Search

Abstract Natural compounds are known as a resource of anti-cancer agents. Anti-cancer capacity toward human epithelial lung cancer cell lines (A549, H460) was examined with and without treatment of trypsin on the extract of Anoplophora glabripennis. IC50 values without trypsin treatment were about 21.3 and 25.0 μg/mL for H460 and A549, respectively. When the extract was treated with trypsin, the IC50 values were 16.0 and 15.6 μg/mL for H460 and A549, respectively, indicating that the trypsin treatment increased the anti-cancer capacity. Because trypsin treatment increased the capacity, the extract was treated with trypsin to isolate the peptide W-0803 which has lysin (K) in C-terminal and α-helix structures. With treatment of W-0803, the cell viability decreased dose-dependently for H460 and A549 cells. Apoptosis analysis showed that the cell death with the treatment of peptide W-0803 was mainly by apoptosis. The wound-healing assay also showed that the peptide W-0803 has an inhibitory capability on cell migration of H460 and A549 cells. All these results suggest that the peptide W-0803 is an anti-cancer agent for lung cancer cell treatment.

Abstract Background G protein-coupled receptor heteromerization is believed to exert dynamic regulatory impact on signal transduction. CXC chemokine receptor 4 (CXCR4) and its ligand CXCL12, both of which are overexpressed in many cancers, play a pivotal role in metastasis. Likewise, lysophosphatidic acid receptor 1 (LPA1) is implicated in cancer cell proliferation and migration. In our preliminary study, we identified LPA1 as a prospective CXCR4 interactor. In the present study, we investigated in detail the formation of the CXCR4-LPA1 heteromer and characterized the unique molecular features and function of this heteromer. Methods We employed bimolecular fluorescence complementation, bioluminescence resonance energy transfer, and proximity ligation assays to demonstrate heteromerization between CXCR4 and LPA1. To elucidate the distinctive molecular characteristics and functional implications of the CXCR4-LPA1 heteromer, we performed various assays, including cAMP, BRET for G protein activation, β-arrestin recruitment, ligand binding, and transwell migration assays. Results We observed that CXCR4 forms heteromers with LPA1 in recombinant HEK293A cells and the human breast cancer cell line MDA-MB-231. Coexpression of LPA1 with CXCR4 reduced CXCL12-mediated cAMP inhibition, ERK activation, Gαi/o activation, and β-arrestin recruitment, while CXCL12 binding to CXCR4 remained unaffected. In contrast, CXCR4 had no impact on LPA1-mediated signaling. The addition of lysophosphatidic acid (LPA) further hindered CXCL12-induced Gαi/o recruitment to CXCR4. LPA or alkyl-OMPT inhibited CXCL12-induced migration in various cancer cells that endogenously express both CXCR4 and LPA1. Conversely, CXCL12-induced calcium signaling and migration were increased in LPAR1 knockout cells, and LPA1-selective antagonists enhanced CXCL12-induced Gαi/o signaling and cell migration in the parental MDA-MB-231 cells but not in LPA1-deficient cells. Ultimately, complete inhibition of cell migration toward CXCL12 and alkyl-OMPT was only achieved in the presence of both CXCR4 and LPA1 antagonists. Conclusions The presence and impact of CXCR4-LPA1 heteromers on CXCL12-induced signaling and cell migration have been evidenced across various cell lines. This discovery provides crucial insights into a valuable regulatory mechanism of CXCR4 through heteromerization. Moreover, our findings propose a therapeutic potential in combined CXCR4 and LPA1 inhibitors for cancer and inflammatory diseases associated with these receptors, simultaneously raising concerns about the use of LPA1 antagonists alone for such conditions. Video Abstract

Abstract Lysophosphatidic acid receptor 4 (LPAR4) exhibits transient expression at the cardiac progenitor stage during pluripotent stem cell (PSC)-derived cardiac differentiation. Using RNA sequencing, promoter analyses, and a loss-of-function study in human PSCs, we discovered that SRY-box transcription factor 17 (SOX17) is an essential upstream factor of LPAR4 during cardiac differentiation. We conducted mouse embryo analyses to further verify our human PSC in vitro findings and confirmed the transient and sequential expression of SOX17 and LPAR4 during in vivo cardiac development. In an adult bone marrow transplantation model using LPAR4 promoter-driven GFP cells, we observed two LPAR4+ cell types in the heart following myocardial infarction (MI). Cardiac differentiation potential was shown in heart-resident LPAR4+ cells, which are SOX17+, but not bone marrow-derived infiltrated LPAR4+ cells. Furthermore, we tested various strategies to enhance cardiac repair through the regulation of downstream signals of LPAR4. During the early stages following MI, the downstream inhibition of LPAR4 by a p38 mitogen-activated protein kinase (p38 MAPK) blocker improved cardiac function and reduced fibrotic scarring compared to that observed following LPAR4 stimulation. These findings improve our understanding of heart development and suggest novel therapeutic strategies that enhance repair and regeneration after injury by modulating LPAR4 signaling.

Degradation of kinetically bulk heterojunction film morphology in organic solar cells is a grand challenge for their practical application. Here, the authors design and synthesise multicomponent photoactive material by facile one-pot polymerization and achieve efficiency of 11.8% and T80 of 1000 h.

