Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue.

Hepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen concentrations resulting from the dual hepatic vascular supply drive the inherent heterogeneity of the tumor microenvironment, which presents challenges in developing an avatar model. In this study, tissue samples from 12 patients with hepatocellular carcinoma are cultured directly on a chip and separated based on preference of oxygen concentration. Establishing a dual gradient system with drug perfusion perpendicular to the oxygen gradient enables the simultaneous separation of cells and evaluation of drug responsiveness. The results are further cross-validated by implanting the chips into mice at various oxygen levels using a patient-derived xenograft model. Hepatocellular carcinoma cells exposed to hypoxia exhibit invasive and recurrent characteristics that mirror clinical outcomes. This chip provides valuable insights into treatment prognosis by identifying the dominant hepatocellular carcinoma type in each patient, potentially guiding personalized therapeutic interventions.

Two-Year Carcinogenicity Study of a Novel Plasticizer, bis(2-Ethylhexyl) Cyclohexane-1,4-Dicarboxylate (Eco-DEHCH), by Oral Diet in Han Wistar Rats.

Plasticizers are necessary for the usability of various products, including food contact materials. Exposure to plasticizers is most commonly made through the oral route. Several plasticizers have been reported to have adverse effects on humans and the environment. Thus, the present study aimed to determine the long-term toxicity and carcinogenicity of a novel plasticizer called bis(2-ethylhexyl) cyclohexane-1,4-dicarboxylate (Eco-DEHCH), which is an ecofriendly and biologically less harmful replacer. Groups of 50 male and 50 female Han Wistar rats were fed Eco-DEHCH at daily doses of 1,600, 5,000, or 16,000 ppm in their diet for at least 104 weeks. The rats were regularly monitored for mortality, clinical signs, body weight, food consumption, food efficiency, and perceivable mass. All animals were subjected to complete necropsy and histopathological examination. The results indicate that the rats well tolerated chronic exposure to Eco-DEHCH at highest daily doses of 16,000 ppm, with was equivalent to 805.1 mg/kg/day in males and 1,060.6 mg/kg/day in females and did not show signs of toxicity or carcinogenicity. In conclusion, Eco-DEHCH could be a safe and promising alternative plasticizer.

Titanium Silicide: A Promising Candidate of Recombination Layer for Perovskite/Tunnel Oxide Passivated Contact Silicon Two-Terminal Tandem Solar Cells.

This study proposes a titanium silicide (TiSi2) recombination layer for perovskite/tunnel oxide passivated contact (TOPCon) 2-T tandem solar cells as an alternative to conventional transparent conductive oxide (TCO)-based recombination layers. TiSi2 was formed while TiO2 was made by oxidizing a Ti film deposited on the p+-Si layer. The reaction formation mechanism was proposed based on the diffusion theory supported by experimental results. The optical and electrical properties of the TiSi2 layer were optimized by controlling the initial Ti thicknesses (5-100 nm). With the initial Ti of 50 nm, the lowest reflectance and highly ohmic contact between the TiO2 and p+-Si layers with a contact resistivity of 161.48 mΩ·cm2 were obtained. In contrast, the TCO interlayer shows Schottky behavior with much higher contact resistivities. As the recombination layer of TiSi2 and the electron transport layer of TiO2 are formed simultaneously, the process steps become simpler. Finally, the MAPbI3/TOPCon tandem device yielded an efficiency of 16.23%, marking the first reported efficiency for a device including a silicide-based interlayer.

SERTAD1 initiates NLRP3-mediated inflammasome activation through restricting NLRP3 polyubiquitination.

