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Background and Purpose: Chitinase‐3‐like 1 (CHI3L1) causes skin inflammation in the progression of atopic dermatitis. We investigated if anti‐CHI3L1 antibody could prevent the development of atopic dermatitis and its mechanisms of action. Experimental Approach: The effect of CHI3L1 antibody on phthalic anhydride‐induced atopic dermatitis animal model and in vitro reconstructed human skin (RHS) model were investigated. Expression and release of atopic dermatitis‐related cytokines were determined using an enzyme‐linked immunosorbent assay, and RT‐qPCR, STAT3 and CXCL8 signalling were measured by western blotting. Key Results: Anti‐CHI3L1 antibody suppressed phthalic anhydride‐induced epidermal thickening, clinical score, IgE level and infiltration of inflammatory cells, and reduced phthalic anhydride‐induced inflammatory cytokines concentration. In addition, CHI3L1 antibody treatment inhibited the expression of STAT3 activity in phthalic anhydride‐treated skin. It was also confirmed that CHI3L1 antibody treatment alleviated atopic dermatitis‐related inflammation in the RHS model. The inhibitory effects of CHI3L1 antibody was similar or more effective compared with that of the IL‐4 antibody. We further found that CHI3L1 is associated with CXCL8 by protein‐association network analysis. siRNA of CHI3L1 blocked the mRNA levels of CHI3L1, IL‐1β, IL‐4, CXCL8, TSLP, and the expression of CHI3L1 and p‐STAT, and the level of CXCL8, whereas recombinant level of CXCL8 was elevated. Moreover, siRNA of STAT3 reduced the mRNA level of these cytokines. CHI3L1 and p‐STAT3 expression correlated with the reduced CXCL8 level in the RHS in vitro model. Conclusion and Implications: Our data demonstrated that CHI3L1 antibody could be a promising effective therapeutic drug for atopic dermatitis. [ABSTRACT FROM AUTHOR]

Human papillomavirus (HPV) is an important causative factor of cervical cancer and is associated with nonsmall cell lung cancer (NSCLC). Merkel cell polyomavirus (MCPyV) is a rare and highly fatal cutaneous virus that can cause Merkel cell carcinoma (MCC). Although coinfection with oncogenic HPV and MCPyV may increase cancer risk, a definitive etiological link has not been established. Recently, genomic variation and genetic diversity in the MCPyV noncoding control region (NCCR) among ethnic groups has been reported. The current study aimed to provide accurate prevalence information on HPV and MCPyV infection/coinfection in NSCLC patients and to evaluate and confirm Korean MCPyV NCCR variant genotypes and sequences. DNA from 150 NSCLC tissues and 150 adjacent control tissues was assessed via polymerase chain reaction (PCR) targeting regions of the large T antigen (LT‐ag), viral capsid protein 1 (VP1), and NCCR. MCPyV was detected in 22.7% (34 of 150) of NSCLC tissues and 8.0% (12 of 150) of adjacent tissues from Korean patients. The incidence rates of HPV with and without MCPyV were 26.5% (nine of 34) and 12.9% (15 of 116). The MCPyV NCCR genotype prevalence in Korean patients was 21.3% (32 of 150) for subtype I and 6% (nine of 150) for subtype IIc. Subtype I, a predominant East Asian strain containing 25 bp tandem repeats, was most common in the MCPyV NCCR data set. Our results confirm that coinfection with other tumor‐associated viruses is not associated with NSCLC. Although the role of NCCR rearrangements in MCPyV infection remains unknown, future studies are warranted to determine the associations of MCPyV NCCR sequence rearrangements with specific diseases. [ABSTRACT FROM AUTHOR]

Salt and drought are documented among the most detrimental and persistent abiotic stresses for crop production. Here, we investigated the impact of Pseudomonas koreensis strain S4T10 on plant performance under salt and drought stress. Arabidopsis thaliana Col-0 wild type and atnced3 mutant plants were inoculated with P. koreensis or tap water and exposed to NaCl (100 mM) for five days and drought stress by withholding water for seven days. P. koreensis significantly enhanced plant biomass and photosynthetic pigments under salt and drought stress conditions. Moreover, P. koreensis activated the antioxidant defence by modulating glutathione (GSH), superoxide dismutase (SOD), peroxidase (POD), and polyphenol oxidase (PPO) activities to scavenge the reactive oxygen species produced due to the stress. In addition, the application of P. koreensis upregulated the expression of genes associated with antioxidant responses, such as AtCAT1, AtCAT3, and AtSOD. Similarly, genes linked to salt stress, such as AtSOS1, AtSOS2, AtSOS3, AtNHX1, and AtHKT1, were also upregulated, affirming the positive role of P. koreensis S4T10 in streamlining the cellular influx and efflux transport systems during salt stress. Likewise, the PGPB inoculation was observed to regulate the expression of drought-responsive genes AtDREB2A, AtDREB2B, and ABA-responsive genes AtAO3, AtABA3 indicating that S4T10 enhanced drought tolerance via modulation of the ABA pathway. The results of this study affirm that P. koreensis S4T10 could be further developed as a biofertilizer to mitigate salt and drought stress at the same time. [ABSTRACT FROM AUTHOR]

