Novel Personalized Cancer Vaccine Using Tumor Extracellular Vesicles with Attenuated Tumorigenicity and Enhanced Immunogenicity.

Cancer vaccines offer a promising avenue in cancer immunotherapy by inducing systemic, tumor-specific immune responses. Tumor extracellular vesicles (TEVs) are nanoparticles naturally laden with tumor antigens, making them appealing for vaccine development. However, their inherent malignant properties from the original tumor cells limit their direct therapeutic use. This study introduces a novel approach to repurpose TEVs as potent personalized cancer vaccines. The study shows that inhibition of both YAP and autophagy not only diminishes the malignancy-associated traits of TEVs but also enhances their immunogenic attributes by enriching their load of tumor antigens and adjuvants. These revamped TEVs, termed attenuated yet immunogenically potentiated TEVs (AI-TEVs), showcase potential in inhibiting tumor growth, both as a preventive measure and a possible treatment for recurrent cancers. They prompt a tumor-specific and enduring immune memory. In addition, by showing that AI-TEVs can counteract cancer growth in a personalized vaccine approach, a potential strategy is presented for developing postoperative cancer immunotherapy that's enduring and tailored to individual patients.

Protective effect of hygrolansamycin C against corticosterone-induced toxicity and oxidative stress-mediated via autophagy and the MAPK signaling pathway.

BACKGROUND: Excessive stress, a major problem in modern societies, affects people of all ages worldwide. Corticosterone is one of the most abundant hormones secreted during stressful conditions and is associated with various dysfunctions in the body. In particular, we aimed to investigate the protective effects of hygrolansamycin C (HYGC) against corticosterone-induced cellular stress, a manifestation of excessive stress prevalent in contemporary societies. METHODS: We isolated HYGC from Streptomyces sp. KCB17JA11 and subjected PC12 cells to corticosterone-induced stress. The effects of HYGC were assessed by measuring autophagy and the expression of mitogen-activated protein kinase (MAPK) phosphorylation-related genes. We used established cellular and molecular techniques to analyze protein levels and pathways. RESULTS: HYGC effectively protected cells against corticosterone-induced injury. Specifically, it significantly reduced corticosterone-induced oxidative stress and inhibited the expression of autophagy-related proteins induced by corticosterone, which provided mechanistic insight into the protective effects of HYGC. At the signaling level, HYGC suppressed c-Jun N-terminal kinase and extracellular signal-regulated kinase phosphorylation and p38 activation. CONCLUSIONS: HYGC is a promising candidate to counteract corticosterone-induced apoptosis and oxidative stress. Autophagy and MAPK pathway inhibition contribute to the protective effects of HYGC. Our findings highlight the potential of HYGC as a therapeutic agent for stress-related disorders and serve as a stepping stone for further exploration and development of stress management strategies.

Optimization of Pore Characteristics of Graphite-Based Anode for Li-Ion Batteries by Control of the Particle Size Distribution.

We investigate the reassembly techniques for utilizing fine graphite particles, smaller than 5 µm, as high-efficiency, high-rate anode materials for lithium-ion batteries. Fine graphite particles of two sizes (0.4-1.2 µm and 5 µm) are utilized, and the mixing ratio of the two particles is varied to control the porosity of the assembled graphite. The packing characteristics of the assembled graphite change based on the mixing ratio of the two types of fine graphite particles, forming assembled graphite with varying porosities. The open porosity of the manufactured assembled graphite samples ranges from 0.94% to 3.55%, while the closed porosity ranges from 21.41% to 26.51%. All the assembled graphite shows improved electrochemical characteristics properties compared with anodes composed solely of fine graphite particles without granulation. The sample assembled by mixing 1.2 µm and 5 µm graphite at a 60:40 ratio exhibits the lowest total porosity (27.45%). Moreover, it exhibits a 92.3% initial Coulombic efficiency (a 4.7% improvement over fine graphite particles) and a capacity of 163.4 mAh/g at a 5C-rate (a 1.9-fold improvement over fine graphite particles).

Optimization of the Filler-and-Binder Mixing Ratio for Enhanced Mechanical Strength of Carbon-Carbon Composites.

