Chlorotoxin-conjugated multifunctional dendrimers labeled with radionuclide 131I were synthesized and utilized for targeted single photon emission computed tomography (SPECT) imaging and radiotherapy of cancer. In this study, generation five amine-terminated poly(amidoamine) dendrimers were used as a platform to be sequentially conjugated with polyethylene glycol (PEG), targeting agent chlorotoxin (CTX), and 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO). This was followed by acetylation of the remaining dendrimer terminal amines and radiolabeling with 131I to form the targeted theranostic dendrimeric nanoplatform. We show that the dendrimer platform possessing approximately 7.7 CTX and 21.1 HPAO moieties on each dendrimer displays excellent cytocompatibility in a given concentration range (0-20 μM) and can specifically target cancer cells overexpressing matrix metallopeptidase 2 (MMP2) due to the attached CTX. With the attached HPAO moiety having the phenol group, the dendrimer platform can be effectively labeled with radioactive 131I with good stability and high radiochemical purity. Importantly, the 131I labeling renders the dendrimer platform with an ability to be used for targeted SPECT imaging and radiotherapy of an MMP2-overexpressing glioma model in vivo. The developed radiolabeled multifunctional dendrimeric nanoplatform may hold great promise to be used for targeted theranostics of human gliomas.

We report the synthesis, characterization, and utilization of radioactive (131)I-labeled multifunctional dendrimers for targeted single-photon emission computed tomography (SPECT) imaging and radiotherapy of tumors. In this study, amine-terminated poly(amidoamine) dendrimers of generation 5 (G5·NH2) were sequentially modified with 3-(4'-hydroxyphenyl)propionic acid-OSu (HPAO) and folic acid (FA) linked with polyethylene glycol (PEG), followed by acetylation modification of the dendrimer remaining surface amines and labeling of radioactive iodine-131 ((131)I). The generated multifunctional (131)I-G5·NHAc-HPAO-PEG-FA dendrimers were characterized via different methods. We show that prior to (131)I labeling, the G5·NHAc-HPAO-PEG-FA dendrimers conjugated with approximately 9.4 HPAO moieties per dendrimer are noncytotoxic at a concentration up to 20 μM and are able to target cancer cells overexpressing FA receptors (FAR), thanks to the modified FA ligands. In the presence of a phenol group, radioactive (131)I is able to be efficiently labeled onto the dendrimer platform with good stability and high radiochemical purity, and render the platform with an ability for targeted SPECT imaging and radiotherapy of an FAR-overexpressing xenografted tumor model in vivo. The designed strategy to use the facile dendrimer nanotechnology may be extended to develop various radioactive theranostic nanoplatforms for targeted SPECT imaging and radiotherapy of different types of cancer.

The natural compound eye has received much attention in recent years due to its remarkable properties, such as its large field of view (FOV), compact structure, and high sensitivity to moving objects. Many studies have been devoted to mimicking the imaging system of the natural compound eye. The paper gives a review of state-of-the-art artificial compound eye imaging systems. Firstly, we introduce the imaging principle of three types of natural compound eye. Then, we divide current artificial compound eye imaging systems into four categories according to the difference of structural composition. Readers can easily grasp methods to build an artificial compound eye imaging system from the perspective of structural composition. Moreover, we compare the imaging performance of state-of-the-art artificial compound eye imaging systems, which provides a reference for readers to design system parameters of an artificial compound eye imaging system. Next, we present the applications of the artificial compound eye imaging system including imaging with a large FOV, imaging with high resolution, object distance detection, medical imaging, egomotion estimation, and navigation. Finally, an outlook of the artificial compound eye imaging system is highlighted.

(131)I-G5.NHAc-HPAO-(PEG-BmK CT)-(mPEG) complex is a promising multifunctional nanoplatform for glioma-specific nuclear imaging and radiotherapy.

