We found that this combined formulation compromises cell structure while also degrading bacterial DNA. Moreover, further investigation showed that the Van@ZIF-8@PDA nanoparticles exhibit good biocompatibility, with low toxicity toward host organs and tissues, while also reducing the antibiotic concentration needed for effective bacterial control. Finally, we treated Mu50 in a mouse model of skin abscess and found that Van@ZIF-8@PDA was effective and safe in vivo. Cumulatively, this study shows that this NIR/pH dual stimuli-responsive nanoparticle-based formulation offers a promising potential strategy for clinical application against bacterial infection that circumvents antibiotic resistance.Mesenchymal stem cell (MSC)-derived exosome plays a central role in the cell-free therapeutics involving MSCs and the contents can be customized under disease-associated microenvironments. However, optimal MSC-preconditioning to enhance its therapeutic potential is largely unknown. Here, we show that preconditioning of gingival tissue-derived MSCs (GMSCs) with tumor necrosis factor-alpha (TNF-α) is ideal for the treatment of periodontitis. TNF-α stimulation not only increased the amount of exosome secreted from GMSCs, but also enhanced the exosomal expression of CD73, thereby inducing anti-inflammatory M2 macrophage polarization. The effect of GMSC-derived exosomes on inflammatory bone loss were examined by ligature-induced periodontitis model in mice. Local injection of GMSC-derived exosomes significantly reduced periodontal bone resorption and the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts, and these effects were further enhanced by preconditioning of GMSCs with TNF-α. Thus, GMSC-derived exosomes also exhibited anti-osteoclastogenic activity. Receptor activator of NF-κB ligand (RANKL) expression was regulated by Wnt5a in periodontal ligament cells (PDLCs), and exosomal miR-1260b was found to target Wnt5a-mediated RANKL pathway and inhibit its osteoclastogenic activity. https://www.selleckchem.com/products/bevacizumab.html These results indicate that significant ability of the TNF-α-preconditioned GMSC-derived exosomes to regulate inflammation and osteoclastogenesis paves the way for establishment of a therapeutic approach for periodontitis.National Institutes of Health (NIH) funding has declined among cardiothoracic surgeons. R01 grants are a well-known mechanism to support high-impact research, and we sought to clarify the association between NIH funding and academic achievement. We hypothesized that cardiothoracic surgeons who acquired R01 funding exhibit greater research output and faster career advancement. All cardiothoracic surgeons (n = 992) working at accredited United States cardiothoracic surgery training hospitals in 2018 were included. Institutional webpages, Scopus, and Grantome were utilized to collect publicly-available data regarding each surgeon's training and career history, research publications, and NIH funding. Seventy-eight (7.9%) surgeons obtained R01 funding as a principal investigator while 914 (92.1%) did not. R01-funded surgeons started their attending careers earlier (1998 vs 2005, P less then 0.0001) and were more likely to have pursued dedicated research training (P less then 0.0001). R01-funded surgeons authored 5.3 publications/year before their first R01 grant, 9.3 during the grant period, and 8.6 after the grant expired, all of which were greater than the publication rate of non-R01-funded surgeons at comparable career timepoints (2.0-3.0 publications/year, P less then 0.0001). Among time-matched surgeons who completed medical school in 1998 or earlier (n = 73 R01-funded vs n = 602 non-funded), R01-funded surgeons have published more total publications (178.0 vs 56.5 papers, P less then 0.0001) and exhibit a greater H-index (41.0 vs 19.0, P less then 0.0001). These R01-funded surgeons have also advanced to higher academic ranks (P less then 0.0001) and are more likely to be chiefs of their departments or divisions (42.5% vs 25.7%, P = 0.0035). Cardiothoracic surgeons who obtain R01 funding exhibit greater research productivity and faster career advancement.WNT ligand transporter Wls is essential for the WNT dependent developmental and pathogenic processes. The spatiotemporal expression pattern of Wls was investigated in this study. Immature female mice (21-22 days old) were treated with 5 IU, pregnant mare's serum gonadotrophin (PMSG) to stimulate follicular development, followed 48 h later by injection with 5 IU, human chorionic gonadotrophin (hCG) to induce ovulation. The expression of Wls was stimulated in granulosa cells and the forming corpus luteum after hCG administration. To study the function of Wls, the Amhr2tm3(cre)Bhr strain was used to target deletion of Wls in granulosa cells. The deletion of Wls caused a significant decrease in the fertility of WlsAmhr2-Cre female mice. In female WlsAmhr2-Cre mice, decreased ovarian size and number of antral follicles were found. The number of corpus luteum in immature PMSG/hCG primed WlsAmhr2-Cre mice was much less than that in the control group. Compared with control animals, WlsAmhr2-Cre mice have lower serum progesterone levels. RNA sequencing was used to identify genes regulated by Wls after hCG treatment. Several genes known to be critical for follicle development and steroidogenesis were significantly down-regulated, such as Fshr, Lhcgr, Sfrp4, Inhba, Cyp17a1, Hsd3b1, and Hsd17b7. The expression of WNT signaling downstream target genes, Bmp2 and Cyp19a1, also decreased significantly in WlsAmhr2-Cre ovary. In summary, the findings of this study suggest that Wls is critical for female fertility and luteinization.Elevated lipogenesis is an important metabolic hallmark of rapidly proliferating tumor such as endometrial carcinoma (EC). The sterol regulatory element-binding protein 1 (SREBP1) is a master regulator of lipogenesis and involved in EC proliferation. BF175 is a novel chemical inhibitor of SREBP pathway, and has shown potent anti-lipogenic effects. However, the effect of BF175 on EC cells are yet to be determined. In the present study, we found that BF175 decreased cell viability, colony formation and migratory capacity, inducing autophagy and mitochondrial related apoptosis in EC cell line AN3CA. Z-VAD-FMK partially attenuated the effect of BF175 on AN3CA. In addition, BF175 significantly downregulated SREBPs and their downstream genes. The levels of free fatty acids and total cholesterol were also inhibited. Microarray analysis suggested BF175 treatment obviously affected lipid metabolic pathways in EC. Taken together, we validated BF175 exhibited anti-tumor activity by targeting SREBP-dependent lipogenesis and inducing apoptosis which mitochondrial pathway involved in, suggesting that it's potential as a novel therapeutic reagent for EC.