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CD98, also known as SLC3A2, is a multifunctional cell surface molecule consisting of amino acid transporters. CD98 is ubiquitously expressed in many types of tissues, but expressed at higher levels in cancerous tissues than in normal tissues. CD98 is also upregulated in most hepatocellular carcinoma (HCC) patients; however, the function of CD98 in HCC cells has been little studied. In this study, we generated a panel of monoclonal antibodies (MAbs) against surface proteins on human embryonic stem cells (hESCs). NPB15, one of the MAbs, bound to hESCs and various cancer cells, including HCC cells and non-small cell lung carcinoma (NSCLC) cells, but not to peripheral blood mononuclear cells (PBMCs) and primary hepatocytes. Immunoprecipitation and mass spectrometry identified the target antigen of NPB15 as CD98. CD98 depletion decreased cell proliferation, clonogenic survival, and migration and induced apoptosis in HCC cells. In addition, CD98 depletion decreased the expression of cancer stem cell (CSC) markers in HCC cells. In tumorsphere cultures, the expression of CD98 interacting with NPB15 was significantly increased, as were known CSC markers. After cell sorting by NPB15, cells with high expression of CD98 (CD98-high) showed higher clonogenic survival than cells with low expression of CD98 (CD98-low) in HCC cells, suggesting CD98 as a potential CSC marker on HCC cells. The chimeric version of NPB15 was able to induce antibody-dependent cellular cytotoxicity (ADCC) against HCC cells in vitro. NPB15 injection showed antitumor activity in an HCC xenograft mouse model. The results suggest that NPB15 may be developed as a therapeutic antibody for HCC patients. [ABSTRACT FROM AUTHOR]

The significance of complex I of the electron transport chain (ETC) in the aging process is widely acknowledged; however, its specific impact on the development of sarcopenia in muscle remains poorly understood. This study elucidated the correlation between complex I inhibition and sarcopenia by conducting a comparative analysis of skeletal muscle gene expression in sarcopenia phenotypes from rats, mice, and humans. Our findings reveal a common mechanistic link across species, particularly highlighting the correlation between the suppression of complex I of ETC activity and dysregulated mitochondrial transcription and translation in sarcopenia phenotypes. Additionally, we observed macrophage dysfunction alongside abnormal metabolic processes within skeletal muscle tissues across all species, implicating their pathogenic role in the onset of sarcopenia. These discoveries underscore the importance of understanding the shared mechanisms associated with complex I of ETC in sarcopenia development. The identified correlations provide valuable insights into potential targets for therapeutic interventions aimed at mitigating the impact of sarcopenia, a condition with substantial implications for aging populations. [ABSTRACT FROM AUTHOR]

Electroencephalography (EEG)-based open-access datasets are available for emotion recognition studies, where external auditory/visual stimuli are used to artificially evoke pre-defined emotions. In this study, we provide a novel EEG dataset containing the emotional information induced during a realistic human-computer interaction (HCI) using a voice user interface system that mimics natural human-to-human communication. To validate our dataset via neurophysiological investigation and binary emotion classification, we applied a series of signal processing and machine learning methods to the EEG data. The maximum classification accuracy ranged from 43.3% to 90.8% over 38 subjects and classification features could be interpreted neurophysiologically. Our EEG data could be used to develop a reliable HCI system because they were acquired in a natural HCI environment. In addition, auxiliary physiological data measured simultaneously with the EEG data also showed plausible results, i.e., electrocardiogram, photoplethysmogram, galvanic skin response, and facial images, which could be utilized for automatic emotion discrimination independently from, as well as together with the EEG data via the fusion of multi-modal physiological datasets. [ABSTRACT FROM AUTHOR]

Background: Breast cancer (BC) is a complex disease with profound genomic aberrations. However, the underlying molecular disparity influenced by age and ethnicity remains elusive. Methods: In this study, we aimed to investigate the molecular properties of 843 primary and metastatic BC patients enrolled in the K-MASTER program. By categorizing patients into two distinct age subgroups, we explored their unique molecular properties. Additionally, we leveraged large-scale genomic data from the TCGA and MSK-IMPACT studies to examine the ethnic-driven molecular and clinical disparities. Results: We observed a high prevalence of PI3KCA mutations in K-MASTER HER2 + tumors, particularly in older patients. Moreover, we identified increased mutation rates in DNA damage response molecules, including ARID1A, MSH6, and MLH1. The K-MASTER patients were mainly comprised of triple-negative breast cancer (TNBC) and HER2-positive tumors, while the TCGA and MSK-IMPACT cohorts exhibited a predominance of hormone receptor-positive (HR +) subtype tumors. Importantly, GATA3 mutations were less frequently observed in East Asian patients, which correlated with poor clinical outcomes. In addition to characterizing the molecular disparities, we developed a gradient-boosting multivariable model to identify a new molecular signature that could predict the therapeutic response to platinum-based chemotherapy. Conclusions: Our findings collectively provide unprecedented insights into the significance of age and ethnicity on the molecular and clinical characteristics of BC patients. [ABSTRACT FROM AUTHOR]

Purpose: Chemotherapy-induced nausea and vomiting (CINV) is a common adverse events in cancer patients and can negatively affect their quality of life (QoL). This study aimed to evaluate the clinical efficacy of an electric massage chair (EMC) for the treatment of CINV. Methods: A randomized phase II cross-over trial was conducted on solid cancer patients who received moderate (MEC) to high emetogenic chemotherapy (HEC). The participants were randomly assigned to receive their first chemotherapy either on a standard bed (Group A) or in an EMC (Group B) during the infusion. The patients were then crossed over to the next cycle. CINV and QoL questionnaires were collected from the participants. Results: A total of 59 patients completed the trial protocol and were included in the analysis, with 29 and 30 patients in Groups A and B, respectively. The mean INVR (Index of Nausea, Vomiting, and Retching) score in the 2nd day of the first cycle was higher in Group B (3.63 ± 5.35) than Group A (2.76 ± 4.78), but the difference was not statistically significant (p = 0.5367). The complete response rate showed little difference between the groups. Among the high-emetic risk subgroups, patients who received HEC (p = 0.04595), younger patients (p = 0.0108), and non-colorectal cancer patients (p = 0.0495) presented significantly lower CINV scores when EMC was applied. Conclusion: Overall, there was no significant difference in INVR scores between standard care and EMC. Applying EMC at the first chemotherapy infusion may help preserve QoL and reduce CINV in high-risk patients. Trial registration: KCT0008200, 17/02/2023, Retrospectively registered. [ABSTRACT FROM AUTHOR]

