This study develops a high-performance stand-alone photovoltaic (PV) generation system. To make the PV generation system more flexible and expandable, the backstage power circuit is composed of a ...high step-up converter and a pulsewidth-modulation (PWM) inverter. In the dc-dc power conversion, the high step-up converter is introduced to improve the conversion efficiency in conventional boost converters to allow the parallel operation of low-voltage PV arrays, and to decouple and simplify the control design of the PWM inverter. Moreover, an adaptive total sliding-mode control system is designed for the voltage control of the PWM inverter to maintain a sinusoidal output voltage with lower total harmonic distortion and less variation under various output loads. In addition, an active sun tracking scheme without any light sensors is investigated to make the PV modules face the sun directly for capturing the maximum irradiation and promoting system efficiency. Experimental results are given to verify the validity and reliability of the high step-up converter, the PWM inverter control, and the active sun tracker for the high-performance stand-alone PV generation system.
Severe cutaneous adverse drug reactions Chung, Wen-Hung; Wang, Chuang-Wei; Dao, Ro-Lan
Journal of dermatology,
July 2016, Letnik:
43, Številka:
7
Journal Article
Recenzirano
The clinical manifestations of drug eruptions can range from mild maculopapular exanthema to severe cutaneous adverse drug reactions (SCAR), including drug‐induced hypersensitivity syndrome/drug ...reaction with eosinophilia and systemic symptoms, Stevens–Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) which are rare but occasionally fatal. Some pathogens may induce skin reactions mimicking SCAR. There are several models to explain the interaction of human leukocyte antigen (HLA), drug and T‐cell receptor (TCR): (i) the “hapten/prohapten” theory; (ii) the “p‐i concept”; (iii) the “altered peptide repertoire”; and (iv) the “altered TCR repertoire”. The checkpoints of molecular mechanisms of SCAR include specific drug antigens interacting with the specific HLA loci (e.g. HLA‐B*15:02 for carbamazepine‐induced SJS/TEN and HLA‐B*58:01 for allopurinol‐induced SCAR), involvement of specific TCR, induction of T‐cell‐mediated responses (e.g. granulysin, Fas ligand, perforin/granzyme B and T‐helper 1/2‐associated cytokines) and cell death mechanism (e.g. miR‐18a‐5p‐induced apoptosis; annexin A1 and formyl peptide receptor 1‐induced necroptosis in keratinocytes). In addition to immune mechanism, metabolism has been found to play a role in the pathogenesis of SCAR, such as recent findings of strong association of CYP2C9*3 with phenytoin‐induced SCAR and impaired renal function with allopurinol SCAR. With a better understanding of the mechanisms, effective therapeutics and prevention for SCAR can be improved.
Recent environmental disasters worldwide have made people consider the need for environmental protection. Therefore, the invisible pressure from these people made a paradigm shift on the economic ...structure as well as the business strategies. Even if these pressures from the environmental-friendly people are not forceful, it is nevertheless inevitable to put more strategic importance on the environment. The aim of this study was to identify determinants of acceptance of green products, including attitude, subjective norm and perceived behavioral control of theory of planned behavior with social impression, environmental consciousness, and environmental ethics and beliefs to understand and predict the adoption of consumer intentions. An online survey with 406 responses has been analyzed by partial least square (PLS). This study found that the attitude, perceived behavioral control, environmental consciousness of consumers and the environmental ethics and beliefs of consumers have a significant positive association with their intention to use green products, while the subjective norms consumers and the social impression consumers are positively but not significantly correlated to their intentions towards using green products. Based on these results, several strategic suggestions for participators and academics as well as policy implications to promote the green production were offered.
