4D Printed Soft Microactuator for Particle Manipulation via Surrounding Medium Variation.

Soft actuators have assumed vital roles in a diverse number of research and application fields, driving innovation and transformative advancements. Using 3D molding of smart materials and combining these materials through structural design strategies, a single soft actuator can achieve multiple functions. However, it is still challenging to realize soft actuators that possess high environmental adaptability while capable of different tasks. Here, the response threshold of a soft actuator is modulated by precisely tuning the ratio of stimulus-responsive groups in hydrogels. By combining a heterogeneous bilayer membrane structure and in situ multimaterial printing, the obtained soft actuator deformed in response to changes in the surrounding medium. The response medium is suitable for both biotic and abiotic environments, and the response rate is fast. By changing the surrounding medium, the precise capture, manipulation, and release of micron-sized particles of different diameters in 3D are realized. In addition, static capture of a single red blood cell is realized using biologically responsive medium changes. Finally, the experimental results are well predicted using finite element analysis. It is believed that with further optimization of the structure size and autonomous navigation platform, the proposed soft microactuator has significant potential to function as an easy-to-manipulate multifunctional robot.

Skin-Inspired Capacitive Flexible Tactile Sensor with an Asymmetric Structure for Detecting Directional Shear Forces.

Flexible pressure sensors based on micro-/nanostructures can be integrated into robots to achieve sensitive tactile perception. However, conventional symmetric structures, such as pyramids or hemispheres, can sense only the magnitude of a force and not its direction. In this study, a capacitive flexible tactile sensor inspired by skin structures and based on an asymmetric microhair structure array to perceive directional shear force is designed. Asymmetric microhair structures are obtained by two-photon polymerization (TPP) and replication. Owing to the features of asymmetric microhair structures, different shear force directions result in different deformations. The designed device can determine the directions of both static and dynamic shear forces. Additionally, it exhibits large response scales ranging from 30 Pa to 300 kPa and maintains high stability even after 5000 cycles; the final relative capacitive change (ΔC/C0 ) is <2.5%. This flexible tactile sensor has the potential to improve the perception and manipulation ability of dexterous hands and enhance the intelligence of robots.

A 4D-Printing Inverse Design Strategy for Micromachines with Customized Shape-Morphing.

An active heterostructure with smart-response material used as "muscle" and inactive material as "skeleton" can deform over time to respond to external stimuli. 4D printing integrated with two-photon polymerization technology and smart material allows the material or characteristic distribution of active heterostructures to be defined directly at the microscale, providing a huge programmable space. However, the high degree of design freedom and the microscale pose a challenge to the construction of micromachines with customized shape morphing. Here, a reverse design strategy based on multi-material stepwise 4D printing is proposed to guide the structural design of biomimetic micromachines. Inspired by the piecewise constant curvature model of soft robot, a reverse design algorithm based on the Timoshenko model is developed. The algorithm can approximate 2D features to a constant-curvature model and determine an acceptable material distribution within the explored printing range. Three Chinese "Long" (Chinese dragon heralds of good fortune) designed by the strategy can deform to the customized shape. In addition, a microcrawler printed using this method can imitate a real inchworm gait. These results demonstrate that this method can be an efficient tool for the action or shape design of bionic soft microrobots or micromachines with predetermined functions.

Novel Optofluidic Imaging System Integrated with Tunable Microlens Arrays.

Optofluidic tunable microlens arrays (MLAs) can manipulate and control light propagation using fluids. Lately, their applicability to miniature lab-on-a-chip systems is being extensively researched. However, it is difficult to incorporate 3D MLAs directly in a narrow microfluidic channel using common techniques. This has resulted in limited research on variable focal length imaging with optofluidic 3D MLAs. In this paper, we propose a method for fabricating MLAs in polydimethylsiloxane (PDMS)-based microchannels via electrohydrodynamic jet (E-jet) printing to achieve optofluidic tunable MLAs. Using this method, MLAs of diameters 15 to 80 µm can be fabricated in microfluidic channels with widths of 200 and 300 µm. By alternately using solutions with different refractive indices in the microchannel, the optofluidic microlenses exhibit reversible modulation properties while retaining the morphologies and refractive indices of the microlenses. The focal length of the resulting optofluidic chip can have threefold tunability, thereby achieving an imaging depth of approximately 450 µm. This outstanding advantage is useful in observing microspheres and cells flowing in the microfluidic system. Thus, the proposed optofluidic chip exhibits great potential for cell counting and imaging applications.

The Comparative Efficacy of Non-ergot Dopamine Agonist and Potential Risk Factors for Motor Complications and Side Effects From NEDA Use in Early Parkinson's Disease: Evidence From Clinical Trials.

