Red fluorescent hydrogels possessing injectable and self-healing properties have widespread potential in biomedical field. It is still a challenge to achieve a biomacromolecules based dynamic hydrogels simultaneously combining with excellent red fluorescence, good mechanical properties, and biocompatibility. Here we firstly exploited hydrophilic inclusion complex of (R-CDs@α-CD) derived from red fluorescent carbon dots (R-CDs) and α-cyclodextrin (α-CD), and then achieved a red fluorescent and dynamic polysaccharide R-CDs@α-CD/CEC-l-OSA hydrogel. The nanocomposite hydrogel can be fabricated through controlling dopant of red fluorescent R-CDs@α-CD into dynamic polymer networks, taking dynamic crosslinked N-carboxyethyl chitosan (CEC) and oxidized sodium alginate (OSA) as an example. The versatile hydrogel simultaneously combines the features of injection, biocompatibility, and augmented mechanical properties and self-healing behavior, especially in rapid self-recovery even after integration. The R-CDs@α-CD uniformly dispersed into dynamic hydrogel played the role of killing two birds with one stone, that is, endowing red fluorescence as a hydrophilic fluorescent substance, and improving mechanical and self-healing properties as a dynamic nano-crosslinker, via providing hydrogen bonds as reversible crosslinkings. The novel red fluorescent and dynamic hydrogel based on polysaccharides hold promise for using as biomaterials in biomedical field.

The novel hollow-magnetite (HFO)/MXene nanohybrids with coral-like structure were successfully prepared via templating and electrostatic self-assembly techniques for electromagnetic (EM) wave adsorption application. The unique coral-like structure of the prepared HFO/MXene hybrids was characterized by transmission electron microscopy (TEM) and scanning electron microscopy (SEM). When mass ratio of HFO to MXene is 2:1, the maximum effective absorption bandwidth (EABmax) of HFO/MXene hybrids is able to reach 5.36GHz. Moreover, when mass ratio of HFO to MXene is 1:1, the minimum reflection loss (RLmin) even achieves -42.48dB with a thickness of 3.1mm. The excellent EM absorption performance of HFO/MXene hybrids is mainly due to the ideal impedance matching and synergistic effect of magnetic loss and dielectric loss caused by unique coral-like structure. This work provides unexplored areas in the design of the spatial structure of MXene for microwave absorption.

Polycystic ovarian syndrome (PCOS) is an endocrine-metabolic condition affecting 5–10

Ultrasound is an acoustic wave which can noninvasively penetrate the skull to deep brain regions, enabling neuromodulation. However, conventional ultrasound’s spatial resolution is diffraction-limited and low-precision. Here, we report acoustic nanobubble-mediated ultrasound stimulation capable of localizing ultrasound’s effects to only the desired brain region in male mice. By varying the delivery site of nanobubbles, ultrasound could activate specific regions of the mouse motor cortex, evoking EMG signaling and limb movement, and could also, separately, activate one of two nearby deep brain regions to elicit distinct behaviors (freezing or rotation). Sonicated neurons displayed reversible, low-latency calcium responses and increased c-Fos expression in the sub-millimeter-scale region with nanobubbles present. Ultrasound stimulation of the relevant region also modified depression-like behavior in a mouse model. We also provide evidence of a role for mechanosensitive ion channels. Altogether, our treatment scheme allows spatially-targetable, repeatable and temporally-precise activation of deep brain circuits for neuromodulation without needing genetic modification.

Biomacromolecules based injectable and self-healing hydrogels possessing high mechanical properties have widespread potential in biomedical field. However, dynamic features are usually inversely proportional to toughness. It is challenging to simultaneously endow these properties to the dynamic hydrogels. Here, we fabricated an injectable nanocomposite hydrogel (CS-NPs@OSA-l-Gtn) stimultaneously possessing excellent autonomous self-healing performance and high mechanical strength by doping chitosan nanoparticles (CS-NPs) into dynamic polymer networks of oxidized sodium alginate (OSA) and gelatin (Gtn) in the presence of borax. The synergistic effect of the multiple reversible interactions combining dynamic covalent bonds (i.e., imine bond and borate ester bond) and noncovalent interactions (i.e., electrostatic interaction and hydrogen bond) provide effective energy dissipation to endure high fatigue resistance and cyclic loading. The dynamic hydrogel exhibited excellent mechanical properties like maximum 2.43 MPa compressive strength, 493.91 % fracture strain, and 89.54 kJ/m3 toughness. Moreover, the integrated hydrogel after injection and self-healing could withstand 150 successive compressive cycles. Besides, the bovine serum albumin embedded in CS-NPs could be sustainably released from the nanocomposite hydrogel for 12 days. This study proposes a novel strategy to synthesize an injectable and self-healing hydrogel combined with excellent mechanical properties for designing high-strength natural carriers with sustained protein delivery.

