Ultrastable 3D Heterogeneous Integration via N-Heterocyclic Carbene Self-Assembled Nanolayers.

The commercialization of 3D heterogeneous integration through hybrid bonding has accelerated, and accordingly, Cu-polymer bonding has gained significant attention as a means of overcoming the limitations of conventional Cu-SiO2 hybrid bonding, offering high compatibility with other fabrication processes. Polymers offer robust bonding strength and a low dielectric constant, enabling high-speed signal transmission with high reliability, but suffer from low thermomechanical stability. Thermomechanical stability of polymers was not achieved previously because of thermal degradation and unstable anchoring. To overcome these limitations, wafer-scale Cu-polymer bonding via N-heterocyclic carbene (NHC) nanolayers was presented for 3D heterogeneous integration, affording ultrastable packing density, crystallinity, and thermal properties. NHC nanolayers were deposited on copper electrodes via electrochemical deposition, and wafer-scale 3D heterogeneous integration was achieved by adhesive bonding at 170 °C for 1 min. Ultrastable conductivity and thermomechanical properties were observed by the spatial mapping of conductivity, work function, and force-distance curves. With regard to the characterization of NHC nanolayers, low-temperature bonding, robust corrosion inhibition, enhanced electrical conductivity, back-end-of-line process compatibility, and fabrication process reduction, NHC Cu/polymer bonding provides versatile advances in 3D heterogeneous integration, indicating that NHC Cu/polymer bonding can be utilized as a platform for future 3D vertical chip architectures.

Evaporation-Driven Energy Generation Using an Electrospun Polyacrylonitrile Nanofiber Mat with Different Support Substrates.

Water evaporation-driven energy harvesting is an emerging mechanism for contributing to green energy production with low cost. Herein, we developed polyacrylonitrile (PAN) nanofiber-based evaporation-driven electricity generators (PEEGs) to confirm the feasibility of utilizing electrospun PAN nanofiber mats in an evaporation-driven energy harvesting system. However, PAN nanofiber mats require a support substrate to enhance its durability and stability when it is applied to an evaporation-driven energy generator, which could have additional effects on generation performance. Accordingly, various support substrates, including fiberglass, copper, stainless mesh, and fabric screen, were applied to PEEGs and examined to understand their potential impacts on electrical generation outputs. As a result, the PAN nanofiber mats were successfully converted to a hydrophilic material for an evaporation-driven generator by dip-coating them in nanocarbon black (NCB) solution. Furthermore, specific electrokinetic performance trends were investigated and the peak electricity outputs of Voc were recorded to be 150.8, 6.5, 2.4, and 215.9 mV, and Isc outputs were recorded to be 143.8, 60.5, 103.8, and 121.4 µA, from PEEGs with fiberglass, copper, stainless mesh, and fabric screen substrates, respectively. Therefore, the implications of this study would provide further perspectives on the developing evaporation-induced electricity devices based on nanofiber materials.

Cyclo His-Pro Attenuates Muscle Degeneration in Murine Myopathy Models.

Among the inherited myopathies, a group of muscular disorders characterized by structural and metabolic impairments in skeletal muscle, Duchenne muscular dystrophy (DMD) stands out for its devastating progression. DMD pathogenesis is driven by the progressive degeneration of muscle fibers, resulting in inflammation and fibrosis that ultimately affect the overall muscle biomechanics. At the opposite end of the spectrum of muscle diseases, age-related sarcopenia is a common condition that affects an increasing proportion of the elderly. Although characterized by different pathological mechanisms, DMD and sarcopenia share the development of progressive muscle weakness and tissue inflammation. Here, the therapeutic effects of Cyclo Histidine-Proline (CHP) against DMD and sarcopenia are evaluated. In the mdx mouse model of DMD, it is shown that CHP restored muscle contractility and force production, accompanied by the reduction of fibrosis and inflammation in skeletal muscle. CHP furthermore prevented the development of cardiomyopathy and fibrosis in the diaphragm, the two leading causes of death for DMD patients. CHP also attenuated muscle atrophy and functional deterioration in a mouse model of age-related sarcopenia. These findings from two different models of muscle dysfunction hence warrant further investigation into the effects of CHP on muscle pathologies in animal models and eventually in patients.

