Nanoengineered Macrophages Armed with TLR7/8 Agonist Enhance Remodeling of Immunosuppressive Tumor Microenvironment.

Although adoptive cell-based therapy is illuminated as one of the promising approaches in cancer immunotherapy, it shows low antitumor efficacy because transferred cells adapt and alter toward a pro-tumoral phenotype in response to the tumor's immunosuppressive milieu. Herein, nanoengineered macrophages anchored with functional liposome armed with cholesterol-conjugated Toll-like receptor 7/8 agonist (masked TLR7/8a, m7/8a) are generated to overcome the shortcomings of current macrophage-based therapies and enhance the remodeling of the immunosuppressive tumor microenvironment (TME). The liposome-anchored macrophages (LAMΦ-m7/8a), are fabricated by anchoring dibenzocyclooctyne-modified liposome(m7/8a) onto azido-expressing macrophages via a bio-orthogonal click reaction, are continuously invigorated due to the slow internalization of liposome(m7/8a) and sustained activation. LAMΦ-m7/8a secreted ≈3 and 33-fold more IL-6 and TNF-α than conventional M1-MΦ, maintained the M1 phenotype, and phagocytosed tumor cells for up to 48 h in vitro. Both intratumoral and intravenous injections of LAMΦ-m7/8a induced effective antitumor efficacy when treated in combination with doxorubicin-loaded liposomes in 4T1-tumor bearing mice. It not only increases the infiltration of antigen-specific CD8+ T cells secreting granzyme B, IFN-γ, and TNF-α within the TME, but also reduces myeloid-derived suppressor cells. These results suggest that LAMΦ-m7/8a may provide a suitable alternative to next-generation cell-based therapy platform.

Adaptive Beam Divergence Control to Mitigate Scintillation Effect Caused by Pointing Error in Vertical FSO Transmissions.

Free-space optical (FSO) communication has been studied for next-generation network systems. Because an FSO system establishes point-to-point communication links, maintaining alignment among the transceivers is a critical challenge. In addition, atmospheric turbulence causes significant signal loss in FSO vertical links. Even in clear weather conditions, transmitted optical signals suffer significant scintillation losses due to random variations. Thus, the effect of atmospheric turbulence should be considered in vertical links. In this paper, we analyze the relationship between pointing error and scintillation from the aspect of beam divergence angle. Furthermore, we propose an adaptive beam that optimizes its divergence angle according to the pointing error between the communicating optical transceivers to mitigate the effect of scintillation due to pointing error. We performed a beam divergence angle optimization and compared it with adaptive beamwidth. The proposed technique was demonstrated using simulations, which revealed an enhanced signal-to-noise ratio and the mitigation of the scintillation effect. The proposed technique would be useful in minimizing the scintillation effect in vertical FSO links.

PGE1 and PGA1 bind to Nurr1 and activate its transcriptional function.

The orphan nuclear receptor Nurr1 is critical for the development, maintenance and protection of midbrain dopaminergic (mDA) neurons. Here we show that prostaglandin E1 (PGE1) and its dehydrated metabolite, PGA1, directly interact with the ligand-binding domain (LBD) of Nurr1 and stimulate its transcriptional function. We also report the crystallographic structure of Nurr1-LBD bound to PGA1 at 2.05 Å resolution. PGA1 couples covalently to Nurr1-LBD by forming a Michael adduct with Cys566, and induces notable conformational changes, including a 21° shift of the activation function-2 helix (H12) away from the protein core. Furthermore, PGE1/PGA1 exhibit neuroprotective effects in a Nurr1-dependent manner, prominently enhance expression of Nurr1 target genes in mDA neurons and improve motor deficits in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse models of Parkinson's disease. Based on these results, we propose that PGE1/PGA1 represent native ligands of Nurr1 and can exert neuroprotective effects on mDA neurons, via activation of Nurr1's transcriptional function.

Cultivar-Specific Changes in Primary and Secondary Metabolites in Pak Choi (Brassica Rapa, Chinensis Group) by Methyl Jasmonate.