Abstract C-X-C chemokine receptor 4 (CXCR4) is widely overexpressed in various types of cancer and is involved in several cancer phenotypes including tumor growth, survival, and metastasis. The roles of histamine and histamine receptor H1 (HRH1) in cancer pathogenesis remain controversial. Here, we show that HRH1 is widely expressed in various cancer cell lines and cancer tissues and that coexpression of CXCR4 and HRH1 is associated with poor prognosis in breast cancer. Using bimolecular fluorescence complementation and bioluminescence resonance energy transfer donor saturation assays, we demonstrate that CXCR4 and HRH1 can assemble into a heteromeric complex. Simultaneous activation of CXCR4 and HRH1 synergistically increases calcium flux in MDA-MB-231 cells that endogenously express CXCR4 and HRH1 but not in cells deficient in CXCR4 or HRH1. Costimulation of CXCR4 and HRH1 also significantly enhances CXCL12-induced MDA-MB-231 cell migration, while histamine alone does not induce cell migration. Synergistic effects on calcium flux and cell migration are inhibited by the Gαi inhibitor pertussis toxin and the Gαq inhibitor YM254890, suggesting that the Gαi and Gαq pathways are involved in the synergy. Enhanced calcium signaling and cell migration are also observed in NCI-H23 and HeLa cells, which coexpress CXCR4 and HRH1. Taken together, our findings demonstrate an interplay between CXCR4 and HRH1, and suggest the possibility of the CXCR4-HRH1 heteromer as a potential therapeutic target for anticancer therapy.

Hydrogen refueling stations are pivotal for renewable energy and carbon neutrality; however, they encounter challenges owing to equipment malfunctions. This study addresses the use of time-series forecasting techniques to predict and diagnose critical equipment failure at these stations. An analysis of the station equipment was conducted to create scenarios for potential malfunctions in compression equipment. Techniques such as the Recurrent Neural Network (RNN), Long Short-Term Memory network (LSTM), and Gated Recurrent Unit (GRU) have been employed to forecast the conditions of high-pressure compression equipment. Deep neural networks were constructed to enhance prediction accuracy, typically achieving an error margin of 0.01. Multi-step predictions using autoregression were utilized to bolster equipment resilience against aging and progressive failures. Autoregressive prediction models, particularly those using LSTMs and GRUs, outperform RNNs. However, predictions may be subject to errors due to algorithmic limitations and environmental factors. This study introduces a stochastic forecasting approach that, utilizes Gaussian distributions to predict probability distributions, not single-point estimates. This method yielded a 95% prediction interval with a standard deviation of 1.96. The reliability of multi-time step forecasts is significantly improved by adopting stochastic autoregressive forecasting and establishing prediction intervals. The proposed model enhances not only the accuracy of equipment failure predictions but also proactive maintenance, thus reducing downtime and boosting the efficiency of the hydrogen fuel infrastructure, which contributes to the wider utilization of hydrogen as a clean energy source.

Abstract In addition to catalyzing coupled transport and phosphorylation of carbohydrates, the phosphoenolpyruvate:carbohydrate phosphotransferase system (PTS) regulates various physiological processes in most bacteria. Therefore, the transcription of genes encoding the PTS is precisely regulated by transcriptional regulators depending on substrate availability. As the distribution of the mannose-specific PTS (PTSMan) is limited to animal-associated bacteria, it has been suggested to play an important role in host-bacteria interactions. In Vibrio cholerae, mannose is known to inhibit biofilm formation. During host infection, the transcription level of the V. cholerae gene encoding the putative PTSMan (hereafter referred to as manP) significantly increases, and mutations in this gene increase host survival rate. Herein, we show that an AraC-type transcriptional regulator (hereafter referred to as ManR) acts as a transcriptional activator of the mannose operon and is responsible for V. cholerae growth and biofilm inhibition on a mannose or fructose-supplemented medium. ManR activates mannose operon transcription by facilitating RNA polymerase binding to the promoter in response to mannose 6-phosphate and, to a lesser extent, to fructose 1-phosphate. When manP or manR is impaired, the mannose-induced inhibition of biofilm formation was reversed and intestinal colonization was significantly reduced in a Drosophila melanogaster infection model. Our results show that ManR recognizes mannose and fructose in the environment and facilitates V. cholerae survival in the host.

Highlights A series of non-conjugated acceptor polymers with flexible conjugation-break spacers (FCBSs) of different lengths were synthesized. The effect of FCBSs length on solubility of the acceptor polymers, and their photovoltaic and mechanical properties in all-polymer solar cells were explored. This work provides useful guidelines for the design of semiconducting polymers by introducing FCBS with proper length, which can giantly improved properties that are not possible to be achieved by the state-of-the-art fully conjugated polymers. Abstract All-polymer solar cells (all-PSCs) possess attractive merits including superior thermal stability and mechanical flexibility for large-area roll-to-roll processing. Introducing flexible conjugation-break spacers (FCBSs) into backbones of polymer donor (P D) or polymer acceptor (P A) has been demonstrated as an efficient approach to enhance both the photovoltaic (PV) and mechanical properties of the all-PSCs. However, length dependency of FCBS on certain all-PSC related properties has not been systematically explored. In this regard, we report a series of new non-conjugated P As by incorporating FCBS with various lengths (2, 4, and 8 carbon atoms in thioalkyl segments). Unlike common studies on so-called side-chain engineering, where longer side chains would lead to better solubility of those resulting polymers, in this work, we observe that the solubilities and the resulting photovoltaic/mechanical properties are optimized by a proper FCBS length (i.e., C2) in P A named PYTS-C2. Its all-PSC achieves a high efficiency of 11.37%, and excellent mechanical robustness with a crack onset strain of 12.39%, significantly superior to those of the other P As. These results firstly demonstrate the effects of FCBS lengths on the PV performance and mechanical properties of the all-PSCs, providing an effective strategy to fine-tune the structures of P As for highly efficient and mechanically robust PSCs.