We recently established a long‐term SARS‐CoV‐2 infection model using lung‐cancer xenograft mice and identified mutations that arose in the SARS‐CoV‐2 genome during long‐term propagation. Here, we applied our model to the SARS‐CoV‐2 Delta variant, which has increased transmissibility and immune escape compared with ancestral SARS‐CoV‐2. We observed limited mutations in SARS‐CoV‐2 Delta during long‐term propagation, including two predominant mutations: R682W in the spike protein and L330W in the nucleocapsid protein. We analyzed two representative isolates, Delta‐10 and Delta‐12, with both predominant mutations and some additional mutations. Delta‐10 and Delta‐12 showed lower replication capacity compared with SARS‐CoV‐2 Delta in cultured cells; however, Delta‐12 was more lethal in K18‐hACE2 mice compared with SARS‐CoV‐2 Delta and Delta‐10. Mice infected with Delta‐12 had higher viral titers, more severe histopathology in the lungs, higher chemokine expression, increased astrocyte and microglia activation, and extensive neutrophil infiltration in the brain. Brain tissue hemorrhage and mild vacuolation were also observed, suggesting that the high lethality of Delta‐12 was associated with lung and brain pathology. Our long‐term infection model can provide mutant viruses derived from SARS‐CoV‐2 Delta and knowledge about the possible contributions of emergent mutations to the properties of new variants. [ABSTRACT FROM AUTHOR]

Preparation of highly enantioenriched six‐membered 1,4‐N,N‐ and N,O‐heterocycles has been developed through [4 + 2] heteroannulation of α‐bromoacetates with 1,4‐binucleophiles. Two consecutive substitutions of highly diastereoenriched L‐serinate‐derived α‐bromoacetates provide convenient access to a wide range of C‐aryl/aliphatic substituted 1,4‐N,N‐ and N,O‐heterocycles with up to 99:1 er. [ABSTRACT FROM AUTHOR]

The industrial potential of Saccharomyces cerevisiae has extended beyond its traditional use in fermentation to various applications, including recombinant protein production. Herein, comparative genomics was performed with three industrial S. cerevisiae strains and revealed a heterozygous diploid genome for the 98‐5 and KSD‐YC strains (exploited for rice wine fermentation) and a haploid genome for strain Y2805 (used for recombinant protein production). Phylogenomic analysis indicated that Y2805 was closely associated with the reference strain S288C, whereas KSD‐YC and 98‐5 were grouped with Asian and European wine strains, respectively. Particularly, a single nucleotide polymorphism (SNP) in FDC1, involved in the biosynthesis of 4‐vinylguaiacol (4‐VG, a phenolic compound with a clove‐like aroma), was found in KSD‐YC, consistent with its lack of 4‐VG production. Phenotype microarray (PM) analysis showed that KSD‐YC and 98‐5 displayed broader substrate utilization than S288C and Y2805. The SNPs detected by genome comparison were mapped to the genes responsible for the observed phenotypic differences. In addition, detailed information on the structural organization of Y2805 selection markers was validated by Sanger sequencing. Integrated genomics and PM analysis elucidated the evolutionary history and genetic diversity of industrial S. cerevisiae strains, providing a platform to improve fermentation processes and genetic manipulation. [ABSTRACT FROM AUTHOR]

Problem: Direct interactions between macrophages and lymphatic vessels have been shown previously. In pre‐eclampsia (PE), macrophages are dominantly polarized into a proinflammatory M1 phenotype and lymphangiogenesis is defective in the decidua. Here, we investigated whether decidual lymphatic endothelial cells (dLECs) affect macrophage polarization in PE. Method of Study: THP‐1 macrophages were cocultured with dLECs or cultured in the conditioned medium (CM) of dLECs. Macrophage polarization was measured using flow cytometry. Granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) expression in dLECs was measured using qRT‐PCR and ELISA. The activation of nuclear translocation of nuclear factor‐κ (NF‐κB), an upstream signaling molecule of GM‐CSF, was assessed by immunocytochemical localization of p65. Through GM‐CSF knockdown and NF‐κB inhibition in dLEC, we evaluated whether the GM‐CSF/NF‐κB pathway of PE dLEC affects decidual macrophage polarization. Results: The ratio of inflammatory M1 macrophages with HLA‐DR+/CD80+ markers significantly increased following coculturing with PE dLECs or culturing in PE dLEC CM, indicating that the PE dLEC‐derived soluble factor acts in a paracrine manner. GM‐CSF expression was significantly upregulated in PE dLECs. Recombinant human GM‐CSF induced macrophage polarization toward an M1‐like phenotype, whereas its knockdown in PE dLECs suppressed it, suggesting PE dLECs induce M1 macrophage polarization by secreting GM‐CSF. The NF‐κB p65 significantly increased in PE dLECs compared to the control, and pretreatment with an NF‐κB inhibitor significantly suppressed GM‐CSF production from PE dLECs. Conclusions: In PE, dLECs expressing high levels of GM‐CSF via the NF‐κB‐dependent pathway play a role in inducing decidual M1 macrophage polarization. [ABSTRACT FROM AUTHOR]

Modular three‐component synthesis of highly enantioenriched 2,4,6‐trisubstituted dihydropyridazinones was developed through the nucleophilic substitution of α‐bromoacetates with silyl enol ethers and subsequent condensation with hydrazine derivatives. [ABSTRACT FROM AUTHOR]