•Extend theory of planned behavior to elucidate the acceptance of green products.•Attitude and perceived behavioral control influence green products acceptance.•Environmental ethics, beliefs and consciousness influence green products acceptance.•Our model has a strong prediction power for the acceptance of green products
Obesity, a known risk factor for cardiovascular disease and heart failure (HF), is associated with adverse cardiac remodeling in the general population. Little is known about how nutritional status ...modifies the relationship between obesity and outcomes. We aimed to investigate the association of obesity and nutritional status with clinical characteristics, echocardiographic changes, and clinical outcomes in the general community. We examined 5,300 consecutive asymptomatic Asian participants who were prospectively recruited in a cardiovascular health screening program (mean age 49.6 ± 11.4 years, 64.8% male) between June 2009 to December 2012. Clinical and echocardiographic characteristics were described in participants, stratified by combined subgroups of obesity and nutritional status. Obesity was indexed by body mass index (BMI) (low, less than or equal to25 kg/m.sup.2 lean; high, >25 kg/m.sup.2 obese) (WHO-recommended Asian cutoffs). Nutritional status was defined primarily by serum albumin (SA) concentration (low, <45 g/L malnourished; high, greater than or equal to45 g/L well-nourished), and secondarily by the prognostic nutritional index (PNI) and Global Leadership Initiative on Malnutrition (GLIM) criteria. Cox proportional hazard models were used to examine a 1-year composite outcome of hospitalization for HF or all-cause mortality while adjusting for age, sex, and other clinical confounders. Our community-based cohort consisted of 2,096 (39.0%) lean-well-nourished (low BMI, high SA), 1,369 (25.8%) obese-well-nourished (high BMI, high SA), 1,154 (21.8%) lean-malnourished (low BMI, low SA), and 681 (12.8%) obese-malnourished (high BMI, low SA) individuals. Obese-malnourished participants were on average older (54.5 ± 11.4 years) and more often women (41%), with a higher mean waist circumference (91.7 ± 8.8 cm), the highest percentage of body fat (32%), and the highest prevalence of hypertension (32%), diabetes (12%), and history of cardiovascular disease (11%), compared to all other subgroups (all p < 0.001). N-terminal pro B-type natriuretic peptide (NT-proBNP) levels were substantially increased in the malnourished (versus well-nourished) groups, to a similar extent in lean (70.7 ± 177.3 versus 36.8 ± 40.4 pg/mL) and obese (73.1 ± 216.8 versus 33.2 ± 40.8 pg/mL) (p < 0.001 in both) participants. The obese-malnourished (high BMI, low SA) group also had greater left ventricular remodeling (left ventricular mass index, 44.2 ± 1.52 versus 33.8 ± 8.28 gm/m.sup.2 ; relative wall thickness 0.39 ± 0.05 versus 0.38 ± 0.06) and worse diastolic function (TDI-e' 7.97 ± 2.16 versus 9.87 ± 2.47 cm/s; E/e' 9.19 ± 3.01 versus 7.36 ± 2.31; left atrial volume index 19.5 ± 7.66 versus 14.9 ± 5.49 mL/m.sup.2) compared to the lean-well-nourished (low BMI, high SA) group, as well as all other subgroups (p < 0.001 for all). Over a median 3.6 years (interquartile range 2.5 to 4.8 years) of follow-up, the obese-malnourished group had the highest multivariable-adjusted risk of the composite outcome (hazard ratio HR 2.49, 95% CI 1.43 to 4.34, p = 0.001), followed by the lean-malnourished (HR 1.78, 95% CI 1.04 to 3.04, p = 0.034) and obese-well-nourished (HR 1.41, 95% CI 0.77 to 2.58, p = 0.27) groups (with lean-well-nourished group as reference). Results were similar when indexed by other anthropometric indices (waist circumference and body fat) and other measures of nutritional status (PNI and GLIM criteria). Potential selection bias and residual confounding were the main limitations of the study. In our cohort study among asymptomatic community-based adults in Taiwan, we found that obese individuals with poor nutritional status have the highest comorbidity burden, the most adverse cardiac remodeling, and the least favorable composite outcome.
Drug hypersensitivity may manifest ranging from milder skin reactions (e.g., maculopapular exanthema and urticaria) to severe systemic reactions, such as anaphylaxis, drug reactions with eosinophilia ...and systemic symptoms (DRESS)/drug-induced hypersensitivity syndrome (DIHS), or Stevens–Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN). Current pharmacogenomic studies have made important strides in the prevention of some drug hypersensitivity through the identification of relevant genetic variants, particularly for genes encoding drug-metabolizing enzymes and human leukocyte antigens (HLAs). The associations identified by these studies are usually drug, phenotype, and ethnic specific. The drug presentation models that explain how small drug antigens might interact with HLA and T cell receptor (TCR) molecules in drug hypersensitivity include the hapten theory, the p-i concept, the altered peptide repertoire model, and the altered TCR repertoire model. The broad spectrum of clinical manifestations of drug hypersensitivity involving different drugs, as well as the various pathomechanisms involved, makes the diagnosis and management of it more challenging. This review highlights recent advances in our understanding of the predisposing factors, immune mechanisms, pathogenesis, diagnostic tools, and therapeutic approaches for drug hypersensitivity.