A ResNet-LSTM hybrid model for predicting epileptic seizures using a pretrained model with supervised contrastive learning.

In this paper, we propose a method for predicting epileptic seizures using a pre-trained model utilizing supervised contrastive learning and a hybrid model combining residual networks (ResNet) and long short-term memory (LSTM). The proposed training approach encompasses three key phases: pre-processing, pre-training as a pretext task, and training as a downstream task. In the pre-processing phase, the data is transformed into a spectrogram image using short time Fourier transform (STFT), which extracts both time and frequency information. This step compensates for the inherent complexity and irregularity of electroencephalography (EEG) data, which often hampers effective data analysis. During the pre-training phase, augmented data is generated from the original dataset using techniques such as band-stop filtering and temporal cutout. Subsequently, a ResNet model is pre-trained alongside a supervised contrastive loss model, learning the representation of the spectrogram image. In the training phase, a hybrid model is constructed by combining ResNet, initialized with weight values from the pre-trained model, and LSTM. This hybrid model extracts image features and time information to enhance prediction accuracy. The proposed method's effectiveness is validated using datasets from CHB-MIT and Seoul National University Hospital (SNUH). The method's generalization ability is confirmed through Leave-one-out cross-validation. From the experimental results measuring accuracy, sensitivity, and false positive rate (FPR), CHB-MIT was 91.90%, 89.64%, 0.058 and SNUH was 83.37%, 79.89%, and 0.131. The experimental results demonstrate that the proposed method outperforms the conventional methods.

Abused drug-induced intracranial self-stimulation is correlated with the alteration of dopamine transporter availability in the medial prefrontal cortex and nucleus accumbens of mice.

Intracranial self-stimulation (ICSS) of the medial forebrain bundle in mice is an experimental model use to assess the relative potential of reward-seeking behaviors. Here, we used the ICSS model to evaluate the abuse potential of 18 abused drugs: 3-Fluoroethamphetamine (3-FEA); methylphenidate; cocaine; dextroamphetamine; alpha-Pyrrolidinobutyrophenone (α-PBT); 4'-Fluoro-4-methylaminorex (4-FPO); methamphetamine; larocaine; phentermine; paramethoxymethamphetamine (PMMA); phendimetrazine; N-(1-adamantyl)-1-pentyl-1H-indazole-3-carboxamide (AKB-48); Naphthalen-1-yl-(4-pentyloxynaphthalen-1-yl)methanone (CB-13); 4-Ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210); Naphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-018); N-(ortho-methoxybenzyl)-4-ethylamphetamine (4-EA-NBOMe); N-[(2-Methoxyphenyl)methyl]-N-methyl-1-(4-methylphenyl)propan-2-amine (4-MMA-NBOMe); and 1-[1-(4-methoxyphenyl)cyclohexyl]piperidine (4-MeO-PCP). We determined dopamine transporter (DAT) availability in the medial prefrontal cortex (mPFC), striatum, and nucleus accumbens (NAc) after drug treatment. DAT availability in the mPFC and NAc significantly correlated with the ICSS threshold after drug treatment. Extracellular dopamine and calcium levels in PC-12 cells were measured following drug treatment. After drug treatment, Spearman rank and Pearson correlation analyses showed a significant difference between the extracellular dopamine level and the ICSS threshold. After drug treatment, Spearman rank correlation analysis showed a significant correlation between Ca2+ signaling and the ICSS threshold. A positive correlation exists between the ICSS threshold and DAT availability in the mPFC and NAc provoked by abused drugs. The relative potential of drug-induced reward-seeking behavior may be related to DAT availability-mediated extracellular dopamine levels in the mPFC and NAc.

Inhibition of chloride intracellular channel protein 1 (CLIC1) ameliorates liver fibrosis phenotype by activating the Ca2+-dependent Nrf2 pathway.

