Neonatal Plasma Exosomes Contribute to Endothelial Cell-Mediated Angiogenesis and Cardiac Repair after Acute Myocardial Infarction.

Acute myocardial infarction (AMI) accompanied by cardiac remodeling still lacks effective treatment to date. Accumulated evidences suggest that exosomes from various sources play a cardioprotective and regenerative role in heart repair, but their effects and mechanisms remain intricate. Here, we found that intramyocardial delivery of plasma exosomes from neonatal mice (npEXO) could help to repair the adult heart in structure and function after AMI. In-depth proteome and single-cell transcriptome analyses suggested that npEXO ligands were majorly received by cardiac endothelial cells (ECs), and npEXO-mediated angiogenesis might serve as a pivotal reason to ameliorate the infarcted adult heart. We then innovatively constructed systematical communication networks among exosomal ligands and cardiac ECs and the final 48 ligand-receptor pairs contained 28 npEXO ligands (including the angiogenic factors, Clu and Hspg2), which mainly mediated the pro-angiogenic effect of npEXO by recognizing five cardiac EC receptors (Kdr, Scarb1, Cd36, etc.). Together, the proposed ligand-receptor network in our study might provide inspiration for rebuilding the vascular network and cardiac regeneration post-MI.

Integrated Fibrous Iontronic Pressure Sensors with High Sensitivity and Reliability for Human Plantar Pressure and Gait Analysis.

Flexible sensing systems (FSSs) designed to measure plantar pressure can deliver instantaneous feedback on human movement and posture. This feedback is crucial not only for preventing and controlling diseases associated with abnormal plantar pressures but also for optimizing athletes' postures to minimize injuries. The development of an optimal plantar pressure sensor hinges on key metrics such as a wide sensing range, high sensitivity, and long-term stability. However, the effectiveness of current flexible sensors is impeded by numerous challenges, including limitations in structural deformability, mechanical incompatibility between multifunctional layers, and instability under complex stress conditions. Addressing these limitations, we have engineered an integrated pressure sensing system with high sensitivity and reliability for human plantar pressure and gait analysis. It features a high-modulus, porous laminated ionic fiber structure with robust self-bonded interfaces, utilizing a unified polyimide material system. This system showcases a high sensitivity (156.6 kPa-1), an extensive sensing range (up to 4000 kPa), and augmented interfacial toughness and durability (over 150,000 cycles). Additionally, our FSS is capable of real-time monitoring of plantar pressure distribution across various sports activities. Leveraging deep learning, the flexible sensing system achieves a high-precision, intelligent recognition of different plantar types with a 99.8% accuracy rate. This approach provides a strategic advancement in the field of flexible pressure sensors, ensuring prolonged stability and accuracy even amidst complex pressure dynamics and providing a feasible solution for long-term gait monitoring and analysis.

Sin3a drives mesenchymal-to-epithelial transition through cooperating with Tet1 in somatic cell reprogramming.

BACKGROUND: Identifying novel regulatory factors and uncovered mechanisms of somatic cell reprogramming will be helpful for basic research and clinical application of induced pluripotent stem cells (iPSCs). Sin3a, a multifunctional transcription regulator, has been proven to be involved in the maintenance of pluripotency in embryonic stem cells (ESCs), but the role of Sin3a in somatic cell reprogramming remains unclear. METHODS: RNA interference of Sin3a during somatic cell reprogramming was realized by short hairpin RNAs. Reprogramming efficiency was evaluated by the number of alkaline phosphatase (AP)-positive colonies and Oct4-GFP-positive colonies. RNA sequencing was performed to identify the influenced biological processes after Sin3a knockdown and further confirmed by quantitative RT-PCR (qRT-PCR), western blotting and flow cytometry. The interaction between Sin3a and Tet1 was detected by coimmunoprecipitation. The enrichment of Sin3a and Tet1 at the epithelial gene promoters was measured by chromatin immunoprecipitation. Furthermore, DNA methylation patterns at the gene loci were investigated by hydroxymethylated DNA immunoprecipitation. Finally, Sin3a mutants that disrupt the interaction of Sin3a and Tet1 were also introduced to assess the importance of the Sin3a-Tet1 interaction during the mesenchymal-to-epithelial transition (MET) process. RESULTS: We found that Sin3a was gradually increased during OSKM-induced reprogramming and that knockdown of Sin3a significantly impaired MET at the early stage of reprogramming and iPSC generation. Mechanistic studies showed that Sin3a recruited Tet1 to facilitate the hydroxymethylation of epithelial gene promoters. Moreover, disrupting the interaction of Sin3a and Tet1 significantly blocked MET and iPSC generation. CONCLUSIONS: Our studies revealed that Sin3a was a novel mediator of MET during early reprogramming, where Sin3a functioned as an epigenetic coactivator, cooperating with Tet1 to activate the epithelial program and promote the initiation of somatic cell reprogramming. These findings highlight the importance of Sin3a in the MET process and deepen our understanding of the epigenetic regulatory network of early reprogramming.

Skin permeation of nickel, cobalt and chromium salts in ex vivo human skin, visualized using mass spectrometry imaging.

Skin permeation and distribution of three of the most common skin sensitizers was investigated using a previously developed animal-free exposure method combined with imaging mass spectrometry. Nickel, cobalt, and chromium (III) salts were dissolved in a buffer and exposed to human skin ex vivo, to be analyzed using time of flight secondary ion mass spectrometry (ToF-SIMS). Our findings demonstrate that metal haptens mainly accumulated in the stratum corneum, however all three metal sensitizers could also be detected in the epidermis. Cobalt and chromium (III) species penetrated into the epidermis to a larger extent than nickel species. The degree of penetration into the epidermis is suggested to be affected by the sensitization potency of the metal salts, as well as their speciation, i.e. the amount of the respective metal present in the solution as bioaccessible and solubilised ions. Our method provided permeation profiles in human skin for known sensitizers, on a level of detail that is not possible to achieve by other means. The findings show that the permeation profiles are different, despite these sensitizers being all metal ions and common causes of contact allergy. Studying skin uptake by only considering penetration through the skin might therefore not give accurate results.