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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.

The green rice leafhopper (GRH, Nephotettix cincticeps Uhler) is one of the most important insect pests causing serious damage to rice production and yield loss in East Asia. Prior to performing RNA-Seq analysis, we conducted an electrical penetration graph (EPG) test to investigate the feeding behavior of GRH on Ilpum (recurrent parent, GRH-susceptible cultivar), a near-isogenic line (NIL carrying Grh1) compared to the Grh1 donor parent (Shingwang). Then, we conducted a transcriptome-wide analysis of GRH-responsive genes in Ilpum and NIL, which was followed by the validation of RNA-Seq data by qPCR. On the one hand, EPG results showed differential feeding behaviors of GRH between Ilpum and NIL. The phloem-like feeding pattern was detected in Ilpum, whereas the EPG test indicated a xylem-like feeding habit of GRH on NIL. In addition, we observed a high death rate of GRH on NIL (92%) compared to Ilpum (28%) 72 h post infestation, attributed to GRH failure to suck the phloem sap of NIL. On the other hand, RNA-Seq data revealed that Ilpum and NIL GRH-treated plants generated 1,766,347 and 3,676,765 counts per million mapped (CPM) reads, respectively. The alignment of reads indicated that more than 75% of reads were mapped to the reference genome, and 8859 genes and 15,815,400 transcripts were obtained. Of this number, 3424 differentially expressed genes (DEGs, 1605 upregulated in Ilpum and downregulated in NIL, 1819 genes upregulated in NIL and downregulated in Ilpum) were identified. According to the quantile normalization of the fragments per kilobase of transcript per million mapped reads (FPKM) values, followed by the Student’s t-test (p &lt, 0.05), we identified 3283 DEGs in Ilpum (1935 upregulated and 1348 downregulated) and 2599 DEGs in NIL (1621 upregulated and 978 downregulated) with at least a log2 (logarithm base 2) twofold change (Log2FC ≥2) in the expression level upon GRH infestation. Upregulated genes in NIL exceeded by 13.3% those recorded in Ilpum. The majority of genes associated with the metabolism of carbohydrates, amino acids, lipids, nucleotides, the activity of coenzymes, the action of phytohormones, protein modification, homeostasis, the transport of solutes, and the uptake of nutrients, among others, were abundantly upregulated in NIL (carrying Grh1). However, a high number of upregulated genes involved in photosynthesis, cellular respiration, secondary metabolism, redox homeostasis, protein biosynthesis, protein translocation, and external stimuli response related genes were found in Ilpum. Therefore, all data suggest that Grh1-mediated resistance against GRH in rice would involve a transcriptome-wide reprogramming, resulting in the activation of bZIP, MYB, NAC, bHLH, WRKY, and GRAS transcription factors, coupled with the induction of the pathogen-pattern triggered immunity (PTI), systemic acquired resistance (SAR), symbiotic signaling pathway, and the activation of genes associated with the response mechanisms against viruses. This comprehensive transcriptome profile of GRH-responsive genes gives new insights into the molecular response mechanisms underlying GRH (insect pest)–rice (plant) interaction.

The green rice leafhopper (GRH, Nephotettix cincticeps Uhler) is one of the most important insect pests causing serious damage to rice production and yield loss in East Asia. Prior to performing RNA-Seq analysis, we conducted an electrical penetration graph (EPG) test to investigate the feeding behavior of GRH on Ilpum (recurrent parent, GRH-susceptible cultivar), a near-isogenic line (NIL carrying Grh1) compared to the Grh1 donor parent (Shingwang). Then, we conducted a transcriptome-wide analysis of GRH-responsive genes in Ilpum and NIL, which was followed by the validation of RNA-Seq data by qPCR. On the one hand, EPG results showed differential feeding behaviors of GRH between Ilpum and NIL. The phloem-like feeding pattern was detected in Ilpum, whereas the EPG test indicated a xylem-like feeding habit of GRH on NIL. In addition, we observed a high death rate of GRH on NIL (92%) compared to Ilpum (28%) 72 h post infestation, attributed to GRH failure to suck the phloem sap of NIL. On the other hand, RNA-Seq data revealed that Ilpum and NIL GRH-treated plants generated 1,766,347 and 3,676,765 counts per million mapped (CPM) reads, respectively. The alignment of reads indicated that more than 75% of reads were mapped to the reference genome, and 8859 genes and 15,815,400 transcripts were obtained. Of this number, 3424 differentially expressed genes (DEGs, 1605 upregulated in Ilpum and downregulated in NIL; 1819 genes upregulated in NIL and downregulated in Ilpum) were identified. According to the quantile normalization of the fragments per kilobase of transcript per million mapped reads (FPKM) values, followed by the Student’s t-test (p < 0.05), we identified 3283 DEGs in Ilpum (1935 upregulated and 1348 downregulated) and 2599 DEGs in NIL (1621 upregulated and 978 downregulated) with at least a log2 (logarithm base 2) twofold change (Log2FC ≥2) in the expression level upon GRH infestation. Upregulated genes in NIL exceeded by 13.3% those recorded in Ilpum. The majority of genes associated with the metabolism of carbohydrates, amino acids, lipids, nucleotides, the activity of coenzymes, the action of phytohormones, protein modification, homeostasis, the transport of solutes, and the uptake of nutrients, among others, were abundantly upregulated in NIL (carrying Grh1). However, a high number of upregulated genes involved in photosynthesis, cellular respiration, secondary metabolism, redox homeostasis, protein biosynthesis, protein translocation, and external stimuli response related genes were found in Ilpum. Therefore, all data suggest that Grh1-mediated resistance against GRH in rice would involve a transcriptome-wide reprogramming, resulting in the activation of bZIP, MYB, NAC, bHLH, WRKY, and GRAS transcription factors, coupled with the induction of the pathogen-pattern triggered immunity (PTI), systemic acquired resistance (SAR), symbiotic signaling pathway, and the activation of genes associated with the response mechanisms against viruses. This comprehensive transcriptome profile of GRH-responsive genes gives new insights into the molecular response mechanisms underlying GRH (insect pest)–rice (plant) interaction.