Glucosinolates, their hydrolysis products and primary metabolites were analyzed in five pak choi cultivars to determine the effect of methyl jasmonate (MeJA) on metabolite flux from primary metabolites to glucosinolates and their hydrolysis products. Among detected glucosinolates (total 14 glucosinolates; 9 aliphatic, 4 indole and 1 aromatic glucosinolates), indole glucosinolate concentrations (153-229%) and their hydrolysis products increased with MeJA treatment. Changes in the total isothiocyanates by MeJA were associated with epithiospecifier protein activity estimated as nitrile formation. Goitrin, a goitrogenic compound, significantly decreased by MeJA treatment in all cultivars. Changes in glucosinolates, especially aliphatic, significantly differed among cultivars. Primary metabolites including amino acids, organic acids and sugars also changed with MeJA treatment in a cultivar-specific manner. A decreased sugar level suggests that they might be a carbon source for secondary metabolite biosynthesis in MeJA-treated pak choi. The result of the present study suggests that MeJA can be an effective agent to elevate indole glucosinolates and their hydrolysis products and to reduce a goitrogenic compound in pak choi. The total glucosinolate concentration was the highest in "Chinese cabbage" in the control group (32.5 µmol/g DW), but indole glucosinolates increased the greatest in "Asian" when treated with MeJA.

Development and Performance Characteristics of Personal Gamma Spectrometer for Radiation Monitoring Applications.

In this study, a personal gamma (γ) spectrometer was developed for use in applications in various fields, such as homeland security and environmental radiation monitoring systems. The prototype consisted of a 3 × 3 × 20 mm³ Ce-doped Gd-Al-Ga-garnet (Ce:GAGG) crystal that was coupled to a Si photomultiplier (SiPM) to measure γ radiation. The γ spectrometer could be accessed remotely via a mobile device. At room temperature, the implemented Ce:GAGG-SiPM spectrometer achieved energy resolutions of 13.5%, 6.9%, 5.8%, and 2.3% for (133)Ba at 0.356 MeV, (22)Na at 0.511 MeV, (137)Cs at 0.662 MeV, and (60)Co at 1.33 MeV, respectively. It consumed only about 2.7 W of power, had a mass of just 340 g (including the battery), and measured only 5.0 × 7.0 cm².

Urine and serum metabolite profiling of rats fed a high-fat diet and the anti-obesity effects of caffeine consumption.

In this study, we investigated the clinical changes induced by a high fat diet (HFD) and caffeine consumption in a rat model. The mean body weight of the HFD with caffeine (HFDC)-fed rat was decreased compared to that of the HFD-fed rat without caffeine. The levels of cholesterol, triglycerides (TGs), and free fatty acid, as well as the size of adipose tissue altered by HFD, were improved by caffeine consumption. To investigate the metabolites that affected the change of the clinical factors, the urine and serum of rats fed a normal diet (ND), HFD, and HFDC were analyzed using ultra performance liquid chromatography quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS), gas chromatography (GC-TOF-MS), and linear trap quadruple mass spectrometry (LTQ-XL-MS) combined with multivariate analysis. A total of 68 and 52 metabolites were found to be different in urine and serum, respectively. After being fed caffeine, some glucuronide-conjugated compounds, lysoPCs, CEs, DGs, TGs, taurine, and hippuric acid were altered compared to the HFD group. In this study, caffeine might potentially inhibit HFD-induced obesity and we suggest possible biomarker candidates using MS-based metabolite profiling.

Desmodianone H and uncinanone B, potential tyrosinase inhibitors obtained from Lespedeza maximowiczii by using bioactivity-guided isolation.

A new bioactive compound, namely desmodianone H(1), and another known compound uncinanone B(2) were first isolated using bioactivity-guided isolation from the leaves of Lespedeza maximowiczii and structures were elucidated by comprehensive analysis of their nuclear magnetic resonance and mass spectrometry data. Compounds 1 and 2 exhibited strong inhibitory effects on mushroom tyrosinase activity.

O-Succinyl-L-homoserine-based C4-chemical production: succinic acid, homoserine lactone, γ-butyrolactone, γ-butyrolactone derivatives, and 1,4-butanediol.

