Economic restructuring, energy planning and environmental protection are subject to inherent uncertainties in a compound system with competing decision objectives. Therefore, an inexact ...multi-objective programming model for regional economy-energy-environment system management has been developed to obtain absolutely “optimal” solutions. Under two comparative scenarios, three subsystems, six industries, four types of energy, and three kinds of air pollution were considered in an optimization model, and a net system benefit and trade-off analysis between subsystems was conducted. The methods of interval-parameter programming and multi-objective programming were incorporated into the model to tackle the uncertainties and complexities reflected in the case study. The model results indicated that the developed model could provide effective linkages among the economy-energy-environment systems and offer decision makers great insight into the reliability tradeoffs for the adjustment of the existing management policy.
•A model was developed to reflect the uncertainty in the compound system.•The influence of the policy orientation to regional development has been shown.•The model could help decision makers formulate regional development plans.•An outrageous economic target will lead inevitable air pollution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Stand-off laser-induced breakdown spectroscopy (ST-LIBS) has developed into an excellent technology for remote analysis of geological samples. In this study, the rock classification capability of ...principal component analysis (PCA) was illustrated. The method of automatic spectral peaks identification with linear discriminant analysis (ASPI-LDA) was first applied for classification of rocks and compared with manual spectral peaks identification with linear discriminant analysis (MSPI-LDA). The spectra of rocks were obtained using Echelle and Czerny-Turner spectrometers at 5 m distance and the spectrum peaks were automatically and rapidly identified with ASPI-LDA, not manually identified one by one. The results suggested that MSPI-LDA outperformed PCA in classification performance and, the predictive classification accuracies were further significantly improved by ASPI-LDA with two spectrometers. Besides, the performances of two spectrometers were compared. The results showed that the ASPI-LDA algorithm remedied for the weakness of a compact Czerny-Turner spectrometer having a narrow spectral range to achieve high accuracy classification. Meanwhile, the compact spectrometer used for field detection in ST-LIBS was miniaturized and of lower cost. This indicates that ASPI-LDA combined with a compact spectrometer has a great potential for field
in situ
remote detection in ST-LIBS.
The ASPI-LDA algorithm combined with a compact spectrometer to achieve high accuracy classification, which has a great potential for field
in situ
remote detection.
To investigate efficacy and safety of the Janus kinase-1 inhibitor filgotinib in patients with active rheumatoid arthritis (RA) with limited or no prior methotrexate (MTX) exposure.
This 52-week, ...phase 3, multicentre, double-blind clinical trial (NCT02886728) evaluated once-daily oral filgotinib in 1252 patients with RA randomised 2:1:1:2 to filgotinib 200 mg with MTX (FIL200 +MTX), filgotinib 100 mg with MTX (FIL100 +MTX), filgotinib 200 mg monotherapy (FIL200), or MTX. The primary endpoint was proportion achieving 20% improvement in American College of Rheumatology criteria (ACR20) at week 24.
The primary endpoint was achieved by 81% of patients receiving FIL200+ MTX versus 71% receiving MTX (p<0.001). A significantly greater proportion treated with FIL100+ MTX compared with MTX achieved an ACR20 response (80%, p=0.017) at week 24. Significant improvement in Health Assessment Questionnaire-Disability Index was seen at week 24; least-squares mean change from baseline was -1.0 and -0.94 with FIL200+MTX and FIL100+MTX, respectively, versus -0.81 with MTX (p<0.001, p=0.008, respectively). Significantly higher proportions receiving FIL200+MTX (54%) and FIL100+MTX (43%) achieved DAS28(CRP) <2.6 versus MTX (29%) (p<0.001 for both) at week 24. Hierarchical testing stopped for comparison of ACR20 for FIL200 monotherapy (78%) versus MTX (71%) at week 24 (p=0.058). Adverse event rates through week 52 were comparable between all treatments.
FIL200+MTX and FIL100+MTX both significantly improved signs and symptoms and physical function in patients with active RA and limited or no prior MTX exposure; FIL200 monotherapy did not have a superior ACR20 response rate versus MTX. Filgotinib was well tolerated, with acceptable safety compared with MTX.
In human, a reduction in estrogen has been proposed as one of the key contributing factors for postmenopausal osteoporosis. Rodents are conventional models for studying postmenopausal osteoporosis, ...but the major limitation is that ovariectomy is needed to mimic the estrogen decline after menopause. Interestingly, in medaka fish (Oryzias latipes), we observed a natural drop in plasma estrogen profile in females during aging and abnormal spinal curvature was apparent in old fish, which are similar to postmenopausal women. It is hypothesized that estrogen associated disorders in bone metabolism might be predicted and prevented by estrogen supplement in aging O. latipes, which could be corresponding to postmenopausal osteoporosis in women.