In this study, we compared the quality characteristics of soft morning roll bread with different contents of two Korean high-yield tongil-type rice varieties, namely Hanareum4 and Keumkang1. The final and setback viscosities increased with increasing rice flour ratio as determined by a Rapid Visco Analyzer. The pH of the dough decreased as the rice flour ratio was decreased from 70% to 0%, regardless of the rice cultivar, and the dough rose more when less rice flour was added. During the final fermentation stage, the volumes of the dough containing Keumkang1 were 32.2, 27.5, 23.0, and 21.0 mL when 0, 30, 50, and 70% rice flour were added, respectively. The SEM images reveal that the dough forms a net-like morphology during fermentation, due to the decomposition of the wheat and rice flour. The volume and moisture contents of soft morning roll bread ranged in 90-192.5 mL and 38.25-40.06%, respectively. The volume of the Keumkang1-containing bread loaf was higher than that of the Hanareum4-containing loaf. Texture profile analysis (TPA) results suggest that the hardness and chewiness of the bread containing 30% Keumkang1 is very similar to that of the 100%-wheat bread regardless of rice varieties. The results suggest that Keumkang1 can replace wheat at a 30% level for morning roll bread purposes.

Biofouling is a major operational problem in reverse osmosis (RO) processes. Numerous studies have focused on the control of biofouling using physical and chemical cleaning methods. However, irreversible biofouling, wherein a biofilm adheres firmly to an RO membrane surface, is hard to remove by physical and chemical cleaning methods. Irreversible biofouling originated from the formation of microbial biofilms, which comprised microbial cells and their self-produced extracellular polymeric substances. In this study, we tried to control irreversible biofouling by using a biofilm inhibitor in the RO process. Prior to testing, biofouling was classified into reversible and irreversible biofouling resistance, through laboratory scale RO unit operations under enhanced biofouling conditions. A tightly attached biofilm, which assumed to be caused by irreversible biofouling resistance, emerges after 30 h of laboratory scale RO operation. We have tested the inhibition of irreversible biofouling by using 4-NPO as a quorum sensing inhibitor. The microbial biofilm formation was found to be reduced 46 – 91% by 4-NPO in a concentration-dependent manner without affecting the microbial growth. In addition, irreversible biofouling on the RO membrane was reduced 36 – 67% by 4-NPO in a concentration-dependent manner. Furthermore, 4-NPO was able to decrease the irreversible biofouling resistance, instead of the reversible biofouling resistance, in laboratory scale RO units. The results of this study clearly demonstrated that 4-NPO was an effective biofilm inhibitor that could reduce the biofouling, especially, irreversible biofouling, in RO processes.