Understanding charge transport in π‐conjugated polymers is critical for the design of high‐mobility polymers. However, charge transport in donor–acceptor (D–A) type copolymers and the roles of D and A units are still unclear. Herein, the charge transport properties of three cyclopentadithiophene (CDT)‐based D–A type copolymers with CDT as a common donor and benzothiadiazole, fluoro‐2,1,3‐benzothiadiazole, or pyridyl‐2,1,3‐thiadiazole (PTz) as an acceptor are investigated. The best charge transport is found for CDT‐PTz showing 0.79 ± 0.01 cm2 V−1 s−1 hole mobility in field‐effect transistors, with the lowest energetic disorder by temperature‐dependent mobility measurements. Using various structural probes and density functional theory simulations, it is found that CDT‐PTz has the most rigid and planar backbone structure and the strongest intramolecular dipole moment thanks to the noncovalent N–S interactions and the strong electron‐withdrawing PTz acceptor unit. These structural properties lead to strong intermolecular interactions in CDT‐PTz, reducing its π–π stacking distance, producing strong aggregation even in hot dilute solutions. The enhanced mobility in CDT‐PTz is attributed to this high quality π–π stacking, driven by increased backbone rigidity and strong molecular dipoles. This work suggests that rigidifying the copolymer backbone with enhanced push–pull strength of the D–A units is a key requirement for high‐mobility D–A copolymers. [ABSTRACT FROM AUTHOR]

During refrigerated storage, aged beef is liable to undergo alterations in its physicochemical properties. This study aimed to evaluate changes in the community of microorganisms, volatile compounds, and amino acids in aged beef under cold storage conditions. In addition, volatile basic nitrogen (VBN) values were measured to determine the putrefaction degree. Raw‐, dry‐, and wet‐aged beef were stored at 4°C for 21 days. The initial pH of beef under the three conditions ranged from 5.52 to 5.60 and decreased from 5.04 to 5.33 over time. After 21 days, VBN values ranged 20.53–22.59 mg/100 g, which exceeded the standard of spoilage (20 mg/100 g) in the Korean Food Code. As time passed, numbers of psychrophilic and lactic acid bacteria increased in the raw beef. In contrast, number of mesophilic, psychrophilic, and lactic acid bacteria decreased in dry‐ and wet‐aged beef. Among the volatile substances and amino acids, 2,3‐butanedione, 2‐butanone, tyrosine, and arginine contributed the most to the high VBN levels in aged beef, where the VBN was 21 mg/100 g at 21 days, which was beyond the acceptable limit. In conclusion, clear alterations were observed in the physicochemical properties and microorganism communities in cold‐stored aged beef, providing basic information that could benefit the beef industry and boost consumer acceptance. [ABSTRACT FROM AUTHOR]

Furthermore, the analysis of the reconstructed human skin (RHS) tissue AD model confirmed that CHI3L1-Ab treatment reduced skin inflammation by inhibiting the CHI3L1/NF- B/ITGA5 axis (Figure 3E-I). After confirming that CHI3L1 regulates AD-related skin inflammation, we examined the therapeutic effect of CHI3L1-antibody (Ab). Furthermore, the inhibition of CHI3L1 by CHI3L1-Ab suppresses AD-like symptoms and inflammatory responses by regulating CHI3L1, the NF- B/ITGA5 axis. [Extracted from the article]

Our previous big data analyses showed a high level of association between chitinase 3 like1 (CHI3L1) expression and lung tumor development. In the present study, we investigated whether a CHI3L1‐inhibiting chemical, 2‐({3‐[2‐(1‐cyclohexen‐1‐yl)ethyl]‐6,7‐dimethoxy‐4‐oxo‐3,4‐dihydro‐2‐quinazolinyl}sulfanyl)‐N‐(4‐ethylphenyl)butanamide (K284), could inhibit lung metastasis and studied its mechanism of action. We investigated the antitumor effect of K284 both in vitro and in vivo. K284 (0.5 mg·kg−1 body weight) significantly inhibited lung metastasis in in vivo models after injection of murine melanoma cells (B16F10) or adenocarcinomic human alveolar basal epithelial cells (A549). K284 significantly and concentration‐dependently also inhibited cancer cell proliferation and migration in the A549 and H460 lung cancer cell lines. We found that the binding of K284 to the chitin‐binding domain (CBD) of CHI3L1 prevented the binding of CHI3L1 to its receptor, interleukin‐13 receptor subunit alpha‐2 (IL‐13Rα2), thereby suppressing the CHI3L1 signal. This blocking of the CHI3L1‐IL‐13Rα2 signal caused the inhibition of c‐Jun N‐terminal kinase (JNK)‐activator protein 1 (AP‐1) signals, resulting in the prevention of lung metastasis and cancer cell growth. Our data demonstrate that K284 may serve as a potential candidate anticancer compound targeting CHI3L1. [ABSTRACT FROM AUTHOR]

Glucose metabolism is a mechanism by which energy is produced in form of adenosine triphosphate (ATP) by mitochondria and precursor metabolites are supplied to enable the ultimate enrichment of mature metabolites in the cell. Recently, glycolytic enzymes have been shown to have unconventional but important functions. Among these enzymes, pyruvate kinase M2 (PKM2) plays several roles including having conventional metabolic enzyme activity, and also being a transcriptional regulator and a protein kinase. Compared with the closely related PKM1, PKM2 is highly expressed in cancer cells and embryos, whereas PKM1 is dominant in mature, differentiated cells. Posttranslational modifications such as phosphorylation and acetylation of PKM2 change its cellular functions. In particular, PKM2 can translocate to the nucleus, where it regulates the transcription of many target genes. It is notable that PKM2 also acts as a protein kinase to phosphorylate several substrate proteins. Besides cancer cells and embryonic cells, astrocytes also highly express PKM2, which is crucial for lactate production via expression of lactate dehydrogenase A (LDHA), while mature neurons predominantly express PKM1. The lactate produced in cancer cells promotes tumor progress and that in astrocytes can be supplied to neurons and may act as a major source for neuronal ATP energy production. Thereby, we propose that PKM2 along with its different posttranslational modifications has specific purposes for a variety of cell types, performing unique functions. [ABSTRACT FROM AUTHOR]

