Effect of strength training with additional acupuncture on balance, ankle sensation, and isokinetic muscle strength in chronic ankle instability among college students.

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.

Asymmetric fin shape changes swimming dynamics of ancient marine reptiles' soft robophysical models.

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.

Metabolic profile of Phellodendron amurense Rupr. in vivo of rat and its metabolomic study on intervention in rheumatoid arthritis.

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 (100 mm × 2.1 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.

Device for Measuring Contact Reaction Forces during Animal Adhesion Landing/Takeoff from Leaf-like Compliant Substrates.

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.

TRIM56: a promising prognostic immune biomarker for glioma revealed by pan-cancer and single-cell analysis.

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.

Time-resolved live-cell spectroscopy reveals EphA2 multimeric assembly.

Ephrin type-A receptor 2 (EphA2) is a receptor tyrosine kinase that initiates both ligand-dependent tumor-suppressive and ligand-independent oncogenic signaling. We used time-resolved, live-cell fluorescence spectroscopy to show that the ligand-free EphA2 assembles into multimers driven by two types of intermolecular interactions in the ectodomain. The first type entails extended symmetric interactions required for ligand-induced receptor clustering and tumor-suppressive signaling that inhibits activity of the oncogenic extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) protein kinases and suppresses cell migration. The second type is an asymmetric interaction between the amino terminus and the membrane proximal domain of the neighboring receptors, which supports oncogenic signaling and promotes migration in vitro and tumor invasiveness in vivo. Our results identify the molecular interactions that drive the formation of the EphA2 multimeric signaling clusters and reveal the pivotal role of EphA2 assembly in dictating its opposing functions in oncogenesis.

Effect of isokinetic muscle strength training on knee muscle strength, proprioception, and balance ability in athletes with anterior cruciate ligament reconstruction: a randomised control trial.

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.

Tissue factor is a critical regulator of radiation therapy-induced glioblastoma remodeling.

Radiation therapy (RT) provides therapeutic benefits for patients with glioblastoma (GBM), but inevitably induces poorly understood global changes in GBM and its microenvironment (TME) that promote radio-resistance and recurrence. Through a cell surface marker screen, we identified that CD142 (tissue factor or F3) is robustly induced in the senescence-associated ß-galactosidase (SA-ßGal)-positive GBM cells after irradiation. F3 promotes clonal expansion of irradiated SA-ßGal+ GBM cells and orchestrates oncogenic TME remodeling by activating both tumor-autonomous signaling and extrinsic coagulation pathways. Intratumoral F3 signaling induces a mesenchymal-like cell state transition and elevated chemokine secretion. Simultaneously, F3-mediated focal hypercoagulation states lead to activation of tumor-associated macrophages (TAMs) and extracellular matrix (ECM) remodeling. A newly developed F3-targeting agent potently inhibits the aforementioned oncogenic events and impedes tumor relapse in vivo. These findings support F3 as a critical regulator for therapeutic resistance and oncogenic senescence in GBM, opening potential therapeutic avenues.

Three-dimensional-cultured MSC-derived exosome with hydrogel for cerebral ischemia repair.

Microglia-mediated neuroinflammatory response, one of the most essential pathological processes of cerebral ischemia-reperfusion (I/R) injury, is acknowledged as the main factors leading to poor prognosis of cerebral ischemia. Exosome derived from mesenchymal stem cell (MSC-Exo) exhibits neuroprotective functions by reducing cerebral ischemia-induced neuroinflammatory response and promoting angiogenesis. However, MSC-Exo has disadvantages such as insufficient targeting capability and low production, which limits their clinical applications. Here, we fabricated gelatin methacryloyl (GelMA) hydrogel for three-dimensional (3D) culture of MSCs. It is indicated that 3D environment could simulate the biological niches of MSCs, thereby significantly increasing the cell stemness of MSCs and improving the yield of MSCs-derived exosomes (3D-Exo). In this study, we utilized the modified Longa method to induce middle cerebral artery occlusion (MCAO) model. Additionally, in vitro and in vivo studies were conducted to interrogate the mechanism of the stronger neuroprotective effect of 3D-Exo. Furthermore, the administration of 3D-Exo in MCAO model could promote neovascularization in infarct region and result in a significant suppression of inflammatory response. This study proposed an exosome-based targeting delivery system for cerebral ischemia and provided a promising strategy for efficient and large-scale production of MSC-Exo.