The timely mobilization of hematopoietic stem and progenitor cells (HSPCs) is essential for maintaining hematopoietic and tissue leukocyte homeostasis. Understanding how HSPCs migrate between bone marrow (BM) and peripheral tissues is of great significance in the clinical setting, where therapeutic strategies for modulating their migration capacity determine the clinical outcome. Here, we identify an epigenetic regulator, Phc2, as a critical modulator of HSPC trafficking. The genetic ablation of Phc2 in mice causes a severe defect in HSPC mobilization through the derepression of Vcam1 in bone marrow stromal cells (BMSCs), ultimately leading to a systemic immunodeficiency. Moreover, the pharmacological inhibition of VCAM-1 in Phc2-deficient mice reverses the symptoms. We further determine that Phc2-dependent Vcam1 repression in BMSCs is mediated by the epigenetic regulation of H3K27me3 and H2AK119ub. Together, our data demonstrate a cell-extrinsic role for Phc2 in controlling the mobilization of HSPCs by finely tuning their bone marrow niche., Mobilization of hematopoietic stem and progenitor cells (HSPCs) into the circulation is essential for maintaining homeostasis. Here, the authors show that Phc2 in bone marrow stromal cells represses the cell adhesion molecule Vcam1 and facilitates mobilization of HSPCs through regulation of epigenetic marks.

This paper aims to analyze the adoption of cooperative strategies by micro and small consulting firms as a competitive advantage tool.Although the literature usually relates the examples of cooperation strategies to cases of large companies, the practice has been usual among small organizations. Increased competition and the need to survive in a competitive environment have been identified as the main causes of cooperation between small companies, who see in cooperative strategies possibilities to add value to their services (BORTOLASO; VERSCHOORE; ANTUNES, 2012; DOZ; HAMEL 1998; CHILD; FAULKNER, TALLMAN, 2005). Through a qualitative, descriptive and interpretative study it aims to relate the motivation in adopting such cooperative strategies to various economic and management lenses that provide theoretical support to the subject. The results showed that cooperative strategies practiced by micro and small consulting firms have enabled competitive advantage over companies that do not adopt them, mitigating the competitive vulnerability and adding more value to their activities.

Humanized mice, containing engrafted human cells and tissues, are emerging as an important in vivo platform for studying human diseases. Since the development of Nod scid gamma (NSG) mice bearing mutations in the IL-2 receptor gamma chain, many investigators have used NSG mice engrafted with human hematopoietic stem cells (HSCs) to generate functional human immune systems in vivo, results in high efficacy of human cell engraftment. The development of NSG mice has allowed significant advances to be made in studies on several human diseases, including cancer and graft-versus-host-disease (GVHD), and in regenerative medicine. Based on the human HSC transplantation, organ transplantation including thymus and liver in the renal capsule has been performed. Also, immune reconstruction of cells, of the lymphoid as well as myeloid lineages, has been partly accomplished. However, crosstalk between pluripotent stem cell derived therapeutic cells with human leukocyte antigen (HLA) mis/matched types and immune CD3 T cells have not been fully addressed. To overcome this hurdle, human major histocompatibility complex (MHC) molecules, not mouse MHC molecules, are required to generate functional T cells in a humanized mouse model. Here, we briefly summarize characteristics of the humanized mouse model, focusing on development of CD3 T cells with MHC molecules. We also highlight the necessity of the humanized mouse model for the treatment of various human diseases.

Background and Objectives Patients suffer from long-term diabetes can result in severe complications in multiple organs through induction of vascular dysfunctions. However, the effects of chronic hyperglycemic conditions on hematopoiesis and the microenvironment in the bone marrow (BM) are not yet well understood. Methods BM cells were harvested from femurs of mice and analyzed using flow cytometry. Human PVCs were cultured in serum-free α-MEM. After 24hrs, PVC-CM was collected and filtered through a 0.22 μm filter. Results In this study, we showed that hyperglycemia alters hematopoietic composition in the BM, which can partially be restored via paracrine mechanisms, including perivascular cells (PVCs) and NADPH oxidase (NOX) inhibition in mice with streptozotocin-induced diabetes. Prolonged hyperglycemic conditions resulted in an increase in the frequency and number of long-term hematopoietic stem cells as well as the number of total BM cells. The altered hematopoiesis in the BM was partially recovered by treatment with PVC-derived conditioned medium (CM). Long-term diabetes also increased the number of myeloid-derived suppressor cells in the BM, which was partially restored by the administration of PVC-CM and diphenyleneiodonium (DPI), a NOX inhibitor. We further showed the downregulation of ERK and p38 phosphorylation in BM cells of diabetic mice treated with PVC-CM and DPI. This may be associated with dysfunction of hematopoietic cells and promotion of subsequent diabetic complications. Conclusions Our data suggested that alterations in BM hematopoietic composition due to prolonged hyperglycemic conditions might be restored by improvement of the hematopoietic microenvironment and modulation of NOX activity.