Background: Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults, with limited treatment modalities and poor prognosis. Recent studies have highlighted the importance of considering sex differences in cancer incidence, prognosis, molecular disparities, and treatment outcomes across various tumor types, including colorectal adenocarcinoma, lung adenocarcinoma, and GBM. Methods: We performed comprehensive analyses of large-scale multi-omics data (genomic, transcriptomic, and proteomic data) from TCGA, GLASS, and CPTAC to investigate the genetic and molecular determinants that contribute to the unique clinical properties of male and female GBM patients. Results: Our results revealed several key differences, including enrichments of MGMT promoter methylation, which correlated with increased overall and post-recurrence survival and improved response to chemotherapy in female patients. Moreover, female GBM exhibited a higher degree of genomic instability, including aneuploidy and tumor mutational burden. Integrative proteomic and phosphor-proteomic characterization uncovered sex-specific protein abundance and phosphorylation activities, including EGFR activation in males and SPP1 hyperphosphorylation in female patients. Lastly, the identified sex-specific biomarkers demonstrated prognostic significance, suggesting their potential as therapeutic targets. Conclusions: Collectively, our study provides unprecedented insights into the fundamental modulators of tumor progression and clinical outcomes between male and female GBM patients and facilitates sex-specific treatment interventions. Highlights Female GBM patients were characterized by increased MGMT promoter methylation and favorable clinical outcomes compared to male patients. Female GBMs exhibited higher levels of genomic instability, including aneuploidy and TMB. Each sex-specific GBM is characterized by unique pathway dysregulations and molecular subtypes. EGFR activation is prevalent in male patients, while female patients are marked by SPP1 hyperphosphorylation. Plain language summary: Glioblastoma (GBM) is the most common and lethal primary brain tumor in adults with limited treatment modalities and dismal prognosis. A thorough understanding of sex differences could facilitate personalized therapeutic strategies in GBM. In this study, we conducted a comprehensive multi-omics analysis from TCGA, CPTAC, and GLASS studies, revealing distinct molecular and clinical disparities between male and female GBM patients. We discovered that female GBM patients exhibited enrichments of MGMT promoter methylation and high genomic instability, including aneuploidy and TMB. While male GBMs were characterized by activation of EGFR protein and phosphorylation activities, female GBM patients demonstrated hyperphosphorylation of SPP1. Notably, these proteins demonstrated prognostic significance, highlighting their potential as therapeutic targets. Our findings provide unprecedented insights into the fundamental modulators of tumor progression and clinical outcomes in male and female GBM patients, offering valuable opportunities for sex-specific treatment interventions. [ABSTRACT FROM AUTHOR]

Formaldehyde occurs naturally in food and alcoholic beverages. Formaldehyde and alcoholic beverages can cause various health problems, including irritation of the eyes, nose, and throat, respiratory problems, and skin rashes. Alcoholic beverage samples (N = 236) were collected and analyzed for formaldehyde by liquid chromatography-tandem mass spectrometry. The highest average concentrations were detected in fruit wines (1.71 µg/g), followed by wines (1.15 µg/g), cheongju (0.95 µg/g), soju (0.85 µg/g), takju (0.64 µg/g) and beers (0.61 µg/g). We assessed the exposure and risk assessment to formaldehyde from alcoholic beverages based on the monitoring data for the general population and consumers in Korea using various schemes for point estimation. The daily intakes of formaldehyde for the general population and consumers were estimated to be 83 µg and 1202 µg, respectively. The mean hazard indexes (HI) for the general population and consumers in Korea were 0.009 and 0.132, respectively. On the other hand, the mean hazard indexes (HI) for the general population and consumers in Korea were 0.009 and 0.132, respectively. The exposure to formaldehyde in these alcoholic beverages for the Korean population was shown to be of low concern, but it is necessary to monitor the level of formaldehyde in alcoholic beverages and continuously conduct exposure assessment for consumers. [ABSTRACT FROM AUTHOR]

Single-target rapid antigen tests (RATs) are commonly used to detect highly transmissible respiratory viruses (RVs), such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza viruses. The simultaneous detection of RVs presenting overlapping symptoms is vital in making appropriate decisions about treatment, isolation, and resource utilization; however, few studies have evaluated multiplex RATs for SARS-CoV-2 and other RVs. We assessed the diagnostic performance of multiplex RATs targeting both the SARS-CoV-2 and influenza A/B viruses with the GenBody Influenza/COVID-19 Ag Triple, InstaView COVID-19/Flu Ag Combo (InstaView), STANDARDTM Q COVID-19 Ag Test, and STANDARDTM Q Influenza A/B Test kits using 974 nasopharyngeal swab samples. The cycle threshold values obtained from the real-time reverse transcription polymerase chain reaction results showed higher sensitivity (72.7–100%) when the values were below, rather than above, the cut-off values. The InstaView kit exhibited significantly higher positivity rates (80.21% for SARS-CoV-2, 61.75% for influenza A, and 46.15% for influenza B) and cut-off values (25.57 for SARS-CoV-2, 21.19 for influenza A, and 22.35 for influenza B) than the other two kits, and was able to detect SARS-CoV-2 Omicron subvariants. Therefore, the InstaView kit is the best choice for routine screening for both SARS-CoV-2 and influenza A/B in local communities. [ABSTRACT FROM AUTHOR]

Arachidonic and adrenic acids in the membrane play key roles in ferroptosis. Here, we reveal that lipoprotein-associated phospholipase A2 (Lp-PLA2) controls intracellular phospholipid metabolism and contributes to ferroptosis resistance. A metabolic drug screen reveals that darapladib, an inhibitor of Lp-PLA2, synergistically induces ferroptosis in the presence of GPX4 inhibitors. We show that darapladib is able to enhance ferroptosis under lipoprotein-deficient or serum-free conditions. Furthermore, we find that Lp-PLA2 is located in the membrane and cytoplasm and suppresses ferroptosis, suggesting a critical role for intracellular Lp-PLA2. Lipidomic analyses show that darapladib treatment or deletion of PLA2G7, which encodes Lp-PLA2, generally enriches phosphatidylethanolamine species and reduces lysophosphatidylethanolamine species. Moreover, combination treatment of darapladib with the GPX4 inhibitor PACMA31 efficiently inhibits tumour growth in a xenograft model. Our study suggests that inhibition of Lp-PLA2 is a potential therapeutic strategy to enhance ferroptosis in cancer treatment. Ferroptosis is an iron-dependent cell death mechanism that is emerging as a target for cancer therapy. Here, the authors find that lipoprotein-associated phospholipase A2 modulates ferroptosis resistance by controlling phospholipid metabolism. [ABSTRACT FROM AUTHOR]

Previously, we found that dysfunctional natural killer (NK) cells with low interferon gamma (IFN-γ) were restored in acute myeloid leukemia (AML) by the FLT4 antagonist MAZ51. Here, we developed 12 peptides targeting FLT4 for clinical application and examined whether they restored the frequency of lymphocytes, especially T cells and NK cells, and high IFN-γ expression, as MAZ51 treatment did in our previous study. Although clinical data from using peptides are currently available, peptides targeting FLT4 to modulate immune cells have not been fully elucidated. In this study, we focus on novel peptide 4 (P4) from the intracellular domain of FLT4 because it had dominant negative activity. Similar to MAZ51, high IFN-γ levels were expressed in AML-mononuclear cells exposed to P4. Additionally, T and NK cell levels were restored, as were high IFN-γ levels, in a leukemic environment when P4 was treated. Interestingly, the regulatory T cells were significantly decreased by P4, implying the role of peptide in tumor niche. Overall, we demonstrated the therapeutic value of functionally modulating lymphocytes using a peptide targeting FLT4 and proposed the development of advanced therapeutic approaches against AML by using immune cells. [ABSTRACT FROM AUTHOR]