Severely chronic dermal wounds with irregular rupture shapes or even cavities are calling for injectable and self-biodegradable wound dressings for skin lesion with complex contours remain a great challenge. Here, we report an injectable, self-biodegradable poly(aspartic acid)-l-poly(aspartyl hydrazide) (PASP-l-PAHy) hydrogel to address these issues. The starting materials were cheap, and the new strategy for fabrication of self-biodegradable poly(aspartic acid) based hydrogel was facile, efficient, mild and environmentally friendly, which is consistent with the concept of green chemistry. The hydrogel possesses the comprehensive merits of injectability, self-biodegradability, shape-adaptability, transparence, biocompatibility, and adhesion, and shows specific autolytic biodegradation. The hydrogel was generated by in-situ gelation of poly(aspartic acid) (PASP) and poly(aspartyl hydrazide) (PAHy) polymers based on dual chemical (amide bond) and physical (hydrogen bond and ionic bond) crosslinks. The acceleration of wound healing could be observed in a rat skin full-thickness wound model for repairing skin tissue defects via hydrogel injection and autolytic biodegradation, highlighting great potential applications in wound dressing for the irregular dermal lesions without secondary skin damage. The injectable and self-biodegradable hydrogel augments formation of blood vessels and mature granulation tissue, thus enabling faster skin tissue restoration outcomes.

The proper microenvironment is critical for the storage and transportation of embryonic stem cells (ESCs). To mimic a dynamic 3D microenvironment as it exists in vivo and consider “off-the-shelf” availability reaching the destination, we proposed an alternative approach that allows for facile storage and transportation of stem cells in the form of ESCs-dynamic hydrogel construct (CDHC) under ambient conditions. To form CDHC, mouse embryonic stem cells (mESCs) were in-situ encapsulated within a polysaccharide-based dynamic and self-biodegradable hydrogel. After storing CDHC in a sterile and hermetic environment for 3 days and then transferring to a sealed vessel with fresh medium for another 3 days, the large and compact colonies retained a 90% survival rate and pluripotency. Furthermore, after transporting and arriving at the destination, the encapsulated stem cell could be automatically released from the self-biodegradable hydrogel. After continuous cultivation of 15 generations of retrieved cells, automatically released from the CDHC, the mESCs underwent 3D encapsulation, storage, transportation, release, and continuous long-term subculture; resumed colony forming capacity and pluripotency were revealed by stem cell markers both in protein and mRNA levels. We believe that the dynamic and self-biodegradable hydrogel provides a simple, cost-effective, and valuable tool for storing and transporting “ready-to-use” CDHC under ambient conditions, facilitating “off-the-shelf” availability and widespread applications.

Transcranial low-intensity ultrasound is a promising neuromodulation modality, with the advantages of noninvasiveness, deep penetration, and high spatiotemporal accuracy. However, the underlying biological mechanism of ultrasonic neuromodulation remains unclear, hindering the development of efficacious treatments. Here, the well-known Piezo1 was studied through a conditional knockout mouse model as a major mediator for ultrasound neuromodulation ex vivo and in vivo. We showed that Piezo1 knockout (P1KO) in the right motor cortex of mice significantly reduced ultrasound-induced neuronal calcium responses, limb movement, and muscle electromyogram (EMG) responses. We also detected higher Piezo1 expression in the central amygdala (CEA), which was found to be more sensitive to ultrasound stimulation than the cortex was. Knocking out the Piezo1 in CEA neurons showed a significant reduction of response under ultrasound stimulation, while knocking out astrocytic Piezo1 showed no-obvious changes in neuronal responses. Additionally, we excluded an auditory confound by monitoring auditory cortical activation and using smooth waveform ultrasound with randomized parameters to stimulate P1KO ipsilateral and contralateral regions of the same brain and recording evoked movement in the corresponding limb. Thus, we demonstrate that Piezo1 is functionally expressed in different brain regions and that it is an important mediator of ultrasound neuromodulation in the brain, laying the ground for further mechanistic studies of ultrasound.

