Obesity is a global health crisis driving insulin resistance (IR), type 2 diabetes (T2D), and metabolic dysfunction-associated steatotic liver disease (MASLD). Chronic low-grade inflammation in adipose tissue, mainly driven by macrophages, lies at the core of this process. Current treatments often lose effectiveness, cause weight regain, or produce systemic side effects. New strategies with better targeting, higher efficacy, and lower toxicity are urgently needed. MicroRNA (miRNA) therapy holds great promise but faces two major hurdles, namely selecting the right miRNA and the lack of an efficient delivery system. In this study, we used a multi-method machine learning ensemble combining PCA, random forest regression, and expert-weighted scoring across nine features to prioritize obesity-related miRNAs, and miR-146a-5p emerged as the top candidate. Guided by this screening, we engineered a sticky-end tetrahedral framework nucleic acid (stFNA) loaded with miRNA via vertex-complementary base pairing. The resulting miR-stFNA nanocomplex has a uniform size, good stability, efficient macrophage uptake, and lysosomal escape. In vitro, miR-stFNA suppressed reactive oxygen species (ROS), nitric oxide (NO), and pro-inflammatory cytokines by curbing MAPK, NF-κB, and PI3K pathways in activated macrophages, outperforming each component alone. In the obese mouse model, miR-stFNA reduced weight gain, improved insulin sensitivity, and decreased liver fat accumulation. This work integrates machine learning-based miRNA selection with DNA origami delivery, providing a smart nanotherapy for obesity-related complications.

This study aimed to introduce a minimally invasive technique for maxillary sinus floor elevation using the lateral approach (lSFE) and to determine the factors that influence the stability of the grafted area in the sinus cavity. Thirty patients (30 implants) treated with lSFE using minimally invasive techniques from 2015 to 2019 were included in the study. Five aspects of the implant (central, mesial, distal, buccal, and palatal bone heights [BHs]) were measured using cone-beam computed tomography (CBCT) before implant surgery, immediately after surgery (T0), 6 months after surgery (T1), and at the last follow-up visit (T2). Patients’ characteristics were collected. A small bone window (height, (4.40 ± 0.74) mm; length, (6.26 ± 1.03) mm) was prepared. No implant failed during the follow-up period (3.67 ± 1.75) years. Three of the 30 implants exhibited perforations. Changes in BH of the five aspects of implants showed strong correlations with each other and BH decreased dramatically before second-stage surgery. Residual bone height (RBH) did not significantly influence BH changes, whereas smoking status and type of bone graft materials were the potentially influential factors. During the approximate three-year observation period, lSFE with a minimally invasive technique demonstrated high implant survival rate and limited bone reduction in grafted area. In conclusion, lSFE using minimally invasive techniques was a viable treatment option. Patients who were nonsmokers and whose sinus cavity was filled with deproteinized bovine bone mineral (DBBM) had significantly limited bone resorption in grafted area.