Programmable Framework Nucleic Acid-Modified Nanomagnetic Beads for Efficient Isolation of Exosomes and Exosomal Proteomics Analysis.

Exosomes are increasingly being regarded as emerging and promising biomarkers for cancer screening, diagnosis, and therapy. The downstream molecular analyses of exosomes were greatly affected by the isolation efficiency from biosamples. Among the current exosome isolation strategies, affinity nanomaterials performed comparably better with selectivity and specificity. However, these techniques did not take the structure and size of exosomes into account, which may lead to a loss of isolation efficiency. In this article, a framework nucleic acid was employed to prepare a well-designed nanosized bead Fe3O4@pGMA@DNA TET@Ti4+ for enrichment of exosomes. The abundant phosphate groups in the framework nucleic acid provide binding sites to immobilize Ti4+, and its rigid three-dimensional skeleton makes them act as roadblocks to barricade exosomes and provide affinity interactions on a three-dimensional scale, resulting in the improvement of isolation efficiency. The model exosomes can be effectively isolated with 92% recovery in 5 min. From 100 µL of HeLa cell culture supernatant, 34 proteins out of the top 100 commonly identified exosomal proteins were identified from the isolated exosomes by the novel beads, which is obviously more than that by TiO2 (19 proteins), indicating higher isolation efficiency and exosome purity by Fe3O4@pGMA@DNA TET@Ti4+ beads. The nanobeads were finally applied for comparing exosomal proteomics analysis from real clinical serum samples. Twenty-five upregulated and 10 downregulated proteins were identified in the lung cancer patients group compared to the health donors group, indicating that the novel nanobeads have great potential in isolation of exosomes for exosomal proteomics analysis in cancer screening and diagnosis.

Biometric-Tuned E-Skin Sensor with Real Fingerprints Provides Insights on Tactile Perception: Rosa Parks Had Better Surface Vibrational Sensation than Richard Nixon.

The dense mechanoreceptors in human fingertips enable texture discrimination. Recent advances in flexible electronics have created tactile sensors that effectively replicate slowly adapting (SA) and rapidly adapting (RA) mechanoreceptors. However, the influence of dermatoglyphic structures on tactile signal transmission, such as the effect of fingerprint ridge filtering on friction-induced vibration frequencies, remains unexplored. A novel multi-layer flexible sensor with an artificially synthesized skin surface capable of replicating arbitrary fingerprints is developed. This sensor simultaneously detects pressure (SA response) and vibration (RA response), enabling texture recognition. Fingerprint ridge patterns from notable historical figures - Rosa Parks, Richard Nixon, Martin Luther King Jr., and Ronald Reagan - are fabricated on the sensor surface. Vibration frequency responses to assorted fabric textures are measured and compared between fingerprint replicas. Results demonstrate that fingerprint topography substantially impacts skin-surface vibrational transmission. Specifically, Parks' fingerprint structure conveyed higher frequencies more clearly than those of Nixon, King, or Reagan. This work suggests individual fingerprint ridge morphological variation influences tactile perception and can confer adaptive advantages for fine texture discrimination. The flexible bioinspired sensor provides new insights into human vibrotactile processing by modeling fingerprint-filtered mechanical signals at the finger-object interface.

Multi-functional adhesive hydrogel as bio-interface for wireless transient pacemaker.

Traditional temporary cardiac pacemakers (TCPs), which employ transcutaneous leads and external wired power systems are battery-dependent and generally non-absorbable with rigidity, thereby necessitating surgical retrieval after therapy and resulting in potentially severe complications. Wireless and bioresorbable transient pacemakers have, hence, emerged recently, though hitting a bottleneck of unfavorable tissue-device bonding interface subject to mismatched mechanical modulus, low adhesive strength, inferior electrical performances, and infection risks. Here, to address such crux, we develop a multifunctional interface hydrogel (MIH) with superior electrical performance to facilitate efficient electrical exchange, comparable mechanical strength to natural heart tissue, robust adhesion property to enable stable device-tissue fixation (tensile strength: ∼30 kPa, shear strength of ∼30 kPa, and peel-off strength: ∼85 kPa), and good bactericidal effect to suppress bacterial growth. Through delicate integration of this versatile MIH with a leadless, battery-free, wireless, and transient pacemaker, the entire system exhibits stable and conformal adhesion to the beating heart while enabling precise and constant electrical stimulation to modulate the cardiac rhythm. It is envisioned that this versatile MIH and the proposed integration framework will have immense potential in overcoming key limitations of traditional TCPs, and may inspire the design of novel bioelectronic-tissue interfaces for next-generation implantable medical devices.