Drug hypersensitivity such as severe cutaneous adverse reactions (SCAR), including Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), could be life-threatening. Here, we enroll SCAR ...patients to investigate the T cell receptor (TCR) repertoire by next-generation sequencing. A public αβTCR is identified from the cytotoxic T lymphocytes of patients with carbamazepine-SJS/TEN, with its expression showing drug/phenotype-specificity and an bias for HLA-B*15:02. This public αβTCR has binding affinity for carbamazepine and its structural analogs, thereby mediating the immune response. Adoptive transfer of T cell expressing this public αβTCR to HLA-B*15:02 transgenic mice receiving oral administration of carbamazepine induces multi-organ injuries and symptoms mimicking SCAR, including hair loss, erythema, increase of inflammatory lymphocytes in the skin and blood, and liver and kidney dysfunction. Our results not only demonstrate an essential role of TCR in the immune synapse mediating SCAR, but also implicate potential clinical applications and development of therapeutics.
Background
Childhood asthma is a multifactorial inflammatory condition of the airways, associated with specific changes in respiratory microbiome and circulating metabolome.
Methods
To explore the ...functional capacity of asthmatic microbiome and its intricate connection with the host, we performed shotgun sequencing of airway microbiome and untargeted metabolomics profiling of serum samples in a cohort of children with mite‐sensitized asthma and non‐asthmatic controls.
Results
We observed higher gene counts and sample‐to‐sample dissimilarities in asthmatic microbiomes, indicating a more heterogeneous community structure and functionality among the cases than in controls. Moreover, we identified airway microbial species linked to changes in circulating metabolites and IgE responses of the host, including a positive correlation between Prevotella sp oral taxon 306 and dimethylglycine that were both decreased in patients. Several control‐enriched species (Eubacterium sulci, Prevotella pallens, and Prevotella sp oral taxon 306) were inversely correlated with total and allergen‐specific IgE levels. Genes related to microbial carbohydrate, amino acid, and lipid metabolism were differentially enriched, suggesting that changes in microbial metabolism may contribute to respiratory health in asthmatics. Pathway modules relevant to allergic responses were differentially abundant in asthmatic microbiome, such as enrichments for biofilm formation by Pseudomonas aeruginosa, membrane trafficking, histidine metabolism, and glycosaminoglycan degradation, and depletions for polycyclic aromatic hydrocarbon degradation. Further, we identified metagenomic and metabolomic markers (eg, Eubacterium sulci) to discriminate cases from the non‐asthmatic controls.
Conclusions
Our dual‐omics data reveal the connections between respiratory microbes and circulating metabolites perturbed in mite‐sensitized pediatric asthma, which may be of etiological and diagnostic implications.
This study demonstrates shotgun sequencing of airway microbiome and untargeted metabolomics profiling of serum samples in children with mite‐sensitized asthma and non‐asthmatic controls. Integrative analysis identifies specific airway dysbiosis at the species level and its associated functional shift in strong associations with circulating metabolites and IgE responses to mites. Overall, dual‐omics integration reveals microbe‐metabolite connections perturbed in mite‐sensitized pediatric asthma.
Abbreviations: KEGG, Kyoto Encyclopedia of Genes and Genomes; AUC, area under the receiver operating characteristic curve
Background Increasing studies have revealed that HLA alleles are the major genetic determinants of drug hypersensitivity; however, the underlying molecular mechanism remains unclear. Objective We ...adopted the HLA-B∗1502 genetic predisposition to carbamazepine (CBZ)–induced Stevens-Johnson syndrome (SJS)/toxic epidermal necrolysis (TEN) as a model to study the pathologic role of HLA in delayed-type drug hypersensitivity. Methods We in vitro expanded CBZ-specific cytotoxic T lymphocytes (CTLs) from patients with CBZ-induced SJS/TEN and analyzed the interaction between HLA-B and CBZ analogs based on CTL response, surface plasmon resonance, peptide-binding assay, site-directed mutagenesis, and computer modeling. Results The endogenous peptide–loaded HLA-B∗1502 molecule presented CBZ to CTLs without the involvement of intracellular drug metabolism or antigen processing. The HLA-B∗1502/peptide/β2 -microglobulin protein complex showed binding affinity toward chemicals sharing 5-carboxamide on the tricyclic ring, as with CBZ. However, modifications of the ring structure of CBZ altered HLA-B∗1502 binding and CTL response. In addition to HLA-B∗1502, other HLA-B75 family members could also present CBZ to activate CTLs, whereas members of the HLA-B62 and HLA-B72 families could not. Three residues (Asn63, Ile95, and Leu156) in the peptide-binding groove of HLA-B∗1502 were involved in CBZ presentation and CTL activation. In particular, Asn63 shared by members of the B75 family was the key residue. Computer simulations revealed a preferred molecular conformation of the 5-carboxamide group of CBZ and the side chain of Arg62 on the B pocket of HLA-B∗1502. Conclusions This study demonstrates a direct interaction of HLA with drugs, provides a detailed molecular mechanism of HLA-associated drug hypersensitivity, and has clinical correlations for CBZ-related drug–induced SJS/TEN.