We here demonstrate that SERTAD1 is an adaptor protein responsible for the regulation of lysine 63 (K63)-linked NLRP3 polyubiquitination by the Cullin1 E3 ubiquitin ligase upon inflammasome activation. SERTAD1 specifically binds to NLRP3 but not to other inflammasome sensors. This endogenous interaction increases after inflammasome activation, interfering with the interaction between NLRP3 and Cullin1. Interleukin (IL)-1ß and IL-18 secretion, as well as the cleavage of gasdermin D, are decreased in SERTAD1 knockout bone-marrow-derived macrophages, together with reduced formation of the NLRP3 inflammasome complex. Additionally, SERTAD1-deficient mice show attenuated severity of monosodium-uric-acid-induced peritonitis and experimental autoimmune encephalomyelitis. Analysis of public datasets indicates that expression of SERTAD1 mRNA is significantly increased in the patients of autoimmune diseases. Thus, our findings uncover a function of SERTAD1 that specifically reduces Cullin1-mediated NLRP3 polyubiquitination via direct binding to NLRP3, eventually acting as a crucial factor to regulate the initiation of NLRP3-mediated inflammasome activation.

Chemical upcycling of PVC-containing plastic wastes by thermal degradation and catalysis in a chlorine-rich environment.

Chlorine (Cl)-containing chemicals, including hydrogen chloride, generated during thermal degradation of polyvinyl chloride (PVC) and corresponding mixture impede the chemical recycling of PVC-containing plastic wastes. While upgrading plastic-derived vapors, the presence of Cl-containing chemicals may deactivate the catalysts. Accordingly, herein, catalytic upgrading of pyrolysis vapor prepared from a mixture of PVC and polyolefins is performed using a fixed-bed reactor comprising zeolites. Among the H-forms of zeolites (namely, ZSM-5, Y, ß, and chabazite) used in this study, a higher yield of gas products composed of hydrocarbons with lower carbon numbers is obtained using H-ZSM-5, thus indicating further decomposition of the pyrolysis vapor to C1-C4 hydrocarbons on it. Although the formation of aromatic compounds is better on H-ZSM-5, product distributions can be adjusted by further modifying the acidic properties via the alteration of the Si/Al molar ratio, and maximum yields of C1-C4 compounds (60.8%) and olefins (64.7%) are achieved using a Si/Al molar ratio of 50. Additionally, metal ion exchange on H-ZSM-5 is conducted, and upgrading of PVC-containing waste-derived vapor to aromatic chemicals and small hydrocarbon molecules was successfully performed using Co-substituted H-ZSM-5. It reveals that the highest yield of gas products on 1.74 wt% cobalt (Co)-substituted H-ZSM-5 is acquired via the selection of an appropriate metal and metal ion concentration adjustment. Nevertheless, introduction of excess Co into the H-ZSM-5 surface decreases the cracking activity, thereby implying that highly distributed Co is required to achieve excellent cracking activity. The addition of Co also adjusted the acid types of H-ZSM-5, and more Lewis acid sites compared to Brønsted acid sites selectively produced olefins and naphthenes over paraffins and aromatics. The proposed approach can be a feasible process to produce valuable petroleum-replacing chemicals from Cl-containing mixed plastic wastes, contributing to the closed loops for upcycling plastic wastes.

Non-targeted metabolomics aids in sex pheromone identification: a proof-of-concept study with the triangulate cobweb spider, Steatoda triangulosa.

Targeted metabolomics has been widely used in pheromone research but may miss pheromone components in study organisms that produce pheromones in trace amount and/or lack bio-detectors (e.g., antennae) to readily locate them in complex samples. Here, we used non-targeted metabolomics-together with high-performance liquid chromatography-mass spectrometry (HPLC-MS), gas chromatography-MS, and behavioral bioassays-to unravel the sex pheromone of the triangulate cobweb spider, Steatoda triangulosa. A ternary blend of three contact pheromone components [N-4-methylvaleroyl-O-isobutyroyl-L-serine (5), N-3-methylbutyryl-O-isobutyroyl-L-serine (11), and N-3-methylbutyryl-O-butyroyl-L-serine (12)] elicited courtship by S. triangulosa males as effectively as female web extract. Hydrolysis of 5, 11 and 12 at the ester bond gave rise to two mate-attractant pheromone components [butyric acid (7) and isobutyric acid (8)] which attracted S. triangulosa males as effectively as female webs. Pheromone components 11 and 12 are reported in spiders for the first time, and were discovered only through the use of non-targeted metabolomics and GC-MS. All compounds resemble pheromone components previously identified in widow spiders. Our study provides impetus to apply non-targeted metabolomics for pheromone research in a wide range of animal taxa.

