Design, synthesis and mechanism study of coumarin-sulfonamide derivatives as carbonic anhydrase IX inhibitors with anticancer activity.

In this study, twenty-nine coumarin-3-sulfonamide derivatives, twenty-seven of which are original were designed and synthesized. Cytotoxicity assay indicated that most of these derivatives exhibited moderated to good potency against A549 cells. Among them, compound 8q showed potent inhibition against the four tested cancer cell lines, especially A549 cells with IC50 value of 6.01 ± 0.81 µM, and much lower cytotoxicity on the normal cells was observed compared to the reference compounds. Bioinformatics analysis revealed human carbonic anhydrase IX (CAIX) was highly expressed in lung adenocarcinoma (LUAD) and associated with poor prognosis. The inhibitory activity of compound 8q against CAIX was assessed by using molecular docking and molecular dynamics simulations, which revealed prominent interactions of both compound 8q and CAIX at the active site and their high affinity. The results of ELISA assays verified that compound 8q possessed strong inhibitory activity against CAIX and high subtype selectivity, and could also down-regulate the expression of CAIX in A549 cells. Furthermore, the significant inhibitory effects of compound 8q on the migration and invasion of A549 cells were also found. After treatment with compound 8q, intracellular reactive oxygen species (ROS) levels increased and mitochondrial membrane potential (MMP) decreased. Mechanistic investigation using western blotting revealed compound 8q exerted the anti-migrative and anti-invasive effects probably through mitochondria-mediated PI3K/AKT pathway by targeting CAIX. In summary, coumarin-3-sulfonamide derivatives were developed as potential and effective CAIX inhibitors, which were worthy of further investigation.

Humidity-Induced Self-Oscillating and Self-Healing Hypercrosslinked Metal-Organic Polyhedra Membranes.

Designing autonomously oscillating materials is highly desirable for emerging smart material fields but challenging. Herein, a type of hypercrosslinked metal-organic polyhedra (HCMOPs) membranes formed by covalent crosslinking of boronic acid-modified Zr-based MOPs with polyvinyl alcohol (PVA) are rationally designed. In these membranes, MOPs serve as high-connectivity nodes and provide dynamic borate bonds with PVA in hypercrosslinked networks, which can be broken/formed reversibly upon the stimulus of water vapor. The humidity response characteristic of HCMOPs promotes their self-oscillating and self-healing properties. HCMOP membranes can realize a self-oscillating property above the water surface even after loading a cargo that is 1.5 times the weight of the membrane due to the fast adsorption and desorption kinetics. Finally, the HCMOP actuator can realize energy conversion from mechanical energy into electricity when coupled with a piezoelectric membrane. This work not only paves a new avenue to construct MOP-polymer hybrid materials but also expands the application scopes of MOPs for smart actuation devices.

Highly Elastic, Robust, and Efficient Hydrogel Solar Absorber against Harsh Environmental Impacts.

Solar distillation is a promising approach for addressing water scarcity, but relentless stress/strain perturbations induced by wind and waves would inevitably cause structural damage to solar absorbers. Despite notable advances in efficient solar absorbers, there have been no reports of compliant and robust solar absorbers withstanding practical mechanical impacts. Herein, an elastic and robust hydrogel absorber that exhibited a high level of evaporation performance was fabricated by introducing ion-coordinated MXene nanosheets as photothermal conversion units and mechanically enhanced fillers. The ion-coordinated MXene nanosheets acting as strong cross-linking points provided excellent elasticity and robustness to the hydrogel absorber. As a result, the evaporation rate of hydrogel absorber, with a high initial value of 2.61 kg m-2 h-1 under one sun irradiation, remained at 2.15 kg m-2 h-1 under a 100% tensile strain state and 2.40 kg m-2 h-1 after 10 000 stretching-releasing cycles. This continuous and stable water desalination approach provides a promising device for actual seawater distillation.

