Antioxidative Impact of Phenolics-Loaded Nanocarriers on Cytoskeletal Network Remodeling of Invasive Cancer Cells.

Natural phenolic compounds have antioxidant properties owing to their free radical-scavenging capability. The combined effect of a mixture of phenolic compounds has been studied; however, the detailed investigation for finding a correlation between single phenolic molecules and antioxidant activity has not been explored. Herein, we revealed that the number of phenolic hydroxyl groups in phenolics played a central role in their antioxidant capacity. Based on the finding, tannic acid showed the most effective antioxidant potential, e.g., 76% in tannic acid versus 22% in vitamin C as a standard antioxidant component. Because cancer progression is closely related to oxidative processes at the cellular level, we further applied the surface treatment of tannic acid drug-delivery nanocarriers. Tannic acid-loaded nanocarriers reduced reactive oxygen species of cancer cells as much as 41% of vehicle treatment and remodeled cytoskeletal network. By a gelatin degradation study, TA-loaded nanocarrier-treated cells induced 44.6% reduction of degraded area than vehicle-treated cells, implying a potential of blocking invasiveness of cancer cells.

Bone morphogenetic protein-7 attenuates pancreatic damage under diabetic conditions and prevents progression to diabetic nephropathy via inhibition of ferroptosis.

Background: Approximately 30% of diabetic patients develop diabetic nephropathy, a representative microvascular complication. Although the etiological mechanism has not yet been fully elucidated, renal tubular damage by hyperglycemia-induced expression of transforming growth factor-ß (TGF-ß) is known to be involved. Recently, a new type of cell death by iron metabolism called ferroptosis was reported to be involved in kidney damage in animal models of diabetic nephropathy, which could be induced by TGF-ß. Bone morphogenetic protein-7 (BMP7) is a well-known antagonist of TGF-ß inhibiting TGF-ß-induced fibrosis in many organs. Further, BMP7 has been reported to play a role in the regeneration of pancreatic beta cells in diabetic animal models. Methods: We used protein transduction domain (PTD)-fused BMP7 in micelles (mPTD-BMP7) for long-lasting in vivo effects and effective in vitro transduction and secretion. Results: mPTD-BMP7 successfully accelerated the regeneration of diabetic pancreas and impeded progression to diabetic nephropathy. With the administration of mPTD-BMP7, clinical parameters and representative markers of pancreatic damage were alleviated in a mouse model of streptozotocin-induced diabetes. It not only inhibited the downstream genes of TGF-ß but also attenuated ferroptosis in the kidney of the diabetic mouse and TGF-ß-stimulated rat kidney tubular cells. Conclusion: BMP7 impedes the progression of diabetic nephropathy by inhibiting the canonical TGF-ß pathway, attenuating ferroptosis, and helping regenerate diabetic pancreas.

Intracellular lipophilic network transformation induced by protease-specific endocytosis of fluorescent Au nanoclusters.

The understanding of the endocytosis process of internalized nanomedicines through membrane biomarker is essential for the development of molecular-specific nanomedicines. In various recent reports, the metalloproteases have been identified as important markers during the metastasis of cancer cells. In particular, MT1-MMP has provoked concern due to its protease activity in the degradation of the extracellular matrix adjacent to tumors. Thus, in the current work, we have applied fluorescent Au nanoclusters which present strong resistance to chemical quenching to the investigation of MT1-MMP-mediated endocytosis. We synthesized protein-based Au nanocluster (PAuNC) and MT1-MMP-specific peptide was conjugated with PAuNC (pPAuNC) for monitoring protease-mediated endocytosis. The fluorescence capacity of pPAuNC was investigated and MT1-MMP-mediated intracellular uptake of pPAuNC was subsequently confirmed by a co-localization analysis using confocal microscopy and molecular competition test. Furthermore, we confirmed a change in the intracellular lipophilic network after an endocytosis event of pPAuNC. The identical lipophilic network change did not occur with the endocytosis of bare PAuNC. By classification of the branched network between the lipophilic organelles at the nanoscale, the image-based analysis of cell organelle networking allowed the evaluation of nanoparticle internalization and impaired cellular components after intracellular accumulation at a single-cell level. Our analyses suggest a methodology to achieve a better understanding of the mechanism by which nanoparticles enter cells.