A Neural Coordination Strategy for Attachment and Detachment of a Climbing Robot Inspired by Gecko Locomotion.

Climbing behavior is a superior motion skill that animals have evolved to obtain a more beneficial position in complex natural environments. Compared to animals, current bionic climbing robots are less agile, stable, and energy-efficient. Further, they locomote at a low speed and have poor adaptation to the substrate. One of the key elements that can improve their locomotion efficiency is the active and flexible feet or toes observed in climbing animals. Inspired by the active attachment-detachment behavior of geckos, a hybrid pneumatic-electric-driven climbing robot with active attachment-detachment bionic flexible feet (toes) was developed. Although the introduction of bionic flexible toes can effectively improve the robot's adaptability to the environment, it also poses control challenges, specifically, the realization of attachment-detachment behavior by the mechanics of the feet, the realization of hybrid drive control with different response characteristics, and the interlimb collaboration and limb-foot coordination with a hysteresis effect. Through the analysis of geckos' limbs and foot kinematic behavior during climbing, rhythmic attachment-detachment strategies and coordination behavior between toes and limbs at different inclines were identified. To enable the robot to achieve similar foot attachment-detachment behavior for climbing ability enhancement, we propose a modular neural control framework comprising a central pattern generator module, a post-processing central pattern generation module, a hysteresis delay line module, and an actuator signal conditioning module. Among them, the hysteresis adaptation module helps the bionic flexible toes to achieve variable phase relationships with the motorized joint, thus enabling proper limb-to-foot coordination and interlimb collaboration. The experiments demonstrated that the robot with neural control achieved proper coordination, resulting in a foot with a 285% larger adhesion area than that of a conventional algorithm. In addition, in the plane/arc climbing scenario, the robot with coordination behavior increased by as much as 150%, compared to the incoordinated one owing to its higher adhesion reliability.

Lead Optimization of Androgen Receptor-HSP27 Disrupting Agents in Glioblastoma.

Glioblastoma (GBM) is the most common malignant brain tumor with poor prognosis under the current standard treatment. It is critical to develop new approaches to selectively battle the disease. GBM sex differences suggest that an androgen receptor (AR) is a potential therapeutic target to treat AR-overexpressed GBM. Heat shock 27 kDa protein (HSP27) is a well-documented chaperone protein that stabilizes AR. Inhibition of HSP27 leads to AR degradation, indicating that HSP27 inhibitors could suppress AR activity in GBM. We have identified a lead HSP27 inhibitor that could induce AR degradation. Lead optimization resulted with two new derivatives (compounds 4 and 26) showing potent anti-GBM activity and improved drug distribution in comparison to the lead compound. Compounds 4 and 6 exhibit IC50s of 35 and 23 nM, respectively, to inhibit cell proliferation and also show significant activity to decrease the tumor growth in vivo.

A Multipronged Unbiased Strategy Guides the Development of an Anti-EGFR/EPHA2-Bispecific Antibody for Combination Cancer Therapy.

PURPOSE: Accumulating analyses of pro-oncogenic molecular mechanisms triggered a rapid development of targeted cancer therapies. Although many of these treatments produce impressive initial responses, eventual resistance onset is practically unavoidable. One of the main approaches for preventing this refractory condition relies on the implementation of combination therapies. This includes dual-specificity reagents that affect both of their targets with a high level of selectivity. Unfortunately, selection of target combinations for these treatments is often confounded by limitations in our understanding of tumor biology. Here, we describe and validate a multipronged unbiased strategy for predicting optimal co-targets for bispecific therapeutics. EXPERIMENTAL DESIGN: Our strategy integrates ex vivo genome-wide loss-of-function screening, BioID interactome profiling, and gene expression analysis of patient data to identify the best fit co-targets. Final validation of selected target combinations is done in tumorsphere cultures and xenograft models. RESULTS: Integration of our experimental approaches unambiguously pointed toward EGFR and EPHA2 tyrosine kinase receptors as molecules of choice for co-targeting in multiple tumor types. Following this lead, we generated a human bispecific anti-EGFR/EPHA2 antibody that, as predicted, very effectively suppresses tumor growth compared with its prototype anti-EGFR therapeutic antibody, cetuximab. CONCLUSIONS: Our work not only presents a new bispecific antibody with a high potential for being developed into clinically relevant biologics, but more importantly, successfully validates a novel unbiased strategy for selecting biologically optimal target combinations. This is of a significant translational relevance, as such multifaceted unbiased approaches are likely to augment the development of effective combination therapies for cancer treatment. See related commentary by Kumar, p. 2570.

