Search

Abstract Photodynamic and photothermal therapies are promising treatments for cancer, dermatological, and ophthalmological conditions. However, photodynamic therapy (PDT) is less effective in oxygen-deficient tumor environments. Combining PDT with photothermal therapy (PTT) can enhance oxygen supply and treatment efficacy. Inorganic PTT agents pose toxicity risks, limiting their clinical use despite their high performance. In this study, we developed a novel nanomedicine integrating an all-organic photothermal agent and an organic photosensitizer, creating a colocalized nanoplatform to enhance phototherapy efficacy in cancer treatment. PTT nanoparticles (NPs) were synthesized through a thermal phase transition of organic chromophores, demonstrating superior photothermal properties and photostability. Utilizing this nanoplatform, we devised ‘Combi NPs’ for combined PDT–PTT nanomedicine. Tests on A549 cancer cell lines have revealed that Combi NPs exhibit superior cytotoxicity and induce apoptosis in hypoxic conditions, outperforming PTT-only NPs. The all-organic Combi NPs show significant potential for clinical cancer phototherapy in hypoxic microenvironments, potentially mitigating long-term nanomedicine accumulation and associated toxicity.

Extracellular matrix (ECM) undergoes dynamic inflation that dynamically changes ligand nanospacing but has not been explored. Here we utilize ECM-mimicking photocontrolled supramolecular ligand-tunable Azo+ self-assembly composed of azobenzene derivatives (Azo+) stacked via cation-π interactions and stabilized with RGD ligand-bearing poly(acrylic acid). Near-infrared-upconverted-ultraviolet light induces cis-Azo+-mediated inflation that suppresses cation-π interactions, thereby inflating liganded self-assembly. This inflation increases nanospacing of “closely nanospaced” ligands from 1.8 nm to 2.6 nm and the surface area of liganded self-assembly that facilitate stem cell adhesion, mechanosensing, and differentiation both in vitro and in vivo, including the release of loaded molecules by destabilizing water bridges and hydrogen bonds between the Azo+ molecules and loaded molecules. Conversely, visible light induces trans-Azo+ formation that facilitates cation-π interactions, thereby deflating self-assembly with “closely nanospaced” ligands that inhibits stem cell adhesion, mechanosensing, and differentiation. In stark contrast, when ligand nanospacing increases from 8.7 nm to 12.2 nm via the inflation of self-assembly, the surface area of “distantly nanospaced” ligands increases, thereby suppressing stem cell adhesion, mechanosensing, and differentiation. Long-term in vivo stability of self-assembly via real-time tracking and upconversion are verified. This tuning of ligand nanospacing can unravel dynamic ligand-cell interactions for stem cell-regulated tissue regeneration.

Immune checkpoint blockade (ICB) therapy targeting PD-L1 via monoclonal antibody (mAb) has shown extensive clinical benefits in the diverse types of advanced malignancies. However, most patients are completely refractory to ICB therapy owing to the PD-L1 recycling mechanism. Herein, we propose photo-induced crosslinked and anti-PD-L1 peptide incorporated liposomes (immune checkpoint blockade liposomes; ICB-LPs) to promote PD-L1 multivalent binding for inducing lysosomal degradation of PD-L1 in tumor cells. The ICB-LPs are prepared by formulation of DC8,9PC with photo-polymerized diacetylenic moiety, 1,2-dipalmitoylphosphatidylcholine (DPPC) and anti-PD-L1 peptide (D-form NYSKPTDRQYHF)-conjugated DSPE-PEG2k (anti-PD-L1-DSPE-PEG2k) in a molar ratio of 45:45:10, followed by cross-linking of liposomal bilayer upon UV irradiation. The 10 mol% anti-PD-L1-DSPE-PEG2k incorporated ICB-LPs have a nano-sized lipid bilayer structure with an average diameter of 137.7 ± 1.04 nm, showing a high stability in serum condition. Importantly, the ICB-LPs efficiently promote the multivalent binding with PD-L1 on the tumor cell membrane, which are endocytosed with aim to deliver PD-L1 to the lysosomes, wherein the durable PD-L1 degradation is observed for 72 h, in contrast to anti PD-L1 mAbs showing the rapid PD-L1 recycling within 9 h. The in vitro co-culture experiments with CD8+ T cells show that ICB-LPs effectively enhance the T cell-mediated antitumor immune responses against tumor cells by blocking the PD-L1/PD-1 axis. When ICB-LPs are intravenously injected into colon tumor-bearing mice, they efficiently accumulate within the targeted tumor tissues via both passive and active tumor targeting, inducing a potent T cell-mediated antitumor immune response by effective and durable PD-L1 degradation. Collectively, this study demonstrates the superior antitumor efficacy of crosslinked and anti-PD-L1 peptide incorporated liposome formulation that promotes PD-L1 multivalent binding for trafficking of PD-L1 toward the lysosomes instead of the recycling endosomes.

In this study, the compositional design of high-formability, high-bake-hardening Al–Mg–Zn-Cu-based aluminum alloys was carried out, and process conditions were established to secure mechanical properties under harsh conditions for Al–Mg–Zn-Cu-based alloys. Using JMatPro13.0 for precipitation phase simulation, the optimal pre-aging temperature and time of the design composition were selected. Through the introduction of pre-aging, it was confirmed that no over-aging phenomena occurred, even after bake-hardening, and it was confirmed that it could have mechanical properties similar to those of test specimens subjected to traditional heat treatment. Through DSC (Differential Scanning Calorimetry) and TEM (Transmission Electron Microscope) analyses, it was found that pre-aging provided sufficient thermal stability to the GP (Guinier–Preston) zone and facilitated transformation to the η’-phase. In addition, it was confirmed that, even under bake-hardening conditions, coarsening of the precipitation phase was prevented and number density was increased, thereby contributing to improvements in the mechanical properties. The designed alloy plate was evaluated as having excellent anisotropy properties through n-value and r¯-value calculations, and it was confirmed that a similar level of formability was secured through FLC (Forming Limit Curve) comparison with commercial plates.