KS10076, a chelator for redox-active metal ions, induces ROS-mediated STAT3 degradation in autophagic cell death and eliminates ALDH1+ stem cells.

Redox-active metal ions are pivotal for rapid metabolism, proliferation, and aggression across cancer types, and this presents metal chelation as an attractive cancer cell-targeting strategy. Here, we identify a metal chelator, KS10076, as a potent anti-cancer drug candidate. A metal-bound KS10076 complex with redox potential for generating hydrogen peroxide and superoxide anions induces intracellular reactive oxygen species (ROS). The elevation of ROS by KS10076 promotes the destabilization of signal transducer and activator of transcription 3, removes aldehyde dehydrogenase isoform 1-positive cancer stem cells, and subsequently induces autophagic cell death. Bioinformatic analysis of KS10076 susceptibility in pan-cancer cells shows that KS10076 potentially targets cancer cells with increased mitochondrial function. Furthermore, patient-derived organoid models demonstrate that KS10076 efficiently represses cancer cells with active KRAS, and fluorouracil resistance, which suggests clinical advantages.

A micellized bone morphogenetic protein-7 prodrug ameliorates liver fibrosis by suppressing transforming growth factor-ß signaling.

Bone morphogenetic protein-7 (BMP-7) antagonizes transforming growth factor-ß (TGF-ß), which is critically involved in liver fibrogenesis. Here, we designed a micelle formulation consisting of a protein transduction domain (PTD) fused BMP-7 polypeptide (mPTD-BMP-7) to enhance endocytic delivery, and investigated its ability to ameliorate liver fibrosis. The mPTD-BMP-7 formulation was efficiently delivered into cells via endocytosis, where it inhibited TGF-ß mediated epithelial-mesenchymal transition. After successfully demonstrating delivery of fluorescently labeled mPTD-BMP-7 into the murine liver in vivo, we tested the mPTD-BMP-7 formulation in a murine liver fibrosis model, developed by repeated intraperitoneal injection of hepatotoxic carbon tetrachloride, twice weekly from 4 to 16 weeks. mPTD-BMP-7 effects were tested by injecting the mPTD-BMP-7 formulation (or vehicle control) into the lateral tail at a dose of 50 (n=8) or 500 µg/kg (n=10), also twice per week from 4 to 16 weeks. Vehicle-treated control mice developed fibrous septa surrounding the liver parenchyma and marked portal-to-portal bridging with occasional nodules, whereas mice treated with mPTD-BMP-7 showed only fibrous expansion of some portal areas, with or without short fibrous septa. Using the Ishak scoring system, we found that the fibrotic burden was significantly lower in mPTD-BMP-7 treated mice than in control mice (all P<0.001). Treatment with mPTD-BMP-7 protected tight junctions between hepatocytes and reduced extracellular matrix protein levels. It also significantly decreased mRNA levels of collagen 1A, smooth muscle α-actin, and connective tissue growth factor compared with that in control mice (all P<0.001). Collectively, out results indicate that mPTD-BMP-7, a prodrug formulation of BMP-7, ameliorates liver fibrosis by suppressing the TGF-ß signaling pathway in a murine liver fibrosis model.

Peroxiredoxin 3 deficiency induces cardiac hypertrophy and dysfunction by impaired mitochondrial quality control.