We investigated differences in quantitative electroencephalogram (EEG) patterns associated with game usage patterns and genre among patients with Internet gaming disorder (IGD). Data from 140 participants (76 IGD patients and 64 healthy controls) were analysed. The IGD group was divided into subgroups based on game usage patterns (single game [SG] or multiple games [MGs]) and genre (multiplayer online battle arena, first-person shooter [FPS], or massively multiplayer online role-playing game [MMORPG; hereafter, MMG]). A resting-state, eye-closed quantitative EEG was recorded, and the absolute power and coherence of brain waves were analysed. IGD patients who played SGs showed increased beta activity compared with those who played MGs and controls. Increased absolute beta power was significantly associated with higher tendencies towards behavioural inhibition compared with controls. FPS gamers showed increased delta power in the frontal region compared with controls, which was related to the severity of IGD. Furthermore, decreased intrahemispheric coherence in the left frontoparietal region was observed in the MMG and FPS groups compared with controls. This decreased coherence was observed in the theta (MMG and FPS), delta (MMG), and beta (FPS) bands. These features were related to impairment in visuospatial working memory. Unique neurophysiological features related to preoccupation with an SG may be associated with the inhibition of behavioural changes. The present study suggests that the underlying neurophysiological networks in IGD differ according to game usage patterns and genre. [ABSTRACT FROM AUTHOR]

Red blood cell (RBC) generation from human pluripotent stem cells (PSCs) offers potential for innovative cell therapy in regenerative medicine as well as developmental studies. Ex vivo erythropoiesis from PSCs is currently limited by the low efficiency of functional RBCs with β-globin expression in culture systems. During induction of β-globin expression, the absence of a physiological microenvironment, such as a bone marrow niche, may impair cell maturation and lineage specification. Here, we describe a simple and reproducible culture system that can be used to generate erythroblasts with β-globin expression. We prepared a two-dimensional defined culture with ferric citrate treatment based on definitive hemogenic endothelium (HE). Floating erythroblasts derived from HE cells were primarily CD45+CD71+CD235a+ cells, and their number increased remarkably upon Fe treatment. Upon maturation, the erythroblasts cultured in the presence of ferric citrate showed high transcriptional levels of β-globin and enrichment of genes associated with heme synthesis and cell cycle regulation, indicating functionality. The rapid maturation of these erythroblasts into RBCs was observed when injected in vivo, suggesting the development of RBCs that were ready to grow. Hence, induction of β-globin expression may be explained by the effects of ferric citrate that promote cell maturation by binding with soluble transferrin and entering the cells. Taken together, upon treatment with Fe, erythroblasts showed advanced maturity with a high transcription of β-globin. These findings can help devise a stable protocol for the generation of clinically applicable RBCs. [ABSTRACT FROM AUTHOR]

Patients with diabetes mellitus (DM) are twice as likely as nondiabetic individuals to develop depression, which is a prevalent but often undiagnosed psychiatric comorbidity. Patients with DM who are depressed have poor glycemic control, worse quality of life, increased risk of diabetic complications, and higher mortality rate. The present study aimed to develop machine learning (ML) models that identify depression in patients with DM, determine the best performing model by evaluating multiple ML algorithms, and investigate features related to depression. We developed six ML models, including random forest, K-nearest neighbor, support vector machine (SVM), Adaptive Boosting, light gradient-boosting machine, and Extreme Gradient Boosting, based on the Korea National Health and Nutrition Examination Survey. The results showed that the SVM model performed well, with a cross-validated area under the receiver operating characteristic curve of 0.835 (95% confidence interval [CI] = 0.730–0.901). Thirteen features were related to depression in patients with DM. Permutation feature importance showed that the most important feature was subjective health status, followed by level of general stress awareness; stress recognition rate; average monthly income; triglyceride (mg/dL) level; activity restriction status; European quality of life (EuroQoL): usual activity and lying in a sickbed in the past 1 month; EuroQoL: pain / discomfort, self-care, and physical discomfort in the last 2 weeks; and EuroQoL: mobility and chewing problems. The current findings may offer clinicians a better understanding of the relationship between DM and depression using ML approaches and may be an initial step toward developing a more predictive model for the early detection of depressive symptoms in patients with DM. [ABSTRACT FROM AUTHOR]

Red blood cell (RBC) transfusion is a lifesaving medical procedure that can treat patients with anemia and hemoglobin disorders. However, the shortage of blood supply and risks of transfusion-transmitted infection and immune incompatibility present a challenge for transfusion. The in vitro generation of RBCs or erythrocytes holds great promise for transfusion medicine and novel cell-based therapies. While hematopoietic stem cells and progenitors derived from peripheral blood, cord blood, and bone marrow can give rise to erythrocytes, the use of human pluripotent stem cells (hPSCs) has also provided an important opportunity to obtain erythrocytes. These hPSCs include both human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs). As hESCs carry ethical and political controversies, hiPSCs can be a more universal source for RBC generation. In this review, we first discuss the key concepts and mechanisms of erythropoiesis. Thereafter, we summarize different methodologies to differentiate hPSCs into erythrocytes with an emphasis on the key features of human definitive erythroid lineage cells. Finally, we address the current limitations and future directions of clinical applications using hiPSC-derived erythrocytes. [ABSTRACT FROM AUTHOR]

Ice cream consumption has increased over the years. In this study, we investigated the potential of using rice varieties with varying amylose contents for ice cream production. We analyzed the physical and chemical properties and sensory quality characteristics (appearance, taste, texture, chewiness, aroma, and rice flavor) of rice-based ice cream made from five varieties with low and high amylose levels. To make the ice cream, we ground rice into a fine powder and combined it with skim milk powder, butter, sugar, glycerin esters of fatty acids, locust bean gum, and water to form a gelatinized mixture. This mixture was then aged, frozen, and hardened. The ice cream's key quality characteristics, such as viscosity (2170–25,030 cP), hardness (4.27–49.55 N cm−2), and overrun (17.95–46.99%), showed a wide range. Ice cream made from Saemimyeon (high amylose content rice variety) exhibited the highest hardness value (49.55 N cm−2) among the varieties tested, but had relatively low viscosity (4030 cP), overrun (17.95%), and drip-through (0.75 g/min) values. These findings suggest that rice varieties with different amylose contents are suitable for making ice cream and have the potential to expand the rice processing market and increase its value. [ABSTRACT FROM AUTHOR]

Acute myocardial infarction (AMI) is highly prevalent and remains the leading cause of mortality. Particularly in women, under-recognition and management of AMI have been raised. The aim of this study was to investigate the long-term trends of prevalence, treatment methodologies, and mortality of AMI by gender. The subjects of this study were patients hospitalized for AMI according to the Korean National Health Insurance Claims Database from 2002 to 2018. Total 633,097 AMI patients were hospitalized, 40% women. The incidence of AMI has been increasing since 2011, with a lower incidence in women. Overall, 53.1% of patients underwent CAG, with a lower tendency in women than in men (39.8% vs. 62.3%). Furthermore, fewer women underwent PCI than men (77.5% vs. 85.8% in 2018, p < 0.0001). Of the 336,463 AMI patients undergoing CAG, women were undertreated with a lower prescription rate of beta-blockers or statins at discharge. When adjusted for age, women showed higher 7-day mortality but lower 1-year mortality relative to men. According to the Korean National Health Insurance Claims Database, women with AMI have been under-recognized, underdiagnosed, and undertreated in terms of revascularization or medical therapy for years suggesting that efforts to close the gender gap are necessary. [ABSTRACT FROM AUTHOR]

