Piezo1-Mediated Neurogenic Inflammatory Cascade Exacerbates Ventricular Remodeling After Myocardial Infarction.

BACKGROUND: Heart failure is associated with a high rate of mortality and morbidity, and ventricular remodeling invariably precedes heart failure. Ventricular remodeling is fundamentally driven by mechanotransduction that is regulated by both the nervous system and the immune system. However, it remains unknown which key molecular factors govern the neuro/immune/cardio axis that underlies mechanotransduction during ventricular remodeling. Here, we investigated whether the mechanosensitive Piezo cation channel-mediated neurogenic inflammatory cascade underlies ventricular remodeling-related mechanotransduction. METHODS: By ligating the left coronary artery of rats to establish an in vivo model of chronic myocardial infarction (MI), lentivirus-mediated thoracic dorsal root ganglion (TDRG)-specific Piezo1 knockdown rats and adeno-associated virus-PHP.S-mediated TDRG neuron-specific Piezo1 knockout mice were used to investigate whether Piezo1 in the TDRG plays a functional role during ventricular remodeling. Subsequently, neutralizing antibody-mediated TDRG IL-6 (interleukin-6) inhibition rats and adeno-associated virus-PHP.S-mediated TDRG neuron-specific IL-6 knockdown mice were used to determine the mechanism underlying neurogenic inflammation. Primary TDRG neurons were used to evaluate Piezo1 function in vitro. RESULTS: Expression of Piezo1 and IL-6 was increased, and these factors were functionally activated in TDRG neurons at 4 weeks after MI. Both knockdown of TDRG-specific Piezo1 and deletion of TDRG neuron-specific Piezo1 lessened the severity of ventricular remodeling at 4 weeks after MI and decreased the level of IL-6 in the TDRG or heart. Furthermore, inhibition of TDRG IL-6 or knockdown of TDRG neuron-specific IL-6 also ameliorated ventricular remodeling and suppressed the IL-6 cascade in the heart, whereas the Piezo1 level in the TDRG was not affected. In addition, enhanced Piezo1 function, as reflected by abundant calcium influx induced by Yoda1 (a selective agonist of Piezo1), led to increased release of IL-6 from TDRG neurons in mice 4 weeks after MI. CONCLUSIONS: Our findings point to a critical role for Piezo1 in ventricular remodeling at 4 weeks after MI and reveal a neurogenic inflammatory cascade as a previously unknown facet of the neuronal immune signaling axis underlying mechanotransduction.

Unlocking the Potential of Amorphous Prussian Blue with Highly Active Mn Sites at Room Temperature for Impressive Oxygen Evolution Reaction and Super Capacitor Electrochemical Performance.

The key to increasing the rate of oxygen evolution reaction (OER) lies in accelerated four-electron dynamics, while the key to facilitating the development of supercapacitors lies in the design of electrode materials. This paper synthesized manganese-iron Prussian blue (MnFe-PBA@IF) at room temperature, and hexagonal concave structures w ere prepared using a fast-reducing matrix. Interestingly, MnFe-PBA@IF has an amorphous structure favorable to exposing more active surfaces. According to Gibbs free energy calculations on MnFe-PBA, charge depletion of manganese atoms can greatly enhance the adsorption of electron-rich oxygen-containing groups on the surface. Furthermore, the overpotential in 1 m KOH is 280 mV. Also, it can be used as a supercapacitor with a stable operating voltage range of -0.9-0 V and a specific capacity of 1260 F g-1 . This work provides new insights into the synthesis of OER catalysts for Prussian blue ferromanganese at room temperature. Non-gold-bonded adsorption, highly active metal centers and active surfaces are the underlying reasons for the superior performance of supercapacitors. Therefore, Prussian blue with good energy storage performance and high active surface can be used as multifunctional energy storage and conversion electrodes.

N6-Methyladenosine-mediated phase separation suppresses NOTCH1 expression and promotes mitochondrial fission in diabetic cardiac fibrosis.

