Towards Human-like Walking with Biomechanical and Neuromuscular Control Features: Personalized Attachment Point Optimization Method of Cable-Driven Exoskeleton

The cable-driven exoskeleton can avoid joint misalignment, and is substantial alterations in the pattern of muscle synergy coordination, which arouse more attention in recent years to facilitate exercise for older adults and improve their overall quality of life. This study leverages principles from neuroscience and biomechanical analysis to select attachment points for cable-driven soft exoskeletons. By extracting key features of human movement, the objective is to develop a subject-specific design methodology that provides precise and personalized support in the attachment points optimization of cable-driven exoskeleton to achieve natural gait, energy efficiency, and muscle coordination controllable in the domain of human mobility and rehabilitation. To achieve this, the study first analyzes human walking experimental data and extracts biomechanical features. These features are then used to generate trajectories, allowing better natural movement under complete cable-driven exoskeleton control. Next, a genetic algorithm-based method is employed to minimize energy consumption and optimize the attachment points of the cable-driven system. This process identifies connections that are better suited for the human model, leading to improved efficiency and natural movement. By comparing the calculated elderly human model driven by exoskeleton with experimental subject in terms of joint angles, joint torques and muscle forces, the human model can successfully replicate subject movement and the cable output forces can mimic human muscle coordination. The optimized cable attachment points facilitate more natural and efficient collaboration between humans and the exoskeleton, making significant contributions to the field of assisting the elderly in rehabilitation

Data_Sheet_1_Towards Human-like Walking with Biomechanical and Neuromuscular Control Features: Personalized Attachment Point Optimization Method of Cable-Driven Exoskeleton.PDF

The cable-driven exoskeleton can avoid joint misalignment, and is substantial alterations in the pattern of muscle synergy coordination, which arouse more attention in recent years to facilitate exercise for older adults and improve their overall quality of life. This study leverages principles from neuroscience and biomechanical analysis to select attachment points for cable-driven soft exoskeletons. By extracting key features of human movement, the objective is to develop a subject-specific design methodology that provides precise and personalized support in the attachment points optimization of cable-driven exoskeleton to achieve natural gait, energy efficiency, and muscle coordination controllable in the domain of human mobility and rehabilitation. To achieve this, the study first analyzes human walking experimental data and extracts biomechanical features. These features are then used to generate trajectories, allowing better natural movement under complete cable-driven exoskeleton control. Next, a genetic algorithm-based method is employed to minimize energy consumption and optimize the attachment points of the cable-driven system. This process identifies connections that are better suited for the human model, leading to improved efficiency and natural movement. By comparing the calculated elderly human model driven by exoskeleton with experimental subject in terms of joint angles, joint torques and muscle forces, the human model can successfully replicate subject movement and the cable output forces can mimic human muscle coordination. The optimized cable attachment points facilitate more natural and efficient collaboration between humans and the exoskeleton, making significant contributions to the field of assisting the elderly in rehabilitation.</p

Inhibition of Euchromatic Histone Methyltransferase 1 and 2 Sensitizes Chronic Myeloid Leukemia Cells to Interferon Treatment

<div><p>Background</p><p>H3K9 methylation is one of the essential histone post-translational modifications for heterochromatin formation and transcriptional repression. Recently, several studies have demonstrated that H3K9 methylation negatively regulates the type I interferon response.</p><p>Results</p><p>We report the application of EHMT1 and EHMT2 specific chemical inhibitors to sensitize CML cell lines to interferon and imatinib treatments. Inhibition of EHMT1 and EHMT2 with BIX01294 enhances the cytotoxicity of IFNα2a in four CML cell lines, K562, KCL22, BV173 and KT1 cells. Chromatin immunoprecipitation assay shows that BIX01294 treatment enhances type I interferon response by reducing H3K9me2 at the promoters of interferon-stimulated genes. Additionally, BIX01294 treatment augments IFNα2a- and imatinib-mediated apoptosis in CML cell lines. Moreover, our data suggest that the expression level of EHMT1 and EHMT2 inversely correlates with the type I interferon responsiveness in CML cell lines.</p><p>Conclusions</p><p>Our study sheds light on the role of EHMT1 and EHMT2 as potential targets in improving the efficacy of standard treatments of CML.</p></div

BIX01294 slightly enhance IFNα2a-induced anti-proliferation in non-CML cells.

<p>Jurkat (<b>A</b>), HeLa (<b>B</b>) and HaCat (<b>C</b>) cells were cultured with various concentrations of BIX01294 and IFNα2a as indicated. After four days, cell proliferation was measured with a MTT assay. Results represent the mean ± SD in quadruplicate experiments.</p

BIX01294 enhances the expressions of ISGs in K562 cells.

