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Background and Objectives This study aimed to investigate the protective effect of polydeoxyribonucleotide (PDRN) against skin flap necrosis in a murine skin flap model.Materials and Method Twenty mice with rectangular skin flaps on the dorsum were randomly divided into the PDRN (n=10) and pentobarbital sodium (PBS) (n=10) injection groups. PDRN (8 mg/kg) was subdermally injected at 12 different points immediately after the operation. After 7 days, the flap perfusions were evaluated using a laser speckle contrast imaging (LSCI) system, and specimens were collected for immunohistochemistry analysis.Results The percentage of survival area relative to the total flap area was significantly higher in the PDRN group (60.87%±7.63%) than in the PBS group (45.23%±10.72%) (ppp

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.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.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.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.

Reprogramming of cellular metabolism is an important, emerging, and universal hallmark of cancer which has received considerable attention during the recent era of cancer research. Cancer cells show characteristic alterations in glucose metabolism in order to fulfill the needs of biosynthesis for tumor proliferation and growth. However, under certain circumstances such as invasion and metastasis, cancer cells are prone to metabolic stress and will require different strategies to meet the high energetic demand from cancer progression. From various metabolic rewiring mechanisms, cancer cells adopt other metabolic pathways with alternative nutrient sources. Therefore, targeting cancer metabolism holds promising but great challenge caused by the metabolic plasticity of cancer cells. This review will discuss characteristic cancer metabolism in detail with special focus on lipid metabolism which is gathering increasingly keen interest, in order to find novel therapeutic approaches to head and neck cancer. By understanding and exploiting the synthesis, oxidation, and storage of fatty acids, we could investigate potential strategies to block cancer proliferation and progression.

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.

This study used magnetic resonance (MR) thermometry to investigate the temperature increases and thermal diffusion that occur during plasmonic photothermal therapy (PTT) with gold nanorods (GNRs). An artificial tumor phantom made of agarose gel containing GNRs was heated by irradiation with an 808 nm laser. The MR thermometer visualized the conditions: a well-localized temperature distribution with suppressed thermal diffusion that depended on laser power and irradiation time. A tumor phantom model was implanted in mice, and MR thermometry evaluated the temperature change in the presence and absence of GNRs and the thermal diffusion into the surrounding tissues. That experiment showed that MR thermometry can be a useful tool for monitoring PTT. These results suggest that MR temperature measurement could help to establish ideal laser irradiation conditions in GNR-mediated PTT, and that it has great potential for visualizing local photothermal induction and evaluating therapeutic effects.

Bone morphogenetic protein-7 (BMP-7) antagonizes transforming growth factor-β (TGF-β), 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-β 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

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.

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.

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.

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.

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.

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.

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.

Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) has been a longstanding challenge for head and neck oncologists, and current treatments still have limited efficacy. ERK is aberrantly overexpressed and activated in HNSCC. Herein, we aimed to investigate the cause of the limited therapeutic effect of selumetinib, a selective inhibitor of MEK in HNSCC, as MEK/ERK reactivation inevitably occurs. We assessed the effects of combining selumetinib with fibroblast growth factor receptor 3 (FGFR3) inhibitor (PD173074) on tumor growth. Selumetinib transiently inhibited MAPK signaling and reactivated ERK signaling in HNSCC cells. Rebound in the ERK and Akt pathways in HNSCC cells was accompanied by increased FGFR3 signaling after selumetinib treatment. Feedback activation of FGFR3 was a result of autocrine secretion of the FGF2 ligand. The FGFR3 inhibitor PD173074 prevented MAPK rebound and sensitized the response of HNSCC cells to selumetinib. These results provided rational therapeutic strategies for clinical studies of this subtype of patients that show a poor prognosis with selumetinib. Our data provide a rationale for combining a MEK inhibitor with inhibitors of feedback activation of FGFR3 signaling in HNSCC cells. ERK rebound as a result of the upregulation of FGFR3 and the ligand FGF2 diminished the antitumor effects of selumetinib, which was overcome by combination treatment with the FGFR3 inhibitor.

