Comparison of three different lactic acid bacteria-fermented proteins on RAW 264.7 osteoclast and MC3T3-E1 osteoblast differentiation.

Osteoporosis is a state of bone weakening caused by an imbalance in osteoblast and osteoclast activity. In this study, the anti-osteoporotic effects of three proteins fermented by lactic acid bacteria (LAB) were assessed. Commercial proteins sodium caseinate (SC), whey protein isolate (WPI), and soy protein isolate (SPI) were fermented by LAB strains for 48 h. The fermented products (F-SC, F-WPI, and F-SPI, respectively) were used in an in vitro osteoclast and osteoblast-like cell model to assess their effects on bone health. Despite no difference in the results of TRAP staining of RANKL-induced osteoclastogenesis, F-WPI and F-SPI were effective in normalizing the altered gene expression of osteoclastogenesis markers such as TRAP, Nfatc1, RANK, and ATP6v0d. F-SPI was also effective in modulating osteoblasts by enhancing the expression of the osteoblastogenesis markers T1Col, Col2a, and OSX to levels higher than those in the SPI group, indicating that protein characteristics could be enhanced through bacterial fermentation. Moreover, these boosted effects of F-SPI may be involved with isoflavone-related metabolism during LAB-fermentation of SPI. These results demonstrate the potential of LAB-fermented proteins as dietary supplements to prevent bone loss. However, further understanding of its effects on balancing osteoblasts and osteoclasts and the underlying mechanisms is needed.

Novel Mechanism-Based Descriptors for Extreme Ultraviolet-Induced Photoacid Generation: Key Factors Affecting Extreme Ultraviolet Sensitivity.

Predicting photolithography performance in silico for a given materials combination is essential for developing better patterning processes. However, it is still an extremely daunting task because of the entangled chemistry with multiple reactions among many material components. Herein, we investigated the EUV-induced photochemical reaction mechanism of a model photoacid generator (PAG), triphenylsulfonium cation, using atomiC-Scale materials modeling to elucidate that the acid generation yield strongly depends on two main factors: the lowest unoccupied molecular orbital (LUMO) of PAG cation associated with the electron-trap efficiency 'before C-S bond dissociation' and the overall oxidation energy change of rearranged PAG associated with the proton-generation efficiency 'after C-S bond dissociation'. Furthermore, by considering stepwise reactions accordingly, we developed a two-parameter-based prediction model predicting the exposure dose of the resist, which outperformed the traditional LUMO-based prediction model. Our model suggests that one should not focus only on the LUMO energies but also on the energy change during the rearrangement process of the activated triphenylsulfonium (TPS) species. We also believe that the model is well suited for computational materials screening and/or inverse design of novel PAG materials with high lithographic performances.

Validity Analysis of Neck Circumference as a Screening Test for Hypoxia Occurrence in Patients Undergoing Sedative Endoscopy.

This study was performed to check the validity of and propose a cutoff point for measuring the neck circumference for screening hypoxia occurrence in patients undergoing sedative endoscopy. Data were collected from 168 patients who visited the Endoscopy Center of G University Hospital between 27 April 2020 and 12 June 2020 to undergo sedative endoscopy. Hypoxia occurrences were measured using sleep questionnaires (STOP-BANG and Berlin questionnaires), and the neck circumference measurements of the patients were compared. Neck circumference as a predictor of hypoxia and its sensitivity and specificity according to the cutoff values were high; thus, it is a valid screening test for hypoxia in patients undergoing sedative endoscopy. The most appropriate cutoff values for sitting neck circumference and lying neck circumference in men were 40.5 and 40.3, respectively, and those for women were 35.3 and 35.8, respectively. Hypoxia can be predicted in patients undergoing sedative endoscopy by measuring their neck circumference.

Corrigendum to "Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund's Adjuvant".

[This corrects the article DOI: 10.1155/2021/8896108.].

Inhibitory Effect of Paquinimod on a Murine Model of Neutrophilic Asthma Induced by Ovalbumin with Complete Freund's Adjuvant.