Triiodothyronine induces a proinflammatory monocyte/macrophage profile and impedes cardiac regeneration.

Neonatal mouse hearts can regenerate post-injury, unlike adult hearts that form fibrotic scars. The mechanism of thyroid hormone signaling in cardiac regeneration warrants further study. We found that triiodothyronine impairs cardiomyocyte proliferation and heart regeneration in neonatal mice after apical resection. Single-cell RNA-Sequencing on cardiac CD45-positive leukocytes revealed a pro-inflammatory phenotype in monocytes/macrophages after triiodothyronine treatment. Furthermore, we observed that cardiomyocyte proliferation was inhibited by medium from triiodothyronine-treated macrophages, while triiodothyronine itself had no direct effect on the cardiomyocytes in vitro. Our study unveils a novel role of triiodothyronine in mediating the inflammatory response that hinders heart regeneration.

Flexible Broadband Organic Photodetectors with Ternary Planar-Mixed Heterojunction Semiconductors and Solution-Processed Polymeric Electrode.

Flexible organic photodetectors (OPDs) hold immense promise in health monitoring sensors, flexible imaging sensors, and portable optical communication. Nevertheless, the actualization of high-performance flexible electronics has been hindered by rigid electrodes such as metals or metal oxides. In this work, we constructed a flexible broadband organic photodetector using a solution-processed polymeric electrode, which exhibits flexibility surpassing that of conventional indium tin oxide (ITO) electrodes. Additionally, we employed a planar-mixed heterojunction (PMHJ) through a sequential deposition method and introduced PC71BM as the third constituent into the PM6/Y6 binary active layer, resulting in enhanced photodetection performance and a broadend spectral range. The optimized OPDs demonstrated remarkable detectivity (D*) exceeding 1012 Jones in brodband from 300 to 900 nm, with a champion D* of 6.31 × 1012 Jones at 790 nm. Furthermore, after undergoing 500 cycles of bending, the D* retained approximately 78% of its original performance, highlighting the outstanding mechanical stability. This work presents a promising pathway toward the development of flexible broadband OPDs using a straightforward method, offering enhanced compatibility in diverse application scenarios and propelling the frontier of flexible optoelectronic research.

Battery-free, wireless, and electricity-driven soft swimmer for water quality and virus monitoring.

Miniaturized mobile electronic system is an effective candidate for in situ exploration of confined spaces. However, realizing such system still faces challenges in powering issue, untethered mobility, wireless data acquisition, sensing versatility, and integration in small scales. Here, we report a battery-free, wireless, and miniaturized soft electromagnetic swimmer (SES) electronic system that achieves multiple monitoring capability in confined water environments. Through radio frequency powering, the battery-free SES system demonstrates untethered motions in confined spaces with considerable moving speed under resonance. This system adopts soft electronic technologies to integrate thin multifunctional bio/chemical sensors and wireless data acquisition module, and performs real-time water quality and virus contamination detection with demonstrated promising limits of detection and high sensitivity. All sensing data are transmitted synchronously and displayed on a smartphone graphical user interface via near-field communication. Overall, this wireless smart system demonstrates broad potential for confined space exploration, ranging from pathogen detection to pollution investigation.

Versican Promotes Cardiomyocyte Proliferation and Cardiac Repair.

