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Radiotherapy, although used worldwide for the treatment of head, neck, and oral cancers, causes acute complications, including effects on vasculature and immune response due to cellular stress. Thus, the ability to diagnose side-effects and monitor vascular response in real-time during radiotherapy would be highly beneficial for clinical and research applications. In this study, recently-developed fluorescence micro-endoscopic technology provides non-invasive, high-resolution, real-time imaging at the cellular level. Moreover, with the application of high-resolution imaging technologies and micro-endoscopy, which enable improved monitoring of adverse effects in GFP-expressing mouse models, changes in the oral vasculature and lymphatic vessels are quantified in real time for 10 days following a mild localized single fractionation, 10 Gy radiotherapy treatments. Fluorescence micro-endoscopy enables quantification of the cardiovascular recovery and immune response, which shows short-term reduction in mean blood flow velocity, in lymph flow, and in transient immune infiltration even after this mild radiation dose, in addition to long-term reduction in blood vessel capacity. The data provided may serve as a reference for the expected cellular-level physiological, cardiovascular, and immune changes in animal disease models after radiotherapy.

Colorectal cancer (CRC) is one of the most frequently lethal forms of cancer. Intramucosal injection allows development of better mouse models of CRC, as orthotopic xenografts allow development of adenocarcinoma in the submucosa of the mouse colon wall. In this paper, a method of orthotopic injection is monitored longitudinally using cellular-resolution real-time in vivo fluorescence microendoscopy, following the injection of three different cell lines: 3T3-GFP to confirm immunosuppression and HCT116-RFP cells to model CRC. Adenoma formation is first observable after 7 to 10 days, and by use of 33 G needles a tumor induction rate of greater than 85% is documented. An additional experiment on the injection of rapamycin reveals drug efficacy and localization between 24 and 48 hours, and suggests the promise of real-time cellular-resolution fluorescence micro-endoscopy for developing longitudinal therapy regimes in mural models of CRC.

Manganese (II) chloride tetrahydrate, classified as an inorganic phase-change material (PCM), can be used as a thermal energy storage material, saving and releasing thermal energy during its phase transitions. In this study, thermophysical properties, such as phase change temperatures, latent heat, and thermal conductivities, of four types of MnCl2·4H2O PCMs were investigated under single and dual phases (liquid-, solid-, and dual-phase PCMs) using differential scanning calorimetry (DSC) and a heat flow meter. PCMs with a liquid or dual phases exhibited superheating issues, and their melting temperatures were 7 to 10 °C higher than the reference melting temperatures. The PCMs had latent heats between 146 and 176 J/g in the temperature range of 23 to 45 °C under the endothermic process. Severe supercooling during the exothermic process was observed in all as-received specimens, but was mitigated in the homogenization-treated specimen, which sustained an increase in solidification temperature of about 15 °C compared with the as-received and treated PCMs. The diffusivities of PCMs were between 9.76 × 10−6 and 2.35 × 10−5 mm2/s. The diffusivities of the PCMs in the solid phase were higher than those in the liquid phase. During the initial holding time of the endothermic process, the PCM in the liquid phase could not be fully solidified due to an insufficient initial holding time and very low diffusivity, which caused superheating during the DSC measurement. Moreover, in the exothermic process, a fast cooling rate of 5 °C/min and low thermal diffusivity caused supercooling. In particular, the diffusivity of the liquid PCM was lower than those of the solid PCM and other PCMs, which caused extremely high supercooling during the DSC measurement. This paper provides the thermophysical properties of MnCl2·4H2O PCMs, which are not available in the literature. The homogeneity of PCMs in their initial states and their heating/cooling rates were identified, and constitute important factors for accurately measuring the thermophysical properties of PCMs.

Breast cancer is the most malignant type of cancer in women and is a global health problem, with mortality by metastasis being the main factor among others. Currently, detection and diagnosis of breast cancer is achieved through a variety of procedures, such as clinical examination, medical imaging, biopsy, and histopathological analysis. In contrast, spectroscopic analysis has a variety of advantages such as being noninvasive, not destroying biological materials, and not requiring additional histological analysis. In this study, various approaches using Raman spectroscopy, atomic force microscopy (AFM), and optical microscopy were used together to differentiate between and characterize normal breast cell lines (MCF-10A) and breast cancer cell lines (MDA-MB-231, MDA-MB-453). Raman spectra of normal breast cell and breast cancer cell lines confirmed visual differences in the concentrations of various compounds. These spectra were also analyzed using principle component analysis (PCA), and the PCA results showed reliable separation of the three cell lines and the cancer cell lines (MDA-MB-231, MDA-MB-453). With these results, optically synchronizing the AFM morphology, the Raman spectroscopy, and the visible RGB optical transmission intensity provided contrasts for not only conformational differences but also intracellular variation between the normal and cancer cell lines. We observed the inherent characteristic that there is no local difference in cancer cells regardless of morphology in a wide range of optical properties such as absorption, scattering and inelastic scattering.

Ribonucleic acid (RNA) plays an important role in many cellular processes. Thus, visualizing and quantifying the molecular dynamics of RNA directly in living cells is essential to uncovering their role in RNA metabolism. Among the wide variety of fluorescent probes available for RNA visualization, exciton-controlled hybridization-sensitive fluorescent oligonucleotide (ECHO) probes are useful because of their low fluorescence background. In this study, we apply fluorescence correlation methods to ECHO probes targeting the poly(A) tail of mRNA. In this way, we demonstrate not only the visualization but also the quantification of the interaction between the probe and the target, as well as of the change in the fluorescence brightness and the diffusion coefficient caused by the binding. In particular, the uptake of ECHO probes to detect mRNA is demonstrated in HeLa cells. These results are expected to provide new insights that help us better understand the metabolism of intracellular mRNA.

