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Abstract A synaptic memristor using 2D ferroelectric junctions is a promising candidate for future neuromorphic computing with ultra‐low power consumption, parallel computing, and adaptive scalable computing technologies. However, its utilization is restricted due to the limited operational voltage memory window and low on/off current (I_ON/OFF) ratio of the memristor devices. Here, it is demonstrated that synaptic operations of 2D In₂Se₃ferroelectric junctions in a planar memristor architecture can reach a voltage memory window as high as 16 V (±8 V) and I_ON/OFFratio of 10⁸, significantly higher than the current literature values. The power consumption is 10⁻⁵ W at the on state, demonstrating low power usage while maintaining a large I_ON/OFFratio of 10⁸compared to other ferroelectric devices. Moreover, the developed ferroelectric junction mimicked synaptic plasticity through pulses in the pre‐synapse. The nonlinearity factors are obtained 1.25 for LTP, −0.25 for LTD, respectively. The single‐layer perceptron (SLP) and convolutional neural network (CNN) on‐chip training results in an accuracy of up to 90%, compared to the 91% in an ideal synapse device. Furthermore, the incorporation of a 3 nm thick SiO₂interface between the α‐In₂Se₃and the Au electrode resulted in ultrahigh performance among other 2D ferroelectric junction devices to date. 

Abstract Nucleic acid delivery with mRNA lipid nanoparticles are being developed for targeting a wide array of tissues and cell types. However, targeted delivery to the bone microenvironment remains a significant challenge in the field, due in part to low local blood flow and poor interactions between drug carriers and bone material. Here we report bone‐targeting ionizable lipids incorporating a piperazine backbone and bisphosphate moieties, which bind tightly with hydroxyapatite ([Ca₅(PO₄)₃OH]), a key component of mineralized tissues. These lipids demonstrate biocompatibility and low toxicity in both vitro and in vivo studies. LNP formulated with these lipids facilitated efficient cellular transfection and improved binding to hydroxyapatite in vitro, and targeted delivery to the bone microenvironment in vivo following systemic administration. Overall, our findings demonstrate the critical role of the piperazine backbone in a novel ionizable lipid, which incorporates a bisphosphonate group to enable efficient bone‐targeted delivery, highlighting the potential of rational design of ionizable lipids for next‐generation bone‐targeting delivery systems. 

Abstract RNA‐based therapeutics have gained traction for the prevention and treatment of a variety of diseases. However, their fragility and immunogenicity necessitate a drug carrier. Lipid nanoparticles (LNPs) have emerged as the predominant delivery vehicle for RNA therapeutics. An important component of LNPs is the ionizable lipid (IL), which is protonated in the acidic environment of the endosome, prompting cargo release into the cytosol. Currently, there is growing evidence that the structure of IL lipid tails significantly impacts the efficacy of LNP‐mediated mRNA translation. Here, we optimized IL tail length for LNP‐mediated delivery of three different mRNA cargos. Using C12‐200, a gold standard IL, as a model, we designed a library of ILs with varying tail lengths and evaluated their potency in vivo. We demonstrated that small changes in lipophilicity can drastically increase or decrease mRNA translation. We identified that LNPs formulated with firefly luciferase mRNA (1929 base pairs) and C10‐200, an IL with shorter tail lengths than C12‐200, enhance liver transfection by over 10‐fold. Furthermore, different IL tail lengths were found to be ideal for transfection of LNPs encapsulating mRNA cargos of varying sizes. LNPs formulated with erythropoietin (EPO), responsible for stimulating red blood cell production, mRNA (858 base pairs), and the C13‐200 IL led to EPO translation at levels similar to the C12‐200 LNP. The LNPs formulated with Cas9 mRNA (4521 base pairs) and the C9‐200 IL induced over three times the quantity of indels compared with the C12‐200 LNP. Our findings suggest that shorter IL tails may lead to higher transfection of LNPs encapsulating larger mRNAs, and that longer IL tails may be more efficacious for delivering smaller mRNA cargos. We envision that the results of this project can be utilized as future design criteria for the next generation of LNP delivery systems for RNA therapeutics.