Background: Quinoline-3-carboxamides have been used to treat autoimmune/inflammatory diseases in humans because they inhibit the functions of S100 calcium-binding protein A9 (S100A9), which participates in the development of neutrophilic inflammation in asthmatics and in an animal model of neutrophilic asthma. However, the therapeutic effects of these chemicals have not been evaluated in asthma. The purpose of this study was to evaluate the effect of paquinimod, one of the quinoline-3-carboxamides, on a murine model of neutrophilic asthma. Methods: Paquinimod was orally administered to 6-week-old C57BL/6 mice sensitized and challenged with ovalbumin (OVA)/complete Freund's adjuvant (CFA) and OVA. Lung inflammation and remodeling were evaluated using bronchoalveolar lavage (BAL) and histologic findings including goblet cell count. S100A9, caspase-1, IL-1ß, MPO, IL-17, IFN-γ, and TNF-α were measured in lung lysates using western blotting. Results: Paquinimod restored the enhancement of airway resistance and the increases in numbers of neutrophils and macrophages of BAL fluids and those of goblet cells in OVA/CFA mice toward the levels of sham-treated mice in a dose-dependent manner (0.1, 1, 10, and 25 mg/kg/day, p.o.). Concomitantly, p20 activated caspase-1, IL-1ß, IL-17, TNF-α, and IFN-γ levels were markedly attenuated. Conclusion: These data indicate that paquinimod effectively inhibits neutrophilic inflammation and remodeling in the murine model of neutrophilic asthma, possibly via downregulation of IL-17, IFN-γ, and IL-1ß.

Source partitioning and emission factor of nitrous oxide during warm and cold cropping seasons from an upland soil in South Korea.

Nitrous oxide (N2O) is a major greenhouse gas (GHG) with high global warming potential. A majority of the N2O flux comes from agricultural sources, mainly due to nitrogen (N) fertilization. The soil N2O flux, induced by N fertilization, mainly originated from two different sources, i.e., fertilizer and soil organic nitrogen (SON). It is essential to know the individual contribution of these two different sources in total N2O flux for planning necessary mitigation strategies. It is also indispensable to know the seasonal difference of emission factors (EF) for having more accurate N2O inventory. Therefore, an experiment was conducted in a South Korean upland soil during summer and winter seasons using 15N labeled urea as an artificial N source and source specific N2O emissions were distinguished under different environmental conditions. To characterize the N2O emissions from urea, 0, 50, 100 and 200% of the Korean N recommendation rate was selected for specified crops. The Korean N recommendation rate for red pepper (Capsicum annuum) and garlic (Allium sativum) was 190 and 250 kg N ha-1, respectively. Direct emissions from urea were estimated from the difference of 15N2O flux emitted from 15N-urea treated soil and the natural abundance of 15N2O. From total N2O fluxes, urea originated N2O flux was 0.87% and 0.13% of the applied N in warm and cold seasons, respectively and the rest comes from SON. Nitrous oxide EF in the warm season was 2.69% of applied N and in the cold season that was 0.25%. Nitrous oxide fluxes showed a significant exponential relationship with soil temperature. The results show the necessity of considering the different N2O EF for warm and cold cropping seasons to reduce uncertainty in N2O inventory. The findings of this research may help better understand N2O source partitioning and the emission budget from warm and cold cropping seasons.

Role of S100A9 in the development of neutrophilic inflammation in asthmatics and in a murine model.

S100A9 is an endogenous danger signal that promotes and exacerbates the neutrophilic inflammatory response. To investigate the role of S100A9 in neutrophilic asthma, S100A9 levels were measured in sputum from 101 steroid-naïve asthmatics using an ELISA kit and the levels were significantly correlated with percentages of neutrophils in sputum. Intranasal administration of recombinant S100A9 markedly increased neutrophil numbers at 8h and 24h later with concomitant elevation of IL-1ß, IL-17, and IFN-γ levels. Treatment with an anti-S100A9 antibody restored the increased numbers of neutrophils and the increased airway resistance in OVA/CFA mice toward the levels of sham-treated mice. Concomitantly, the S100A9 and neutrophil elastase double positive cells were markedly reduced with attenuation of IL-1ß, IL-17, and IFN-γ levels by the treatment with the anti-S100A9 antibody. Our data support a role of S100A9 to initiate and amplify the neutrophilic inflammation in asthma, possibly via inducing IL-1ß, IL-17 and IFN-γ.

Visible light sensitization of benzoyl azides: cascade cyclization toward oxindoles via a non-nitrene pathway.

Visible light sensitization of benzoyl azides was examined in reaction with N-phenylmethacrylamides to afford biologically important oxindoles and spirooxindoles via a cascade cyclization under mild reaction conditions. Mechanistic studies suggested a non-nitrene pathway, where triplet benzoyl azides act as the reactive intermediate.

Upregulation of interleukin-33 and thymic stromal lymphopoietin levels in the lungs of idiopathic pulmonary fibrosis.