Mitochondrial quality control (MQC) consists of multiple processes: the prevention of mitochondrial oxidative damage, the elimination of damaged mitochondria via mitophagy and mitochondrial fusion and fission. Several studies proved that MQC impairment causes a plethora of pathological conditions including cardiovascular diseases. However, the precise molecular mechanism by which MQC reverses mitochondrial dysfunction, especially in the heart, is unclear. The mitochondria-specific peroxidase Peroxiredoxin 3 (Prdx3) plays a protective role against mitochondrial dysfunction by removing mitochondrial reactive oxygen species. Therefore, we investigated whether Prdx3-deficiency directly leads to heart failure via mitochondrial dysfunction. Fifty-two-week-old Prdx3-deficient mice exhibited cardiac hypertrophy and dysfunction with giant and damaged mitochondria. Mitophagy was markedly suppressed in the hearts of Prdx3-deficient mice compared to the findings in wild-type and Pink1-deficient mice despite the increased mitochondrial damage induced by Prdx3 deficiency. Under conditions inducing mitophagy, we identified that the damaged mitochondrial accumulation of PINK1 was completely inhibited by the ablation of Prdx3. We propose that Prdx3 interacts with the N-terminus of PINK1, thereby protecting PINK1 from proteolytic cleavage in damaged mitochondria undergoing mitophagy. Our results provide evidence of a direct association between MQC dysfunction and cardiac function. The dual function of Prdx3 in mitophagy regulation and mitochondrial oxidative stress elimination further clarifies the mechanism of MQC in vivo and thereby provides new insights into developing a therapeutic strategy for mitochondria-related cardiovascular diseases such as heart failure.

Fabrication and evaluation of bilateral Helmholtz radiofrequency coil for thermo-stable breast image with reduced artifacts.

PURPOSE: The positron emission tomography (PET)-magnetic resonance (MR) system is a newly emerging technique that yields hybrid images with high-resolution anatomical and metabolic information. With PET-MR imaging, a definitive diagnosis of breast abnormalities will be possible with high spatial accuracy and images will be acquired for the optimal fusion of anatomic locations. Therefore, we propose a PET-compatible two-channel breast MR coil with minimal disturbance to image acquisition which can be used for simultaneous PET-MR imaging in patients with breast cancer. MATERIALS AND METHODS: For coil design and construction, the conductor loops of the Helmholtz coil were tuned, matched, and subdivided with nonmagnetic components. Element values were optimized with an electromagnetic field simulation. Images were acquired on a GE 600 PET-computed tomography (CT) and GE 3.0 T MR system. For this study, we used the T1-weighted image (volunteer; repetition time (TR), 694 ms; echo time (TE), 9.6 ms) and T2-weighted image (phantom; TR, 8742 ms; TE, 104 ms) with the fast spin-echo sequence. RESULTS: The results of measuring image factors with the proposed radiofrequency (RF) coil and standard conventional RF coil were as follows: signal-to-noise ratio (breast; 207.7 vs. 175.2), percent image uniformity (phantom; 89.22%-91.27% vs. 94.63%-94.77%), and Hounsfield units (phantom; -4.51 vs. 2.38). CONCLUSIONS: Our study focused on the feasibility of proposed two-channel Helmholtz loops (by minimizing metallic components and soldering) for PET-MR imaging and found the comparable image quality to the standard conventional coil. We believe our work will help significantly to improve image quality with the development of a less metallic breast MR coil.

Suppression of DYRK1A/B Drives Endoplasmic Reticulum Stress-mediated Autophagic Cell Death Through Metabolic Reprogramming in Colorectal Cancer Cells.