In this paper, a method for optimizing the mixing ratio of filler coke and binder for high-strength carbon-carbon composites is proposed. Particle size distribution, specific surface area, and true density were analyzed to characterize the filler properties. The optimum binder mixing ratio was experimentally determined based on the filler properties. As the filler particle size was decreased, a higher binder mixing ratio was required to enhance the mechanical strength of the composite. When the d50 particle size of the filler was 62.13 and 27.10 µm, the required binder mixing ratios were 25 and 30 vol.%, respectively. From this result, the interaction index, which quantifies the interaction between the coke and binder during carbonization, was deduced. The interaction index had a higher correlation coefficient with the compressive strength than that of the porosity. Therefore, the interaction index can be used in predicting the mechanical strength of carbon blocks and optimizing their binder mixing ratios. Furthermore, as it is calculated from the carbonization of blocks without additional analysis, the interaction index can be easily used in industrial applications.

Ex Situ Study on the Co-Preparation of Pitch and Carbon Black from Petroleum Residue to Improve the Cost-Efficiency of the Pitch Synthesis Plant.

This study aims to improve the economic efficiency of the pitch synthesis reaction on the pilot plant by optimizing the pitch synthesis reaction and utilization of the byproduct. The pitch was synthesized using a 150 L pilot plant with pyrolyzed fuel oil as a precursor. The pitch synthesis reaction is carried out through volatilization and polycondensation, which occur at 300 and 400 °C. Volatilization is terminated during heating; thus, additional soaking time is meaningless and reduces the process efficiency. Soaking time is a major variable when the synthesis temperature exceeds 400 °C. The byproduct is generated through volatilization; thus, its chemical characteristics are only influenced by the reaction temperature. The byproduct consists of various polycyclic aromatic hydrocarbons. The average molecular weight and yield of the byproduct increase with the reaction temperature. Carbon black was synthesized using chemical vapor deposition from the byproduct. The particle size of carbon black was controlled by the used precursor (byproduct), and the electrical conductivity of prepared carbon black has a maximum of 58.0 S/cm. Therefore, carbon black, which is synthesized from the byproduct of pitch synthesis, is expected to be used as a precursor for conductive material used in lithium-ion batteries or supercapacitors.

Structural Analysis of Mo Thin Films on Sapphire Substrates for Epitaxial Growth of AlN.

Aluminum nitride (AlN) thin film/molybdenum (Mo) electrode structures are typically required in microelectromechanical system applications. However, the growth of highly crystalline and c-axis-oriented AlN thin films on Mo electrodes remains challenging. In this study, we demonstrate the epitaxial growth of AlN thin films on Mo electrode/sapphire (0001) substrates and examine the structural characteristics of Mo thin films to determine the reason contributing to the epitaxial growth of AlN thin films on Mo thin films formed on sapphire. Two differently oriented crystals are obtained from Mo thin films grown on sapphire substrates: (110)- and (111)-oriented crystals. The dominant (111)-oriented crystals are single-domain, and the recessive (110)-oriented crystals comprise three in-plane domains rotated by 120° with respect to each other. The highly ordered Mo thin films formed on sapphire substrates serve as templates for the epitaxial growth by transferring the crystallographic information of the sapphire substrates to the AlN thin films. Consequently, the out-of-plane and in-plane orientation relationships among the AlN thin films, Mo thin films, and sapphire substrates are successfully defined.

Development of an Implantable Capacitive Pressure Sensor for Biomedical Applications.

In this study, a subminiature implantable capacitive pressure sensor is proposed for biomedical applications. The proposed pressure sensor comprises an array of elastic silicon nitride (SiN) diaphragms formed by the application of a polysilicon (p-Si) sacrificial layer. In addition, using the p-Si layer, a resistive temperature sensor is also integrated into one device without additional fabrication steps or extra cost, thus enabling the device to measure pressure and temperature simultaneously. The sensor with a size of 0.5 × 1.2 mm was fabricated using microelectromechanical systems (MEMS) technology and was packaged in needle-shaped metal housing that is both insertable and biocompatible. The packaged pressure sensor immersed in a physiological saline solution exhibited excellent performance without leakage. The sensor achieved a sensitivity of approximately 1.73 pF/bar and a hysteresis of about 1.7%, respectively. Furthermore, it was confirmed that the pressure sensor operated normally for 48 h without experiencing insulation breakdown or degradation of the capacitance. The integrated resistive temperature sensor also worked properly. The response of the temperature sensor varied linearly with temperature variation. It had an acceptable temperature coefficient of resistance (TCR) of approximately 0.25%/°C.