Persistent damage to liver cells leads to liver fibrosis, which is characterized by the accumulation of scar tissue in the liver, ultimately leading to cirrhosis and serious complications. Because it is difficult to reverse cirrhosis once it has progressed, the primary focus has been on preventing the progression of liver fibrosis. However, studies on therapeutic agents for liver fibrosis are still lacking. Here, we investigated that the natural dipeptide cyclic histidine-proline (CHP, also known as diketopiperazine) shows promising potential as a therapeutic agent in models of liver injury by inhibiting the progression of fibrosis through activation of the Nrf2 pathway. To elucidate the underlying biological mechanism of CHP, we used the Cellular Thermal Shift Assay (CETSA)-LC-MS/MS, a label-free compound-based target identification platform. Chloride intracellular channel protein 1 (CLIC1) was identified as a target whose thermal stability is increased by CHP treatment. We analyzed the direct interaction of CHP with CLIC1 which revealed a potential interaction between CHP and the E228 residue of CLIC1. Biological validation experiments showed that knockdown of CLIC1 mimicked the antioxidant effect of CHP. Further investigation using a mouse model of CCl4-induced liver fibrosis in wild-type and CLIC1 KO mice revealed the critical involvement of CLIC1 in mediating the effects of CHP. Taken together, our results provide evidence that CHP exerts its anti-fibrotic effects through specific binding to CLIC1. These insights into the mechanism of action of CHP may pave the way for the development of novel therapeutic strategies for fibrosis-related diseases.

Cyclo(His-Pro): A further step in the management of steatohepatitis.

Background & Aims: Non-alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) have become the world's most common liver diseases, placing a growing strain on healthcare systems worldwide. Nonetheless, no effective pharmacological treatment has been approved. The naturally occurring compound cyclo histidine-proline (His-Pro) (CHP) is an interesting candidate for NAFLD management, given its safety profile and anti-inflammatory effects. Methods: Two different mouse models of liver disease were used to evaluate protective effects of CHP on disease progression towards fibrosis: a model of dietary NAFLD/NASH, achieved by thermoneutral housing (TN) in combination with feeding a western diet (WD), and liver fibrosis caused by repeated injections with carbon tetrachloride (CCl4). Results: Treatment with CHP limited overall lipid accumulation, lowered systemic inflammation, and prevented hyperglycaemia. Histopathology and liver transcriptomics highlighted reduced steatosis and demonstrated remarkable protection from the development of inflammation and fibrosis, features which herald the progression of NAFLD. We identified the extracellular signal-regulated kinase (ERK) pathway as an early mediator of the cellular response to CHP. Conclusions: CHP was active in both the preventive and therapeutic setting, reducing liver steatosis, fibrosis, and inflammation and improving several markers of liver disease. Impact and implications: Considering the incidence and the lack of approved treatments, it is urgent to identify new strategies that prevent and manage NAFLD. CHP was effective in attenuating NAFLD progression in two animal models of the disease. Overall, our work points to CHP as a novel and effective strategy for the management of NAFLD, fuelling optimism for potential clinical studies.

Isolation and characterization of single domain antibodies from banded houndshark (Triakis scyllium) targeting SARS-CoV-2 spike RBD protein.

The COVID-19 pandemic has significantly impacted human health for three years. To mitigate the spread of SARS-CoV-2, the development of neutralizing antibodies has been accelerated, including the exploration of alternative antibody formats such as single-domain antibodies. In this study, we identified variable new antigen receptors (VNARs) specific for the receptor binding domain (RBD) of SARS-CoV-2 by immunizing a banded houndshark (Triakis scyllium) with recombinant wild-type RBD. Notably, the CoV2NAR-1 clone showed high binding affinities in the nanomolar range to various RBDs and demonstrated neutralizing activity against SARS-CoV-2 pseudoviruses. These results highlight the potential of the banded houndshark as an animal model for the development of VNAR-based therapeutics or diagnostics against future pandemics.

CycloZ Improves Hyperglycemia and Lipid Metabolism by Modulating Lysine Acetylation in KK-Ay Mice.