BACKGROUND/AIM: We previously identified KS40008 (4-(3-(4-hydroxyphenyl)-1H-pyrazolo[3,4-b]pyridin-5-yl)benzene-1,2-diol), a novel inhibitor of dual-specificity tyrosine phosphorylation-regulated kinase family (DYRK) 1A/B, which exhibited high enzymatic activity and cell proliferation-inhibitory effects in colorectal cancer (CRC) cell lines. In the present study, we aimed to elucidate the antitumor mechanisms of KS40008. MATERIALS AND METHODS: To assess the cytotoxicity of KS40008, we utilized a human cell line and organoid model and performed a CCK-8 assay and real-time cell analysis. Mitochondrial function was determined through mitochondrial staining, mito-stress test, and glycolysis test. In addition, we investigated the mechanisms of cancer cell death induced by KS40008 through immunoblotting, real-time quantitative polymerase chain reaction, reactive oxygen species staining, and immunofluorescence staining. RESULTS: KS40008 exhibited significant cytotoxicity in CRC and non-CRC cell lines, and organoid models compared to 5-fluorouracil, a conventional chemotherapeutic drug. Moreover, KS40008-induced inhibition of DYRK1A/B led to mitochondrial dysfunction and endoplasmic reticulum stress, promoting autophagic cancer cell death. CONCLUSION: KS40008 exerts antitumor activity through the inhibition of DYRK1A/B. Here, we demonstrated a mechanism by which KS40008 affects endoplasmic reticulum stress-mediated autophagy through the induction of mitochondrial stress, leading to cytotoxicity in CRC.

ER-associated CTRP1 regulates mitochondrial fission via interaction with DRP1.

C1q/TNF-related protein 1 (CTRP1) is a CTRP family member that has collagenous and globular C1q-like domains. The secreted form of CTRP1 is known to be associated with cardiovascular and metabolic diseases, but its cellular roles have not yet been elucidated. Here, we showed that cytosolic CTRP1 localizes to the endoplasmic reticulum (ER) membrane and that knockout or depletion of CTRP1 leads to mitochondrial fission defects, as demonstrated by mitochondrial elongation. Mitochondrial fission events are known to occur through an interaction between mitochondria and the ER, but we do not know whether the ER and/or its associated proteins participate directly in the entire mitochondrial fission event. Interestingly, we herein showed that ablation of CTRP1 suppresses the recruitment of DRP1 to mitochondria and provided evidence suggesting that the ER-mitochondrion interaction is required for the proper regulation of mitochondrial morphology. We further report that CTRP1 inactivation-induced mitochondrial fission defects induce apoptotic resistance and neuronal degeneration, which are also associated with ablation of DRP1. These results demonstrate for the first time that cytosolic CTRP1 is an ER transmembrane protein that acts as a key regulator of mitochondrial fission, providing new insight into the etiology of metabolic and neurodegenerative disorders.

Recent Developments of ICG-Guided Sentinel Lymph Node Mapping in Oral Cancer.

Sentinel lymph node (SLN) biopsy has gained attention as a method of minimizing the extent of neck dissection with a similar survival rate as elective neck dissection in oral cancer. Indocyanine green (ICG) imaging is widely used in the field of surgical oncology. Real-time ICG-guided SLN imaging has been widely used in minimally invasive surgeries for various types of cancers. Here, we provide an overview of conventional SLN biopsy and ICG-guided SLN mapping techniques for oral cancer. Although ICG has many strengths, it still has limitations regarding its potential use as an ideal compound for SLN mapping. The development of novel fluorophores and imaging technology is needed for accurate identification of SLNs, which will allow precision surgery that would reduce morbidities and increase patient survival.

Deep Generative Adversarial Networks: Applications in Musculoskeletal Imaging.

In recent years, deep learning techniques have been applied in musculoskeletal radiology to increase the diagnostic potential of acquired images. Generative adversarial networks (GANs), which are deep neural networks that can generate or transform images, have the potential to aid in faster imaging by generating images with a high level of realism across multiple contrast and modalities from existing imaging protocols. This review introduces the key architectures of GANs as well as their technical background and challenges. Key research trends are highlighted, including: (a) reconstruction of high-resolution MRI; (b) image synthesis with different modalities and contrasts; (c) image enhancement that efficiently preserves high-frequency information suitable for human interpretation; (d) pixel-level segmentation with annotation sharing between domains; and (e) applications to different musculoskeletal anatomies. In addition, an overview is provided of the key issues wherein clinical applicability is challenging to capture with conventional performance metrics and expert evaluation. When clinically validated, GANs have the potential to improve musculoskeletal imaging. Keywords: Adults and Pediatrics, Computer Aided Diagnosis (CAD), Computer Applications-General (Informatics), Informatics, Skeletal-Appendicular, Skeletal-Axial, Soft Tissues/Skin © RSNA, 2021.

