Search

Background: Benign bladder tumors are rare disease entities, and insufficient studies have assessed their epidemiological characteristics. The authors investigated the prevalence of benign bladder tumors by retrospectively investigating pathology reports of transurethral resection of bladder tumor (TURBT) procedures over the past 20 years.Methods: We analyzed 1,674 pathology reports of TURBT conducted in 1,160 patients from January 1, 2000, to April 30, 2022. The prevalence of benign tumors and histological classification according to the presence of primary (group 1) and recurrent (group 2) bladder lesions were retrospectively investigated. Results: The mean age of patients was 65.2±11.5 years, and 1,284 cases (79.1%) were in men. Benign bladder tumors comprised 278 cases (248 patients) accounting for about 17.1% of the total TURBT cases (278/1,624). Furthermore, 184 patients (16.0%, 184/1,147) belonged to group 1 and 78 patients (27.4%, 78/285) belonged to group 2. Among all benign lesions that underwent TURBT, cystitis was the most common (41.0%, 114/278), and this rate was higher in group 2 (64/184 [34.8%] vs. 50/94 [53.2%], p

Distinctive surface functional groups on 3D MXenes as Pt-supports are correlated with optimized Pt–H affinity and HER activity in alkaline media.

Osteoporosis is characterized by low bone mass and elevated structural deterioration of the bone tissue, resulting in bone weakness with an increased risk of fracture. Considering biological activities of various phytochemicals extracted from apples, we herein demonstrated the potential antiosteoporotic effects of apple-derived nanovesicles (apple NVs) using osteoblastic MC3T3-E1 cells. Apple NVs significantly stimulated the growth of MC3T3-E1 cells. The cellular alkaline phosphatase (ALP) activity was significantly upregulated in the 5

The recent emerging significance of the Internet of Things (IoT) demands sensor devices to be integrated with many different functional structures and devices while conserving their original functionalities. To this end, optical transparency and mechanical flexibility of sensor devices are critical requirements for optimal integration as well as high sensitivity. In this work, a transparent, flexible, and sensitive gas sensor building platform is introduced by using multilevel self-assembly of block copolymers (BCPs) and polystyrene (PS) colloids. For the demonstration of an H

Metal-halide perovskite light-emitting diodes (PeLEDs) are considered as new-generation highly efficient luminescent materials for application in displays and solid-state lighting. Since the first successful demonstration of PeLEDs in 2014, the research on the development of efficient PeLEDs has progressed significantly. Although the device efficiency has significantly improved over a short period of time, their overall performance has not yet reached the levels of mature technologies for practical applications. Various degradation processes are the major impediment to improving the performance and stability of PeLED devices. In this review, we discuss various analysis techniques that are necessary to gain insights into the effects of various degradation mechanisms on the performance and stability of PeLEDs. Based on the causes and effects of external and internal factors, the degradation processes and associated mechanisms are examined in terms of critical physical and chemical parameters. Further, according to the progress of the current research, the challenges faced in studying degradation mechanisms are also elucidated. Given the universality of the degradation behavior, an in-depth understanding of the device degradation may promote the development of optimization strategies and further improve the performance and stability of PeLEDs.

This study demonstrates an approach to expand and improve the current prediction capability of the National Water Model (NWM). The primary objective is to examine the potential benefit of real-time local stage measurements in streamflow prediction, particularly for local communities that do not benefit from the improved streamflow forecasts due to the current data assimilation (DA) scheme. The proposed approach incorporates real-time local stage measurements into the NWM streamflow DA procedure by using synthetic rating curves (SRC) developed based on an established open-channel flow model. For streamflow DA and its evaluation, we used 6-yr (2016–21) data collected from 140 U.S. Geological Survey (USGS) stations, where quality-assured rating curves are consistently maintained (verification stations), and 310 stage-only stations operated by the Iowa Flood Center and the USGS in Iowa. The evaluation result from NWM’s current DA configuration based on the USGS verification stations indicated that DA improves streamflow prediction skills significantly downstream from the station locations. This improvement tends to increase as the drainage scale becomes larger. The result from the new DA configuration including all stage-only sensors showed an expanded domain of improved predictions, compared to those from the open-loop simulation. This reveals that the real-time low-cost stage sensors are beneficial for streamflow prediction, particularly at small basins, while their utility appears to be limited at large drainage areas because of the inherent limitations of lidar-based channel geometry used for the SRC development. The framework presented in this study can be readily applied to include numerous stage-only stream gauges nationwide in the NWM modeling and forecasting procedures.

