Search

Abstract Background Phospholipase C gamma 1 (PLCγ1) is an important mediator of the T cell receptor (TCR) and growth factor signaling. PLCγ1 is activated by Src family kinases (SFKs) and produces inositol 1,4,5-triphosphate (InsP3) from phosphatidylinositol 4,5-bisphosphate (PIP2). Inositol polyphosphate multikinase (IPMK) is a pleiotropic enzyme with broad substrate specificity and non-catalytic activities that mediate various functional protein-protein interactions. Therefore, IPMK plays critical functions in key biological events such as cell growth. However, the contribution of IPMK to the activation of PLCγ1 in TCR signaling remains mostly unelucidated. The current study aimed to elucidate the functions of IPMK in TCR signaling and to uncover the mode of IPMK-mediated signaling action in PLCγ1 activation. Methods Concanavalin A (ConA)-induced acute hepatitis model was established in CD4+ T cell-specific IPMK knockout mice (IPMKΔCD4). Histological analysis was performed to assess hepatic injury. Primary cultures of naïve CD4+ T cells were used to uncover the role of mechanisms of IPMK in vitro. Western blot analysis, quantitative real-time PCR, and flow cytometry were performed to analyze the TCR-stimulation-induced PLCγ1 activation and the downstream signaling pathway in naïve CD4+ T cells. Yeast two-hybrid screening and co-immunoprecipitation were conducted to identify the IPMK-binding proteins and protein complexes. Results IPMKΔCD4 mice showed alleviated ConA-induced acute hepatitis. CD4+ helper T cells in these mice showed reduced PLCγ1 Y783 phosphorylation, which subsequently dampens calcium signaling and IL-2 production. IPMK was found to contribute to PLCγ1 activation via the direct binding of IPMK to Src-associated substrate during mitosis of 68 kDa (Sam68). Mechanistically, IPMK stabilizes the interaction between Sam68 and to PLCγ1, thereby promoting PLCγ1 phosphorylation. Interfering this IPMK-Sam68 binding interaction with IPMK dominant-negative peptides impaired PLCγ1 phosphorylation. Conclusions Our results demonstrate that IPMK non-catalytically promotes PLCγ1 phosphorylation by stabilizing the PLCγ1–Sam68 complex. Targeting IPMK in CD4+ T cells may be a promising strategy for managing immune diseases caused by excessive stimulation of TCR.

Although biofilms contribute to bacterial tolerance to desiccation and survival in low-moisture foods, the molecular mechanisms underlying biofilm formation have not been fully understood. This study created a mutant library from Salmonella Enteritidis using mini-Tn10 transposon mutagenesis. The biofilm-forming potential of acquired mutants was assessed before the genomic DNA of the mutants that formed significantly (p ≤ 0.05) less biofilm mass than their wildtype parent strain was extracted for deep DNA sequencing. The gene of each mutant interrupted by mini-Tn10 insertion was identified by aligning obtained sequencing data with the reference Genbank sequences using a BLAST search. Sixty-four mutant colonies were selected, and five mutants that formed the least amount of biofilm mass compared to the wildtype parent strain were selected for sequencing analysis. The results of the BLAST search revealed that the gene interrupted by mini-Tn10 in each mutant is responsible for the biosynthesis of aldehyde dehydrogenase (EutE), cysteine desulfurase (SufS or SufE), a transporter protein, porin OmpL, and a ribbon–helix–helix protein from the CopG family, respectively. Knock-off mutant construction is a possible approach to verify the potential of the identified genes to serve as targets of antimicrobial intervention to control Salmonella colonization on low-moisture foods and in their production environment.

Background: Emotional abuse during childhood and adolescence is thought to be associated with the brain; however, the neural mechanism underlying the cognitive process remains unknown. Therefore, we aimed to investigate the mediating effect of negative automatic thoughts on the relationship between emotional abuse and resting-state functional connectivity (rsFC) during adolescence. Method: Our community sample included 54 adolescents aged 13–17 years in the statistical analysis. Resting-state functional and structural magnetic resonance imaging (MRI) was performed, while emotional abuse and negative automatic thoughts were assessed using self-reported scales. A mediation analysis was used to assess the contributions of early traumatic events and negative automatic thoughts to resting functional connectivity. Result: Higher negative automatic thoughts were associated with lower connectivity in the context of greater emotional abuse (i.e., suppression effect). Thus, the relationships between emotional abuse and connectivity in the precuneus (pCun)-medial prefrontal cortex, parahippocampal cortex-extrastriate cortex, and temporal cortex-temporal pole were decreased by negative automatic thoughts. In contrast, functional connections in the pCun-pCun, pCun-precuneus/posterior cingulate cortex, and nucleus accumbens-somatomotor areas were strongly mediated when emotionally abused adolescents reported a high tendency for negative automatic thoughts. Conclusion: Negative automatic thoughts strengthened the relationship between emotional abuse and rsFC. These findings highlight the underlying cognitive processing of the traumatic event-neural system, supporting the use of cognitive therapy for post-traumatic symptoms.