By adapting azobenzene polymer layer, both linear and concentric surface relief gratings (SRGs) have been successfully inscribed over optical fiber endfaces based on developing

Intravital microscopy has emerged as a powerful technique for the fluorescent visualization of cellular- and subcellular-level biological processes in vivo. However, the size of objective lenses used in standard microscopes currently makes it difficult to access internal organs with minimal invasiveness in small animal models, such as mice. Here we describe front- and side-view designs for small-diameter endoscopes based on gradient-index lenses, their construction, their integration into laser scanning confocal microscopy platforms, and their applications for in vivo imaging of fluorescent cells and microvasculature in various organs, including the kidney, bladder, heart, brain, and gastrointestinal tracts, with a focus on the new techniques developed for each imaging application. The combination of novel fluorescence techniques with these powerful imaging methods promises to continue providing novel insights into a variety of diseases.

Using the Raman spectroscopic analysis system that gives the chemical information of the biomaterials, classification is performed through the acquisition of fingerprint signals for each cell line, and the basis of the diagnosis is provided. The origin of diagnosis can be clarified by precise analysis through comparison of local signals and morphology in cells, including measurement at tissue level. In this result, normal breast cell line (MCF-10A) and breast cancer cell lines (MDA-MB-231, MDA-MB-453) were characterized using Raman spectroscopy, atomic force microscopy (AFM), and optical microscopy. These three modalities were combined in order to not only separate cancerous and noncancerous cell lines but to analyze their morphological and optical properties. From the results, the inherent optical properties of cancer cells separated from normal cells in terms of local variation were observed. Bright-field (BF) transmission imaging is also compared to the morphological height difference obtained from AFM and is correlated with surface Raman spectra.

Mesenchymal stem cell (MSC) therapy is a promising treatment for various intractable disorders including interstitial cystitis/bladder pain syndrome (IC/BPS). However, an analysis of fundamental characteristics driving in vivo behaviors of transplanted cells has not been performed, causing debates about rational use and efficacy of MSC therapy. Here, we implemented two-photon intravital imaging and single cell transcriptome analysis to evaluate the in vivo behaviors of engrafted multipotent MSCs (M-MSCs) derived from human embryonic stem cells (hESCs) in an acute IC/BPS animal model. Two-photon imaging analysis was performed to visualize the dynamic association between engrafted M-MSCs and bladder vasculature within live animals until 28 days after transplantation, demonstrating the progressive integration of transplanted M-MSCs into a perivascular-like structure. Single cell transcriptome analysis was performed in highly purified engrafted cells after a dual MACS−FACS sorting procedure and revealed expression changes in various pathways relating to pericyte cell adhesion and cellular stress. Particularly, FOS and cyclin dependent kinase-1 (CDK1) played a key role in modulating the migration, engraftment, and anti-inflammatory functions of M-MSCs, which determined their in vivo therapeutic potency. Collectively, this approach provides an overview of engrafted M-MSC behavior in vivo, which will advance our understanding of MSC therapeutic applications, efficacy, and safety.

Using the Raman spectroscopic analysis system that gives the chemical information of the biomaterials, classification is performed through the acquisition of fingerprint signals for each cell line, and the basis of the diagnosis is provided. The origin of diagnosis can be clarified by precise analysis through comparison of local signals and morphology in cells, including measurement at tissue level. In this result, normal breast cell line (MCF-10A) and breast cancer cell lines (MDA-MB-231, MDA-MB-453) were characterized using Raman spectroscopy, atomic force microscopy (AFM), and optical microscopy. These three modalities were combined in order to not only separate cancerous and noncancerous cell lines but to analyze their morphological and optical properties. From the results, the inherent optical properties of cancer cells separated from normal cells in terms of local variation were observed. Bright-field (BF) transmission imaging is also compared to the morphological height difference obtained from AFM and is correlated with surface Raman spectra.

Intravital microscopy has emerged as a powerful technique for the fluorescent visualization of cellular- and subcellular-level biological processes in vivo. However, the size of objective lenses used in standard microscopes currently makes it difficult to access internal organs with minimal invasiveness in small animal models, such as mice. Here we describe front- and side-view designs for small-diameter endoscopes based on gradient-index lenses, their construction, their integration into laser scanning confocal microscopy platforms, and their applications for in vivo imaging of fluorescent cells and microvasculature in various organs, including the kidney, bladder, heart, brain, and gastrointestinal tracts, with a focus on the new techniques developed for each imaging application. The combination of novel fluorescence techniques with these powerful imaging methods promises to continue providing novel insights into a variety of diseases.

Purpose: Three-dimensional (3D) measurement of intracranial aneurysms is important in planning endovascular treatment, and 3D rotational angiography (RA) is effective in accurate measurement. The purpose of this study was to evaluate the feasibility of low dose 3D RA (5 seconds 0.10 μGy/frame) in measuring an intracranial aneurysm using an in vitro phantom.Materials and Methods: We investigated an in vitro 3D phantom of an intracranial aneurysm with 10 acquisitions of 3D RA with a conventional dose (5 seconds 0.36 μGy/frame) and 10 acquisitions with a low-dose (5 seconds 0.10 μGy/frame). 3D size and neck diameters of the aneurysm were measured and compared between the 2 groups (conventional and low-dose) using noninferiority statistics.Results: The aneurysm measurements were well-correlated between the 2 readers, and noninferiority in the measurement of aneurysmal size of low-dose 3D RA was demonstrated, as the upper margin of the 1-sided 97.5% confidence interval did not cross the pre-defined noninferiority margin of 0.2 mm by the 2 readers.Conclusion: Low-dose (5 seconds 0.10 μGy/frame) cerebral 3D RA is technically feasible and not inferior in in vitro 3D measurement of an intracranial aneurysm. Thus, low-dose 3D RA is promising and needs further evaluation for its clinical utility in the planning of endovascular treatment of an intracranial aneurysm.