Effect and Mechanism of Pitch Coating on the Rate Performance Improvement of Lithium-Ion Batteries.

This study evaluated the effect of pitch coating on graphite anode materials used in lithium-ion batteries and investigated the mechanism whereby pitch coating improves the electrochemical properties. The FG (flake graphite) and pitch were mixed in weight ratios of 95:5-80:20. The mixture was pressed and prepared into a block form. Additionally, heat treatment was performed at 900 °C for 1 h and pulverized in the size range of 10-25 µm. The results showed that the particles of uniform pitch-coated graphite became more spherical. However, when the pitch is added excessively, pitch aggregation occurs rather than a thicker coating, indicating a nonuniform particle shape. Pitch has a randomly oriented structure and a small crystal size. Therefore, pitch serves as a lithium-ion diffusion pathway, resulting in an improved rate of performance. Notably, the uniform pitch-coated graphite exhibited an outstanding rate of performance owing to the relieving of particle orientation in the electrode rolling process. During the rolling process, the particles are oriented perpendicular to the lithium-ion diffusion pathway, making it difficult for the lithium ions to diffuse. Adding an excessive amount of pitch was found to deteriorate the rate of performance. Pitch aggregation increased the interfacial resistance by forming a heterogeneous surface.

Long-Term Outcomes of Preoperative Atrial Fibrillation in Cardiac Surgery.

Background: Atrial fibrillation (Afib) is a marker of increased cardiovascular morbidity and mortality. Owing to the increased prevalence of Afib in patients undergoing cardiac surgery, assessing the effect of Afib on postsurgical outcomes is important. We aimed to analyze the effect of preoperative Afib on clinical outcomes in patients undergoing cardiac surgery using a large surgical database. Methods: This retrospective cohort study was based on the national health claims database established by the National Health Insurance Service of the Republic of Korea from 2009 to 2015. Diagnosis and procedure codes were used to identify diseases according to the International Statistical Classification of Diseases, 10th revision. Results: We included 1,037 patients (0.1%) who had undergone cardiac surgery from a randomized 1,000,000-patient cohort, and 15 patients (1.5%) treated with isolated surgical Afib ablation were excluded. Of these 1,022 patients, 412 (39.7%), 303 (29.2%), and 92 (9.0%) underwent coronary artery bypass, heart valve surgery, and Cox-maze surgery, respectively. Preoperative Afib was associated with higher patient mortality (p=0.028), regardless of the surgical procedure. Patients with preoperative Afib (n=190, 18.6%) experienced a higher cumulative risk of overall mortality (hazard ratio [HR], 1.435; 95% confidence interval [CI], 1.263-2.107; p=0.034). Subgroup analysis revealed a reduced risk of overall mortality with Cox-maze surgery in Afib patients (HR, 0.500; 95% CI, 0.266-0.938; p=0.031). Postoperative cerebral ischemia or hemorrhage events were not related to Afib. Conclusion: Preoperative Afib was independently associated with worse long-term postoperative outcomes after cardiac surgery. Concomitant Cox-maze surgery may improve the survival rate.

A Redox-Mediator-Integrated Flexible Micro-Supercapacitor with Improved Energy Storage Capability and Suppressed Self-Discharge Rate.