BACKGRUOUND: CycloZ, a combination of cyclo-His-Pro and zinc, has anti-diabetic activity. However, its exact mode of action remains to be elucidated. METHODS: KK-Ay mice, a type 2 diabetes mellitus (T2DM) model, were administered CycloZ either as a preventive intervention, or as a therapy. Glycemic control was evaluated using the oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) levels. Liver and visceral adipose tissues (VATs) were used for histological evaluation, gene expression analysis, and protein expression analysis. RESULTS: CycloZ administration improved glycemic control in KK-Ay mice in both prophylactic and therapeutic studies. Lysine acetylation of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, liver kinase B1, and nuclear factor-κB p65 was decreased in the liver and VATs in CycloZ-treated mice. In addition, CycloZ treatment improved mitochondrial function, lipid oxidation, and inflammation in the liver and VATs of mice. CycloZ treatment also increased the level of ß-nicotinamide adenine dinucleotide (NAD+), which affected the activity of deacetylases, such as sirtuin 1 (Sirt1). CONCLUSION: Our findings suggest that the beneficial effects of CycloZ on diabetes and obesity occur through increased NAD+ synthesis, which modulates Sirt1 deacetylase activity in the liver and VATs. Given that the mode of action of an NAD+ booster or Sirt1 deacetylase activator is different from that of traditional T2DM drugs, CycloZ would be considered a novel therapeutic option for the treatment of T2DM.

Vaccinia-related kinase 2 variants differentially affect breast cancer growth by regulating kinase activity.

Genetic information is transcribed from genomic DNA to mRNA, which is then translated into three-dimensional proteins. mRNAs can undergo various post-transcriptional modifications, including RNA editing that alters mRNA sequences, ultimately affecting protein function. In this study, RNA editing was identified at the 499th base (c.499) of human vaccinia-related kinase 2 (VRK2). This RNA editing changes the amino acid in the catalytic domain of VRK2 from isoleucine (with adenine base) to valine (with guanine base). Isoleucine-containing VRK2 has higher kinase activity than the valine-containing VRK2, which leads to an increase in tumor cell proliferation. Earlier we reported that VRK2 directly interacts with dystrobrevin-binding protein (dysbindin) and results in reducing its stability. Herein, we demonstrate that isoleucine-containing VRK2 decreases the level of dysbindin than valine-containing VRK2. Dysbindin interacts with cyclin D and thereby regulates its expression and function. The reduction in the level of dysbindin by isoleucine-containing VRK2 further enhances the cyclin D expression, resulting in increased tumor growth and reduction in survival rates. It has also been observed that in patient samples, VRK2 level was elevated in breast cancer tissue compared to normal breast tissue. Additionally, the isoleucine form of VRK2 exhibited a greater increase in breast cancer tissue. Therefore, it is concluded that VRK2, especially dependent on the 167th variant amino acid, can be one of the indexes of tumor progression and proliferation.

An Fc variant with two mutations confers prolonged serum half-life and enhanced effector functions on IgG antibodies.

The pH-selective interaction between the immunoglobulin G (IgG) fragment crystallizable region (Fc region) and the neonatal Fc receptor (FcRn) is critical for prolonging the circulating half-lives of IgG molecules through intracellular trafficking and recycling. By using directed evolution, we successfully identified Fc mutations that improve the pH-dependent binding of human FcRn and prolong the serum persistence of a model IgG antibody and an Fc-fusion protein. Strikingly, trastuzumab-PFc29 and aflibercept-PFc29, a model therapeutic IgG antibody and an Fc-fusion protein, respectively, when combined with our engineered Fc (Q311R/M428L), both exhibited significantly higher serum half-lives in human FcRn transgenic mice than their counterparts with wild-type Fc. Moreover, in a cynomolgus monkey model, trastuzumab-PFc29 displayed a superior pharmacokinetic profile to that of both trastuzumab-YTE and trastuzumab-LS, which contain the well-validated serum half-life extension Fcs YTE (M252Y/S254T/T256E) and LS (M428L/N434S), respectively. Furthermore, the introduction of two identified mutations of PFc29 (Q311R/M428L) into the model antibodies enhanced both complement-dependent cytotoxicity and antibody-dependent cell-mediated cytotoxicity activity, which are triggered by the association between IgG Fc and Fc binding ligands and are critical for clearing cancer cells. In addition, the effector functions could be turned off by combining the two mutations of PFc29 with effector function-silencing mutations, but the antibodies maintained their excellent pH-dependent human FcRn binding profile. We expect our Fc variants to be an excellent tool for enhancing the pharmacokinetic profiles and potencies of various therapeutic antibodies and Fc-fusion proteins.

Gossypetin ameliorates 5xFAD spatial learning and memory through enhanced phagocytosis against Aß.