Sanghwa Lee,1,* Jung-Man Namgoong,2,* Miyeon Jue,1 Yujin Joung,1 Chae-Min Ryu,3,4 Dong-Myung Shin,4 Myung-Soo Choo,3 Jun Ki Kim1,5 1Biomedical Engineering Research Center, Asan Medical Center, Seoul 05505, Republic of Korea; 2Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea; 3Department of Urology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea; 4Department of Biomedical Sciences, Asan Medical Center, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea; 5Department of Convergence Medicine, University of Ulsan College of Medicine, Seoul 05505, Republic of Korea*These authors contributed equally to this workCorrespondence: Jun Ki Kim Email kim@amc.seoul.krBackground: This study investigated the diagnosis of renal diseases using a biochip capable of detecting nano-sized biomarkers. Raman measurements from a kidney injury model were taken, and the feasibility of early diagnosis was assessed.Materials and Methods: Rat models with mild and severe unilateral ureteral obstructions were created, with the injury to the kidney varying according to the tightness of the stricture. After generating the animal ureteral obstruction models, urine was collected from the kidney and bladder.Results and Discussion: After confirming the presence of renal injury, urine drops were placed onto a Raman chip whose surface had been enhanced with Au-ZnO nanorods, allowing nano-sized biomarkers that diffused into the nanogaps to be selectively amplified. The Raman signals varied according to the severity of the renal damage, and these differences were statistically confirmed.Conclusion: These results confirm that ureteral stricture causes kidney injury and that signals in the urine from the release of nano-biomarkers can be monitored using surface-enhanced Raman spectroscopy.Keywords: ureteral obstruction, renal injury, nano-sized biomarker, ZnO nanorods, surface-enhanced Raman spectroscopy, principal component analysis

Balloon-assisted coiling (BAC) is an endovascular treatment that may be associated with increased complications and thromboembolic events compared with other coiling techniques. We compared clinical outcomes of endovascular treatment (simple coiling, stent-assisted coiling, and BAC) in patients with unruptured intracranial aneurysms at the internal carotid artery and assessed risk factors that could cause cerebral infarction in patients who underwent BAC.We retrospectively reviewed the records of 528 patients with 544 aneurysms who underwent endovascular treatment for unruptured intracranial aneurysms between January 2013 and November 2019. Demographic features, clinical information, balloon inflation time, fetal posterior cerebral artery, anterior cerebral artery (ACA) variants, and angiographic results were analyzed to determine risk factors for cerebral infarction.There were no significant differences among the 3 groups in terms of general characteristics. In the BAC group, 14 of 39 patients showed a significantly higher incidence of cerebral infarction on diffusion magnetic resonance imaging compared with the stent-assisted coiling (37/238) and simple coiling (21/267) groups (P 0.001). There was no significant difference between the ACA variants (normal vs. hypoplasia or aplasia) and cerebral infarction in the simple coiling and stent-assisted coiling groups, but the proportion of aplasia or hypoplasia in the BAC group was significantly higher (P = 0.001).There is a significant association between anatomic ACA variants and cerebral infarction occurrence after BAC. Identifying the variant of the anatomic ACA using digital subtraction angiography would help to predict cerebral infarction after BAC.

This study aimed to evaluate the image quality and dose reduction of low-dose three-dimensional (3D) rotational angiography (RA) for evaluating intracranial aneurysms.We retrospectively evaluated the clinical data and 3D RA datasets obtained from 146 prospectively registered patients (male:female, 46:100; median age, 58 years; range, 19-81 years). The subjective image quality of 79 examinations obtained from a conventional method and 67 examinations obtained from a low-dose (5-seconds and 0.10-µGy/frame) method was assessed by two neurointerventionists using a 3-point scale for four evaluation criteria. The total image quality score was then obtained as the average of the four scores. The image quality scores were compared between the two methods using a noninferiority statistical testing, with a margin of -0.2 (i.e., score of low-dose group - score of conventional group). For the evaluation of dose reduction, dose-area product (DAP) and air kerma (AK) were analyzed and compared between the two groups.The mean total image quality score ± standard deviation of the 3D RA was 2.97 ± 0.17 by reader 1 and 2.95 ± 0.20 by reader 2 for conventional group and 2.92 ± 0.30 and 2.95 ± 0.22, respectively, for low-dose group. The image quality of the 3D RA in the low-dose group was not inferior to that of the conventional group according to the total image quality score as well as individual scores for the four criteria in both readers. The mean DAP and AK per rotation were 5.87 Gy-cm² and 0.56 Gy, respectively, in the conventional group, and 1.32 Gy-cm² (Low-dose 3D RA was not inferior in image quality and reduced the radiation dose by 70%-77% compared to the conventional 3D RA in evaluating intracranial aneurysms.