Gold nanorods (GNRs) are of great interest in cancer therapy given their ability to ablate tumor cells using deep tissue-penetrating near-infrared light. GNRs coated with tumor-specific moieties have the potential to target tumor tissue to minimize damage to normal tissue. However, perfect targeting is difficult to achieve given that nanoparticles could be broadly dispersed inside the body. Moreover, interaction between targeting groups and biological molecules could lower targeting abilities, resulting in off-target accumulation which might produce nanotoxicity. Here we introduce GNR-encapsulated microcubes (GNR@MCs) that can be utilized as implantable photothermal agents. GNR@MCs are created by encapsulating GNRs in polymeric networks via stop flow lithography (SFL), a one-phase synthesis technique which allows for creation of surfactant-free, uniform particles, and injection of GNR@MCs into the body after a simple rinse step. GNRs are highly packed and firmly encapsulated inside MCs, and entrapped GNRs exhibit optical properties comparable to that of unbound GNRs and photothermal efficiency (58%) in line with that of nano-sized agents (51–95%). Photothermal ablation in murine models is achieved using GNR@MCs stably implanted into the tumor tissue, which suggests that GNR@MCs can be a safe and effective platform for cancer therapy.

The aim of this study was the development of a human epidermal growth factor receptor 2 (HER2)-targetable contrast agent for magnetic resonance imaging (MRI) with a high magnetic sensitivity. An anti-HER2 aptamer-modified magnetic nanosensitizer (AptHER2-MNS) was prepared by conjugation with 5′-thiol-modified aptamers and maleimidylated magnetic nanocrystals (MNCs). The physicochemical characteristics and targeting ability of AptHER2-MNS were confirmed, and the binding affinity (K d ) onto HER2 protein of AptHER2-MNS was 0.57 ± 0.26 nM. In vivo MRI contrast enhancement ability was also verified at HER2+ cancer cell (NIH3T6.7)-xenograft mouse models (n = 3) at 3T clinical MRI instrument. The control experiment was carried out using non-labeled MNCs. The results indicated that up to 150% contrast enhancement was achieved at the tumor region in the T2-weighted MR images after the injection of the AptHER2-MNS agent in mice that received the NIH3T6.7 cells.

Here, we demonstrate a powerful method to discriminate DNA mismatches at single-nucleotide resolution from 0 to 5 mismatches (χ0 to χ5) using Kelvin probe force microscopy (KPFM). Using our previously developed method, we quantified the surface potentials (SPs) of individual DNA-capped nanoparticles (DCNPs, ∼100 nm). On each DCNP, DNA hybridization occurs between ∼2200 immobilized probe DNA (pDNA) and target DNA with mismatches (tDNA, ∼80 nM). Thus, each DCNP used in the bioassay (each pDNA-tDNA interaction) corresponds to a single ensemble in which a large number of pDNA-tDNA interactions take place. Moreover, one KPFM image can scan at least dozens of ensembles, which allows statistical analysis (i.e., an ensemble average) of many bioassay cases (ensembles) under the same conditions. We found that as the χn increased from χ0 to χ5 in the tDNA, the average SP of dozens of ensembles (DCNPs) was attenuated owing to fewer hybridization events between the pDNA and the tDNA. Remarkably, the SP attenuation vs. the χn showed an inverse-linear correlation, albeit the equilibrium constant for DNA hybridization exponentially decreased asymptotically as the χn increased. In addition, we observed a cascade reaction at a 100-fold lower concentration of tDNA (∼0.8 nM); the average SP of DCNPs exhibited no significant decrease but rather split into two separate states (no-hybridization vs. full-hybridization). Compared to complementary tDNA (i.e., χ0), the ratio of no-hybridization/full-hybridization within a given set of DCNPs became ∼1.6 times higher in the presence of tDNA with single mismatches (i.e., χ1). The results imply that our method opens new avenues not only in the research on the DNA hybridization mechanism in the presence of DNA mismatches but also in the development of a robust technology for DNA mismatch detection.

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.

Herein, we report a de novo synthesis approach to produce bandgap-controlled polyaniline (PAni) nanostructure via Mn-mediated oxidative polymerization at the catalytic nanoreactor. To achieve systemic nanoconfined polymerization, manganese oxide (MnOx) nanoparticles coated with silica were used as the sacrificial nanotemplate. Interestingly, the catalytic nanoreactor simultaneously allowed the nanoconfined oxidative polymerization and controlling of the bandgap. MnOx could be reduced by the addition of aniline monomers and consecutive redox reaction at the nanoreactor. Furthermore, core cavity was generated, and ionized Mn could control the bandgap by coordination at the nanostructures.