A Microphase-Separated Design toward an All-Round Ionic Hydrogel with Discriminable and Anti-Disturbance Multisensory Functions.

Stretchable ionic hydrogels with superior all-round properties that can detect multimodal sensations with excellent discriminability and robustness against external disturbances are highly required for artificial electronic skinapplications. However, some critical material parameters exhibit intrinsic tradeoffs with each other for most ionic hydrogels. Here, a microphase-separated hydrogel is demonstrated by combining three strategies: (1) using of a low crosslinker/monomer ratio to obtain highly entangled polymer chains as the first network; (2) the introduction of zwitterions into the first network; (3) the synthesis of an ultrasoft polyelectrolyte as the second network. This all-round elastic ionic hydrogel exhibits a low Young's modulus (< 60 kPa), large stretchability (> 900%), high resilience (> 95%), unique strain-stiffening behavior, excellent fatigue tolerance, high ionic conductivity (> 2.0 S m⁻1), and anti-freezing capability, which have not been achieved before. These properties allow the ionic hydrogel to operate as a stretchable multimodal sensor that can detect and decouple multiple stimuli (temperature, pressure, and proximity) with excellent discriminability, high sensitivity, and strong sensing-robustness against strains or temperature perturbations. The ionic hydrogel sensor exhibits great potential for intelligent electronic skin applications such as reliable health monitoring and accurate object identification.

Biomimetic Ultratough, Strong, and Ductile Artificial Polymer Fiber Based on Immovable and Slidable Cross-links.

It remains a challenge to artificially fabricate fibers with the macroscopic mechanical properties and characteristics of spider silk. Herein, a covalently cross-linked double-network strategy was proposed to disrupt the inverse relation of strength and toughness in the fabrication of ultratough and superstrong artificial polymer fibers. Our design utilized a strong fishnet-like structure based on immovable cellulose nanocrystal cross-links to mimic the function of the ß-sheet nanocrystallites and a slidable mechanically interlocked network based on polyrotaxane to imitate the dissipative stick-slip motion of the ß-strands in spider silk. The resultant fiber exhibited superior mechanical properties, including gigapascal tensile strength, a ductility of over 60%, and a toughness exceeding 420 MJ/m3. The fibers also showed robust biological functions similar to those of spider silks, demonstrating mechanical enhancement, energy absorption ability, and shape memory. A composite with our artificial fibers as reinforcing fibers exhibited remarkable tear and fatigue resistance.

Rapid Evaluation of Lung Adenocarcinoma Progression by Detecting Plasma Extracellular Vesicles with Lateral Flow Immunoassays.

Extracellular vesicles (EVs) have been widely used in liquid biopsy to diagnose and monitor cancers. However, since samples containing EVs are usually body fluids with complex components, the cumbersome separation steps for EVs during detection limit the clinical application and promotion of EV detection methods. In this study, a dyad lateral flow immunoassay (LFIA) strip for EV detection, containing CD9-CD81 and EpCAM-CD81, was developed to detect universal EVs and tumor-derived EVs, respectively. The dyad LFIA strip can directly detect trace plasma samples and effectively distinguish the cancerous sample from healthy plasma. The limit of detection for detecting universal EVs was 2.4 × 105 mL-1. The whole immunoassay can be performed in 15 min and only consumes 0.2 µL of plasma for one test. To improve the suitability of a dyad LFIA strip in complex scenarios, a smartphone-based photographic method was developed, which provided a consistency of 96.07% to a specialized fluorescence LFIA strip analyzer. In further clinical testing, EV-LFIA discriminated lung cancer patient groups (n = 25) from healthy controls (n = 22) with 100% sensitivity and 94.74% specificity at the best cutoff. The detection of EpCAM-CD81 tumor EVs (TEVs) in lung cancer plasma revealed the differences in TEVs in individuals, which reflected the different treatment effects. TEV-LFIA results were compared with CT scan findings (n = 30). The vast majority of patients with increased TEV-LFIA detection intensity had lung masses that enlarged or remained unchanged in size, which reported no response to treatment. In other words, patients who reported no response (n = 22) had a high TEV level compared with patients who reported a response to treatment (n = 8). Taken together, the developed dyad LFIA strip provides a simple and rapid platform to characterize EVs to monitor lung cancer therapy outcomes.