2‐Aminophenol displays a diverse pattern of reactivity in the substitution reaction of α‐bromoacetate. The substitution under neutral or basic conditions results in the formation of 1,4‐benzoxazinones, whereas Lewis acid‐promoted substitution leads to Friedel–Crafts alkylation of 2‐aminophenol. Asymmetric synthesis of two regioisomeric 1,4‐benzoxazinones is accomplished from the nucleophilic substitution of highly diastereoenriched α‐aryl‐α‐bromoacetates with N‐alkyl‐2‐aminophenols under varied reaction conditions. [ABSTRACT FROM AUTHOR]

The development of new methods for the direct synthesis of bioactive molecules is a pivotal topic in organic and medicinal chemistry. Herein, we describe the rhodium(III)‐catalyzed C−H functionalization of N‐aryl phthalazinones with maleimides. The complete site‐selectivity and broad functional group tolerance are observed. Notably, this protocol allows the direct integration of phthalazinones and succinimides, which are vital motifs found in bioactive natural products and pharmaceuticals. [ABSTRACT FROM AUTHOR]

Preeclampsia is a syndrome characterized by deterioration of either the maternal condition or the fetal condition. The adverse intrauterine environment made by preeclampsia results into intrauterine growth restriction and increased risk of a variety of diseases in future life. Given the adverse environment of fetal circulation made in the preeclamptic condition, and the role of mesenchymal stem cell (MSC) as a multipotent progenitor cell, we hypothesized that MSCs derived from human umbilical cord blood (hUCB-MSCs) obtained from preeclampsia are adversely altered or affected compared with normal pregnancy. The aim of this study was to analyze the biological characteristics and compare the functional abilities and gene expression patterns of hUCB-MSCs originating from pregnant women with and without severe preeclampsia. hUCB-MSCs were isolated and cultured from 28 pregnant women with severe preeclampsia and 30 normal pregnant women. hUCB-MSCs obtained from women with preeclampsia were less proliferative and more senescent and had lower telomerase activity and higher ROS activity than cells from women with normal pregnancy. In addition, many senescence-related differentially expressed genes (DEGs) were identified by analysis of microarray gene expression profiles and significantly associated with the Gene Ontology term cell aging. In conclusion, hUCB-MSCs obtained from women with preeclampsia showed the poorly proliferative, more senescent, and decreased telomerase activity, and these characters may be related with functional impairment of MSC from preeclampsia compared with cells from normal pregnancy. [ABSTRACT FROM AUTHOR]

We determined the toxin gene profile, toxin production, antibiotic resistance coagulase serotype, and genetic diversity of 42 coagulase‐positive Staphylococcus aureus (CPS) isolates collected from 1,464 cream‐filled bakery products in Korea. Among the CPS isolates, 37 (88.1%) produced enterotoxin genes in combination with another toxin; 26 (61.9%) of the strains were positive for sea, 1 (2.4%) for sea‐seb, and 4 (9.5%) for sea‐sec. Among the strains showing antibiotic resistance, 28 (66.7%) showed resistance to only one antibiotic, whereas nine (21.4%) showed resistance to multiple antibiotics: 4 (9.5%) strains were both mecA‐positive and oxacillin‐resistant. Most strains are resistant to at least one antibiotic—benzyl penicillin. The CPS isolates were classified into eight coagulase serotypes. This information will be valuable for assessing the capability risks of CPS food poisoning, contributing a better known of the epidemiology result associated with CPS contamination in bakery products. [ABSTRACT FROM AUTHOR]

Highly stereoselective C–O bond formation in AgOTf‐catalyzed substitution of configurationally labile α‐bromo aryl acetates with neutral alcohol is developed. Also, application of this asymmetric synthetic methodology to the preparation of highly enantioenriched 2‐aryl‐substituted morpholine derivatives is presented. [ABSTRACT FROM AUTHOR]

Problem: The lymphatic vasculature controls leukocytes trafficking and limits the adaptive immune response. In previous models of preeclampsia (PE), defective immune function caused by disruption of lymphangiogenesis was shown to be involved in the disease pathophysiology. Especially, the dysfunction of regulatory T cells (Treg) at the maternal‐fetal interface may be one of the causes of severe PE. In particular, activation of Tregs to obtain immune tolerance requires adequate antigen presentation through the lymphatic system. We hypothesized that impaired lymphangiogenesis and imbalanced Tregs at the maternal‐fetal interface are associated with the pathophysiology of severe PE. However, the current research addressing this hypothesis is limited. Therefore, to compare differences in lymphangiogenesis in severe PE and normal conditions, we aimed to examine the location of lymphatics at the maternal‐fetal interface and to investigate the association between lymphangiogenesis and Tregs in severe PE. Method of Study: We obtained entire uterus from normal pregnant mice. Placental and fetal membranes, including decidua, were obtained from 10 pregnant women with severe PE and 10 gestational age‐matched controls. Immunohistochemistry for LYVE1 was used to localize the distribution of lymphatic vessels and CD4, CD25, and FOXP3 for Treg. Results: LYVE1‐positive vessels were present in the uterine wall of mice. LYVE1‐positive lymphatic vessels were localized on the human decidua. Tubular lymphatics were abundant in the control decidua, but significantly reduced in severe PE. Furthermore, lymphatic vessel density correlated with the number of decidual Tregs. Conclusion: Abnormal decidual lymphangiogenesis is associated with reduced numbers of decidual Tregs in severe PE. [ABSTRACT FROM AUTHOR]