Background Lichens, which represent symbiotic associations of fungi and algae, are potential sources of numerous natural products. Physciosporin (PHY) is a potent secondary metabolite found in lichens and was recently reported to inhibit the motility of lung cancer cells via novel mechanisms. Purpose The present study investigated the anticancer potential of PHY on colorectal cancer (CRC) cells. Methods PHY was isolated from lichen extract by preparative TLC. The effect of PHY on cell viability, motility and tumourigenicity was elucidated by MTT assay, hoechst staining, flow cytometric analysis, transwell invasion and migration assay, soft agar colony formation assay, Western blotting, qRT-PCR and PCR array in vitro as well as tumorigenicity study in vivo. Results PHY decreased the viability of various CRC cell lines (Caco2, CT26, DLD1, HCT116 and SW620). Moreover, PHY elicited cytotoxic effects by inducing apoptosis at toxic concentrations. At non-toxic concentrations, PHY dose-dependently suppressed the invasion, migration and colony formation of CRC cells. PHY inhibited the motility of CRC cells by suppressing epithelial-mesenchymal transition and downregulating actin-based motility markers. In addition, PHY downregulated β-catenin and its downstream target genes cyclin-D1 and c-Myc. Moreover, PHY modulated KAI1 C-terminal-interacting tetraspanin and KAI1 expression, and downregulated the downstream transcription factors c-jun and c-fos. Finally, PHY administration showed considerable bioavailability and effectively decreased the growth of CRC xenografts in mice without causing toxicity. Conclusion PHY suppresses the growth and motility of CRC cells via novel mechanisms.

The Rh(III)-catalyzed C-H functionalization and subsequent intramolecular cyclization between azobenzenes and vinylene carbonate is described herein. Depending on the electronic property of azobenzenes, this transformation results in the formation of (2

Background Although the efficacy of epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR- TKI) therapy has been proven in non-small cell lung cancer (NSCLC) patients, acquired resistance to EGFR-TKIs presents a serious clinical problem. Hence, the identification of new therapeutic strategy is needed to treat EGFR-TKI-resistant NSCLC. MethodsAcquired EGFR-TKI resistant lung cancer cell lines (HCC827, H1993 and H292 cells with acquired resistance to gefitinib or erlotinib) were used for cell-based studies. IncuCyte live cell analysis system and XFp analyzer were used for the determination of cell proliferation and energy metabolism, respectively. In vivo anti-cancer effect of phenformin was assessed in xenografts implanting HCC827 and gefitinib-resistant HCC827 (HCC827 GR) cells. ResultsHCC827 GR and erlotinib-resistant H1993 (H1993 ER) cells exhibited different metabolic properties compared with their respective parental cells, HCC827 and H1993. In EGFR-TKI-resistant NSCLC cells, glycolysis markers including the glucose consumption rate, intracellular lactate level, and extracellular acidification rate were decreased; however, mitochondrial oxidative phosphorylation (OXPHOS) markers including mitochondria-driven ATP production, mitochondrial membrane potential, and maximal OXPHOS capacity were increased. Cell proliferation and tumor growth were strongly inhibited by biguanide phenformin via targeting of mitochondrial OXPHOS complex 1 in EGFR-TKI-resistant NSCLC cells. Inhibition of OXPHOS resulted in a reduced NAD+/NADH ratio and intracellular aspartate levels. Recovery of glycolysis by hexokinase 2 overexpression in erlotinib-resistant H292 (H292 ER) cells significantly reduced the anti-cancer effects of phenformin.Conclusion Long-term treatment with EGFR-TKIs causes reactivation of mitochondrial metabolism, resulting in vulnerability to OXPHOS inhibitor such as phenformin. We propose a new therapeutic option for NSCLC with acquired EGFR-TKI resistance that focuses on cancer metabolism.

This study aimed to examine the relationship of general cognitive function with gaming use, and to identify elements of intelligence predicting increased gaming use. In total, 160 young adults participated in this study. Two clinical groups (n = 97) were defined: excessive gaming users diagnosed with internet gaming disorder (IGD) (n = 64) and the high-risk users (n = 33). The control group (n = 63) was also divided into regular gamers (n = 14) and non-gamers (n = 49). Participants completed the Wechsler Adult Intelligence Scale-IV and self-reported questionnaires regarding IGD severity and gaming hours. The IGD group had significantly lower Full Scale Intelligence Quotient (FSIQ), Verbal Comprehension Index (VCI), and Processing Speed Index (PSI) scores, compared with regular gamers and non-gamers. The IGD group also exhibited lower Working Memory Index (WMI) scores, compared with non-gamers. The high-risk group demonstrated significantly lower PSI score, compared with non-gamers. Furthermore FSIQ, VCI, WMI, and PSI scores were significant predictors of gaming hours in the IGD group. For the high-risk group, FSIQ, WMI, and VCI scores were negatively associated with gaming hours. Our study demonstrates the need to address the importance of enhancing working memory and verbal ability, thus, preventing the development of gaming addiction among individuals at high-risk gamers.