We improved the interfacial bonding strength and heat transfer performance between wrought and cast Al alloy parts by implementing an interfacial Al-Si-Zn-based alloy coating layer. An additive manufacturing (AM)-based combinatorial experiment was employed to determine the optimal composition of coating layers. Various compositional combinations of Al-Si-Zn layers were deposited onto an Al plate using a multi-nozzle direct energy deposition system, and the wetting behavior of the cast materials onto the combinatorial samples was examined to select the best composition of the coating layer. The selected coating layer was sprayed on the cooling pipes, and an actual-scale motor housing integrated by the pipe was produced by a compound die casting. The Al-Si-Zn coating layer caused the surface of the coating layers on pipes to partially melt when in contact with the molten alloy during the casting. Consequently, a reactive layer was rapidly formed between the coating and cast materials before solidification. As a result, the interfacial bonding strength increased to 13 MPa and heat transferability between the wrought and cast materials was improved. Therefore, we described the AM-based combinatorial exploring method for the interfacial coating layer to overcome the interfacial issues between the wrought and cast materials of compound casting.

Methylene blue (MB) is a well-known pharmaceutical ingredient that is thought to have a multi-targeted therapeutic effect as an anti-malarial and neuroprotective agent and has recently been identified as a treatment for coronavirus disease 2019 (COVID-19). In this review, we present an overview of relevant clinical trials, including ongoing trials, on the therapeutic uses of MB. A search for clinical trials on clinicaltrials.gov was performed using the terms “methylene blue” and “methylthionine chloride.” This review focuses on clinical trials of MB-based therapies applied to brain diseases, cancer imaging and diagnosis, infectious diseases such as malaria or COVID-19, and cardiovascular diseases. Nanoparticle-based delivery techniques have also been briefly discussed in addition to common delivery methods.

IntroductionMyxomatous mitral valve disease (MMVD) is the most common cause of heart failure in dogs, and assessing the risk of heart failure in dogs with MMVD is often challenging. Machine learning applied to electronic health records (EHRs) is an effective tool for predicting prognosis in the medical field. This study aimed to develop machine learning-based heart failure risk prediction models for dogs with MMVD using a dataset of EHRs.MethodsA total of 143 dogs with MMVD between May 2018 and May 2022. Complete medical records were reviewed for all patients. Demographic data, radiographic measurements, echocardiographic values, and laboratory results were obtained from the clinical database. Four machine-learning algorithms (random forest, K-nearest neighbors, naïve Bayes, support vector machine) were used to develop risk prediction models. Model performance was represented by plotting the receiver operating characteristic (ROC) curve and calculating the area under the curve (AUC). The best-performing model was chosen for the feature-ranking process.ResultsThe random forest model showed superior performance to the other models (AUC = 0.88), while the performance of the K-nearest neighbors model showed the lowest performance (AUC = 0.69). The top three models showed excellent performance (AUC ≥ 0.8). According to the random forest algorithm’s feature ranking, echocardiographic and radiographic variables had the highest predictive values for heart failure, followed by packed cell volume (PCV) and respiratory rates. Among the electrolyte variables, chloride had the highest predictive value for heart failure.DiscussionThese machine-learning models will enable clinicians to support decision-making in estimating the prognosis of patients with MMVD.

Accurate demand forecasting is important for automotive manufacturing and sales planning because it allows firms to minimize costs and improve their effectiveness. Based on the limitations of existing literature, this paper seeks to establish a novel machine learning-assisted hybrid-input automobile demand forecast model by focusing on the research gaps in input data, methodology, and the scope of demand forecast. To achieve the research aim, the firm-level forecasting performance of the machine learning algorithms based on the hybrid micro-/firm-level (endogenous) and macro-level (exogenous) factors were analyzed to present the optimal approach. The study collected and used monthly vehicle sales and related firm-level data from South Korea from 2011 to 2020. Linear regression, neural network, random forest, stochastic gradient descent, and ensemble learning were used to build the models and verify significant input features using the RReliefF algorithm. The paper presents significant theoretical and managerial contributions that advance the methodological frameworks in the auto demand forecasting literature based on the ML-assisted hybrid-input model, highlighting less well-known endogenous factors that affect company precision to enhance businesses' practical operations.

Abstract In diabetes, platelets are activated by several stimuli, and the activated platelets generate reactive oxygen species (ROS) to induce the aggregation of platelets followed by thrombus formation resulting in various cardiovascular diseases. Therefore, detecting ROS perturbations in platelets can provide a clue to diagnosing diabetes. In this paper, iridium‐based self‐immolative probes (1a‐1c) are reported to monitor perturbations of ROS in the blood through photoluminescence (PL) and electrochemiluminescence (ECL). The probes are designed based on an iridium complex conjugated with phenylboronic acid pinacol ester through carbamate moiety. Three probes contain distinct electron‐withdrawing groups at the ortho‐position in the benzyl linker; thus, subtle reactivity differences are expected against ROS. As expected, all three probes exhibit the most apparent PL changes against hydrogen peroxide (H2O2), but their response patterns against ROS are interestingly distinctive. Utilizing such differential ROS responsive pattern, a discrimination strategy is established using a combination of PL and ECL responses, and discrimination of platelets from diabetic and control rats is successfully demonstrated.

Abstract Background The use of fenbendazole (FBZ) in terminal cancer patients has recently increased, as anthelminthic drugs, such as FBZ and benzimidazole, exhibit anti‐tubulin effects in tumour cells. Objectives The present study evaluated the in vitro anti‐cancer effects of FBZ in five canine melanoma cell lines originating from the oral cavity (UCDK9M3, UCDK9M4, UCDK9M5, KMeC and LMeC). Methods Five canine melanoma cell lines were treated with FBZ and analysed with cell viability assay, cell cycle analysis, western blot assay and immunofluorescence staining to identify apoptotic effect, cell cycle arrest, microtubule disruption and mitotic slippage. Results Cell viability was reduced in all melanoma cell lines in a dose‐dependent manner after FBZ treatment. Through cell cycle analysis, G2/M arrest and mitotic slippage were identified, which showed a time‐dependent change. All treatment concentrations induced increased cleaved PARP signals in western blot analysis compared to the control groups. Immunofluorescence of cells treated for 24 h revealed defects in microtubule structure, multinucleation or macronucleation. With the exception of UCDK9M3, the melanoma cells showed mitotic slippage and post‐slippage death, indicative of mitotic catastrophe. Conclusions These results indicate that FBZ exhibits anti‐cancer effects in vitro against canine melanoma cells; however, further in vivo studies regarding the clinical applications of FBZ are required.