To effectively improve the energy density and reduce the self-discharging rate of micro-supercapacitors, an advanced strategy is required. In this study, we developed a hydroquinone (HQ)-based polymer-gel electrolyte (HQ-gel) for micro-supercapacitors. The introduced HQ redox mediators (HQ-RMs) in the gel electrolyte composites underwent additional Faradaic redox reactions and synergistically increased the overall energy density of the micro-supercapacitors. Moreover, the HQ-RMs in the gel electrolyte weakened the self-discharging behavior by providing a strong binding attachment of charged ions on the porous graphitized carbon electrodes after the redox reactions. The micro-supercapacitors with HQ gel (HQ-MSCs) showed excellent energy storage performance, including a high energy volumetric capacitance of 255 mF cm-3 at a current of 1 µA, which is 2.7 times higher than the micro-supercapacitors based on bare-gel electrolyte composites without HQ-RMs (b-MSCs). The HQ-MSCs showed comparatively low self-discharging behavior with an open circuit potential drop of 37% compared to the b-MSCs with an open circuit potential drop of 60% after 2000 s. The assembled HQ-MSCs exhibited high mechanical flexibility over the applied external tensile and compressive strains. Additionally, the HQ-MSCs show the adequate circuit compatibility within series and parallel connections and the good cycling performance of capacitance retention of 95% after 3000 cycles.

Advanced Kidney Volume Measurement Method Using Ultrasonography with Artificial Intelligence-Based Hybrid Learning in Children.

In this study, we aimed to develop a new automated method for kidney volume measurement in children using ultrasonography (US) with image pre-processing and hybrid learning and to formulate an equation to calculate the expected kidney volume. The volumes of 282 kidneys (141 subjects, <19 years old) with normal function and structure were measured using US. The volumes of 58 kidneys in 29 subjects who underwent US and computed tomography (CT) were determined by image segmentation and compared to those calculated by the conventional ellipsoidal method and CT using intraclass correlation coefficients (ICCs). An expected kidney volume equation was developed using multivariate regression analysis. Manual image segmentation was automated using hybrid learning to calculate the kidney volume. The ICCs for volume determined by image segmentation and ellipsoidal method were significantly different, while that for volume calculated by hybrid learning was significantly higher than that for ellipsoidal method. Volume determined by image segmentation was significantly correlated with weight, body surface area, and height. Expected kidney volume was calculated as (2.22 × weight (kg) + 0.252 × height (cm) + 5.138). This method will be valuable in establishing an age-matched normal kidney growth chart through the accumulation and analysis of large-scale data.

Capacitive Humidity Sensor Based on Carbon Black/Polyimide Composites.

A novel capacitive humidity sensor based on carbon black/polyimide composites is presented in this paper. The details of the fabrication, sensor characteristics, and effect of the carbon black additive are described. It was confirmed that the polyimide composite filled with a tiny amount of carbon black was suitable for a humidity sensing dielectric. The humidity sensors with three different dielectrics, which were pure polyimide, 0.01 wt% carbon black/polyimide, and 0.05 wt% carbon black/polyimide, were fabricated by a micro-electro-mechanical-system (MEMS) process. As the amount of the carbon black additive increased, the sensitivity of the humidity sensor increased. The humidity sensor with 0.05 wt% of carbon black had a much higher sensitivity of 15.21% (20-80% RH, 0.2535%/% RH) than that of the sensor with pure polyimide, which was 9.73% (0.1622%/% RH). The addition of carbon black also led to an enhancement in the hysteresis and response speed. The hysteresis of the humidity sensor decreased from 2.17 to 1.80% when increasing the amount of the carbon black additive. The response speed of the humidity sensor with 0.05 wt% of carbon black was measured to be ~10% faster than that of the sensor with pure polyimide. The long-term stability of the humidity sensors was demonstrated as well.

Handheld Near-Infrared Fluorescence Imaging Device Using Modified Action Cameras for Peri-Operative Guidance of Microvascular Flap Surgery.

Indocyanine green near-infrared fluorescence (ICG-NIRF) imaging has recently come into use as a novel method in peri-operative microvascular flap assessment. However, a majority of the many commercial devices launched for clinical use lack mobility, portability, and cost-efficiency and are thus unsuitable for intra-oral applications. This study introduces a cost-effective, customized, handheld NIRF device following principles of ICG-NIRF imaging. Moreover, the novel characteristics of our prototype, considered in conjunction with a literature review highlighting the significance of fluorescence devices in microvascular surgery, point to a new generation of devices for use in microvascular flap surgery.