// Hyung Kwon Byeon 1 , Hwi Jung Na 1 , Yeon Ju Yang 1 , Sooah Ko 1 , Sun Och Yoon 2 , Minhee Ku 3, 4 , Jaemoon Yang 3, 5 , Jae Wook Kim 6 , Myung Jin Ban 6 , Ji-Hoon Kim 7 , Da Hee Kim 1 , Jung Min Kim 1 , Eun Chang Choi 1 , Chang-Hoon Kim 1, 8 , Joo-Heon Yoon 1, 8, 9 , Yoon Woo Koh 1, 8 1 Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Republic of Korea 2 Department of Pathology, Yonsei University College of Medicine, Seoul, Republic of Korea 3 Department of Radiology, Yonsei University College of Medicine, Seoul, Republic of Korea 4 Brain Korea 21 Plus Project for Medical Science, Yonsei University College of Medicine, Seoul, Republic of Korea 5 YUHS-KRIBB Medical Convergence Research Institute, Seoul, Republic of Korea 6 Department of Otorhinolaryngology, Soonchunhyang University College of Medicine, Republic of Korea 7 Department of Otorhinolaryngology-Head and Neck Surgery, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea 8 The Airway Mucus Institute, Yonsei University College of Medicine, Seoul, Republic of Korea 9 Research Center for Human Natural Defense System, Yonsei University College of Medicine, Seoul, Republic of Korea Correspondence to: Yoon Woo Koh, email: ywkohent@yuhs.ac Keywords: thyroid cancer, molecular targeted therapy, drug resistance, BRAF mutation, epithelial-mesenchymal transition Received: September 23, 2016 Accepted: November 12, 2016 Published: November 21, 2016 ABSTRACT Previously, the authors have identified that c-Met mediates reactivation of the PI3K/AKT pathway following BRAF inhibitor treatment in BRAF (V600E) mutant anaplastic thyroid cancer, thereby contributing to the acquired drug resistance. Therefore dual inhibition of BRAF and c-Met led to sustained treatment response, thereby maximizing the specific anti-tumor effect of targeted therapy. The present study goes one step further and aims to investigate the effect of acquired resistance of BRAF inhibitor on epithelial-to-mesenchymal transition (EMT) in BRAF mutant thyroid cancer cells and the effect of dual inhibition from combinatorial therapy. Two thyroid cancer cell lines, 8505C and BCPAP were selected and treated with BRAF inhibitor, PLX4032 and its effect on EMT were examined and compared. Further investigation was carried out in orthotopic xenograft mouse models. Unlike BCPAP cells, the BRAF inhibitor resistant 8505C cells showed increased expressions of EMT related markers such as vimentin, β-catenin, and CD44. The combinatorial treatment of PLX4032 and PHA665752, a c-Met inhibitor reversed EMT. Similar results were confirmed in vivo . c-Met-mediated reactivation of the PI3K/AKT pathway contributes to the drug resistance to PLX4032 in BRAF (V600E) mutant anaplastic thyroid cancer cells and further promotes tumor cell migration and invasion by upregulated EMT mechanism. Dual inhibition of BRAF and c-Met leads to reversal of EMT, suggesting a maximal therapeutic response.

Near-infrared (NIR) fluorophores attract increasing attention as a molecular marker (or probe) for in vivo and in vitro biological fluorescence imaging. Three types of new NIR fluorescent conjugated oligoelectrolytes (COEs: Q-FlTBTTFl, Q-FlBBTFl, and Q-FlTBBTTFl) are synthesized with quaternized ammonium ionic groups in their side-chains for water solubility. The emission wavelength is modulated in the range 600-1300 nm, by adjusting the intramolecular charge transfer in the molecular backbone based on the electron-rich fluorene (and/or thiophene) and electron-deficient benzo[2,1,3]thiadiazole (or benzo[1,2-c:4,5-c']bis[1,2,5]thiadiazole) moieties. The COEs show a remarkably larger Stokes shift (147-276 nm) compared to commercial rhodamine and cyanine dyes in water, avoiding self-quenching and interference from the excitation backscattered light. The photoluminescence (PL) quantum efficiency is improved substantially by up to 27.8% in water by fabricating a vesicular complex, COE/v, with a block ionomer, poly[(ethylene oxide)-block-(sodium 2-acrylamido-2-methyl-1-propanesulfonate)]. In vitro cellular uptake images with the COEs are obtained with good biocompatibility by confocal single-photon and two-photon microscopy. The ex vivo and in vivo images of a mouse xenograft model treated with the Q-FlBBTFl/v exhibit a substantially stronger fluorescence signal at the tumor site than at the other organs, highlighting the potential of the COE/v as an NIR fluorescent imaging agent for the diagnosis of cancer.