Patterns of Locoregional Recurrence after Radical Cystectomy for Stage T3-4 Bladder Cancer: A Radiation Oncologist's Point of View.

PURPOSE: Adjuvant radiotherapy (RT) has been performed to reduce locoregional failure (LRF) following radical cystectomy for locally advanced bladder cancer; however, its efficacy has not been well established. We analyzed the locoregional recurrence patterns of post-radical cystectomy to identify patients who could benefit from adjuvant RT and determine the optimal target volume. MATERIALS AND METHODS: We retrospectively reviewed 160 patients with stage ≥ pT3 bladder cancer who were treated with radical cystectomy between January 2006 and December 2015. The impact of pathologic findings, including the stage, lympho-vascular invasion, perineural invasion, margin status, nodal involvement, and the number of nodes removed on failure patterns, was assessed. RESULTS: Median follow-up period was 27.7 months. LRF was observed in 55 patients (34.3%), 12 of whom presented with synchronous local and regional failures as the first failure. The most common failure pattern was distant metastasis (40%). Among LRFs, the most common recurrence site was the cystectomy bed (15.6%). Patients with positive resection margins had a significantly higher recurrence rate compared to those without (28% vs. 10%, p=0.004). The pelvic nodal recurrence rate was < 5% in pN0 patients; the rate of recurrence in the external and common iliac nodes was 12.5% in pN+ patients. The rate of recurrence in the common iliac nodes was significantly higher in pN2-3 patients than in pN0-1 patients (15.2% vs. 4.4%, p=0.04). CONCLUSION: Pelvic RT could be beneficial especially for those with positive resection margins or nodal involvement after radical cystectomy. Radiation fields should be optimized based on the patient-specific risk factors.

Artificial intelligence in musculoskeletal ultrasound imaging.

Ultrasonography (US) is noninvasive and offers real-time, low-cost, and portable imaging that facilitates the rapid and dynamic assessment of musculoskeletal components. Significant technological improvements have contributed to the increasing adoption of US for musculoskeletal assessments, as artificial intelligence (AI)-based computer-aided detection and computer-aided diagnosis are being utilized to improve the quality, efficiency, and cost of US imaging. This review provides an overview of classical machine learning techniques and modern deep learning approaches for musculoskeletal US, with a focus on the key categories of detection and diagnosis of musculoskeletal disorders, predictive analysis with classification and regression, and automated image segmentation. Moreover, we outline challenges and a range of opportunities for AI in musculoskeletal US practice.

Micellized Protein Transduction Domain-Bone Morphogenetic Protein-7 Efficiently Blocks Renal Fibrosis Via Inhibition of Transforming Growth Factor-Beta-Mediated Epithelial-Mesenchymal Transition.

Tubulointerstitial renal fibrosis is a chronic disease process affecting chronic kidney disease (CKD). While the etiological role of transforming growth factor-beta (TGF-ß) is well known for epithelial-mesenchymal transition (EMT) in chronic kidney disease, effective therapeutics for renal fibrosis are largely limited. As a member of the TGF-ß superfamily, bone morphogenetic protein-7 (BMP-7) plays an important role as an endogenous antagonist of TGF-ß, inhibiting fibrotic progression in many organs. However, soluble rhBMP-7 is hardly available for therapeutics due to its limited pharmacodynamic profile and rapid clearance in clinical settings. In this study, we have developed a novel therapeutic approach with protein transduction domain (PTD) fused BMP-7 in micelle (mPTD-BMP-7) for long-range signaling in vivo. Contrary to rhBMP-7 targeting its cognate receptors, the nano-sized mPTD-BMP-7 is transduced into cells through an endosomal pathway and secreted to the exosome having active BMP-7. Further, transduced mPTD-BMP-7 successfully activates SMAD1/5/8 and inhibits the TGF-ß-mediated epithelial-mesenchymal transition process in vitro and in an in vivo unilateral ureter obstruction model. To determine the clinical relevance of our strategy, we also developed an intra-arterial administration of mPTD-BMP-7 through renal artery in pigs. Interestingly, mPTD-BMP-7 through renal artery intervention effectively delivered into Bowman's space and inhibits unilateral ureter obstruction-induced renal fibrosis in pigs. Our results provide a novel therapeutic targeting TGF-ß-mediated renal fibrosis and other organs as well as a clinically available approach for kidney.