Chronic hepatitis B (CHB) seriously threatens human health. About 820,000 deaths annually are due to related complications such as hepatitis B and hepatocellular carcinoma (HCC). Recently, the use of oral antiviral agents has significantly improved the prognosis of patients with CHB infection and reduced the risk of HCC. However, hepatitis B virus still remains a major factor in the development of HCC, raising many concerns. Therefore, numerous studies have been conducted to assess the risk of HCC in patients with CHB infection and many models have been proposed to predict the risk of developing HCC. However, as each study has different models for predicting HCC development that can be applied depending on the use of antiviral agents or the type of antiviral agents, it is necessary to properly understand characteristics of each model when using it for the evaluation of HCC in patients with CHB infection. In addition, because different variables such as host factor, viral activity, and cirrhosis are used to evaluate the risk of HCC development, it is necessary to assess the risk by carefully verifying which variables are used. Recently, studies have also evaluated the risk of HCC using risk prediction models through transient elastography and artificial intelligence (AI) system. These HCC risk predication models are also noteworthy. In this review, we aimed to compare HCC risk prediction models in patients with CHB infection reported to date to confirm variables used and specificity between each model to determine an appropriate HCC risk prediction method.

Background/Aims We compared the post-treatment overall survival (OS) and recurrence-free survival (RFS) between patients with Child-Turcotte-Pugh (CTP) class-A and single small (≤3 cm) hepatocellular carcinoma (HCC) treated by surgical resection (SR) and radiofrequency ablation (RFA). Methods We retrospectively analyzed 391 HCC patients with CTP class-A who underwent SR (n=232) or RFA (n=159) as first-line therapy for single small (≤3 cm) HCC. Survival was compared according to the tumor size (≤2 cm/2–3 cm) and the presence of cirrhosis. Inverse probability of treatment weighting (IPW) method was used to estimate the average causal effect of treatment. Results The median follow-up period was 64.8 months (interquartile range, 0.1–162.6). After IPW, the estimated OS was similar in the SR and RFA groups (P=0.215), and even in patients with HCC of ≤2 cm (P=0.816) and without cirrhosis (P=0.195). The estimated RFS was better in the SR group than in the RFA groups (P=0.005), also in patients without cirrhosis (P

Background/Aims: Glecaprevir/pibrentasvir (G/P) is the first pan-genotypic direct-acting antiviral combination therapy approved in Korea. An integrated analysis of five phase II and III trials was conducted to evaluate the efficacy and safety of G/P in Korean patients with chronic hepatitis C virus (HCV) infection. Methods: The study analyzed pooled data on Korean patients with HCV infection enrolled in the ENDURANCE 1 and 2, SURVEYOR II part 4 and VOYAGE I and II trials, which evaluated the efficacy and safety of 8 or 12 weeks of G/P treatment. The patients were either treatment-naïve or had received sofosbuvir or interferon-based treatment. Efficacy was evaluated by assessing the rate of sustained virologic response at 12 weeks posttreatment (SVR12). Safety was evaluated by monitoring adverse events (AEs) and laboratory assessments. Results: The analysis included 265 patients; 179 (67.5%) were HCV treatment-naïve, and most patients were either subgenotype 1B (48.7%) or 2A (44.5%). In the intention-to-treat population, 262 patients (98.9%) achieved SVR12. Three patients did not achieve SVR12: one had virologic failure and two had non-virologic failures. Most AEs were grade 1/2; eight patients (3.0%) experienced at least one grade ≥3 AE. No serious AEs related to G/P treatment were reported, and grade ≥3 hepatic laboratory abnormalities were rare (0.8%). Conclusions: G/P therapy was highly efficacious and well tolerated in Korean patients with HCV infection, with most patients achieving SVR12. The safety profile was comparable to that observed in a pooled analysis of a global pan-genotypic population of patients with HCV infection who received G/P.

Abstract Background Little is known about endogenous inhibitors of angiogenic growth factors. In this study, we identified a novel endogenous anti-angiogenic factor expressed in pericytes and clarified its underlying mechanism and clinical significance. Methods Herein, we found Kai1 knockout mice showed significantly enhanced angiogenesis. Then, we investigated the anti-angiogenic roll of Kai1 in vitro and in vivo. Results KAI1 was mainly expressed in pericytes rather than in endothelial cells. It localized at the membrane surface after palmitoylation by zDHHC4 enzyme and induced LIF through the Src/p53 pathway. LIF released from pericytes in turn suppressed angiogenic factors in endothelial cells as well as in pericytes themselves, leading to inhibition of angiogenesis. Interestingly, KAI1 had another mechanism to inhibit angiogenesis: It directly bound to VEGF and PDGF and inhibited activation of their receptors. In the two different in vivo cancer models, KAI1 supplementation significantly inhibited tumor angiogenesis and growth. A peptide derived from the large extracellular loop of KAI1 has been shown to have anti-angiogenic effects to block the progression of breast cancer and retinal neovascularization in vivo. Conclusions KAI1 from PC is a novel molecular regulator that counterbalances the effect of angiogenic factors.

Abstract Telomere length has been linked to the prevalence and progression of metabolic disease. However, clinical implications of telomere length in biopsy-proven non-alcoholic fatty liver disease (NAFLD) patients remain unclear. Therefore, this study aimed to investigate the association of telomere length with the histological severity of NAFLD. The cross-sectional data derived from the prospectively enrolled Boramae NAFLD registry (n = 91) were analyzed. The liver tissues and clinical information were obtained from both NAFLD patients and non-NAFLD subjects. Binary logistic regression was performed to identify the independent association between telomere length and the histological severity of NAFLD. A total of 83 subjects with or without biopsy-proven NAFLD were included for analysis: non-NAFLD in 23 (27.7%), non-alcoholic fatty liver in 15 (18.1%), and non-alcoholic steatohepatitis (NASH) in 45 (54.2%). Telomere length measured from liver tissues showed a strong negative correlation (p