Design, synthesis and anticancer activity studies of 3-(coumarin-3-yl)-acrolein derivatives: Evidenced by integrating network pharmacology and vitro assay.

Coumarin derivatives have diverse structures and show various significant biological activities. Aiming to develop more potent coumarin derivatives for cancer treatment, a series of coumarin acrolein hybrids were designed and synthesized by using molecular hybridization approach, and investigated for their antiproliferative activity against A549, KB, Hela and MCF-7 cancer cells as well as HUVEC and LO2 human normal cells. The results indicated that most of the synthesized compounds displayed remarkable inhibitory activity towards cancer cells but low cytotoxicity on normal cells. Among all the compounds, 5d and 6e were the most promising compounds against different cancer cell lines, especially for A549 and KB cells. The preliminary action mechanism studies suggested that compound 6e, the representative compound, was capable of dose-dependently suppressing migration, invasion and inducing significant apoptosis. Furthermore, the combined results of network pharmacology and validation experiments revealed that compound 6e induced mitochondria dependent apoptosis via the PI3K/AKT-mediated Bcl-2 signaling pathway. In summary, our study indicated compound 6e could inhibit cell proliferation, migration, invasion and promote cell apoptosis through inhibition of PI3K/AKT signaling pathway in human oral epidermoid carcinoma cells. These findings demonstrated the potential of 3-(coumarin-3-yl)-acrolein derivatives as novel anticancer chemotherapeutic candidates, providing ideas for further development of drugs for clinical use.

Quantum Size Effect to Induce Colossal High-Temperature Energy Storage Density and Efficiency in Polymer/Inorganic Cluster Composites.

Polymer dielectrics need to operate at high temperatures to meet the demand of electrostatic energy storage in modern electronic and electrical systems. The polymer nanocomposite approach, an extensively proved strategy for performance improvement, encounters a bottleneck of reduced energy density and poor discharge efficiency beyond 150 °C. In this work, a polymer/metal oxide cluster composite prepared based on the "site isolation" strategy is reported. Capitalizing on the quantum size effect, the bandgap and surface defect states of the ultrasmall inorganic clusters (2.2 nm diameter) are modulated to markedly differ from regular-sized nanoparticles. Experimental results in conjunction with computational simulation demonstrate that the presence of ultrasmall inorganic clusters can introduce more abundant, deeper traps in the composite dielectric with respect to conventional polymer/nanoparticle blends. Unprecedented high-temperature capacitive performance, including colossal energy density (6.8 J cm-3 ), ultrahigh discharge efficiency (95%) and superior stability at different electric field frequencies, are achieved in these polymer/cluster composites up to 200 °C. Along with the advantages in material preparation (inexpensive precursors and one-pot synthesis), such polymer/inorganic cluster composite approach is promising for high-temperature dielectric energy storage in practical power apparatus and electronic devices.

Extremely Robust and Multifunctional Nanocomposite Fibers for Strain-Unperturbed Textile Electronics.

