Multicomponent Solar Cells with High Fill Factors and Efficiencies Based on Non-Fullerene Acceptor Isomers.

Multicomponent organic solar cells (OSCs), such as the ternary and quaternary OSCs, not only inherit the simplicity of binary OSCs but further promote light harvesting and power conversion efficiency (PCE). Here, we propose a new type of multicomponent solar cells with non-fullerene acceptor isomers. Specifically, we fabricate OSCs with the polymer donor J71 and a mixture of isomers, ITCF, as the acceptors. In comparison, the ternary OSC devices with J71 and two structurally similar (not isomeric) NFAs (IT-DM and IT-4F) are made as control. The morphology experiments reveal that the isomers-containing blend film demonstrates increased crystallinity, more ideal domain size, and a more favorable packing orientation compared with the IT-DM/IT-4F ternary blend. The favorable orientation is correlated with the balanced charge transport, increased exciton dissociation and decreased bimolecular recombination in the ITCF-isomer-based blend film, which contributes to the high fill factor (FF), and thus the high PCE. Additionally, to evaluate the generality of this method, we examine other acceptor isomers including IT-M, IXIC-2Cl and SY1, which show same trend as the ITCF isomers. These results demonstrate that using isomeric blends as the acceptor can be a promising approach to promote the performance of multicomponent non-fullerene OSCs.

Controlling the Treatment Time for Ideal Morphology towards Efficient Organic Solar Cells.

In this work, we performed a systematic comparison of different duration of solvent vapor annealing (SVA) treatment upon state-of-the-art PM6:SY1 blend film, which is to say for the first time, the insufficient, appropriate, and over-treatment's effect on the active layer is investigated. The power conversion efficiency (PCE) of corresponding organic solar cell (OSC) devices is up to 17.57% for the optimized system, surpassing the two counterparts. The properly tuned phase separation and formed interpenetrating network plays an important role in achieving high efficiency, which is also well-discussed by the morphological characterizations and understanding of device physics. Specifically, these improvements result in enhanced charge generation, transport, and collection. This work is of importance due to correlating post-treatment delicacy, thin-film morphology, and device performance in a decent way.

Inhibition of miRNA-1-Mediated Inflammation and Autophagy by Astragaloside IV Improves Lipopolysaccharide-Induced Cardiac Dysfunction in Rats.

Introduction: Astragaloside IV (AS-IV) is one of the main active components isolated from the traditional Chinese medicinal herb, Astragalus membranaceus. The present study was designed to investigate whether the regulation of microRNA-1 (miR-1)-mediated inflammation and autophagy contributes to the protective effect of AS-IV against cardiac dysfunction in rats treated with lipopolysaccharides (LPS). Methods: Animal model of cardiac dysfunction in rats or cellular model of injured H9c2 heart cell line was established by using LPS. Echocardiography, electron microscopy, enzyme-linked immunosorbent assay, immunofluorescence, quantitative RT-PCR, and Western blotting were used to determine the cardiac function and expression of inflammation- and autophagy-related proteins at both the mRNA and protein levels. Results: LPS caused cardiac dysfunction in rats or injury in H9c2 cells and induced inflammation and autophagy. Compared with LPS treatment, AS-IV treatment attenuated cardiac dysfunction or cell injury, accompanied by inhibition of inflammation and autophagy. However, the miR-1 mimics partly abolished the effects of AS-IV. In addition, the effect of the miR-1 inhibitor was similar to that of AS-IV in the LPS model. Further analyses showed that AS-IV treatment decreased the mRNA expression of miR-1 in the heart tissue of rats and H9c2 cells treated with LPS. Conclusion: These results suggest that AS-IV attenuated cardiac dysfunction caused by LPS by inhibiting miR-1-mediated inflammation and autophagy, thereby providing a novel mechanism for the protection against cardiac diseases.

Calpain inhibitor prevents atherosclerosis in apolipoprotein E knockout mice by regulating mRNA expression of genes related to cholesterol uptake and efflux.