BACKGROUND: N6-methyladenosine (m6A) modification of messenger RNA (mRNA) is crucial for liquid-liquid phase separation in mammals. Increasing evidence indicates that liquid-liquid phase separation in proteins and RNAs affects diabetic cardiomyopathy. However, the molecular mechanism by which m6A-mediated phase separation regulates diabetic cardiac fibrosis remains elusive. METHODS: Leptin receptor-deficient mice (db/db), cardiac fibroblast-specific Notch1 conditional knockout (POSTN-Cre × Notch1flox/flox) mice, and Cre mice were used to induce diabetic cardiac fibrosis. Adeno-associated virus 9 carrying cardiac fibroblast-specific periostin (Postn) promoter-driven small hairpin RNA targeting Alkbh5, Ythdf2, or Notch1, and the phase separation inhibitor 1,6-hexanediol were administered to investigate their roles in diabetic cardiac fibrosis. Histological and biochemical analyses were performed to determine how Alkbh5 and Ythdf2 regulate Notch1 expression in diabetic cardiac fibrosis. NOTCH1 was reconstituted in ALKBH5- and YTHDF2-deficient cardiac fibroblasts and mouse hearts to study its effects on mitochondrial fission and diabetic cardiac fibrosis. Heart tissue samples from patients with diabetic cardiomyopathy were used to validate our findings. RESULTS: In mice with diabetic cardiac fibrosis, decreased Notch1 expression was accompanied by high m6A mRNA levels and mitochondrial fission. Fibroblast-specific deletion of Notch1 enhanced mitochondrial fission and cardiac fibroblast proliferation and induced diabetic cardiac fibrosis in mice. Notch1 downregulation was associated with Alkbh5-mediated m6A demethylation in the 3'UTR of Notch1 mRNA and elevated m6A mRNA levels. These elevated m6A levels in Notch1 mRNA markedly enhanced YTHDF2 phase separation, increased the recognition of m6A residues in Notch1 mRNA by YTHDF2, and induced Notch1 degradation. Conversely, epitranscriptomic downregulation rescues Notch1 expression, resulting in the opposite effects. Human heart tissues from patients with diabetic cardiomyopathy were used to validate the findings in mice with diabetic cardiac fibrosis. CONCLUSIONS: We identified a novel epitranscriptomic mechanism by which m6A-mediated phase separation suppresses Notch1 expression, thereby promoting mitochondrial fission in diabetic cardiac fibrosis. Our findings provide new insights for the development of novel treatment approaches for patients with diabetic cardiac fibrosis.

Polymerization Strategies to Construct a 3D Polymer Passivation Network toward High Performance Perovskite Solar Cells.

The spontaneously formed uncoordinated Pb2+ defects usually make the perovskite films demonstrate strong n-type with relatively lower carrier diffusion length and serious non-radiative recombination energy loss. In this work, we adopt different polymerization strategies to construct three-dimensional passivation frameworks in the perovskite layer. Thanks to the strong C≡N⋅⋅⋅Pb coordination bonding and the penetrating passivation structure, the defect state density is obviously reduced, accompanied by a significant increase in the carrier diffusion length. Additionally, the reduction of iodine vacancies also changed the Fermi level of the perovskite layer from strong n-type to weak n-type, which substantially promotes the energy level alignment and carrier injection efficiency. As a result, the optimized device achieved an efficiency exceeded 24 % (the certified efficiency is 24.16 %) with a high open-circuit voltage of 1.194 V, and the corresponding module achieved an efficiency of 21.55 %.

Alteration in cartilage matrix stiffness as an indicator and modulator of osteoarthritis.