Background/Aims Besifovir dipivoxil maleate (BSV), an acyclic nucleotide phosphonate, shows potent antiviral activity against hepatitis B virus. Our previous 48-week trial revealed that BSV has comparable antiviral efficacy to tenofovir disoproxil fumarate (TDF) and better safety profiles in terms of improved renal and bone safety. This extension study evaluated the prolonged efficacy and safety of BSV in treatment-naive chronic hepatitis B patients. Methods Patients continued to participate in an open-label BSV study after an initial 48-week double-blind comparison of BSV and TDF treatment. The antiviral efficacy and drug safety was evaluated up to 192 weeks in two groups: patients continuing BSV treatment (BSV-BSV) and patients switching from TDF to BSV after 48 weeks (TDF-BSV). Results Among 197 patients receiving randomized treatments, 170 (86%) entered the open-label phase and 152 (77%) entered the 192-week extension study. Virological response rates over 192 weeks were 92.50% and 93.06% in the BSV-BSV and TDF-BSV groups, respectively (P=0.90). Hepatitis B envelop antigen seroconversion and alanine aminotransferase normalization rates were similar between the groups (P=0.75 and P=0.36, respectively). There were no drug-resistant mutations to BSV. Bone mineral density and renal function were well preserved in the BSV-BSV group, whereas these initially worsened then recovered after switching therapy in the TDF-BSV group. Conclusions BSV maintained potent antiviral efficacy after 192 weeks and showed no evidence of drug resistance. BSV was safe, well tolerated, and effective in patients who switched from TDF to BSV. Trial Registration Number: NCT01937806 (date: 10 Sep 2013).

There is some dissatisfaction with the term “nonalcoholic fatty liver disease (NAFLD),” which overemphasizes alcohol and underemphasizes the importance of metabolic risk factors in this disease. Recently, a consensus recommended “metabolic (dysfunction)-associated fatty liver disease (MAFLD)” as a more appropriate term to describe fatty liver diseases (FLD) associated with metabolic dysfunction. During the definition change from NAFLD to MAFLD, subjects with FLD and metabolic abnormalities, together with other etiologies of liver diseases such as alcohol, virus, or medication who have been excluded from the NAFLD criteria, were added to the MAFLD criteria, while subjects with FLD but without metabolic abnormality, who have been included in the NAFLD criteria, were excluded from the MAFLD criteria. This means that there is an emphasis on the metabolic dysfunction in MAFLD which may underestimate the prognostic value of hepatic steatosis itself, whereas the MAFLD criteria might better identify subjects who are at a higher risk of hepatic or cardiovascular outcomes. However, non-metabolic risk NAFLD subjects who are excluded from the MAFLD criteria are missed from the diagnosis, and their potential risk can be the cause of future diseases. Although huge controversies remain, this review focused on summarizing recent studies that compared the clinical and prognostic characteristics between subjects with NAFLD and MAFLD.

Abstract Background Gastrointestinal tumor bleeding remains a clinical challenge because it is difficult to treat with conventional endoscopic hemostatic options. Recently, an endoscopic hemostatic powder (UI-EWD) was developed and reported to provide effective control of upper gastrointestinal bleeding. The aim of current study was to evaluate the feasibility and efficacy of this novel hemostatic powder in tumor bleeding. Methods A total of 41 consecutive patients with upper gastrointestinal tumor bleeding were included. UI-EWD was applied in all patients as an auxiliary hemostatic method as a salvage therapy or monotherapy during endoscopic treatment. Hemostasis success rates, adverse event related to UI-EWD, and rates of re-bleeding were evaluated. Results In all cases, UI-EWD application was successful at tumor bleeding sites. Immediate hemostasis occurred in 40/41 (97.5%) patients, and re-bleeding within 28 days occurred in 10 of 40 (22.5%) patients that achieved initial hemostasis. The success rate of immediate hemostasis for UI-EWD monotherapy was 100% (23/23). The re-bleeding rate at 28 days after UI-EWD monotherapy was 26.1% (6/23). No adverse events associated with UI-EWD application were encountered. Conclusions The success rate of UI-EWD for immediate hemostasis in cases of GI tumor bleeding was excellent and UI-EWD produced promising results with respect to the prevention of re-bleeding. Based on these results, we suggest that UI-EWD be considered an effective salvage therapy or even monotherapy for GI tumor bleeding.

Background: Red ginseng contains components, including microelements, vitamins, essential oils, and fatty acids, that can be used in skincare to delay the aging process. We investigated the effects of red ginseng treatment on skin elasticity by assessing cellular stiffness and measuring collagen protein synthesis. Methods: Human dermal fibroblasts were treated with red ginseng, and the resulting changes in stiffness were investigated using atomic force microscopy. Cytoskeletal changes and mRNA expression of biomarkers of aging, including that of procollagens I and VII, elastin, and fibrillin-1, were investigated. Collagen in a human skin equivalent treated with red ginseng was visualized via hematoxylin and eosin staining, scanning electron microscopy, and atomic force microscopy. Results and conclusion: The stiffness of fibroblasts was significantly reduced by treatment with red ginseng concentrations of ≥ 0.8 mg/mL. The ratio of F-actin to G-actin decreased after treatment, which corresponded to a change in fibroblast stiffness. The storage modulus (G′) and loss modulus (G″) of the skin equivalent were both lowered by red ginseng treatment. This result indicates that the viscoelasticity of the skin equivalent can be restored by red ginseng treatment.

An induced gas flotation (IGF) machine is a type of water treatment equipment that separates oil droplets or particles from waste-water using the characteristics of floating air bubbles. In general, bubble movement inside an IGF is difficult to predict since the internal flow in an IGF is not linear due to vortex formation and recirculating flow. Furthermore, the actual bubbles are distributed in various sizes and it is very difficult to accurately simulate them. Therefore, the MUltiple-SIze-Group (MUSIG) method is used to correct this in the numerical analysis. The MUSIG method is to divide the bubbles into groups by size. It can predict relatively accurate bubble movements, coalescence and break-up. In this study, numerical analysis with the MUSIG model was conducted on various types of rotor blade configurations to determine water treatment. The results of void fraction, power consumption, air residence time, air mean bubble diameter, and drag coefficient were predicted and compared between the various configuration of rotor blade. Comparison of the results showed that the backward IGF rotor exhibited an increased void fraction by about 2.6 % and a decreased power number by about 37.6 % compared to the values seen using the reference model.

