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Entropy-Driven Design of Depolymerizable Polyolefins from Strained Bridged Bicyclic Monomers

Biocatalytic Production of a Key Chiral Intermediate of the HIV Capsid Inhibitor Lenacapavir

Harnessing FBXO31 with Terminal Amide-Functionalized Molecules for Targeted Protein Degradation

Architectured Mesoporous Vaterite Nanohourglasses for High-Efficiency Uranium Capture

Enzyme-Triggered Self-Immobilization of an NIR Prodrug for Tumor-Selective Cancer Vaccination

From Anisotropic Aluminum-MOF Rods to Oriented Membranes: Stepwise Coordination-Editing for Geometry-Governed Isomer Separation

Discovery and Enzymatic Regulation of Lysine Fumarylation, a Post-Translational Modification in Bacteria

Inorganic Tricarbonate: High-Pressure Synthesis and Structure of K ₂ C ₃ O ₇

Facile Synthesis of Gem-Difluoroalkene-Based <i>Bis</i> (silanes) via Copper-Catalyzed Disilylative Defluorination of 1-Chloro-1-trifluoromethylalkenes

Machine-Learning-Guided Discovery of CH ₄ Combustion Catalysts Operating in the Presence of SO ₂

Reactive Hydrogen-Driven Dehydroxylation of Hydroxyapatite Enables Anti-Ostwald Ripening of Ag Nanoparticles for Ethanol Valorization to Aromatics

Conformational Switching Controls Biradical Spin Dynamics in Flavin–Tryptophan Dyads

A Versatile Strategy for Head-to-Tail Macrocyclization and Traceless Backbone Editing of Short Peptides

Bifunctional Lipid–Protein Cross-linking Efficiency and Reaction Products

Spatially Quantitative Profiling of Defect Density for Hydrogen-Induced Passivation Mechanism of Metal–Insulator–Semiconductor Photoanodes

Endothelial <i>Adgrl2</i> Expression and Alternative Splicing Controls the Cerebrovasculature

Central nervous system development requires parallel but interrelated processes of neural circuit assembly and vascularization. Intersecting between these two processes is the cell-adhesion G-protein coupled receptor Adgrl2. In select neuronal populations, Adgrl2 is localized and control the assembly of specific synaptic sites. In non-neuronal brain cells, Adgrl2 is restricted in expression to endothelial cells. Testing for Adgrl2 function in these cells in mice (of either sex), here we find that endothelial cell-specific Adgrl2 deletion results in an impairment in cerebrovascular integrity. To understand how it might be possible for Adgrl 2 to function independently in neuronal and endothelial contexts, we surveyed Adgrl2 transcripts within these cell classes. By analyzing single-cell RNA sequencing datasets, we find that Adgrl2 mRNA is subject to robust cell type-specific alternative splicing that results in distinct isoforms being produced in neurons compared with endothelial cells. To probe the functional significance of this alternative splicing, we forced expression of the neuronal isoform of Adgrl2 in endothelial cells. This resulted in altered cerebrovascular properties including the formation of ectopic glutamatergic synaptic contacts onto endothelial cells, indicating alterations in the cell–cell recognition process. Functionally, in direct contrast to endothelial Adgrl2 deletion, this genetic expression switch instead enhances blood–brain barrier integrity. This overly restrictive cerebrovascular function results in dysregulation of blood to cerebrospinal fluid homeostasis, enlargement of brain ventricles, and a higher risk of hydrocephalus. Thus, alternative splicing serves as a cell type-specific mechanism that provides isoform-specific Adgrl2 for discerning functions controlling neural circuit assembly and cerebrovascular homeostasis.