Squamous Cell Carcinoma and Lymphoma of the Oropharynx: Differentiation Using a Radiomics Approach.

The purpose of this study was to evaluate the diagnostic performance of magnetic resonance (MR) radiomics-based machine learning algorithms in differentiating squamous cell carcinoma (SCC) from lymphoma in the oropharynx. MR images from 87 patients with oropharyngeal SCC (n=68) and lymphoma (n=19) were reviewed retrospectively. Tumors were semi-automatically segmented on contrast-enhanced T1-weighted images registered to T2-weighted images, and radiomic features (n=202) were extracted from contrast-enhanced T1- and T2-weighted images. The radiomics classifier was built using elastic-net regularized generalized linear model analyses with nested five-fold cross-validation. The diagnostic abilities of the radiomics classifier and visual assessment by two head and neck radiologists were evaluated using receiver operating characteristic (ROC) analyses for distinguishing SCC from lymphoma. Nineteen radiomics features were selected at least twice during the five-fold cross-validation. The mean area under the ROC curve (AUC) of the radiomics classifier was 0.750 [95% confidence interval (CI), 0.613-0.887], with a sensitivity of 84.2%, specificity of 60.3%, and an accuracy of 65.5%. Two human readers yielded AUCs of 0.613 (95% CI, 0.467-0.759) and 0.663 (95% CI, 0.531-0.795), respectively. The radiomics-based machine learning model can be useful for differentiating SCC from lymphoma of the oropharynx.

Elimination of Unreacted Acrylate Double Bonds in the Polymer Networks of Microparticles Synthesized via Flow Lithography.

Flow lithography (FL), a versatile technique used to synthesize anisotropic multifunctional microparticles, has attracted substantial interest, given that the resulting particles with complex geometries and multilayered biochemical functionalities can be used in a wide variety of applications. However, after this process, there are double bonds remaining from the cross-linkable groups of monomers. The unreacted cross-linkable groups can affect the particles' biochemical properties. Here, we verify that the microparticles produced by FL contain a significant number of unreacted acrylate double bonds (UADBs), which could cause irreversible biochemical changes in the particle and pernicious effects to biological systems. We also confirm that the particles contain a considerable number of UADBs, regardless of the various synthetic (lithographic) conditions that can be used in a typical FL process. We present an effective way to eliminate a substantial amount of UADBs after synthesis by linking biochemically inert poly(ethylene glycol) based on click chemistry. We verify that eliminating UADBs by using this click chemistry approach can efficiently resolve problems, such as the occurrence of random reactions and the cytotoxicity of UADBs.

Surface potential microscopy of surfactant-controlled single gold nanoparticle.

The surface potential of nanoparticles plays a key role in numerous applications, such as drug delivery and cellular uptake. The estimation of the surface potential of nanoparticles as drug carriers or contrast agents is important for the design of nanoparticle-based biomedical platforms. Herein, we report the direct measurement of the surface potential of individual gold nanorods (GNRs) via Kelvin probe force microscopy (KPFM) at the nanoscale. GNRs were capped by a surfactant, cetyltrimethylammonium bromide (CTAB), which was removed by centrifugation. CTAB removal is essential for GNR-based biomedical applications because of the cytotoxicity of CTAB. Applying KPFM analysis, we found that the mean surface potential of the GNRs became more negative as the CTAB was removed from the GNR. The results indicate that the negative charge of GNRs is covered by the electrostatic charge of the CTAB molecules. Similar trends were observed in experiments with gold nanospheres (GNS) capped by citrates. Overall, KPFM-based techniques characterize the surfactant of individual nanoparticles (i.e. GNR or GNS) with high resolution by mapping the surface potential of a single nanoparticle, which aids in designing engineered nanoparticles for biomedical applications.