Non-inferiority study of the efficacy of two hyaluronic acid products in post-extraction sockets of impacted third molars.

BACKGROUND: Hyaluronic acid (HA) is well known to exert an anti-inflammatory effect during oral wound healing and is commonly applied after tooth extraction. However, no double-blind randomized controlled study comparing two hyaluronate mouthwash products has been conducted so far. The aim of this study was to comparatively analyze the efficacy of Mucobarrier® and Aloclair® in terms of clinical symptoms. RESULTS: A total of 112 patients were randomly assigned to assess the degree of discomfort, pain reduction, redness, burning sensation, and swelling between two groups on the day of surgery and 7 days later in a double blind test, with a total 56 Aloclair patients and 56 Mucobarrier patients. There was no statistically significant difference in the overall discomfort, degree of pain reduction, redness, burning sensation, and swelling between the Mucobarrier and Aloclair groups. CONCLUSION: The local application of hyaluronic acid mouth wash after wisdom tooth extraction is beneficial in reducing overall discomfort and pain reduction, and the clinical utility of Mucobarrier® is no different from Aloclair®. TRIAL REGISTRATION: Institutional Review Board of Yonsei University College of Dentistry, 2-2018-0036. Registered 10 September 2018-prospectively registered, https://eirb.yuhs.ac/.

Formation of Large Crystalline Domains in a Semiconducting Polymer with Semi-fluorinated Alkyl Side Chains and Application to High-Performance Thin-Film Transistors.

The semi-fluorinated alkyl (SFA) side chain introduced thienylenevinylene (TV)-based p-type polymer, PC12TVC5F7T, was synthesized for use in organic thin-film transistors (OTFTs). Herein, we investigated the influence of SFA side chains on the morphology, molecular orientation, and crystalline structure using a combination of atomic force microscopy (AFM), scanning electron microscopy (SEM), two-dimensional (2D) grazing-incidence wide-angle X-ray scattering (GIWAXS), and density functional theory (DFT) calculations. Interestingly, the incorporation of SFA side chains led to the evolution of plate-like large-sized domains and also strongly intermolecular stacked high crystalline structures. Furthermore, due to the strong interactions between SFA side chains, several (00h) peaks could be observed for PC12TVC5F7T, in spite of their fairly large dihedral angle. As a result, due to the well-developed microstructure of PC12TVC5F7T, the OTFT devices based on it exhibited a high hole mobility of 1.91 cm2 V-1 s-1, which is an outstanding value among the poly(thiophene) derivative polymers. These observations indicate that large-sized domains and strongly intermolecular stacked high crystalline structures, which are beneficial for charge carrier transport, could be attained by the introduction of SFA side chains, further enhancing the performance of the OTFTs.

NMR mapping of the highly flexible regions of 13C/15N-labeled antibody TTAC-0001-Fab.

Monoclonal antibody (mAb) drugs are clinically important for the treatment of various diseases. TTAC-0001 is under development as a new anti-cancer antibody drug targeting VEGFR-2. As the less severe toxicity of TTAC-0001 compared to Bevacizumab, likely due to the decreased in vivo half-life, seems to be related to its structural flexibility, it is important to map the exact flexible regions. Although the 13C/15N-labeled protein is required for NMR analyses, it is difficult to obtain antibody fragments (Fab and scFv) containing disulfide bonds through general cytosolic expression in Escherichia coli (E. coli). Here, we notably increased the periplasmic expression of the 13C/15N-labeled TTAC-0001-Fab (13C/15N-TTAC-Fab) through simple isopropyl ß-D-1-thiogalactopyranoside (IPTG)-induction at an increased optical density (1.5 OD600nm). Through NMR triple resonance experiments, two loop insertions (LI-1 between the VH and CH1; LI-2 between the VL and CL) were confirmed to be highly flexible. The additional LIs could be another way to engineer the antibody by changing the pharmacokinetic properties.

Unsymmetrical Small Molecules for Broad-Band Photoresponse and Efficient Charge Transport in Organic Phototransistors.