Hemogenic endothelium (HE) plays a pivotal and inevitable role in haematopoiesis and can generate all blood and endothelial lineage cells in the aorta‐gonad‐mesonephros of mouse embryos. Whether definitive HE can prospectively isolate pure HE from human pluripotent stem cells that can spontaneously differentiate into heterogeneous cells remains unknown. Here, we identified and validated a CD34dim subpopulation with hemogenic potential. We also purified CD34 cells with a CXCR4−CD73− phenotype as a definitive HE population that generated haematopoietic stem cells and lymphocytes. The frequency of CXCR4−CD73−CD34dim was evidently increased by bone morphogenetic protein 4, and purified HE cells differentiated into haematopoietic cells with myeloid and T lymphoid lineages including Vδ2+ subset of γ/δ T cells. We developed a simple method to purify HE cells that were enriched in CD34dim cells. We uncovered an initial step in differentiating haematopoietic lineage cells that could be applied to basic and translational investigations into regenerative medicine. [ABSTRACT FROM AUTHOR]

Bakanae disease caused by Fusarium fujikuroi causes crop failure and yield losses in the majority of rice-growing countries. In this study, we employed a joint strategy quantitative trait locus (QTL) mapping–Genome-Wide Association Study (GWAS) to investigate novel genetic loci associated with Bakanae disease resistance using a population of 143 BC1F8 RILs derived from a cross between Ilpum × Tung Tin Wan Hien1. The phenotypic data from the bioassay and the genotypic data generated using a DNA chip were utilized to perform QTL mapping and GWAS study. Our results identified a novel genetic locus qBK4T associated with Bakanae disease resistance, which was mapped on chromosome 4 and flanked by AX-116847364 (33.12 Mbp) and AX-115752415 (33.44 Mbp) markers covering a region of 324kbp. There were 34 genes in this region including Os04g55920 (encoding a zinc-finger protein, OsJAZ1), Os04g55970 (encoding AP2-like ethylene-responsive transcription factor), etc. This study proposes qBK4T as a novel locus for Bakanae disease resistance. The identification of qBK4T and its flanking marker information could be useful for marker-assisted breeding and functional characterization of resistance genes against bakanae disease. [ABSTRACT FROM AUTHOR]

Ophiorrhiza pumila is a medicinal plant that grows in subtropical forests and produces camptothecin (CPT). To determine an optimal harvest time of O. pumila in a plant factory with artificial light (PFAL), we investigated the CPT distribution in each organ and at the developmental stage and estimated the annual CPT production. For this study, the O. pumila plants were grown in controlled environments (16 h light period, photosynthetic photon flux density of 100 μmol m−2 s−1 under white light-emitting diode lamps, air temperature of 28 °C, relative humidity of 80%, and CO2 concentration of 1000 μmol mol−1). First, the stem, root, and seed pod had higher CPT contents than the leaves, flower, and ovary. The optimal harvest time of O. pumila in a PFAL was 63 days after transplanting (DAT), because the CPT content in the whole organs was the highest at the seed-ripening stage. Second, based on these results, the estimated annual CPT production of O. pumila cultivated in a PFAL was 380 mg m−2 y−1 (63 DAT). This value was 4.3 times greater than the annual CPT production by Camptotheca acuminata in a greenhouse. We concluded that the CPT production by O. pumila in a PFAL throughout the year has many advantages, although the demand for electrical energy was high compared to that of Camptotheca acuminata in a greenhouse. [ABSTRACT FROM AUTHOR]

Background: The two key mechanisms affected by internet gaming disorder (IGD) are cognitive and reward processing. Despite their significance, little is known about neurophysiological features as determined using resting-state electroencephalography (EEG) source functional connectivity (FC). Methods: We compared resting-state EEG source FC within the default mode network (DMN) and reward/salience network (RSN) between patients with IGD and healthy controls (HCs) to identify neurophysiological markers associated with cognitive and reward processing. A total of 158 young male adults (79 patients with IGD and 79 HCs) were included, and the source FC of the DMN and RSN in five spectral bands (delta, theta, alpha, beta, and gamma) were assessed. Results: Patients with IGD showed increased theta, alpha, and beta connectivity within the DMN between the orbitofrontal cortex and parietal regions compared with HCs. In terms of RSN, patients with IGD exhibited elevated alpha and beta connectivity between the anterior cingulate gyrus and temporal regions compared with HCs. Furthermore, patients with IGD showed negative correlations between the severity of IGD symptoms and/or weekly gaming time and theta and alpha connectivity within the DMN and theta, alpha, and beta connectivity within the RSN. However, the duration of IGD was not associated with EEG source FC. Conclusions: Hyper-connectivities within the DMN and RSN may be considered potential state markers associated with symptom severity and gaming time in IGD. [ABSTRACT FROM AUTHOR]

In regenerative medicine, humanized mice (hu-mice) are extremely valuable for verifying the cross talk between immune cells and therapeutic cells. Given the highly dynamic nature of the activities of immune cells, the in vitro platform does not allow for screening of their exact interactions with different therapeutic cells. By contrast, hu-mice have been widely applied for in vivo studies, especially those on immune rejection. However, the full reconstitution of lymphoid lineage cells in hu-mice remains to be realized. In this study, we investigated whether lysates from healthy donor-derived pooled mononuclear cells (MNCs) can promote the increase of lymphoid lineage cells in hu-mice. The pooled MNC lysate treatment of hu-mice possessing a low proportion of CD45 cells resulted in significant increases in CD3 cells and CD45 cells with the RO phenotype. The diverse epitopes from the pooled MNC lysates significantly induced the proportion of lymphoid lineage cells in the thymus and spleen after therapeutic cells with mismatched HLAs were co-injected into the hu-mice. These findings demonstrate the technical benefits of using pooled MNC lysates for reconstituting lymphoid lineage cells in hu-mice, providing a valuable in vivo platform for investigating the cross talk between lymphoid immune cells and therapeutic cells. [ABSTRACT FROM AUTHOR]

Nitrogen (N) is a gas and the fifth most abundant element naturally found in the atmosphere. N's role in agriculture and plant metabolism has been widely investigated for decades, and extensive information regarding this subject is available. However, the advent of sequencing technology and the advances in plant biotechnology, coupled with the growing interest in functional genomics-related studies and the various environmental challenges, have paved novel paths to rediscovering the fundamentals of N and its dynamics in physiological and biological processes, as well as biochemical reactions under both normal and stress conditions. This work provides a comprehensive review on multiple facets of N and N-containing compounds in plants disseminated in the literature to better appreciate N in its multiple dimensions. Here, some of the ancient but fundamental aspects of N are revived and the advances in our understanding of N in the metabolism of plants is portrayed. It is established that N is indispensable for achieving high plant productivity and fitness. However, the use of N-rich fertilizers in relatively higher amounts negatively affects the environment. Therefore, a paradigm shift is important to shape to the future use of N-rich fertilizers in crop production and their contribution to the current global greenhouse gases (GHGs) budget would help tackle current global environmental challenges toward a sustainable agriculture. [ABSTRACT FROM AUTHOR]