Abstract This study compared the marginal and internal fit of zirconia crowns fabricated using conventional and high-speed induction sintering. A typodont mandibular right first molar was prepared and 60 zirconia crowns were fabricated: 30 crowns using conventional sintering and 30 crowns using high-speed sintering. We presented a new evaluation methodology to measure the marginal and internal fit of restorations through digital scanning, aligning the two datasets, and measuring the distance between two arbitrary point sets of the datasets. For the marginal fit, we calculated the maximum values of the shortest distances between the marginal line of the prepared tooth and that of the crown. The calculated values ranged from 359 to 444 μm, with smaller values for the high-speed sintered crowns (P 0.05). Based on our results, the high-speed sintering method can be considered a promising option for single-visit zirconia treatment in dental practice.

Abstract Background This study was conducted to investigate the effects of combining nutritional and physical activity (PA) factors on four different categories, according to the presence or absence of sarcopenia and central obesity. Methods From the 2008–2011 Korea National Health and Nutrition Examination Survey, 2971 older adults aged ≥ 65 years were included and divided into four groups based on their sarcopenia and central obesity status: healthy control (39.3%), central obesity (28.9%), sarcopenia (27.4%), and sarcopenic obesity (4.4%). Central obesity was defined as a waist circumference of ≥ 90 cm in men and ≥ 85 cm in women. Sarcopenia was defined as an appendicular skeletal mass index of

Abstract We propose an Eulerian approach to investigate the motion of particles in turbulence under the assumption that the motion of particles remains smooth in space and time until a collision between particles occurs. When the first collision happens, particle velocity loses $$C^1$$ C 1 continuity, resulting in a finite-time blowup. The corresponding singularities in particle velocity gradient, particle number density, and particle vorticity for various Stokes numbers and gravity factors are numerically investigated for the first time in a simple two-dimensional Taylor-Green vortex flow, two-dimensional decaying turbulence, and three-dimensional isotropic turbulence. In addition to the critical Stokes number above which a collision begins to occur, the flow condition leading to collision is revealed; particles tend to collide in very thin shear layer constructed by two parallel same-signed vortical structures when Stokes number is above the critical one.

It is well known that the neuropeptide Y (NPY)/agouti-related peptide (AgRP) neurons increase appetite and decrease thermogenesis. Previous studies demonstrated that optogenetic and/or chemogenetic manipulations of NPY/AgRP neuronal activity alter food intake and/or energy expenditure (EE). However, little is known about intrinsic molecules regulating NPY/AgRP neuronal excitability to affect long-term metabolic function. Here, we found that the G protein-gated inwardly rectifying K+ (GIRK) channels are key to stabilize NPY/AgRP neurons and that NPY/AgRP neuron-selective deletion of the GIRK2 subunit results in a persistently increased excitability of the NPY/AgRP neurons. Interestingly, increased body weight and adiposity observed in the NPY/AgRP neuron-selective GIRK2 knockout mice were due to decreased sympathetic activity and EE, while food intake remained unchanged. The conditional knockout mice also showed compromised adaptation to coldness. In summary, our study identified GIRK2 as a key determinant of NPY/AgRP neuronal excitability and driver of EE in physiological and stress conditions.

OBJECTIVES This study was conducted to examine the differences in food literacy between adults and older adults and the association of food literacy with food group intake. METHODS In total, 4,039 participants from the 2021 Survey for Food Consumption in Seoul were included in this study. The intake of whole grains, high-protein foods, total vegetables, vegetables excluding kimchi and pickles, fresh fruits, and milk and dairy products was assessed using a simple food frequency questionnaire. Food literacy was measured using a food literacy measurement questionnaire. RESULTS With the exception of milk and dairy, adults had a significantly higher proportion of insufficient food intake than older adults (p

Bak is a critical executor of apoptosis belonging to the Bcl-2 protein family. Bak contains a hydrophobic groove where the BH3 domain of proapoptotic Bcl-2 family members can be accommodated, which initiates its activation. Once activated, Bak undergoes a conformational change to oligomerize, which leads to mitochondrial destabilization and the release of cytochrome c into the cytosol and eventual apoptotic cell death. In this study, we investigated the molecular aspects and functional consequences of the interaction between Bak and peroxisomal testis-specific 1 (Pxt1), a noncanonical BH3-only protein exclusively expressed in the testis. Together with various biochemical approaches, this interaction was verified and analyzed at the atomic level by determining the crystal structure of the Bak-Pxt1 BH3 complex. In-depth biochemical and cellular analyses demonstrated that Pxt1 functions as a Bak-activating proapoptotic factor, and its BH3 domain, which mediates direct intermolecular interaction with Bak, plays a critical role in triggering apoptosis. Therefore, this study provides a molecular basis for the Pxt1-mediated novel pathway for the activation of apoptosis and expands our understanding of the cell death signaling coordinated by diverse BH3 domain-containing proteins.

