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 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.