The National Institute of Crop Science, Rural Development Administration (RDA) of Korea is presently developing new rice varieties suitable for producing Western rice-based foods, such as risotto, a well-known Italian-style product. The study considered different milled rice from five Tongil-type and six Japonica-type varieties. Besides the biometric properties, cooking behaviour, starch properties, and in vitro digestibility of Korean rice samples were compared with those of the 'Carnaroli' Italian variety. The physicochemical traits of the Korean varieties extended over a vast range; the amylose content stood out (from 13.0 to 41.7%), influencing the hardness and stickiness of cooked samples, and their starch digestibility. Although none of the Korean varieties seemed to guarantee cooking performances for risotto similar to the 'Carnaroli' one, 'Saemimyeon' and 'Shingil' cvs were judged the best for this purpose up-to-now. [ABSTRACT FROM AUTHOR]

Stress plays an important role in the pathophysiology of addictive disorders. The kynurenine (KYN) pathway involved in neuroimmune and cognitive functions is activated under stress. However, the neuroimmunological–neurocognitive mechanisms in the role of stress in addictive disorders are unclear still now. Ninety-nine young adults aged 18–35 years [alcohol use disorder (AUD), N = 30; Internet gaming disorder (IGD), N = 34; healthy controls (HCs), N = 35] participated in this study. Stress levels, resilience, addiction severity, and neurocognitive functions were evaluated, and serum levels of tryptophan (TRP), 5-hydroxytryptamine (5-HT), KYN, and kynurenine acid (KYNA) were determined using liquid chromatography coupled with tandem mass spectrometry through blood samples. Both addictive disorder groups showed higher levels of stress, lower resilience, and impaired executive functions compared to the HC group. Importantly, the AUD group revealed significantly increased KYN levels and KYN/TRP ratios, as well as decreased KYNA levels and KYNA/KYN ratios compared to HCs (p < 0.001, p < 0.001, p = 0.033, and p < 0.001, respectively). The IGD group showed KYN levels and KYNA/KYN ratios intermediate between those of the AUD group and HCs. Furthermore, in the AUD group, the mediating effect of AUD on KYN through stress level was moderated by resilience [index of moderated mediation = −0.557, boot S.E = 0.331, BCa CI (−1.349, −0.081)]. Stress may induce an imbalance in downstream of KYN pathway metabolites, and the KYN/TRP ratio may play as a neuromediator between stress and behavioral changes in both addictive disorders. This study suggests that regulation of the KYN pathway is critical in the pathophysiology of addictive disorders and it may serve as an important target for future treatment modalities. [ABSTRACT FROM AUTHOR]

Here, we determined the effects of mild water deficit (WD) and high CO2 concentration (HC) on the growth and bioactive compounds of dropwort and proposed culture conditions for producing high-quality plants. Plantlets with two to three offshoots were transplanted to a controlled environment room with artificial light and cultivated for 6 weeks. To investigate the effects of HC, plantlets were grown under relatively low CO2 concentration (LC; 600 μmol mol−1 CO2) or HC (1000 μmol mol−1 CO2) conditions for 6 weeks (HC6) or grown under standard conditions for 3 weeks and transferred to HC conditions for the remaining 3 weeks (HC3). To investigate the effects of WD, control plantlets were subirrigated by keeping the pots in a tray of nutrient solution, whereas WD-treated plants were allowed to absorb water through wicks extending from the pot bottoms to a nutrient solution below. Leaf water potential of WD-treated plantlets was significantly lower than that of controls. Both WD and HC significantly decreased leaf area but did not significantly affect shoot fresh and dry weights. The photosynthetic rates of HC6- and HC3-treated plantlets were 53% and 64% greater, respectively, than that of LC; the stomatal conductance and transpiration rate exhibited opposite trends. WD significantly decreased net photosynthetic rate, transpiration rate, and stomatal conductance. The total nonstructural carbohydrate content of HC6- and HC3-treated plantlets was 8% and 14% greater, respectively, than that of LC. Total phenolic content and antioxidant capacity of WD plantlets were 17% and 23% greater, respectively, than those of controls. In controls, total phenolic content of HC6- and HC3-treated plantlets was increased significantly (by 24% and 34%, respectively) than that of LC plantlets. Phenylalanine ammonia-lyase (PAL) activity of WD-treated plantlets was 14% higher than that of controls; in the controls, PAL activity of HC-treated plantlets increased significantly (by 19%) compared to that of LC plantlets. However, HC did not affect PAL activity under WD. Cyanidin content was increased by both WD and HC treatments. These results indicate that reddish small dropwort (WD treated plantlets) is more useful than greenish dropwort as a functional food and can be easily produced through HC when grown in a closed environment (e.g., a greenhouse or plant factory). Finally, the cultural practice of HC can improve the industrial value of small dropwort grown for food processing. [ABSTRACT FROM AUTHOR]

While previous studies have demonstrated the feasibility of using ear-electroencephalography (ear-EEG) for the development of brain-computer interfaces (BCIs), most of them have been performed using exogenous paradigms in offline environments. To verify the reliable feasibility of constructing ear-EEG-based BCIs, the feasibility of using ear-EEG should be further demonstrated using another BCI paradigm, namely the endogenous paradigm, in real-time online environments. Exogenous and endogenous BCIs are to use the EEG evoked by external stimuli and induced by self-modulation, respectively. In this study, we investigated whether an endogenous ear-EEG-based BCI with reasonable performance can be implemented in online environments that mimic real-world scenarios. To this end, we used three different mental tasks, i.e., mental arithmetic, word association, and mental singing, and performed BCI experiments with fourteen subjects on three different days to investigate not only the reliability of a real-time endogenous ear-EEG-based BCI, but also its test-retest reliability. The mean online classification accuracy was almost 70%, which was equivalent to a marginal accuracy for a practical two-class BCI (70%), demonstrating the feasibility of using ear-EEG for the development of real-time endogenous BCIs, but further studies should follow to improve its performance enough to be used for practical ear-EEG-based BCI applications. [ABSTRACT FROM AUTHOR]