Homeostasis and regeneration of corneal epithelia are sustained by limbal epithelial stem cells (LESCs); thus, an LESC deficiency is a major cause of blindness worldwide. Despite the generally promising results of cultivated LESC transplantation, it has been limited by variations in long-term success rates, the use of xenogeneic and undefined culture components, and a scarcity of donor tissues. In this study, we identified the culture conditions required to expand LESCs in vitro and established human limbus-derived highly proliferative ABCG2+/ABCB5+ double-positive LESCs. These LESCs exhibited the LESC marker profile and differentiated into corneal epithelial cells. In addition, cultured LESCs expressed high levels of the stem cell markers Sox2, Oct4, c-Myc, and Klf4, had high telomerase activity, and had stable, normal genomes. These results suggest that our novel cultivation protocol affects the phenotype and differentiation capacity of LESCs. From the limbus, which contains a heterogenous cell population, we have derived highly proliferative ABCG2+/ABCB5+ double-positive cells with the ability to differentiate into corneal epithelial cells. This study opens a new avenue for investigation of the molecular mechanism of LESC maintenance and expansion in vitro and may impact the treatment of corneal disease, particularly corneal blindness due to an LESC deficiency. [ABSTRACT FROM AUTHOR]

Ascertaining the authenticity of the unrefined sesame oil presents an ongoing challenge. Here, the determination of 2-propenal was performed by headspace solid-phase microextraction (HS-SPME) under mild temperature coupled to gas chromatography with time-of-flight mass spectrometry, enabling the detection of adulteration of unrefined sesame oil with refined corn or soybean oil. Employing this coupled technique, 2-propenal was detected in all tested refined corn and soybean oils but not in any of the tested unrefined sesame oil samples. Using response surface methodology, the optimum extraction temperature, equilibrium time, and extraction time for the HS-SPME analysis of 2-propenal using carboxen/polydimethylsiloxane fiber were determined to be 55°C, 15 min, and 15 min, respectively, for refined corn oil and 55°C, 25 min, and 15 min, respectively, for refined soybean oil. Under these optimized conditions, the adulteration of unrefined sesame oil with refined corn or soybean oils (1–5%) was successfully detected. The detection and quantification limits of 2-propenal were found to be in the range of 0.008–0.010 and 0.023–0.031 µg mL−1, respectively. The overall results demonstrate the potential of this novel method for the authentication of unrefined sesame oil. [ABSTRACT FROM AUTHOR]

ABSTRACT A hydrophobic polyacrylamide (HPAM) was synthesized by aqueous free-radical chain polymerization to understand the adsorption action of the polymer on the calcite during operating stimulation. The polymer was designed as acrylamide (AM)/2-acrylamide-2-methylpropanesulfonic acid (AMPS)/2-methacryloyloxyethyl 12-alkyl dimethyl ammonium bromide (MADA). The structure of the polymer was characterized by Fourier transform infrared spectroscopy. The adsorption properties of the polyacrylamide onto pure calcite was investigated. When we compared the ζ potentials of the calcite particles in the presence and absence of HPAM, the adsorbed amount was affected by different factors, and the adsorption behaviors were examined to determine the adsorption layer. The results of the ζ potential measurements indicated that the particles were negatively charged between pHs of 6 and 12, and the presence of HPAM did not reverse that. Equilibrium adsorption studies showed that the adsorbed amount was affected by the concentration of HPAM, liquid-to-solid ratio, calcite particle size, concentration of background ions, and temperature, which were related the adsorption behaviors of HPAM. Hydrogen bonds between HPAM and calcite were important because the adsorbed amount was significantly reduced when the hydrogen bonds were broken by urea. It is necessary to develop a more active reagent that can break the hydrogen bonds and improve the effect of hydraulic fracturing. © 2017 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2017, 134, 45314. [ABSTRACT FROM AUTHOR]

Endoplasmic reticulum ( ER) stress is emerging as a factor for the pathogenesis of granular corneal dystrophy type 2 ( GCD2). This study was designed to investigate the molecular mechanisms underlying the protective effects of melatonin on ER stress in GCD2. Our results showed that GCD2 corneal fibroblasts were more susceptible to ER stress-induced death than were wild-type cells. Melatonin significantly inhibited GCD2 corneal cell death, caspase-3 activation, and poly ( ADP-ribose) polymerase 1 cleavage caused by the ER stress inducer, tunicamycin. Under ER stress, melatonin significantly suppressed the induction of immunoglobulin heavy-chain-binding protein (BiP) and activation of inositol-requiring enzyme 1α ( IRE1α), and their downstream target, alternative splicing of X-box binding protein 1(XBP1). Notably, the reduction in BiP and IRE1α by melatonin was suppressed by the ubiquitin-proteasome inhibitor, MG132, but not by the autophagy inhibitor, bafilomycin A1, indicating involvement of the ER-associated protein degradation ( ERAD) system. Melatonin treatment reduced the levels of transforming growth factor-β-induced protein ( TGFBIp) significantly, and this reduction was suppressed by MG132. We also found reduced mRNA expression of the ERAD system components HRD1 and SEL1L, and a reduced level of SEL1L protein in GCD2 cells. Interestingly, melatonin treatments enhanced SEL1L levels and suppressed the inhibition of SEL1L N-glycosylation caused by tunicamycin. In conclusion, this study provides new insights into the mechanisms by which melatonin confers its protective actions during ER stress. The results also indicate that melatonin might have potential as a therapeutic agent for ER stress-related diseases including GCD2. [ABSTRACT FROM AUTHOR]