BACKGROUND: The adult mammalian heart is incapable of regeneration, whereas a transient regenerative capacity is maintained in the neonatal heart, primarily through the proliferation of preexisting cardiomyocytes. Neonatal heart regeneration after myocardial injury is accompanied by an expansion of cardiac fibroblasts and compositional changes in the extracellular matrix. Whether and how these changes influence cardiomyocyte proliferation and heart regeneration remains to be investigated. METHODS: We used apical resection and myocardial infarction surgical models in neonatal and adult mice to investigate extracellular matrix components involved in heart regeneration after injury. Single-cell RNA sequencing and liquid chromatography-mass spectrometry analyses were used for versican identification. Cardiac fibroblast-specific Vcan deletion was achieved using the mouse strains Col1a2-2A-CreER and Vcanfl/fl. Molecular signaling pathways related to the effects of versican were assessed through Western blot, immunostaining, and quantitative reverse transcription polymerase chain reaction. Cardiac fibrosis and heart function were evaluated by Masson trichrome staining and echocardiography, respectively. RESULTS: Versican, a cardiac fibroblast-derived extracellular matrix component, was upregulated after neonatal myocardial injury and promoted cardiomyocyte proliferation. Conditional knockout of Vcan in cardiac fibroblasts decreased cardiomyocyte proliferation and impaired neonatal heart regeneration. In adult mice, intramyocardial injection of versican after myocardial infarction enhanced cardiomyocyte proliferation, reduced fibrosis, and improved cardiac function. Furthermore, versican augmented the proliferation of human induced pluripotent stem cell-derived cardiomyocytes. Mechanistically, versican activated integrin ß1 and downstream signaling molecules, including ERK1/2 and Akt, thereby promoting cardiomyocyte proliferation and cardiac repair. CONCLUSIONS: Our study identifies versican as a cardiac fibroblast-derived pro-proliferative proteoglycan and clarifies the role of versican in promoting adult cardiac repair. These findings highlight its potential as a therapeutic factor for ischemic heart diseases.

Wireless, battery-free, multifunctional integrated bioelectronics for respiratory pathogens monitoring and severity evaluation.

The rapid diagnosis of respiratory virus infection through breath and blow remains challenging. Here we develop a wireless, battery-free, multifunctional pathogenic infection diagnosis system (PIDS) for diagnosing SARS-CoV-2 infection and symptom severity by blow and breath within 110 s and 350 s, respectively. The accuracies reach to 100% and 92% for evaluating the infection and symptom severity of 42 participants, respectively. PIDS realizes simultaneous gaseous sample collection, biomarker identification, abnormal physical signs recording and machine learning analysis. We transform PIDS into other miniaturized wearable or portable electronic platforms that may widen the diagnostic modes at home, outdoors and public places. Collectively, we demonstrate a general-purpose technology for rapidly diagnosing respiratory pathogenic infection by breath and blow, alleviating the technical bottleneck of saliva and nasopharyngeal secretions. PIDS may serve as a complementary diagnostic tool for other point-of-care techniques and guide the symptomatic treatment of viral infections.

Muscle-inspired soft robots based on bilateral dielectric elastomer actuators.

Muscle groups perform their functions in the human body via bilateral muscle actuation, which brings bionic inspiration to artificial robot design. Building soft robotic systems with artificial muscles and multiple control dimensions could be an effective means to develop highly controllable soft robots. Here, we report a bilateral actuator with a bilateral deformation function similar to that of a muscle group that can be used for soft robots. To construct this bilateral actuator, a low-cost VHB 4910 dielectric elastomer was selected as the artificial muscle, and polymer films manufactured with specific shapes served as the actuator frame. By end-to-end connecting these bilateral actuators, a gear-shaped 3D soft robot with diverse motion capabilities could be developed, benefiting from adjustable actuation combinations. Lying on the ground with all feet on the ground, a crawling soft robot with dexterous movement along multiple directions was realized. Moreover, the directional steering was instantaneous and efficient. With two feet standing on the ground, it also acted as a rolling soft robot that can achieve bidirectional rolling motion and climbing motion on a 2° slope. Finally, inspired by the orbicularis oris muscle in the mouth, a mouthlike soft robot that could bite and grab objects 5.3 times of its body weight was demonstrated. The bidirectional function of a single actuator and the various combination modes among multiple actuators together allow the soft robots to exhibit diverse functionalities and flexibility, which provides a very valuable reference for the design of highly controllable soft robots.

Thin, soft, wearable system for continuous wireless monitoring of artery blood pressure.

Continuous monitoring of arterial blood pressure (BP) outside of a clinical setting is crucial for preventing and diagnosing hypertension related diseases. However, current continuous BP monitoring instruments suffer from either bulky systems or poor user-device interfacial performance, hampering their applications in continuous BP monitoring. Here, we report a thin, soft, miniaturized system (TSMS) that combines a conformal piezoelectric sensor array, an active pressure adaptation unit, a signal processing module, and an advanced machine learning method, to allow real wearable, continuous wireless monitoring of ambulatory artery BP. By optimizing the materials selection, control/sampling strategy, and system integration, the TSMS exhibits improved interfacial performance while maintaining Grade A level measurement accuracy. Initial trials on 87 volunteers and clinical tracking of two hypertension individuals prove the capability of the TSMS as a reliable BP measurement product, and its feasibility and practical usability in precise BP control and personalized diagnosis schemes development.