Osteoarthritis (OA) is characterized by cartilage degeneration and destruction, leading to joint ankylosis and disability. The major challenge in diagnosing OA at early stage is not only lack of clinical symptoms but also the insufficient histological and immunohistochemical signs. Alteration in cartilage stiffness during OA progression, especially at OA initiation, has been confirmed by growing evidences. Moreover, the stiffness of cartilage extracellular matrix (ECM), pericellular matrix (PCM) and chondrocytes during OA development are dynamically changed in unique and distinct fashions, revealing possibly inconsistent conclusions when detecting cartilage matrix stiffness at different locations and scales. In addition, it will be discussed regarding the mechanisms through which OA-related cartilage degenerations exhibit stiffened or softened matrix, highlighting some critical events that generally incurred to cartilage stiffness alteration, as well as some typical molecules that participated in constituting the mechanical properties of cartilage. Finally, in vitro culturing chondrocytes in various stiffness-tunable scaffolds provided a reliable method to explore the matrix stiffness-dependent modulation of chondrocyte metabolism, which offers valuable information on optimizing implant scaffolds to maximally promote cartilage repair and regeneration during OA. Overall, this review systematically and comprehensively elucidated the current progresses in the relationship between cartilage stiffness alteration and OA progression. We hope that deeper attention and understanding in this researching field will not only develop more innovative methods in OA early detection and diagnose but also provide promising ideas in OA therapy and prognosis.

Enhancing Hot Carrier Photoelectric Efficiency through the Boosted Collection of Hot Holes via Au/ZrO2/Si Tunneling Junctions.

Metallic nanoparticles can generate photoexcited hot carriers on the femtosecond scale under light excitation, which holds immense significance for applications such as optical communication and ultrafast imaging. In this study, a tunnelling junction structure with ZrO2 as the dielectric layer is designed and fabricated to achieve efficient hot hole collection between Au nanoparticles and P-type Si. Through characterizations of photoconductive atomic force microscopy, the electrical transition from an ohmic contact to a tunneling junction is confirmed, and the transfer pathway of Au hot holes to P-type Si upon 520 nm excitation is clearly observed. The impact of the tunneling structure on device performance is investigated through the fabrication of Si/ZrO2/Au/TiO2 photodiodes. The performance tests show that hot hole collection by the tunneling effect significantly enhances a range of parameters, e.g., external quantum efficiency by 250%. Noticeably, the external quantum efficiency attributed to photogenerated hot carriers under 520 nm excitation is estimated to exceed 2.5%. Moreover, the transient photoresponse of the photodiodes is examined with a typical rising time of less than 20 ns.

Self-Healing and Shear-Stiffening Electrodes for Wearable Biopotential Sensing and Gesture Recognition.

The achievement of flexible skin electrodes for dynamic monitoring of biopotential is one of the challenging issues in flexible electronics due to the interference of large acceleration and heavy sweat that influence the stability of skin-electrode interfaces. This work presents materials and techniques to achieve self-healing and shear-stiffening electrodes and an associated flexible system that can be used for multichannel biopotential measurement on the skin. The electrode that is based on a composite of silver (Ag) flakes, Ag nanowires, and polyborosiloxane offers an electrical conductivity of 9.71 × 104 S/m and a rheological characteristic that ensures stable and fully conformal contact with skin and easy removal under different shear rates. The electrode can maintain its conductivity even after being stretched by more than 60% and becomes self-healed after mechanical damage. The combination of the electrodes with a screen-printed multichannel flexible sensor allows stable monitoring of both static and dynamic electromyography signals, leading to the acquisition of high-quality multilead biopotential signals that can be readily extracted to yield gesture recognition results with over 97.42% accuracy. The conductive self-healing materials and flexible sensors may be utilized in various daily biopotential sensing applications, allowing highly stable dynamic measurement to facilitate artificial intelligence-enabled health condition diagnosis and human-computer interface.

Noncoding RNA network crosstalk in organ fibrosis.