The effect of the channel interface of top-gate InGaZnO (IGZO) thin film transistors (TFTs) on the electrical properties caused by exposure to various wet chemicals such as deionized water, photoresist (PR), and strippers during the photolithography process was studied. Contrary to the good electrical characteristics of TFTs including a protective layer (PL) to avoid interface damage by wet chemical processes, TFTs without PL showed a conductive behavior with a negative threshold voltage shift, in which the ratio of Ga and Zn on the IGZO top surface reduced due to exposure to a stripper. In addition, the wet process in photolithography increased oxygen vacancy and oxygen impurity on the IGZO surface. The photo-patterning process increased donor-like defects in IGZO due to organic contamination on the IGZO surface by PR, making the TFT characteristics more conductive. The introduction of ozone (O3) annealing after photo-patterning and stripping of IGZO reduced the increased defect states on the surface of IGZO due to the wet process and effectively eliminated organic contamination by PR. In particular, by controlling surface oxygens on top of the IGZO surface excessively generated with O3 annealing using UV irradiation of 185 and 254 nm, IGZO TFTs with excellent current–voltage characteristics and reliability could be realized comparable to IGZO TFTs containing PL.

Abstract Indocyanine green (ICG) is a clinically approved dye that has shown great promise as a phototheranostic material with fluorescent, photoacoustic and photothermal responses in the near-infrared region. However, it has certain limitations, such as poor photostability and non-specific binding to serum proteins, subjected to rapid clearance and decreased theranostic efficacy in vivo. This study reports stable and biocompatible nanoparticles of ICG (ICG-Fe NPs) where ICG is electrostatically complexed with an endogenously abundant metal ion (Fe3+) and subsequently nanoformulated with a clinically approved polymer surfactant, Pluronic F127. Under near-infrared laser irradiation, ICG-Fe NPs were found to be more effective for photothermal temperature elevation than free ICG molecules owing to the improved photostability. In addition, ICG-Fe NPs showed the markedly enhanced tumor targeting and visualization with photoacoustic/fluorescent signaling upon intravenous injection, attributed to the stable metal complexation that prevents ICG-Fe NPs from releasing free ICG before tumor targeting. Under dual-modal imaging guidance, ICG-Fe NPs could successfully potentiate photothermal therapy of cancer by applying near-infrared laser irradiation, holding potential as a promising nanomedicine composed of all biocompatible ingredients for clinically relevant phototheranostics.

National Systems of Entrepreneurship is defined as a nation’s resource allocation structure leading to entrepreneurial behaviors. However, the existing indicators of national framework conditions may have limitations in comparing the entrepreneurial efficiency of countries. Based on institutional theory, this paper presents a model to examine the efficiency of entrepreneurial activities stemming from the given conditions of a country and find benchmarks based on data envelopment analysis by scrutinizing inputs and outputs with static efficiency, dynamic efficiency, and strategic quadrant analysis. For this purpose, the study utilizes the Global Entrepreneurship Monitor dataset from 2015 to 2020 for 24 countries and presents the research questions regarding the differences in global entrepreneurial efficiencies, the countries for benchmarking, and the implications for entrepreneurial activities. The research implications suggest that diversifying the views on entrepreneurial efficiency may be valuable, and policymakers may focus on institutional conditions and entrepreneurial efficiency regarding the activity of early-stage businesses.

The quality of sales processes is crucial in automotive and directly related to the firm’s competitive advantage and financial success. Sales training is the most prevalent intervention to guarantee quality and productivity. Extant literature has attempted to measure training effectiveness adequately, and the Context, Input, Process, and Product evaluation (CIPP) model has been a popular approach. This study endeavored to advance current literature and suggest a novel effectiveness framework, Content, Instructional design, Programmed learning, and Recommendation (CIP-R). The framework was applied to examine three different methodologies—traditional, pure digital, and hybrid training—collecting 583 instances from the automotive sales training conducted from 2019 to 2020 in South Korea. The findings advocate the importance of human elements, the role of efficacy, and self-determination in generating learning transferability, leading to performance in the digital age.

Abstract Molecular aggregates are receiving tremendous attention, demonstrating immense potential for biomedical applications in vitro and in vivo. For instance, the molecular aggregates of conventional fluorophores influence the electronic excitation states of the aggregates, causing characteristic photophysical property changes. A fundamental understanding of this classical relationship between molecular aggregate structures and photophysics has allowed for innovative biological applications. The chemical characteristics of drug molecules generally trigger the formation of colloidal aggregates, and this is considered detrimental to the drug discovery process. Furthermore, nano‐sized supramolecular aggregates have been used in biomedical imaging and therapy owing to their optimal properties for in vivo utility, including enhanced cell permeability, passive tumor targeting, and convenient surface engineering. Herein, we provide an overview of the recent trends in molecular aggregates for biomedical applications. The changes in photophysical properties of conventional fluorophores and their biological applications are discussed, followed by the effects of conventional drug molecule‐aggregates on drug discovery and therapeutics development. Recent trends in the investigation of biologically important analytes with aggregation‐induced emission are discussed for conventional and unconventional fluorophores. Lastly, we discuss nano‐sized supramolecular aggregates used in imaging and therapeutic purposes, with a focus on in vivo utilization.

In this community review report, we discuss applications and techniques for fast machine learning (ML) in science—the concept of integrating powerful ML methods into the real-time experimental data processing loop to accelerate scientific discovery. The material for the report builds on two workshops held by the Fast ML for Science community and covers three main areas: applications for fast ML across a number of scientific domains; techniques for training and implementing performant and resource-efficient ML algorithms; and computing architectures, platforms, and technologies for deploying these algorithms. We also present overlapping challenges across the multiple scientific domains where common solutions can be found. This community report is intended to give plenty of examples and inspiration for scientific discovery through integrated and accelerated ML solutions. This is followed by a high-level overview and organization of technical advances, including an abundance of pointers to source material, which can enable these breakthroughs.