Textile electronics are needed that can achieve strain-unaltered performance when they undergo irregular and repeated strain deformation. Such strain-unaltered textile electronics require advanced fibers that simultaneously have high functionalities and extreme robustness as fabric materials. Current synthetic nanocomposite fibers based on inorganic matrix have remarkable functionalities but often suffer from low robustness and poor tolerance against crack formation. Here, we present a design for a high-performance multifunctional nanocomposite fiber that is mechanically and electrically robust, which was realized by crosslinking titanium carbide (MXene) nanosheets with a slide-ring polyrotaxane to form an internal mechanically-interlocked network. This inorganic matrix nanocomposite fiber featured distinct strain-hardening mechanical behavior and exceptional load-bearing capability (toughness approaching 60 MJ m-3 and ductility over 27%). It retained 100% of its ductility after cyclic strain loading. Moreover, the high electrical conductivity (>1.1 × 105 S m-1 ) and electrochemical performance (>360 F cm-3 ) of the nanocomposite fiber can be well retained after subjecting the fiber to extensive (>25% strain) and long-term repeated (10 000 cycles) dimensional changes. Such superior robustness allowed for the fabrication of the nanocomposite fibers into various robust wearable devices, such as textile-based electromechanical sensors with strain-unalterable sensing performance and fiber-shaped supercapacitors with invariant electrochemical performance for 10 000 strain loading cycles.

Development of receptor binding domain-based double-antigen sandwich lateral flow immunoassay for the detection and evaluation of SARS-CoV-2 neutralizing antibody in clinical sera samples compared with the conventional virus neutralization test.

Vaccination is an effective strategy to fight COVID-19. However, the effectiveness of the vaccine varies among different populations in varying immune effects. Neutralizing antibody (NAb) level is an important indicator to evaluate the protective effect of immune response after vaccination. Lateral flow immunoassay (LFIA) is a rapid, safe and sensitivity detection method, which has great potential in the detection of SARS-CoV-2 NAb. In this study, a fluorescent beads-based lateral flow immunoassay (FBs-LFIA) and a latex beads-based LFIA (LBs-LFIA) using double antigen sandwich (DAS) strategy were established to detect NAbs in the serum of vaccinated people. The limit of detection (LoD) of the FBs-LFIA was 1.13 ng mL- 1 and the LBs-LFIA was 7.11 ng mL- 1. The two LFIAs were no cross-reactive with sera infected by other pathogenic bacteria. Furthermore, the two LFIAs showed a good performance in testing clinical samples. The sensitivity of FBs-LFIA and LBs-LFIA were 97.44% (95%CI: 93.15%-99.18%) and 98.29% (95%CI: 95.84%-99.37%), and the specificity were 98.28% (95%CI: 95.37%-99.45%) and 97.70% (95%CI: 94.82%-99.06%) compared with the conventional virus neutralization test (cVNT), respectively. Notably, the LBs-LFIA was also suitable for whole blood sample, requiring only 3 µL of whole blood, which provided the possibility to detect NAbs at home. To sum up, the two LFIAs based on double antigen sandwich established by us can rapidly, safely, sensitively and accurately detect SARS-CoV-2 NAb in human serum.

Detecting mitochondrial mutations associated with aminoglycoside ototoxicity by noninvasive prenatal testing.

OBJECTIVES: Numerous diseases and disorders are associated with mitochondrial DNA (mtDNA) mutations, among which m.1555A > G and m.1494C > T mutations in the 12 S ribosomal RNA gene contribute to aminoglycoside-induced and nonsyndromic hearing loss worldwide. METHODS: A total of 76,842 qualified non-invasive prenatal (NIPT) samples were subjected to mtDNA mutation and haplogroup analysis. RESULTS: We detected 181 m.1555A > G and m.1494C > T mutations, 151 of which were subsequently sequenced for full-length mitochondrial genome verification. The positive predictive values for the m.1555A > G and m.1494C > T mutations were 90.78% and 90.00%, respectively, a performance comparable to that attained with newborn hearing screening. Furthermore, mitochondrial haplogroup analysis revealed that the 12 S rRNA 1555A > G mutation was enriched in sub-haplotype D5[p = 0, OR = 4.6706(2.81-7.78)]. CONCLUSIONS: Our findings indicate that the non-invasive prenatal testing of cell-free DNA obtained from maternal plasma can successfully detect m.1555A > G and m.1494C > T mutations.

Correlating the Interfacial Polar-Phase Structure to the Local Chemistry in Ferroelectric Polymer Nanocomposites by Combined Scanning Probe Microscopy.