Fibrosis is a process involving excessive accumulation of extracellular matrix components, the severity of which interferes with the function of the organ in question. With the advances in RNA sequencing and in-depth molecular studies, a large number of current studies have pointed out the irreplaceable role of non-coding RNAs (ncRNAs) in the pathophysiological development of organ fibrosis. Here, by summarizing the results of a large number of studies on the interactions between ncRNAs, some studies have found that long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs), among others, are able to act as sponges or decoy decoys for microRNAs (miRNAs), act as competing endogenous RNAs (ceRNAs) to regulate the expression of miRNAs, and subsequently act on different mRNA targets, playing a role in the development of fibrosis in a wide variety of organs, including the heart, liver, kidneys, and spleen. parenchymal organs, including heart, liver, kidney, and spleen, play important roles in the development of fibrosis. These findings elucidate the intricate involvement of the lncRNA/circRNA-miRNA-mRNA axis in the pathophysiological processes underpinning organ fibrosis, thereby enhancing our comprehension of the onset and progression of this condition. Furthermore, they introduce novel potential therapeutic targets within the realm of ncRNA-based therapeutics, offering avenues for the development of innovative drugs aimed at mitigating or reversing the effects of organ fibrosis.

Ultrahigh-sensitivity multi-parameter tacrolimus solution detection based on an anchor planar millifluidic microwave biosensor.

To detect drug concentration in tacrolimus solution, an anchor planar millifluidic microwave (APMM) biosensor is proposed. The millifluidic system integrated with the sensor enables accurate and efficient detection while eliminating interference caused by the fluidity of the tacrolimus sample. Different concentrations (10-500 ng mL-1) of the tacrolimus analyte were introduced into the millifluidic channel, where it completely interacts with the radio frequency patch electromagnetic field, thereby effectively and sensitively modifying the resonant frequency and amplitude of the transmission coefficient. Experimental results indicate that the sensor has an extremely low limit of detection (LoD) of 0.12 pg mL-1 and a frequency detection resolution (FDR) of 1.59 (MHz (ng mL-1)). The greater the FDR and the lower the LoD, the more the feasibility of a label-free biosensing method. Regression analysis revealed a strong linear correlation (R2 = 0.992) between the concentration of tacrolimus and the frequency difference of the two resonant peaks of APMM. In addition, the difference in the reflection coefficient between the two formants was measured and calculated, and a strong linear correlation (R2 = 0.998) was found between the difference and tacrolimus concentration. Five measurements were performed on each individual sample of tacrolimus to validate the biosensor's high repeatability. Consequently, the proposed biosensor is a potential candidate for the early detection of tacrolimus drug concentration levels in organ transplant recipients. This study presents a simple method for constructing microwave biosensors with high sensitivity and rapid response.

A flexible omnidirectional rotating magnetic array for MRI-safe transdermal wireless energy harvesting through flexible electronics.

Magnetic resonance imaging (MRI)-safe implantable wireless energy harvester offers substantial benefits to patients suffering from brain disorders, hearing impairment, and arrhythmias. However, rigid magnets in cutting-edge systems with limited numbers of rotation axis impose high risk of device dislodgement and magnet failure. Here, a flexible omnidirectional rotating magnetic array (FORMA) and a flexible MRI-safe implantable wireless energy-harvesting system have been developed. Miniaturized flexible magnetic balls 1 millimeter in diameter achieved by molding three-dimensional printed templates can rotate freely in elastomer cavities and supply a magnetic force of 2.14 Newtons at a distance of 1 millimeter between an implantable receiver and a wearable transceiver. The system can work stably under an acceleration of 9g and obtain a power output of 15.62 decibel milliwatts at a transmission frequency of 8 megahertz. The development of the FORMA may lead to life-long flexible and batteryless implantable systems and offers the potential to promote techniques for monitoring and treating acute and chronic diseases.

In Situ Formation of Conductive Epidermal Electrodes Using a Fully Integrated Flexible System and Injectable Photocurable Ink.