Stereotaxic instruments are increasingly used in research animals for the study of disease, but typically require restraints and anesthetic procedures. A stereotaxic head mount that enables imaging of the anterior chamber of the eye in alert and freely mobile mice is presented in this study. The head mount is fitted based on computed tomography scans and manufactured using 3D printing. The system is placed noninvasively using temporal mount bars and a snout mount, without breaking the skin or risking suffocation, while an instrument channel stabilizes the ocular probes. With a flexible micro-endoscopic probe and a confocal scanning laser microscopy system

Targeting cancer stem cells (CSCs) without damaging normal stem cells could contribute to the development of novel radical cancer therapies. Cells expressing leucine-rich repeat-containing G-protein coupled receptor 5 (Lgr5) constitute a cancer-causing population in the colon, therefore, targeting of Lgr5+ cells is expected to provide an opportunity to mitigate colon cancer. However, the expression of Lgr5 in normal stem cells makes it difficult to prove the efficacy of therapies targeted exclusively at Lgr5+ cancer cells. We used a modified photodynamic therapy technique involving cellular radiative transfer between green fluorescent protein (GFP)-expressing cells and a rose bengal photosensitizer. After treatment, tumors containing GFP-Lgr5+ cells were observed to be significantly suppressed or retarded with little effect on GFP-Lgr5+ stem cells at the crypt bottom. Lgr5+ CSCs were specifically eradicated in situ, when localized based on the depth from the colon lumen, revealing the potential preventive efficacy of Lgr5-targeted therapy on tumor growth. This study supports the idea that Lgr5+ cells localized near the colon luminal surface are central to colorectal cancer. With further development, the targeting of localized Lgr5+ cancer stem cells, which this study demonstrates in concept, may be feasible for prevention of colon cancer in high-risk populations.

In recent, performances of smartphones are highly developed and they can acquire high resolution image with high framerates. The objective of this study is the development of smartphone-based laryngoscope to reduce the cost of device and demonstrate possibility of highspeed vocal cord imaging by utilizing high performance smartphone camera. We designed customized smartphone adapter for combining clinical laryngoscope and Samsung smartphone. By attaching conventional clinical probes into our customized smartphone adaptor• the high-speed vocal cord endoscopic images were acquired. We could confirm the high-speed digital images of 940fps were acquired from 5 healthy volunteers as a preliminary study.

The development of size-selective and non-destructive detection techniques for nanosized biomarkers has many reasons, including the study of living cells and diagnostic applications. We present an approach for Raman signal enhancement on biocompatible sensing chips based on surface enhancement Raman spectroscopy (SERS). A sensing chip was fabricated by forming a ZnO-based nanorod structure so that the Raman enhancement occurred at a gap of several tens to several hundred nanometers. The effect of coffee-ring formation was eliminated by introducing the porous ZnO nanorods for the bio-liquid sample. A peculiarity of this approach is that the gold sputtered on the ZnO nanorods initially grows at their heads forming clusters, as confirmed by secondary electron microscopy. This clustering was verified by finite element analysis to be the main factor for enhancement of local surface plasmon resonance (LSPR). This clustering property and the ability to adjust the size of the nanorods enabled the signal acquisition points to be refined using confocal based Raman spectroscopy, which could be applied directly to the sensor chip based on the optimization process in this experiment. It was demonstrated by using common cancer cell lines that cell growth was high on these gold-clad ZnO nanorod-based surface-enhanced Raman substrates. The porosity of the sensing chip, the improved structure for signal enhancement, and the cell assay make these gold-coated ZnO nanorods substrates promising biosensing chips with excellent potential for detecting nanometric biomarkers secreted by cells.

OBJECTIVE The purpose of this study was to compare the cosmetic outcome and complications after cranioplasty (CP) due to three different implant materials, and analyze the mean implant survival and cumulative survival rate based on these results. METHODS We reviewed 108 patients retrospectively who underwent CP between January 2014 and November 2016. Autologous bone (AB; 45 patients) and synthetic materials with porous polyethylene (PP; 32 patients) and custom-made 3-dimensional printed titanium mesh (CT; 31 patients) were used as implants. RESULTS Regardless of implanted materials, more than 89.8% of the CP patients were satisfied with the cosmetic outcome. No statistically significant difference was observed among the three groups. The overall postoperative complication rates of each group were 31.1% in the AB group, 15.6% in the PP group and 3.2% in the CT group. The CT group showed lower complication rates compared with AB and PP groups (χ2-test : AB vs. PP, p=0.34; AB vs. CT, p=0.00; PP vs. CT, p=0.03). The AB and PP groups demonstrated a higher post-CP infection rate (11.1% and 6.3%) than the CT group (3.2%). However, no significant difference in the incidence of post-CP infection was observed among the three groups. The PP and CT groups demonstrated a higher mean implant survival time and cumulative survival rate than the AB group at the last follow-up (p

Purpose To evaluate the therapeutic effect of human embryonic stem cell (hESC)-derived multipotent mesenchymal stem cells (M-MSCs) on ketamine-induced cystitis (KC) in rats. Methods To induce KC, 10-week-old female rats were injected with 25-mg/kg ketamine hydrochloride twice weekly for 12 weeks. In the sham group, phosphate buffered saline (PBS) was injected instead of ketamine. One week after the final injection of ketamine, the indicated doses (0.25, 0.5, and 1×106 cells) of M-MSCs (KC+M-MSC group) or PBS vehicle (KC group) were directly injected into the bladder wall. One week after M-MSC injection, the therapeutic outcomes were evaluated via cystometry, histological analyses, and measurement of gene expression. Next, we compared the efficacy of M-MSCs at a low dose (1×105 cells) to that of an identical dose of adult bone marrow (BM)-derived MSCs. Results Rats in the KC group exhibited increased voiding frequency and reduced bladder capacity compared to rats of the sham group. However, these parameters recovered after transplantation of M-MSCs at all doses tested. KC bladders exhibited markedly increased mast cell infiltration, apoptosis, and tissue fibrosis. Administration of M-MSCs significantly reversed these characteristic histological alterations. Gene expression analyses indicated that several genes associated with tissue fibrosis were markedly upregulated in KC bladders. However the expression of these genes was significantly suppressed by the administration of M-MSCs. Importantly, M-MSCs ameliorated bladder deterioration in KC rats after injection of a low dose (1×105) of cells, at which point BM-derived MSCs did not substantially improve bladder function. Conclusions This study demonstrates for the first time the therapeutic efficacy of hESC-derived M-MSCs on KC in rats. M-MSCs restored bladder function more effectively than did BM-derived MSCs, protecting against abnormal changes including mast cell infiltration, apoptosis and fibrotic damage.