There has been a significant global interest to produce bulk chemicals from renewable resources using engineered microorganisms. Large research programs have been launched by academia and industry towards this goal. Particularly, C4 chemicals such as succinic acid (SA) and 1,4-butanediol have been leading the path towards the commercialization of biobased technology with the effort of replacing chemical production. Here we present O-Succinyl-L-homoserine (SH) as a new, potentially important platform biochemical and demonstrate its central role as an intermediate in the production of SA, homoserine lactone (HSL), γ-butyrolactone (GBL) and its derivatives, and 1,4-butanediol (BDO). This technology encompasses (1) the genetic manipulation of Escherichia coli to produce SH with high productivity, (2) hydrolysis into SA and homoserine (HS) or homoserine lactone hydrochloride, and (3) chemical conversion of either HS or homoserine lactone HCL (HSL·HCl) into drop-in chemicals in polymer industry. This production strategy with environmental benefits is discussed in the perspective of targeting of fermented product and a process direction compared to petroleum-based chemical conversion, which may reduce the overall manufacturing cost.

Effect of the Mandibular Orthopedic Repositioning Appliance (MORA) on Forearm Muscle Activation and Grasping Power during Pinch and Hook Grip.

[Purpose] This study verified the changes in muscle activities and grasping power during maximal isometric exercise of the forearm and masseter muscle with and without a mandibular orthopedic repositioning appliance (MORA). It also offers basic data for defining the correlation of function of hand with mouth. [Methods] EMG was used to measure masticatory muscle, flexor bundle and extensor bundle activities with or without MORA while subjects performed the hook grip and pinch grip. The measuring tool used for measuring grip strength was the same as that used for measuring pinch and hook strength. The subjects were 28 healthy young adults. [Result] Muscle activity and grasping power significantly increased when wearing the MORA. [Conclusion] The result indicates that wearing MORA can increase muscle activity and grasping power of forearm and masseter muscle. We think wearing MORA might help improve the function of the forearm because it activates the function of the masseter.

Effectiveness of the triglyceride-glucose index and triglyceride-glucose-related indices in predicting cardiovascular disease in middle-aged and older adults: A prospective cohort study.

BACKGROUNDS: Cardiovascular disease (CVD) risk assessment is a crucial component of public health. We aimed to determine the predictive value of the triglyceride-glucose (TyG) index and TyG-related indices for new-onset CVD. METHODS: This prospective study included 7,808 participants aged 40-69 years from the Ansung-Ansan cohort database. Our analysis was stratified by diabetes status. The hazard ratio (HR) with a 95% confidence interval (CI) for incident CVD was computed using multiple Cox proportional-hazards regression models. To evaluate the predictive performance of these indices for new-onset CVD, we calculated the Harrell's C-index (95% CI). RESULTS: In this study, a total of 6,890 participants did not have diabetes at baseline, while 918 participants had diabetes. In participants without diabetes, compared to the lowest tertile, fully adjusted HR and 95% CI for new-onset CVD in the highest tertile were as follows: TyG (HR 1.42, 95% CI 1.06-1.90), TyG-body mass index (BMI) (HR 1.92, 95% CI 1.19-3.10), TyG-waist circumference (WC) (HR 2.37, 95% CI 1.61-3.49), and TyG-waist-to-height ratio (WHtR) (HR 2.20, 95% CI 1.47-3.28). However, no significant associations were observed between TyG, modified TyG indices, and new-onset CVD in participants with diabetes. Notably, the C-indice of TyG-WC and TyG-WHtR were significantly higher than those of TyG and TyG-BMI in participants without diabetes. CONCLUSIONS: TyG-BMI, TyG-WC, and TyG-WHtR were associated with an increased risk of new-onset CVD in participants without diabetes. Furthermore, TyG-WC and TyG-WHtR showed better predictive performances for new-onset CVD than TyG and TyG-BMI in participants without diabetes.

Characterization of high Zn content Cd0.87Zn0.13Te0.98Se0.02 grown using Bridgman technique.

