Macrophages play a central role in the pathogenesis of atherosclerosis. The inflammatory properties of these cells are dictated by their metabolism, of which the mechanistic target of rapamycin (mTOR) signaling pathway is a key regulator. Using myeloid cell–specific nanobiologics in apolipoprotein E–deficient (Apoe−/−) mice, we found that targeting the mTOR and ribosomal protein S6 kinase-1 (S6K1) signaling pathways rapidly diminished plaque macrophages’ inflammatory activity. By investigating transcriptome modifications, we identified Psap, a gene encoding the lysosomal protein prosaposin, as closely related with mTOR signaling. Subsequent in vitro experiments revealed that Psap inhibition suppressed both glycolysis and oxidative phosphorylation. Transplantation of Psap−/− bone marrow to low-density lipoprotein receptor knockout (Ldlr−/−) mice led to a reduction in atherosclerosis development and plaque inflammation. Last, we confirmed the relationship between PSAP expression and inflammation in human carotid atherosclerotic plaques. Our findings provide mechanistic insights into the development of atherosclerosis and identify prosaposin as a potential therapeutic target.

IMPORTANCE The Mobile Health Technology for Improved Screening and Optimized IntegratedCare in Atrial Fibrillation (mAFA-II) trial is a prospective cluster randomized trial that found a significant reduction in the composite clinical outcome of stroke or thromboembolism, all-cause death, and rehospitalization among patients with atrial fibrillation (AF) who used a mobile health (mHealth) technology that implemented the Atrial Fibrillation Better Care (ABC) pathway (ie, A, anticoagulation/avoid stroke; B, better symptom control; and C, cardiovascular disease and comorbidity management) compared with those receiving usual care. Multimorbidity (defined as Ն2 chronic long-term conditions) is common in older patients with AF, but the impact of integrated or holistic care (based on the ABC pathway) on clinical outcomes in this population is uncertain. OBJECTIVE To evaluate whether implementation of the integrated ABC pathway, supported by mHealth technology, would reduce AF-related adverse events in patients with multimorbidity. DESIGN, SETTING, AND PARTICIPANTSThis prespecified ancillary analysis of data from the extended follow-up of the mAFA II trial was conducted between June 2018 and April 2021. Adult patients with AF were included in the analysis if they had at least 2 comorbidities. Participants were enrolled across 40 centers in China. INTERVENTION Integrated care supported by mHealth technology (mAFA intervention) vs usual care. MAIN OUTCOMES AND MEASURES The main outcome was the composite outcome of stroke or thromboembolism, all-cause death, and rehospitalization. Cox proportional hazard modeling was performed for adverse outcomes after adjusting for cluster effect and baseline risk factors. RESULTS Of 1890 patients, 833 (mean [SD] age, 72.0 [12.0] years; 278 [33.4%] women) with multimorbidity were allocated to the intervention group (ABC pathway), with a mean (SD) follow-up of 419 (257) days, and 1057 patients (mean [SD] age, 72.8 [13.0] years; 443 [41.9%] women) with multimorbidity were allocated to usual care, with a mean (SD) follow-up of 457 (154) days. Compared with usual care, the composite outcome of stroke or thromboembolism, all-cause death, and rehospitalization was significantly reduced in the intervention group (hazard ratio [HR], 0.37; 95% CI, 0.26-0.53; P < .001), as were rehospitalizations alone (HR, 0.42; 95% CI, 0.27-0.64; P < .001). For the C criterion of the ABC pathway, rates of acute coronary syndrome, heart failure, and uncontrolled blood pressure during follow-up were lower in the intervention group than the usual care group (27 patients [3.2%] vs 145 patients [13.7%]; HR, 0.29; 95% CI, 0.19-0.45; P < .001). Subgroup analyses by age, prior stroke, and sex demonstrated consistently lower HRs for the primary composite outcome (continued) Key Points Question Does implementing mobile health technology-supported integrated care reduce atrial fibrillation (AF)-related adverse events in patients with multimorbidity? Findings In this prespecified ancillary analysis of data that included 1890 ...