Embryos produced with serum show the alterations in their ultrastructure, impaired compaction, abnormal blastulation, aberrant mRNA expression profiles and large calf syndrome with greater incidences of stillbirths and deaths after birth. The aim of the present study was to describe in vitro embryo production by analyzing embryo production, fetal production and pregnancy rate in free-serum medium. The OPU-IVP data used in this study from 2016. Approximately, sixteen cows (Hanwoo), which belonged to the Institute of Gyeongsang National University, were used. Two experimental group is used in this study. Serum groups were conducted in March to July and free-serum group was conducted in September to December. The recovered cumulus-oocyte complexes were morphologically classified to four grades based on the compaction of cumulus cells layers and homogeneity of the cytoplasm. The number of oocyte was significantly greater in serum groups than that in free-serum groups (29.61 ± 0.63 vs. 15.6 ± 0.62; p < 0.05). Between serum and free-serum groups indicate that average of 1st and 2nd grade oocytes were no difference (2.38 ± 1.67 vs. 2.38 ± 1.48; p > 0.05), but number of 3rd and 4th grade oocytes were greater in serum groups than that in free-serum groups (7.31 ± 7.64 vs. 5.60 ± 6.29; p < 0.05). Embryo cleaved competence was higher in rate in free-serum groups than that in serum groups (62.1% vs. 58.3; p < 0.05). However, blastocyst developmental rate was no difference between serum and free-serum groups (33.1% vs. 43.5%; p < 0.05). 986 recipients were used for embryo transfer. Pregnancy rate was indicated that between serum and free-serum group was no difference (54.6% vs. 56.3%; p < 0.05). In conclusion, we developed the free-serum system for production of in vitro bovine embryos in order to meet the developmental and qualitative requirements for large scale commercial use.

Introduction: Adequate bone quality is essential for long term biologic fixation of cementless total knee arthroplasty (TKA). Recently, vertebral bone quality evaluation using dual-energy computed tomography (DECT) has been introduced. However, the DECT bone mineral density (BMD) in peripheral skeleton has not been correlated with Hounsfield units (HU) or central dual-energy X-ray absorptiometry (DXA), and the accuracy remains unclear. Materials and methods: Medical records of 117 patients who underwent TKA were reviewed. DXA was completed within three months before surgery. DECT was performed with third-generation dual source CT in dual-energy mode. Correlations between DXA, DECT BMD and HU for central and periarticular regions were analyzed. Receiver operating characteristic (ROC) curves were plotted and area under the curve (AUC), optimal threshold, and sensitivity and specificity of each region of interest (ROI) were calculated. Results: Central DXA BMD was correlated with DECT BMD and HU in ROIs both centrally and around the knee (all p < 0.01). The diagnostic accuracy of DECT BMD was higher than that of DECT HU and was also higher when the T-score for second lumbar vertebra (L2), rather than for the femur neck, was used as the reference standard (all AUC values: L2 > femur neck; DECT BMD > DECT HU, respectively). Using the DXA T-score at L2 as the reference standard, the optimal DECT BMD cut-off values for osteoporosis were 89.2 mg/cm3 in the distal femur and 78.3 mg/cm3 in the proximal tibia. Conclusion: Opportunistic volumetric BMD assessment using DECT is accurate and relatively simple, and does not require extra equipment. DECT BMD and HU are useful for osteoporosis screening before cementless TKA.

Although human induced pluripotent stem cells (iPSCs) can serve as a universal cell source for regenerative medicine, the use of iPSCs in clinical applications is limited by prohibitive costs and prolonged generation time. Moreover, allogeneic iPSC transplantation requires preclusion of mismatches between the donor and recipient human leukocyte antigen (HLA). We, therefore, generated universally compatible immune nonresponsive human iPSCs by gene editing. Transcription activator-like effector nucleases (TALENs) were designed for selective elimination of HLA DR expression. The engineered nucleases completely disrupted the expression of HLA DR on human dermal fibroblast cells (HDF) that did not express HLA DR even after stimulation with IFN-γ. Teratomas formed by HLA DR knockout iPSCs did not express HLA DR, and dendritic cells differentiated from HLA DR knockout iPSCs reduced CD4+ T cell activation. These engineered iPSCs might provide a novel translational approach to treat multiple recipients from a limited number of cell donors.

Chronic osteomyelitis is mostly caused by bacteria such as S. aureus, and is often treated with oral antibiotics or injections to suppress the bacteria. In severe cases, however, surgical treatment using antibiotic beads and metal supports may be required. In these surgeries, bacterial attachment to the metal may lead to biofilm formation and reduce antibiotics’ penetration to the bacteria. Reoperation must be performed to prevent bacterial inflammatory reactions and antibiotic resistance. Thus, in this study, we developed a dual-drug-releasing PCL/sodium-alginate-based 3D-printed scaffold to effectively treat osteomyelitis by removing the biofilm. We proposed an antibiotic-loaded biodegradable polymer scaffold using 3D printing, which was encapsulated by a second antibiotic-containing hydrogel. Then, we successfully established a dual-drug-based scaffold that consisted of a cefazolin (CFZ)-containing polycaprolactone 3D scaffold and a rifampicin (RFP)-loaded alginate hydrogel encapsulating the 3D scaffold. Our scaffold showed a synergistic effect, whereby biofilm formation was inhibited by RFP, which is an external drug, and bacterial activity was inhibited by CFZ, which is an internal drug that increases antibacterial activity. We also confirmed that the dual-drug-based scaffold did not affect the proliferation of human osteoblasts. Our findings suggest that this dual drug delivery system may serve as a new therapeutic treatment for osteomyelitis that overcomes the limitations of individual drugs.