Background and objectives Human CD34＋ hematopoietic stem cells can reconstitute the human hematopoietic system when transplanted into immunocompromised mice after irradiation. Human leukapheresis peripheral blood (LPB)- and cord blood (CB)-derived CD34＋ cells have a similar capacity to reconstitute myeloid lineage cells in a humanized mice (hu-mice) model. However, potent stem cells, such as CB-CD34＋ cells, efficiently reconstitute the lymphoid system in vivo compared to LPB-CD34＋ cells. Modeling the human hematolymphoid system is vital for studying immune cell crosstalk in human xenografted mice, with CB-CD34＋ cells used as an optimized cell source because they are essential in reconstituting lymphoid lineage cells. Methods and results In this study, we established hu-mice that combined human characteristics with long-term survival and investigated the efficiency of the engraftment of lymphoid lineage cells derived from LPB- and CB-CD34＋ cells in the bone marrow, spleen, and LPB. We found an overall increase in the transcriptional activity of lymphoid lineage genes in CB-CD34＋ cells. Our results revealed that potent CB-CD34＋ cells displaying a general upregulation of the expression of genes involved in lymphopoiesis could contribute to the hematolymphoid system in the humanized mice model with longevity. Conclusions Our data suggest that humanized mouse model by usage of CB-CD34＋ cells displaying high expression of TFs for lymphoid lineage cells can contribute to study the immune response against lymphocytes.

Drug metabolism and pharmacokinetics (DMPK) are fundamental in drug discovery. New chemical entities (NCEs) are typically evaluated with various in vitro and in vivo assays, which are time-consuming and labor intensive. These experiments are essential in identifying potential new drugs. Recently, mass spectrometry (MS) has played a key role in examining the drug-like properties of NCEs. Quantitative and qualitative mass spectrometry approaches are routinely utilized to obtain high-quality data in an efficient, timely, and cost-effective manner. Especially, liquid chromatography (LC) coupled with MS technology has been refined for metabolite identification (Met ID), which is critical for lead optimization. These qualitative and quantitative MS approaches and their specific utility in DMPK characterization will be described in this chapter.

Probiotics must not only exert a health-promoting effect but also be capable of adapting to the harsh environment of the gastrointestinal (GI) tract. Probiotics in the GI tract must survive the cell wall-disrupting effect of bile acids. We investigated the exoproteome of Lactobacillus johnsonii PF01 and C1-10 under bile stress. A comparative analysis revealed the similarities between the two L. johnsonii exoproteomes, as well as their different responses to bile. The large number of metabolic proteins in L. johnsonii revealed its metabolic adaptation to meet protein synthesis requirements under bile stress. In addition, cell wall modifications occurred in response to bile. Furthermore, some extracellular proteins of L. johnsonii may have moonlighting function in the presence of bile. Enolase, L-lactate dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, triosephosphate isomerase, 50s ribosomal protein L7/L12, and cellobiose-specific phosphotransferase system (PTS) sugar transporter were significantly upregulated under bile stress, suggesting a leading role in the collective bile stress response of L. johnsonii from its exoproteome perspective.

e24099 Background: Taxane-associated lower extremity edema is a distinctive adverse effect of taxane, which severely compromise patients’ quality-of-life. Aroma lymphatic tressage (ALT) has been established as a complementary technique that uses a combination of aromatherapy and hand massage to relieve distress and modulate lymphatic drainage in cancer patients. This study aimed to evaluate the symptom-relieving efficacy of a short course ALT on taxane-induced lower extremity edema. Methods: Patients treated with taxane-based chemotherapy for early or advanced stage breast cancer were screened for the study. Patients were enrolled when they presented more than CTCAE G3 of lower-extremity edema. A total of 8 sessions of ALT were applied twice a week for 4 weeks after completing taxane. The primary endpoint was to determine the leg circumference change before and after receiving ALT. Patients’ subjective degree of edema, and quality-of-life were also assessed. Results: A total of 37 patients completed all sessions of planned treatment. All of the participants were female, with the median age of 55.4-years-old. 30.8% of them were premenopausal. The median height of the patients was 157.6cm, median weight was 60.9kg, and median BMI was 1.6kg/m2. Most of the patients received docetaxel (87.2%). The baseline thigh, calf, and ankle circumferences were 56.5cm, 37.4cm, and 22.6cm, each. After 8 sessions of ALT, the median circumferences decreased to 54.7cm, 36.2cm, and 21.9cm. 23 (62.2%) participants experienced a 3% or more reduction in circumference change with a month of ALT. Patients’ subjective degree of edema decreased 56.9% for 4 weeks compared to baseline, while mean body weight decreased from 62.6kg to 61.2kg. All the differences before and after the ALT were statistically significant (p-value < 0.0001) Most of the indicators assessing patients’ quality-of-life improved during the ALT periods, especially physical subscale (from 14.8 to 19.1, p-value < 0.0001). EORTC-QLQ-C30 score also improved from 70.8 to 57.1 (p-value < 0.0001). Conclusions: To our knowledge, this is the first clinical trial to evaluate clinical efficacy of ALT on taxane-associated lower extremity edema. Patients who received ALT after taxane-based chemotherapy presented significant decline of leg circumference and improvement of QoL.