Herein, we describe a novel approach for the practical synthesis of tetrasubstituted thiophenes 8. The developed method was particularly used for the facile preparation of thienyl heterocycles 8. The mechanism for this reaction is based on the formation of a sulfur ylide-like intermediate. It was clearly suggested by (i) the intramolecular cyclization of ketene N,S-acetals 7 to the corresponding thiophenes 8, (ii) 1H NMR studies of Meldrum’s acid-substituted aminothioacetals 9, and (iii) substitution studies of the methoxy group on Meldrum’s acid containing N,S-acetals 9b. Notably, in terms of structural effects on the reactivity and stability of sulfur ylide-like intermediates, 2-pyridyl substituted compound 7a exhibited superior properties over those of others.

Rationale: Mesenchymal stem cell (MSC) therapy may be a novel approach to improve interstitial cystitis/bladder pain syndrome (IC/BPS), an intractable disease characterized by severe pelvic pain and urinary frequency. Unfortunately, the properties of transplanted stem cells have not been directly analyzed in vivo, which hampers elucidation of the therapeutic mechanisms of these cells and optimization of transplantation protocols. Here, we monitored the behaviors of multipotent stem cells (M-MSCs) derived from human embryonic stem cells (hESCs) in real time using a novel combination of in vivo confocal endoscopic and microscopic imaging and demonstrated their improved therapeutic potency in a chronic IC/BPS animal model. Methods: Ten-week-old female Sprague-Dawley rats were instilled with 10 mg of protamine sulfate followed by 750 μg of lipopolysaccharide weekly for 5 weeks. The sham group was instilled with phosphate-buffered saline (PBS). Thereafter, the indicated dose (0.1, 0.25, 0.5, and 1×106 cells) of M-MSCs or PBS was injected once into the outer layer of the bladder. The distribution, perivascular integration, and therapeutic effects of M-MSCs were monitored by in vivo endoscopic and confocal microscopic imaging, awake cystometry, and histological and gene expression analyses. Results: A novel combination of longitudinal intravital confocal fluorescence imaging and microcystoscopy in living animals, together with immunofluorescence analysis of bladder tissues, demonstrated that transplanted M-MSCs engrafted following differentiation into multiple cell types and gradually integrated into a perivascular-like structure until 30 days after transplantation. The beneficial effects of transplanted M-MSCs on bladder voiding function and the pathological characteristics of the bladder were efficient and long-lasting due to the stable engraftment of these cells. Conclusion: This longitudinal bioimaging study of transplanted hESC-derived M-MSCs in living animals reveals their long-term functional integration, which underlies the improved therapeutic effects of these cells on IC/BPS.

Label-free optical diffraction tomography (ODT), an imaging technology that does not require fluorescent labeling or other pre-processing, can overcome the limitations of conventional cell imaging technologies, such as fluorescence and electron microscopy. In this study, we used ODT to characterize the cellular organelles of three different stem cells-namely, human liver derived stem cell, human umbilical cord matrix derived mesenchymal stem cell, and human induced pluripotent stem cell-based on their refractive index and volume of organelles. The physical property of each stem cell was compared with that of fibroblast. Based on our findings, the characteristic physical properties of specific stem cells can be quantitatively distinguished based on their refractive index and volume of cellular organelles. Altogether, the method employed herein could aid in the distinction of living stem cells from normal cells without the use of fluorescence or specific biomarkers.

A wideband electromagnetic (EM) wave absorber for the X-band (8–12 GHz) is designed using M-type hexaferrite, SrFe12-2xCoxTixO19 (x = 1.1, 1.2, 1.25, and 1.3)–CNT (0–3 wt%)–epoxy (10 wt%) composites. As x increases from 1.1 to 1.3, the ferromagnetic resonance (FMR) of the hexaferrite powder gradually decreases from 15.0 GHz to 6.4 GHz due to the decrease of magnetocrytalline anisotropy. The EM absorption frequency range changes in accordance with changes in the FMR frequency. Among the series of samples, the x = 1.25 sample demonstrates EM absorption properties optimized for the X-band with the lowest reflection loss (RL) of −40 dB and satisfying RL

Background Owing to the COVID-19 pandemic, social distancing has become mandatory. Wireless endoscopy in contactless examinations promises to protect health care workers and reduce viral spread. Objective This study aimed to introduce a contactless endoscopic diagnosis system using a wireless endoscope resembling a mask. Methods The Wi-Fi–based contactless mask endoscopy system comprises a disposable endoscope and a controller. First, the effective force applied by the tip during insertion was evaluated in a simple transoral model consisting of a force sensor on a simulated oropharynx wall. Second, the delay in video streaming was evaluated by comparing the frame rate and delays between a movement and its image over direct and Wi-Fi connections. Third, the system was applied to a detailed laryngopharyngeal tract phantom. Results The smartphone-controlled wireless endoscopy system was successfully evaluated. The mean, maximum, and minimum collision forces against the wall of the transoral model were 296 mN (30 gf), 363 mN (37 gf), and 235 mN (24 gf), respectively. The delay resulting from the wireless connection was 0.72 seconds. Using the phantom, an inexperienced user took around 1 minute to orient the endoscope to a desired area via the app. Conclusions Device articulation does not pose a significant risk of laryngopharyngeal wall penetration, and latency does not significantly impede its use. Contactless wireless video streaming was successful within the access point range regardless of the presence of walls. The mask endoscope can be controlled and articulated wirelessly, minimizing contact between patients and device operators. By minimizing contact, the device can protect health care workers from infectious viruses like the coronavirus.