The material with irregular atomic structures such as polymer material exhibits low thermal conductivity because of the complex structural properties. Even materials with same atomic configurations, thermal conductivity may be different based on their structural properties. It is expected that nanoparticles with conductivity will change non-conductive polymer base materials to electrical conductors, and improve the thermal conductivity even with extremely small filling amount. Nano-composite materials contain nanoparticles with a higher surface ratio which makes the higher interface percentage to the total surface of nanoparticles. Therefore, thermal resistance of the interface becomes a dominating factor determines the effective thermal conductivity in nano-composite materials. Carbon fiber has characteristic of resistance or magnetic induction and Also, Carbon nanotube (CNT) has electronic and thermal property. It can be applied for heating system. These characteristic are used as heating composite. In this research, the exothermic characteristics of Carbon fiber reinforced composite added CNT were evaluated depend on CNT length and particle size. It was found that the CNT dispersed in the resin reduces the resistance between the interfaces due to the decrease in the total resistance of the heating element due to the addition of CNTs. It is expected to improve the life and performance of the carbon fiber composite material as a result of the heating element resulting from this paper. Keywords: Carbon Nanotube (CNT), Carbon Fiber Reinforcement Plastic (CFRP), Heater, Exothermic characteristics

For safe UAV navigation and to avoid collision, it is essential to have accurate and real-time perception of the environment surrounding the UAV, such as free area detection and recognition of dynamic and static obstacles. The perception system of the UAV needs to recognize information such as the position and velocity of all objects in the surrounding local area regardless of the type of object. At the same time, a probability based representation taking into account the noise of the sensor is also essential. In addition, a software design with efficient memory usage and operation time is required in consideration of the hardware limitations of the UAVs. In this paper, we propose a 3D Local Dynamic Map (LDM) generation algorithm for a perception system for UAVs. The proposed LDM uses a circular buffer as a data structure to ensure low memory usage and fast operation speed. A probability based occupancy map is created using sensor data and the position and velocity of each object are calculated through clustering between grid voxels using the occupancy map and velocity estimation based on a particle filter. The objects are predicted using the position and velocity of each object and this is reflected in the occupancy map. This process is continuously repeated and the flying environment of the UAV can be expressed in a three-dimensional grid map and the state of each object. For the evaluation of the proposed LDM, we constructed simulation environments and the UAV for outdoor flying. As an evaluation factor, the occupancy grid is accuracy evaluated and the ground truth velocity and the estimated velocity are compared.

Abstract Background The optimal surgical option for patients requiring bilateral hip replacement remains controversial. The purpose of this study was to compare surgical accuracy; functional outcome and health-related quality of life; and prosthetic-related complications and revision surgery of a simultaneous bilateral total hip arthroplasty (THA) with those of a staged bilateral THA with an interval between procedures 3 mm were significantly lower in the simultaneous group (P

Background/AimsData are lacking regarding the management of chronic hepatitis B (CHB) with resistance to clevudine (CLV). This study evaluated the efficacy of different rescue therapies for CLV-resistant CHB.Methods : Patients with CLV-resistant CHB were enrolled in the cohort, and all patients developed virologic breakthrough during CLV therapy and had confirmed-genotypic resistance to CLV (rtM204I mutation) before enrollment.Results : Of the 107 patients, 12 received adefovir (ADV), 21 received a CLV plus ADV combination (CLV+ADV), 34 received a lamivudine plus ADV combination (LAM+ADV), and 40 received entecavir (ETV) therapy for 48 weeks. The CLV+ADV group had the lowest hepatitis B virus (HBV) DNA level (p

The optimal vessel pressure of the bioreactor for cell growth and the production of cellulase, as well as the effect of a shift in pressure within the reactor on cellulase production were investigated. The optimal vessel pressure for the cell growth of E. coli JM109/LBH-10 was 0.08 MPa, whereas that for the production of cellulase was 0.04 MPa. The maximal production of cellulase by E. coli JM109/LBH-10 with a shift in the vessel pressure from 0.08 to 0.04 MPa after 24 h was 636.8 U/mL, which was 1.2 times higher than that without a shift. The shift in vessel pressure optimized for cell growth to that for the production of cellulase after the mid-term log-phase resulted in higher cell growth and cellulase production. A simple process with a shift in the vessel pressure of bioreactors to enhance the production of cellulase from agricultural by-products has been developed and can be directly applied to the industrial-scale production of cellulases.

The commercial method for isolation of ampelopsin, one of the most common flavonoids isolated from the plant species Ampelopsis grossedentata, is a simple hydrothermal extraction at high temperature. To develop an improved process to isolate ampelopsin, the effects of treatment of cellulase on hydrolysis of the dried fruit of A. grossedentata were investigated. The treatment of cellulase was found to decrease the temperature and time for hydrolysis of the dried fruit of A. grossedentata. The conditions of the filter press and continuous flow centrifuge for removal of insoluble materials from the hydrolysate of the dried fruit of A. grossedentata were optimized. The recovery yield of ampelopsin from the dried fruits of A. grossedentata was 39.4%, as determined by HPLC chromatographic analysis. A safe and economical process at low temperature with treatment of cellulase for the isolation of ampelopsin was developed in this study.