In rice, high radial oxygen loss (ROL) has been associated with the reduction in the activity of methanogens, therefore reducing the formation of methane (CH4) due to the abundance in application of nitrogen (N)-rich fertilizers. In this study, we evaluated the root growth behavior and ROL rate of a doubled haploid (DH) population (n = 117) and parental lines 93-11 (P1, indica) and Milyang352 (P2, japonica) in response to iron (II) sulfide (FeS). In addition, we performed a linkage mapping and quantitative trait locus (QTL) analysis on the same population for the target traits. The results of the phenotypic evaluation revealed that parental lines had distinctive root growth and ROL patterns, with 93-11 (indica) and Milyang352 (japonica) showing low and high ROL rates, respectively. This was also reflected in their derived population, indicating that 93.2% of the DH lines exhibited a high ROL rate and about 6.8% had a low ROL pattern. Furthermore, the QTL and linkage map analysis detected two QTLs associated with the control of ROL and root area on chromosomes 2 (qROL-2-1, 127 cM, logarithm of the odds (LOD) 3.04, phenotypic variation explained (PVE) 11.61%) and 8 (qRA-8-1, 97 cM, LOD 4.394, PVE 15.95%), respectively. The positive additive effect (2.532) of qROL-2-1 indicates that the allele from 93-11 contributed to the observed phenotypic variation for ROL. The breakthrough is that the qROL-2-1 harbors genes proposed to be involved in stress signaling, defense response mechanisms, and transcriptional regulation, among others. The qPCR results revealed that the majority of genes harbored by the qROL-2-1 recorded a higher transcript accumulation level in Milyang352 over time compared to 93-11. Another set of genes exhibited a high transcript abundance in P1 compared to P2, while a few were differentially regulated between both parents. Therefore, OsTCP7 and OsMYB21, OsARF8 genes encoding transcription factors (TFs), coupled with OsTRX, OsWBC8, and OsLRR2 are suggested to play important roles in the positive regulation of ROL in rice. However, the recorded differential expression of OsDEF7 and OsEXPA, and the decrease in OsNIP2, Oscb5, and OsPLIM2a TF expression between parental lines proposes them as being involved in the control of oxygen flux level in rice roots. [ABSTRACT FROM AUTHOR]

Postoperative thromboembolism (TE) is a serious, but preventable, complication in surgical patients. Orthopedic surgery, neurosurgery, and vascular surgery are considered high risk for TE, and current guidelines recommend TE prophylaxis. However, insufficient data exist regarding TE risk in other general surgeries. This study identified the actual incidence and relative risk of postoperative TE in the real world, according to surgery type. Twenty-six surgeries between 1 December 2017 and 31 August 2019 were selected from the Health Insurance Review and Assessment Service database and analyzed for postoperative TE events. Among all patients, 2.17% had a TE event within 6 months of surgery and 0.75% had a TE event owing to anticoagulant treatment. The incidence of total TE events was the highest in total knee replacement (12.77%), hip replacement (11.46%), and spine surgery (5.98%). The incidence of TE with anticoagulant treatment was the highest in total knee replacement (7.40%), hip replacement (7.20%), and coronary artery bypass graft (CABG) surgery (3.81%). Hip replacement, total knee replacement, CABG surgery, spine surgery, and cardiac surgery except CABG surgery, showed relatively higher risks for total claimed venous TE. The relative risk of venous TE with anticoagulant treatment was the highest for hysterectomy, partial hepatectomy, hip replacement, cardiac surgery except CABG surgery, and total knee replacement. The relative risk of arterial TE was the highest for cardiac surgery, total knee replacement, and hip replacement. In the real world, the incidence of postoperative TE events from total knee replacement and those from hip replacement remain high, and some surgeries could have a relatively higher risk of TE than other surgeries. For patients undergoing these surgeries, studies to reduce the incidence of postoperative TE in clinical practice should be conducted. [ABSTRACT FROM AUTHOR]

Background: Tumor-based classification of human glioma portends patient prognosis, but considerable unexplained survival variability remains. Host factors (eg, age) also strongly influence survival times, partly reflecting a compromised immune system. How blood epigenetic measures of immune characteristics and age augment molecular classifications in glioma survival has not been investigated. We assess the prognostic impact of immune cell fractions and epigenetic age in archived blood across glioma molecular subtypes for the first time.Methods: We evaluated immune cell fractions and epigenetic age in archived blood from the University of California San Francisco Adult Glioma Study, which included a training set of 197 patients with IDH-wild type, 1p19q intact, TERT wild type (IDH/1p19q/TERT-WT) glioma, an evaluation set of 350 patients with other subtypes of glioma, and 454 patients without glioma.Results: IDH/1p19q/TERT-WT patients had lower lymphocyte fractions (CD4+ T, CD8+ T, natural killer, and B cells) and higher neutrophil fractions than people without glioma. Recursive partitioning analysis delineated 4 statistically significantly different survival groups for patients with IDH/1p19q/TERT-WT based on an interaction between chronological age and 2 blood immune factors, CD4+ T cells, and neutrophils. Median overall survival ranged from 0.76 years (95% confidence interval = 0.55-0.99) for the worst survival group (n = 28) to 9.72 years (95% confidence interval = 6.18 to not available) for the best (n = 33). The recursive partitioning analysis also statistically significantly delineated 4 risk groups in patients with other glioma subtypes.Conclusions: The delineation of different survival groups in the training and evaluation sets based on an interaction between chronological age and blood immune characteristics suggests that common host immune factors among different glioma types may affect survival. The ability of DNA methylation-based markers of immune status to capture diverse, clinically relevant information may facilitate noninvasive, personalized patient evaluation in the neuro-oncology clinic. [ABSTRACT FROM AUTHOR]

DNA methylation plays key roles in various areas, such as gene expression, regulation, epigenetics, and cancers. Since 5-methylcytosine (5mC) is commonly present in methylated DNA, characterizing the binding kinetics and thermodynamics of the nucleotide to the enzymatic pocket can help to understand the DNA replication process. Furthermore, 5-carboxycytosine (5caC) is a form that appears through the iterative oxidation of 5mC, and its effect on the DNA replication process is still not well known. Here, we immobilized a DNA polymerase (DNAP) with an orientation control on a tip of an atomic force microscope (AFM), and observed the interaction between the immobilized deoxyguanosine triphosphate (dGTP) on the surface and the DNAP in the presence of a DNA duplex. The interaction probability increased as the concentration of the DNA strand, and the affinity constant between the DNAP and DNA was obtained by fitting the change. Increasing the concentration of dGTP in solution diminished the interaction probability, and a fitting allowed us to retrieve the affinity constant between dGTP and the DNAP holding the DNA in the reaction pocket. Because the dissociation constant could be obtained through the loading rate dependence of the unbinding force value, both affinity and kinetic constants for cytosine (C), 5mC, and 5caC in the DNAP were compared in the light of the steric and electronic effect of the substituents at 5-position of cytosine. [ABSTRACT FROM AUTHOR]

