Co Nanoparticles Encapsulated in N‑Doped Carbon Nanosheets: Enhancing Oxygen Reduction Catalysis without Metal–Nitrogen Bonding

It is known that introducing metal nanoparticles (e.g., Fe and Co) into N-doped carbons can enhance the activity of N-doped carbons toward the oxygen reduction reaction (ORR). However, introducing metals into N-doped carbons inevitably causes the formation of multiple active sites. Thus, it is challenging to identify the active sites and unravel mechanisms responsible for enhanced ORR activity. Herein, by developing a new N-heterocyclic carbene (NHC)–Co complex as the nitrogen- and metal-containing precursor, we report the synthesis of N-doped carbon nanosheets embedded with Co nanoparticles as highly active ORR catalysts without direct metal–nitrogen bonding. Electrochemical measurements and X-ray absorption spectroscopy indicate that the carbon–nitrogen sites surrounding Co nanoparticles are responsible for the observed ORR activity and stability. Density functional theory calculations further reveal that Co nanoparticles could facilitate the protonation of O₂ and thus promote the ORR activity. These results provide new prospects in the rational design and synthesis of heteroatom-doped carbon materials as non-precious-metal catalysts for various electrochemical reactions

Data_Sheet_2_Plin4-Dependent Lipid Droplets Hamper Neuronal Mitophagy in the MPTP/p-Induced Mouse Model of Parkinson’s Disease.DOCX

<p>Epidemiological studies have shown that both lipid metabolism disorder and mitochondrial dysfunction are correlated with the pathogenesis of neurodegenerative diseases (NDDs), including Parkinson’s disease (PD). Emerging evidence suggests that deposition of intracellular lipid droplets (LDs) participates in lipotoxicity and precedes neurodegeneration. Perilipin family members were recognized to facilitate LD movement and cellular signaling interactions. However, the direct interaction between Perilipin-regulated LD deposition and mitochondrial dysfunction in dopaminergic (DA) neurons remains obscure. Here, we demonstrate a novel type of lipid dysregulation involved in PD progression as evidenced by upregulated expression of Plin4 (a coating protein and regulator of LDs), and increased intracellular LD deposition that correlated with the loss of TH-ir (Tyrosine hydroxylase-immunoreactive) neurons in the MPTP/p-induced PD model mouse mesencephalon. Further, in vitro experiments showed that inhibition of LD storage by downregulating Plin4 promoted survival of SH-SY5Y cells. Mechanistically, reduced LD storage restored autophagy, leading to alleviation of mitochondrial damage, which in turn promoted cell survival. Moreover, the parkin-poly-Ub-p62 pathway was involved in this Plin4/LD-induced inhibition of mitophagy. These findings were further confirmed in primary cultures of DA-nergic neurons, in which autophagy inhibitor treatment significantly countermanded the ameliorations conferred by Plin4 silencing. Collectively, these experiments demonstrate that a dysfunctional Plin4/LD/mitophagy axis is involved in PD pathology and suggest Plin4-LDs as a potential biomarker as well as therapeutic strategy for PD.</p

Controlled Intercalation and Chemical Exfoliation of Layered Metal–Organic Frameworks Using a Chemically Labile Intercalating Agent

Creating ordered two-dimensional (2D) metal–organic framework (MOF) nanosheets has attracted extensive interest. However, it still remains a great challenge to synthesize ultrathin 2D MOF nanosheets with controlled thickness in high yields. In this work, we demonstrate a novel intercalation and chemical exfoliation approach to obtain MOF nanosheets from intrinsically layered MOF crystals. This approach involves two steps: first, layered porphyrinic MOF crystals are intercalated with 4,4′-dipyridyl disulfide through coordination bonding with the metal nodes; subsequently, selective cleavage of the disulfide bond induces exfoliation of the intercalated MOF crystals, leading to individual freestanding MOF nanosheets. This chemical exfoliation process can proceed efficiently at room temperature to produce ultrathin (∼1 nm) 2D MOF nanosheets in ∼57% overall yield. The obtained ultrathin nanosheets exhibit efficient and far superior heterogeneous photocatalysis performance compared with the corresponding bulk MOF

Catalytic Mechanism of Histone Acetyltransferase p300: From the Proton Transfer to Acetylation Reaction

The transcriptional coactivator and histone acetyltransferase (HAT) p300 acetylates the four core histones and other transcription factors to regulate a plethora of fundamental biological processes including cell growth, development, oncogenesis and apoptosis. Recent structural and biochemical studies on the p300 HAT domain revealed a Theorell–Chance, or “hit-and-run”, catalytic mechanism. Nonetheless, the chemical mechanism of the entire reaction process including the proton transfer (PT) scheme and consequent acetylation reaction route remains unclear. In this study, a combined computational strategy consisting of molecular modeling, molecular dynamic (MD) simulation, and quantum mechanics/molecular mechanics (QM/MM) simulation was applied to elucidate these important issues. An initial p300/H3/Ac-CoA complex structure was modeled and optimized using a 100 ns MD simulation. Residues that play important roles in substrate binding and the acetylation reaction were comprehensively investigated. For the first time, these studies reveal a plausible PT scheme consisting of Y1394, D1507, and a conserved crystallographic water molecule, with all components of the scheme being stable during the MD simulation and the energy barrier low for PT to occur. The two-dimensional potential energy surface for the nucleophilic attack process was also calculated. The comparison of potential energies for two possible elimination half-reaction mechanisms revealed that Y1467 reprotonates the coenzyme-A leaving group to form product. This study provides new insights into the detailed catalytic mechanism of p300 and has important implications for the discovery of novel small molecule regulators for p300