To demonstrate the anti-inflammatory activity of Aronia melanocarpa fruit extract, human bronchial epithelial cells (BEAS-2B) were treated with lipopolysaccharide (LPS) and the effects of aronia bioactive fraction (ABF®), anthocyanin enriched extract from the fruit of A. melanocarpa, were evaluated. Following pretreatment with ABF® at 10–25 µg /mL, BEAS-2B cells were exposed to LPS and the expression of inflammatory mediators (tumor necrosis factor [TNF]-α, interleukin [IL]-6, IL-8, regulated upon activation, normal T cell expressed and presumably secreted [RANTES], IL-1β, cyclooxygenase-2 [COX-2], and inducible nitric oxide synthase [iNOS]) was analyzed. In LPS-stimulated BEAS-2B cells, ABF® pretreatment significantly decreased the mRNA expression of TNF-α, IL-6, IL-8, RANTES, IL-1β, and COX-2 at doses of 10 and 25 µg/mL. ABF® also attenuated the secretion of TNF- α, IL-6, IL-8, and RANTES protein, as demonstrated by enzyme linked immunosorbent assay. Western blot analyses revealed the decreased expression of COX-2 and iNOS following ABF® treatment. ROS production was decreased, and the cell cycle was arrested at the G0/G1 and S phases following ABF® pretreatment. Our results suggest that ABF® may have potential as a nutraceutical agent for the suppression of airway inflammation.

ObjectivesChronic rhinosinusitis (CRS) with eosinophilic mucin is relatively rare in Korea. We categorized CRS patients with characteristic eosinophilic mucin into several groups and compared the groups based on their clinicopathological features.MethodsIn total, 52 CRS patients with eosinophilic mucin were enrolled. Based on the presence or absence of an allergy (A) to a fungus or fungal element (F) in the mucin, the patients were divided into four groups: allergic fungal rhinosinusitis (AFRS, A+F+), AFRS-like sinusitis (A+F-), eosinophilic fungal rhinosinusitis (EFRS, A-F+), and eosinophilic mucin rhinosinusitis (EMRS, A-F-). Clinical and immunological variables were compared between the groups.ResultsThere were 13 patients in the AFRS group, 13 in the EFRS group, and 26 in the EMRS group. No patient was assigned to the AFRS-like sinusitis group. The AFRS group showed a significantly higher association with allergic rhinitis than did the EFRS and EMRS groups. The mean total serum IgE level in the AFRS patients was significantly higher than in the EFRS and EMRS patients. While 7.7% of the patients with AFRS and EFRS were asthmatic, 65.4% of the patients with EMRS had bronchial asthma. In the AFRS and EFRS groups, 31% had bilateral disease, in contrast to 100% of EMRS patients with bilateral disease. The prevalence of high attenuation areas by computed tomography was significantly higher in the AFRS group than in the EMRS group, and the mean Hounsfield unit values of the areas of high attenuation in the AFRS patients were significantly greater than those in the EMRS patients.ConclusionAFRS is believed to be an allergic response to colonizing fungi in atopic individuals. In EFRS, local allergies to fungi may play a role in the pathogenesis of the disease. EMRS is thought to be unconnected with fungal allergies.

The optimal conditions including the aeration rate and agitation speed of bioreactors for the production of carboxymethylcellulase (CMCase) by a recombinant Escherichia coli KACC 91335P, expressing CMCase gene of B. velezensis A-68, were different from those for its cell growth. The enhanced production of CMCase by E. coli KACC 91335P with the conventional multistage process needs at least two bioreactors. Shifts in the optimal conditions of the aeration rate and agitation speed of the bioreactor from the cell growth of E. coli KACC 91335P to those for its production of CMCase were investigated for development of the simple and economic process with the high productivity and low cost. The production of CMCase by E. coli KACC 91335P with shifts in the optimal conditions of the aeration rate and agitation speed from the cell growth to its production of CMCase in a 100 L pilot-scale bioreactor was 1.36 times higher than that with a fixed optimal conditions of the aeration rate and agitation speed for the production of CMCase and it was even 1.54 times higher than that with a fixed optimal conditions of the aeration rate and agitation speed for cell growth. The best time for the shift in the optimal conditions was found to be the mid-log phase of cell growth. Owing to the mixed-growth-associated production of CMCase by E. coli KACC 91335P, shifts in the optimal conditions of the aeration rate and agitation speed of bioreactors from the cell growth to its production of CMCase seemed to result in relatively more cells for the participation in its production of CMCase, which in turn enhanced its production of CMCase. The process with a simple control for shifts in the aeration rate and agitation speed of a bioreactor for the enhanced production of CMCase by E. coli KACC 91335P on the pilot-scale can be directly applied to the industrial-scaled production of cellulase.

Background: Iatrogenic meningitis after spinal anesthesia is a rare condition. Most cases of iatrogenic meningitis have a bacterial etiology; however, there are a few reports of chemical meningitis associated with intrathecal administration of bupivacaine. Case Report: A 74-year-old man underwent cystoscopy, with anesthesia by intrathecal bupivacaine hydrochloride injection. Two hours post-procedurally, he complained of a severe headache and his mental status subsequently deteriorated from alertness to confusion. Cerebrospinal fluid examination on the day of admission showed an increase in cell count (841/mm3; polymorphonuclear 78%: mononuclear 10%) and total protein (460 mg/dL). His clinical findings and laboratory abnormalities were consistent with the diagnosis of bupivacaine-induced chemical meningitis, rather than the bacterial meningitis. Conclusion: We report a case of chemical meningitis after spinal anesthesia with bupivacaine. Differential diagnosis should include chemical meningitis in cases of meningitis after spinal anesthesia.

In this research, we developed a wearable temperature-sensing element by dip dyeing threads in poly (3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) (p-type conducting polymer) solution. The PEDOT:PSS was used to dye the textile and it exhibited negative temperature coefficient characteristics in which the resistance decreases as the temperature increases. The fabricated temperature-detection thread achieved a sensitivity of 167.1 Ω/°C with 99.8% linearity in the temperature range of −50 °C to 80 °C. We anticipate that temperature sensors that apply our technology will be made as stitch- or textile-type for wearable devices, and they will be widely adopted for different applications such as in fitness, leisure, healthcare, medical treatment, infotainment, industry, and military applications, among others.

