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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. 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. [Display omitted] [ABSTRACT FROM AUTHOR]

• UPLC-Q-TOF-MS and R software were used to identify YSH absorbable chemicals and predict its treatment mechanism. • The efficacy of YSH in alleviating chronic liver injury was studied for the first time. • YSH absorbable chemicals treat chronic liver injury by regulating AKT phosphorylation. Chronic liver injury (CLI) is a complex condition that requires effective therapeutic interventions. The Yi-Shan-Hong (YSH) formula is an empirically derived remedy that has shown effectiveness and safety in the management of chronic liver damage. However, the bioactive components and multifaceted mechanisms of YSH remain inadequately understood. To examine the bioactive compounds and functional processes that contribute to the therapeutic benefits of YSH against CLI. Serum pharmacochemistry and network pharmacology were employed to identify active compounds and possible targets of YSH in CLI. In addition, YSH was also given in three doses to d -(+)-galactosamine hydrochloride (D -GalN) -induced CLI rats to test its therapeutic efficacy. The analysis of serum samples successfully detected 25 compounds from YSH. Searches on the databases resulted in 277 genes as being correlated with chemicals in YSH, and 397 genes associated with CLI. In vivo experiments revealed that YSH displayed a notable therapeutic impact on liver injury caused by d -GalN. This was evidenced by enhanced liver function and histopathological improvements, reduced oxidative stress response, proinflammatory factors, and fibrosis levels. Importantly, no discernible adverse effects were observed. Furthermore, the administration of YSH treatment reversed the activation of AKT phosphorylation caused by d -GalN, aligning with the findings of the network pharmacology study. These findings provide preclinical evidence of YSH's therapeutic value in CLI and highlight its hepatoprotective action via the PI3K/AKT signaling pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Gamma-aminobutyric acid (GABA), a non-protein-producing amino acid synthesized from the excitatory amino acid glutamate via the enzyme glutamic acid decarboxylase, is extensively found in microorganisms, plants and vertebrates, and is abundantly expressed in the spinal cord and brain. It is the major inhibitory neurotransmitter in the mammalian nervous system. GABA plays crucial roles in the regulation of synaptic transmission, the promotion of neuronal development and relaxation, and the prevention of insomnia and depression. As the major inhibitory neurotransmitter, GABA plays pivotal roles in the regulation of pain sensation, which is initiated by the activation of peripheral nociceptors and transmitted to the spinal cord and brain along nerves. GABA exerts these roles by directly acting on three types of receptors: ionotropic GABA A and GABA C receptors and G protein-coupled GABA B receptor. The chloride-permeable ion channel receptors GABA A and GABA C mediate fast neurotransmission, while the metabotropic GABA B receptor mediates slow effect. Different GABA receptors regulate pain sensation via different signaling pathways. Here we highlight recent updates on the involvement of specific GABA receptors and their subtypes in the process of pain sensation. Further understanding of different GABA receptors and signaling pathways in pain sensation will benefit the development of novel analgesics for pain management by targeting specific GABA receptor subtypes and signaling pathways. [Display omitted] • GABA regulates synaptic transmission contributing to pain sensation. • GABA A receptor regulates membrane potential depending on transmembrane chloride gradient. • GABA A receptor-mediated analgesic effects rely on subunits compositions. • GABA B receptor modulates pain transmission. [ABSTRACT FROM AUTHOR]

The applications of dielectric capacitors are essential for modern pulsed-power and high-power electronic devices. Antiferroelectric ceramics have garnered much attention as promising materials for capacitive energy storage on account of their ultrahigh recoverable energy density (W rec). However, the relatively high energy loss originating from electric field induced antiferroelectric-ferroelectric (AFE-FE) phase transition results in low energy storage efficiency (η). Herein, the La3+ ions incorporated (Pb 0.98 Sr 0.02)(Zr 0.85 Sn 0.15)O 3 antiferroelectric ceramics were explored to obtain stable antiferroelectric phase and trigger a unique multistage AFE-FE(Ⅰ)-FE(Ⅱ) phase transition simultaneously. Consequently, this strategy led to the achievement of an ultrahigh W rec of 13.9 J/cm3 and an enhanced η of 80.4% in the optimal composition. Notably, these ceramics have also demonstrated exceptional thermal reliability of W rec and η in a wide temperature range, outperforming other previously reported PbZrO 3 -based ceramics. These results offer an efficient approach to promote the capacitive energy storage behavior in antiferroelectric ceramics. [ABSTRACT FROM AUTHOR]

A novel poly(aspartic acid) based PASP-l-PAHy hydrogel possesses the comprehensive merits of injectability, self-biodegradability, shape-adaptability, transparence, biocompatibility, and adhesion is reported. The hydrogel could seamlessly fill and stably adhere to skin incisions, and accelerate wound healing process. [Display omitted] • Designing and developing a novel versatile poly(aspartic acid) hydrogel. • The multiple crosslinks of chemical bonds (amide bond) and physical bonds (ionic bond and hydrogen bond) endows the hydrogel with comprehensive merits. • Desired autolytic biodegradation ensures removal trauma of wound dressing after 10 days. • The poly(aspartic acid) based hydrogel accelerates rat skin full-thickness wound healing. 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. [ABSTRACT FROM AUTHOR]