In O. latipes, plasma estrogen was peaked at 8 months old and significantly declined after 10, 11 and 22 months in females. Spinal bone mineral density (BMD) and micro-architecture by microCT measurement progressively decreased and deteriorated from 8 to 10, 12 and 14 months old, which was more apparent in females than the male counterparts. After 10 months old, O. latipes were supplemented with 17α-ethinylestradiol (EE2, a potent estrogen mimic) at 6 and 60 ng/mg fish weight/day for 4 weeks, both reduction in spinal BMD and deterioration in bone micro-architecture were significantly prevented. The estrogenic effect of EE2 in O. latipes was confirmed by significant up-regulation of four key estrogen responsive genes in the liver. In general, bone histomorphometric analyses indicated significantly lowered osteoblasts and osteoclasts numbers and surfaces on vertebrae of EE2-fed medaka.
We demonstrate osteoporosis development associated with natural drop in estrogen level during aging in female medaka, which could be attenuated by estrogen treatment. This small size fish is a unique alternative non-mammalian vertebrate model for studying estrogen-related molecular regulation in postmenopausal skeletal disorders in vivo without ovariectomy.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Six DNA regions were evaluated as potential DNA barcodes for Fungi, the second largest kingdom of eukaryotic life, by a multinational, multilaboratory consortium. The region of the mitochondrial ...cytochrome c oxidase subunit 1 used as the animal barcode was excluded as a potential marker, because it is difficult to amplify in fungi, often includes large introns, and can be insufficiently variable. Three subunits from the nuclear ribosomal RNA cistron were compared together with regions of three representative protein-coding genes (largest subunit of RNA polymerase II, second largest subunit of RNA polymerase II, and minichromosome maintenance protein). Although the protein-coding gene regions often had a higher percent of correct identification compared with ribosomal markers, low PCR amplification and sequencing success eliminated them as candidates for a universal fungal barcode. Among the regions of the ribosomal cistron, the internal transcribed spacer (ITS) region has the highest probability of successful identification for the broadest range of fungi, with the most clearly defined barcode gap between inter-and intraspecific variation. The nuclear ribosomal large subunit, a popular phylogenetic marker in certain groups, had superior species resolution in some taxonomic groups, such as the early diverging lineages and the ascomycete yeasts, but was otherwise slightly inferior to the ITS. The nuclear ribosomal small subunit has poor species-level resolution in fungi. ITS will be formally proposed for adoption as the primary fungal barcode marker to the Consortium for the Barcode of Life, with the possibility that supplementary barcodes may be developed for particular narrowly circumscribed taxonomic groups.
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BFBNIB, NMLJ, NUK, PNG, SAZU, UL, UM, UPUK
•Energy drinks can contain H2O2 that is shelf-stable and increases after opening.•Ascorbic acid is a key driver of H2O2 production in formulated beverages.•Production of H2O2 by ascorbic acid was ...confirmed by cyclic voltammetry.•Mixtures of ‘anti-oxidants’ in formulated beverages can drive autoxidation.•Products of autoxidation in foods and beverages should be monitored.
Recently, autoxidation mediated by ascorbic acid (AA) and other ingredients, has been implicated in generation of hydrogen peroxide (H2O2) in so-called Energy beverages. Here, we report the use of cyclic voltammetry and the FOX assay to monitor at short and long incubation times, respectively, the production and stability of H2O2 generated by AA and redox-active ingredients. Levels of H2O2 in Energy drinks (36.5 ± 4.0 µM at 4 °C and 64.2 ± 7.6 µM at 20 °C) were found to be stable or increased (p < 0.05) upon vessel opening. A predictive model for the production of H2O2 as a function of AA concentration, temperature and incubation time, and depending on ingredients present, indicated that H2O2 peaked at 91–726 µM after 1 day and declined to ∼ 42–60 µM (4 °C) or zero after ∼10 days. The research supports that levels of H2O2 in beverages containing anti-oxidant mixtures and dissolved oxygen should be monitored and formulations modified to avoid AA autoxidation.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
The regulatory mechanism of DBT-induced EPO gene expression via HIF-1α in HEK293T cell was revealed. This regulation involves two distinct mechanisms: (i) transcriptional level by increasing the ...HIF-1α mRNA and (ii) translational level by enhancing the HIF-1α protein.
Danggui Buxue Tang (DBT), a Chinese medicinal decoction that is being commonly used as hematopoietic medicine to treating woman menopausal irregularity, contains two herbs: Radix Astragali and Radix Angelicae Sinensis. Pharmacological results indicate that DBT can stimulate the production of erythropoietin (EPO), a specific hematopoietic growth factor, in cultured cells.
In order to revealing the mechanism of DBT's hematopoietic function, this study investigated the activity of the DBT-induced EPO expression and the upstream regulatory cascade of EPO via hypoxia-induced signaling in cultured kidney fibroblasts (HEK293T).