Ferroelectric polymer nanocomposites possess exceptional electric properties with respect to the two otherwise uniform phases, which is commonly attributed to the critical role of the matrix-particle interfacial region. However, the structure-property correlation of the interface remains unestablished, and thus, the design of ferroelectric polymer nanocomposite has largely relied on the trial-and-error method. Here, a strategy that combines multi-mode scanning probe microscopy-based electrical characterization and nano-infrared spectroscopy is developed to unveil the local structure-property correlation of the interface in ferroelectric polymer nanocomposites. The results show that the type of surface modifiers decorated on the nanoparticles can significantly influence the local polar-phase content and the piezoelectric effect of the polymer matrix surrounding the nanoparticles. The strongly coupled polar-phase content and piezoelectric effect measured directly in the interfacial region as well as the computed bonding energy suggest that the property enhancement originates from the formation of hydrogen bond between the surface modifiers and the ferroelectric polymer. It is also directly detected that the local domain size of the ferroelectric polymer can impact the energy level and distribution of charge traps in the interfacial region and eventually influence the local dielectric strength.

Polymer Nanocomposite Dielectrics: Understanding the Matrix/Particle Interface.

Polymer nanocomposite dielectrics possess exceptional electric properties that are absent in the pristine dielectric polymers. The matrix/particle interface in polymer nanocomposite dielectrics is suggested to play decisive roles on the bulk material performance. Herein, we present a critical overview of recent research advances and important insights in understanding the matrix/particle interfacial characteristics in polymer nanocomposite dielectrics. The primary experimental strategies and state-of-the-art characterization techniques for resolving the local property-structure correlation of the matrix/particle interface are dissected in depth, with a focus on the characterization capabilities of each strategy or technique that other approaches cannot compete with. Limitations to each of the experimental strategy are evaluated as well. In the last section of this Review, we summarize and compare the three experimental strategies from multiple aspects and point out their advantages and disadvantages, critical issues, and possible experimental schemes to be established. Finally, the authors' personal viewpoints regarding the challenges of the existing experimental strategies are presented, and potential directions for the interface study are proposed for future research.

Platinum nanoparticles (PtNPs)-based CRISPR/Cas12a platform for detection of nucleic acid and protein in clinical samples.

Early rapid screening diagnostic assay is essential for the identification, prevention, and evaluation of many contagious or refractory diseases. The optical density transducer created by platinum nanoparticles (PtNPs) (OD-CRISPR) is reported in the present research as a cheap and easy-to-execute CRISPR/Cas12a-based diagnostic platform. The OD-CRISPR uses PtNPs, with ultra-high peroxidase-mimicking activity, to increase the detection sensitivity, thereby enabling the reduction of detection time and cost. The OD-CRISPR can be utilized to identify nucleic acid or protein biomarkers within an incubation time of 30-40min in clinical specimens. In the case of taking severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) N gene as an instance, when compared to a quantitative reverse transcription-polymerase chain reaction (RT-qPCR), the OD-CRISPR test attains a sensitivity of 79.17% and a specificity of 100%. In terms of detecting prostate-specific antigen (PSA), aptamer-based OD-CRISPR assay achieves the least discoverable concentration of 0.01 ng mL-1. In general, the OD-CRISPR can detect nucleic acid and protein biomarkers, and is a potential strategy for early rapid screening diagnostic tools.

Viscoelastic Metal-in-Water Emulsion Gel via Host-Guest Bridging for Printed and Strain-Activated Stretchable Electrodes.