Development of Thiol-Ene Reaction-Based HA Hydrogel with Sustained Release of EGF for Enhanced Skin Wound Healing.

This study develops a novel drug delivery system using a hyaluronic acid (HA) hydrogel for controlled release of epidermal growth factor (EGF) to enhance skin wound healing. Conventional hydrogel-based methods suffer from a burst release and limited drug delivery times. To address this, we employ bioconjugation to introduce an acrylate group to EGF, enabling chemical bonding to the HA hydrogel matrix through thiol-ene cross-linking. This approach results in sustained-release delivery of EGF based on the degradation rate of the HA matrix, overcoming diffusion-based limitations. We confirm the introduction of the acrylate group using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. We evaluated the hydrogel morphology and rheological properties following binding of acrylate-conjugated EGF to the HA matrix. Assessment of the EGF release profile demonstrates delayed release compared to unconjugated EGF. We evaluate the impact on cells through cell proliferation and scratch assays, indicating the system's efficacy. In a rat wound healing model, the sustained release of EGF from the hydrogel system promotes appropriate tissue healing and restores it to a normal state. These findings suggest that this practical drug delivery system, involving the modification of growth factors or drugs to chemically bind healing factors to hydrogels, can achieve long-lasting effects.

Deep Learning-Based Evaluation of Ultrasound Images for Benign Skin Tumors.

In this study, a combined convolutional neural network for the diagnosis of three benign skin tumors was designed, and its effectiveness was verified through quantitative and statistical analysis. To this end, 698 sonographic images were taken and diagnosed at the Department of Dermatology at Severance Hospital in Seoul, Korea, between 10 November 2017 and 17 January 2020. Through an empirical process, a convolutional neural network combining two structures, which consist of a residual structure and an attention-gated structure, was designed. Five-fold cross-validation was applied, and the train set for each fold was augmented by the Fast AutoAugment technique. As a result of training, for three benign skin tumors, an average accuracy of 95.87%, an average sensitivity of 90.10%, and an average specificity of 96.23% were derived. Also, through statistical analysis using a class activation map and physicians' findings, it was found that the judgment criteria of physicians and the trained combined convolutional neural network were similar. This study suggests that the model designed and trained in this study can be a diagnostic aid to assist physicians and enable more efficient and accurate diagnoses.

Rice Bran Extract Suppresses High-Fat Diet-Induced Hyperlipidemia and Hepatosteatosis through Targeting AMPK and STAT3 Signaling.

Rice bran, a by-product of rice milling, is abundant in bioactive molecules and is highly recognized for its health-promoting properties, particularly in improving metabolic conditions. Building on this knowledge, we aimed to optimize the extraction conditions to maximize the functional efficacy of rice bran extract (RBE) and further validate its impact on lipid metabolism. We found that the optimized RBE (ORBE) significantly suppressed high-fat diet-induced weight gain, hyperlipidemia, and hepatosteatosis in mouse models. ORBE treatment not only suppressed lipid uptake in vivo, but also reduced lipid accumulation in HepG2 cells. Importantly, we discovered that ORBE administration resulted in activation of AMPK and inhibition of STAT3, which are both crucial players in lipid metabolism in the liver. Collectively, ORBE potentially offers promise as a dietary intervention strategy against hyperlipidemia and hepatosteatosis. This study underlines the value of optimized extraction conditions in enhancing the functional efficacy of rice bran.

Seroprevalence of Measles IgG Antibodies in Married Immigrant Women from Multicultural Families in Korea.