Ex vivo culture of human limbal epithelial cells (LECs) is used to treat limbal stem cell (LSC) deficiency, a vision loss condition, and suitable culture systems using feeder cells or serum without animal elements have been developed. This study evaluated the use of human umbilical cord or placenta mesenchymal stem cells (C-MSCs or P-MSCs, resp.) as feeder cells in an animal/serum-free coculture system with human LECs. C-/P-MSCs stimulated LEC colony formation of the stem cell markers (p63, ABCG2) and secreted known LEC clonal growth factors (keratinocyte growth factor, β-nerve growth factor). Transforming growth factor-β-induced protein (TGFBIp), an extracellular matrix (ECM) protein, was produced by C-/P-MSCs and resulted in an increase in p63+ ABCG2+ LEC colonies. TGFBIp-activated integrin signaling molecules (FAK, Src, and ERK) were expressed in LECs, and TGFBIp-induced LEC proliferation was effectively blocked by a FAK inhibitor. In conclusion, C-/P-MSCs enhanced LEC culture by increasing growth of the LSC population by secreting growth factors and the ECM protein TGFBIp, which is suggested to be a novel factor for promoting the growth of LECs in culture. C-/P-MSCs may be useful for the generation of animal-free culture systems for the treatment of LSC deficiency. [ABSTRACT FROM AUTHOR]

In this study, an aquaporin protein, Aqp1, in Cryptococcus neoformans, which can lead either saprobic or parasitic lifestyles and causes life-threatening fungal meningitis was identified and characterized. AQP1 expression was rapidly induced (via the HOG pathway) by osmotic or oxidative stress. In spite of such transcriptional regulation, Aqp1 was found to be largely unnecessary for adaptation to diverse environmental stressors, regardless of the presence of the polysaccharide capsule. The latter is shown here to be a key environmental-stress protectant for C. neoformans. Furthermore, Aqp1 was not required for the development and virulence of C. neoformans. Deletion of AQP1 increased hydrophobicity of the cell surface. The comparative metabolic profiling analysis of the aqp1Δ mutant and AQP1-overexpressing strains revealed that deletion of AQP1 significantly increased cellular accumulation of primary and secondary metabolites, whereas overexpression of AQP1 depleted such metabolites, suggesting that this water channel protein performs a critical function in metabolic homeostasis. In line with this result, it was found that the aqp1Δ mutant (which is enriched with diverse metabolites) survived better than the wild type and a complemented strain, indicating that Aqp1 is likely to be involved in competitive fitness of this fungal pathogen. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to assess whether nestin is expressed during differentiation of endothelial progenitor cells (EPCs) obtained from human umbilical cord blood (HUCB), and nestin expression is changed in hypoxia-conditioned culture of human umbilical vein endothelial cells (HUVECs). Methods: Among deliveries at our institute, 20 normal pregnant women who delivered by cesarean section at 37-40 weeks' gestation were selected. HUCB mononuclear cells (MNCs) from HUCB were isolated and cultivated. After characterization of CXCR4/KDR/CD34 positive cells (EPCs) by flow cytometry and fluorescent chemical staining, EPC culture was continued through day 10 for differentiation to outgrowth endothelial cell (OEC). For identification of EPC and OEC, RT-PCR was performed for each specific cell markers, such as AC133, CD45, CXCR4, CDH5, vWF, eNOs, CD34, and Flt 1. HUVECs were isolated from human umbilical cord veins by collagenase treatment. Culture of HUVEC in hypoxic and normoxic conditions was performed for 24 h. Nestin expression in EPCs, OECs and HUVECs was detected by RT-PCR and Western blotting. Results: Western blot analysis and RT-PCR revealed that nestin was not expressed in EPC, but well expressed in OECs and HUVECs. During 24 h of HUVEC culture, time course gene expression of VEGF was significantly increased, but nestin was not changed. Conclusions: Our results showed that nestin could be used as a new differentiation marker of EPCs, and hypoxic stimuli did not directly affect nestin gene expression. [ABSTRACT FROM AUTHOR]

Purpose. To determine the association between the progression of upper lung fibrosis and paratracheal air cysts (PACs) size. Materials and Methods. The thoracic CT images of 4573 patients were reviewed for the prevalence, size, and location of PACs and their communication with trachea. In addition, the presence of upper lung fibrosis, emphysema, and bronchiectasis was evaluated in patients with PACs and compared with a control group without PACs. Upper lung fibrosis was analyzed using a fibrosis score system. Results. The prevalence of PACs was 6.8%. Communication with tracheal lumen was demonstrated by 31.5% of patients with PACs. The prevalence of fibrosis, emphysema, and bronchiectasis in patients with PACs were 67.5%, 21.9%, and 28.3%, respectively. The prevalence of fibrosis was significantly different in the two groups by univariable and multivariable analysis (odds ratio = 2.077, P<0.001). 140 patients with fibrosis among PAC group underwent a previous or follow-up CT; the prevalence with increase in PAC sizes was higher in patients with increase in fibrosis score than those without it (66.2% versus 17.3%, P<0.001). Conclusions. PACs appear to be highly related to upper lung fibrosis and moderately related to bronchiectasis. In patients with fibrosis, PAC sizes tended to increase with the progression of upper lung fibrosis. [ABSTRACT FROM AUTHOR]