BACKGROUND: Innate T helper type 2 (Th2) immune responses mediated by interleukin (IL)-33, thymic stromal lymphopoietin (TSLP), and IL-25 have been shown to play an important role in pulmonary fibrosis of animal models; however, their clinical implications remain poorly understood. METHODS: TSLP, IL-25, and IL-33 concentrations were measured in bronchoalveolar lavage fluids obtained from normal controls (NCs; n = 40) and from patients with idiopathic pulmonary fibrosis (IPF; n = 100), non-specific interstitial pneumonia (NSIP; n = 22), hypersensitivity pneumonitis (HP; n = 20), and sarcoidosis (n = 19). RESULTS: The TSLP and IL-33 levels were significantly higher in patients with IPF relative to the NCs (p = 0.01 and p = 0.0001, respectively), NSIP (p = 4.95E - 7 and p = 0.0002, respectively), HP (p = 0.00003 and p = 0.000005, respectively), and sarcoidosis groups (p = 0.003 and p = 0.0001, respectively). However, the IL-25 levels were not significantly different between NC and IPF group (p = 0.432). Receiver operating characteristic curves of the TSLP and IL-33 levels revealed clear differences between the IPF and NC groups (AUC = 0.655 and 0.706, respectively), as well as between the IPF and the other lung disease groups (AUC = 0.786 and 0.781, respectively). Cut-off values of 3.52 pg/µg TSLP and 3.77 pg/µg IL-33 were shown to differentiate between the IPF and NC groups with 99.2 and 94.3% accuracy. Cut-off values of 4.66 pg/µg TSLP and 2.52 pg/µg IL-33 possessed 99.4 and 93.2% accuracy for differentiating among the IPF and other interstitial lung disease groups. CONCLUSIONS: Innate immune responses may be associated with the development of IPF. Furthermore, the IL-33 and TSLP levels in BAL fluids may be useful for differentiating IPF from other chronic interstitial lung diseases.

Association between TAAR6 polymorphisms and airway responsiveness to inhaled corticosteroids in asthmatic patients.

BACKGROUND: Genetic polymorphisms may be responsible for the wide variation in response to inhaled corticosteroids in asthmatic patients. We had previously reported that one polymorphism rs7772821, located on the 3'-UTR of trace amine-associated receptor 6 (TAAR6), is significantly associated with percentile changes in the forced expiratory volume in 1 s (%ΔFEV1) after inhaled corticosteroid treatment in asthmatics using a genome-wide association study. The aim of the present study was to validate the association between 15 single-nucleotide polymorphisms (SNPs) on the TAAR6 and airway responsiveness to inhaled corticosteroids in the asthmatics. METHODS: The %ΔFEV1 induced by 4 weeks' treatment with inhaled fluticasone propionate (1000 µg daily) was measured in 246 asthmatics. The 15 SNPs of TAAR6 were genotyped using a TaqMan assay. An association analysis between %ΔFEV1 and TAAR6 polymorphisms was carried out using a linear regression model controlling for age, sex, smoking status, presence of atopy, and baseline FEV1 as covariates. RESULTS: Among the 15 SNPs and seven haplotypes of TAAR6, rs7772821 (T>G) on the 3'-UTR showed the strongest correlation with inhaled corticosteroid-induced %ΔFEV1 (Pcorr=0.002 in the codominant model, Pcorr=0.03 in the dominant model, Pcorr=0.01 in the recessive model). The %ΔFEV1 of the rs7772821T>G minor homozygotes (60.77%) was higher than that of patients harboring either the rs7772821 T/G or T/T genotypes (21.32 and 31.60%, respectively). CONCLUSION: The TAAR6 rs7772821 polymorphism may be one of the important genetic factors for predicting the response to treatment with inhaled corticosteroids in asthmatics.

Role of inflammasome activation in development and exacerbation of asthma.

Human airways contact with pathogen-associated molecular patterns and danger-associated molecular patterns present in many environments. Asthmatic's airways may be more susceptible to these patterns and lead to inflammasome activation; however, the participation of inflammasome in the development and exacerbation of asthma is not fully understood and remains controversial. Asthma is a heterogeneous group composed of different airway inflammation patterns with different underlying immune mechanisms. One mechanism is neutrophilic airway inflammation based on the axis of inflammasome activation, interleukin (IL) 1ß/IL-18 production, T helper 17 activation, IL-8/IL-6 overproduction, and neutrophilic inflammation. The role of inflammasome activation has been highlighted in experimental asthma models and some evidence of inflammasome activation has been recently demonstrated in human neutrophilic asthmatic airways. In addition to caspase-1 activation, proteinase 3 and other protease from activated neutrophils directly cleave pro-IL-1ß and pro-IL-18 to IL-1ß and IL-18, which contribute to the phenotype of subsequent adaptive immune responses without inflammasome activation. Data suggests that neutrophilics in asthmatic airways may have an additional effect in initiating inflammasome activation and amplifying immune responses. Among the mediators from neutrophils, S100A9 seems to be one candidate mediator to explain the action of neutrophils in amplifying the airway inflammation in concert with inflammasome.