Real-time screening of cellular response on the drugs could provide valuable insights for the early detection of therapeutic efficiency and the evaluation of disease progression. Cancer cells have the ability to vary widely in response to stress in a manner to adjust the signaling pathway to promote the survival or having a resistance to stimulation. Cell-based label-free technologies using electronic impedance sensor have strategies for constructing the signature profiles of each cells. To achieve exquisite sensitivity to substantially change of live-cell response have an important role that predict the potential of therapeutic effects. In this study, we use an impedance-based real-time cell analysis system to investigate dynamic phenotypes of cells described as a cellular index value. We show that gastric cancer cells generated characteristic kinetic patterns that corresponded to the treatment order of therapeutics. The kinetic feature of the cells offers insightful information that cannot be acquired from a conventional single end-point assay. Furthermore, we employ a 'sequential treatment strategy' to increase cytotoxic effects with minimizing the use of chemotherapeutics. Specifically, treatment of paclitaxel (PTX) after down-regulating Akt gene expression using RNAi reduces the cell proliferation and increases apoptosis. We propose that the sequential treatment may exhibit more effective approach rather than traditional combination therapy. Moreover, the dynamic monitoring of cell-drug interaction enables us to obtain a better understanding of the temporal effects in vitro.

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.

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 (

Recently, Near-infrared (NIR)-induced photothermal killing of pathogenic bacteria has received considerable attention due to the increase in antibiotic resistant bacteria. In this paper, we report a simple aqueous solution-based strategy to construct an effective photothermal nanocomposite composed of poly(3,4-ethylenedioxythiophene):poly(styrene-sulfonate) (PEDOT:PSS) and agarose with thermo-processability, light triggered self-healing, and excellent antibacterial activity. Our experiments revealed that PEDOT:PSS/agarose was easily coated on both a 2D glass substrate and 3D cotton structure. Additionally, PEDOT:PSS/agarose can be designed into free-standing objects of diverse shape as well as restored through an NIR light-induced self-healing effect after damage. Taking advantage of strong NIR light absorption, PEDOT:PSS/agarose exhibited a sharp temperature increase of 24.5 °C during NIR exposure for 100 s. More importantly, we demonstrated that the temperature increase on PEDOT:PSS/agarose via photothermal conversion resulted in the rapid and effective killing of nearly 100% of the pathogenic bacteria within 2 min of NIR irradiation.

Figure S1. Physicochemical characterization of Tm80. (a) Absorbance spectra, FT-IR spectra; and (b) 1H-NMR spectra of 3-MPA (black line), T80 (blue line), and Tm80 (red line). Figure S2. Schematics showing the volume of oxygen ionic radius in single FCC unit. Figure S3. Half-life of anti-HER2 aptamer in serum: the half-life of control (non-modified), 3 h; NapdU-modified, 151 h. Figure S4. In vivo MR images of HER2+ tumor mouse model (a) AptHER2-MNS—injected group, (b) WMNC—injected group. Scale bars, 5 mm. Table S1. Relative intensities of in vivo MR images measured from figure 5 and S4 (red solid-lined ROI) (DOCX 1110 kb)

Herein, we demonstrate an acidic environmental sensing technique based on polyaniline (PAni) nanoparticles and a nanoscattering spectrum imaging analysis (NSSIA) system. PAni nanoparticles (PNs) were formulated by a homogeneous coating process using Tween® 80 as a surfactant. Subsequently, PNs were immobilized to an aminated glass substrate to sense environmental pH conditions for single PNs, using the NSSIA system. In contrast to dark-field scattering imaging of the PN, the NSSIA system enabled us to obtain scattering spectra for a single PN to specifically identify the environmental pH conditions. Furthermore, the immobilized PN on the substrate exhibited excellent reversibility for the acquisition of the scattering spectra after repeated change of environmental pH.

