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.

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.

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.

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.

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.

Transient, Implantable, Ultrathin Biofuel Cells Enabled by Laser-Induced Graphene and Gold Nanoparticles Composite.

Transient power sources with excellent biocompatibility and bioresorablility have attracted significant attention. Here, we report high-performance, transient glucose enzymatic biofuel cells (TEBFCs) based on the laser-induced graphene (LIG)/gold nanoparticles (Au NPs) composite electrodes. Such LIG electrodes can be easily fabricated from polyimide (PI) with an infrared CO2 laser and exhibit a low impedance (16 Ω). The resulted TEBFC yields a high open circuit potential (OCP) of 0.77 V and a maximum power density of 483.1 µW/cm2. The TEBFC not only exhibits a quick response time that enables reaching the maximum OCP within 1 min but also owns a long lifetime over 28 days in vitro. The excellent biocompatibility and transient performance from in vitro and in vivo tests allow long-term implantation of TEBFCs in rats for energy harvesting. The TEBFCs with advanced processing methods provide a promising power solution for transient electronics.

Electronic skin as wireless human-machine interfaces for robotic VR.

The coronavirus pandemic has highlighted the importance of developing intelligent robotics to prevent infectious disease spread. Human-machine interfaces (HMIs) give a chance of interactions between users and robotics, which play a significant role in teleoperating robotics. Conventional HMIs are based on bulky, rigid, and expensive machines, which mainly focus on robots/machines control, but lack of adequate feedbacks to users, which limit their applications in conducting complicated tasks. Therefore, developing closed-loop HMIs with both accurate sensing and feedback functions is extremely important. Here, we present a closed-loop HMI system based on skin-integrated electronics, whose electronics compliantly interface with the whole body for wireless motion capturing and haptic feedback via Bluetooth, Wireless Fidelity (Wi-Fi), and Internet. The integration of visual and haptic VR via skin-integrated electronics together into a closed-loop HMI for robotic VR demonstrates great potentials in noncontact collection of bio samples, nursing infectious disease patients and many others.

Miniaturization of mechanical actuators in skin-integrated electronics for haptic interfaces.

Skin-integrated electronics, also known as electronic skin (e-skin), are rapidly developing and are gradually being adopted in biomedical fields as well as in our daily lives. E-skin capable of providing sensitive and high-resolution tactile sensations and haptic feedback to the human body would open a new e-skin paradigm for closed-loop human-machine interfaces. Here, we report a class of materials and mechanical designs for the miniaturization of mechanical actuators and strategies for their integration into thin, soft e-skin for haptic interfaces. The mechanical actuators exhibit small dimensions of 5 mm diameter and 1.45 mm thickness and work in an electromagnetically driven vibrotactile mode with resonance frequency overlapping the most sensitive frequency of human skin. Nine mini actuators can be integrated simultaneously in a small area of 2 cm × 2 cm to form a 3 × 3 haptic feedback array, which is small and compact enough to mount on a thumb tip. Furthermore, the thin, soft haptic interface exhibits good mechanical properties that work properly during stretching, bending, and twisting and therefore can conformally fit onto various parts of the human body to afford programmable tactile enhancement and Braille recognition with an accuracy rate over 85%.

Low dark current and high-performance hybrid perovskite photodetectors with a PBDB-T:IHIC ultrathin passivation layer.

In this Letter, the reduction of undesired high dark current caused by defect states in solution-processed perovskite for photodetectors is realized with the introduction of an ultrathin buffer layer of PBDB-T:IHIC bulk heterojunction (BHJ). By controlling the concentration of BHJ precisely during a solution process, a low dark current density (Jd) of 1.01×10-4mA/cm2 and a high specific detectivity (D∗) of 2.61×1012Jones were achieved. It was found that low Jd is attributed to the passivation effect of BHJ on defect states, where BHJ acts as a Lewis base and interacts with unbonded Pb2+ in perovskite. This Letter demonstrates that the application of ultrathin organic BHJ has significant potential for the manufacturing of high-performance optoelectronic devices.