PURPOSE: We previously reported that a calpain inhibitor (CAI) prevents the development of atherosclerosis in rats. This study aimed to investigate the effects of CAI (1 mg/kg) on atherosclerosis in apolipoprotein E knockout (ApoE KO) mice that were fed a high-fat diet (HFD) and explore the underlying mechanism by analyzing the expression of genes related to the uptake and efflux of cholesterol. METHODS: Atherosclerotic plaques were evaluated. The activity of calpain in the aorta and that of superoxide dismutase (SOD) in the serum were assessed. Lipid profiles in the serum and liver were examined. Serum oxidized low-density lipoprotein (oxLDL), malondialdehyde (MDA), tumor necrosis factor (TNF-α), and interleukin-6 (IL-6) levels were measured. The mRNA expressions of CD68, TNF-α, IL-6, CD36, scavenger receptor (SR-A), peroxisome proliferator-activated receptor gamma (PPAR-γ), liver-x-receptor alpha (LXR-α), and ATP-binding cassette transporter class A1 (ABCA1) in the aorta and peritoneal macrophages were also evaluated. RESULTS: CAI reduced calpain activity in the aorta. CAI also impeded atherosclerotic lesion formation and mRNA expression of CD68 in the aorta and peritoneal macrophages of ApoE KO mice compared with those of mice receiving HFD. However, CAI had no effect on body weight and lipid levels in both the serum and liver. CAI significantly decreased MDA, oxLDL, TNF-α, and IL-6 levels and increased SOD activity in the serum. Moreover, CAI significantly inhibited the mRNA expression of TNF-α and IL-6 genes in the aorta and peritoneal macrophages. In addition, CAI significantly downregulated the mRNA expression of scavenger receptors CD36 and SR-A and upregulated the expression of genes involved in the cholesterol efflux pathway, i.e., PPAR-γ, LXR-α, and ABCA1 in the aorta and peritoneal macrophages. CONCLUSIONS: CAI inhibited the development of atherosclerotic lesions in ApoE KO mice, and this effect might be related to the reduction of oxidative stress and inflammation and the improvement of cholesterol intake and efflux pathways.

Astragaloside IV-targeting miRNA-1 attenuates lipopolysaccharide-induced cardiac dysfunction in rats through inhibition of apoptosis and autophagy.

Astragaloside IV (AS-IV), the major active constituent purified from Astragalus membranaceus, was previously reported to have protective effects against cardiac dysfunction. However, the underlying mechanism remains unknown. In the present study, we investigated the protective effect of AS-IV on lipopolysaccharide (LPS)-induced cardiac dysfunction and explored the potential mechanism by focusing on miRNA-1 (miR-1) at the animal and cellular levels. A series of methods were used, including echocardiography, flow cytometry, ELISA, immunofluorescence, transmission electron microscopy, RT-PCR, and western blotting. The results showed that both AS-IV and the miR-1 inhibitor improved cardiac dysfunction, reduced heart injury, inhibited apoptosis and autophagy, and regulated the expression of calcium- and mitochondrial energy metabolism-related proteins in the heart tissue of rats treated with LPS. Importantly, AS-IV downregulated the expression of miR-1 mRNA in heart tissue. All effects of AS-IV were at least partly abolished by miR-1 mimics. In the in vitro study, both AS-IV and the miR-1 inhibitor inhibited apoptosis and autophagy and regulated the expression of calcium- and mitochondrial energy metabolism-related proteins in heart cells treated with LPS. Similarly, AS-IV downregulated the expression of miR-1 mRNA in heart cells. All effects of AS-IV on cells were at least partly abolished by miR-1 mimics. Furthermore, miR-1 mimics exhibited effects similar to LPS both in animal and cellular studies. Taken together, these results suggest that AS-IV protects against LPS-induced cardiac dysfunction by inhibiting calcium-mediated apoptosis and autophagy by targeting miR-1, highlighting a new mechanism for the therapeutic effect of AS-IV on cardiac dysfunction.

Baicalin inhibits Salmonella typhimurium-induced inflammation and mediates autophagy through TLR4/MAPK/NF-κB signalling pathway.

Baicalin has been reported to protect mice against Salmonella typhimurium (S. typhimurium) infection, while its molecular mechanisms are unclear. In this study, multiplicity of infection (MOI) and observation time were measured. Cell viability and LDH levels were examined in RAW264.7 cells and H9 cells. RAW264.7 cells were stimulated with S typhimurium in the presence or absence of Baicalin, and the levels of pro-inflammatory cytokines were detected by enzyme-linked immunosorbent assay (ELISA). The changes in reactive oxygen species (ROS) production were determined by fluorescence microscopy and ELISA. The autophagy and TLR4/MAPK/NF-κB signalling pathway were examined by immunofluorescence microscopy, quantitative reverse transcription-polymerase chain reaction and Western blotting. The results indicated that MOI of 30 and duration of autophagy evident at 5 h were applicable to this study. Baicalin prevented death of macrophages, promoted bactericidal activity, decreased the levels of pro-inflammatory cytokines and ROS and reduced the changes of key biomarkers in autophagy and TLR4/MAPK/NF-κB signalling pathway infected by S typhimurium. TLR4-overexpressed cells, autophagy and TLR4/MAPK/NF-κB signalling pathway were activated by S typhimurium, which was suppressed by Baicalin. Our findings indicated that Baicalin exerts anti-inflammatory and cell-protective effects, and it mediates autophagy by down-regulating the activity of TLR4 infected by S typhimurium.