BACKGROUND: Although an effective vaccine has been available, measles still causes mast morbidity and mortality world widely. In Korea, a small number of measles cases have been reported through exposure to imported cases among young people with vaccine-induced measles immunity. Recently due to international migration including marriage, marriage migrants were the second-largest group of foreign population in Korea. Our study was carried out to obtain positive rate of measles antibody among married immigrant women from 12 countries in 10 Gun-Counties and 6 Cities, Korea. MATERIALS AND METHODS: A total of 547 blood samples were collected from maternal multicultural members from 12 countries. The measles-specific IgG antibody was measured by ELISA (Enzyme-linked immunosorbent assay; Enzygnost® Anti-measles virus/IgG, Siemens Healthcare Diagnostics Products GmbH, Marburg, Germany). We performed a simple logistic regression to test whether the measles antibody seroprevalence differed by participant age, location, or country of birth and then calculated the likelihood ratio statistics to determine whether measles antibody seroprevalence differed by country of birth. RESULTS: Overall positive measles seroprevalence was 75.3% (95% confidence interval: 71.7 - 78.9). Participants aged 20 - 24 years, 25 - 29 years, and 30 - 63 years has respective seropositivities of 52.5%, 55.3%, and 82.7%. In this study, the geometric mean titers of participants aged 21 - 29 years were slightly lower than those of participants aged over 30 years, which were 1,372 mIU/ml and 2,261 mIU/ml, respectively (average of total participants: 2,027 mIU/ml). CONCLUSION: The study provides detailed information about seroimmunity of the married immigrant population in Korea, which is important for measles elimination. Since the 1980s, most vaccine-preventable diseases including measles have been well-controlled. Nevertheless, sporadic measles outbreaks are still reported. Thus, special attention should be paid to the possible importation of infectious diseases such as measles by immigration.

A nystagmus extraction system using artificial intelligence for video-nystagmography.

Benign paroxysmal positional vertigo (BPPV), the most common vestibular disorder, is diagnosed by an examiner changing the posture of the examinee and inducing nystagmus. Among the diagnostic methods used to observe nystagmus, video-nystagmography has been widely used recently because it is non-invasive. A specialist with professional knowledge and training in vertigo diagnosis is needed to diagnose BPPV accurately, but the ratio of vertigo patients to specialists is too high, thus necessitating the need for automated diagnosis of BPPV. In this paper, a convolutional neural network-based nystagmus extraction system, ANyEye, optimized for video-nystagmography data is proposed. A pupil was segmented to track the exact pupil trajectory from real-world data obtained during field inspection. A deep convolutional neural network model was trained with the new video-nystagmography dataset for the pupil segmentation task, and a compensation algorithm was designed to correct pupil position. In addition, a slippage detection algorithm based on moving averages was designed to eliminate the motion artifacts induced by goggle slippage. ANyEye outperformed other eye-tracking methods including learning and non-learning-based algorithms with five-pixel error detection rate of 91.26%.

Room-temperature ammonia gas sensing via Au nanoparticle-decorated TiO2 nanosheets.

A high-performance gas sensor operating at room temperature is always favourable since it simplifies the device fabrication and lowers the operating power by eliminating a heater. Herein, we fabricated the ammonia (NH3) gas sensor by using Au nanoparticle-decorated TiO2 nanosheets, which were synthesized via two distinct processes: (1) preparation of monolayer TiO2 nanosheets through flux growth and a subsequent chemical exfoliation and (2) decoration of Au nanoparticles on the TiO2 nanosheets via hydrothermal method. Based on the morphological, compositional, crystallographic, and surface characteristics of this low-dimensional nano-heterostructured material, its temperature- and concentration-dependent NH3 gas-sensing properties were investigated. A high response of ~ 2.8 was obtained at room temperature under 20 ppm NH3 gas concentration by decorating Au nanoparticles onto the surface of TiO2 nanosheets, which generated oxygen defects and induced spillover effect as well.

CRISPR/Cas9-mediated gene editing to confer turnip mosaic virus (TuMV) resistance in Chinese cabbage (Brassica rapa).