Objective: Bilateral ureteral calculi, hydronephrosis, pyometra, pyocolpos, vestibulovaginal steno¬sis, and imperforate hymen in a dog are uncommon and can be difficult to diagnose. The aim of this article is to report diagnostic challenges and successful surgical treatment of this rare event and the long-term outcomes. Materials and methods: A 5-year-old, spayed (partial ovariohysterectomy) female dog was pri¬marily diagnosed with bilateral hydronephrosis and ureter obstruction due to urolithiasis along with pyometra. The urolith was removed carefully by the right-side ureterectomy, an appropriate ureteral stent was inserted from the bladder to the right kidney, and then, a vasectomy and hys¬terectomy were performed. The dog improved and was discharged. However, 50 days after surgery, pyocolpos due to imperforate hymen and vestibulovaginal stenosis were diagnosed and sur¬gically corrected, and the ureteral stent was removed because the ureter had completely healed. Results: During the first admission, serum biochemistry results revealed the increased blood urea nitrogen (5.9 mg/dl), creatinine (116.2 mg/dl), amylase (1,345 U/l), and lipase (141 U/l) values. After surgical correction, all parameters returned to normal. However, 50 days after surgery, the C-reactive protein concentration (143 mg/l) and white blood cell level increased (18.4 × 109/l). After a second surgical correction, the dog recovered fully within 10 days, and no postoperative complications were observed during the follow-up of 6 months. Conclusion: This report provides diagnostic assistance and surgical treatment options for a com¬plex urogenital case. Careful examination during puberty is recommended to prevent the associ¬ated complications of this disorder. [J Adv Vet Anim Res 2020; 7(3.000): 384-390]

Objective: In Korea, small dogs are more common than large breeds. This study was performed to measure the influence of body weight, sex, breed, age, and cranial cruciate ligament rupture (RCCL) on the tibial plateau angle (TPA) in small-breed dogs. Materials and methods: A total of 274 dogs (221 normal dogs and 53 RCCL dogs) were selected for this study based on medical records. The TPA was measured from stifle joint radiographs. The dogs were divided according to body weight, sex (male and female; normal and neutered), age, breed, and RCCL, and the TPAs of the dogs were compared. Results: In general, the TPAs of male dogs were significantly (p < 0.05) higher than those of female dogs, and those of healthy neutered dogs were higher than those of healthy intact dogs. The TPA had a tendency to increase along with the animals age but was not significantly different among the four age groups. In general, the TPA of RCCL dogs was 27.12° ± 0.62°, which was significantly higher (p < 0.001) than that of normal dogs (20.21° ± 0.32°), indicating that an increased TPA is associated with a higher risk for RCCL. Similar results were also observed among dogs with similar body weights, breeds, and ages for male and female RCCL dogs. Conclusion: This study suggested that the sex and neutering status of dogs could affect the TPA. This study also confirmed the use of TPA in the veterinary clinic as a possible indicator of RCCL, as the TPA is higher in RCCL dogs than in normal dogs. [J Adv Vet Anim Res 2020; 7(2.000): 220-228]

Objective: The purpose of this study was to evaluate the clinical outcome of surgical decompression and rehabilitation therapy in dogs with thoracolumbar intervertebral disk herniation (IVDH). Materials and Methods: After surgery, physiotherapeutic rehabilitation was performed by a combination of electrotherapy, infrared therapy, training for standing, deep tendon reflex, and aquatic treadmill exercise. A total of 186 dogs were selected from the hospital records and included in two groups: the rehabilitated group (RG, n = 96) and non-rehabilitated group (NRG, n = 90). Dogs in each group were subdivided into three groups based on a pre-operative clinical severity grading system and those in grades 24 were included in this study. Post-operative neurologic functions, unassisted standing, walking, and the success rate of both groups were evaluated and compared Results: Overall, 86.46% (83/96) of dogs had a successful neurologic outcome in the RG group, which was significantly (p < 0.01) higher than the NRG group 52.22% (47/90). Interestingly, the success rate differed when the preoperative grading system was considered. The success rates of grades 2, 3, and 4 were 97.14% (34/35), 97.33% (42/45), and 43.75% (7/16), respectively, in the rehabilitated groups, whereas in the non-rehabilitated groups, success rates were 82.35% (28/34), 51.85% (14/27), and 17.24% (5/29), respectively. The differences in success rates among the groups according to grading were 14.79%, 41.48%, and 26.51%, respectively, indicating that the proposed rehabilitation therapy is remarkably advantageous for increasing the success rate. Conclusion: Rehabilitation therapy after surgical decompression of thoracolumbar IVDH improves neurologic functions and increases the success rate, especially when the preoperative pathological condition is severe. [J Adv Vet Anim Res 2019; 6(3.000): 394-402]

Photoswitchable nanoparticles can be used for selective imaging in biological systems but usually have only one color. Here the authors develop a two-color fluorescent emissive system that allows full on-off switching of one component color of the system while the other color is unaffected, which has implications for super-resolution imaging.

The objective of this study was to evaluate the clinical outcome of ventral slot decompression and rehabilitation therapy in dogs with cervical intervertebral disc herniation (IVDH). Surgical decompression was performed in dogs with IVDH using the ventral slot procedure. After surgery, physiotherapeutic rehabilitation consisted of a combination of electrotherapy, infrared therapy and mechanical massage; treadmill exercise was started when the animal could stand up. A total of 58 dogs were selected from the hospital and included in two groups: rehabilitated group (RG, n = 34) and non-rehabilitated group (NRG, n = 24). Dogs of each group were subdivided into five groups based on a pre-operative clinical grading system. Grade 1 designated spinal pain only, grade 2 designated ambulatory paraparesis, grade 3 designated non-ambulatory paraparesis, grade 4 designated paraplegia with deep-pain perception intact and grade 5 designated paraplegia without deep-pain perception. Post-operative changes of both groups were evaluated and compared, including time until unassisted standing and walking after surgery and the success rate. Overall, 79.41% (27/34) of dogs had a successful neurologic outcome in the RG group, which was significantly (P < 0.05) higher than the NRG group 62.50% (15/24). Interestingly, the success rate differed when the preoperative grading system was considered. The success rates of grades 1, 2, 3, 4 and 5 were 100% (9/9), 100% (7/7), 75% (3/4), 53.85% (7/13) and 100% (1/1), respectively, in the rehabilitated groups, whereas in the non-rehabilitated groups success rates were 100% (5/5), 83.33% (5/6), 60.00% (3/5), 28.57% (2/7) and 0% (0/1), respectively. The differences in success rates between the two groups according to grading were 0, 16.67, 15, 25.57 and 100%, respectively. The proposed rehabilitation therapy after surgical decompression of cervical IVDH can improve the success rate when the preoperative pathological condition is severe.