Abstract Autophagy is a biological process that maintains cellular homeostasis and regulates the internal cellular environment. Hyperactivating autophagy to trigger cell death has been a suggested therapeutic strategy for cancer treatment. Mechanistic target of rapamycin (mTOR) is a crucial protein kinase that regulates autophagy; therefore, using a structure-based virtual screen analysis, we identified lomitapide, a cholesterol-lowering drug, as a potential mTOR complex 1 (mTORC1) inhibitor. Our results showed that lomitapide directly inhibits mTORC1 in vitro and induces autophagy-dependent cancer cell death by decreasing mTOR signaling, thereby inhibiting the downstream events associated with increased LC3 conversion in various cancer cells (e.g., HCT116 colorectal cancer cells) and tumor xenografts. Lomitapide also significantly suppresses the growth and viability along with elevated autophagy in patient-derived colorectal cancer organoids. Furthermore, a combination of lomitapide and immune checkpoint blocking antibodies synergistically inhibits tumor growth in murine MC38 or B16-F10 preclinical syngeneic tumor models. These results elucidate the direct, tumor-relevant immune-potentiating benefits of mTORC1 inhibition by lomitapide, which complement the current immune checkpoint blockade. This study highlights the potential repurposing of lomitapide as a new therapeutic option for cancer treatment.

A novel, natural, and effective antimicrobial intervention is in demand for improving the microbial safety of vegetable seeds/sprouts. This study assessed the efficacy of ascaroside treatment in the control of Salmonella enterica on alfalfa and fenugreek sprouts. Sanitized commercial seeds were treated with 1 mM or 1 µM ascaroside (ascr)#18, a plant immunity modulator (PIM) and dried for an hour before being inoculated with lyophilized S. Cubana or S. Stanley cells in sandy soil (104 CFU/g). Treated and untreated seeds were spouted on 1% water agar at 25°C in the dark. Seed or sprout samples were collected on days 0, 1, 3, 5, and 7, and the population of Salmonella was determined. Data were fit into the general linear arrangement, and means were separated using Fisher’s least significant difference test. Seed type, strain type, treatment type, and sprouting time were significant factors (P ≤ 0.05) influencing Salmonella growth on sprouts. The populations of Salmonella were significantly higher on fenugreek than on alfalfa sprouts. S. Stanley had a significantly higher population than S. Cubana. The population of Salmonella increased from day 0 to day 3 and reached the peak population on Day 5. Treatments with both concentrations of ascaroside significantly decreased the populations of Salmonella compared to the controls. The mean Salmonella population reduction was ca. 4 or 1 log CFU/g by treatment with 1 mM and 1 µM of the PIM, respectively. Treatment with the PIM could be potentially used to improve the microbial safety of vegetable seeds and sprouts.

Inositol hexakisphosphate kinase (IP6K) is an important mammalian enzyme involved in various biological processes such as insulin signalling and blood clotting. Recent analyses on drug metabolism and pharmacokinetic properties on TNP (N2-(m-trifluorobenzyl), N6-(p-nitrobenzyl)purine), a pan-IP6K inhibitor, have suggested that it may inhibit cytochrome P450 (CYP450) enzymes and induce unwanted drug-drug interactions in the liver. In this study, we confirmed that TNP inhibits CYP3A4 in type I binding mode more selectively than the other CYP450 isoforms. In an effort to find novel purine-based IP6K inhibitors with minimal CYP3A4 inhibition, we designed and synthesised 15 TNP analogs. Structure-activity relationship and biochemical studies, including ADP-Glo kinase assay and quantification of cell-based IP7 production, showed that compound 9 dramatically reduced CYP3A4 inhibition while retaining IP6K-inhibitory activity. Compound 9 can be a tool molecule for structural optimisation of purine-based IP6K inhibitors.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by widespread joint inflammation, which leads to joint damage, disability, and mortality. Among the several types of immune cells, myeloid cells such as macrophages are critical for controlling the pathogenesis of RA. Inositol phosphates are water-soluble signaling molecules, which are synthesized by a series of enzymes including inositol phosphate kinases. Previous studies revealed actions of inositol phosphates and their metabolic enzymes in the modulation of inflammation such as Toll-like receptor-triggered innate immunity. However, the physiological roles of inositol polyphosphate (IP) metabolism in the regulation of RA remain largely uncharacterized. Therefore, our study sought to determine the role of inositol polyphosphate multikinase (IPMK), a key enzyme for IP metabolism and various cellular signaling control mechanisms, in mediating RA. Using myeloid cell-specific IPMK knockout (KO) mice, arthritis was induced via intraperitoneal K/BxN serum injection, after which disease severity was evaluated. Both wild-type and IPMK KO mice developed similar RA phenotypes; however, conditional deletion of IPMK in myeloid cells led to elevated arthritis scores during the resolution phase, suggesting that IPMK deficiency in myeloid cells impairs the resolution of inflammation. Bone marrow-derived IPMK KO macrophages exhibited no apparent defects in immunoglobulin Fc receptor (FcR) activation, osteoclast differentiation, or resolvin signaling. Taken together, our findings suggest that myeloid IPMK is a key determinant of RA resolution.