To validate the usefulness of a newly developed tracer for preoperative gastric sentinel lymph node (LN) (SLN) mapping and intraoperative navigation after a single preoperative submucosal injection in rat and beagle models.This study was approved by the Experimental Animal Ethical Committee of Yonsei University College of Medicine according to the eighth edition of the Guide for the Care and Use of Laboratory Animals published in 2011. An emulsion was developed that contained indocyanine green in iodized oil, which can be visualized with both computed tomography (CT) and near-infrared (NIR) optical imaging and has the property of delayed washout. This emulsion was injected into the footpad of rats (n = 6) and the gastric submucosa of beagles (n = 8). CT lymphography was performed. The degree of enhancement of popliteal LNs was measured in rats, and the enhancing LNs were identified and the degree of enhancement of the enhancing LNs was measured in beagles. Next, NIR imaging was performed in beagles during open, laparoscopic, and robotic surgery to identify LNs containing the fluorescent signals of indocyanine green. The enhanced LNs detected with CT lymphography and NIR imaging were matched to see if they corresponded.Preoperative CT lymphography facilitated SLN mapping, and 26 SLNs were identified in eight beagles. NIR imaging enabled high-spatial-resolution visualization of both SLNs and the intervening lymphatic vessels and was useful for intraoperative SLN navigation.SLN mapping with fluorescent iodized oil emulsion is effective and feasible for both CT and NIR imaging.

To access smart optical theragnosis for cancer, an easily processable heterocyclic conjugated polymer (poly(sodium3-((3-methyl-3,4-dihydro-2H-thieno[3,4-b][1,4]dioxepin-3-yl)methoxy)propane-1-sulfonate), PPDS) nanoassembly is fabricated by a surfactant-free one-step process, without the laborious ordinary multicoating process. The conjugated nanoassembly, with a self-doped structure, provides strong absorbance in the near-infrared (NIR) range even in a neutral pH medium and exhibits excellent stability (>six months). In addition, the prepared PPDS nanoassembly shows a high photothermal conversion efficiency of 31.4% in organic photothermal nanoparticles. In particular, the PPDS nanoassembly is stably suspended in the biological medium without any additives. Through a simple immobilization with the anti-CD44 antibody, the prepared biomarker-targetable PPDS nanoassembly demonstrates specific targeting toward CD44 (expressed in stem-like cancer cells), allowing NIR absorbance imaging and the efficient targeted photothermal damaging of CD44-expressing cancer cells, from in vitro 3D mammospheres (similar to the practical structure of tumor in the body) to in vivo xenograft mice tumor models (breast cancer and fibrosarcoma). In this study, the most simplified preparation method is for this organic conjugated polymer-based nanoassembly by a molecular approach is reported, and demonstrated as a highly promising optical nanoagent for optical cancer theragnosis.

The objectives of the study are to introduce the development of supervising software for double-checking of laterality error in radiology reports and to evaluate the usefulness of detection and correction software by applying it to radiology report systems. An AutoHotkey macro program was applied to the design for double-checking of laterality errors. The software was performed according to the flowchart below: (1) detecting laterality discrepancies between radiologic examination names and the context of the radiology report and (2) providing conditioned discrepancy correction with a pop-up window. The accuracy of the detection was evaluated with 300 radiologic examinations that include the intended discrepancies and concordance of lateralities. The number of detections and corrections were quantified, and the confidence intervals were calculated for accuracy. We also applied this module to previous radiology reports with laterality errors from the radiologic examination database to validate the module. The AutoHotkey-scripted macro program functioned well in the reading workstation, and it was acted successfully as additional software. The detection accuracy was 99.67 % (95 % CI; 99.01―%) in the 300 radiologic examinations from the radiologic reading session. There was one running failure, caused by a temporary lag in the hospital’s computer network, but no failures resulted during the second trial. We found that there were laterality errors in 0.048 % (n = 14/29,257) of the examinations from the database. We developed detection and correction software aimed at double-checking for laterality errors. This method can be successfully adopted in any hospital software and is expected to be included for a better radiologic reading environment.

Cells constantly adjust their metabolic state in response to extracellular signals and nutrient availability to meet their demand for energy and building blocks. Recently, there has been significant research into the metabolic aspects of embryonic stem cells/pluripotent stem cells (ESCs/PSCs) and cancer stem cells (CSCs), which has revealed the unique metabolic status of different stem cell lineages. While ESCs and CSCs were largely thought to harbor similar metabolic states, recent evidence demonstrates that their metabolic dependency is distinctly different. The glucose metabolism of ESCs largely depends on glycolysis, including a one-carbon pathway during differentiation. While proliferating cancer cells share the glycolytic phenotype of ESCs, the mitochondria-centric oxidative phosphorylation constitutes an important metabolic circuit of CSCs under metabolic stress, indicating the dynamic nature of metabolic plasticity. In this review, we catalogued metabolic signatures of cellular "stemness" to provide insights into the therapeutic potential of ESCs and CSCs.