BACKGROUND: Microglia are the resident immune cells found in our brain. They have a critical role in brain maintenance. Microglia constantly scavenge various waste materials in the brain including damaged or apoptotic neurons and Aß. Through phagocytosis of Aß, microglia prevent the accumulation of Aß plaque in the brain. However, in Alzheimer's disease (AD) patients, chronic exposure to Aß makes microglia to become exhausted, which reduces their phagocytic activity against Aß. Since microglia play an important role in Aß clearance, enhancing microglial phagocytic activity against Aß is a promising target for AD treatment. Therefore, there is a great need for therapeutic candidate that enhances microglial Aß clearance while inhibiting microglia's pathogenic properties. METHODS: In vivo studies were conducted with 5xFAD AD model mice by treating gossypetin for 13 weeks through intragastric administration. Their spatial learning and memory were evaluated through behavior tests such as Y-maze and Morris Water Maze test. Hippocampus and cortex were acquired from the sacrificed mice, and they were used for histological and biochemical analysis. Also, mouse tissues were dissociated into single cells for single-cell RNA sequencing (scRNA-seq) analysis. Transcriptome of microglial population was analyzed. Mouse primary microglia and BV2 mouse microglial cell line were cultured and treated with fluorescent recombinant Aß to evaluate whether their phagocytic activity is affected by gossypetin. RESULTS: Gossypetin treatment improved the spatial learning and memory of 5xFAD by decreasing Aß deposition in the hippocampus and cortex of 5xFAD. Gossypetin induced transcriptomic modulations in various microglial subpopulations, including disease-associated microglia. Gossypetin enhanced phagocytic activity of microglia while decreasing their gliosis. Gossypetin also increased MHC II+ microglial population. CONCLUSIONS: Gossypetin showed protective effects against AD by enhancing microglial Aß phagocytosis. Gossypetin appears to be a novel promising therapeutic candidate against AD.

The designer benzodiazepine, flubromazepam, induces reward-enhancing and cardiotoxic effects in rodents.

The use of many benzodiazepines is controlled worldwide due to their high likelihood of abuse and potential adverse effects. Flubromazepam-a designer benzodiazepine-is a long-acting gamma-aminobutyric acid subtype A receptor agonist. There is currently a lack of scientific evidence regarding the potential for flubromazepam dependence or other adverse effects. This study aimed to evaluate the dependence potential, and cardiotoxicity via confirmation of the QT and RR intervals which are the factors on the electrical properties of the heart of flubromazepam in rodents. Using a conditioned place preference test, we discovered that mice treated intraperitoneally with flubromazepam (0.1 mg/kg) exhibited a significant preference for the flubromazepam-paired compartment, suggesting a potential for flubromazepam dependence. In addition, we observed several cardiotoxic effects of flubromazepam; 100-µM flubromazepam reduced cell viability, increased RR intervals but not QT intervals in the electrocardiography measurements, and considerably inhibited potassium channels in a human ether-à-go-go-related gene assay. Collectively, these findings suggest that flubromazepam may have adverse effects on psychological and cardiovascular health, laying the foundation for further efforts to list flubromazepam as a controlled substance at both national and international levels.

8-Methoxybutin inhibits α-MSH induced melanogenesis and proliferation of skin melanoma by suppression of the transactivation activity of microphthalmia-associated transcription factor.

Microphthalmia-associated transcription factor (MITF) is highly expressed in melanocytes and is the main regulator of melanogenesis and melanocyte cell fate. Although MITF is important for the differentiation and development of melanocytes, it is also considered an oncogene of skin melanoma. Based on these findings, MITF could be an attractive therapeutic target for skin cancer intervention. This study identified 8-methoxybutin as an inhibitor of MITF and investigated the underlying mechanism. 8-Methoxybutin inhibited α-MSH-induced melanogenesis in murine melanoma cells (B16F10) and skin melanoma proliferation by reducing melanogenic gene expression via blockade of the transactivation activity of MITF. In silico docking analysis and pull-down analysis suggested that 8-methoxybutin binds to the DNA-binding domain of MITF and further inhibits its binding to the E-box in the promoter of target genes, including tyrosinase. In addition, 8-methoxybutin suppressed growth of skin melanoma in a xenograft mouse model. These results indicate that 8-methoxybutin has potential as a therapeutic agent for hyperpigmentation disorder and skin cancer. SIGNIFICANCE STATEMENT: 8-Methoxybutin inhibits MITF transactivation activity resulting suppression of melanogenesis and skin melanoma growth.

