Objective : Cas9-RNP biomimetic nanoparticles cas9-RNP@ MMs were prepared by encapsulating the Cas9 Ribonucleoprotein complex (RNP) using mouse macrophage membranes，with the aim of utilizing this biomimetic nanoparticle to deliver the Cas9-RNP complex for gene editing ，and further study the endocytosis of Cas9- RNP@ MMs and its gene editing effect in mouse macrophage RAW264. 7 in vitro ，providing evidence for the development oflow-toxicity biomimetic nanoparticle carriers that inhibit NLRP3 therapeutic targets． Methods : The purified mouse macrophage membrane was mixed with the prepared cas9-RNP mixture，and after ultrasound，the CAS9- RNP@ MMS was obtained by liposome extrusion instrument ; The particle size of Cas9-RNP@ MMswas measured by nanoparticle tracking analysis，and the particle morphology of Cas9-RNP@ MMs was observed under transmission electron microscope．Laser confocal Fluorescence microscope imaging was used to analyze the endocytosis Cas9-RNP @ MMs．The Biocompatibility of Cas9-RNP@ MMs was measured by MTT assay．The expression of NLRP3 was detected by qPCR and Western blot to verify the knockdown effect of Cas9-RNP@ MMs on NLRP3 gene. Results: The average particle diameter of Cas9-RNP@ MMs prepared from macrophages was about 216 nm．Under laser confocal fluorescence microscope，the Cas9-RNP@ MMs could be successfully endocysed by Raw246. 7 cell．MTT assay indicated that the Cas9-RNP@ MMs-treated mouse macrophage RAW246. 7 had good biocompatibility．qPCR and Western blot showed that two NLRP3-specific guide RNA were mediated by Cas9-RNP@ MMs，with good effect of knockdown NLRP3 gene expression． Conclusion Nano-scale vesicles Cas9-RNP@ MMs loaded with Cas9-RNP complexes were successfully prepared by biomimetic nanoparticles． Cas9-RNP@ MMs have good biocompatibility and can be efficiently endocytosed by RAW246. 7 cells．Cas9-RNP@ MMs containing NLRP3-specific sgRNA can specifically knock down NLRP3 gene expression.

Objective : To investigate the effect and mechanism of all-trans retinoic acid (ATRA) on lipopolysaccharide (LPS) -induced acute myocardial injury in C57BL/6 mice． Methods : Male mice of C57BL/6 strain were randomly divided into normal group，model group，ATRA group，and ferrostatin-1 group．Mice in the ATRA group were injected intraperitoneally with ATRA 15mg / (kg · d) ，ferrostatin-1 group received ferrostatin-1 2 mg / ( kg · d) ，the normal group and the model group were given solvent．After one week of continuous administration，the model group，ATRA group ，and ferrostatin-1 group were intraperitoneally injected with LPS 6 mg / kg． All mice were sacrificed after 6 hours．The contents of malondialdehyde ( MDA) and glutathione ( GSH) in serum of mice were detected． qPCR was used to detect mRNA levels of interleukin-6 ( IL-6 ) and tumor necrosis factor-alpha (TNF-α) in heart tissue．Hematoxylin-eosin ( HE) staining was used to observe the changes of heart tissue in mice．Transmission electron microscopy (TEM) was used to observe the structure of mouse myocardial mitochondria．Western blot was used to detect the expression of ferroptosis markers glutathione peroxidase 4 ( GPX4) ，ferritin heavy chain 1 ( FTH1 ) ，Solute carrier family 7 member 11 ( SLC7A11 ) ，acyl-CoA synthetase long-chain family member 4 (ACSL4) and related regulatory proteins，Nuclear factor erythroid 2-related factor 2 ( NRF2 ) ，kelchlike ECH-associated protein 1 (KEAP1) . Results: Compared with the normal group，the MDA content in the serum of the model group increased and the GSH content decreased，the above changes were reversed in the ATRA group as well as in the ferrostatin-1 group．Compared with normal group，the mRNA levels of IL-6 and TNF-α in the heart tissue of model group increased steeply，the above changes were relieved in the ATRA group and the ferrostatin-1 group．There was no significant difference in HE staining of myocardial tissue among the groups of mice. Compared with the normal group，myocardial mitochondria in the model group showed the phenomenon of cristaereduction or disappearance under TEM，while myocardial mitochondrial injury was alleviated in the ATRA group and the ferrostatin-1 group．Western blot showed that GPX4，FTH1，SLC7A11，and NRF2 expression were reduced in the myocardial tissue of mice in the model group compared with the normal group，ACSL4 and KEAP1 expression increased．The above changes were reversed in the ATRA group as well as in the ferrostatin-1 group． Conclusion ATRA alleviates lipopolysaccharide-induced acute myocardial injury in mice by inhibiting ferroptosis.