Purpose The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized phase I/IIa clinical trial.Materials and Methods Overall, 18 patients with advanced non–small cell lung cancer (NSCLC) and a programmed death ligand 1 tumor proportion score of 1% or greater who had a history of failed frontline platinum-based therapy were randomized (2:1) to receive pembrolizumab every 3 weeks +/– 6 weekly infusions of SNK01 at either 2×109 or 4×109 cells per infusion (pembrolizumab monotherapy vs. SNK01 combination). The primary endpoint was safety, whereas the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), overall survival, and quality of life.Results Since no dose-limiting toxicity was observed, the maximum tolerated dose was determined as SNK01 4×109 cells/dose. The safety data did not show any new safety signals when SNK01 was combined with pembrolizumab. The ORR and the 1-year survival rate in the NK combination group were higher than those in patients who underwent pembrolizumab monotherapy (ORR, 41.7% vs. 0%; 1-year survival rate, 66.7% vs. 50.0%). Furthermore, the median PFS was higher in the SNK01 combination group (6.2 months vs. 1.6 months, p=0.001).Conclusion Based on the findings of this study, the NK cell combination therapy may consider as a safe treatment method for stage IV NSCLC patients who had a history of failed platinum-based therapy without an increase in adverse events.

The process of exsolution for the synthesis of strongly anchored metal nanoparticles (NPs) on host oxide lattices has been proposed as a promising strategy for designing robust catalyst-support composite systems. However, because conventional exsolution processes occur in harsh reducing environments at high temperatures for long periods of time, the choice of support materials and dopant metals are limited to those with inherently high thermal and chemical stability. Herein, we report the exsolution of a series of noble metal catalysts (Pt, Rh, and Ir) from metal oxide nanofibers (WO

With the development of deep learning technology and the abundance of sensors, machine vision applications that utilize vast amounts of image/video data are rapidly increasing in the autonomous vehicle, video surveillance and smart city fields. However, achieving a more compact image/video representation and lower latency solutions is challenging for such machine-based applications. Therefore, it is essential to develop a more efficient video coding standard for machine vision applications. Currently, the Moving Picture Experts Group (MPEG) is developing a new standard called video coding for machines (VCM) with two tracks, each mainly dealing with compression of the input image/video (Track 2) and compression of the features extracted from it (Track 1). In this paper, an enhanced multiscale feature compression (E-MSFC) method is proposed to efficiently compress multiscale features generated by a feature pyramid network (FPN), which is the backbone network of machine vision networks specified in the VCM evaluation framework. The proposed E-MSFC reduces the feature channels to be included in a single feature map and compresses the feature map using versatile video coding (VVC), the latest video standard, rather than the single stream feature compression (SSFC) module in the existing MSFC. In addition, the performance of the E-MSFC is further enhanced by adding a bottom-up structure to the multiscale feature fusion (MSFF) module, which performs the channel-wise reduction in the E-MSFC. Experimental results reveal that the proposed E-MSFC significantly outperforms the VCM image anchor with a BD-rate gain of up to 85.94%, which includes an additional gain of 0.96% achieved by the MSFF with the bottom-up structure.

The unique physicochemical and localized surface plasmon resonance assets of gold nanorods (GNRs) have offered combined cancer treatments with real-time diagnosis by integrating diverse theragnostic modalities into a single nanoplatform. In this work, a unique multifunctional nanohybrid material based on GNRs was designed for

Osteoblasts and osteoclasts play crucial roles in bone formation and bone resorption. We found that plum-derived exosome-like nanovesicles (PENVs) suppressed osteoclast activation and modulated osteoblast differentiation. PENVs increased the proliferation, differentiation, and mineralization of osteoblastic MC3T3-E1 cells and osteoblasts from mouse bone marrow cultures. Notably, PENVs elevated the expression of osteoblastic transcription factors and osteoblast differentiation marker proteins in MC3T3-E1 cells. Higher levels of phosphorylated BMP-2, p38, JNK, and smad1 proteins were detected in PENV-treated MC3T3-E1 cells. Additionally, the number of TRAP-positive cells was significantly decreased in PENV-treated osteoclasts isolated from osteoblasts from mouse bone marrow cultures. Importantly, osteoclastogenesis of marker proteins such as PPAR-gamma, NFATc1, and c-Fos were suppressed by treatment with PENVs (50 μg/mL). Taken together, these results demonstrate that PENVs can be used as therapeutic targets for treating bone-related diseases by improving osteoblast differentiation and inhibiting osteoclast activation for the first time.