Downregulation of ß-Catenin Contributes to type II Alveolar Epithelial Stem Cell Resistance to Epithelial-Mesenchymal Transition by Lowing Lin28/let-7 Ratios in Fibrosis-Resistant Mice after Thoracic Irradiation.

Transdifferentiation of type II alveolar cells (AECII) is a major cause for radiation-induced lung fibrosis (RILF). Cell differentiation phenotype is determined by Lin28 (undifferentiated marker) and let-7 (differentiated marker) in a see-saw-pattern. Therefore, differentiation phenotype can be extrapolated based on Lin28/let-7 ratio. Lin28 is activated by ß-catenin. To the best of our knowledge this study was the first to use the single primary AECII freshly isolated from irradiated lungs of fibrosis-resistant C3H/HeNHsd strain to further confirm RILF mechanism by comparing its differences in AECII phenotype status/state and cell differentiation regulators to fibrosis-prone C57BL/6j mice. Results showed that radiation pneumonitis and fibrotic lesions were seen in C3H/HeNHsd and C57BL/6j mouse strains, respectively. mRNAs of E-cadherin, EpCAM, HOPX and proSP-C (epithelial phenotype biomarkers) were significantly downregulated in single primary AECII isolated from irradiated lungs of both strains. Unlike C57BL/6j, α-SMA and Vimentin (mesenchymal phenotype biomarkers) were not upregulated in single AECII from irradiated C3H/HeNHsd. Profibrotic molecules, TGF-ß1 mRNA was upregulated and ß-catenin was significantly downregulated in AECII after irradiation (both P < 0.01). In contrast, transcriptions for GSK-3ß, TGF-ß1 and ß-catenin were enhanced in isolated single AECII from irradiated C57BL/6j (P < 0.01-P < 0.001). The Lin28/let-7 ratios were much lower in single primary AECII from C3H/HeNHsd after irradiation vs. C57BL/6j. In conclusion, AECII from irradiated C3H/HeNHsd did not undergo epithelial-mesenchymal transition (EMT) and lower ratios of Lin28/let-7 contributed to AECII relatively higher differentiated status, leading to increased susceptibility to radiation stress and a failure in transdifferentiation in the absence of ß-catenin. Reducing ß-catenin expression and the ratios of Lin28/let-7 may be a promising strategy to prevent radiation fibrosis.

Wafer-patterned, permeable, and stretchable liquid metal microelectrodes for implantable bioelectronics with chronic biocompatibility.

Implantable bioelectronics provide unprecedented opportunities for real-time and continuous monitoring of physiological signals of living bodies. Most bioelectronics adopt thin-film substrates such as polyimide and polydimethylsiloxane that exhibit high levels of flexibility and stretchability. However, the low permeability and relatively high modulus of these thin films hamper the long-term biocompatibility. In contrast, devices fabricated on porous substrates show the advantages of high permeability but suffer from low patterning density. Here, we report a wafer-scale patternable strategy for the high-resolution fabrication of supersoft, stretchable, and permeable liquid metal microelectrodes (µLMEs). We demonstrate 2-µm patterning capability, or an ultrahigh density of ~75,500 electrodes/cm2, of µLME arrays on a wafer-size (diameter, 100 mm) elastic fiber mat by photolithography. We implant the µLME array as a neural interface for high spatiotemporal mapping and intervention of electrocorticography signals of living rats. The implanted µLMEs have chronic biocompatibility over a period of eight months.

Label-free serum proteomics for the identification of the putative biomarkers of postoperative pain in patients with gastric cancer.

Background: Individualized pain therapy conforms to the concept of precision medicine and contributes to adequate pain management after surgery. Preoperative biomarkers associated with postoperative pain may instruct anesthesiologists to improve personalized suitable analgesia. Therefore, it is essential to explore the association between preoperative proteins and postoperative acute pain using the proteomics platform. Methods: In this study, the 24 hours postoperative sufentanil consumption of 80 male patients with gastric cancer was ranked. Patients with sufentanil consumption in the lowest 12% were included in the sufentanil low consumption group, while patients with sufentanil consumption in the highest 12% were included in the sufentanil high consumption group. The secretion of serum proteins in both groups was analyzed using label-free proteomics technology. The results were validated by ELISA. Results: Proteomics identified 29 proteins that were significantly differentially expressed between groups. ELISA confirmed that secretion of TNC and IGFBP2 was down-regulated in the SLC group. The differential proteins were mainly extracellular and were involved in several terms, including calcium ion binding, laminin-1 binding, and so on. Pathway analysis showed that they were mainly enriched in focal adhesion and extracellular matrix-receptor interaction. The protein-protein interaction network analysis showed 22 proteins that interacted with other proteins. F13B had the strongest correlation with sufentanil consumption and its AUC value was 0.859. Conclusions: Several differential proteins are associated with postoperative acute pain and are involved in ECM-related processes, inflammation, and blood coagulation cascades. F13B may be a novel marker for postoperative acute pain. Our results may benefit postoperative pain management.