Reversible Adhesive Bio-Toe with Hierarchical Structure Inspired by Gecko.

The agile locomotion of adhesive animals is mainly attributed to their sophisticated hierarchical feet and reversible adhesion motility. Their structure-function relationship is an urgent issue to be solved to understand biologic adhesive systems and the design of bionic applications. In this study, the reversible adhesion/release behavior and structural properties of gecko toes were investigated, and a hierarchical adhesive bionic toe (bio-toe) consisting of an upper elastic actuator as the supporting/driving layer and lower bionic lamellae (bio-lamellae) as the adhesive layer was designed, which can adhere to and release from targets reversibly when driven by bi-directional pressure. A mathematical model of the nonlinear deformation and a finite element model of the adhesive contact of the bio-toe were developed. Meanwhile, combined with experimental tests, the effects of the structure and actuation on the adhesive behavior and mechanical properties of the bio-toe were investigated. The research found that (1) the bending curvature of the bio-toe, which is approximately linear with pressure, enables the bio-toe to adapt to a wide range of objects controllably; (2) the tabular bio-lamella could achieve a contact rate of 60% with a low squeeze contact of less than 0.5 N despite a ±10° tilt in contact posture; (3) the upward bending of the bio-toe under negative pressure provided sufficient rebounding force for a 100% success rate of release; (4) the ratio of shear adhesion force to preload of the bio-toe with tabular bio-lamellae reaches approximately 12, which is higher than that of most existing adhesion units and frictional gripping units. The bio-toe shows good adaptability, load capacity, and reversibility of adhesion when applied as the basic adhesive unit in a robot gripper and wall-climbing robot. Finally, the proposed reversible adhesive bio-toe with a hierarchical structure has great potential for application in space, defense, industry, and daily life.

Effects of different diets used to induce obesity/metabolic syndrome on bladder function in rats.

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.

Cross-sectional study of depression tendency and sleep quality in 1352 people practicing Tai Chi.

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.

Cuproptosis-related gene signature stratifies lower-grade glioma patients and predicts immune characteristics.

Cuproptosis is the most recently discovered type of regulated cell death and is mediated by copper ions. Studies show that cuproptosis plays a significant role in cancer development and progression. Lower-grade gliomas (LGGs) are slow-growing brain tumors. The majority of LGGs progress to high-grade glioma, which makes it difficult to predict the prognosis. However, the prognostic value of cuproptosis-related genes (CRGs) in LGG needs to be further explored. mRNA expression profiles and clinical data of LGG patients were collected from public sources for this study. Univariate Cox regression analysis and the least absolute shrinkage and selection operator (LASSO) Cox regression model were used to build a multigene signature that could divide patients into different risk groups. The differences in clinical pathological characteristics, immune infiltration characteristics, and mutation status were evaluated in risk subgroups. In addition, drug sensitivity and immune checkpoint scores were estimated in risk subgroups to provide LGG patients with precision medication. We found that all CRGs were differentially expressed in LGG and normal tissues. Patients were divided into high- and low-risk groups based on the risk score of the CRG signature. Patients in the high-risk group had a considerably lower overall survival rate than those in the low-risk group. According to functional analysis, pathways related to the immune system were enriched, and the immune state differed across the two risk groups. Immune characteristic analysis showed that the immune cell proportion and immune scores were different in the different groups. High-risk group was characterized by low sensitivity to chemotherapy but high sensitivity to immune checkpoint inhibitors. The current study revealed that the novel CRG signature was related to the prognosis, clinicopathological features, immune characteristics, and treatment perference of LGG.

Effects of vacancy defects on the interfacial thermal resistance of partially overlapped bilayer graphene.

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.

Pharmacokinetic and brain distribution study of an anti-glioblastoma agent in mice by HPLC-MS/MS.

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.

Unobtrusive monitoring of sedentary behaviors with fusion of bluetooth and ballistocardiogram signals.

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.

The Ephb2 Receptor Uses Homotypic, Head-to-Tail Interactions within Its Ectodomain as an Autoinhibitory Control Mechanism.

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.