DBT-induced mRNA expressions were revealed by real-time PCR, while the change of protein expressions were analyzed by Western blotting. For the analysis of hypoxia-dependent signaling, a luciferase reporter was used to report the transcriptional activity of hypoxia response element (HRE).
The plasmid containing HRE, being transfected into HEK293T, was highly responsive to the challenge of DBT application. To account for the transcriptional activation of HRE, DBT treatment was shown to increase the mRNA and protein expressions of
hypoxia-
inducible
factor-1α (HIF-1α). In addition, the activation of Raf/MEK/ERK signaling pathway by DBT could also enhance the translation of HIF-1α, suggesting the dual actions of DBT in stimulating the EPO expression in kidney cells.
Our study indicates that HIF pathway plays an essential role in directing DBT-induced EPO expression in kidney. These results provide one of the molecular mechanisms of this ancient herbal decoction for its hematopoietic function.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
In recent years, Helicobacter pylori (H. pylori) has been increasingly associated with extra-digestive manifestations, including scleroderma, rheumatism, and blood system diseases. Iron deficiency ...anemia (IDA) is a common chronic disease worldwide, with an insidious onset, but as the disease progresses, it will eventually seriously affect the quality of life of patients. The aim of our study was to investigate the relationship between H. pylori infection, iron deficiency (ID), and IDA, and to identify potential serological markers.
We conducted a cross-sectional study of 998 individuals who had regular physical examinations at Beijing Shijitan Hospital from January 2021 to March 2022. We detected H. pylori infection by the 13C breath test, and recorded the patient's serum iron, ferritin, transferrin saturation, blood count, etc. We assessed the association between IDA and H. pylori infection and related serum markers using logistic regression and multiple linear regression. Afterward, we analyzed the correlation between sex and potential serum biomarkers.
Among all study participants, 57.5% of patients had H. pylori and 42.5% did not have H. pylori. ID and IDA were significantly associated with H. pylori infection in women (p=0.031). This association persisted after further adjustment for sex, metabolic variables, liver function, and kidney function. Fasting blood glucose, triglycerides, and uric acid may be associated with IDA.
In women, H. pylori infection is associated with ID and IDA. The relationship between H. pylori and IDA may be mediated by glycometabolism, lipid metabolism, and uric acid metabolism.
Evasion of immunosurveillance is critical for cancer initiation and development. The expression of "don't eat me" signals protects cancer cells from being phagocytosed by macrophages, and the ...blockade of such signals demonstrates therapeutic potential by restoring the susceptibility of cancer cells to macrophage-mediated phagocytosis. However, whether additional self-protective mechanisms play a role against macrophage surveillance remains unexplored. Here, we derived a macrophage-resistant cancer model from cells deficient in the expression of CD47, a major "don't eat me" signal,
a macrophage selection assay. Comparative studies performed between the parental and resistant cells identified self-protective traits independent of CD47, which were examined with both pharmacological or genetic approaches in
phagocytosis assays and
tumor models for their roles in protecting against macrophage surveillance. Here we demonstrated that extracellular acidification resulting from glycolysis in cancer cells protected them against macrophage-mediated phagocytosis. The acidic tumor microenvironment resulted in direct inhibition of macrophage phagocytic ability and recruitment of weakly phagocytic macrophages. Targeting V-ATPase which transports excessive protons in cancer cells to acidify extracellular medium elicited a pro-phagocytic microenvironment with an increased ratio of M1-/M2-like macrophage populations, therefore inhibiting tumor development and metastasis. In addition, blockade of extracellular acidification enhanced cell surface exposure of CD71, targeting which by antibodies promoted cancer cell phagocytosis. Our results reveal that extracellular acidification due to the Warburg effect confers immune evasion ability on cancer cells. This previously unrecognized role highlights the components mediating the Warburg effect as potential targets for new immunotherapy harnessing the tumoricidal capabilities of macrophages.
•Silane coatings were electrodeposited on magnesium alloys.•The resulted coatings had good durability and anti-corrosion properties.•The resulted coatings had good cyto- and hemo-compatibility.•The ...optimal electrodeposition voltage is −2.0V.
The major obstacle to the clinical use of magnesium alloys is their fast degradation behaviors. In the present study, the triethoxy(octyl)silane coatings were electrodeposited on magnesium alloy to improve the corrosion resistance and biocompatibility. The effects of the electrodeposition potential on the corrosion properties of the silane coatings were investigated. The resulted coatings were characterized by SEM, FTIR, surface hydrophobicity, in addition, the corrosion behaviors and biocompatibilities were also evaluated. The results indicated that the coatings deposited at −2.0V were more corrosion resistant than the other two silane coatings. Furthermore, the silane coatings showed good biocompatibilities, as demonstrated by significant increased cell viability, reduced hemolysis and platelet adhesion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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