The recent years has witnessed an exponential growth in the field of natural killer (NK) cell-based immunotherapy for cancer treatment. As a prerequisite to precise evaluations and on-demand interventions, the noninvasive tracking of adoptive NK cells plays a crucial role not only in post-treatment monitoring, but also in offering opportunities for preclinical studies on therapy optimizations. Here, we describe an NK cell tracking strategy for cancer immunotherapy based on ultrasound imaging modality. Nanosized ultrasound contrast agents, gas vesicles (GVs), were surface-functionalized to label NK cells. Unlike traditional microbubble contrast agents, nanosized GVs with their unique thermodynamical stability enable the detection of labeled NK cells under nonlinear contrast-enhanced ultrasound (nCEUS), without a noticeable impact on cellular viability or migration. By such labeling, we were able to monitor the trafficking of systematically infused NK cells to a subcutaneous tumor model. Upon co-treatment with interleukin (IL)-2, we observed a rapid enhancement in NK cell trafficking at the tumor site as early as 3 h post-infusion. Altogether, we show that the proposed ultrasound-based tracking strategy is able to capture the dynamical changes of cell trafficking in NK cell-based immunotherapy, providing referencing information for early-phase monotherapy evaluation, as well as understanding the effects of modulatory co-treatment. STATEMENT OF SIGNIFICANCE: In cellular immunotherapies, the post-infusion monitoring of the living therapeutics has been challenging. Several popular imaging modalities have been explored the monitoring of the adoptive immune cells, evaluating their trafficking and accumulation in the tumor. Here we demonstrated, for the first time, the ultrasound imaging-based immune cell tracking strategy. We showed that the acoustic labeling of adoptive immune cells was feasible with nanosized ultrasound contrast agents, overcoming the size and stability limitations of traditional microbubbles, enabling dynamical tracking of adoptive natural killer cells in both monotherapy and synergic treatment with cytokines. This article introduced the cost-effective and ubiquitous ultrasound imaging modality into the field of cellular immunotherapies, with broad prospectives in early assessment and on-demand image-guided interventions.

Microglia are the brain's resident immune cells, performing surveillance to promote homeostasis and healthy functioning. While microglial chemical signaling is well-studied, mechanical cues regulating their function are less well-understood. Here, we investigate the role of the mechanosensitive ion channel Piezo1 in microglia migration, pro-inflammatory cytokine production, and stiffness sensing. In Piezo1 knockout transgenic mice, we demonstrated the functional expression of Piezo1 in microglia and identified genes whose expression was consequently affected. Functional assays revealed that Piezo1 deficiency in microglia enhanced migration toward amyloid β-protein, and decreased levels of pro-inflammatory cytokines produced upon stimulation by lipopolysaccharide, both in vitro and in vivo. The phenomenon could be mimicked or reversed chemically using a Piezo1-specific agonist or antagonist. Finally, we also showed that Piezo1 mediated the effect of substrate stiffness-induced migration and cytokine expression. Altogether, we show that Piezo1 is an important molecular mediator for microglia, its activation modulating microglial migration and immune responses.

Optogenetics has become a widely used technique in neuroscience research, capable of controlling neuronal activity with high spatiotemporal precision and cell-type specificity. Expressing exogenous opsins in the selected cells can induce neuronal activation upon light irradiation, and the activation depends on the power of incident light. However, high optical power can also lead to off-target neuronal activation or even cell damage. Limiting the incident power, but enhancing power distribution to the targeted neurons, can improve optogenetic efficiency and reduce off-target effects. Here, the use of optical lenses made of polystyrene microspheres is demonstrated to achieve effective focusing of the incident light of relatively low power to neighboring neurons via photonic jets. The presence of microspheres significantly localizes and enhances the power density to the target neurons both in vitro and ex vivo, resulting in increased inward current and evoked action potentials. In vivo results show optogenetic stimulation with microspheres that can evoke significantly more motor behavior and neuronal activation at lowered power density. In all, a proof-of-concept of a strategy is demonstrated to increase the efficacy of optogenetic neuromodulation using pulses of reduced optical power.

