Correlates of pre-exposure prophylaxis amongst transgender women of color taking gender-affirming hormone therapy: Findings from the TURNNT cohort study.

Globally, neurological diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), traumatic brain injury (TBI), intracerebral hemorrhage (ICH), spinal cord injury (SCI) and ischemic stroke (IS) have become the main contributors to mortality, disability, and disability-adjusted life years (DALYs). These conditions have brought a heavy burden to public health . A recent assessment of brain health and the burden of neurological diseases by the Global Burden of Disease Study shows that neurological diseases have cumulatively affected as many as 3.4 billion people in the world—accounting for 43% of the world's population—a figure that continues to climb with the aging of the global population. Among these diseases, the annual economic burden of specific diseases such as dementia alone is close to or more than a trillion dollars . In addition, in the past two or three decades, the failure rate of phase II/III clinical trials of central nervous system (CNS) drugs for neurodegenerative diseases such as AD has been high. Effective interventions that can truly prevent or significantly change the course of these diseases are still extremely limited . Fundamentally, these seemingly heterogeneous diseases share a self-amplifying pathological loop—oxidative damage and oxidative stress–inflammatory interactions driven by excessive reactive oxygen species (ROS); when the central nervous system encounters trauma, ischemia, hemorrhage, or when misfolded proteins accumulate, damaged neurons and axons quickly release high-mobility group box 1, adenosine triphosphate (ATP), heat shock proteins and other damage-associated molecular patterns (DAMPs). This activates microglia and astrocytes, whereby pro-inflammatory cytokines (, IL-1β, TNF-α, and IL-18) and ROS amplify the NLRP3 inflammasome signaling through positive feedback loops. This inflammatory cascade further induces the deposition of toxic proteins such as amyloid-β (Aβ), α-synuclein (α-syn) and myelin debris to form a closed loop of "inflammation–oxidation–protein". This leads to loss of synaptic plasticity, axonal transport disruption and neuronal death, eventually manifesting as irreversible functional defects, including memory loss, cognitive decline and motor disorders , . However, at present, most drugs and biotherapies target a single pathway or mechanism, and it is difficult to simultaneously cross the blood–brain barrier (BBB) and the blood–spinal cord barrier (BSCB), continuously scavenge ROS, and remodel the pathological lesion microenvironment. Although endogenous antioxidant enzymes are the main defense against oxidative stress, their clinical translation for CNS applications as an exogenous therapeutic agent is subject to many restrictions, such as poor barrier penetration ability, short half-life in the body, susceptibility to proteolytic degradation and high preparation and storage costs , . This prompts the scientific community to seek functional alternatives. Since Gao first reported in 2007 that iron oxide (FeO) nanoparticles have inherent peroxidase (POD) activity and formally proposed the new concept of "nanozymes" , this emerging interdisciplinary field has rapidly developed. A broad range of nanomaterials—including precious metals, metal oxides, carbon-based materials and metal-organic frameworks (MOFs)—have been reported to mimic the activity of one or more antioxidant enzymes . Compared with natural enzymes, these materials have shown significant advantages in terms of stability, tunability, cost-effectiveness, and multifunctional integration, making them strong candidates for the next generation of "artificial enzymes" with great application potential. With the advantages of long-lasting catalytic activity, excellent ROS-regulatory capacity and high stability in the physiological environment, nanozymes have been proven to have application value in many fields such as biosensing, antibacterial applications, acute kidney/lung injury treatment and tumor treatment . Among them, antioxidant nanozymes can dismutate superoxide anions (O), decompose hydrogen peroxide (HO), and attenuate highly reactive species such as hydroxyl radicals (OH) and peroxynitrite (ONOO) through cascade redox reactions thus alleviating cell oxidative stress . In the past decade, this strategy has been rapidly extended to various rodent of SCI, IS, TBI, and PD. Relying on their multienzyme cascade catalysis mechanism, surface modification and targeted delivery ability, a variety of nanozymes pass through or bypass the BBB/BSCB to achieve lesion-specific accumulation, where they exert neuroprotective and repair-promoting effects by scavenging ROS, inhibiting neuroinflammation, suppressing glial scar formation, and promoting neurovascular remodeling and axonal regeneration, thus providing a new material-biological intervention model for the treatment of CNS disorders .