In situ fabrication of wearable devices through coating approaches is a promising solution for the fast deployment of wearable devices and more adaptable devices for different sensing demands. However, heat, solvent, and mechanical sensitivity of biological tissues, along with personal compliance, pose strict requirements for coating materials and methods. To address this, a biocompatible and biodegradable light-curable conductive ink and an all-in-one flexible system that conducts in situ injection and photonic curing of the ink as well as monitoring of biophysiological information have been developed. The ink can be solidified through spontaneous phase changes and photonic cured to achieve a high mechanical strength of 7.48 MPa and an excellent electrical conductivity of 3.57 × 105 S/m. The flexible system contains elastic injection chambers embedded with specially designed optical waveguides to uniformly dissipate visible LED light throughout the chambers and rapidly cure the ink in 5 min. The resulting conductive electrodes offer intimate skin contact even with the existence of hair and work stably even under an acceleration of 8 g, leading to a robust wearable system capable of working under intense motion, heavy sweating, and varied surface morphology. Similar concepts may lead to various rapidly deployable wearable systems that offer excellent adaptability to different monitoring demands for the health tracking of large populations.

A flexible wearable device coupled with injectable Fe3O4 nanoparticles for capturing circulating tumor cells and triggering their deaths.

Elimination of circulating tumor cells (CTCs) in the blood can be an effective therapeutic approach to disrupt metastasis. Here, a strategy is proposed to implement flexible wearable electronics and injectable nanomaterials to disrupt the hematogenous transport of CTCs. A flexible device containing an origami magnetic membrane is used to attract Fe3O4@Au nanoparticles (NPs) that are surface modified with specific aptamers and intravenously injected into blood vessels, forming an invisible hand and fishing line/bait configuration to specifically capture CTCs through bonding with aptamers. Thereafter, thinned flexible AlGaAs LEDs in the device offer an average fluence of 15.75 mW mm-2 at a skin penetration depth of 1.5 mm, causing a rapid rise of temperature to 48 °C in the NPs and triggering CTC death in 10 min. The flexible device has been demonstrated for intravascular isolation and enrichment of CTCs with a capture efficiency of 72.31% after 10 cycles in a simulated blood circulation system based on a prosthetic upper limb. The fusion of nanomaterials and flexible electronics reveals an emerging field that utilizes wearable and flexible stimulators to activate biological effects offered by nanomaterials, leading to improved therapeutical effects and postoperative outcomes of diseases.

Microfluidic microwave biosensor based on biomimetic materials for the quantitative detection of glucose.

This paper presents a microwave microfluidic biosensor for monitoring blood glucose levels. The glucose sensor is a triple ring microstrip patch antenna integrated with a biomimetic microfluidic device capable of measuring a fixed volume of glucose solution. The sensor was utilized to detect 50-500 mg/dL glucose solutions. The interaction of the glucose solution with the electromagnetic field on the patch's surface influences both the resonance frequency and the magnitude of reflection coefficient. The results indicate that the microfluidic device can reduce experimental error and enhance the correlation between glucose concentration, resonant frequency, and reflection coefficient. Finally, the microfluidic sensor had a sensitivity of 0.25 MHz/(mg/dL), a detection limit as low as 7.7 mg/dL, and correlation coefficients of resonance frequency and reflection coefficient with a glucose concentration of 0.996 and 0.984, respectively. The experiment on the sensor's stability verifies the sensor's excellent stability and rapid response (~ 150 ms). Consequently, the device can be used to differentiate the concentration of glucose solutions, as well as to detect blood glucose levels at an early stage.

Excellent Photonic and Mechanical Properties of Macromorphic Fibers Formed by Eu3+-Complex-Anchored, Unzipped, Multiwalled Carbon Nanotubes.

