Small‐molecule acceptors (SMAs)‐based organic solar cells (OSCs) have exhibited great potential for achieving high power conversion efficiencies (PCEs). Meanwhile, developing asymmetric SMAs to improve photovoltaic performance by modulating energy level distribution and morphology has drawn lots of attention. In this work, based on the high‐performance SMA (Y6), three asymmetric SMAs are developed by substituting the fluorine atoms on the terminal group with chlorine atoms, namely SY1 (two F atoms and one Cl atom), SY2 (two F atoms and two Cl atoms), and SY3 (three Cl atoms). Y6 (four F atoms) and Y6‐4Cl (four Cl atoms) are synthesized as control molecules. As a result, SY1 exhibits the shallowest lowest unoccupied molecular orbital energy level and the best molecular packing among these five acceptors. Consequently, OSCs based on PM6:SY1 yield a champion PCE of 16.83% with an open‐circuit voltage (VOC) of 0.871 V, and a fill factor (FF) of 0.760, which is the best result among the five devices. The highest FF for the PM6:SY1‐based device is mainly ascribed to the most balanced charge transport and optimal morphology. This contribution provides deeper understanding of applying asymmetric molecule design method to further promote PCEs of OSCs.
Background
Aspirin-exacerbated respiratory disease (AERD) is an inflammatory condition of the respiratory tract and is characterized by overproduction of leukotrienes (LT) and large numbers of circulating granulocyte-platelet complexes. LT production can be suppressed by prostaglandin E2 (PGE2) and the cyclic AMP-dependent protein kinase A (PKA).
Objective
To determine if PGE2-dependent control of LT production by granulocytes is dysregulated in AERD.
Methods
Granulocytes from well-characterized patients with and without AERD were activated ex vivo and subjected to a range of functional and biochemical analyses.
Results
Granulocytes from subjects with AERD generated more LTB4 and cysteinyl LTs than did granulocytes from controls with aspirin-tolerant asthma and controls without asthma. When compared with controls, granulocytes from subjects with AERD had comparable levels of EP2 protein expression and PGE2-mediated cAMP accumulation, yet were resistant to PGE2-mediated suppression of LT generation. Percentages of platelet-adherent neutrophils correlated positively with LTB4 generation and inversely with responsiveness to PGE2-mediated suppression of LTB4. The PKA inhibitor H89 potentiated LTB4 generation by control granulocytes but was inactive in granulocytes from individuals with AERD and had no effect on platelet P-selectin induction. Both tonic PKA activity and levels of PKA catalytic gamma subunit protein were significantly lower in granulocytes from individuals with AERD relative to those from controls.
Conclusions
Impaired granulocyte PKA function in AERD may lead to dysregulated control of 5-lipoxygenase activity by PGE2, whereas adherent platelets lead to increased production of LTs, which contributes to the features of persistent respiratory tract inflammation and LT overproduction.
Trichophyton rubrum is the most common fungal pathogen in the world, which has been studied as an important dermatophyte model organism. Despite the prevalence of T. rubrum, the available antifungal therapies are not sufficiently efficient. In this study, we performed the first comparison between the two major growth stages of T. rubrum: conidial and mycelial stages, based on their whole-cell proteomes and lysine acetylomes. In total, 4343 proteins were identified in both stages, and 1879 proteins were identified as differentially expressed between the two stages. The results showed that secretory proteases were more abundant in conidia, while aerobic metabolism and protein synthesis were significantly activated in the mycelial stage. In addition, 386 acetylated sites on 285 proteins and 5414 acetylated sites on 2335 proteins were identified in conidia and mycelia, respectively. The acetylation modifications were highly involved in metabolism and protein synthesis in both stages but differentially involved in Kyoto Encyclopedia of Genes and Genomes pathways and in epigenetic regulation between the two stages. Furthermore, inhibition of acetyltransferases or deacetylases significantly inhibited fungal growth and induced apoptosis. These results will enhance our understanding of the biological and physiological characteristics of T. rubrum and facilitate the development of improved therapies targeting these medically important pathogenic fungi.
BackgroundDermatophytes, the most common cause of fungal infections, affect millions of individuals worldwide. They pose a major threat to public health because of the severity and longevity of infections caused by dermatophytes and their refractivity to therapy. Trichophyton rubrum (T. rubrum), the most common dermatophyte species, is a promising model organism for dermatophyte research. Post-translational modifications (PTMs) have been shown to be essential for many biological processes, particularly in the regulation of key cellular processes that contribute to pathogenicity. Although PTMs have important roles, little is known about their roles in T. rubrum and other dermatophytes. Succinylation is a new PTM that has recently been identified. In this study, we assessed the proteome-wide succinylation profile of T. rubrum. This study sought to systematically identify the succinylated sites and proteins in T. rubrum and to reveal the roles of succinylated proteins in various cellular processes as well as the differences in the succinylation profiles in different growth stages of the T. rubrum life cycle.ResultsA total of 569 succinylated lysine sites were identified in 284 proteins. These succinylated proteins are involved in various cellular processes, such as metabolism, translation and epigenetic regulation. Additionally, 24 proteins related to pathogenicity were found to be succinylated. Comparison of the succinylome at the conidia and mycelia stages revealed that most of the succinylated proteins and sites were growth-stage specific. In addition, the succinylation modifications on histone and ribosomal proteins were significantly different between these two growth stages. Moreover, the sequence features surrounding the succinylated sites were different in the two stages, thus indicating the specific recognition of succinyltransferases in each growth phase.ConclusionsIn this study, we explored the first T. rubrum succinylome, which is also the first PTM analysis of dermatophytes reported to date. These results revealed the major roles of the succinylated proteins involved in T. rubrum and the differences in the succinylomes between the two major growth stages. These findings should improve understanding of the physiological and pathogenic properties of dermatophytes and facilitate future development of novel drugs and therapeutics for treating superficial fungal infections.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3977-y) contains supplementary material, which is available to authorized users.
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