Pyridine to Pyridazine Skeletal Editing via CN-to-NN Atom-Pair Swap

Mild Neonatal Hypoxia Targets Synaptic Maturation, Disrupts Adult Hippocampal Learning and Memory, and Is Associated with CK2-Mediated Loss of Synaptic Calcium-Activated Potassium Channel KCNN2 Activity

Preterm infants frequently sustain brief hypoxic insults of unclear clinical significance. Since preterm survivors commonly sustain lifelong memory impairment without apparent gray matter injury, we tested whether mild hypoxia alone without ischemia could persistently disrupt adult hippocampal learning and memory mechanisms without causing brain injury. We developed a neonatal mouse model of mild hypoxia that generated clinically relevant oxygen desaturation, but without responses typically associated with hypoxia-ischemia including bradycardia, seizures, neuroinflammation, and neuronal or glial degeneration. RNA transcriptomic studies identified that expression of immature hippocampal synaptic components was broadly targeted by mild hypoxia. Neonatal hypoxia resulted in hippocampal learning and memory deficits and abnormal maturation of CA1 (cornu ammonis 1) neurons that persisted into adulthood. Memory deficits were accompanied by reduced adult hippocampal CA3→CA1 synaptic strength and LTP and abolished synaptic activity of calcium-sensitive SK2 (small conductance Ca 2 + -activated potassium) channels, a regulator of spike timing-dependent neuroplasticity, including LTP and memory encoding. Structural illumination microscopy revealed reduced synaptic density without altered synaptic SK2 distribution. Persistent loss of SK2 activity was mediated by increased CK2 phosphorylation of synaptic calmodulin and restored by CK2 blockade. Clinically relevant mild hypoxia in neonatal mice is thus sufficient to disrupt hippocampal maturation into adulthood independently of cerebral gray or white matter injury and trigger persistent loss of synaptic SK2 channel activity that disrupts excitatory synaptic function. Our findings suggest that neonatal hypoxia contributes to the broad spectrum of neurobehavioral, cognitive, and learning disabilities that paradoxically persist into adulthood without overt gray matter injury in preterm survivors.

Repurposing Dexmedetomidine: Early Pharmacological Hypothermia Enhances Neuroprotection and Improves Locomotor and Bladder Functional Recovery after Spinal Cord Injury

Spinal cord injury (SCI) causes progressive secondary damage, yet translation of hypothermia, one of the few preclinical neuroprotectants, has been limited by slow, equipment-dependent cooling that rarely meets the therapeutic window. We tested whether repurposing dexmedetomidine (Dex), an FDA-approved α 2 -agonist that blocks shivering and has intrinsic neuroprotection, could provide early pharmacological hypothermia to enhance recovery after SCI. Adult mice received moderate thoracic contusive SCI followed by intraperitoneal Dex (100 µg/kg) at 1 h postinjury. Core temperature, vital signs, and ECG were monitored for 24 h. Locomotor recovery, bladder function, tissue preservation, neuronal and axonal sparing, serotonergic circuitry, raphe activation, cytokine profiles, and ERK and RIPK1 signaling were assessed. Comparator groups included untreated injury, conventional surface cooling, hypothermia-prevention by heating, and ERK inhibition. At ambient room temperature (∼24°C), Dex induced rapid, stable moderate hypothermia (∼29–32°C for ∼16 h) without respiratory compromise or arrhythmia. This pharmacological hypothermia, combined with Dex's intrinsic actions, produced greater locomotor and bladder recovery than untreated injury or conventional cooling. Dex preserved perilesional tissue, neuronal survival, axonal integrity, and descending serotonergic input while restoring raphe activation. Mechanistically, Dex plus hypothermia synergistically suppressed acute proinflammatory cytokines, increased IL-10 at Days 7 and 14, activated early ERK-dependent survival signaling, and reduced acute RIPK1-associated injury; blocking hypothermia or ERK signaling attenuated these benefits. The neuroprotective effects of Dex were similar in both sexes. A single clinically relevant Dex dose provides dual-action therapy—pharmacological hypothermia plus intrinsic neuroprotection—offering an immediately translatable, equipment-free strategy for acute SCI and other neurotrauma.

Polydopamine Nanocages Orchestrate Multi-Site Networks on the Ni ₄ Mo Electrocatalyst for Efficient and Ultrastable Hydrogen Evolution