Background: Amnion-derived mesenchymal stem cells (AM-MSCs) are an attractive source of stem cell therapy for patients with irreversible liver disease. However, there are obstacles to their use due to low efficiency and xeno-contamination for hepatic differentiation. Methods: We established an efficient protocol for differentiating AM-MSCs into hepatic progenitor cells (HPCs) by analyzing transcriptome-sequencing data. Furthermore, to generate the xeno-free conditioned differentiation protocol, we replaced fetal bovine serum (FBS) with polyvinyl alcohol (PVA). We investigated the hepatocyte functions with the expression of mRNA and protein, secretion of albumin, and activity of CYP3A4. Finally, to test the transplantable potential of HPCs, we transferred AM-MSCs along with hepatic progenitors after differentiated days 11, 12, and 13 based on the expression of hepatocyte-related genes and mitochondrial function. Further, we established a mouse model of acute liver failure using a thioacetamide (TAA) and cyclophosphamide monohydrate (CTX) and transplanted AM-HPCs in the mouse model through splenic injection. Results: We analyzed gene expression from RNA sequencing data in AM-MSCs and detected downregulation of hepatic development-associated genes including GATA6, KIT, AFP, c-MET, FGF2, EGF, and c-JUN, and upregulation of GSK3. Based on this result, we established an efficient hepatic differentiation protocol using the GSK3 inhibitor, CHIR99021. Replacing FBS with PVA resulted in improved differentiation ability, such as upregulation of hepatic maturation markers. The differentiated hepatocyte-like cells (HLCs) not only synthesized and secreted albumin, but also metabolized drugs by the CYP3A4 enzyme. The best time for translation of AM-HPCs was 12 days from the start of differentiation. When the AM-HPCs were transplanted into the liver failure mouse model, they settled in the damaged livers and differentiated into hepatocytes. Conclusion: This study offers an efficient and xeno-free conditioned hepatic differentiation protocol and shows that AM-HPCs could be used as transplantable therapeutic materials. Thus, we suggest that AM-MSC-derived HPCs are promising cells for treating liver disease. [ABSTRACT FROM AUTHOR]

Purpose: The potential effects of herbal medicine for patients with cognitive disorders have been reported in various human and animal studies. This study aimed to explore the effect of herbal medicine treatment according to the Korean Medicine (KM) pattern identification for patients with mild cognitive impairment and early dementia. Patients and Methods: Twenty patients with mild cognitive impairment or mild dementia who planned to receive herbal medicine treatment were enrolled. Herbal formulae were prescribed based on the KM pattern for 12– 24 weeks. Seoul Neuropsychological Screening Battery II (SNSB-II) and Montreal Cognitive Assessment (MoCA) were assessed at the baseline, after 12 weeks, and after 24 weeks (Trial registration: cris.nih.go.kr, KCT0004799). Results: Herbal medicine products, including Yukmijihwang-tang, Samhwangsasim-tang, Palmul-tang, Banhasasim-tang, and Yukgunja-tang, were prescribed to the patients. Among the SNSB-II five cognitive function domains, the T scores for language, visuospatial function, memory, and frontal/executive function increased over time. The MoCA score also improved following the treatment (mean difference 4.23 [95% CI: 2.60, 5.86], p < 0.0001 at 12-week follow-up compared to the baseline). Considering the KM pattern scores, phlegm-dampness and fire-heat scores tended to improve after the treatment. No serious adverse events related to the intervention were reported. Conclusion: The potential effect of herbal medicine formulae products on improving cognitive functions in patients with cognitive impairment was observed. Further research is needed to objectify the KM pattern identification process and evaluate the KM pattern-related signs and symptoms. [ABSTRACT FROM AUTHOR]

Background: Nuclear receptor are major regulators of hepatic drug metabolizing enzymes and antioxidants enzymes. Nuclear receptor humanized mice were used for overcome species differences between experimental animals and human. Objective: The present study was performed to investigate the hepatic regulation of antioxidant enzymes in pregnane X receptor (PXR) and constitutive androstane receptor (CAR) double humanized mice treated with the human PXR ligand, rifampicin (RIF; 10 mg/kg for 4 days). Results: RIF decreased the hepatic protein levels of superoxide dismutase-1, thioredoxin-1, and γ-glutamylcysteine ligase catalytic subunit in wild-type (WT) mice, but not in the double humanized mice. Catalase protein levels were decreased by RIF in both WT and double humanized mice. The hepatic protein level and activity of glutathione reductase (GR) were increased in the humanized mice treated with RIF, but decreased in WT mice. Glutathione S-transferase (GST) alpha-class (GSTA) and mu-class (GSTM) but not pi-class were induced by RIF in the humanized mice, but not in WT mice. The activities of total GST, GSTA and GSTM were also increased only in humanized mice treated with RIF. Conclusion: These results suggest that PXR and CAR may play roles in xenobiotic-induced hepatic regulation of GSTA, GSTM, and GR. The PXR/CAR double humanized mouse can be used as a suitable predictive model of the regulation of human antioxidant enzymes by xenobiotics. [ABSTRACT FROM AUTHOR]

Transition‐metal‐free and site‐selective C–H selenylation of heterocyclic N‐oxides with diselenides is described. This method can be also applied for the formation of C2‐sulfenylated and C2‐tellurinated quinoline derivatives. Notably, the simple reaction conditions with the use of anisole as a green solvent have been employed in this coupling reaction. Combined mechanistic investigations elucidate a plausible reaction mechanism of this process. The synthetic transformations demonstrate the utility of the developed method. [ABSTRACT FROM AUTHOR]

Heart rate variability (HRV) can be used to represent the regulatory adaptive system and is a proxy for neurovisceral integration. Consistent with the view that, like other addictions, Internet gaming disorder (IGD) involves disrupted regulatory function, the present study hypothesized that IGD patients would show (a) decreased HRV, (b) ineffective functional neural connectivity, and (c) differential patterns of association between HRV and functional neural connectivity relative to healthy controls (HCs). The present study included 111 young adults (53 IGD patients and 58 age- and sex-matched HCs) who underwent simultaneous recordings with an electrocardiogram and electroencephalogram during a resting state. Heart rate (HR), HRV, and functional neural connectivity were calculated using the graph theory approach. Compared with the HCs, the IGD patients exhibited elevated HR and decreased HRV based on the high frequency (HF), which reflects suppression of parasympathetic and/or vagal tone. The IGD patients also exhibited a heightened theta band characteristic path length (CPL) compared with HCs, indicating decreased efficacy of the functional network. Furthermore, IGD patients exhibited negative correlations between the standard deviation of the normal-to-normal interval index (SDNNi) and theta and delta CPL values, which were not observed in HCs. In conclusion, the present findings suggest that IGD patients might have maladaptive brain-body integration features involving disruptions of the autonomic nervous system and brain function. [ABSTRACT FROM AUTHOR]

Increased grain yield will be critical to meet the growing demand for food, and could be achieved by delaying crop senescence. Here, via quantitative trait locus (QTL) mapping, we uncover the genetic basis underlying distinct life cycles and senescence patterns of two rice subspecies, indica and japonica. Promoter variations in the Stay-Green (OsSGR) gene encoding the chlorophyll-degrading Mg++-dechelatase were found to trigger higher and earlier induction of OsSGR in indica, which accelerated senescence of indica rice cultivars. The indica-type promoter is present in a progenitor subspecies O. nivara and thus was acquired early during the evolution of rapid cycling trait in rice subspecies. Japonica OsSGR alleles introgressed into indica-type cultivars in Korean rice fields lead to delayed senescence, with increased grain yield and enhanced photosynthetic competence. Taken together, these data establish that naturally occurring OsSGR promoter and related lifespan variations can be exploited in breeding programs to augment rice yield. Breeding crops with delayed senescence could plausibly increase grain yield. Here the authors show that variation at the rice SGR locus contributes to differences in senescence between indica and japonica subspecies and show that introgression can increase yield in an elite indica rice variety. [ABSTRACT FROM AUTHOR]