Genome editing approaches, particularly the CRISPR/Cas9 technology, are becoming state-of-the-art for trait development in numerous breeding programs. Significant advances in improving plant traits are enabled by this influential tool, especially for disease resistance, compared to traditional breeding. One of the potyviruses, the turnip mosaic virus (TuMV), is the most widespread and damaging virus that infects Brassica spp. worldwide. We generated the targeted mutation at the eIF(iso)4E gene in the TuMV-susceptible cultivar "Seoul" using CRISPR/Cas9 to develop TuMV-resistant Chinese cabbage. We detected several heritable indel mutations in the edited T0 plants and developed T1 through generational progression. It was indicated in the sequence analysis of the eIF(iso)4E-edited T1 plants that the mutations were transferred to succeeding generations. These edited T1 plants conferred resistance to TuMV. It was shown with ELISA analysis the lack of accumulation of viral particles. Furthermore, we found a strong negative correlation (r = -0.938) between TuMV resistance and the genome editing frequency of eIF(iso)4E. Consequently, it was revealed in this study that CRISPR/Cas9 technique can expedite the breeding process to improve traits in Chinese cabbage plants.

Peli3 ablation ameliorates acetaminophen-induced liver injury through inhibition of GSK3ß phosphorylation and mitochondrial translocation.

The signaling pathways governing acetaminophen (APAP)-induced liver injury have been extensively studied. However, little is known about the ubiquitin-modifying enzymes needed for the regulation of APAP-induced liver injury. Here, we examined whether the Pellino3 protein, which has E3 ligase activity, is needed for APAP-induced liver injury and subsequently explored its molecular mechanism. Whole-body Peli3-/- knockout (KO) and adenovirus-mediated Peli3 knockdown (KD) mice showed reduced levels of centrilobular cell death, infiltration of immune cells, and biomarkers of liver injury, such as alanine aminotransferase (ALT) and aspartate aminotransferase (AST), upon APAP treatment compared to wild-type (WT) mice. Peli3 deficiency in primary hepatocytes decreased mitochondrial and lysosomal damage and reduced the mitochondrial reactive oxygen species (ROS) levels. In addition, the levels of phosphorylation at serine 9 in the cytoplasm and mitochondrial translocation of GSK3ß were decreased in primary hepatocytes obtained from Peli3-/- KO mice, and these reductions were accompanied by decreases in JNK phosphorylation and mitochondrial translocation. Pellino3 bound more strongly to GSK3ß compared with JNK1 and JNK2 and induced the lysine 63 (K63)-mediated polyubiquitination of GSK3ß. In rescue experiments, the ectopic expression of wild-type Pellino3 in Peli3-/- KO hepatocytes restored the mitochondrial translocation of GSK3ß, but this restoration was not obtained with expression of a catalytically inactive mutant of Pellino3. These findings are the first to suggest a mechanistic link between Pellino3 and APAP-induced liver injury through the modulation of GSK3ß polyubiquitination.

Green Chemistry for Crosslinking Biopolymers: Recent Advances in Riboflavin-Mediated Photochemistry.

Riboflavin (RF), which is also known as vitamin B2, is a water-soluble vitamin. RF is a nontoxic and biocompatible natural substance. It absorbs light (at wavelengths of 380 and 450 nm) in the presence of oxygen to form reactive singlet oxygen (1O2). The generated singlet oxygen acts as a photoinitiator to induce the oxidation of biomolecules, such as amino acids, proteins, and nucleotides, or to initiate chemical reactions, such as the thiol-ene reaction and crosslinking of tyramine and furfuryl groups. In this review, we focus on the chemical mechanism and utilization of the photochemistry of RF, such as protein crosslinking and hydrogel formation. Currently, the crosslinking method using RF as a photoinitiator is actively employed in ophthalmic clinics. However, a significant broadening is expected in its range of applications, such as in tissue engineering and drug delivery.

Associations of Serum Vitamin D Concentration with Cardiovascular Risk Factors and the Healthy Lifestyle Score.

Vitamin D status is reportedly associated with risk factors for cardiovascular disease (CVD), although conflicting data have been generated. The healthy lifestyle score (HLS) was formulated as a primary approach toward preventing CVD; however, data on the association between the HLS and vitamin D status remain insufficient. This study aimed to investigate the associations of CVD risk factors and the HLS with serum 25-hydroxyvitamin D concentration in adults who participated in a national survey. HLS components, including body mass index, smoking status, alcohol consumption, physical activity, and dietary pattern, as well as other risk factors, including diabetes mellitus (DM), hypertension (HTN), and dyslipidemia (DL), were fitted in multiple linear regression models to determine their association with vitamin D status. DM, HTN, and DL were inversely associated whereas a balanced dietary pattern, alcohol consumption, and physical activity were positively associated with serum vitamin D concentration (p < 0.01). Furthermore, a strong association was observed between the total HLS and serum vitamin D concentration (p for trend <0.01); the regression coefficient estimate (95% confidence interval) for the highest score was 1.41 (0.65, 2.17) (p < 0.01) compared with that for the lowest. These findings suggest that CVD risk factors and the HLS may reflect vitamin D status.