Conceptualizing the climate change perspective of crop growth and evapotranspiration (ETc) rates and subsequent irrigation water requirements (IWR) is necessary for sustaining the agriculture sector and tackling food security issues in Pakistan. This article projects the future growth periods and water demands for the wheat-rice system of Punjab. Intense and hotter transitions in the future thermal regimes and erratic monsoon rainfall increments were envisaged. The crop growth rates were accelerated by the probable temperature rise resulting in shortened growth periods. The temperature rise increased the reference evapotranspiration rates; however, the future ETc declined due to reduced growth period and net radiation. Highly unpredictable, but mostly increasing, cumulative seasonal and annual rainfalls were indicative of more effective rainfalls during the future crop seasons. Reduced ETc and increments in seasonal effective rainfalls gave rise to the declining IWR for both crops. The study findings seemingly undermined the harmful climate change influences on the water requirements of the wheat-rice system of Punjab but alarmingly shortening of growth periods indicates a higher crop failure tendency under the projected future thermal regime. HIGHLIGHTS The crop water demands were projected after considering the probable changes in the future growing season lengths.; A projected decline in future net radiation counteracted the warming-driven increments in crop evapotranspiration rates and irrigation water requirements.; The early maturing future crops yielded an overall decline/incline in seasonal/daily water demands making the crops more irrigation-dependent and temperature-sensitive.; Compared to the rice, the wheat was more vulnerable to future climate change threats.; A new outlook was provided for developing the optimized irrigation schedules to mitigate the climate stresses on the future crop water demands.;

Ground reaction force (GRF) is essential for estimating muscle strength and joint torque in inverse dynamic analysis. Typically, it is measured using a force plate. However, force plates have spatial limitations, and studies of gaits involve numerous steps and thus require a large number of force plates, which is disadvantageous. To overcome these challenges, we developed a deep learning model for estimating three-axis GRF utilizing shoes with three uniaxial load cells. GRF data were collected from 81 people as they walked on two force plates while wearing shoes with three load cells. The three-axis GRF was calculated using a seq2seq approach based on long short-term memory (LSTM). To conduct the learning, validation, and testing, random selection was performed based on the subjects. The 60 selected participants were divided as follows: 37 were in the training set, 12 were in the validation set, and 11 were in the test set. The estimated GRF matched the force plate-measured GRF with correlation coefficients of 0.97, 0.96, and 0.90 and root mean square errors of 65.12 N, 15.50 N, and 9.83 N for the vertical, anterior–posterior, and medial–lateral directions, respectively, and there was a mid-stance timing error of 5.61% in the test dataset. A Bland–Altman analysis showed good agreement for the maximum vertical GRF. The proposed shoe with three uniaxial load cells and seq2seq LSTM can be utilized for estimating the 3D GRF in an outdoor environment with level ground and/or for gait research in which the subject takes several steps at their preferred walking speed, and hence can supply crucial data for a basic inverse dynamic analysis.

Lumazine protein from marine luminescent bacteria of Photobacterium species bind with very high affinity to the fluorescent chromophore 6,7-dimethyl-8-ribitylumazine. The light emission of bacterial luminescent systems is used as a sensitive, rapid, and safe assay for an ever-increasing number of biological systems. Plasmid pRFN4, containing the genes encoding riboflavin from the rib operon of Bacillus subtilis, was designed for the overproduction of lumazine. To construct fluorescent bacteria for use as microbial sensors, novel recombinant plasmids (pRFN4-Pp N-lumP and pRFN4-Pp luxLP N-lumP) were constructed by amplifying the DNA encoding the N-lumP gene (luxL) from P. phosphoreum and the promoter region (luxLP) present upstream of the lux operon of the gene by PCR and ligating into the pRFN4-Pp N-lumP plasmid. A new recombinant plasmid, pRFN4-Pp luxLP-N-lumP, was constructed with the expectation that the fluorescence intensity would be further increased when transformed into Escherichia coli. When this plasmid was transformed into E. coli 43R, the fluorescence intensity of transformants was 500 times greater than that of E. coli alone. As a result, the recombinant plasmid in which the gene encoding N-LumP and DNA containing the lux promoter exhibited expression that was so high as to show fluorescence in single E. coli cells. The fluorescent bacterial systems developed in the present study using lux and riboflavin genes can be utilized in the future as biosensors with high sensitivity and rapid analysis times.

Background Pneumococcal diseases among children aged 0.35 μg/mL was lower for some serotypes in the GBP411 group than in the comparator group (6B: 20.83% vs. 39.22%, P=0.047 and 19A: 58.33% vs. 90.20%, P97% of the subjects in each group achieved IgG concentrations of ≥0.35 μg/mL for all 12 serotypes. Increased immunogenicity was observed for some serotypes that showed significant intergroup differences after administration of the primary doses but not after the booster dose. We also found no significant intergroup difference in the overall incidence of solicited local adverse events. Furthermore, the overall incidence of solicited systemic adverse events was significantly lower in the GBP411 group than in the comparator vaccine group (79.59% vs. 98.04%; P=0.003). Conclusion The GBP411 vaccine with a dosing schedule of 2p+1 may be immunogenic and safe for healthy infants.

This paper proposes a hybrid precoding technique based on multiple-input multiple-output orthogonal frequency division multiplexing (MIMO-OFDM) system to improve bit error rate (BER) performance in hybrid beamforming system. The conventional hybrid beamforming system cannot outperform the performance of full-digital beamforming system in OFDM. In the proposed algorithm, the analog precoding matrices are designed by iterative algorithm and one proper analog precoding matrix with the highest power of hybrid precoder is selected to achieve the highest performance. According to the number of analog precoding matrices, the diversity gain is increased and the performance is improved. The simulation results show that the BER performance and average sum rate for the proposed scheme are higher than the conventional hybrid beamforming system.