Protective Effect of Alpinia oxyphylla Fruit against tert-Butyl Hydroperoxide-Induced Toxicity in HepG2 Cells via Nrf2 Activation and Free Radical Scavenging and Its Active Molecules.

Alpinia oxyphylla Miq. (Zingiberaceae) extract exerts protective activity against tert-butyl hydroperoxide-induced toxicity in HepG2 cells, and the antioxidant response element (ARE) luciferase activity increased 6-fold at 30 µg/mL in HepG2 cells transiently transfected with ARE-luciferase. To identify active molecules, activity-guided isolation of the crude extract led to four sesquiterpenes (1, 2, 5, 6) and two diarylheptanoids (3 and 4) from an n-hexane extract and six sesquiterpenes (7-12) from an ethyl acetate extract. Chemical structures were elucidated by one-dimensional, two-dimensional nuclear magnetic resonance (1D-, 2D-NMR), and mass (MS) spectral data. Among the isolated compounds, eudesma-3,11-dien-2-one (2) promoted the nuclear accumulation of nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and increased the promoter property of the ARE. Diarylheptanoids, yakuchinone A (3), and 5'-hydroxyl-yakuchinone A (4) showed radical scavenging activity in 2,2-diphenyl-1-picrylhydrazyl (DPPH) and 3-ethylbenzothiazoline-6-sulphonic acid (ABTS) assays. Furthermore, optimization of extraction solvents (ratios of water and ethanol) was performed by comparison of contents of active compounds, ARE-inducing activity, radical scavenging activity, and HepG2 cell protective activity. As a result, 75% ethanol was the best solvent for the extraction of A. oxyphylla fruit. This study demonstrated that A. oxyphylla exerted antioxidant effects via the Nrf2/HO-1 (heme oxygenase-1) pathway and radical scavenging along with active markers eudesma-3,11-dien-2-one (2) and yakuchinone A (3).

Peroxiredoxin 6 Overexpression Induces Anxiolytic and Depression-Like Behaviors by Regulating the Serotonergic Pathway in Mice.

Peroxiredoxin 6 (PRDX6) is a bifunctional protein with both glutathione peroxidase and calcium-independent phospholipase activity. Recently, we reported that PRDX6 plays an important role in dopaminergic neurodegeneration in Parkinson's disease. However, the relationship between PRDX6 function and emotional behavior remains elusive. In the present study, we examined depression- and anxiety-like behaviors in PRDX6-overexpressing transgenic (PRDX6-Tg) mice using the forced swim test, tail suspension test, open field paradigm, and elevated plus-maze. PRDX6-Tg mice exhibited depression-like behaviors and low anxiety. In particular, female PRDX6-Tg mice exhibited anxiolytic behavior in the open field test. Furthermore, the serotonin content in the cortex and 5-hydroxytryptophan-induced head twitch response were both reduced in PRDX6-Tg mice. Interestingly, levels of dopa decarboxylase expression in the cortex were decreased in male PRDX6-Tg mice but not in female mice. Our findings provide novel insights into the role of PRDX6 in 5-HT synthesis and suggest that PRDX6 overexpression can induce depression-like behaviors via downregulation of the serotonergic neuronal system.

Experimental and Digimat-FE Based Representative Volume Element Analysis of Dye-Mixed Colored Resin and Carbon Fiber.

Recently, the automobile industry has demanded weight reduction, so research on materials is being actively conducted. Among this research, carbon fiber-reinforced composite materials are being studied a lot in the automobile industry due to their excellent mechanical properties, chemical resistance, and heat resistance. However, carbon fiber-reinforced composite materials have disadvantages, in that they are not free from color selection, and have weak interfacial bonding strength. In this study, a colored epoxy resin was prepared by mixing epoxy-which is a thermosetting resin according to the pigment concentration (0.1, 0.3, 0.5, 1.0 wt%)-and curing shrinkage. Thermal expansion characteristics were analyzed and the concentration of 0.5 wt% pigment showed the lowest shrinkage and thermal expansion characteristics. In addition, to measure the interfacial shear strength (IFSS) of the carbon fiber and the colored epoxy resin, the IFSS was obtained by performing a microdroplet debonding test, and the strength of the pigment concentration of 0.5 wt% was reduced to a relatively low level. Through these experiments, it was determined that an epoxy resin in which 0.5 wt% pigment is mixed is the optimal condition. Finally, using the composite material modeling software (Digimat 2020.0), the representative volume element (RVE) of the meso-scale was set, and interfacial properties of carbon fibers and colored epoxy resins were analyzed by interworking with general-purpose finite element analysis software (Abaqus CAE).