Recent evidence suggests that mononuclear cells (MNCs) derived from bone marrow and cord blood can differentiate into mesenchymal stem cells (MSCs) or outgrowth endothelial cells (OECs). However, controversy exists as to whether MNCs have the pluripotent capacity to differentiate into MSCs or OECs or are a mixture of cell lineage-determined progenitors of MSCs or OECs. Here, using CD133+/C-kit+/Lin− mononuclear cells (CKL− cells) isolated from human umbilical cord blood using magnetic cell sorting, we characterized the potency of MNC differentiation. We first found that CKL− cells cultured with conditioned medium of OECs or MSCs differentiated into OECs or MSCs and this differentiation was also induced by cell-to-cell contact. When we cultured single CKL− cells on OEC- or MSC-conditioned medium, the cells differentiated morphologically and genetically into OEC- or MSC-like cells, respectively. Moreover, we confirmed that OECs or MSCs differentiated from CKL− cells had the ability to form capillary-like structures in Matrigel and differentiate into osteoblasts, chondrocytes, and adipocytes. Finally, using microarray analysis, we identified specific factors of OECs or MSCs that could potentially be involved in the differentiation fate of CKL− cells. Together, these results suggest that cord blood-derived CKL− cells possess at least bipotential differentiation capacity toward MSCs or OECs. [ABSTRACT FROM AUTHOR]

Piscidin 1 (Pis-1) from hybrid striped bass possesses antibacterial activities with high cytotoxicity. Previously, we reported that Pis-1[ NkG], where Gly8 was substituted with positively charged Lys peptoid in Pis-1, shows high antibacterial activity with more potent bacterial cell selectivity than parent Pis-1 and Pis-1[ PG] with Pro substitution at Gly8. Here, we investigated the effects of hydrophobic peptoid substitutions on antimicrobial activity and cytotoxicity of Pis-1. We designed Pis-1[ NaG] and Pis-1[ NlG] peptides, where Gly8 was replaced with alanine or leucine peptoids. Although hydrophobicity was increased in Pis-1[ NaG] and Pis-1[ NlG] compared with that in Pis-1[ NkG], Pis-1, and Pis-1[ PG], these peptides retained high antibacterial activity and showed no hemolytic activity when used at 100 μM. All peptoid-substituted peptides penetrated well the bacterial membrane and localized inside of the cytoplasm, while Pis-1 and Pis-1[ PG] depolarized membrane severely. The flexible hinge structure formed by peptoid residues compared with the rigid bent structure formed by proline may explain their differential mechanisms of action. Most hydrophobic peptide, Pis-1[ NlG], showed the most efficient inhibition of LPS (lipopolysaccharide)-induced nitric oxide production, indicating that it can be a potent antimicrobial peptide with anti-inflammatory activities. Peptoid substitution may facilitate the development of potent peptide drugs with bacterial cell selectivity. [ABSTRACT FROM AUTHOR]

The article focuses on research related to stereoselective nucleophilic substitution of α-bromo tertiary amides for asymmetric synthesis of highly substituted 2,5-diketopiperazines. Topics discussed include dynamic kinetic resolution of L-amino acid-derived α-bromo tertiary acetamides in the nucleophilic substitution with p-anisidine; understanding the effect of the N-alkyl group on the reversed stereochemical outcome; and N-alkylation of trisubstituted diketopipaerazine.

We developed a highly stereoselective C-N and C-C bond-forming reaction by carrying out a crystallization-induced dynamic resolution (CIDR) of α-bromo arylacetates followed by a stereoselective substitution reaction with an amine or azlactone nucleophile. Applications of this synthetic method to the preparation of highly enantioenriched nitrogen-containing six-membered heterocycles and α,β-disubstituted aspartates are also presented. [ABSTRACT FROM AUTHOR]

This work carried out systematic geological field investigation, petrography observation, zircon geochronology and whole rock geochemistry on Late Paleozoic intrusions in the Xingxingxia region near the Xinjiang-Gansu provincial boundary, western China, aiming to constrain the Late Paleozoic tectonic framework of the Xingxingxia region and the final closure time of South Tianshan Ocean in the East Tianshan. The Xingxingxia area is located in the east part of the Tianshan orogen, and adjacent to the north of the Tarim Basin. The Late Paleozoic magma activities in the Xingxingxia region can be mainly divided into three stages. The first stage includes intrusive magma activities under a collision setting between Late Ordovician to the Late Devonian. The second stage is intrusive magma activities under a subduction setting during (304±3)-(278±3) Ma, and the third stage involves intrusive magma activities under a collision and post-collision setting during (268±5)-(259.9±2.6) Ma. The final suture zone of South Tianshan Ocean should be between the Central Tianshan Block and South Tianshan accretionary complex. Based on previous work, both the first stage magma activities (i.e., intrusive magmatic activities between the Late Ordovician to Late Devonian) and the Hongliuhe ophiolitic complex indicate a close event between Central Tianshan Block and South Tianshan Accretionary Complex. The 304±3 Ma dioritic metamorphic gneiss of the XingXingxia complex and the 278±3 Ma diorite are all island arc calc-alkaline rocks, the 289±3 Ma gabbro is island arc tholeiitic gabbro formed by magma from metasomatic enrichment mantle. All these results indicate that the second stage of magmatic activities is under a subduction setting. The third stage magma activities i.e. the granitic magma activities of (268±5)-(259.9±2.6) Ma occurred at a transitional setting from compressional to post-collision extensional tectonic setting. Thus, around (268±5)-(260±3) Ma, the final closure of the South Tianshan Ocean occurred and the Tianshan orogen shifted into the intracontinental evolution stage. During and after the closure process, a wide range of metamorphism and large dextral strike-slip faults developed. [ABSTRACT FROM AUTHOR]

This paper presents an interactive digital painting system that allows a user to draw graffiti on a virtual 3D canvas with a digital spray can. The system visualizes a stereoscopic representation of the canvas by tracking the user's head. It also emulates real-time spray painting by tracking the spray can in the user's hand as well as sensing the button pressure of the spray device. After painting a 3D object, the user can interact with the object on the display and see it flying in the 3D environment through a tracked head-mounted display. As demonstrated in the results of our evaluation, we verified that the system resembles real graffiti in regard to a natural and realistic graffiti experience. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The article reports the development of novel catalysts derived from D-phenylglycine-L-proline (D-Phg-L-Pro) dipeptide and the achievement of dual stereocontrol in the addition of diethylzinc to aldehydes. It details the general procedures for the preparation of various chiral catalysts and the enantioselective addition of diethylzinc to aldehydes.

