TAIJI Small Animal Anesthesia Solutions

There is an urgent need for vaccines against coronavirus disease 2019 (COVID-19) because of the ongoing SARS-CoV-2 pandemic. Among all approaches, a messenger RNA (mRNA)-based vaccine has emerged as a rapid and versatile platform to quickly respond to this challenge. Here, we developed a lipid nanoparticle-encapsulated mRNA (mRNA-LNP) encoding the receptor binding domain (RBD) of SARS-CoV-2 as a vaccine candidate (called ARCoV). Intramuscular immunization of ARCoV mRNA-LNP elicited robust neutralizing antibodies against SARS-CoV-2 as well as a Th1-biased cellular response in mice and non-human primates. Two doses of ARCoV immunization in mice conferred complete protection against the challenge of a SARS-CoV-2 mouse-adapted strain. Additionally, ARCoV is manufactured as a liquid formulation and can be stored at room temperature for at least 1 week. ARCoV is currently being evaluated in phase 1 clinical trials.

Functional bioelectronic implants require energy storage units as power sources. Current energy storage implants face challenges of balancing factors including high-performance, biocompatibility, conformal adhesion, and mechanical compatibility with soft tissues. An all-hydrogel micro-supercapacitor is presented that is lightweight, thin, stretchable, and wet-adhesive with a high areal capacitance (45.62 F g-1) and energy density (333 μWh cm-2, 4.68 Wh kg-1). The all-hydrogel micro-supercapacitor is composed of polyaniline@reduced graphene oxide/Mxenes gel electrodes and a hydrogel electrolyte, with its interfaces robustly crosslinked, contributing to efficient and stable electrochemical performance. The in vitro and in vivo biocompatibility of the all-hydrogel micro-supercapacitor is evaluated by cardiomyocytes and mice models. The latter is systematically conducted by performing histological, immunostaining, and immunofluorescence analysis after adhering the all-hydrogel micro-supercapacitor implants onto hearts of mice for two weeks. These investigations offer promising energy storage modules for bioelectronics and shed light on future bio-integration of electronic systems.

The young circulatory milieu capable of delaying aging in individual tissues is of interest as rejuvenation strategies, but how it achieves cellular- and systemic-level effects has remained unclear. Here, we constructed a single-cell transcriptomic atlas across aged tissues/organs and their rejuvenation in heterochronic parabiosis (HP), a classical model to study systemic aging. In general, HP rejuvenated adult stem cells and their niches across tissues. In particular, we identified hematopoietic stem and progenitor cells (HSPCs) as one of the most responsive cell types to young blood exposure, from which a continuum of cell state changes across the hematopoietic and immune system emanated, through the restoration of a youthful transcriptional regulatory program and cytokine-mediated cell-cell communications in HSPCs. Moreover, the reintroduction of the identified rejuvenating factors alleviated age-associated lymphopoiesis decline. Overall, we provide comprehensive frameworks to explore aging and rejuvenating trajectories at single-cell resolution and revealed cellular and molecular programs that instruct systemic revitalization by blood-borne factors.

Peripheral nerve injuries represent one of the most common causes of permanent disabilities. Therapeutic electrical stimulation has been widely used in neural regeneration for decades. Combined with the implantation of a nerve cuff, several outcomes have proven effectiveness and feasibility in neuroprosthetic applications. However, the current electrical stimulation strategy fails to complete nerve repair. There is a lack of research on long-term implantable nanogenerators in the neurostimulation scenario. Especially considering many disease models, those devices may not reach the in vitro simulative working setting. Thus, an implanted sciatic nerve stimulation system that spontaneously generates biphasic electric pulses in response to rats’ movement is developed. The electric signals generated by this device could stimulate injured sciatic nerve by cuff electrode. This work introduces an implantable self-regulated neural electrical stimulation system generated by a contact separation triboelectric nanogenerator with a nerve cuff electrode and compares it with chronic therapeutic electrical stimulation for sciatic nerve restoration effect. Neural function restoration is observed in gait and histological analysis. Moreover, the upregulation of growth associated protein 43 can be a protentional target. This could have potential clinical application in facilitating closed-loop energy harvesting for long-term electrical stimulation. This work introduces an implantable self-regulated neural electrical stimulation system generated by a contact separation triboelectric nanogenerator with a nerve cuff electrode and compares it with chronic therapeutic electrical stimulation for sciatic nerve restoration.

Ischemic stroke can cause secondary myelin damage in the white matter distal to the primary injury site. The contribution of astrocytes during secondary demyelination and the underlying mechanisms are unclear. Here, using a mouse of distal middle cerebral artery occlusion, we show that lipocalin-2 (LCN2), enriched in reactive astrocytes, expression increases in nonischemic areas of the corpus callosum upon injury. LCN2-expressing astrocytes acquire a phagocytic phenotype and are able to uptake myelin. Myelin removal is impaired in Lcn2^−/− astrocytes. Inducing re-expression of truncated LCN2(Δ2–20) in astrocytes restores phagocytosis and leads to progressive demyelination in Lcn2^−/− mice. Co-immunoprecipitation experiments show that LCN2 binds to low-density lipoprotein receptor-related protein 1 (LRP1) in astrocytes. Knockdown of Lrp1 reduces LCN2-induced myelin engulfment by astrocytes and reduces demyelination. Altogether, our findings suggest that LCN2/LRP1 regulates astrocyte-mediated myelin phagocytosis in a mouse model of ischemic stroke.