The mechanical strength of Sn-3.0Ag-0.5Cu (SAC305) and Au-20Sn solder joints and their interfacial reaction with a Ni-plated ceramic substrate were evaluated to assess their suitability for use as die attach materials in power module applications. The compatibility between the two solder alloys and the Ni substrate was assessed during isothermal long-term aging, while the mechanical strength of the two solder joints was measured by die shear testing. A higher intermetallic compound (IMC) growth rate and Ni consumption rate was observed in the SAC305 solder joint, with the formation of a thick IMC layer and weak interface resulting in brittle fracture. The Au-20Sn solder joint, on the other hand was found to exhibit superior high temperature interfacial stability and joint strength.

BACKGROUND Endoscopes are widely used for visualizing the respiratory tract, urinary tract, uterus, and gastrointestinal tracts. Despite high demand, people in underdeveloped and developing countries cannot obtain proper access to endoscopy. Moreover, commercially available endoscopes are mostly nonarticulable as well as not actively controlled, limiting their use. Articulating endoscopes are required for some diagnosis procedures, due to their ability to image wide areas of internal organs. Furthermore, actively controlled articulating endoscopes are less likely to harm the lumen than rigid endoscopes because they can avoid contact with endothelial tissues. OBJECTIVE The study aimed to demonstrate the feasibility and acceptability of smartphone-based wide-field articulable endoscope system for minimally invasive clinical applications in developing and less developed countries. METHODS A thin articulable endoscope system that can be attached to and actively controlled by a smartphone was designed and constructed. The system consists of a flexible endoscopic probe with a continuum mechanism, 4 motor modules for articulation, a microprocessor for controlling the motor with a smartphone, and a homebuilt app for streaming, capturing, adjusting images and video, and controlling the motor module with a joystick-like user interface. The smartphone and motor module are connected via an integrated C-type On-The-Go (OTG) USB hub. RESULTS We tested the device in several human-organ phantoms to evaluate the usability and utility of the smartphone-based articulating endoscope system. The resolution (960 × 720 pixels) of the device was found to be acceptable for medical diagnosis. The maximum bending angle of 110° was designed. The distance from the base of the articulating module to the tip of the endoscope was 45 mm. The angle of the virtual arc was 40.0°, for a curvature of 0.013. The finest articulation resolution was 8.9°. The articulating module succeeded in imaging all 8 octants of a spherical target, as well as all 4 quadrants of the indices marked in human phantoms. CONCLUSIONS The portable wide-field endoscope was successfully controlled using a smartphone, yielding clear images with a resolution of 960 × 720 pixels at realistic focal distances. Actively and precisely controlled articulating movements have resulted in minimally invasive monitoring in the narrow space of internal organs providing a wide-area view. We found our smartphone-based active articulated endoscope to be suitable for point-of-care applications in developing and less developed countries.

The cell nucleus is a three-dimensional, dynamic organelle organized into subnuclear compartments such as chromatin and nucleoli. The structure and function of these compartments are maintained by diffusion and interactions between related factors as well as by dynamic and structural changes. Recent studies using fluorescent microscopic techniques suggest that protein factors can access and are freely mobile in heterochromatin and in mitotic chromosomes, despite their densely packed structure. However, the physicochemical properties of the chromosome during cell division are not fully understood. In the present study, characteristic properties such as the refractive index (RI), volume of the mitotic chromosomes, and diffusion coefficient (D) of fluorescent probes inside the chromosome were quantified using an approach combining label-free optical diffraction tomography with complementary confocal laser-scanning microscopy and fluorescence correlation spectroscopy. Variations in these parameters correlated with osmotic conditions, suggesting that changes in RI are consistent with those of the diffusion coefficient for mitotic chromosomes and cytosol. Serial RI tomography images of chromosomes in live cells during mitosis were compared with three-dimensional confocal micrographs to demonstrate that compaction and decompaction of chromosomes induced by osmotic change were characterized by linked changes in chromosome RI, volume, and the mobilities of fluorescent proteins.

Porous silicon nanoparticles (PSiNPs) have attracted increasing interest for imaging and treatment of diseases due to biocompatibility, large specific capacity for drug loading, non-toxic degradation products, and intrinsic photoluminescence (PL). In particular, the PL lifetime is typically on the order of microseconds, significantly longer than the nanosecond lifetimes exhibited by fluorescent molecules naturally presented in cells and tissues, thus allows discrimination of the silicon nanoparticle from the tissue autofluorescence. Herein, the long-lived PL is employed to monitor the status of drug payload elution, associated with biodegradation of the silicon nanocarriers, and demonstrated as a “self-reporting” system. Dissolution of the silicon matrix in physiological environment triggers drug release, along with decreasing intensity and blue shift of the PL spectra. Furthermore, by tracking the PL lifetime, the drug releasing status and the residual lifespan of the silicon nanocarriers are correspondingly acquired. The PL lifetime is a physically intensive property that can report only the inherent characteristics of the PSiNPs regardless of surrounding noise while the intensity-based reporting is substantially affected by many unwanted factors. We investigate a unique means to inform the lifespan of the PSiNPs as a biodegradable drug nanocarrier in vivo. This study presents a promising potential of the photoluminescent PSiNPs toward advanced drug delivery systems for translational medical platform including theranostics and visualized drug delivery tracking.

