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While exoskeleton technology is becoming more and more common for gait rehabilitation in children with neurological disorders, evaluation of gait performance still faces challenges and concerns. The reasoning behind evaluating the spinal locomotor output is that, while exoskeleton's guidance forces create the desired walking kinematics, they also affect sensorimotor interactions, which may lead to an abnormal spatiotemporal integration of activity in particular spinal segments and the risk of abnormalities in gait recovery. Therefore, traditional indicators based on kinematic or kinetic characteristics for optimizing exoskeleton controllers for gait rehabilitation may be supplemented by performance measures associated with the neural control mechanisms. The purpose of this study on a sample of children was to determine the basic features of lower limb muscle activity and to implement a method for assessing the neuromechanics of spinal locomotor output during exoskeleton-assisted gait. To this end, we assessed the effects of a robotic exoskeleton (ExoAtlet Bambini) on gait performance, by recording electromyographic activity of leg muscles and analyzing the corresponding spinal motor pool output. A slower walking setting (about 0.2 m/s) was chosen on the exoskeleton. The results showed that, even with slower walking, the level of muscle activation was roughly comparable during exoskeleton-assisted gait and normal walking. This suggests that, despite full assistance for leg movements, the child's locomotor controllers can interpret step-related afferent information promoting essential activity in leg muscles. This is most likely explained by the active nature of stepping in the exoskeleton (the child was not fully relaxed, experienced full foot loading and needed to maintain the upper trunk posture). In terms of the general muscle activity patterns, we identified notable variations for the proximal leg muscles, coactivation of the lumbar and sacral motor pools, and weak propulsion from the distal extensors at push-off. These changes led to the lack of characteristic lumbosacral oscillations of the center of motoneuron activity, normally associated with the pendulum mechanism of bipedal walking. This work shows promise as a useful technique for analyzing exoskeleton performance to help children develop their natural gait pattern and to guide system optimization in the future for inclusion into clinical care. [ABSTRACT FROM AUTHOR]

Background: Ovarian cancer is a highly aggressive malignancy with limited therapeutic options and a poor prognosis. Deubiquitinating enzymes (DUBs) have emerged as critical regulators of protein ubiquitination and proteasomal degradation, influencing various cellular processes relevant to cancer pathogenesis. In this study, the research progress between ovarian cancer and DUBs was mapped and visualized using bibliometrics, and the expression patterns and biological roles of DUBs in ovarian cancer were summarized. Methods: Studies related to DUBs in ovarian cancer were extracted from the Web of Science Core Collection (WoSCC) database. VOSviewer 1.6.20, CiteSpace 6.3.R1, and R4.3.3 were used for bibliometric analysis and visualization. Results: For analysis 243 articles were included in this study. The number of publications on DUBs in ovarian cancer has gradually increased each year. China, the United States, and the United Kingdom are at the center of this field of research. The Johns Hopkins University, Genentech, and Roche Holding are the main research institutions. David Komander, Zhihua Liu, and Richard Roden are the top authors in this field. The top five journals with the largest publication volumes in this field are Biochemical and Biophysical Research Communications, Journal of Biological Chemistry, PLOS One, Nature Communications, and Oncotarget. Keyword burst analysis identified five research areas: "deubiquitinating enzyme," "expression," "activation," "degradation," and "ubiquitin." In addition, we summarized the expression profiles and biological roles of DUBs in ovarian cancer, highlighting their roles in tumor initiation, growth, chemoresistance, and metastasis. Conclusion: An overview of the research progress is provided in this study on DUBs in ovarian cancer over the last three decades. It offers insight into the most cited papers and authors, core journals, and identified new trends. [ABSTRACT FROM AUTHOR]

Biped robots usually adopt feet with a rigid structure that simplifies walking on flat grounds and yet hinders ground adaptation in unstructured environments, thus jeopardizing stability. We recently explored in the SoftFoot the idea of adapting a robotic foot to ground irregularities along the sagittal plane. Building on the previous results, we propose in this paper a novel robotic foot able to adapt both in the sagittal and frontal planes, similarly to the human foot. It features five parallel modules with intrinsic longitudinal adaptability that can be combined in many possible designs through optional rigid or elastic connections. By following a methodological design approach, we narrow down the design space to five candidate foot designs and implement them on a modular system. Prototypes are tested experimentally via controlled application of force, through a robotic arm, onto a sensorized plate endowed with different obstacles. Their performance is compared, using also a rigid foot and the previous SoftFoot as a baseline. Analysis of footprint stability shows that the introduction of the transverse arch, by elastically connecting the five parallel modules, is advantageous for obstacle negotiation, especially when obstacles are located under the forefoot. In addition to biped robots' locomotion, this finding might also benefit lower-limb prostheses design. [ABSTRACT FROM AUTHOR]

Dienone compounds have been demonstrated to display tumor-selective anti-cancer activity independently of the mutational status of TP53. Previous studies have shown that cell death elicited by this class of compounds is associated with inhibition of the ubiquitin-proteasome system (UPS). Here we extend previous findings by showing that the dienone compound b-AP15 inhibits proteasomal degradation of long-lived proteins. We show that exposure to b-AP15 results in increased association of the chaperones VCP/p97/Cdc48 and BAG6 with proteasomes. Comparisons between the gene expression profile generated by b-AP15 to those elicited by siRNA showed that knock-down of the proteasome-associated deubiquitinase (DUB) USP14 is the closest related to drug response. USP14 is a validated target for b-AP15 and we show that b-AP15 binds covalently to two cysteines, Cys203 and Cys257, in the ubiquitin-binding pocket of the enzyme. Consistent with this, deletion of USP14 resulted in decreased sensitivity to b-AP15. Targeting of USP14 was, however, found to not fully account for the observed proteasome inhibition. In search for additional targets, we utilized genome-wide CRISPR/Cas9 library screening and Proteome Integral Solubility Alteration (PISA) to identify mechanistically essential genes and b-AP15 interacting proteins respectively. Deletion of genes encoding mitochondrial proteins decreased the sensitivity to b-AP15, suggesting that mitochondrial dysfunction is coupled to cell death induced by b-AP15. Enzymes known to be involved in Phase II detoxification such as aldo-ketoreductases and glutathione-S-transferases were identified as b-AP15-targets using PISA. The finding that different exploratory approaches yielded different results may be explained in terms of a "target" not necessarily connected to the "mechanism of action" thus highlighting the importance of a holistic approach in the identification of drug targets. We conclude that b-AP15, and likely also other dienone compounds of the same class, affect protein degradation and proteasome function at more than one level. [ABSTRACT FROM AUTHOR]