No abstract

Extracellular vesicles (EVs) have emerged as potential mediators of intercellular communication. EVs are nano-sized, lipid membrane–bound vesicles that contains biological information in the form of proteins, metabolites and/or nucleic acids. EVs are key regulators of tissue repair mechanisms, such as in the context of lung injuries. Recent studies suggest that EVs have the ability to repair COVID19-associated acute lung damage. EVs hold great promise for therapeutic treatments, particularly in treating a potentially fatal autoimmune response and attenuate inflammation. They are known to boost lung immunity and are involved in the pathogenesis of various lung diseases, including viral infection. EV-based immunization technology has been proven to elicit robust immune responses in many models of infectious disease, including COVID-19. The field of EV research has tremendous potential in advancing our understanding about viral infection pathogenesis, and can be translated into anti-viral therapeutic strategies.

Microbubbles are nanosized gas-filled bubbles. They are used in clinical diagnostics, in medical imaging, as contrast agents in ultrasound imaging, and as transporters for targeted drug delivery. They can also be used to treat thrombosis, neoplastic diseases, open arteries and vascular plaques and for localized transport of chemotherapies in cancer patients. Microbubbles can be filled with any type of therapeutics, cure agents, growth factors, extracellular vesicles, exosomes, miRNAs, and drugs. Microbubbles protect their cargo from immune attack because of their specialized encapsulated shell composed of lipid and protein. Filled with curative medicine, they could effectively circulate through the whole body safely and efficiently to reach the target area. The advanced bubble-based drug-delivery system, integrated with artificial intelligence for guidance, holds great promise for the targeted delivery of drugs and medicines.

Tumor-specific CD8 T cells (TST) found in patients with cancer are unable to halt cancer progression. TST are dysfunctional and cannot produce effector cytokines or kill target cells 1 . TST dysfunction, also known as exhaustion, has been thought to be driven by chronic T cell receptor (TCR)/antigen stimulation over days to weeks, encoded by exhaustion/dysfunction-associated epigenetic and transcriptional programs 1,2 . However, we know little about (i) the interplay between CD8 T cell function and epigenetics during the initial hours after activation in both functional (acute infection) or dysfunctional contexts (tumors) or (ii) the kinetics of CD8 T cell effector or dysfunction differentiation and relationship to cell division. Nevertheless, is it widely thought that T cell effector differentiation requires cell division 3 . Here we tracked differentiation of naive antigen-specific CD8 T cells by cell division within the first hours (0-60 hours) after antigen activation in tumor-bearing hosts, comparing to T cells undergoing functional effector differentiation during acute infection (E). Surprisingly, while TST and E exhibited the same rapid activation and cell division kinetics, TST failed to acquire effector function and implemented exhaustion-associated chromatin features. Notably, epigenetic encoding of TST dysfunction began within 6 hours of antigen encounter, even prior to cell division. These findings not only challenge the paradigm that chronic T cell receptor stimulation drives dysfunction/exhaustion in tumors, but also refute for CD8 T cells the prevailing notion that cell division is required to initiate epigenetic remodeling and differentiation [3][4][5][6][7] .Interestingly, while T cell dysfunctional fate decisions are made within hours of antigen encounter, continued TCR stimulation and epigenetic remodeling progressively stabilize, or "imprint" the dysfunctional state. Our study defines for the first time the regulation and kinetics driving the rapid divergence of T cell fate choice prior to cell division in the context of tumors versus infection.

The CD9 is transmembrane protein that plays a critical role in many cellular processes including aging associated cardiac pathologies. The heart function declines in the aged population. Ageing is strongly associated with many age-related conditions such as increased risk of heart failure. If aging can be prevented slowed down or even reversed, heart failure and other signs of aging could be controlled or even cured. It is unknown whether CD9 is cardioprotective. The objective of this study is to investigate whether a decline CD9 levels contributes to aging-related heart failure. Our data shows that CD9-deficient aged mice develop cardiac abnormalities and pathological cardiac hypertrophy, Cardioprotection by CD9 in old mice is followed by the downregulation of SIRT6 in the heart, and CD9 overexpressed exosomes ameliorates cardiac pathologies in treated mice and improves their long-term survival. Additionally, the serum level of CD9 decreased significantly in aged mice. CD9 overexpressed exosomes are cardioprotective and improve cardiac function in aged mice. These exosomes mediate their paracrine effects by attenuating, blood pressure, heart beat, reactive oxygen species and fibrosis. Remarkably, CD9 overexpression reversed fibrosis associated brain natriuretic peptide (BNP), Sirt6, and galectin 3 (Gal-3). These results provide a new perspective on the pathogenesis of cardiomyopathies and open new avenues for treatment of the disease.