Background Uveal melanoma (UM) is the most frequent intraocular malignancy and is resistant to immunotherapy. Nearly 50% of patients with UM develop metastatic disease, and the overall survival outcome remains very poor. Therefore, a treatment regimen that simultaneously targets primary UM and prevents metastasis is needed. Here, we suggest an immunotherapeutic strategy for UM involving a combination of local photodynamic therapy (PDT), rho-kinase (ROCK) inhibitor, and PD-1/PD-L1 immune checkpoint blockade.Methods The antitumor efficacy and immune response of monotreatment or combinational treatment were evaluated in B16F10-bearing syngeneic mouse models. Abscopal antitumor immune responses induced by triple-combinational treatment were validated in syngeneic bilateral B16F10 models. After each treatment, the immune profiles and functional examinations were assessed in tumors and tumor draining lymph nodes by flow cytometry, ELISA, and immunofluorescence assays. In orthotopic intraocular melanoma models, the location of the immune infiltrate in the tumor microenvironment (TME) was evaluated after each treatment by multiplex immunohistochemistry and metastatic nodules were monitored.Results PDT with Ce6-embedded nanophotosensitizer (FIC-PDT) elicited immunogenic cell death and stimulated antigen-presenting cells. In situ immunogenic clearance induced by a combination of FIC-PDT with ripasudil, a clinically approved ROCK inhibitor, stimulated antigen-presenting cells, which in turn primed tumor-specific cytotoxic T cells. Moreover, local immunogenic clearance sensitized PD-1/PD-L1 immune checkpoint blockade responses to reconstruct the TME immune phenotypes of cold tumors into hot tumors, resulting in recruitment of robust cytotoxic CD8+ T cells in the TME, propagation of systemic antitumor immunity to mediate abscopal effects, and prolonged survival. In an immune-privileged orthotopic intraocular melanoma model, even low-dose FIC-PDT and ripasudil combined with anti-PD-L1 antibody reduced the primary tumor burden and prevented metastasis.Conclusions A combination of localized FIC-PDT and a ROCK inhibitor exerted a cancer vaccine-like function. Immunogenic clearance led to the trafficking of CD8+ T cells into the primary tumor site and sensitized the immune checkpoint blockade response to evoke systemic antitumor immunity to inhibit metastasis, one of the major challenges in UM therapy. Thus, immunogenic clearance induced by FIC-PDT and ROCK inhibitor combined with anti-PD-L1 antibody could be a potent immunotherapeutic strategy for UM.

Strategic information system planning (SISP) is a central process that enables organizations to identify the strategic alignment of their IT portfolio to achieve their business needs and objectives. The extant SISP literature has focused on theoretical and processual aspects and has left methodological ambiguity about how SISP is practiced. This paper contributes to the current knowledge by providing a mixed-methods SISP framework labeled CSF-MCDM for company-wide strategic alignment. The paper conducts a methodological synthesis, embracing an expert-based qualitative approach based on a PEST-SWOT and causal layered analysis to draw the critical success factors of a next-generation business system for an automotive company in South Korea. The derived CSF dimensions and sub-criteria are evaluated by the multi-criteria decision-making model, engaging a strategy-as-practice lens to SISP to enable an integrative analysis of IS strategy formulation, planning, and implementation. The findings reveal the relative strategic priorities of dimensions, the following core activities, and the global priorities for resource distribution planning for IS strategy of the firm. This paper argues that bringing replicability with SISP and diversifying methodological approaches within the organization is substantial. This paper also suggests that future researchers validate the suggested framework for scientific replicability and expand the SISP research stream within the entire IS/IT ecosystem.

In this study, novel 800 nm-excitable and highly intense green-emitting non-NaY(Gd)F4-based core/shell/shell (CSS) upconversion nanophosphors (UCNPs) are reported. Scheelite-structured Li(Gd,Y)F4:Yb,Er core UCNPs are synthesized, followed by the formation of a Nd3+-doped active shell and inert shell, and the novel Li(Gd,Y)F4:Yb,Er/LiYF4:Nd,Yb/LiGdF4 CSS UCNPs are applied to liver cancer cell-targeted upconversion luminescence imaging. X-ray diffraction and electron energy loss spectroscopy confirm that single tetragonal phase scheelite-structured CSS UCNPs are successfully synthesized. Because of the formation of the active shell and inert shell on the core, CSS UCNPs display bright green light under both 800 and 980 nm excitations. In particular, the synthesized CSS UCNPs exhibit a high absolute upconversion quantum yield of 0.15% under 800 nm excitation. For liver cancer cell targeting, free amine and poly(ethylene glycol) (PEG)-introduced glycyrrhetinic acid (GA) (GA-PEG-NH2) is synthesized, and the GA-PEG-NH2 is conjugated with the CSS UCNPs, whose surface was modified with poly(acrylic acid sodium salt). HepG2 liver cancer cells are imaged with the GA-PEG-NH2-conjugated CSS UCNPs and an 808 nm near-infrared laser, and in vivo liver cancer cell imaging is successfully conducted.

This article examines the mechanisms that influence team-level performance. It investigates psychological safety, a shared belief that the team is safe for interpersonal risk taking and a causal model mediated by learning behavior and efficacy. This model hypothesizes that psychological safety and efficacy are related, which have been believed to be same-dimension constructs. It also explains the process of how learning behavior affects the team’s efficacy. In a study of 104 field sales and service teams in South Korea, psychological safety did not directly affect team effectiveness. However, when mediated by learning behavior and efficacy, a full-mediation effect was found. The results show (i) that psychological safety is the engine of performance, not the fuel, and (ii) how individuals contribute to group performance under a psychologically safe climate, enhancing team processes. Based on the findings, this article suggests theoretical and methodological implications for future research to maximize teams’ effectiveness.

Considering the priority of water supply, agricultural water supply capacity downstream of the Yeongsan River Basin was evaluated in this study. The water balance was analyzed using the Please check all author names carefullyMODSIM-decision support system (MODSIM-DSS) to evaluate the agricultural water supply capacity. MODSIM-DSS can also be used to analyze the watershed demand status and agricultural water supply facilities. In this study, the watershed inflow and agricultural reservoir inflow (supply) data for each watershed were obtained using the SWAT outflow data. SWAT was calibrated and validated using 16-years (2005–2020) of daily streamflow data from one water level station and two weirs, by considering water withdrawal and return flows from agricultural, domestic, and industrial water use. The coefficient of determination (R2) was analyzed as 0.50 to 0.80 at three stations. Then, water balance analyses were performed for 41 years (1980–2020) by applying the SWAT outflow results to MODSIM-DSS. The results showed that agricultural water shortages of 517.8 × 106 m3, 520.0 × 106 m3, 579.8 × 106 m3, and 517.5 × 106 m3, occurred in 1992, 1994, 1995, and 2015, respectively. The efficiencies of agricultural water supply for these years were 58.2%, 58.0%, 53.2%, and 58.2%, respectively, which were lower than the 40-year average of 84.5%.