CdZnTe (CZT) is a promising commercial material used as a room-temperature operating semiconductor detector for gamma-ray detection. Recently, CdZnTeSe (CZTS) detectors improved upon the properties of CZT by improving homogeneity and reducing defect properties, thereby enabling higher production yield of high-quality crystals. However, addition of selenium to CZT will reduce the bandgap and increase the amount of thermally stimulated electrons, resulting in low resistivity of the crystal. In this study, the enhancement of zinc content was introduced to compensate the bandgap reduction owing to selenium addition, while maintaining the improved properties of selenium addition. The morphology and stoichiometry of CZTS were determined using scanning electron microscopy and electron probe micro-analyzer. Furthermore, the calculated bandgap with stoichiometry was compared with the measured bandgap using UV-Vis measurement and Tauc plot. The electrical, chemical, and other spectroscopic properties were characterized using an I-V curve, X-ray photoelectron spectroscopy, and gamma-spectroscopic techniques, respectively. Moreover, it was proven that the high zinc CZTS can exhibit superior properties owing to selenium addition without affecting the bandgap reduction.

Metabolic engineering of Escherichia coli for the production of 5-aminovalerate and glutarate as C5 platform chemicals.

5-Aminovalerate (5AVA) is the precursor of valerolactam, a potential building block for producing nylon 5, and is a C5 platform chemical for synthesizing 5-hydroxyvalerate, glutarate, and 1,5-pentanediol. Escherichia coli was metabolically engineered for the production of 5-aminovalerate (5AVA) and glutarate. When the recombinant E. coli WL3110 strain expressing the Pseudomonas putidadavAB genes encoding delta-aminovaleramidase and lysine 2-monooxygenase, respectively, were cultured in a medium containing 20g/L of glucose and 10g/L of L-lysine, 3.6g/L of 5AVA was produced by converting 7g/L of L-lysine. When the davAB genes were introduced into recombinant E. coli strainXQ56allowing enhanced L-lysine synthesis, 0.27 and 0.5g/L of 5AVA were produced directly from glucose by batch and fed-batch cultures, respectively. Further conversion of 5AVA into glutarate could be demonstrated by expression of the P. putida gabTD genes encoding 5AVA aminotransferase and glutarate semialdehyde dehydrogenase. When recombinant E. coli WL3110 strain expressing the davAB and gabTD genes was cultured in a medium containing 20g/L glucose, 10g/L L-lysine and 10g/L α-ketoglutarate, 1.7g/L of glutarate was produced.

Inverse Association between Oxidative Balance Score and Incident Type 2 Diabetes Mellitus.

Mitigating the risk of type 2 diabetes mellitus (T2DM) can be achieved through the maintenance of a healthy weight, the adoption of a healthy diet, and engaging in regular physical activity. The oxidative balance score (OBS), an integrated measure of pro- and antioxidant exposure conditions, represents an individual's overall oxidative balance status. This study aimed to evaluate the association between OBS and T2DM incidence using data from a large, community-based, prospective cohort study. Data from 7369 participants aged 40-69 years who engaged in the Korean Genome and Epidemiology Study (KoGES) were analyzed. The hazard ratio (HR) and 95% confidence interval (CI) for T2DM incidence of sex-specific OBS tertile groups were calculated using univariable and multivariable Cox proportional hazard regression analyses. During the mean 13.6-year follow-up period, 908 men and 880 women developed T2DM. The fully-adjusted HR (95% CI) for incident T2DM of the middle and highest tertile groups, compared with the referent lowest tertile group, were 0.86 (0.77-1.02) and 0.83 (0.70-0.99) in men and were 0.94 (0.80-1.11) and 0.78 (0.65-0.94) in women, respectively. Individuals with a high OBS are at lower risk for the development of T2DM. This implies that lifestyle modification with more antioxidant properties could be a preventive strategy for T2DM.

Oxidative balance score inversely associated with the prevalence and incidence of metabolic syndrome: analysis of two studies of the Korean population.