S-ketamine promotes postoperative recovery of gastrointestinal function and reduces postoperative pain in gynecological abdominal surgery patients: a randomized controlled trial.

BACKGROUND: This prospective randomized controlled study was designed to evaluate the effect of S-ketamine with sufentanil given intraoperatively and postoperatively on recovery of gastrointestinal (GI) function and postoperative pain in gynecological patients undergoing open abdomen surgery. METHODS: One hundred gynecological patients undergoing open abdomen surgery were randomized into an S-ketamine group (group S) or placebo group (0.9% saline; group C). Anesthesia was maintained with S-ketamine, sevoflurane, and remifentanil-propofol target-controlled infusion in group S and with sevoflurane and remifentanil-propofol target-controlled infusion in group C. All patients were connected to patient-controlled intravenous analgesia (PCIA) pump at the end of the surgery with sufentanil, ketorolac tromethamine, and tropisetron in group C and additional S-ketamine in group S. The primary outcome was the time of first postoperative flatus, and the secondary outcome was postoperative pain score of patients. Postoperative sufentanil consumption within the first postoperative 24 h and adverse events such as nausea and vomiting were recorded. RESULTS: The time of first postoperative flatus in group S was significantly shorter (mean ± SD, 50.3 ± 13.5 h) than that in group C (mean ± SD, 56.5 ± 14.3 h, p = 0.042). The patient's visual analog scale (VAS) pain score 24 h after surgery at rest was significantly lower in group S than in group C (p = 0.032). There were no differences in sufentanil consumption within the first postoperative 24 h, postoperative complications related to PCIA between the two groups. CONCLUSIONS: S-ketamine accelerated postoperative GI recovery and reduced 24 h postoperative pain in patients undergoing open gynecological surgery. TRIAL REGISTRATION: ChiCTR2200055180. Registered on 02/01/2022. It is a secondary analysis of the same trial.

Ultrathin, Soft, Bioresorbable Organic Electrochemical Transistors for Transient Spatiotemporal Mapping of Brain Activity.

A critical challenge lies in the development of the next-generation neural interface, in mechanically tissue-compatible fashion, that offer accurate, transient recording electrophysiological (EP) information and autonomous degradation after stable operation. Here, an ultrathin, lightweight, soft and multichannel neural interface is presented based on organic-electrochemical-transistor-(OECT)-based network, with capabilities of continuous high-fidelity mapping of neural signals and biosafety active degrading after performing functions. Such platform yields a high spatiotemporal resolution of 1.42 ms and 20 µm, with signal-to-noise ratio up to ≈37 dB. The implantable OECT arrays can well establish stable functional neural interfaces, designed as fully biodegradable electronic platforms in vivo. Demonstrated applications of such OECT implants include real-time monitoring of electrical activities from the cortical surface of rats under various conditions (e.g., narcosis, epileptic seizure, and electric stimuli) and electrocorticography mapping from 100 channels. This technology offers general applicability in neural interfaces, with great potential utility in treatment/diagnosis of neurological disorders.

Thin, soft, 3D printing enabled crosstalk minimized triboelectric nanogenerator arrays for tactile sensing.

With the requirements of self-powering sensors in flexible electronics, wearable triboelectric nanogenerators (TENGs) have attracted great attention due to their advantages of excellent electrical outputs and low-cost processing routes. The crosstalk effect between adjacent sensing units in TENGs significantly limits the pixel density of sensor arrays. Here, we present a skin-integrated, flexible TENG sensor array with 100 sensing units in an overall size of 7.5 cm × 7.5 cm that can be processed in a simple, low-cost, and scalable way enabled by 3D printing. All the sensing units show good sensitivity of 0.11 V/kPa with a wide range of pressure detection from 10 to 65 kPa, which allows to accurately distinguish various tactile formats from gentle touching (as low as 2 kPa) to hard pressuring. The 3D printing patterned substrate allows to cast triboelectric layers of polydimethylsiloxane in an independent sensing manner for each unit, which greatly suppresses the cross talk arising from adjacent sensing units, where the maximum crosstalk output is only 10.8%. The excellent uniformity and reproducibility of the sensor array offer precise pressure mapping for complicated pattern loadings, which demonstrates its potential in tactile sensing and human-machine interfaces.