Background and Objectives Human CD34＋ hematopoietic stem cells can reconstitute the human hematopoietic system when transplanted into immunocompromised mice after irradiation. Human leukapheresis peripheral blood (LPB)- and cord blood (CB)-derived CD34＋ cells have a similar capacity to reconstitute myeloid lineage cells in a humanized mice (hu-mice) model. However, potent stem cells, such as CB-CD34＋ cells, efficiently reconstitute the lymphoid system in vivo compared to LPB-CD34＋ cells. Modeling the human hematolymphoid system is vital for studying immune cell crosstalk in human xenografted mice, with CB-CD34＋ cells used as an optimized cell source because they are essential in reconstituting lymphoid lineage cells. Methods and Results In this study, we established hu-mice that combined human characteristics with long-term survival and investigated the efficiency of the engraftment of lymphoid lineage cells derived from LPB- and CB-CD34＋ cells in the bone marrow, spleen, and LPB. We found an overall increase in the transcriptional activity of lymphoid lineage genes in CB-CD34＋ cells. Our results revealed that potent CB-CD34＋ cells displaying a general upregulation of the expression of genes involved in lymphopoiesis could contribute to the hematolymphoid system in the humanized mice model with longevity. Conclusions Our data suggest that humanized mouse model by usage of CB-CD34＋ cells displaying high expression of TFs for lymphoid lineage cells can contribute to study the immune response against lymphocytes.

Drug metabolism and pharmacokinetics (DMPK) are fundamental in drug discovery. New chemical entities (NCEs) are typically evaluated with various in vitro and in vivo assays, which are time-consuming and labor intensive. These experiments are essential in identifying potential new drugs. Recently, mass spectrometry (MS) has played a key role in examining the drug-like properties of NCEs. Quantitative and qualitative mass spectrometry approaches are routinely utilized to obtain high-quality data in an efficient, timely, and cost-effective manner. Especially, liquid chromatography (LC) coupled with MS technology has been refined for metabolite identification (Met ID), which is critical for lead optimization. These qualitative and quantitative MS approaches and their specific utility in DMPK characterization will be described in this chapter.

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.

Purpose The atmospheric pressure plasma jet (APPJ) has been introduced as an effective disinfection method for titanium surfaces due to their massive radical generation at low temperatures. Helium (He) has been widely applied as a discharge gas in APPJ due to its bactericidal effects and was proven to be effective in our previous study. This study aimed to evaluate the safety and effects of He-APPJ application at both the cell and tissue levels. Methods Cellular-level responses were examined using human gingival fibroblasts and osteoblasts (MC3T3-E1 cells). He-APPJ was administered to the cells in the experimental group, while the control group received only He-gas treatment. Immediate cell responses and recovery after He-APPJ treatment were examined in both cell groups. The effect of He-APPJ on osteogenic differentiation was evaluated via an alkaline phosphatase activity assay. In vivo, He-APPJ treatment was administered to rat calvarial bone and the adjacent periosteum, and samples were harvested for histological examination. Results He-APPJ treatment for 5 minutes induced irreversible effects in both human gingival fibroblasts and osteoblasts in vitro. Immediate cell detachment of human gingival fibroblasts and osteoblasts was shown regardless of treatment time. However, the detached areas in the groups treated for 1 or 3 minutes were completely repopulated within 7 days. Alkaline phosphatase activity was not influenced by 1 or 3 minutes of plasma treatment, but was significantly lower in the 5 minute-treated group (P=0.002). In vivo, He-APPJ treatment was administered to rat calvaria and periosteum for 1 or 3 minutes. No pathogenic changes occurred at 7 days after He-APPJ treatment in the He-APPJ-treated group compared to the control group (He gas only). Conclusions Direct He-APPJ treatment for up to 3 minutes showed no harmful effects at either the cell or tissue level., Graphical Abstract