Poor survival of human pluripotent stem cells (hPSCs) following freezing, thawing, or passaging hinders the maintenance and differentiation of stem cells. Rho-associated kinases (ROCKs) play a crucial role in hPSC survival. To date, a typical ROCK inhibitor, Y-27632, has been the primary agent used in hPSC research. Here, we report that another ROCK inhibitor, fasudil, can be used as an alternative and is cheaper than Y-27632. It increased hPSC growth following thawing and passaging, like Y-27632, and did not affect pluripotency, differentiation ability, and chromosome integrity. Furthermore, fasudil promoted retinal pigment epithelium (RPE) differentiation and the survival of neural crest cells (NCCs) during differentiation. It was also useful for single-cell passaging of hPSCs and during aggregation. These findings suggest that fasudil can replace Y-27632 for use in stem research. [ABSTRACT FROM AUTHOR]

The development of new improved varieties is one of the major goals of plant breeding. Concomitantly, the demand for stable, eco-friendly, and high-quality rice production is constantly increasing. However, most farmers prefer to cultivate familiar rice varieties developed more than 10 years ago to minimize economic risk. A strategy is needed to develop rice varieties without the limitations of the preferred old varieties. Here, we tested the rapid development of near isogenic lines (NILs) using a rapid generation advance system together with marker-assisted backcrossing to overcome the shortcomings of parental materials. For this purpose, we chose rice stripe virus (RSV) susceptible variety Unkwang and RSV resistant variety Haedamssal as experimental materials. First, we backcrossed and screened BC1F1 and BC2F1 plants having similar agronomic traits as Unkwang and the heterozygous genotype for RSV resistant specific marker InDel7 from Haedamssal. Secondly, the genetic background of 11 BC2F1 plants was identified with 73 KASP markers; plants of line YR32548-8 showed 84.5% of recovery of the recurrent parent genome. Among 28 BC2F2 plants, YR32548-8-16 was the line that showed maximum recovery of the recurrent parent genome (96.2%) while effectively introgressed with RSV-resistance loci on chromosome 11. Finally, we selected line YR32548-8-16 as an NIL showing an RSV resistant phenotype and similar agronomic traits to Unkwang. This fast breeding approach will be useful in rice breeding programs for the improvement of varieties preferred by farmers for their stress tolerance, yield, or quality. [ABSTRACT FROM AUTHOR]

Objectives: Because primary mesenchymal progenitor cells (adult‐MPCs) have various functions that depend on the tissue origin and donor, de novo MPCs from human pluripotent stem cells (hPSCs) would be required in regenerative medicine. However, the characteristics and function of MPCs derived from reprogrammed hPSCs have not been well studied. Thus, we show that functional MPCs can be successfully established from a single cell‐derived clonal expansion following MPC derivation from somatic cell nuclear transfer‐derived (SCNT)‐hPSCs, and these cells can serve as therapeutic contributors in an animal model of Asherman's syndrome (AS). Materials and methods: We developed single cell‐derived clonal expansion following MPC derivation from SCNT‐hPSCs to offer a pure population and a higher biological activity. Additionally, we investigated the therapeutic effects of SCNT‐hPSC‐MPCs in model mice of Asherman's syndrome (AS), which is characterized by synechiae or fibrosis with endometrial injury. Results: Their humoral effects in proliferating host cells encouraged angiogenesis and decreased pro‐inflammatory factors via a host‐dependent mechanism, resulting in reduction in AS. We also addressed that cellular activities such as the cell proliferation and population doubling of SCNT‐hPSC‐MPCs resemble those of human embryonic stem cell‐derived MPCs (hESC‐MPCs) and are much higher than those of adult‐MPCs. Conclusions: Somatic cell nuclear transfer‐derived‐hPSCs‐MPCs could be an advanced therapeutic strategy for specific diseases in the field of regenerative medicine. [ABSTRACT FROM AUTHOR]

Previously, we found that dual therapy by the CXCR4 inhibitor Plerixafor and cytosine arabinoside (Ara-C) effectively eradicated leukemia cells and concurrently activated immune cells in acute myeloid leukemia (AML). To reveal the significance of programmed death-ligand1 (PD-L1) in AML and as a strategic approach, we investigated the anti-leukemic effect of a triple combinational therapy by utilizing Plerixafor and anti-PD-L1 in combination with chemotherapy in an AML mouse model. We examined leukemic myeloid blast cells in multiple organs after the successive treatment with Ara-C, Plerixafor, and anti-PD-L1. The results showed that noticeable benefits of triple combinational therapy for eradication of myeloid blast cells in vivo with prolonged survival rates. The frequencies of regulatory T cells (Tregs), monocytic-myeloid-derived suppressor cells (M-MDSCs), and granulocytic-myeloid-derived suppressor cells (G-MDSCs), in the peripheral blood of leukemic mice were consistently decreased, even when mice were sacrificed alive at D + 26 after completion of the triple combinational therapy, compared to the other subgroups. These findings imply that the modulation by the triple combinational therapy may lead to more efficient leukemic myeloid blast cell ablation through the suppression of Tregs or M-MDSCs and G-MDSCs in AML. Although Plerixafor and PD-L1 antagonist do not have a direct anti-leukemic role, our results provide some clues and guidelines to develop clinically therapeutic strategies for chemotherapy-resistant patients by the modulation of leukemic microenvironments. [ABSTRACT FROM AUTHOR]

How plants defend themselves from microbial infection is one of the most critical issues for sustainable crop production. Some TGA transcription factors belonging to bZIP superfamily can regulate disease resistance through NPR1-mediated immunity mechanisms in Arabidopsis. Here, we examined biological roles of OsTGA2 (grouped into the same subclade as Arabidopsis TGAs) in bacterial leaf blight resistance. Transcriptional level of OsTGA2 was accumulated after treatment with salicylic acid, methyl jasmonate, and Xathomonas oryzae pv. Oryzae (Xoo), a bacterium causing serious blight of rice. OsTGA2 formed homo- and hetero-dimer with OsTGA3 and OsTGA5 and interacted with rice NPR1 homologs 1 (NH1) in rice. Results of quadruple 9-mer protein-binding microarray analysis indicated that OsTGA2 could bind to TGACGT DNA sequence. Overexpression of OsTGA2 increased resistance of rice to bacterial leaf blight, although overexpression of OsTGA3 resulted in disease symptoms similar to wild type plant upon Xoo infection. Overexpression of OsTGA2 enhanced the expression of defense related genes containing TGA binding cis-element in the promoter such as AP2/EREBP 129, ERD1, and HOP1. These results suggest that OsTGA2 can directly regulate the expression of defense related genes and increase the resistance of rice against bacterial leaf blight disease. [ABSTRACT FROM AUTHOR]

A correction is presented to the article "Enhanced resting-state EEG source functional connectivity within the default mode and reward-salience networks in Internet gaming disorder" which appeared in the May 11, 2022 issue.