Targeted drugs have been used to treat mitochondrial dysfunction-related diseases, including metabolic disorders and cancer; however, targeting and penetrating intracellular organelles remains a challenge. Dominant targeting approaches for therapeutic delivery are detailed in many nanoemulsion studies and show the tremendous potential of targeted delivery to inhibit cancer cell growth. Dequalinium (DQA) and α-tocopherol succinate (α-TOS) are good agents for targeting mitochondria. In this study, we aimed to develop a mitochondria-targeting emulsion, using DQA and α-TOS (DTOS), for cancer treatment. DTOS emulsions of 150–170 nm in diameter were formulated using homogenization. DQA and α-TOS were used as bifunctional agents (surfactants) to stabilize the nanoemulsion and anticancer drugs. Various molar ratios of DQA and α-TOS were tested to determine the optimal condition, and DTOS 5-5 was selected for further study. The DTOS emulsion showed improved stability, as evidenced by its ability to remain stable for three years at room temperature. This stability, combined with its effective targeting of mitochondria, led to inhibition of 71.5% of HeLa cells after 24 h. The DTOS emulsion effectively inhibited spheroid growth in the 3D model, as well as prevented the growth of HeLa cells grafted onto zebrafish larvae. These results highlight the DTOS emulsion’s promising potential for mitochondria-targeting and cancer treatment.

Recently, a novel electrochemical regulation associated with a deposition/dissolution reaction on an electrode surface has been proven to show superiority in large-scale energy storage systems (ESSs). Hence, in the search for high-performance electrodes showcasing these novel regulations, we utilized a low-cost ZnO microsphere electrode to construct aqueous rechargeable batteries (ARBs) that supplied a harvestable and storable charge through electrochemical deposition/dissolution via a reversible manganese oxidation reaction (MOR)/manganese reduction reaction (MRR), respectively, induced by the inherent formation/dissolution of zinc basic sulfate in a mild aqueous electrolyte solution containing 2 M ZnSO4 and 0.2 M MnSO4.

The world’s sustainable growth is being severely hampered by the inefficient use of water resources. Despite the widely acknowledged importance of trade in global and regional water and food security, societal reliance on local production, as well as international trade, remains inadequately assessed. Therefore, using South Korea as a case study, this study fills in this research gap by applying the virtual water concept, the logarithmic mean divisia index (LMDI) method, and the Tapio decoupling model. The virtual water concept was used to estimate South Korea’s net virtual water trade for major grain crops from 1992 to 2017. Then, the LMDI method was utilized to assess the driving factors causing changes in net virtual water trade. Lastly, the Tapio decoupling model was used to investigate the decoupling relationships between economic growth and the driving factors of net virtual water trade. The results showed that South Korea remains a net importer of virtual water flows with respect to grain crops, with an average import of 16,559.24 million m3 over the study period. In addition, the change in net virtual water trade could be attributed to the water intensity effect, product structure effect, economic effect, and population effect. However, water intensity and economic effects were the major decisive factors for decreases and increases in net virtual water trade, respectively, while the population and product structure effects had minor positive influences on the net virtual water trade. Furthermore, water intensity and economic growth showed a strong decoupling in most periods, while the decoupling state between product structure and economic growth was observed as expansive negative decoupling. Likewise, population size and economic growth showed a weak decoupling in most periods. The results reveal South Korea’s status as it concerns the virtual water trade of grain crops, thus providing valuable insights into the sustainability of trade activities for the management of local water resources.

Pigs are promising donors of biological materials for xenotransplantation; however, cell surface carbohydrate antigens, including galactose-alpha-1,3-galactose (α-Gal), N-glycolylneuraminic acid (Neu5Gc), and Sd blood group antigens, play a significant role in porcine xenograft rejection. Inactivating swine endogenous genes, including GGTA1, CMAH, and B4GALNT2, decreases the binding ratio of human IgG/IgM in peripheral blood mononuclear cells and erythrocytes and impedes the effectiveness of α-Gal, Neu5Gc, and Sd, thereby successfully preventing hyperacute rejection. Therefore, in this study, an effective transgenic system was developed to target GGTA1, CMAH, and B4GALNT2 using CRISPR-CAS9 and develop triple-knockout pigs. The findings revealed that all three antigens (α-Gal, Neu5Gc, and Sd) were not expressed in the heart, lungs, or liver of the triple-knockout Jeju Native Pigs (JNPs), and poor expression of α-Gal and Neu5G was confirmed in the kidneys. Compared with the kidney, heart, and lung tissues from wild-type JNPs, those from GGTA1/CMAH/ B4GALNT2 knockout-recipient JNPs exhibited reduced human IgM and IgG binding and expression of each immunological rejection component. Hence, reducing the expression of swine xenogeneic antigens identifiable by human immunoglobulins can lessen the immunological rejection against xenotransplantation. The findings support the possibility of employing knockout JNP organs for xenogeneic transplantation to minimize or completely eradicate rejection using multiple gene-editing methods.