Stretchable conductive electrodes that can be made by printing technology with high resolution is desired for preparing wearable electronics. Printable inks composed of liquid metals are ideal candidates for these applications, but their practical applications are limited by their low stability, poor printability, and low conductivity. Here, thixotropic metal-in-water (M/W) emulsion gels (MWEGs) were designed and developed by stabilizing and bridging liquid metal droplets (LMDs) via a host-guest polymer. In the MWEGs, the hydrophilic main chain of the host-guest polymers emulsified and stabilized LMDs via coordination bonds. The grafted cyclodextrin and adamantane groups formed dynamic inclusion complexes to bridge two neighboring LMDs, leading to the formation of a dynamically cross-linked network of LMDs in the aqueous phase. The MWEGs exhibited viscoelastic and shear-thinning behavior, making them ideal for direct three-dimensional (3D) and screen printing with a high resolution (∼65 µm) to assemble complex patterns consisting of ∼95 wt % liquid metal. When stretching the printed patterns, strong host-guest interactions guaranteed that the entire droplet network was cross-linked, while the brittle oxide shell of the droplets ruptured, releasing the liquid metal core and allowing it to fuse into continuous conductive pathways under an ultralow critical strain (<1.5%). This strain-activated conductivity exceeded 15800 S/cm under a large strain of 800% and exhibited long-term cyclic stability and robustness.

Highly Sensitive Temperature-Pressure Bimodal Aerogel with Stimulus Discriminability for Human Physiological Monitoring.

Multimodal sensor with high sensitivity, accurate sensing resolution, and stimuli discriminability is very desirable for human physiological state monitoring. A dual-sensing aerogel is fabricated with independent pyro-piezoresistive behavior by leveraging MXene and semicrystalline polymer to assemble shrinkable nanochannel structures inside multilevel cellular walls of aerogel for discriminable temperature and pressure sensing. The shrinkable nanochannels, controlled by the melt flow-triggered volume change of semicrystalline polymer, act as thermoresponsive conductive channels to endow the pyroresistive aerogel with negative temperature coefficient of resistance of -10.0% °C-1 and high accuracy within 0.2 °C in human physiological temperature range of 30-40 °C. The flexible cellular walls, working as pressure-responsive conductive channels, enable the piezoresistive aerogel to exhibit a pressure sensitivity up to 777 kPa-1 with a detectable pressure limit of 0.05 Pa. The pyro-piezoresistive aerogel can detect the temperature-dependent characteristics of pulse pressure waveforms from artery vessels under different human body temperature states.

Tailoring Silver Nanowire Nanocomposite Interfaces to Achieve Superior Stretchability, Durability, and Stability in Transparent Conductors.

Silver nanowires (AgNWs) have been considered as a promising candidate for transparent stretchable conductors (TSCs). However, the strong interface mismatch of stiff AgNWs and elastic substrates leads to the stress concentration at their interface and ultimately the low stretchability and poor durability of TSCs. Here, to address the interfacial mismatch of AgNWs-based TSCs we put forward a universal interface tailoring strategy that introduces the mercapto compound as the intermediate cross-linked layer. The mercapto compound strongly interacts with the AgNWs, forming a dense protective layer on their surface to improve their corrosion resistance, and reacts with the polymer substrate, forming a buffer layer to release the concentrated stress. As a result, the optimized TSCs showed superior stretchability (160%), exceptional durability (230 000 cycles), competent optoelectrical performance (18.0 ohm·sq-1 with a transmittance of 86.5%), and prominent stability. This work provides clear guidance and a strong impetus for the development of transparent stretchable electronics.

Pushing detectability and sensitivity for subtle force to new limits with shrinkable nanochannel structured aerogel.

There is an urgent need for developing electromechanical sensor with both ultralow detection limits and ultrahigh sensitivity to promote the progress of intelligent technology. Here we propose a strategy for fabricating a soft polysiloxane crosslinked MXene aerogel with multilevel nanochannels inside its cellular walls for ultrasensitive pressure detection. The easily shrinkable nanochannels and optimized material synergism endow the piezoresistive aerogel with an ultralow Young's modulus (140 Pa), numerous variable conductive pathways, and mechanical robustness. This aerogel can detect extremely subtle pressure signals of 0.0063 Pa, deliver a high pressure sensitivity over 1900 kPa-1, and exhibit extraordinarily sensing robustness. These sensing properties make the MXene aerogel feasible for monitoring ultra-weak force signals arising from a human's deep-lying internal jugular venous pulses in a non-invasive manner, detecting the dynamic impacts associated with the landing and take-off of a mosquito, and performing static pressure mapping of a hair.