Contractility detection of isolated mouse papillary muscle using myotronic Myostation-Intact device.

BACKGROUND: To understand the relationship between myocardial contractility and external stimuli, detecting ex vivo myocardial contractility is necessary. METHODS: We elaborated a method for contractility detection of isolated C57 mouse papillary muscle using Myostation-Intact system under different frequencies, voltages, and calcium concentrations. RESULTS: The results indicated that the basal contractility of the papillary muscle was 0.27 ± 0.03 mN at 10 V, 500-ms pulse duration, and 1 Hz. From 0.1 to 1.0 Hz, contractility decreased with an increase in frequency (0.45 ± 0.11-0.10 ± 0.02 mN). The voltage-initiated muscle contractility varied from 3 to 6 V, and the contractility gradually increased as the voltage increased from 6 to 10 V (0.14 ± 0.02-0.28 ± 0.03 mN). Moreover, the muscle contractility increased when the calcium concentration was increased from 1.5 to 3 mM (0.45 ± 0.17-1.11 ± 0.05 mN); however, the contractility stopped increasing even when the concentration was increased to 7.5 mM (1.02 ± 0.23 mN). CONCLUSIONS: Our method guaranteed the survivability of papillary muscle ex vivo and provided instructions for Myostation-Intact users for isolated muscle contractility investigations.

High-detectivity organic photodetectors with double bulk heterojunction enabled by water transfer printing.

Suppressing the dark current is an effective strategy to boost the detection capability of organic photodetectors (OPDs). In this Letter, the water transfer printing method is demonstrated in double bulk heterojunction (BHJ) OPDs, which is solvent-independent rather than the traditional sequential spin-coating method, enabling the elimination of the negative effects of solvents on the underlying film and the suppressing of the dark current. As a result, a photo detectivity up to 1012 Jones was obtained in the wide spectral range of 400-900 nm with a small working area of 3 mm2.

Implantable Electronic Medicine Enabled by Bioresorbable Microneedles for Wireless Electrotherapy and Drug Delivery.

A combined treatment using medication and electrostimulation increases its effectiveness in comparison with one treatment alone. However, the organic integration of two strategies in one miniaturized system for practical usage has seldom been reported. This article reports an implantable electronic medicine based on bioresorbable microneedle devices that is activated wirelessly for electrostimulation and sustainable delivery of anti-inflammatory drugs. The electronic medicine is composed of a radio frequency wireless power transmission system and a drug-loaded microneedle structure, all fabricated with bioresorbable materials. In a rat skeletal muscle injury model, periodic electrostimulation regulates cell behaviors and tissue regeneration while the anti-inflammatory drugs prevent inflammation, which ultimately enhance the skeletal muscle regeneration. Finally, the electronic medicine is fully bioresorbable, excluding the second surgery for device removal.

Origami-inspired folding assembly of dielectric elastomers for programmable soft robots.

Origami has become an optimal methodological choice for creating complex three-dimensional (3D) structures and soft robots. The simple and low-cost origami-inspired folding assembly provides a new method for developing 3D soft robots, which is ideal for future intelligent robotic systems. Here, we present a series of materials, structural designs, and fabrication methods for developing independent, electrically controlled origami 3D soft robots for walking and soft manipulators. The 3D soft robots are based on soft actuators, which are multilayer structures with a dielectric elastomer (DE) film as the deformation layer and a laser-cut PET film as the supporting flexible frame. The triangular and rectangular design of the soft actuators allows them to be easily assembled into crawling soft robots and pyramidal- and square-shaped 3D structures. The crawling robot exhibits very stable crawling behaviors and can carry loads while walking. Inspired by origami folding, the pyramidal and square-shaped 3D soft robots exhibit programmable out-of-plane deformations and easy switching between two-dimensional (2D) and 3D structures. The electrically controllable origami deformation allows the 3D soft robots to be used as soft manipulators for grasping and precisely locking 3D objects. This work proves that origami-inspired fold-based assembly of DE actuators is a good reference for the development of soft actuators and future intelligent multifunctional soft robots.