Immune Responses to Plant-Derived Recombinant Colorectal Cancer Glycoprotein EpCAM-FcK Fusion Protein in Mice.

Epidermal cell adhesion molecule (EpCAM) is a tumor-associated antigen (TAA), which has been considered as a cancer vaccine candidate. The EpCAM protein fused to the fragment crystallizable region of immunoglobulin G (IgG) tagged with KDEL endoplasmic reticulum (ER) retention signal (EpCAM-FcK) has been successfully expressed in transgenic tobacco (Nicotiana tabacum cv. Xanthi) and purified from the plant leaf. In this study, we investigated the ability of the plant-derived EpCAM-FcK (EpCAM-FcKP) to elicit an immune response in vivo. The animal group injected with the EpCAM-FcKP showed a higher differentiated germinal center (GC) B cell population (~9%) compared with the animal group injected with the recombinant rhEpCAM-Fc chimera (EpCAM-FcM). The animal group injected with EpCAM-FcKP (~42%) had more differentiated T follicular helper cells (Tfh) than the animal group injected with EpCAM-FcM (~7%). This study demonstrated that the plant-derived EpCAM-FcK fusion antigenic protein induced a humoral immune response in mice.

A Prediction Algorithm for Hypoglycemia Based on Support Vector Machine Using Glucose Level and Electrocardiogram.

A prediction algorithm for hypoglycemic events is proposed using glucose levels and electrocardiogram (ECG) with support vector machine (SVM). We extracted the corrected QT interval and five heart rate variability parameters from the ECG, along with glucose level from a continuous glucose monitoring system (CGMS). This feature set is used as input to the SVM, and hypoglycemic events are predicted every 5 min using the trained SVM model for up to 30 min in advance. The proposed algorithm was developed and evaluated for nine Type-1 diabetes patients in the D1NAMO dataset. The prediction sensitivity, specificity, and accuracy values for the test set were 91.1%, 87.0%, and 89.0% (10 min before); 88.0%, 84.3%, and 86.2% (20 min before); 80.1%, 83.3%, and 81.7% (30 min before), respectively. These results show higher performance of the proposed method compared to previous studies and suggest the possibility of predicting hypoglycemia in advance.

SOCS3 Attenuates Dexamethasone-Induced M2 Polarization by Down-Regulation of GILZ via ROS- and p38 MAPK-Dependent Pathways.

Suppressors of cytokine signaling (SOCS) have emerged as potential regulators of macrophage function. We have investigated mechanisms of SOCS3 action on type 2 macrophage (M2) differentiation induced by glucocorticoid using human monocytic cell lines and mouse bone marrow-derived macrophages. Treatment of THP1 monocytic cells with dexamethasone (Dex) induced ROS generation and M2 polarization promoting IL-10 and TGF-ß production, while suppressing IL-1ß, TNF-α and IL-6 production. SOCS3 over-expression reduced, whereas SOCS3 ablation enhanced IL-10 and TGF-ß induction with concomitant regulation of ROS. As a mediator of M2 differentiation, glucocorticoid-induced leucine zipper (GILZ) was down-regulated by SOCS3 and up-regulated by shSOCS3. The induction of GILZ and IL-10 by Dex was dependent on ROS and p38 MAPK activity. Importantly, GILZ ablation led to the inhibition of ROS generation and anti-inflammatory cytokine induction by Dex. Moreover, GILZ knock-down negated the up-regulation of IL-10 production induced by shSOCS3 transduction. Our data suggest that SOCS3 targets ROS- and p38-dependent GILZ expression to suppress Dex-induced M2 polarization.