Gabapentin was developed as an anticonvulsant, but has also been used to alleviate hyperalgesia in neuropathic pain. In this study, the protective effect of gabapentin against N-methyl-D-aspartate (NMDA)-induced excitotoxicity in rat hippocampal CA1 neurons was investigated. Pre-treatment with gabapentin reduced the degree of neuronal damage induced by NMDA exposure in cultured hippocampal slices. Patch-clamp studies revealed that gabapentin significantly inhibited the NMDA receptor–activated ion current in dissociated hippocampal CA1 neurons, resulting in suppression of glutamate-induced neuronal injury. These results show that gabapentin may exert protective effects against glutamate-induced neuronal injury at least in part by inhibiting the NMDA receptor–activated ion current. Keywords:: gabapentin, N-methyl-D-aspartate, neuroprotection

The heart of composite materials depends on the characteristics of their interface. The physical properties of composite materials are often described by the rule of mixtures, representing the average physical properties of the reinforcement and the matrix resin. However, in practical applications there are situations which arise where the rule of mixtures is not followed. This is because when an external energy applied to the composite material is transferred from the matrix to the reinforcement, the final physical properties are affected by the interface between them rather than the intrinsic properties of both the reinforcement and the matrix. The internal bonding strength of the interface of these composites can be enhanced by enhancing the bonding strength by adding a small amount of material at the interface. In this study, the mechanical properties were evaluated by producing a carbon fiber-reinforced composite material and improved by dispersing halloysite nanotubes (HNTs) and the epoxy resin using an ultrasonic homogenizer. The interfacial bond strength increased with the addition of HNT. On the other hand, the addition of HNTs more than 3 wt % did not show the reinforcing effect by HNT agglomeration.

Conventional cell spheroid production methods are largely manual, leading to variations in size and shape that compromise consistency and reliability for use in cell-based therapeutic applications. To enhance spheroid production, a spherical shell bioprinting system was implemented, enabling the high-throughput generation of uniform cell spheroids with precisely controlled sizes. The system encapsulates cells within thin alginate hydrogel shells formed through bioprinting and ion crosslinking reactions. Alginate–calcium ion crosslinking created alginate shells that contained gelatin-based bioinks with embedded cells, facilitating spontaneous cell aggregation within the shells and eliminating the need for plastic wells. By adjusting cell concentrations in the alginate–gelatin bioink, we achieved precise control over spheroid size, maintaining a sphericity above 0.94 and size deviations within ±10 µm. This method has been successfully applied to various cell types including cancer cells, fibroblasts, chondrocytes, and epithelial cells, demonstrating its versatility. This scalable approach enhances the reliability of cell therapy and drug screening, offering a robust platform for future biomedical applications.

Since the discovery that exosomes can exchange genes, their potential use as tools for tissue regeneration, disease diagnosis, and therapeutic applications has drawn significant attention. Emerging three-dimensional (3D) printing technologies, such as bioprinting, which allows the printing of cells, proteins, DNA, and other biological materials, have demonstrated the potential to create complex body tissues or personalized 3D models. The use of 3D spheroids in bioprinting facilitates volumetric tissue reconstruction and accelerates tissue regeneration via exosome secretion. In this review, we discussed a convergence approach between two promising technologies for bioprinting and exosomes in regenerative medicine. Among the various 3D cell culture methods used for exosome production, we focused on spheroids, which are suitable for mass production by bioprinting. We then summarized the research results on cases of bioprinting applications using the spheroids and exosomes produced. If a large number of spheroids can be supplied through bioprinting, the spheroid-exosome-based bioprinting technology will provide new possibilities for application in tissue regeneration, disease diagnosis, and treatment.

This paper considers coordinated transmission for interference mitigation and power allocation in a correlated two-user two-hop multi-input multioutput (MIMO) relay system. The proposed transmission scheme utilizes statistical channel state information (CSI) (e.g., transmit correlation) to minimize the cochannel interference (CCI) caused by the relay. To this end, it is shown that the CCI can be represented in terms of the eigenvalues and the angle difference between the eigenvectors of the transmit correlation matrix of the intended and CCI channel, and that the condition minimizing the CCI can be characterized by the correlation amplitude and the phase difference between the transmit correlation coefficients of these channels. Then, a coordinated user-scheduling strategy is designed with the use of eigen-beamforming to minimize the CCI in an average sense. The transmit power of the base station and relay is optimized under separate power constraint. Analytic and numerical results show that the proposed scheme can maximize the achievable sum rate when the principal eigenvectors of the transmit correlation matrix of the intended and the CCI channel are orthogonal to each other, yielding a sum rate performance comparable to that of the minimum mean-square error-based coordinated beamforming which uses instantaneous CSI.

Orthogonal frequency division multiplexing (OFDM) is considered as one of the most promising techniques for next-generation wireless access systems. However, it may suffer from the so-called other-cell interference (OCI) in cellular environments. In this paper, we consider a novel resource allocation scheme to reduce the OCI in OFDM-based asynchronous cellular systems. The proposed scheme can reduce the OCI by exploiting repetitive properties of cyclic prefix of OFDM symbol and asynchronous properties between the user and the base stations in other cells. The proposed scheme can be applied to various types of OFDM-based systems such as orthogonal frequency division multiple access (OFDMA) and multicarrier code division multiple access (MC-CDMA) systems. Simulation results show that the proposed scheme can reduce the OCI by nearly up to 1 dB compared to conventional schemes, yielding an increase of the throughput of about 15% near the cell boundary in OFDM-based asynchronous cellular environments.