Organic photosensitizers have been investigated as effective light-sensing elements that can promote strong absorption with high field-effect mobility in organic phototransistors (OPTs). In this study, a novel organic photosensitizer is synthesized to demonstrate broad-band photoresponse with enhanced electrical performance. An unsymmetrical small molecule of a solubilizing donor (Dsol)-acceptor (A)-dye donor (Ddye) type connected with a twisted conjugation system is designed for broad-band detection (ranging from 250 to 700 nm). This molecule has high solubility, thereby facilitating the formation of uniformly dispersed nanoparticles in an insulating polymer matrix, which is deposited on top of OPT semiconductors by a simple solution process. The broad-band photodetection shown by the organic photosensitizer is realized with improved mobility close to an order of magnitude and high on/off current ratio (∼105) of the organic semiconductor. Furthermore, p-type charge transport behavior in the channel of the OPT is enhanced through the intrinsic electron-accepting ability of the organic photosensitizer caused by the unique molecular configuration. These structural properties of organic photosensitizers contribute to an improvement in broad-band photosensing systems with new optoelectronic properties and functionalities.

An Updated Nomogram for Predicting Invasiveness in Preoperative Ductal Carcinoma In Situ of the Breast.

PURPOSE: To validate and update a nomogram for predicting ductal carcinoma in situ (DCIS) upstaging in preoperative biopsy. MATERIALS AND METHODS: Medical records of 444 preoperative DCIS patients were evaluated and used to validate a previous version of the Severance nomogram for predicting DCIS upstaging in preoperative biopsy. Patients were divided into two groups according to the final postoperative pathology. Univariate and multivariate analyses with the chi-square test, Student's t-test, and binary logistic regression method identified new significant variables. The updated nomogram was evaluated with the C-index and Hosmer-Lemeshow goodness of fit test. RESULTS: The area under a receiver operating characteristic curve for comparison with the previous nomogram was 0.48. In postoperative pathology, the pure DCIS and invasive cancer groups comprised 345 and 99 cases, respectively. Approximately 22.3% of patients preoperatively diagnosed with DCIS were upstaged to invasive cancer. Significant variables in the univariate analysis were operation type, human epidermal growth factor receptor 2 overexpression, comedo necrosis, sonographic mass, mammographic mass, preoperative biopsy method, and suspicious microinvasion in preoperative biopsy. In multivariate analysis, operation type, sonographic mass, mammographic mass, and suspicious microinvasion were risk factors for upstaging. The updated model with these variables showed moderate discrimination and was appropriate in the calibration test. CONCLUSION: The previous nomogram did not effectively discriminate upstaging of preoperative DCIS in an independent cohort. An updated version of the nomogram appears to provide more accurate information for predicting preoperative DCIS upstaging.

Prognostic Role of TMED3 in Clear Cell Renal Cell Carcinoma: A Retrospective Multi-Cohort Analysis.

Transmembrane p24 trafficking protein 3 (TMED3) is a metastatic suppressor in colon cancer and hepatocellular carcinoma. However, its function in the progression of clear cell renal cell carcinoma (ccRCC) is unknown. Here, we report that TMED3 could be a new prognostic marker for ccRCC. Patient data were extracted from cohorts in the Cancer Genome Atlas (TCGA) and the International Cancer Genome Consortium (ICGC). Differential expression of TMED3 was observed between the low stage (Stage I and II) and high stage (Stage III and IV) patients in the TCGA and ICGC cohorts and between the low grade (Grade I and II) and high grade (Grade III and IV) patients in the TCGA cohort. Further, we evaluated TMED3 expression as a prognostic gene using Kaplan-Meier survival analysis, multivariate analysis, the time-dependent area under the curve (AUC) of Uno's C-index, and the AUC of the receiver operating characteristics at 5 years. The Kaplan-Meier analysis revealed that TMED3 overexpression was associated with poor prognosis for ccRCC patients. Analysis of the C-indices and area under the receiver operating characteristic curve further supported this. Multivariate analysis confirmed the prognostic significance of TMED3 expression levels (P = 0.005 and 0.006 for TCGA and ICGC, respectively). Taken together, these findings demonstrate that TMED3 is a potential prognostic factor for ccRCC.