Highly mono-disperse carbon spheres (CSs) with a tunable diameter of 300-4000 nm are shown to be successfully synthesised using sugar-rich wastewater as carbon sources and polyacrylamide (PAM) as a size-controlling agent. The effects of PAM and pH on the morphology and size were also investigated. Experimental results showed that PAM acted as a size-directing agent which directs the self-assembly of sugar from wastewater to form the spheroidal particles. The size of CSs could be increased from 300 to 600 nm without any alteration in the morphologies by altering the solution pH from 7 to 12. Furthermore, the size of spheroidal carbon particles can be easily controlled by increasing the concentration of PAM from 0.05 to 0.1% (w/v) at pH 12. The largest sizes of CSs grew nearly 4000 nm without damage to their morphology or broadening of their size distribution with the addition of 0.1% PAM. On the basis of the experimental results, a mechanism is proposed to elucidate the formation of CSs with a wide diameter range. It is believed that this work not only provides a novel potential way to utilise wastewater, but also puts forward a facile sustainable approach to synthesise size-controllable CSs. [ABSTRACT FROM AUTHOR]

The CO2 sorption capacity of the 3D In-MOF (Et2NH2)[In(2,6-NDC)2] ·2H2O ·DEF ( I) (where 2,6-NDC is 2,6-naphthalenedicarboxylate and DEF is N, N-diethylformamide) was investigated. The solvent-free I contains three distinct types of 1D micropores with different shapes and pore dimensions. The evacuated I sorbed 297.2 cm3 g-1 (13.3 mmol g-1) of CO2 at 196 K, 72.2 cm3 g-1 (3.22 mmol g-1) at 273 K, and 39.8 cm3 g-1 (1.78 mmol g-1) at 298 K. The difference between the uptake at 196 K and those at 273 and 298 K is relatively large. The shapes of the sorption isotherms are also dramatically different. At 196 K, the adsorption-desorption isotherms are S-shaped without significant hysteretic behavior between the adsorption and desorption branches. On the contrary, the adsorption isotherms measured at 273 and 298 K fit well with the Langmuir-Freundlich equation. The low-surface-coverage isosteric heat ( Qst) of CO2 adsorption by I is 19.6 kJ mol-1. Detailed estimations of the adsorption sites for CO2 were then performed by DFT calculations. The calculated binding energies were typically dependent on the dimension of the micropores when nonbonding (van der Waals) interactions were considered; the larger the micropore dimensions, the smaller the calculated binding energy. In addition, not only the framework CH ···OCO contacts for Ch3 but also the counter-cation CH ···OCO contacts for Ch1 and Ch2 were found to be important. [ABSTRACT FROM AUTHOR]

A novel approach to produce a large-area hierarchical structure array is presented. The method combines replica molding and atmospheric pressure plasma (APP) etching processes. Liquid blends consisting of siliconized silsesquioxane acrylate (Si-SSQA), polyethylene glycol dimethacrylate (PEGDMA), and photoinitiator are used as roughness formable materials during APP etching. Microstructures composed of the Si-SSQA/PEGDMA mixtures are fabricated by replica molding. Nanoroughness is realized on the microstructures by argon/oxygen (Ar/O2) APP etching in air. The nano­roughness on molded microstructures is efficiently controlled by varying the weight ratio of Si-SSQA to PEGDMA and the etching time. The hierarchical structures fabricated by combining replica molding and Ar/O2 APP etching show superhydrophilicity with a long-term stability, resulting in the formation of hydroxyl-terminated silicon oxide layer with the reorientation limit. On the other hand, the hierarchical structures treated with a perfluorinated self-assembled monolayer (SAM) show increased the water contact angles of up to 161° depending on the morphology of the hierarchical structures. The increment of water contact angles is consistent with increment of the nano-/microroughness of hierarchical structures. [ABSTRACT FROM AUTHOR]

Local hypoxia in tumors is an undesirable consequence of photodynamic therapy (PDT), which will lead to greatly reduced effectiveness of this therapy. Bioreductive prodrugs that can be activated at low-oxygen conditions will be highly cytotoxic under hypoxia in tumors. Based on this principle, double silica-shelled upconversion nanoparticles (UCNPs) nanostructure capable of co-delivering photosensitizer (PS) molecules and a bioreductive pro-drug (tirapazamine, TPZ) were designed (TPZ-UC/PS), with which a synergetic tumor therapeutic effect has been achieved first by UC-based (UC-) PDT under normal oxygen environment, immediately followed by the induced cytotoxicity of activated TPZ when oxygen is depleted by UC-PDT. Treatment with TPZ-UC/PS plus NIR laser resulted in a remarkably suppressed tumor growth as compared to UC-PDT alone, implying that the delivered TPZ has a profound effect on treatment outcomes for the much-enhanced cytotoxicity of TPZ under PDT-induced hypoxia. [ABSTRACT FROM AUTHOR]

The article focuses on asymmetric syntheses of 3,4-disubstituted tetrahydroquinoline derivatives using (+)-sparteine-mediated electrophilic substitution. Topics include the use of epoxide for electrophilic substitution and amino alcohol as the derivative, the use of diastereomeric mixtures, and stereoselective lithiation.