Background/Objectives: Non-ergot dopamine agonist (NEDA) are recommended as the first-line treatment for patients with early Parkinson's disease (PD) because of their efficacy in treating PD motor symptoms. However, systematic evaluations of the risk of motor complications induced by NEDA and risk factors potentially associated with motor complications are still lacking. Methods: Medline, Embase, the Cochrane Central Register of Controlled Trials, and Web of Science were searched for potentially eligible randomized controlled trials. The incidence of motor complications (dyskinesia, motor fluctuations), impulsive-compulsive behaviors and adverse events and clinical disability rating scale (UPDRS) scores were evaluated using standard meta-analytic methods. Metaregression was conducted on the incidence of motor complications (dyskinesia) with treatment duration and NEDA dose as covariates. Results: Patients treated with NEDA had significantly lower UPDRS total scores, motor scores and activity of daily living (ADL) scores than those receiving a placebo (weighted mean difference (WMD) -4.81, 95% CI -6.57 to -3.05; WMD -4.901, 95% CI -7.03 to -2.77; WMD -1.52, 95% CI -2.19 to -0.84, respectively). Patients in the NEDA and NEDA+open Levodopa (LD) groups had lower odds for dyskinesia than patients in the LD group (OR = 0.21, 95% CI: 0.15-0.29; OR = 0.31, 95% CI 0.24-0.42, respectively). Metaregressions indicated that the mean LD dose of the NEDA group increased, and the odds of developing dyskinesia increased (p = 0.012). However, the odds of developing dyskinesia in the NEDA group were not related to treatment duration (p = 0.308). PD patients treated with NEDA or NEDA+open LD had a lower risk of wearing-off implications than those treated with LD (all p < 0.05). No significant difference was found between the NEDA and placebo groups in impulsive-compulsive behavior development (p > 0.05). Patients in the NEDA group were more likely to suffer somnolence, edema, constipation, dizziness, hallucinations, nausea and vomiting than those in the placebo or LD group. Conclusion: NEDA therapy reduces motor symptoms and improves ADLs in early PD. The odds of developing motor complications were lower with NEDA than with LD, and dyskinesia increased with increasing LD equivalent dose and was not influenced by NEDA treatment duration. Therefore, long-term treatment with an appropriate dosage of NEDA might be more suitable than LD for early PD patients. Registration: PROSPERO CRD42021287172.

Effects of Aerobic Exercise and Mind-Body Exercise in Parkinson's Disease: A Mixed-Treatment Comparison Analysis.

Background/Objectives: Aerobic exercise and mind-body exercise, are vital for improving motor and non-motor functional performance of Parkinson's disease (PD). However, evidence-based recommendations on which type of exercise is most suitable for each individual are still lacking. Therefore, we conduct a network meta-analysis to assess the relative efficacy of aerobic and mind-body exercise on motor function and non-motor symptoms in Parkinson's disease and to determine which of these therapies are the most suitable. Design: A network meta-analysis and dose-response analysis. Setting and Participants: Medline, Embase (all via Ovid), and the Cochrane Central Register of Controlled Trials were comprehensively searched for related trials through April 2021. Measurements: Study quality was evaluated using the Cochrane Risk of Bias Tool. The effect sizes of continuous outcomes were calculated using mean differences (MDs) or standardized mean differences (SMDs). A network meta-analysis with a frequentist approach was conducted to estimate the efficacy and probability rankings of the therapies. The dose-response relationship was determined based on metaregression and SUCRA. Results: Fifty-two trials with 1971 patients evaluating six different therapies were identified. For the UPDRS-motor score and TUG score, yoga all ranked highest (SUCRA = 92.8%, 92.6%, respectively). The SUCRA indicated that walking may best improve the BBS score (SUCRA = 90.2%). Depression, cognitive and activities of daily living scores were significantly improved by yoga (SUCRA: 86.3, 95.1, and 79.5%, respectively). In the dose-response analysis, 60-min sessions, two times a week might be the most suitable dose of yoga for reducing the UPDRS-motor score of PD patients. Conclusion: Yoga and walking are important options for increasing functional mobility and balance function, and yoga might be particularly effective for decreasing depressive symptoms and cognitive impairment and improving activities of daily living in PD. The potential optimal dose of yoga for enhancing motor ability in PD patients is 60-min sessions, two times a week. Registration: PROSPERO CRD42021224823.

Integrated Bioinformatics Analysis of Potential mRNA and miRNA Regulatory Networks in Mice With Ischemic Stroke Treated by Electroacupuncture.

Background: The complicated molecular mechanisms underlying the therapeutic effect of electroacupuncture (EA) on ischemic stroke are still unclear. Recently, more evidence has revealed the essential role of the microRNA (miRNA)-mRNA networks in ischemic stroke. However, a systematic analysis of novel key genes, miRNAs, and miRNA-mRNA networks regulated by EA in ischemic stroke is still absent. Methods: We established a middle cerebral artery occlusion (MCAO) mouse model and performed EA therapy on ischemic stroke mice. Behavior tests and measurement of infarction area were applied to measure the effect of EA treatment. Then, we performed RNA sequencing to analyze differentially expressed genes (DEGs) and functional enrichment between the EA and control groups. In addition, a protein-protein interaction (PPI) network was built, and hub genes were screened by Cytoscape. Upstream miRNAs were predicted by miRTarBase. Then hub genes and predicted miRNAs were verified as key biomarkers by RT-qPCR. Finally, miRNA-mRNA networks were constructed to explore the potential mechanisms of EA in ischemic stroke. Results: Our analysis revealed that EA treatment could significantly alleviate neurological deficits in the affected limbs and reduce infarct area of the MCAO model mice. A total of 174 significant DEGs, including 53 upregulated genes and 121 downregulated genes, were identified between the EA and control groups. Functional enrichment analysis showed that these DEGs were associated with the FOXO signaling pathway, NF-kappa B signaling pathway, T-cell receptor signaling pathway, and other vital pathways. The top 10 genes with the highest degree scores were identified as hub genes based on the degree method, but only seven genes were verified as key genes according to RT-qPCR. Twelve upstream miRNAs were predicted to target the seven key genes. However, only four miRNAs were significantly upregulated and indicated favorable effects of EA treatment. Finally, comprehensive analysis of the results identified the miR-425-5p-Cdk1, mmu-miR-1186b-Prc1, mmu-miR-434-3p-Prc1, and mmu-miR-453-Prc1 miRNA-mRNA networks as key networks that are regulated by EA and linked to ischemic stroke. These networks might mainly take place in neuronal cells regulated by EA in ischemic stroke. Conclusion: In summary, our study identified key DEGs, miRNAs, and miRNA-mRNA regulatory networks that may help to facilitate the understanding of the molecular mechanism underlying the effect of EA treatment on ischemic stroke.