Investigation of gender differences in multivariate associations between physical activity and psychological distress.

ObjectiveThe study examined gender differences in the relationship between physical activity (PA) and psychological distress in college students. Participants: The participants were recruited at a university in the U.S. (91 subjects) and another university in South Korea (164 subjects) in November 2016. Methods: The subjects participated in an online survey. Results: PA had a significant association with a decrease of Psychological Distress only in women (ß = -.27). Moreover, Social Support for PA (ß = -.11) and PA Self-Efficacy (ß = -.08) had an indirect effect on Psychological Distress only in Women. Conclusions: Only women showed a significant association between PA and psychological distress. PA Self-Efficacy and Social Support for PA were indirectly associated with Psychological Distress only in women. Moreover, women could be motivated to be physically active by both Social Support for PA and PA Self-Efficacy, whereas men could be motivated to exercise by PA Self-Efficacy.

Inflammation resolution circuits are uncoupled in acute sepsis and correlate with clinical severity.

Sepsis is a critical illness characterized by dysregulated inflammatory responses lacking counter-regulation. Specialized proresolving mediators are agonists for antiinflammation and for promoting resolution, and they are protective in preclinical sepsis models. Here, in human sepsis, we mapped resolution circuits for the specialized proresolving mediators resolvin D1 and resolvin D2 in peripheral blood neutrophils and monocytes, their regulation of leukocyte activation and function ex vivo, and their relationships to measures of clinical severity. Neutrophils and monocytes were isolated from healthy subjects and patients with sepsis by inertial microfluidics and resolvin D1 and resolvin D2 receptor expression determined by flow cytometry. The impact of these resolvins on leukocyte activation was determined by isodielectric separation and leukocyte function by stimulated phagolysosome formation. Leukocyte proresolving receptor expression was significantly higher in sepsis. In nanomolar concentrations, resolvin D1 and resolvin D2 partially reversed sepsis-induced changes in leukocyte activation and function. Principal component analyses of leukocyte resolvin receptor expression and responses differentiated sepsis from health and were associated with measures of sepsis severity. These findings indicate that resolvin D1 and resolvin D2 signaling for antiinflammation and resolution are uncoupled from leukocyte activation in early sepsis and suggest that indicators of diminished resolution signaling correlate with clinical disease severity.

Examining the effects of social determinants of health on COVID-19 related stress, family's stress and discord, and personal diagnosis of COVID-19.

BACKGROUND: COVID-19 is a significant threat to people's mental health and social well-being. The research examined the effects of social determinants of health on COVID-19 related stress, family's stress and discord, and personal diagnosis of COVID-19. METHODS: In November 2020, the data collection was conducted from 97 counties in North Carolina (N = 1500). Adult residents in North Carolina completed an online COVID-19 impact survey conducted using quota-based sampling on race, income, and county to provide a rapid quasi-representative assessment of COVID impact. The study investigated the variables in a structural model through structural equation modeling. For data analysis, IBM SPSS 26 and AMOS 27 were deployed. RESULTS: Social determinants of health had direct effects on COVID-19 related stress (ß = 0.66, p < 0.001, r 2 = 0.43), family's stress and discord (ß = 0.73, p < 0.001, r 2 = 0.53), and personal diagnosis of COVID-19 (ß = 0.52, p < 0.001, r 2 = 0.27). These findings indicate that underserved populations experienced higher stress and discord at both individual and family levels and more severe COVID-19 symptoms. Moreover, black participants, whose family income and food access declined significantly more, had worse stress, discord, and COVID-19 symptoms than white participants. CONCLUSIONS: The study suggests that the government and health professionals enhance mental health and family support service accessibility for underprivileged populations through telehealth and community health programs to prevent associated social and health issues such as suicide, violence, and cancer.