The ongoing spread of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused hundreds of millions of cases and millions of victims worldwide with serious consequences to global health and economies. Although many vaccines protecting against SARS-CoV-2 are currently available, constantly emerging new variants necessitate the development of alternative strategies for prevention and treatment of COVID-19. Inhibitors that target the main protease (M^pro) of SARS-CoV-2, an essential enzyme that promotes viral maturation, represent a key class of antivirals. Here, we showed that a peptidomimetic compound with benzothiazolyl ketone as warhead, YH-53, is an effective inhibitor of SARS-CoV-2, SARS-CoV, and MERS-CoV M^pros. Crystal structures of M^pros from SARS-CoV-2, SARS-CoV, and MERS-CoV bound to the inhibitor YH-53 revealed a unique ligand-binding site, which provides new insights into the mechanism of inhibition of viral replication. A detailed analysis of these crystal structures defined the key molecular determinants required for inhibition and illustrate the binding mode of M^pros from other coronaviruses. In consideration of the important role of M^pro in developing antivirals against coronaviruses, insights derived from this study should add to the design of pan-coronaviral M^pro inhibitors that are safer and more effective.

Spinal cord injury (SCI) is exacerbated by the formation of an acidic microenvironment and extensive neuronal loss, both of which contribute to poor functional recovery. To address this, we developed lysine-polydopamine nanoparticles (Lys-PDA) as a multifunctional therapeutic platform for SCI. Lysine, a naturally occurring amino acid, possesses weak alkalinity and neuroprotective properties, but suffers from poor in vivo stability and non-specific distribution. Polydopamine (PDA), a biocompatible polymer with inherent antioxidant and anti-inflammatory capabilities, was employed as a nanocarrier to enhance lysine delivery and local retention. In vitro and in vivo assessments confirmed that Lys-PDA exhibit excellent biocompatibility and enable sustained release of lysine for up to three days. Upon administration into SCI mice, Lys-PDA significantly neutralized the acidic lesion milieu, with pH values increasing by approximately 0.33 units-approaching levels observed in uninjured spinal tissue. After 28 days of treatment, Lys-PDA markedly reduced neuronal apoptosis, suppressed reactive oxygen species (ROS) and lactate accumulation, and significantly improved hindlimb motor function. Behavioral analyses demonstrated a substantial increase in Basso Mouse Scale (BMS) scores from 0.0 to 5.8, alongside a corresponding increase in hindlimb stride length from 2.0 cm to 4.3 cm. Collectively, these findings suggest that Lys-PDA not only modulate the hostile post-injury microenvironment but also promote neuroprotection and functional recovery, positioning them as a promising candidate for SCI repair.

Mitochondria are self-replicating organelles with their own DNA. They play a crucial role in biological, cellular and functional processes, such as energy production, metabolism, and signal transduction. Abnormal mitochondrial function can cause various diseases such as diabetes, tumour, Parkinson's disease, hereditary optic neuropathy, and others. Although mitochondrial functions have been extensively and widely explored, studies on mitochondrial inheritance have been limited. Mitochondrial inheritance is traditionally thought to be maternal although small amounts of paternally transmitted mitochondria have been discovered on rare occasions, and the role of paternal mitochondria transmission to offspring has been largely ignored. This review highlights the present knowledge on mitochondrial inheritance, especially the controversy and the difficulties in investigating paternal mitochondrial inheritance. More significantly, we present a comprehensive description of the physiological functions of paternal mitochondria in children and discuss the animal model to explore the mechanism of paternal mitochondrial inheritance. This review may provide a theoretical and experimental basis for improving our understanding of paternal mitochondrial inheritance, and also provide new ideas for treating mitochondrial diseases.

Spinal cord injury (SCI) represents a devastating central nervous system trauma that results in the loss of sensory and motor function. Due to its complex pathological mechanisms and the unsatisfactory therapeutic effects of surgery, medication, and rehabilitation methods currently used in clinical practice, the treatment of this disease still faces enormous challenges. Over the past few decades, researchers have been committed to identify a reliable and potent therapeutic strategy for SCI, and the nano-delivery system has been proven to be more effective. The nanoparticles exhibit favorable controllable release characteristics and targeting ability toward spinal cord tissue, which may overcome the limitations of conventional drug delivery methods and confer exceptional therapeutic efficacy upon the nano-delivery system through sophisticated design, assembly, and surface modification. This review outlines a multimodal treatment strategy and the current application status based on nanoparticles for repairing SCI, with special emphasis on their application prospects, characteristics, and limitations. The discussion delves into the efforts and challenges involved in applying nanoparticle drug delivery technology for clinical SCI repair.