Background: Pro-oxidant/antioxidant imbalances leading to chronic inflammation and insulin resistance can contribute to the development of metabolic syndrome (MetS). Oxidative Balance Score (OBS), a comprehensive measure of exposure to pro- and anti-oxidants, represents an individual's total oxidative balance. This study aimed to evaluate the association between OBS and MetS using two large datasets. Methods: We analyzed data from 2,735 adults older than 19 years from the 2021 Korean National Health and Nutritional Examination Survey (KNHANES) and 5,807 adults aged 40-69 years from the Korean Genome and Epidemiology Study (KoGES). In each dataset, OBS was categorized into sex-specific tertiles (T). Results: In KNHANES, the odds ratios and 95% confidence intervals for prevalent MetS in T3, compared to T1, were 0.44 (0.29-0.65) in men and 0.34 (0.23-0.50) in women after adjusting for confounders. In KoGES, the hazard ratios and 95% confidence intervals for incident MetS in T3, compared to T1, were 0.56 (0.48-0.65) in men and 0.63 (0.55-0.73) in women after adjusting for confounders. Conclusion: OBS appears to be inversely related to MetS, which suggests that adopting lifestyle behaviors that decrease oxidative stress could be an important preventive strategy for MetS.

Assessment of the viability of integrating virtual reality programs in practical tests for the Korean Radiological Technologists Licensing Examination: a survey study

PURPOSE: The objective of this study was to assess the feasibility of incorporating virtual reality/augmented reality (VR/AR) programs into practical tests administered as part of the Korean Radiological Technologists Licensing Examination (KRTLE). This evaluation is grounded in a comprehensive survey that targeted enrolled students in departments of radiology across the nation. METHODS: In total, 682 students from radiology departments across the nation were participants in the survey. An online survey platform was used, and the questionnaire was structured into 5 distinct sections and 27 questions. A frequency analysis for each section of the survey was conducted using IBM SPSS ver. 27.0. RESULTS: Direct or indirect exposure to VR/AR content was reported by 67.7% of all respondents. Furthermore, 55.4% of the respondents expressed that VR/AR could be integrated into their classes, which signified a widespread acknowledgment of VR among the students. With regards to the integration of a VR/AR or mixed reality program into the practical tests for purposes of the KRTLE, a substantial amount of the respondents (57.3%) exhibited a positive inclination and recommended its introduction. CONCLUSION: The application of VR/AR programs within practical tests of the KRTLE will be used as an alternative for evaluating clinical examination procedures and validating job skills.

Tinnitus and Its Association With Mental Health and Health-Related Quality of Life in an Older Population: A Nationwide Cross-Sectional Study.

This study investigated the relationship of tinnitus with mental health and health-related quality of life (QoL) in older people. Data source included 5,129 community-dwelling men and women ≥60 years old from the Korean National Health and Nutrition Examination Survey. Tinnitus was categorized into three groups: normal, tolerable tinnitus, and annoying tinnitus. Mental health and health-related QoL were assessed according to three dimensions (depressive mood, psychological distress, and suicidal ideation) and five domains (impaired mobility, impaired self-care, impaired usual activities, pain/discomfort, and anxiety/depression). The odds ratios (ORs) and 95% confidence intervals (CIs) of mental health and health-related QoL were calculated using multiple logistic regression analyses. Annoying tinnitus was positively and independently associated with deteriorated mental health and health-related QoL, suggesting comprehensive care is needed in older people with annoying tinnitus.

Inhibition of GP130/STAT3 and EMT by combined bazedoxifene and paclitaxel treatment in ovarian cancer.