There is a recognized need in the area of explosives detection for fluorescence-based sensing systems that are capable of not only producing a turn-on response but also generating a distinctive spectral signature for a given analyte. Here, we report several supramolecular ensembles displaying efficient fluorophore displacement that give rise to an increase in fluorescence intensity upon exposure to various nitroaromatic compounds. The synthetic supramolecular constructs in question consist of a tetrathiafulvalene (TTF)-based pyrrolic macrocycle, benzo-TTF-calix[4]pyrrole (Bz-TTF-C4P), and fluorescent dyes, monomeric or dimeric naphthalenediimide (NDI) and perylenediimide (PDI) derivatives, as well as chloride or hexafluorophosphate (PF6-) salts of rhodamine 6G (Rh-6G). In chloroform solution, these assemblies exist in the form of discrete supramolecular complexes or oligomeric aggregates depending on the specific dye combinations in question. Each ensemble was tested as a potential explosive-responsive fluorescence indicator displacement assay (FIDA) by challenging it with a series of di- and trinitroaromatic compounds and examining the change in fluorescence spectral characteristics. Upon addition of nitroaromatic compounds (NACs), either a "turn-on"or a "turn-off"fluorescent response was observed depending on the nature of the constituent fluorophore and, where applicable, the counteranion. The FIDAs based on the PDI derivatives were found to display not only a ratiometric fluorescence enhancement but also analyte-dependent spectral changes when treated with NACs. The NAC-induced fluorescence spectral response of each ensemble was rationalized on the basis of various solution-phase spectroscopic studies, as well as single-crystal X-ray diffraction analyses.

Accurate prediction of pharmacokinetic (PK) and pharmacodynamic (PD) characteristics is critical for drug development. Oral drugs are particularly difficult because they are absorbed by the intestine and metabolized in the liver before systemic metabolism in vivo; this is called the first-pass effect and is a critical factor for predicting oral bioavailability (BA). Here, we fabricated a new networking and circulating cell culture system (NCCS), mimicking the circulatory system and interaction of organs for studying the pharmacokinetic and pharmacodynamics of oral drugs in vitro. NCCS consisted of a micro-pump for circulating fluids, two types of multi-insert culture dishes for culturing different cell types, and an orbital shaker for mixing; flow rate and shaking-speed were controlled by weight-sensors and drivers. A first-pass effect test was performed using functionally differentiated HepaRG and Caco-2 cell lines, using a new modified spheroid forming unit (SFU) protocol. To verify the similarity of PK (first-pass effect) data of NCCS with the data from the human body, 15 reference drugs were chosen and their associated data were obtained by liquid chromatography-mass spectrometry analysis. NCCS generated absorption and metabolism data showed >70% similarity to human data respectively. NCCS can also be used to demonstrate species differences. Animal models are the primary basis for drug discovery, development, and testing. However, the weak correlation between humans and animals, particularly regarding absorption and metabolism, is a substantial limitation for the use of animal models. Here we compare human and mouse acetaminophen (APAP) metabolism using NCCS, and its application can be extended to assess cellular responses, such as efficacy and toxicity, simultaneously.

This study investigated differences in the self-efficacy and clinical characteristics which were found relevant to addictive behaviors in young adults according to time spent gaming. To our knowledge, this is the first study to explore self-efficacy in casual gamers relative to patients with internet gaming disorder (IGD) and non-gamers. In total, 158 young adults participated in this study and were divided into three groups: excessive gamers, who were diagnosed with IGD based on the Diagnostic and Statistical Manual of Mental Disorder-fifth edition (DSM-5, n = 71); casual gamers, who played games regularly but did not meet the criteria for IGD (n = 37); and non-gamers/controls, who did not engage in gaming (n = 50). All participants completed self-administered questionnaires, including measures of self-efficacy and clinical features such as the Barratt Impulsiveness Scale, Beck Depression Inventory, Beck Anxiety Inventory, Behavioral Activation/Inhibition Systems, aggression, and psychosocial well-being. There were significant differences in the self-efficacy according to the extent of gaming (excessive gamers < casual gamers < non-gamers). In addition, aggression, impulsivity, depression, anxiety, level of stress, and behavioral inhibition system scores were significantly higher in excessive gamers than in casual gamers and non-gamers. These findings showed that individuals who spend more time playing games tend to have lower self-efficacy. Our study suggests that self-efficacy may protect against or constitute a risk of excessive gaming, particularly among casual gamers. It is necessary to pay attention to enhancing psychological well-being through self-efficacy to prevent addiction in young adult gamers.

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.

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.