Fiber-reinforced hydrogel (FrH) possesses the capability as flexible structural materials. The state-of-the-art FrH left a number of key issues untouched, including interfacial effects and the tolerance against salt disturbance. Herein, we report a saline-tolerant and strong-yet-tough FrH. This is achieved by infiltrating gel-nacre matrix into a polyaramid fabric via a multiscale reinforcement at the interface. The incorporation of strong yet geometrically compliant fabric skeleton into saline-induced shrinking gel-nacre matrix with mechanical superiority resolves the swelling mismatch between swollen hydrogel and rigid fiber, relieving the trade-off property between strength and toughness. Such integration leads to a tight interfacial binding between both components, where fabricated FrH can sustain its structure up to 5 months in artificial sea water yet exhibit superior toughyet-strong mechanical performances, i.e., ultimate fracture strength of 111.6 MPa, toughness of 383.3 MJ/m3, and fracture energy of 195.8 kJ/m2. The prototype of a bilayer petalage-like actuator that reversibly transfers from 2D to 3D structure in water and saline driving by osmotic pressure gradient was demonstrated. These inspiring results open the door for developing flexible, tough yet stable materials for applications in salty environments including soft robots, energy absorption structural materials, etc.

In this study, a high-entropy perovskite oxide Sr(Zr0.2Sn0.2Hf0.2Ti0.2Nb0.2)O-3 (SZSHTN) was first introduced to Na0.5Bi0.5TiO3 (NBT) lead-free ferroelectric ceramics to boost both the high-temperature dielectric stability and energy storage performance. Excellent comprehensive performance was simultaneously obtained in the 0.8NBT-0.2SZSHTN ceramic with high epsilon ' value (> 2000), wide epsilon '-temperature stable range (TCC < 5%, 52.4-362 degrees C), low tan delta value in a wide range (<0.01, 90-341 degrees C) and high energy storage performance (W-rec = 3.52 J/cm(3), W-rec and eta varies +/- 6.08% and +/- 7.4% from 20 to 150 degrees C), which endows it the promising potential to be used in high-temperature environments.

Objective: The beneficial effect of angiotensin(1–7) (Ang(1–7)), via the ac tivation of its receptor, MAS-1, has been noted in diabetes treatment; however, how Ang(1–7) or MAS-1 affects insulin secretion remains elusive and whether the endoge nous level of Ang(1–7) or MAS-1 is altered in diabetic individuals remains unexplored. We recently identified an important role of cystic fibrosis transmembrane conductance regu lator (CFTR), a cAMP-activated Cl− channel, in the regulation of insulin secretion. Here, we tested the possible involvement of CFTR in mediating Ang(1–7)’s effect on insulin se cretion and measured the level of Ang(1–7), MAS-1 as well as CFTR in the blood of in dividuals with or without type 2 diabetes. Methods: Ang(1–7)/MAS-1/CFTR pathway was determined by specific inhibito rs, gene manipulation, Western blotting as well as insulin ELISA in a pancreatic β-cell line, RINm5F. Human blood samples were collected from 333 individuals with (n = 197) and without (n = 136) type 2 diabetes. Ang(1–7), MAS-1 and CFTR levels in the human blood were determined by ELISA. Results: In RINm5F cells, Ang(1–7) induced intracellular cAMP increase, cAMP-response element binding protein (CREB) activation, enhanced CFTR expres sion and potentiated glucose-stimulated insulin secretion, which were abolished by a selective CFTR inhibitor, RNAi-knockdown of CFTR, or inhibition of MAS-1. In human subjects, the blood levels of MAS-1 and CFTR, but not Ang(1–7), were significantly higher in i ndividuals with type 2 diabetes as compared to those in non-diabetic healthy subjects. In addition, blood levels of MAS-1 and CFTR were in significant positive correlation in ty pe-2 diabetic but not non-diabetic subjects. Conclusion: These results suggested that MAS-1 and CFTR as key players in mediating Ang(1–7)-promoted insulin secretion in pancreatic β-cells; MAS-1 and CFTR are positively correlated and both upregulated in type 2 diabetes.