Exonic variants associated with development of aspirin exacerbated respiratory diseases.

Aspirin-exacerbated respiratory disease (AERD) is one phenotype of asthma, often occurring in the form of a severe and sudden attack. Due to the time-consuming nature and difficulty of oral aspirin challenge (OAC) for AERD diagnosis, non-invasive biomarkers have been sought. The aim of this study was to identify AERD-associated exonic SNPs and examine the diagnostic potential of a combination of these candidate SNPs to predict AERD. DNA from 165 AERD patients, 397 subjects with aspirin-tolerant asthma (ATA), and 398 normal controls were subjected to an Exome BeadChip assay containing 240K SNPs. 1,023 models (210-1) were generated from combinations of the top 10 SNPs, selected by the p-values in association with AERD. The area under the curve (AUC) of the receiver operating characteristic (ROC) curves was calculated for each model. SNP Function Portal and PolyPhen-2 were used to validate the functional significance of candidate SNPs. An exonic SNP, exm537513 in HLA-DPB1, showed the lowest p-value (p = 3.40×10-8) in its association with AERD risk. From the top 10 SNPs, a combination model of 7 SNPs (exm537513, exm83523, exm1884673, exm538564, exm2264237, exm396794, and exm791954) showed the best AUC of 0.75 (asymptotic p-value of 7.94×10-21), with 34% sensitivity and 93% specificity to discriminate AERD from ATA. Amino acid changes due to exm83523 in CHIA were predicted to be "probably damaging" to the structure and function of the protein, with a high score of '1'. A combination model of seven SNPs may provide a useful, non-invasive genetic marker combination for predicting AERD.

Enantioselective Friedel-Crafts alkylations catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes.

The enantioselective Friedel-Crafts addition of a variety of indoles catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes (Sc(III)-pybox) was accomplished utilizing a series of beta-substituted alpha,beta-unsaturated phosphonates and alpha,beta-unsaturated 2-acyl imidazoles. The acyl phosphonate products were efficiently transformed into esters and amides, whereas the acyl imidazole adducts were converted to a broader spectrum of functionalities such as esters, amides, carboxylic acids, ketones, and aldehydes. The sense of stereoinduction and level of enantioselectivity were found to be functions of the size of the substrate employed, the substitution on the ligand, and the catalyst loading. Molecular modeling of the catalyst with the bound substrates was performed based on the crystal structures of the catalyst complexes and the sense of stereoinduction observed in the addition reaction. Nonlinear effects over a range of catalyst concentrations implicate a mononuclear complex as the active catalyst.

Tin-free radical alkylation of ketones via N-silyloxy enamines.

The radical alkylation of ketones is achieved by their conversion into corresponding N-silyloxy enamines, followed by a radical reaction with alkyl halides bearing electron-withdrawing groups.

Enantioselective nitrone cycloadditions of alpha,beta-unsaturated 2-acyl imidazoles catalyzed by bis(oxazolinyl)pyridine-cerium(IV) triflate complexes.

[Structure: see text] Enantioselective nitrone cycloadditions with beta-substituted alpha,beta-unsaturated 2-acyl imidazoles catalyzed by bis(oxazolinyl)pyridine-cerium(IV) triflate complexes 1 have been reported. The isoxazolidine products were efficiently transformed into densely functionalized beta'-hydroxy-beta-amino acid derivatives.

Enantioselective Friedel-Crafts alkylations of alpha,beta-unsaturated 2-acyl imidazoles catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes.

An enantioselective Friedel-Crafts alkylation with alpha,beta-unsaturated 2-acyl imidazoles and electron-rich aromatic nucleophiles catalyzed by bis(oxazolinyl)pyridine-scandium(III) triflate complexes has been accomplished. These alpha,beta-unsaturated 2-acyl imidazoles are effective electrophiles for the Friedel-Crafts reaction. The resulting adduct 2-acyl imidazole is easily converted to amides, esters, carboxylic acids, ketones, and aldehydes by methylation and subsequent displacement of the imidazole residue.

Tin-Free Radical Acylation Reactions with Methanesulfonyl Oxime Ether.

A simple strategy involving thermal decomposition of the methanesulfonyl radical into the methyl radical and the subsequent transfer of an iodine atom or phenyl telluride group was used to develop a tin-free radical acylation reaction (see scheme; V-40=1,1'-azobis(cyclohexane-1-carbonitrile). The key was finding reaction conditions under which the I or PhTe transfer is faster than the direct addition of the alkyl radical to the methanesulfonyl oxime ether.