Supplementary Data from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer

Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02–011, a reversible fourth-generation EGFR-TKI that overcomes the EGFR C797S mutation. Compared with approved EGFR-TKIs, OBX02–011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. In addition, in transgenic mouse models (EGFRL858R/T790M/C797S), OBX02–011 treatment effectively inhibited tumor growth and EGFR activity, leading to enhanced survival. Collectively, these results suggest that OBX02–011 may be a promising new EGFR-TKI to overcome C797S-mediated resistance in NSCLC.Significance:OBX02–011 is designed to target EGFR C797S and can overcome EGFR double and triple mutations to effectively treat lung cancer.

Supplementary Table from The Reversible Fourth-Generation EGFR Tyrosine Kinase Inhibitor OBX02–011 Overcomes C797S-Mediated Resistance in Lung Cancer

Small cell lung cancer (SCLC) has an exceptionally poor prognosis; as most of the cases are initially diagnosed as extensive disease with hematogenous metastasis. Therefore, the early diagnosis of SCLC is very important and may improve its prognosis. To investigate the feasibility of early diagnosis of SCLC, we examined exosomal microRNAs (miRNAs) present in serum obtained from patients with SCLC. First, exosomes were isolated in serum from patients with SCLC and healthy individuals and were characterized using particle size and protein markers. Additionally, miRNA array was performed to define SCLC-specific exosomal miRNAs. From the miRNA array results, we selected 51-miRNAs based on p-values and top 10 differentially expressed genes, and 25-miRNAs were validated using quantitative reverse transcription-polymerase chain reaction. Second, the 25-miRNAs were further validated employing a large cohort. Among them, 7-miRNAs showed significant differences. Furthermore, 6-miRNAs (miR-3565, miR-3124-5p, miR-200b-3p, miR-6515, miR-3126-3p and miR-9-5p) were up-regulated and 1-miRNA (miR-92b-5p) was down-regulated. Finally, the ability to diagnose SCLC of the 7-miRNAs was estimated by area under the curve (AUC). The AUC value of each miRNA sets between 0.64 and 0.76, however the combined application of 3-miRNAs (miR-200b-3p, miR-3124-5p and miR-92b-5p) remarkably improved the diagnostic value (AUC=0.93). Gene ontology analysis revealed that the 3-miRNA panel is linked to various oncogene pathways and nervous system development. When the 3-miRNAs were introduced to cells, the resulting changes in total mRNA expression strongly indicated the presence of lung diseases, including lung cancer. In addition, the 3-miRNA panel was significantly associated with a poorer prognosis, although individual miRNAs have not been validated as prognostic markers. In conclusion, our study identified SCLC-specific exosomal miRNAs, and the 3-miRNAs panel (miR-200b-3p, miR-3124-5p and miR-92b-5p) may serve as a diagnostic and prognostic marker for SCLC.

Walking promotes active aging; however, walking prevalence changes among older adults by age and environmental conditions remain unclear. Age-period-cohort (APC) differences in walking trends among Korean older adults were examined. Data included adults aged ≥ 65 years (n = 592,235) from the nationally representative Korean Community Health Survey. Regional units examined were metropolitan cities, small- and medium-sized cities, and rural areas. Environment-stratified APC modeling was applied for walking prevalence (walking days/time during the past week). From 2008 to 2017, the walking prevalence gap between regional units widened. Decreasing trends were most apparent in rural areas, including by birth year. In all areas, walking decreased with increased age. No distinct period effects were found. Each effect’s magnitude was larger in rural areas than cities. Differential APC effects by environmental conditions likely influence walking prevalence changes among older adults. Walking promotion for older adults should consider APC effects and environmental conditions.

Perovskite nanocrystals with high chirality and stability were synthesized via chirality transfer from a chiral supramolecular nanoreactor assembled from an achiral block copolymer complexed with racemic alanine.

