AD16 attenuates neuroinflammation induced by cerebral ischemia through down-regulating astrocytes A1 polarization.

A1 polarization of astrocytes mediated prolonged inflammation contributing to brain injury in ischemic stroke. We have previously shown that AD16 protects against neonatal hypoxic-ischemic brain damage in vivo and oxygen-glucose deprivation in vitro. More recently, AD16 has demonstrated safety, tolerability, and favorable pharmacokinetics in a randomized controlled phase I trial. In this study, we utilized a rat model of transient middle cerebral artery occlusion (tMCAO) to explore whether the anti-inflammatory compound AD16 protects against ischemic brain injury by regulating A1 polarization and its underlying mechanisms. Our results showed that AD16 treatment significantly reduced the brain infarcted volume and improved neurological function in tMCAO rats. GO analysis results show that differential genes among the Sham, tMCAO and AD16 treatment groups are involved in the regulation of cytokine and inflammatory response. KEGG enrichment pathways analysis mainly enriched in cytokine-cytokine receptor interaction, viral protein interaction with cytokine-cytokine receptor, TNF, chemokine, NF-κB and IL-17 signaling pathway. Furthermore, AD16 treatment decreased the permeability of the blood-brain barrier and suppressed neuroinflammation. AD16 treatment also significantly reduced the polarization of A1 and inhibited NF-κB and JAK2/STAT3 signaling pathways. This study demonstrates that AD16 protects against brain injury in ischemic stroke by reducing A1 polarization to suppress neuroinflammation through downregulating NF-κB and JAK2/STAT3 signaling. Our findings uncover a potential molecular mechanism for AD16 and suggest that AD16 holds promising therapeutic potential against cerebral ischemia.

An antiferromagnetic spin phase change memory.

The electrical outputs of single-layer antiferromagnetic memory devices relying on the anisotropic magnetoresistance effect are typically rather small at room temperature. Here we report a new type of antiferromagnetic memory based on the spin phase change in a Mn-Ir binary intermetallic thin film at a composition within the phase boundary between its collinear and noncollinear phases. Via a small piezoelectric strain, the spin structure of this composition-boundary metal is reversibly interconverted, leading to a large nonvolatile room-temperature resistance modulation that is two orders of magnitude greater than the anisotropic magnetoresistance effect for a metal, mimicking the well-established phase change memory from a quantum spin degree of freedom. In addition, this antiferromagnetic spin phase change memory exhibits remarkable time and temperature stabilities, and is robust in a magnetic field high up to 60 T.

Emerging Antiferromagnets for Spintronics.

Antiferromagnets constitute promising contender materials for next-generation spintronic devices with superior stability, scalability, and dynamics. Nevertheless, the perception of well-established ferromagnetic spintronics underpinned by spontaneous magnetization seemed to indicate the inadequacy of antiferromagnets for spintronics-their compensated magnetization has been perceived to result in uncontrollable antiferromagnetic order and subtle magnetoelectronic responses. However, remarkable advancements have been achieved in antiferromagnetic spintronics in recent years, with consecutive unanticipated discoveries substantiating the feasibility of antiferromagnet-centered spintronic devices. It is emphasized that, distinct from ferromagnets, the richness in complex antiferromagnetic crystal structures is the unique and essential virtue of antiferromagnets that can open up their endless possibilities of novel phenomena and functionality for spintronics. In this Perspective, the recent progress in antiferromagnetic spintronics is reviewed, with a particular focus on that based on several kinds of antiferromagnets with special antiferromagnetic crystal structures. The latest developments in efficiently manipulating antiferromagnetic order, exploring novel antiferromagnetic physical responses, and demonstrating prototype antiferromagnetic spintronic devices are discussed. An outlook on future research directions is also provided. It is hoped that this Perspective can serve as guidance for readers who are interested in this field and encourage unprecedented studies on antiferromagnetic spintronic materials, phenomena, and devices.

Magnetic-Field Response and Giant Electric-Field Modulation of Cu2S.

Cu2S likely plays an important role in the sharp resistivity transition of LK-99. Nevertheless, this immediately arouses an intriguing question of whether the extraordinary room-temperature colossal magnetoresistance in the initial reports, which has been less focused, originates from Cu2S as well. To resolve this issue, we have systematically investigated the electrical transport and magnetotransport properties of near-stoichiometric Cu2S pellets and thin films. Neither Cu2S nor LK-99 containing Cu2S in this study was found to exhibit the remarkable magnetoresistance effect implied by Lee et al. This implies that Cu2S could not account for all of the intriguing transport properties of the initially reported LK-99, and the initially reported LK-99 samples might contain magnetic impurities. Moreover, based on the crystal-structure-sensitive electrical properties of Cu2S, we have constructed a piezoelectric-strain-controlled device and obtained a giant and reversible resistance modulation of 2 orders of magnitude at room temperature, yielding a huge gauge factor of 160,000.