Endoscopic imaging allows longitudinal observation of epithelial pathologies in tubular organs throughout the body. However, the imaging and optical diagnosis of tubular biostructures such as small animal models and small pediatric organs require appropriately miniaturized devices. A miniaturized catadioptric flexible side-view endoscope is proposed with omnidirectional field of view (FOV) in the transverse direction and sub-mm-scale feature resolution. The FOV in the longitudinal direction is 50°. Images are unwrapped and stitched together to form composite images of the target by two different algorithms, revealing a composite FOV of more than 3.5 cm × 360°. The endoscope is well suited for minimally invasive rapid monitoring of thin tubular organs in pediatric patients, as well as for imaging of small animal disease models at near-cellular resolution.

Nanorods based on ZnO for surface enhanced Raman spectroscopy are promising for the non-invasive and rapid detection of biomarkers and diagnosis of disease. However, optimization of nanorod and coating parameters is essential to their practical application. With the goal of establishing a baseline for early detection in biological applications, gold-coated ZnO nanorods were grown and coated to form porous structures. Prior to gold deposition, the grown nanorods were 30&ndash, 50 nm in diameter and 500&ndash, 600 nm in length. Gold coatings were grown on the nanorod structure to a series of thicknesses between 100 and 300 nm. A gold coating of 200 nm was found to optimize the Rhodamine B model analyte signal, while performance for rat urine depended on the biomarkers to be detected. These results establish design guidelines for future use of Au-ZnO nanorods in the study and early diagnosis of inflammatory diseases.

To evaluate the feasibility of ZnO nanorod-based surface enhanced Raman scattering (SERS) diagnostics for disease models, particularly for interstitial cystitis/bladder pain syndrome (IC/BPS), ZnO-based SERS sensing chips were developed and applied to an animal disease model. ZnO nanorods were grown to form nano-sized porous structures and coated with gold to facilitate size-selective biomarker detection. Raman spectra were acquired on a surface enhanced Raman substrate from the urine in a rat model of IC/BPS and analyzed using a statistical analysis method called principal component analysis (PCA). The nanorods grown after the ZnO seed deposition were 30 to 50 nm in diameter and 500 to 600 nm in length. A volume of gold corresponding to a thin film thickness of 100 nm was deposited on the grown nanorod structure. Raman spectroscopic signals were measured in the scattered region for nanometer biomarker detection to indicate IC/BPS. The Raman peaks for the control group and IC/BPS group are observed at 641, 683, 723, 873, 1002, 1030, and 1355 cm&minus, 1, which corresponded to various bonding types and compounds. The PCA results are plotted in 2D and 3D. The Raman signals and statistical analyses obtained from the nano-sized biomarkers of intractable inflammatory diseases demonstrate the possibility of an early diagnosis.

Controlling the uptake of nanoparticles into cells so as to balance therapeutic effects with toxicity is an essential unsolved problem in the development of nanomedicine technologies. From this point of view, it is useful to use standard nanoparticles to quantitatively evaluate the physical properties of the nanoparticles in solution and in cells, and to analyze the intracellular dynamic motion and distribution of these nanoparticles at a single-particle level. In this study, standard nanoparticles are developed based on a variant silica-based nanoparticle incorporating fluorescein isothiocyanate (FITC) or/and rhodamine B isothiocyanate (RITC) with a variety of accessible diameters and a matching fluorescent cobalt ferrite core-shell structure (Fe2O4/SiO2). The physical and optical properties of the nanoparticles in vitro are fully evaluated with the complementary methods of dynamic light scattering, electron microscopy, and two fluorescence correlation methods. In addition, cell uptake of dual-colored and core/shell nanoparticles via endocytosis in live HeLa cells is detected by fluorescence correlation spectroscopy and electron microscopy, indicating the suitability of the nanoparticles as standards for further studies of intracellular dynamics with multi-modal methods.

To evaluate clinical outcomes of fluoroscopic removal of retrievable self-expandable metal stents (SEMSs) for malignant oesophageal strictures, to compare clinical outcomes of three different removal techniques, and to identify predictive factors of successful removal by the standard technique (primary technical success). A total of 137 stents were removed from 128 patients with malignant oesophageal strictures. Primary overall technical success and removal-related complications were evaluated. Logistic regression models were constructed to identify predictive factors of primary technical success. Primary technical success rate was 78.8 % (108/137). Complications occurred in six (4.4 %) cases. Stent location in the upper oesophagus (P=0.004), stricture length over 8 cm (P=0.030), and proximal granulation tissue (P