Although epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have shown dramatic response and improvement in treating lung cancer with mutant EGFR, the emergence of drug resistance remains a major problem. In particular, some mutations including T790 M and C797S have been recognized as mechanisms of acquired resistance because they weaken binding affinity to drugs. To date, many attempts have been made to develop a new drug for overcoming acquired resistance to EGFR-TKIs, including secondary mutations. However, an appropriate animal model to evaluate in vivo efficacy during novel drug development remains lacking. In this study, we generated a novel transgenic mouse model that conditionally expresses human EGFR

Osimertinib is an irreversible third-generation EGFR tyrosine kinase inhibitor (TKI) that was initially developed to overcome the EGFR T790M mutation and is used as a standard therapy in patients with advanced non–small cell lung cancer (NSCLC) with EGFR-activating mutations. Despite the remarkable initial efficacy, osimertinib, like other EGFR-TKIs, is limited by the emergence of acquired resistance. As the EGFR mutation C797S has been identified as a key driver of acquired resistance to osimertinib, development of a drug that targets this clinically relevant mutation could help improve patient outcomes. Here, we report the discovery and preclinical efficacy of OBX02–011, a reversible fourth-generation EGFR-TKI that overcomes the EGFR C797S mutation. Compared with approved EGFR-TKIs, OBX02–011 showed potent anticancer effects and inhibited EGFR-related signaling in various models, including those harboring the EGFR C797S mutation. In addition, in transgenic mouse models (EGFRL858R/T790M/C797S), OBX02–011 treatment effectively inhibited tumor growth and EGFR activity, leading to enhanced survival. Collectively, these results suggest that OBX02–011 may be a promising new EGFR-TKI to overcome C797S-mediated resistance in NSCLC. Significance: OBX02–011 is designed to target EGFR C797S and can overcome EGFR double and triple mutations to effectively treat lung cancer.

Layered group-IV monochalcogenides, including GeS, GeSe, SnS, and SnSe, garner attention because of their anisotropic structures and properties. Here, we report on the growth of GeS microribbons via chemical vapor transport (CVT), which affords each of them with a low-symmetry orthorhombic structure and anisotropic optical and electronic properties. The single-crystalline nature of the GeS microribbon, which has a typical thickness of ~30 nm, is confirmed. Polarized Raman spectra reveal angle-dependent intensities that are attributed to the anisotropic layered structure of GeS microribbons. The photoluminescence (PL) spectra reveal a peak at ~1.66 eV. The angle-dependent PL and anisotropic absorption spectroscopy results provide evidence for a distinct anisotropic optical transition near the energy band edges; this phenomenon is also predicted by our density functional theory (DFT)-based calculations. Strong in-plane direct-current transport anisotropy is observed under dark and white illumination by using back-gate cross-shaped field effect transistors (CSFETs) fabricated with the GeS microribbon; significant gate-tunable conductivity is also confirmed. The strong anisotropy is further confirmed by the DFT-calculated effective mass ratio. Our findings not only support the application of GeS microribbons in anisotropic photoelectronic transistors but also provide more possibilities for other functional device applications.

AXL is a receptor tyrosine kinase (RTK) that has a various role in tumor progression such as proliferation, metastasis, angiogenesis, drug resistance and immune tolerance. Although targeting AXL exhibits an anti-cancer effects partially depending on the immune system, their molecular mechanisms have not been fully elucidated. To search the roles of AXL in immune tolerance of tumor, we generated AXL knockout (KO) mice. These AXL KO mice showed the reduced tumor growth in syngeneic LLC-1 model compared to wild type mice. To validate the mechanisms underlying the inhibition of AXL KO-derived tumor growth, we examined tumor-infiltrating lymphocytes (TIL). Compared with tumor-bearing wild type mouse, CD45-positive cells were significantly enhanced in tumor-bearing AXL KO mouse. Especially, these results were dominant in CD8-positive cells and dendritic cells (DCs). Tumor-infiltrating DCs showed the reduction of PD-L1 and Tim3 expression. In addition, the inhibition of AXL led to induce the DCs migration. In conclusion, our data demonstrated that targeting AXL may inhibit tumor growth through the activation of DCs including the enhancement of migration and reduced expression of immune check point proteins. Citation Format: Da-Som Kim, Cha Won Lee, Kyungtaek Im, Yun Jung Choi, Dong Ha Kim, Chang-Min Choi, Wonjun Ji, Jae Cheol Lee, Jin Kyung Rho. Suppression of AXL inhibits tumor growth through promotion of dendritic cell migration in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3416.