Background: Ginseng is one of the well-known medicinal plants, exhibiting diverse medicinal effects. Its roots possess anticancer and antiaging properties and are being used in the medical systems of East Asian countries. It is grown in low-light and low-temperature conditions, and its growth is strongly inhibited at temperatures above 25°C. However, the molecular responses of ginseng to heat stress are currently poorly understood, especially at the protein level. Methods: We used a shotgun proteomics approach to investigate the effect of heat stress on ginseng leaves. We monitored their photosynthetic efficiency to confirm physiological responses to a high-temperature stress. Results: The results showed a reduction in photosynthetic efficiency on heat treatment (35°C) starting at 48 h. Label-free quantitative proteome analysis led to the identification of 3,332 proteins, of which 847 were differentially modulated in response to heat stress. The MapMan analysis showed that the proteins with increased abundance were mainly associated with antioxidant and translation-regulating activities, whereas the proteins related to the receptor and structural-binding activities exhibited decreased abundance. Several other proteins including chaperones, G-proteins, calcium-signaling proteins, transcription factors, and transfer/carrier proteins were specifically downregulated. Conclusion: These results increase our understanding of heat stress responses in the leaves of ginseng at the protein level, for the first time providing a resource for the scientific community. Keywords: High temperature, Panax ginseng, Photosynthetic efficiency, Shotgun proteomics

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.

This study identified the characteristics of fashion rental service users as well as analyzed their purchase decisionmaking processes. A qualitative investigation was conducted through in-depth interviews with 13 women in their 20s-30s who have experienced renting fashion items due to a high interest in fashion. The results of the study are summarized as follows. The need recognition stage analyzed ventilation by mass media, SNS impact, curiosity, saving shopping time and money, awareness of situational necessity, and creation of various styles. The information search stage analyzed how users obtained information from 2 different sources of nonmarketer-dominated sources and marketer-dominated sources. The pre-purchase stage analyzed the evaluation of alternatives in which study participants used 2 evaluation criteria for fashion rental services and fashion rental items. The purchase stage analyzed how participants wait and select desired items (when receiving the notification of rentable items) or select alternative products. The consumption stage examined the usage frequency and usage method. The study divided the post-consumption evaluation stage into 2 categories for evaluation: personal feelings and service. The post-consumption behavior stage analyzed how participants displayed WOM, eWOM and purchase rental product behavior. Clothing shopping orientation of study participants is displayed in 5 dimensions of brand-seeking propensity, individuality-seeking propensity, economic efficiency-seeking propensity, rationality-seeking propensity, and pleasure-seeking propensity. This study identified three main characteristics in the study participants: interest in the fashion, favorable attitude toward used fashion items, consciousness of others.

Usnic acid (UA), a lichen secondary substance, has considerable anticancer activity in vitro, whereas its effect in vivo is limited. Here, potassium usnate (KU) was prepared by the salinization of UA to enhance its water solubility. KU showed increased bioavailability compared with UA in the tumor, liver, and plasma of a CT26 syngeneic mouse tumor xenograft model after oral administration, as determined by LC-MS/MS analysis. KU exhibited potent anticancer effects on colorectal cancer cells and inhibited liver metastasis in an orthotopic murine colorectal cancer model. KU treatment downregulated the epithelial-mesenchymal markers Twist, Snail, and Slug and the metastasis-related genes CAPN1, CDC42, CFL1, IGF1, WASF1, and WASL in cells and tumor tissues. The present results suggest the potential application of the water-soluble form of UA, KU, in anticancer therapy.

This study was carried out to compare the physiochemical properties and quality characteristics of porridge made from different Korean rice varieties, including high yield tongil-type rice. The rice varieties used in this study were 4 tongil-type (Areum, Namcheon, Hanareum3, Hanareum4) and 5 japonica-type rices (Unkwang, Daebo, Goami4, Dodamssal and Hwaseonchal). The protein and amylose contents of the varieties ranged from 6.0% (Namcheon) to 7.3% (Hanareum3) and from 5.0% (Hwaseonchal) to 42.8% (Dodamssal). Compared to the other varieties, Hwaseonchal and Dodamssal had low final and setback viscosity values in the rapid-visco analyzer test. The color value of the porridge ranged between 52.90 and 71.12 for the L value, -2.06 and -1.01 for the a value, and -5.59 and -2.62 for the b value. SEM images revealed distinct differences in the endosperm structure of rice varieties as well as the porridge. Furthermore, porridge made from Hwaseonchal rice had the highest spreadability, followed by porridge made from others non-glutinous rice varieties, Goami4 rice, and Dodamssal rice. The results of this study suggested that rice varieties with different amylose contents could be effectively used to control the viscosity of rice porridge. In laboratory experiments, the sensory test did not indicate significant differences except for the mouthfeel. The mouthfeel of the porridge depended on the amylose content of rice. This study suggested that tongil-type rice variety such as Hanareum4 could be substituted with Japonica type rice for making porridge.