Objective: The objective of this retrospective study was to evaluate the preoperative clinical characteristics to predict postoperative neurologic recovery in dogs with intervertebral herniated disk disease (IVDD). Materials and Methods: The dogs were classified according to postoperative neurologic recovery from clinical history of the hospital e-book. Excellent when dogs (n=13) were neurologically normal; good (n=8) when postoperative neurologic grade was improved from preoperative condition had improved sufficiently to require no or minor therapy after discharge; fair (n=4) is considered when postoperative neurologic status was unchanged from preoperative condition and poor (n=5) when major postoperative complication developed as a consequences neurologic grade had worsened at discharge than their preoperative score or the patient died. The evaluated preoperative clinical characteristics in all groups are breed, age, sex, duration of clinical sings appearance (DCSA), preoperative neurologic grading system (PNGS), compression rate (pre and post-operative) in MRI and CT scan, housefield unit (HU), type of IVDD and surgical procedures, and compared with excellent group. Results: no definitive relationship was found between the clinical characteristics and neurologic recovery, except, DCSA and preclinical neurologic pathological condition. The DCSA were 73.54±15.00, 117.63±31.58, 171.25±99.56 and 175.00±94.83 (P [J Adv Vet Anim Res 2018; 5(2.000): 240-246]

Objective: The aim of this paper is to report surgical correction of ureteric rupture due to stenosis induced secondary to accidental injury by placing nephrovesical subcutaneous ureteric bypass in a dog and postoperative long term outcomes. Materials and methods: Imaging techniques revealed multiple bone fractures as well as left proximal ureter injury. The all bone fractures were corrected using standard techniques while left proximal ureter injury was treated as conservation medical therapy. One month later, contrast media were also found in proximal ureter and abdomen which indicated ureter rupture. This rupture was corrected surgically by nephrovesical subcutaneous ureteric bypass (SUB) under fluoroscopy guidance. Results: First day after accidental injury, the serum BUN and CRE were 10.7 mg/dL and 0.9 mg/dL, respectively which indicated kidney injury but by conservative therapy these parameters were lowered gradually. On the 5th day after considering these parameters, the dog was judged normal. However, on the 31st day BUN and CRE were 14.3 mg/dL and 0.8 mg/Kg, respectively. The Doppler ultrasonography revealed hydroneprosis, proximal ureter stenosis and high resistive index (0.72±0.02) in the renal arcuate artery indicating renal abnormalities due to ureter obstruction. On re-examination by radiography after one month postoperatively, revealed that patency of the device and normal renal function. The dog was clinically normal with normal urination and no complications were found 6 months postoperatively. Conclusion: In view of the above findings, it is suggested that the SUB system can be a better alternative to preserve the kidney in non-reparable traumatic ureteral damage in dogs. [J Adv Vet Anim Res 2018; 5(2.000): 247-254]

Purpose The Korean Triage and Acuity Scale (KTAS) is a triage tool for patients in the emergency department (ED). We aimed to investigate the association between the KTAS level and hospitalization of children with abdominal pain, a common chief complaint in the ED. Methods This study retrospectively reviewed medical records of children aged 3 to 14 years who visited the ED with abdominal pain as a chief complaint. KTAS level (1-3 vs. 4-5), age, gender, presence of associated symptoms (vomiting, diarrhea, hematochezia, and fever), and disposition (rapid discharge, discharge after intravenous hydration, and hospitalization) were collected and compared between the children with KTAS 1-3 and 4-5. Results Of 1,050 children enrolled, 618 (58.9%) were classified as KTAS 1-3, and 36 (3.4%) were hospitalized. Vomiting was the most common associated symptom in both groups (63.6%), and 41.5% underwent discharge after intravenous hydration. The children with KTAS 1-3 were more frequently hospitalized (5.0% vs. 1.2%, P < 0.001). Conclusion The KTAS may be reliable to predict the hospitalization of children with abdominal pain in the ED with additional consideration of the associated symptoms.

This study aims to develop a reservoir operation rule adding downstream environmental flow release (EFR) to the exclusive use of irrigation water supply (IWS) from agricultural reservoirs through canals to rice paddy areas. A reservoir operation option was added in the Soil and Water Assessment Tool (SWAT) to handle both EFR and IWS. For a 366.5 km2 watershed including three agricultural reservoirs and a rice paddy irrigation area of 4744.7 ha, the SWAT was calibrated and validated using 21 years (1998–2018) of daily reservoir water levels and downstream flow data at Gongdo (GD) station. For reservoir water level and streamflow, the average root means square error (RMSE) ranged from 19.70 mm to 19.54 mm, and the coefficient of determination (R2) and Nash–Sutcliffe efficiency (NSE) had no effect on the improved SWAT. By applying the new reservoir option, the EFR amount for a day was controlled by keeping the reservoir water level up in order to ensure that the IWS was definitely satisfied in any case. The downstream mean wet streamflow (Q95) decreased to 5.70 m3/sec from 5.71 m3/sec and the mean minimum flow (Q355) increased to 1.05 m3/sec from 0.94 m3/sec. Through the development of a SWAT reservoir operation module that satisfies multiple water supply needs such as IWR and EFR, it is possible to manage agricultural water in the irrigation period and control the environmental flow in non-irrigation periods. This study provides useful information to evaluate and understand the future impacts of various changes in climate and environmental flows at other sites.

Objective: Postoperative complication of extramural ectopic ureters (EEUs) with persistent urinary incontinence (UI) is common in Siberian Huskies. This case report was aimed at reporting the successful correction procedure of EEU in Siberian Huskies by surgical procedure. Materials and methods: A three-month-old and weighing 7.9 kg Siberian Husky dog was presented with history of an acute dermatitis around the genitals, swelling of the genitals and dribbling urination. Abdominal radiographs, ultrasonography, and 3D computed tomography scanning revealed presence of the ectopic ureter with urinary incontinence. Ureteroneocystostomy was applied as the first choice of corrective procedure in this case, and clinical sings were corrected apparently after surgery. Unfortunately, UI with cystitis was developed two months postoperatively. To correct the condition, surgical procedure of colposuspension with ovarianhystectomy and cystopexy was opted. Results: Post-operative progression showed good prognosis and the dog recovered fully. Follow up checkup of the patient after 4 months postoperative and follow up phone call 27 months later did not reveal any abnormalities. Conclusion: This case report recommends surgical procedure of modified colposuspension following ureteroneocystostomy to correct EEUs and its postoperative complication. [J Adv Vet Anim Res 2017; 4(3.000): 301-306]

