia and the 30° and 60° position sense decreased by 36.2%, 32.3%, 40.0%, and 18.9% (p < 0.05). The anterior-posterior and medial-lateral displacement and speed decreased by 30.2%, 44.2%, 38.4%, and 24.0% (p < 0.05). Control group: the knee peak torque (60°/s) increased by 18.8% (p < 0.01). The anterior-posterior and medial-lateral displacement and speed decreased by 14.9%, 40.0%, 26.8%, and 19.5% (p < 0.01). 2) After 4 weeks, compared with the control group, the knee flexion and extension peak torque (60°/s), extension, peak torque (240°/s), and extension muscular endurance of the treatment group increased to varying degrees (p < 0.05). However, the kinaesthesia, 30° position sense, and anterior-posterior displacement decreased to varying degrees (p < 0.05). Conclusion: Adding regular isokinetic muscle strength training to rehabilitation training further improved the knee flexion and extensor strength and extensor endurance of athletes with ACL reconstruction, as well as enhanced the kinaesthesia and 30° position sense and the balance between the anterior and posterior directions. However, the treatment had limited effects on knee flexion kinaesthesia and muscle endurance.