<p>(<b>A</b>) K562 cells were incubated with 2.5 µM BIX01294 for 24 hours. The cells were then treated with various concentrations of IFNα2a as indicated. After two hours of IFNα2a stimulation, the expression of various ISGs was measured with RT-qPCR. Error bars represent the variation range of duplicate experiments. *: p<0.05, **: p<0.01. (<b>B</b>) K562 cells were incubated with 2.5 µM BIX01294 for 24 hours. The cells were then treated with IFNβ or IFNγ for two hours. The expression of <i>IFIT2</i> and <i>IFIT3</i> was measured with RT-qPCR. Error bars represent the variation range of duplicate experiments. *: p<0.05.</p

UNC06398 inhibits the proliferation of K562 cells and potentiates the expression of ISGs.

<p>(<b>A</b>) K562 cells were cultured with various concentrations of UNC0638 and IFNα2a as indicated. After four days, cell proliferation was measured with a MTT assay. Results represent the mean ± SD in quadruplicate experiments. (<b>B</b>) K562 cells were incubated with 5 µM UNC0638 for 24 hours followed with various concentrations of IFNα2a stimulation as indicated. After two hours of IFNα2a stimulation, the expression of various ISGs was measured with RT-qPCR. Error bars represent the variation range of duplicate experiments. *: p<0.05, **: p<0.01. (<b>C</b>) Whole cell extracts or total RNA were generated from K562 cells infected with control or lentiviruses carrying EHMT1- or EHMT2-specific shRNAs (left). EHMT1 or EHMT2 protein levels were analyzed by immunoblotting using indicated antibodies while mRNA levels were measured with RT-qPCR. Error bars represent the variation range of duplicate experiments. The same cells were stimulated with 1000 IU/ml IFNα2a for two hours (right). The expression of various ISGs was measured with RT-qPCR<b>.</b> Error bars represent the variation range of duplicate experiments. **: p<0.01. (<b>D</b>) K562 cells as in (<b>C</b>) were cultured with various concentrations of IFNα2a as indicated. After four days, cell proliferation was measured with a MTT assay. Results represent the mean ± SD in quadruplicate experiments.</p

BIX01294 inhibits the proliferation of CML cells.

<p>K562 (<b>A</b>), KCL22 (<b>B</b>), BV173 (<b>C</b>) and KT1 (<b>D</b>) cells were cultured with various concentrations of BIX01294 and IFNα2a as indicated. After four days, cell proliferation was measured with a MTT assay. Results represent the mean ± SD in quadruplicate experiments.</p

Expression level of EHMT1 inversely correlates with the sensitivity of CML cells to interferon.

<p>(<b>A</b>) KT1, K562, KCL22 and BV173 cells were treated with or without 1000 IU/ml IFNα2a for 2 hours, the expression of <i>IFIT2</i> and <i>IFIT3</i> was measured with RT-qPCR. Error bars represent the variation range of duplicate experiments. *: p<0.05, **: p<0.01. (<b>B</b>) KT1, K562, KCL22 and BV173 cells were incubated with or without 2.5 µM BIX01294 for 24 hours. Cells were then infected with VSV-GFP at a MOI of 0.5 for 24 hours. GFP positive cells were sorted by FACS. Results represent the mean ± SD in triplicate experiments (<b>C)</b> Whole cell extracts were prepared from K562, KT1, BV173 and KCL22 cells, and examined by immunoblotting using the indicated antibodies. (<b>D</b>) The relative mRNA levels of EHMT1 and EHMT2 were measured with RT-qPCR. Results represent the mean ± SD in quadruplicate experiments. *: p<0.05. (<b>E</b>) Empty vector or FLAG-mEHMT1-HA-mEHMT2 KT1 cells were treated with or without IFNα2a (1000 IU/ml) for two hours, the expression of <i>IFIT2</i> and <i>IFIT3</i> was measured with RT-qPCR<b>.</b> Error bars represent the variation range of duplicate experiments. **: p<0.01.</p

BIX01294 enhances imatinib- and IFNα2a-induced apoptosis in K562 cells.

<p>(<b>A</b>) K562 cells were cultured with various concentrations of BIX01294 and imatinib as indicated. After four days, cell proliferation was measured with a MTT assay. Results represent the mean ± SD in quadruplicate experiments. (<b>B</b>) K562 cells were treated with or without IFNα2a (15 k IU/ml), or imatinib (150 nM) in the presence or absence of BIX01294 (2 µM) for 2 days. Cells were washed with PBS and fixed with 70% ethanol. Fixed cells were then stained with PI and analyzed with FACS. (<b>C</b>) K562 cells were stimulated with or without IFNα2a (10 k IU/ml), or imatinib (75 nM) in the presence or absence of BIX01294 (2 µM) for 2 days. Whole cell extracts were prepared and subjected to immunoblotting using the indicated antibodies.</p