Time synchronization for wireless sensors is important for a proper interpretation of measurements, particularly for acceleration measurements to estimate mode-shapes. This paper presents a new time synchronization method working independently on each node without exchanging time-sync packets among nodes. This stand-alone operation can make field measurement campaigns very time-efficient without constructing and validating the wireless sensor network. The proposed method firstly time-stamps measurements using the accurate time-source from a GPS module on each node, and secondly re-samples the time-stamped data to get time-synchronized data. The time-stamping method proposed in the study utilizes Pulse-Per-Second (PPS) signals and NMEA (National Marine Electronics Association) sentences generated by a low-cost GPS module, and the internal timer/counter unit of Arduino. Error analysis on the proposed time-stamping method was carried out and derived an analytical expression for the maximum variance of time-stamping error of the proposed method. Four experiments have been carried out to observe (1) the long-term operational stability of the GPS module, (2) the accuracy of the PPS signals, (3) the accuracy of the proposed time-stamping method, and (4) the validity of the proposed time-synchronization method for output-only modal analysis on a laboratory floor structure. The GPS module was found to operate or to resume operating stably for the entire test period of 7 days even with the limited field of view to the sky. The relative time errors of two PPS signals from four GPS modules were found to be within ±400 ns. The time-stamping error measured by two identical time-stamping Arduinos for common trigger signals was found to have a standard deviation of 40.8 ns, which agreed well with the maximum value of 42.0 ns predicted by the error analysis. From the output-only modal analysis, the estimated modal parameters were found to agree well with that from the wired acceleration sensors. The phase angle of the cross spectral density of the two wireless accelerations showed that there was no apparent time-synchronization error observable. These observations indicated a successful operation of the proposed time-synchronization method.

The immune-suppressive effects of omega-3 (n-3) polyunsaturated fatty acids (PUFAs) on T cells have been observed via multiple in vitro and in vivo models. However, the precise mechanism that causes these effects is still undefined. In this study, we investigated whether n-3 PUFAs regulated T cell receptor (TCR) and peptide-major histocompatibility complex (pMHC) interactions. The expansion of anti-viral CD8+ T cells that endogenously synthesize n-3 PUFAs (FAT-1) dramatically decreased upon lymphocytic choriomeningitis virus (LCMV) infection in vivo. This decrease was not caused by the considerable reduction of TCR expression or the impaired chemotactic activity of T cells. Interestingly, a highly inclined and laminated optical sheet (HILO) microscopic analysis revealed that the TCR motility was notably reduced on the surface of the FAT-1 CD8+ T cells compared to the wild type (WT) CD8+ T cells. Importantly, the adhesion strength of the FAT-1 CD8+ T cells to the peptide-MHC was significantly lower than that of the WT CD8+T cells. Consistent with this result, treatment with docosahexaenoic acid (DHA), one type of n-3 PUFA, significantly decreased CD8+ T cell adhesion to the pMHC. Collectively, our results reveal a novel mechanism through which n-3 PUFAs decrease TCR-pMHC interactions by modulating TCR mobility on CD8+ T cell surfaces.

Atherosclerosis is a well-known cause of cardiovascular disease and is associated with a variety of inflammatory reactions. However, an adequate large-animal model of advanced plaques to investigate the pathophysiology of atherosclerosis is lacking. Therefore, we developed and assessed a swine model of advanced atherosclerotic plaques with macrophage polarization.Mini-pigs were fed a 2% high-cholesterol diet for 7 weeks followed by withdrawal periods of 4 weeks. Endothelial denudation was performed using a balloon catheter on 32 coronary and femoral arteries of 8 mini-pigs. Inflammatory proteins (high-mobility group box 1 [HMGB1] or tumor necrosis factor alpha (TNF-α) were injected via a micro-infusion catheter into the vessel wall. All lesions were assessed with angiography and optical coherence tomography and all tissues were harvested for histological evaluation.Intima/plaque area was significantly higher in the HMGB1- and TNF-α-injected groups compared to the saline-injected group (p = 0.002). CD68 antibody detection and polarization of M1 macrophages significantly increased in the inflammatory protein-injected groups (p

By virtue of the advances in sensing techniques, finite element (FE) model updating (FEMU) using static and dynamic data has been recently employed to improve identification on updating parameters. Using heterogeneous data can provide useful information to improve parameter identifiability in FEMU. It is worth noting that the useful information from the heterogeneous data may be diluted in the conventional FEM framework. The conventional FEMU framework in previous studies have used heterogeneous data at once to compute residuals in the objective function, and they are condensed to be a scalar. In this implementation, it should be careful to formulate the objective function with proper weighting factors to consider the scale of measurement and relative significances. Otherwise, the information from heterogeneous data cannot be efficiently utilized. For FEMU of the bridge, parameter compensation may exist due to mutual dependence among updating parameters. This aggravates the parameter identifiability to make the results of the FEMU worse. To address the limitation of the conventional FEMU method, this study proposes a sequential framework for the FEMU of existing bridges. The proposed FEMU method uses two steps to utilize static and dynamic data in a sequential manner. By using them separately, the influence of the parameter compensation can be suppressed. The proposed FEMU method is verified through numerical and experimental study. Through these verifications, the limitation of the conventional FEMU method is investigated in terms of parameter identifiability and predictive performance. The proposed FEMU method shows much smaller variabilities in the updating parameters than the conventional one by providing the better predictions than those of the conventional one in calibration and validation data. Based on numerical and experimental study, the proposed FEMU method can improve the parameter identifiability using the heterogeneous data and it seems to be promising and efficient framework for FEMU of the existing bridge.

To analytically evaluate buffeting responses, the analysis of wind characteristics such as turbulence intensity, turbulence length, gust, and roughness coefficient must be a priority. The analytical buffeting response is affected by the static aerodynamic force coefficient, flutter coefficient, structural damping ratio, aerodynamic damping ratio, and natural frequencies of the bridge. The cable-stayed bridge of interest in this study has been used for 32 years. In that time, the terrain conditions around the bridge have markedly changed from the conditions when the bridge was built. Further, the wind environments have varied considerably due to climate change. For these reasons, the turbulence intensity, length, spectrum coefficient, and roughness coefficient of the bridge site must be evaluated from full-scale measurements using a structural health monitoring system. Although the bridge is located on a coastal area, the evaluation results indicated that the wind characteristics of bridge site were analogous to those of open terrain. The buffeting response of the bridge was analyzed using the damping ratios, static aerodynamic force coefficients, and natural frequencies obtained from measured data. The analysis was performed for four cases. Two case analyses were performed by applying the variables obtained from measured data, while two other case analyses were performed based on the Korean Society of Civil Engineers (KSCE) Design Guidelines for Steel Cable Supported Bridges. The calculated responses of each analysis case were compared with the buffeting response measured at wind speeds of less than 25 m/s. The responses obtained by numerical analysis using estimated variables based on full-scale measurements agreed well with the measured buffeting responses measured at wind speeds of less than 25 m/s. Moreover, an extreme wind speed of 44 m/s, corresponding to a recurrence interval of 200 years, was derived from the Gumbel distribution. Therefore, the buffeting responses at wind speeds of 45 m/s were also determined by applying the estimated variables. From these results, management criteria based on measurement data for in-service bridge are determined and each level of management is proposed.