The interleukin 6 (IL­6)/glycoprotein 130 (GP130)/signal transducer and activator of transcription 3 (STAT3) signalling pathway, with GP130 as an intermediate membrane receptor, is involved in the survival, metastasis, and resistance of ovarian cancer. Bazedoxifene, an FDA­approved drug, is an inhibitor of GP130 and a selective estrogen modulator (SERM). We studied the mechanism of the combination therapy of bazedoxifene and paclitaxel in inhibiting the IL­6­mediated GP130/STAT3 signaling pathway in ovarian cancer. Surface plasmon resonance (SPR) was used to assess the binding of bazedoxifene to GP130. Migration, invasion, and apoptosis of ovarian cancer cells were assessed using bazedoxifene and paclitaxel. In addition, we determined the effects of bazedoxifene and paclitaxel alone or in combination on the GP130/STAT3 pathway and epithelial­mesenchymal transition (EMT). The results revealed that the combination of bazedoxifene and paclitaxel suppressed cell viability, migration, and invasion in the ovarian cancer cells. In addition, the combination treatment increased apoptosis. Furthermore, bazedoxifene combined with paclitaxel inhibited the growth of ovarian cancer cells in a xenograft tumour model. This combination reduced STAT3 phosphorylation and suppressed gene expression and EMT. In conclusion, inhibition of GP130/STAT3 signalling and EMT via a combination of bazedoxifene and paclitaxel could be used as a therapeutic strategy by which to overcome ovarian cancer.

Effects of Induction Culture on Osteogenesis of Scaffold-Free Engineered Tissue for Bone Regeneration Applications.

BACKGROUND: Restoration of the bone defects caused by infection or disease remains a challenge in orthopedic surgery. In recent studies, scaffold-free engineered tissue with a self-secreted extracellular matrix has been proposed as an alternative strategy for tissue regeneration and reconstruction. Our study aimed to engineer and fabricate self-assembled osteogenic and scaffold-free tissue for bone regeneration. METHODS: Osteogenic scaffold-free tissue was engineered and fabricated using fetal cartilage-derived progenitor cells, which are capable of osteogenic differentiation. They were cultured in osteogenic induction environments or using demineralized bone powder for differentiation. The fabricated tissue was subjected to real-time qPCR, biochemical, and histological analyses to estimate the degree of in vitro osteogenic differentiation. To demonstrate bone formation in an in vivo environment, scaffold-free tissue was transplanted into the dorsal subcutaneous site of nude mice. Bone development was monitored postoperatively over 8 weeks by the observation of calcium deposition in the matrix. RESULTS: In the in vitro experiments, engineered osteogenically induced scaffold-free tissue demonstrated three-dimensional morphological characteristics, and sufficient osteogenic differentiation was confirmed through the quantification of specific osteogenic gene markers expressed and calcium accumulation within the matrix. Following the evaluation of differentiation efficacy, in vivo experiments revealed distinct bone formation, and that blood vessels had penetrated the fabricated tissue. CONCLUSION: The novel engineering of scaffold-free tissue with osteogenic potential can be used as an optimal bone graft substitute for bone regeneration.

New markers in metabolic syndrome.

Metabolic syndrome (MetS) is increasing globally and is clinically significant due to its association with cardiovascular disease, type 2 diabetes and cancer. Although the pathogenesis of MetS has not been clearly elucidated, insulin resistance and chronic low-grade inflammation derived from central obesity are the most widely accepted as underlying pathophysiology. Accordingly, insulin resistance indices, adipokines and various inflammatory markers have been suggested as reliable biomarkers for MetS. Others, such as uric acid, alkaline phosphatase, γ-glutamyl transferase, are also known to positively correlate with MetS and could be diagnostically useful. In this review, we provide a comprehensive overview of MetS biomarkers and the development of a systematic approach to laboratory analysis.

Pure copper nanoparticles prepared by coating-assisted vapor phase synthesis without agglomeration.

Modern electronic devices, such as smartphones and electric vehicles, require multilayer ceramic capacitors (MLCCs), which comprise highly pure Cu terminations and Ni electrodes. Vapor-phase synthesis (VPS) is a promising method for synthesizing nanoparticles (NPs) with high purity and crystallinity. However, the agglomeration of the NPs occurs during their synthesis, which degrades the performance of the MLCC electrodes owing to several factors, including electrical shorts and low packing density. This paper proposes a coating-assisted VPS to inhibit agglomeration using potassium chloride (KCl) as the coating agent. The agglomeration ratio of the Cu NPs synthesized by in-flight coating with KCl at 950 °C significantly decreased from 48.20% to 3.80%, compared to without KCl coating. Furthermore, X-ray fluorescence and X-ray diffraction analyses confirmed that the KCl coating agent and residual copper chloride were removed by washing with ammonium hydroxide.