To develop a pre‐emptive genetic test that comprises multiple predisposing alleles for the prevention of phenytoin‐related severe cutaneous adverse reactions (SCARs), three sets of patients with ...phenytoin‐SCAR and drug‐tolerant controls from Taiwan, Thailand, and Japan, were enrolled for this study. In addition to cytochrome P450 (CYP)2C9*3, we found that HLA‐B*13:01, HLA‐B*15:02, and HLA‐B*51:01 were significantly associated with phenytoin hypersensitivity with distinct phenotypic specificities. Strikingly, we showed an increase in predictive sensitivity of concurrently testing CYP2C9*3/HLA‐B*13:01/HLA‐B*15:02/HLA‐B*51:01 from 30.5–71.9% for selecting the individuals with the risk of developing phenytoin‐SCAR in Taiwanese cohorts, accompanied by a specificity of 77.7% (combined sensitivity, 64.7%; specificity, 71.9% for three Asian populations). Meta‐analysis of the four combined risk alleles showed significant associations with phenytoin‐SCAR in three Asian populations. In conclusion, combining the assessment of risk alleles of HLA and CYP2C9 potentiated the usefulness of predictive genetic tests to prevent phenytoin hypersensitivity in Asians.
Abstract
Background
The Wnt/β-catenin signaling pathway plays an important role in embryogenesis and tumorigenesis. In human cancer, abnormal activity of Wnt/β-catenin signaling pathway induces ...overexpressed of downstream genes, and initiate oncogene. There are several target genes known to be key players in tumorigenesis, such as c-myc, cyclin D1, MMPs or survivin. Therefore, identifying the target genes of Wnt/β-catenin signaling pathway is important to understanding Wnt/β-catenin-mediated carcinogenesis. In this study, we developed a combined bioinformatics and experimental approach to find potential target genes.
Methods
Luciferase reporter assay was used to analyze the promoter activity of RMI2. WST1 cell proliferation assays and transwell assays were performed to determine the proliferation and migration capacities of RMI2 overexpressing or knockdown stable hepatic cells. Finally, xenograft experiments were performed to measure the tumor formation capacity in vivo.
Results
The results showed that
RMI2
mRNA was upregulated after LiCl treatment and Wnt3a-conditioned medium in a culture of SK-hep-1 cell lines. A chromatin immunoprecipitation (ChIP) assay showed that the β-catenin/T cell-specific factor (TCF) complex binds to the putative TCF binding site of the
RMI2
promoter. We then found a TCF binding site at − 333/− 326 of the
RMI2
promoter, which is crucial for β-catenin responsiveness in liver cell lines.
RMI2
was overexpressed in hepatoma tissue and cell lines, and it promoted the migration and invasion of HCC cells. Moreover,
RMI2
upregulated the expression of epithelial-mesenchymal transition (EMT) markers and the Wnt3a/β-catenin-related genes, but silencing
RMI2
had the opposite effects. Notably, the expression of
RMI2
was positively correlated with the clinical data of HCC patients who had significantly shorter overall survival (OS) and disease-free survival (DFS) (Both:
P
< 0.05). In addition, a total of 373 HCC patients’ data from the Caner Genome Atlas project (TCGA) were used to validate our findings.
Conclusions
Taking all these findings together, we determined that
RMI2
was a new target gene of the Wnt/β-catenin signaling pathway. We also found that
RMI2
promotes EMT markers, HCC cell invasion, and metastasis, which indicated that
RMI2
is a potential target for preventing or at least mitigating the progression of HCC.
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