Accumulating evidence has demonstrated that nucleic acid-based therapies are promising for atherosclerosis. However, nearly all nucleic acid delivery systems developed for atherosclerosis necessitate injection, which results in rapid elimination and poor patient compliance. Consequently, oral delivery strategies capable of targeting atherosclerotic plaques are imperative for nucleic acid therapeutics. Herein we report the development of yeast-derived capsules (YCs) packaging an antisense oligonucleotide (AM33) targeting microRNA-33 (miR-33) for the oral treatment of atherosclerosis. YCs provide stability for AM33, preventing its premature release in the gastrointestinal tract. AM33-containing YCs, defined as YAM33, showed high transfection in macrophages, thus promoting cholesterol efflux and inhibiting foam cell formation by regulating the target genes/proteins of miR-33. Orally delivered YAM33 effectively accumulated within atherosclerotic plaques in ApoE ^-/- mice, primarily by transepithelial absorption via M cells in Peyer's patches and subsequent translocation via macrophages through the lymphatic system. Inhibition of miR-33 by oral YAM33 significantly delayed the progression of atherosclerosis. Moreover, oral treatment with YCs co-delivering AM33 and atorvastatin afforded significantly enhanced anti-atherosclerotic effects. Our findings suggest that yeast-based microcapsules represent an effective carrier for oral delivery of nucleic acids, either alone or in combination with existing drugs, offering a promising approach for precision therapy of atherosclerotic diseases.

Objective To provide an effective strategy for the prevention and treatment of radiation-induced infections by preparing platelet membrane-modified catalase/silica nanoparticles(PCNP)capable of targeting leukocytes.Methods PCNP and catalase/silica nanoparticles(CNP)were prepared by using platelet membrane,catalase(CAT)and silica,and its biological safety was preliminarily evaluated with cell survival test,hemolysis test and acute toxicity test in mice after tail vein administration;The culture medium,FITC labeled(FITC+)PCNP and FITC labeled(FITC+)CNP were co-incubated with human peripheral blood B lymphocytes(AHH-1)and mouse monocyte macrophages(RAW264.7),respectively.Thus,there were control group,FITC+PCNP group and FITC+CNP group of AHH-1 and RAW264.7 cells.Laser confocal microscopy was used to observe the intracellular fluorescence intensity of PCNP to evaluate the leukocytes targeting function.AHH-1 cells were divided into control,irradiation,platelet membrane,CNP(100 μg/mL)and PCNP(100 μg/mL)groups.After corresponding co-incubation,the cell media were exposed to6 Gy Co60 γ irradiation.The generation of reactive oxygen species(ROS)and cell apoptosis were measured to determine the effect of nanoparticles on reducing radiation injury of leukocytes.Twenty C57BL/6 male mice(weighing 18～20 g)were randomly divided into irradiation group(n=10)and 10 mg/kg PCNP group(n=10).In 2 h after corresponding agents were injected into the mice through tail vein,the mice received whole-body irradiation of 5 Gy Co60 γ ray,and then in 2 h later,they were given intraperitoneal injection of multidrug resistant Acinetobacter baumannii(MDR-AB).The infection inhibitory effect of PCNP after irradiation was evaluated by detecting the bacterial load in main organs.Results The hydration particle of PCNP is 91.3 nm in size,and does not exhibit significant cytotoxicity or hemolytic toxicity at concentrations＜400 μg/mL.Intravenous injection of 20 mg/kg PCNP resulted in normal increase in the body weight but no obvious pathological changes in the major organs such as the heart,liver,spleen,lungs,and kidneys.In AHH-1 and RAW264.7 cells,PCNP showed significant advantages in targeting compared to the FITC+CNP group[(15.45±3.48)%vs(9.33±2.03)%,P＜0.01;(11.25±2.08)%vs(7.06±0.71)%,P＜0.001].PCNP also effectively reduced the generation of ROS[(22.73±3.71)%vs(60.90±9.08)%,P＜0.001]and apoptotic rate[(9.84±0.92)%vs(38.96±3.62)%,P＜0.001]in AHH-1 cells.In in vitro study,bacterial colonization after irradiation showed that there was significantly less MDR-AB colonies in the spleen of mice intervened with PCNP than those of the irradiation group[(17.50±1.38)×104 vs(13.20±2.29)×106 CFU/g,P＜0.001].Conclusion PCNP can effectively inhibit the complications of radiation infection in mice,which is due to its direct protective effect on leukocytes.

Objective To observe prenatal ultrasonic manifestations of fetal rhomboencephalosynapsis(RES).Methods Data of 15 singletons with RES were retrospectively analyzed,and the prenatal intracranial and extracranial ultrasonic manifestations were observed.Results All 15 fetuses were found with transverse cerebellar diameter lower than the 3rd percentile of normal value in the same gestational week and bilateral cerebellar hemisphere fusion(15/15,100％).Cerebellar vermis completely loss was observed in 14 fetuses(14/15,93.33％),while partially loss was noticed in 1 fetus(1/15,6.67％).Invisible of the fourth cerebral ventricle was detected in 4 fetuses(4/15,26.67％),while the fourth cerebral ventricular index(4Vi)＜1 was found in 11 fetuses(11/15,73.33％).No"split line"sign between vermis and cerebellar hemisphere was detected.A total of 14(14/15,93.33％)were found with combining intracranial or extracranial malformations,including 13(13/14,92.86％)with other intracranial malformations,10(10/14,71.43％)with extracranial malformations,whereas 1(1/15,6.67％)fetus had no other malformation.Conclusion Prenatal ultrasonic manifestations of fetal RES mainly included small cerebellum transverse diameter,complete or partial loss of vermis,invisible or dysplasia of the fourth cerebral ventricle,fusion of bilateral cerebellar hemispheres,as well as combining with other intracranial and extracranial malformations.