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Cucurbit crops are suitable models for studying long-distance signaling in horticultural plants. Although thousands of substances are graft transmissible in cucurbits, functional studies have been hampered by the lack of efficient genetic transformation systems. Here, we report a convenient and efficient root transformation method for several cucurbit crops that will facilitate studies of functional genes and shoot–root crosstalk. We obtained healthy plants with completely transformed roots and non-transgenic shoots within 6 weeks. Furthermore, we combined this root transformation method with grafting, which allowed for gene manipulation in the rootstock. We validated our system by exploring salt tolerance mechanisms using a cucumber (Cucumis sativus)/pumpkin (Cucurbita moschata Duch.) (scion/rootstock) graft in which the sodium transporter gene High-affinity K+ transporter1 (CmoHKT1;1) was edited in the pumpkin rootstock, and by overexpressing the pumpkin tonoplast Na+/H+ antiporter gene Sodium hydrogen exchanger4 (CmoNHX4) in cucumber roots.

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Brown adipose tissues (BATs) convert to a “white-like” phenotype with age, which is also known as “aging-related BAT whitening (ARBW)”. Emerging evidence suggested that long non-coding RNAs (lncRNAs) were widely involved in adipose biology. Rabbit is an ideal model for studying the dynamics of ARBW. In this study, we performed histological analysis and strand-specific RNA-sequencing (ssRNA-seq) of rabbit interscapular adipose tissues (iATs). Our data indicated that the rabbit iATs underwent the ARBW from 0 days to 2 years and a total of 2281 novel lncRNAs were identified in the iATs. The classical rabbit BATs showed low lncRNA transcriptional complexity compared to white adipose tissues (WATs). A total of 631 differentially expressed lncRNAs (DELs) were identified in four stages. The signal pathways of purine metabolism, Wnt signaling pathway, peroxisome proliferator-activated receptor (PPAR) signaling pathway, cyclic guanosine monophosphate (cGMP)/cGMP-dependent protein kinase (cGMP-PKG) signaling pathway and lipid and atherosclerosis were significantly enriched by the DELs with unique expression patterns. A novel lncRNA that was highly expressed in the iATs of aged rabbits was validated to impair brown adipocyte differentiation in vitro. Our study provided a comprehensive catalog of lncRNAs involved in ARBW in rabbits, which facilitates a better understanding of adipose biology.

BackgroundLimited findings have been reported to systematically study miRNA and mRNA expression profiles in aged human atria. In this study, we aimed to identify miRNAs, genes, and miRNA-mRNA interaction networks for human atrial aging (AA).MethodsRight atrial appendages from twelve patients who received aortic valve replacement were subjected to miRNA-seq and RNA-seq. All the patients were in sinus rhythm (SR) and stratified by age into four groups. Differential expression analysis was carried out to identify miRNAs and genes for human AA. The miRNA-mRNA interactions for human AA were identified by Pearson correlation analysis and miRNA target prediction programs.ResultsSeven miRNAs (4 upregulation and 3 downregulation) and 42 genes (23 upregulation and 19 downregulation) were differentially expressed in human right atrial tissues between older samples and younger samples. Bioinformatic analysis identified 114 pairs of putative miRNA-mRNA interactions on AA and four types of correlation. Pathway enrichment analysis identified over 40 significant pathways and the top three pathways included rhythmic process (P = 7.5 × 10–5, Q = 0.034), senescence and autophagy in cancer (P = 9.0 × 10–5, Q = 0.034), and positive regulation of cytokine biosynthetic process (P = 1.1 × 10–4, Q = 0.034).ConclusionOur study revealed novel miRNA-mRNA interaction networks and signaling pathways for AA, providing novel insights into the development of human AA. Future studies are needed to investigate the potential significance of these miRNA-mRNA interactions in human AA or AA-related cardiovascular diseases.