Abstract Background Chronic hepatitis B (CHB) is a major cause of liver-related morbidity and mortality. High HBV prevalence in immigrants and ethnic minorities and numerous barriers to healthcare access are associated with serious health disparities in the United States. Reportedly, self-awareness of HBV infection is low, suggesting a greater need for effective screening and education. Further, low levels of linkage to care (LTC) (completion of a first doctor’s visit after the diagnosis of chronic HBV infection) may be responsible for the lack of engagement over the continuum of care and for needed services. Methods Demographics and survey data were obtained from 97 Korean American adults chronically infected with HBV, initially identified through a series of community screening events in northern New Jersey between Dec. 2009 and June 2015. Eight year follow-up on these HBV-infected individuals was obtained to determine their access to care, and thus the efficacy of a campaign to improve LTC. The participants’ self-awareness of HBV infection and other factors for LTC were also evaluated. Results Of a total of 97 HBV-infected participants (age range 30 to 79), 74 were aware of their infections at screening. The remaining 23 had been unaware of their infections until screening. Eight years after the campaign, some 66 of these 97 individuals accessed care (LTC rate 68%). Health insurance status, presence or absence of symptoms and level of knowledge of CHB were among the most significant factors in LTC. Conclusion A community-based hepatitis B screening and education campaign can be instrumental in prompting HBV infected individuals to access care, as demonstrated in the cumulative increase in LTC in our cohort. Despite many years of awareness of HBV infection, many are not accessing care owing to a lack of health insurance, suggesting a pressing need for advocacy and health education to improve access to affordable coverage in the Asian American population. Community efforts and strategies similar to the ones employed in the current study may serve as a model to improve the engagement of HBV-infected individuals in high risk immigrant populations.

Abstract Objective There are three major serologic markers for hepatitis B virus (HBV) infection: hepatitis B surface antigen (HBsAg); hepatitis B surface antibody (anti-HBs); and hepatitis B core antibody (anti-HBc). HBV screening programs, however, often test only HBsAg and anti-HBs, missing those individuals who have anti-HBc as the only detectable marker. Isolated anti-HBc can represent chronic infection in which HBsAg is not detectable by serology. We, therefore, investigated the prevalence of isolated anti-HBc in an ethnic community at moderate to high risk for HBV infection. Results Of 7157 Korean American adults in New Jersey, 2736 (38.2%) lacked anti-HBs, potentially susceptible to HBV. Of these 2736 subjects, 771 subjects had anti-HBc. The prevalence of isolated anti-HBc increased with age: 0.8% (age 21–30); 2.4% (age 31–40); 6.05% (age 41–50); 11.7% (age 51–60); 18.3% (age 61–70); and 24.5% (age 71–91). Similarly, the percentage of the individuals with isolated anti-HBc in anti-HBs lacking subjects showed a striking age dependence. We conclude that serologic HBV screening should include anti-HBc to accurately assess the prevalence of HBV exposure. Serologic screening with only HBsAg and anti-HBs may overestimate the prevalence of non-immune population. It can also underestimate the prevalence of HBV and increase the risk of HBV reactivation during immunosuppression.

Abstract Manganese (Mn)‐based cathode materials have garnered huge research interest for rechargeable aqueous zinc‐ion batteries (AZIBs) due to the abundance and low cost of manganese and the plentiful advantages of manganese oxides including their different structures, wide range of phases, and various stoichiometries. A novel in situ generated Mn‐deficient ZnMn2O4@C (Mn‐d‐ZMO@C) nanoarchitecture cathode material from self‐assembly of ZnO‐MnO@C for rechargeable AZIBs is reported. Analytical techniques confirm the porous and crystalline structure of ZnO‐MnO@C and the in situ growth of Mn deficient ZnMn2O4@C. The Zn/Mn‐d‐ZMO@C cell displays a promising capacity of 194 mAh g−1 at a current density of 100 mA g−1 with 84% of capacity retained after 2000 cycles (at 3000 mA g−1 rate). The improved performance of this cathode originates from in situ orientation, porosity, and carbon coating. Additionally, first‐principles calculations confirm the high electronic conductivity of Mn‐d‐ZMO@C cathode. Importantly, a good capacity retention (86%) is obtained with a year‐old cell (after 150 cycles) at 100 mA g−1 current density. This study, therefore, indicates that the in situ grown Mn‐d‐ZMO@C nanoarchitecture cathode is a promising material to prepare a durable AZIB.

Inositol pyrophosphates (PP-IPs) such as 5-diphosphoinositol pentakisphosphate (5-IP7) are inositol metabolites with high-energy phosphoanhydride bonds. The formation of PP-IPs is catalyzed by two groups of enzymes, the IP6 kinases and the PPIP5 kinases, which both phosphorylate inositol hexakisphosphate (IP6). In mammals, PP-IPs are implicated in diverse biological phenomena including cellular growth, vesicular trafficking, apoptosis, and metabolic homeostasis. Mechanistically, all the diverse actions of PP-IPs proceed in one of two ways: the PP-IPs modulate the activity of their target proteins either through allosteric binding or protein pyrophosphorylation. In this review, we highlight recent advances in our understanding of the pleiotropic functions of the mammalian PP-IPs and the metabolic enzymes that produce them. We also discuss some future challenges in the exploration of areas where PP-IPs play important but unknown roles in physiology and disease.

