Supported ordered intermetallic compounds exhibit superior catalytic performance over their disordered alloy counterparts in diverse reactions. But the synthesis of intermetallic compounds catalysts often requires high-temperature annealing that leads to the sintering of metals into larger crystallites. Herein, we report a small molecule-assisted impregnation approach to realize the general synthesis of a family of intermetallic catalysts, consisting of 18 binary platinum intermetallic compounds supported on carbon blacks. The molecular additives containing heteroatoms (that is, O, N, or S) can be coordinated with platinum in impregnation and thermally converted into heteroatom-doped graphene layers in high-temperature annealing, which significantly suppress alloy sintering and insure the formation of small-sized intermetallic catalysts. The prepared optimal PtCo intermetallics as cathodic oxygen-reduction catalysts exhibit a high mass activity of 1.08 A mg_Pt^–1 at 0.9 V in H₂-O₂ fuel cells and a rated power density of 1.17 W cm^–2 in H₂-air fuel cells.

Cognitive disorders and psychiatric pathologies, particularly Alzheimer’s disease (AD) and Major depressive disorder (MDD), represent a considerable health burden, impacting millions of people in the United States and worldwide. Notably, comorbidities of MDD and anxiety are prevalent in the early stages of mild cognitive impairment (MCI), which is the preceding phase of Alzheimer’s disease and related dementia (ADRD). The symptoms of MDD and anxiety affect up to 80% of individuals in the advanced stages of the neurodegenerative conditions. Despite overlapping clinical manifestations, the pathogenesis of AD/ADRD and MDD remains inadequately elucidated. Until now, dozens of drugs for treating AD/ADRD have failed in clinical trials because they have not proven beneficial in reversing or preventing the progression of these neuropsychiatric indications. This underscores the need to identify new drug targets that could reverse neuropsychiatric symptoms and delay the progress of AD/ADRD. In this context, phosphodiesterase 4 (PDE4) arises as a primary enzyme in the modulation of cognition and mood disorders, particularly through its enzymatic action on cyclic adenosine monophosphate (cAMP) and its downstream anti-inflammatory pathways. Despite the considerable cognitive and antidepressant potential of PDE4 inhibitors, their translation into clinical practice is hampered by profound side effects. Recent studies have focused on the effects of PDE4 and its subtype-selective isoform inhibitors, aiming to delineate their precise mechanistic contributions to neuropsychiatric symptoms with greater specificity. This review aims to analyze the current advances regarding PDE4 inhibition—specifically the selective targeting of its isoforms and elucidate the therapeutic implications of enhanced cAMP signaling and the consequent anti-inflammatory responses in ameliorating the symptomatology associated with AD and ADRD.

Cognitive impairment is a defining feature of neurodegenerative diseases such as Alzheimer's disease (AD) and vascular dementia (VaD). However, the pathogenesis of cognitive impairment remains unclear, mainly because it involves complex pathological processes in which multiple cytokines and pathways contribute to its progression. Among key molecular regulators, cyclic nucleotide phosphodiesterase 1 (PDE1), a Calcium/calmodulin (Ca²⁺/CaM) activated enzyme that regulates intracellular levels of cAMP and cGMP by degrading them to inactive forms. PDE1 may play a critical role in influencing cognitive function through modulating these second messengers. PDE1 integrates calcium fluctuations with cyclic nucleotide metabolism, affecting a series of events including synaptic plasticity, neuronal survival, vascular tone, and neuroinflammatory responses. This review summarizes the distribution of PDE1 and its isoforms, and their regulatory mechanisms and functional roles, particularly those of PDE1A, PDE1B, and PDE1C, in the central nervous system (CNS) disorders. We also discussed the involvement of PDE1 in modulating cAMP/PKA and cGMP/PKG signaling pathways, and its impact on oxidative stress, neuroinflammation, and apoptotic cascades associated with cognitive dysfunction. In addition, this review integrates current evidence on PDE1 isoforms in both neuronal and vascular regulation of cognition, emphasizing their dual neurovascular roles in cognitive impairment. We further summarized recent progress on PDE1 target validation and the reported efficacy of PDE1A inhibitors in alleviating memory deficits associated with neurodegenerative disorders, such as AD and VaD.