The macromorphic properties of carbon nanotubes perform poorly because of their size limitations: nanosize in diameters and microsize in length. In this work, to realize these dual purposes, we first used an electrochemical method to tear the surface of multiwalled carbon nanotubes (MWCNTs) to anchor photonic Eu3+-complexes there. Through the polar reactive groups endowed by the tearing, the Eu3+-complexes coordinate at the defected structures, obtaining the Eu3+-complex-anchored, unzipped, multiwalled carbon nanotubes (E-uMWCNTs). The controllable surface-breaking retains the MWCNTs' original, excellent mechanical properties. Then, to obtain the macromorphic structure with infinitely long fibers, a wet-spinning process was applied via the binding of a small quantity of polyvinyl alcohol (PVA). Thus, the wet-spun fibers with high contents of E-uMWCNTs (E-uMWCNT-Fs) were produced, in which the E-uMWCNTs took 33.3 wt%, a high ratio in E-uMWCNT-Fs. On the other hand, due to the reinforcing effect of E-uMWCNTs, the highest tensile strength can reach 228.2 MPa for E-uMWCNT-Fs. Meanwhile, the E-uMWCNT-Fs show high-efficiency photoluminescence and excellent media resistance performance due to the embedding effect of PVA on the E-uMWCNTs. Therefore, E-uMWCNT-Fs can exhibit excellent luminescence properties in aqueous solutions at pH 4~12 and in some high-concentration metal-ion solutions. Those distinguished performances promise outstanding innovations of this work.

The Created Excellent Thermal, Mechanical and Fluorescent Properties by Doping Eu3+-Complex-Anchored Carbon Nanotubes in Polycyanate Resins.

In the blending process of the composites, the clustering of MWCNTs under high concentration leads to poor dispersion and difficult complexing with luminescent elements. Cyanate ester resins (CERs) have a brittle network structure when cured caused by a conjugation effect that forms a strong emission peak in the ultraviolet-visible region and quenches the luminescent elements of the fluorescent nanofillers. In this paper, by anchoring of the Eu complex (Eu(TTA)3Phen, ETP) on a surface of longitudinal split unzipped carbon nanotubes (uMWCNTs); fluorescent nanoparticles were prepared as ETP anchor unzipper carbon nanotubes (ETP-uCNTs). Dicyanate ester of bisphenol E (CER-E monomer) is cured to polycyanurate at a lower temperature to achieve a high conversion, promoting a uniform blend with ETP-uCNTs, providing the fluorescence environment with high color purity. Studies show the ETP-uCNTs solve the agglomeration of MWCNTs and improve the interface binding ability. Compared with the pure CER-E, the tensile strength, bending strength and impact strength of CER-E/0.8 wt.% ETP-uCNT hybrid nanocomposites are increased by 94.6%, 92.8% and 101.1%, respectively. The carbon residue rate of CER-E/ETP-uCNTs is up to 47.14% at 800 °C, the temperature of the maximum reaction rate decreases by 67.81 °C, and the partial absorption of ultraviolet light is realized between 200 and 400 nm.

Effects of Modified Graphene Oxide on Thermal and Crystallization Properties of PET.

In this article, graphene oxide nanosheets grafted with low molecular weight poly(ethylene terephthalate) were in situ synthesized via carboxylation, acyl chlorination and grafting modification in order to improve the compatibility between GO and PET phases and enhance the thermal stability and crystallization properties of PET. Fourier Transform Infrared (FTIR), X-ray Photoelectron Spectroscopy (XPS), and Atomic Force Microscopy (AFM) characterization results demonstrated that LMPET chains have been successfully grafted onto the surface of GO. To further investigate the influence of modified GO on properties of PET, modified PET was prepared by incorporating the GL-g-LMPET nanofillers into the PET matrix using the melt-blending method. Due to the similar polarity and strong interaction between LMPET and PET molecules, GL-g-LMPET nanofillers were homogeneously dispersed in PET matrix. Thermal properties and crystallization properties of obtained nanocomposites were systematically characterized using Differential Scanning Calorimetry (DSC), X-ray Diffraction (XRD), and Thermo Gravimetric Analysis (TGA). Results show that GL-g-LMPET nanofillers could improve the thermal stability of PET, e.g., increase up to 16.6 °C in temperature at the maximum rate of weight loss. In addition, the GL-g-LMPET also acts as an efficient nucleating agent for PET, exhibiting (1) higher crystallization temperatures; (2) higher degrees of crystallinity; and (3) faster rates of crystallization.