Organic thin films with smooth surfaces are mandated for high-performance organic electronic devices. Abrupt nucleation and aggregation during film formation are two main factors that forbid smooth surfaces. Here, we report a simple fast cooling (FC) adapted physical vapor deposition (FCPVD) method to produce ultrasmooth organic thin films through effectively suppressing the aggregation of adsorbed molecules. We have found that thermal energy control is essential for the spread of molecules on a substrate by diffusion and it prohibits the unwanted nucleation of adsorbed molecules. FCPVD is employed for cooling the horizontal tube-type organic vapor deposition setup to effectively remove thermal energy applied to adsorbed molecules on a substrate. The organic thin films prepared using the FCPVD method have remarkably ultrasmooth surfaces with less than 0.4 nm root mean square (RMS) roughness on various substrates, even in a low vacuum, which is highly comparable to the ones prepared using conventional high-vacuum deposition methods. Our results provide a deeper understanding of the role of thermal energy employed to substrates during organic film growth using the PVD process and pave the way for cost-effective and high-performance organic devices.

Reduced graphene oxide (rGO) sheets were synthesized by a modified Hummer's method without additional reducing procedures, such as chemical and thermal treatment, by appropriate drying of graphite oxide under ambient atmosphere. The use of a moderate drying temperature (250°C) led to mesoporous characteristics with enhanced electrochemical activity, as confirmed by electron microscopy and N2 adsorption studies. The dimensions of the sheets ranged from nanometres to micrometres and these sheets were entangled with each other. These morphological features of rGO tend to facilitate the movement of guest ions larger than Li+. Impressive electrochemical properties were achieved with the rGO electrodes using various charge-transfer ions, such as Li+, Na+ and K+, along with high porosity. Notably, the feasibility of this system as the carbonaceous anode material for sodium battery systems is demonstrated. Furthermore, the results also suggest that the high-rate capability of the present rGO electrode can pave the way for improving the full cell characteristics, especially for preventing the potential drop in sodium-ion batteries and potassium-ion batteries, which are expected to replace the lithium-ion battery system

In recent decades, several types of anticancer drugs that inhibit cancer cell growth and cause cell death have been developed for chemotherapeutic application. However, these agents are usually associated with side effects resulting from nonspecific delivery, which may induce cytotoxicity in healthy cells. To reduce the nonspecific delivery issue, nanoparticles have been successfully used for the delivery of anticancer drugs to specific target sites. In this study, a functional polymeric lipid, PEG-GLFG-K(C16)2 (PEG-GLFG, polyethylene glycol-Gly-Leu-Phe-Gly-Lys(C16)2), was synthesized to enable controlled anticancer drug delivery using cathepsin B enzyme-responsive liposomes. The liposomes composed of PEG-GLFG/DOTAP (1,2-dioleoyl-3-trimethylammonium-propane (chloride salt))/DPPC (dipalmitoylphosphatidylcholine)/cholesterol were prepared and characterized at various ratios. The GLFG liposomes formed were stable liposomes and were degraded when acted upon by cathepsin B enzyme. Doxorubicin (Dox) loaded GLFG liposomes (GLFG/Dox) were observed to exert an effective anticancer effect on Hep G2 cells in vitro and inhibit cancer cell proliferation in a zebrafish model.

This paper proposes a high performance wireless commmunication technology in MU-MIMO systems. The millimeter wave (mmWave) communication technology was considered for the future wireless communication systems such as the fifth-generation new radio (5G NR). In 5G NR, the mmWave communication technology was studied to increase the use of wide bandwidth and the data rate. Therefore, MU-MIMO systems can be used in mmWave. To decrease the complexity of conventional digital beamforming system, the hybrid beamforming system was studied. In particular, the proposed hybrid beamforming system improves the error performance and average sum rate in partially connected structure (PCS) hybrid beamforming system. The proposed PCS hybrid beamforming system forms variously combined beam patterns using the information of azimuth and elevation angles for the multi-paths according to the number of bits. In addition, the azimuth and elevation angles among the formed beam patterns are estimated according to the received signal strength (RSS). In the simulation results, the proposed PCS hybrid beamforming system has better error performance and the average sum rate than the conventional hybrid beamforming system.

Inositol pyrophosphates (PP-IPs) such as 5-diphosphoinositol pentakisphosphate (5-IP7) are inositol metabolites containing high-energy phosphoanhydride bonds. Biosynthesis of PP-IPs is mediated by IP6 kinases (IP6Ks) and PPIP5 kinases (PPIP5Ks), which transfer phosphate to inositol hexakisphosphate (IP6). Pleiotropic actions of PP-IPs are involved in many key biological processes, including growth, vesicular remodeling, and energy homeostasis. PP-IPs function to regulate their target proteins through allosteric interactions or protein pyrophosphorylation. This review summarizes the current understanding of how PP-IPs control mammalian cellular signaling networks in physiology and disease.