This study was to evaluate the groundwater-level behavior in Geum River Basin (9645.5 km2) of South Korea with HadGEM3-RA RCP 4.5 and 8.5 climate change scenarios and future groundwater use data using the soil and water assessment tool (SWAT). Before evaluating future groundwater behavior, the SWAT model was calibrated and validated using the daily inflows and storage of two dams (DCD and YDD) in the basin for 11 years (2005−2015), the daily groundwater-level observation data at five locations (JSJS, OCCS, BEMR, CASS, and BYBY), and the daily inflow and storage of three weir locations (SJW, GJW, and BJW) for three years and five months (August 2012 to December 2015). The Nash−Sutcliffe efficiency (NSE) and the coefficient of determination (R2) of two dam inflows was 0.55−0.70 and 0.67−0.75. For the inflows of the three weirs, NSE was 0.57−0.77 and R2 was 0.62−0.81. The average R2 value for the groundwater levels of the five locations ranged from 0.53 to 0.61. After verifying the SWAT for hydrologic components, we evaluated the behavior of future groundwater levels by future climate change scenarios and estimated future ground water use by Korean water vision 2020 based on ground water use monitoring data. The future groundwater-level decreased by −13.0, −5.0, and −9.0 cm at three upstream locations (JSJS, OCCS, and BEMR) among the five groundwater-level observation locations and increased by +3.0 and +1.0 cm at two downstream locations (CASS and BYBY). The future groundwater level was directly affected by the groundwater recharge, which was dependent on the seasonal and spatial precipitations in the basin.

The transcription factor nuclear factor-κB (NF-κB) is a central mediator of growth and homeostasis for both normal and neoplastic cells. IκBα is the natural intracellular inhibitor of NF-κB and can effectively complex with and thereby inhibit the biologic activity and translocation of NF-κB to the nucleus. We designed a fusion protein designated IκBα/scFvMEL composing of human IκBα and the single-chain antibody scFvMEL, targets melanoma gp240 antigen. Cells treated with IκBα/scFvMEL before irradiation showed specifically inhibition of both constitutive and radiation-induced NF-κB activity on gp240 antigen-positive A375M cells. Pretreatment of A375M cells with IκBα/scFvMEL significantly sensitized melanoma cells to ionizing radiation assessed using a clonogenic survival assay. Mechanistic studies showed that IκBα/scFvMEL, when exogenously added to A375M cells, could be coimmunoprecipitated with the p65 subunit of NF-κB. IκBα/scFvMEL inhibited in a time and/or dose-dependent manner of tumor necrosis factor α- or radiation-induced NF-κB activity in vitro. IκBα/scFvMEL was also shown to specifically inhibit the translocation of the NF-κB p65 subunit to the cell nucleus and NF-κB-mediated gene transcription. Further, initial studies showed that mice bearing well-established A375M xenografts were treated (intravenously) with IκBα/scFvMEL and showed a significant suppression of tumor growth. We also observed a decrease in levels of Bcl-2 and Bcl-XL signaling events downstream of NF-κB in the tumor model. These studies demonstrate for the first time that tumor cell-targeted delivery of IκBα may be beneficial for the treatment of melanoma when combined with standard anticancer therapies such as radiation.

In a semiconductor manufacturing process, defect cause analysis is a challenging task because the process includes consecutive fabrication phases involving numerous facilities. Recently, in accordance with the shrinking chip pitches, fabrication (FAB) processes require advanced facilities and designs for manufacturing microcircuits. However, the sizes of the particle defects remain constant, in spite of the increasing modernization of the facilities. Consequently, this increases the particle defect ratio. Therefore, this study proposes a particle defect management method for the reduction of the defect ratio. The proposed method provides a kernel-density-based particle map that can overcome the limitations of the conventional method. The method consists of two phases. The first phase is the acquisition of cumulative coordinates of the defect locations on the wafer using the FAB database. Subsequently, this cumulative data is used to generate a particle defect map based on the estimation of kernel density; this map establishes the advanced monitoring statistics. In order to validate this method, we conduct an experiment for comparison with the previous industrial method.

Dynamic characteristics of structures have been monitored for safe operation and efficient maintenance of large civil infrastructures. For vibration data measurement, the conventional system uses cables, which cause very expensive costs and inconvenient installation. Therefore, various wireless sensor nodes have been developed to replace the conventional wired system. However, there still remain lots of issues to be resolved such as time synchronization between sensor nodes, data loss, data security, and power supply. In this study, Smart One-Channel Sensor Node (SOSN) was developed to measure vibration data, which can practically solve the issues on installation, time synchronization, and data storage. It is designed for temporal measurement with a limited capacity to operate for several hours using embedded batteries. Laboratory tests were carried out to verify the performance of the developed SOSN compared with conventional wired system. Its practical advantages were investigated through three full-scale tests on large civil infrastructures. Three field applications revealed that SOSN is a very practical tool for short-term monitoring of large civil infrastructures with respect to traffic control, installation time and convenience, secure data gathering, and so forth.

Superparamagnetic Fe3O4 nanoparticles (NPs) based nanomaterials have been exploited in various biotechnology fields including biomolecule separation. However, slow accumulation of Fe3O4 NPs by magnets may limit broad applications of Fe3O4 NP-based nanomaterials. In this study, we report fabrication of Fe3O4 NPs double-layered silica nanoparticles (DL MNPs) with a silica core and highly packed Fe3O4 NPs layers. The DL MNPs had a superparamagnetic property and efficient accumulation kinetics under an external magnetic field. Moreover, the magnetic field-exposed DL MNPs show quantitative accumulation, whereas Fe3O4 NPs single-layered silica nanoparticles (SL MNPs) and silica-coated Fe3O4 NPs produced a saturated plateau under full recovery of the NPs. DL MNPs are promising nanomaterials with great potential to separate and analyze biomolecules.