Rheumatoid arthritis (RA), a chronic systemic disease, is featured with inflammatory synovitis, which can lead to destruction on bone and cartilage and even cause disability. Emerging studies demonstrated that Fibroblast-like synoviocytes (FLS) is a vital cellular participant in RA progression. Long non-coding RNAs (lncRNAs) are also reported to participate in the pathogenesis of RA. In our present study, lncRNA microarray analysis was applied to screen out lncRNAs differentially expressed in RA FLS. Among which, cytoskeleton regulator RNA (LINC00152) presented biggest fold change. Gain- or loss-of function assays were further carried out in RA FLS, and the results revealed that LINC00152 promoted proliferation but induced apoptosis in RA FLS. Furthermore, up-regulation of LINC00152 may induce promotion of Wnt/β-catenin signaling pathway in RA FLS. Mechanistically, we found that forkhead box M1 (FOXM1) transcriptionally activated LINC00152 in RA FLS. Additionally, LINC00152 positively regulated FOXM1 via sponging miR-1270. In conclusion, the present study focused on elucidating the function of FOXM1/LINC00152 positive feedback loop in RA FLS and its association with Wnt/β-catenin signaling.

Objective/Background: To conduct a randomized controlled trial to test the efficacy of a culturally tailored heart failure (HF) education program, to reduce HF hospital readmissions and/or cardiovascular disease death (HF outcomes) among Native Hawaiian and Other Pacific Islander (NHOPI) patients with HF. Methods: One hundred fifty HF patients aged ≥21 years, NHOPI race, and discharged to home were enrolled and randomized to the Mālama Puʻuwai Program (MPP) or the usual care (UC). The MPP group received a culturally tailored HF program, and the UC received similar standard HF education materials. Clinical and health behavior data were measured at baseline and 12 months. HF outcomes were monitored throughout the entire study period. Two-sample t-test, chi-square, and Cox proportional hazard modeling assessed the efficacy of intervention (MPP or UC) on HF outcomes using an intention-to-treat approach. A sensitivity post hoc analysis was performed on patients who completed the full intervention (n=127). Results: Overall, 69% were men, mean age 54.4±13.4 years, 62% were Native Hawaiian, and 24% reported methamphetamine use. More UC participants reported methamphetamine use (32% vs. 16%), hypertension (81% vs. 63%), but less myocardial infarction (27% vs. 48%). HF outcomes were higher in UC (31%) compared with MPP (19%) with higher risk for HF outcomes (hazard ratio [HR] 1.74; 95% CI: 0.89-3.40). Sensitivity post hoc analysis of intervention compliance revealed that UC was at significantly higher risk for HF outcomes than MPP (HR 2.83; 95% CI: 1.19-6.72). Conclusions: Culturally tailored HF programs have the potential to reduce HF outcomes among compliant minority patients with HF such as NHOPI.

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This work aims to demonstrate that radial acquisition with k-space variant reduced-FOV reconstruction can enable real-time cardiac MRI with an affordable computation cost. Due to non-uniform sampling, radial imaging requires k-space variant reconstruction for optimal performance. By converting radial parallel imaging reconstruction into the estimation of correlation functions with a previously-developed correlation imaging framework, Cartesian k-space may be reconstructed point-wisely based on parallel imaging relationship between every Cartesian datum and its neighboring radial samples. Furthermore, reduced-FOV correlation functions may be used to calculate a subset of Cartesian k-space data for image reconstruction within a small region of interest, making it possible to run real-time cardiac MRI with an affordable computation cost. In a stress cardiac test where the subject is imaged during biking with a heart rate of >100 bpm, this k-space variant reduced-FOV reconstruction is demonstrated in reference to several radial imaging techniques including gridding, GROG and SPIRiT. It is found that the k-space variant reconstruction outperforms gridding, GROG and SPIRiT in real-time imaging. The computation cost of reduced-FOV reconstruction is ~2 times higher than that of GROG. The presented work provides a practical solution to real-time cardiac MRI with radial acquisition and k-space variant reduced-FOV reconstruction in clinical settings.