In this study, driving data for various types of drivers are collected using a VIDE (virtual integrated driving environment), and a driver model is developed. To represent the driver tendencies quantitatively, the DDA (degree of driver aggression) is proposed based on fuzzy logic. DDA has a 0-1 value; the closer the DDA is to one, the more aggressive the driver. Using the DDA, an engine on/off and battery charging power control algorithm are developed to improve the fuel economy of a power-split-type plug-in hybrid electric vehicle. The engine on/off control reduces the frequent engine on/off caused by aggressive driving, whereas the battery charging power control maintains the battery state of charge (SOC) by operating the engine according to the DDA. It is found that the proposed control algorithm improves fuel economy by 17.3% compared to the existing control for an aggressive driver.

Anthocyanins are flavonoid compounds that protect plant tissues from many environmental stresses including high light irradiance, freezing temperatures, and pathogen infection. Regulation of anthocyanin biosynthesis is intimately associated with environmental changes to enhance plant survival under stressful environmental conditions. Various factors, such as UV, visible light, cold, osmotic stress, and pathogen infection, can induce anthocyanin biosynthesis. In contrast, high temperatures are known to reduce anthocyanin accumulation in many plant species, even drastically in the skin of fruits such as grape berries and apples. However, the mechanisms by which high temperatures regulate anthocyanin biosynthesis in Arabidopsis thaliana remain largely unknown. Here, we show that high ambient temperatures repress anthocyanin biosynthesis through the E3 ubiquitin ligase CONSTITUTIVE PHOTOMORPHOGENIC1 (COP1) and the positive regulator of anthocyanin biosynthesis ELONGATED HYPOCOTYL5 (HY5). We show that an increase in ambient temperature decreases expression of genes required in both the early and late steps of the anthocyanin biosynthesis pathway in Arabidopsis seedlings. As a result, seedlings grown at a high temperature (28°C) accumulate less anthocyanin pigment than those grown at a low temperature (17°C). We further show that high temperature induces the degradation of the HY5 protein in a COP1 activity-dependent manner. In agreement with this finding, anthocyanin biosynthesis and accumulation do not respond to ambient temperature changes in cop1 and hy5 mutant plants. The degradation of HY5 derepresses the expression of MYBL2, which partially mediates the high temperature repression of anthocyanin biosynthesis. Overall, our study demonstrates that high ambient temperatures repress anthocyanin biosynthesis through a COP1-HY5 signaling module.

Background and Objectives: The attentional bias and information processing model explained that individuals who interpret pain stimuli as threatening may increase their attention toward pain-related information. Previous eye tracking studies found pain attentional bias among individuals with chronic pain; however, those studies investigated this phenomenon by using only one stimulus modality. Therefore, the present study investigated attentional engagement to pain-related information and the role of pain catastrophizing on pain attentional engagement to pain-related stimuli among chronic pain patients by utilizing both linguistic and visual stimulus. Materials and Methods: Forty chronic pain patients were recruited from the rehabilitation center, the back pain clinic, and the rheumatology department of Chung-Ang University Hospital in Seoul, Korea. Patients observed pictures of faces and words displaying pain, presented simultaneously with neutral expressions, while their eye movements were measured using the eye tracking system. A t-test and ANOVA were conducted to compare stimulus pairs for the total gaze duration. Results: Results revealed that chronic pain patients demonstrated attentional preference toward pain words but not for pain faces. An ANOVA with bias scores was conducted to investigate the role of pain catastrophizing on attentional patterns. Results indicated that chronic pain patients with high pain catastrophizing scores gazed significantly longer at pain- and anger-related words than neutral words compared to those with low pain catastrophizing scores. The same patterns were not observed for the facial expression stimulus pairs. Conclusions: The results of the present study revealed attentional preference toward pain-related words and the significant role of pain catastrophizing on pain attentional engagement to pain-related words. However, different patterns were observed between linguistic and visual stimuli. Clinical implications related to use in pain treatment and future research suggestions are discussed.

Because of the complex mechanisms mediating cancer onset, prognosis, and metastatic behavior, different therapeutic approaches targeting these mechanisms have been investigated. Recent advancements in nanocarrier-based drug and gene delivery methods have encouraged scientific groups to investigate various novel therapeutic techniques. In this study, a poly(amidoamine) (PAMAM) polymer-based gene carrier containing the cathepsin B-enzyme sensitive sequence (glycine-phenylalanine-leucine-glycine, GFLG) was evaluated to determine transfection efficiency. Following the GFLG sequence, the surface of PAMAM generation 4 (G4) was conjugated with histidine (H) and arginine (R) for improved endosomal escape and cellular uptake, respectively. The successful synthesis of G4-GLFG-H-R was confirmed by 1H-nuclear magnetic resonance spectroscopy. The polyplex composed of G4-GLFG-H-R and pDNA was simulated by the enzyme cathepsin B and induced endosomal escape of pDNA, which was confirmed by gel electrophoresis. Compared with the G4 control, enzyme-sensitive G4-GLFG-H-R showed higher transfection efficiency and lower cytotoxicity in HeLa cells. These results demonstrated that G4-GLFG-H-R may be a highly potent and efficient carrier for gene therapy applications.