Labeling-free detection of ECD-HER2 protein using aptamer-based nano-plasmonic sensor.

A gold nanoparticle-based localized surface plasmon resonance substrate has been developed as nano-sensors for various bio-applications. However, reproducible and robust sensing substrates anchored gold nanoparticles has not yet been explored. In this study, dopamine-coated gold nanorods (DGNRs) were prepared and immobilized onto the micro-grooving PDMS substrates (mgPDMS). Subsequently, HER2-specific aptamers were conjugated with DGNR/mgPDMS for ECD-HER2 detection. By screening of the optimal concentration of DGNR and aptamers, the effective HER2-specific aptasensor was built up. In particular, the real-time binding assay for the evaluation of limit-of-detection (<5 ng ml-1) was conducted. Furthermore, the binding kinetics for ECD-HER2 was investigated under the biological fluid using a rat serum. Our HER2-specific aptasensor demonstrated the effective sensitivity and selectivity for ECD-HER2.

Radiological assessment of effectiveness of soluble RAGE in attenuating Angiotensin II-induced LVH mouse model using in vivo 9.4T MRI.

We investigated the effectiveness of soluble Receptor for Advanced Glycation Endproducts (sRAGE) in attenuating angiotensin II (AngII)-induced left ventricular hypertrophy (LVH) using in vivo 9.4T cine-magnetic resonance imaging (CINE-MRI). Mice were divided into four groups: AngII (n = 9), saline (n = 10), sRAGE (n = 10), and AngII + sRAGE (n = 10). CINE-MRI was performed in each group after administration of the AngII or sRAGE, and CINE-MR images were analyzed to obtain parameters indicating cardiac anatomical and functional changes including end-diastolic and end-systolic blood volume, end-diastolic and end-systolic myocardial volume, ejection fraction, end-diastolic and end-systolic myocardial mass, and LV wall thickness. LVH observed in AngII group was significantly attenuated by sRAGE. These trends were also observed in histological analysis, demonstrating that cardiac function tracking using in vivo and real-time 9.4T MR imaging provides valuable information about the cardiac remodeling induced by AngII and sRAGE in an AngII-induced LV hypertrophy mice model.

Smart Microcapsules with Molecular Polarity- and Temperature-Dependent Permeability.

Microcapsules with molecule-selective permeation are appealing as microreactors, capsule-type sensors, drug and cell carriers, and artificial cells. To accomplish molecular size- and charge-selective permeation, regular size of pores and surface charges have been formed in the membranes. However, it remains an important challenge to provide advanced regulation of transmembrane transport. Here, smart microcapsules are designed that provide molecular polarity- and temperature-dependent permeability. With capillary microfluidic devices, water-in-oil-in-water (W/O/W) double-emulsion drops are prepared, which serve as templates to produce microcapsules. The oil shell is composed of two monomers and dodecanol, which turns to a polymeric framework whose continuous voids are filled with dodecanol upon photopolymerization. One of the monomers provides mechanical stability of the framework, whereas the other serves as a compatibilizer between growing polymer and dodecanol, preventing macrophase separation. Above melting point of dodecanol, molecules that are soluble in the molten dodecanol are selectively allowed to diffuse across the shell, where the rate of transmembrane transport is strongly influenced by partition coefficient. The rate is drastically lowered for temperatures below the melting point. This molecular polarity- and temperature-dependent permeability renders the microcapsules potentially useful as drug carriers for triggered release and contamination-free microreactors and microsensors.