The miR-23b/27b/24-1 Cluster Inhibits Hepatic Fibrosis by Inactivating Hepatic Stellate Cells.

BACKGROUND & AIMS: Hepatic fibrosis is characterized by hepatic stellate cell (HSC) activation and transdifferentiation-mediated extracellular matrix (ECM) deposition, which both contribute to cirrhosis. However, no antifibrotic regimen is available in the clinic. microRNA-23b/27b/24-1 cluster inhibition of transforming growth factor-ß (TGF-ß) signaling during hepatic development prompted us to explore whether this cluster inhibits HSC activation and hepatic fibrosis. METHODS: Experimental fibrosis was studied in carbon tetrachloride (CCl4)-treated C57BL/6 mice. After administration of miR-23b/27b/24-1 lentivirus or vehicle, animals were euthanized for liver histology. In primary rat HSC and HSC-T6, the anti-fibrotic effect of miR-23b/27b/24-1 cluster was furtherly investigated by RNA-sequencing, luciferase reporter assay, western blotting and bioinformatic means. RESULTS: In this study, we showed that increasing the miR-23b/27b/24-1 level through intravenous delivery of miR-23b/27b/24-1 lentivirus ameliorated mouse hepatic fibrosis. Mechanistically, the miR-23b/27b/24-1 cluster directly targeted messenger RNAs, which reduced the protein expression of 5 secretory profibrotic genes (TGF-ß2, Gremlin1, LOX, Itgα2, and Itgα5) in HSCs. Suppression of the TGF-ß signaling pathway by down-regulation of TGF-ß2, Itgα2, and Itgα5, and activation of the bone morphogenetic protein signaling pathway by inhibition of Gremlin1, decreased extracellular matrix secretion of HSCs. Furthermore, down-regulation of LOX expression softened the ECM. Moreover, a reduction in tissue inhibitors of metalloproteinase 1 expression owing to weakened TGF-ß signaling increased ECM degradation. CONCLUSIONS: Hepatic overexpression of the miR-23b/27b/24-1 cluster blocked hepatic fibrosis and may be a novel therapeutic regimen for patients with hepatic fibrosis.

An in situ and rapid self-healing strategy enabling a stretchable nanocomposite with extremely durable and highly sensitive sensing features.

Progress toward the development of wearable electromechanical sensors with durable and reliable sensing performance is critical for emerging wearable integrated electronic applications. However, it remains a long-standing challenge to realize mechanically stretchable sensing materials with extremely durable and high-performing sensing ability due to the fundamental dilemma lying in the sensing mechanism. In this work, we proposed an in situ and rapid self-healing strategy through nano-confining a dynamic host-guest supramolecular polymer network in a graphene-based multilevel nanocomposite matrix to fabricate a mechanically stretchable and structurally healable sensing nanocomposite which is provided with intriguing sensing durability and sensitivity simultaneously. When repeatedly stretching and releasing the nanocomposite sensing film, the fast association kinetics of cyclodextrin and adamantane host-guest inclusion complexes and good polymer chain dynamics in the supramolecular polymer network endowed by the nanoconfinement effect enable autonomous and rapid repair of the micro-cracks in situ generated in the sensing material. As a result, our strain sensing devices can achieve an extremely high durability and retain stable sensing performance even after over 100 000 stretching-releasing cycles at large strain of 50%. Moreover, the brittle nature originated from the inorganically dominated structure in conjunction with the thermodynamically stable host-guest interactions and dynamic hydrogen bonds inside the multilevel nanocomposite allow the sensing material to exhibit an ultrahigh gauge factor over 1500 with a large working strain of 58%. This work presents a reliable approach for the construction of ultradurable and high-performing wearable electronics.