Liver fibrosis and cirrhosis, the late stage of fibrosis, are threatening diseases that lead to liver failure and patient death. Although aberrantly activated hepatic stellate cells (HSCs) are the main cause of disease initiation, the symptoms are primarily related to damaged hepatocytes. Thus, damaged hepatocytes, as well as HSCs, need to be simultaneously considered as therapeutic targets to develop more efficient treatments. Here, we suggest cromolyn sodium as an anti-fibrotic agent to commonly modulate hepatocytes and hepatic stellate cells. The differentially expressed genes from 6 normal and 40 cirrhotic liver tissues which were collected from GEO data were assessed by pharmacokinetic analysis using a connectivity map to identify agents that commonly revert abnormal hepatocytes and HSCs to normal conditions. Based on a series of analyses, a few candidates were selected. Candidates were tested in vitro to determine their anti-fibrotic efficacy on HSCs and hepatocytes. Cromolyn, which was originally developed as a mast cell stabilizer, showed the potential to ameliorate activated HSCs in vitro. The activation and collagen accumulation for HSC cell lines LX2 and HSC-T6 were reduced by 50% after cromolyn treatment at a low concentration without apoptosis. Furthermore, cromolyn treatment compromised the TGF-β-induced epithelial mesenchyme transition and replicative senescence rate of hepatocytes, which are generally associated with fibrogenesis. Taken together, cromolyn may be the basis for an effective cure for fibrosis and cirrhosis because it targets both HSCs and hepatocytes.

When imaging brain vasculature with optical coherence tomography angiography (OCTA), volumetric analysis of cortical vascular networks in OCTA datasets is frequently challenging due to the presence of artifacts, which appear as multiple-scattering tails beneath superficial large vessels in OCTA images. These tails shadow underlying small vessels, making the assessment of vascular morphology in the deep cortex difficult. In this work, we introduce an image processing technique based on mean subtraction of the depth profile that can effectively reduce these tails to better reveal small hidden vessels compared to the current tail removal approach. With the improved vascular image quality, we demonstrate that this simple method can provide better visualization of three-dimensional vascular network topology for quantitative cerebrovascular studies.

Long-period fiber gratings (LPFGs) were fabricated by self-annealing of a polymer-filled silica hollow optical fiber without an amplitude mask show high temperature sensitivity. The spectral characteristics are modeled using the transfer matrix method, achieving good match with experimental results, and making possible further application.

BACKGROUND AND STUDY AIM: To develop a molecular imaging endoscopic system that eliminates tissue autofluorescence and distinguishes multiple fluorescent markers specifically on the cancerous lesions. METHODS: Newly developed multi-spectral fluorescence endoscope device has the potential to eliminate signal interference due to autofluorescence and multiplex fluorophores in fluorescent probes. The multiplexing capability of the multi-spectral endoscope device was demonstrated in the phantom studies and multi-spectral imaging with endoscopy and macroscopy was performed to analyze fluorescence signals after administration of fluorescent probe that targets cancer in the colon. Because of the limitations in the clinical application using rigid-type small animal endoscope, we developed a flexible channel insert-type fluorescence endoscope, which was validated on the colonoscopy of dummy and porcine model. RESULTS: We measured multiple fluorescent signals simultaneously, and the fluorescence spectra were unmixed to separate the fluorescent signals of each probe, in which multiple fluorescent probes clearly revealed spectral deconvolution at the specific targeting area in the mouse colon. The positive area of fluorescence signal for each probe over the whole polyp was segmented with analyzing software, and showed distinctive patterns and significantly distinguishable values: 0.46 ± 0.04, 0.39 ± 0.08 and 0.73 ± 0.12 for HMRG, CET-553 and TRA-675 probes, respectively. The spectral unmixing was finally demonstrated in the dummy and porcine model, corroborating the targeted multi-spectral fluorescence imaging of colon dysplasia. CONCLUSION: The multi-spectral endoscopy system may allow endoscopists to clearly identify cancerous lesion that has different patterns of various target expression using multiple fluorescent probes.

Intravital optical imaging technology is essential for minimally invasive optical diagnosis and treatment in small animal disease models. High-resolution imaging requires high-resolution optical probes, and high-resolution optical imaging systems based on highly precise and advanced technologies and therefore, associated with high-system costs. Besides, in order to acquire small animal live images, special types of animal imaging setups are indispensable. In this paper, a microendoscopic system is designed as an add-on to existing conventional imaging microscopes, reducing the price of complete confocal endomicroscopic systems. The proposed attachable system can be configured for confocal microscopes from common manufacturers and this enables users to acquire live animal cellular images from a conventional system. It features a 4f optical plane relay system, a rotary stage for side-view endoscopic probes, and an endoscopic probe mount which swings between the horizontal and the vertical. The system could be widely useful for biological studies of animal physiology and disease models.

Purpose To evaluate the feasibility of self-expanding metal stent (SEMS) placement and fluorescence microendoscopic monitoring for determination of fibroblast cell proliferation after stent placement in an esophageal mouse model. Materials and Methods Twenty fibroblast-specific protein (FSP)-1 green fluorescent protein (GFP) transgenic mice were analyzed. Ten mice (Group A) underwent SEMS placement, and fluoroscopic and fluorescence microendoscopic images were obtained biweekly until 8 weeks thereafter. Ten healthy mice (Group B) were used for control esophageal values. Results SEMS placement was technically successful in all mice. The relative average number of fibroblast GFP cells and the intensities of GFP signals in Group A were significantly higher than in Group B after stent placement. The proliferative cellular response, including granulation tissue, epithelial layer, submucosal fibrosis, and connective tissue, was increased in Group A. FSP-1-positive cells were more prominent in Group A than in Group B. Conclusions SEMS placement was feasible and safe in an esophageal mouse model, and proliferative cellular response caused by fibroblast cell proliferation after stent placement was longitudinally monitored using a noninvasive fluorescence microendoscopic technique. The results have implications for the understanding of proliferative cellular response after stent placement in real-life patients and provide initial insights into new clinical therapeutic strategies for restenosis.