[Celastrol inhibits growth and increases apoptosis of human lung cancer A549 cells].

Objective To investigate the inhibitory effect of celastrol on the proliferation of human lung cancer A549 cells and its possible mechanism. Methods A549 cells were treated with 0, 1, 2, 3, 4, 5, 6 µmol/L celastrol for 0, 24, 48, 72 hours. The effects of different concentrations and durations on the cell proliferation were evaluated by MTT assay to determine the optimal concentration and treatment time. In the subsequent experiments, A549 cells were treated with (0, 1, 3) µmol/L of celastrol for 48 hours. The effects of celastrol on the expression of BAX, B-cell lymphoma 2 (Bcl2), caspase-3, caspase-8, caspase-9 mRNA in A549 cells were detected by real-time quantitative PCR. The protein levels of BAX, Bcl-2, cleaved caspase-3(c-caspase-3), c-caspase-8, c-caspase-9 were assessed by Western blot analysis. Results Celastrol inhibited the viability of A549 cells in a concentration- and time-dependent manner. Compared with the group without celastrol treatment, the mRNA and protein level of Bcl2 in A549 cells treated with (1, 3) µmol/L celastrol decreased significantly, while the expression levels of BAX, caspase-3, caspase-8, caspase-9, c-caspase-3, c-caspase-8, c-caspase-9 increased significantly. Conclusion Celastrol could suppress the proliferation and induced the apoptosis of A549 cells through mitochondrial pathway.

Inhibition of TNF-α-mediated NF-κB Activation by Ginsenoside Rg1 Contributes the Attenuation of Cardiac Hypertrophy Induced by Abdominal Aorta Coarctation.

Ginsenoside Rg1 (Rg1), a protopanaxadiol saponin extracted from Chinese medicine Panax ginseng C.A. Meyer, has been demonstrated to inhibit the cardiac hypertrophy. However, the molecular mechanisms underlying the inhibition remain poorly understood. Activation of nuclear factor-kappa B (NF-κB) mediated by tumor necrosis factor α (TNF-α) gets involved in the cardiac hypertrophy. This study is designed to investigate the effects and the potential mechanism of Rg1 on the abdominal aorta coarctation (AAC)-induced cardiac hypertrophy with focus on TNF-α/NF-κB signaling pathway. The results showed that oral administration of Rg1 dose-dependently improved the pathological changes, decreased the ratios of left ventricular weight/body weight (LVW/BW) and heart weight/BW (HW/BW), corrected the dysfunction of the cardiac hemodynamics by decreasing the left ventricular systolic pressure and left ventricular end-diastolic pressure and increasing the maximal rate of left ventricular systolic and diastolic pressure (±dp/dtmax) compared with the AAC alone. Rg1 also downregulated the atrial natriuretic peptide mRNA expression and decreased the mRNA and protein expression of TNF-α in the heart tissue of rats compared with the AAC alone. In addition, Rg1 and BAY, the specific inhibitor of NF-κB, decreased the protein content and downregulated the mRNA expression of atrial natriuretic peptide in neonatal rat ventricular myocytes treated with TNF-α. Furthermore, Rg1 increased the protein expression of p65, the subunit of NF-κB, in cytoplasm and decreased the expression p65 in nucleus of the heart tissue of rats undergoing the AAC and of neonatal rat ventricular myocytes treated with TNF-α. The results suggested that Rg1 attenuates the AAC-induced cardiac hypertrophy through inhibition of TNF-α/NF-κB signaling pathway.

Effects of UGT2B7 Genetic Polymorphisms on Serum Concentrations of Valproic Acid in Chinese Children With Epilepsy Comedicated With Lamotrigine.

BACKGROUND: Valproic acid (VPA) is widely used in the treatment of children with epilepsy. Genetic polymorphisms in genes encoding drug-metabolizing enzymes may be an important source of interindividual variability in VPA metabolism. VPA is a substrate of uridine diphosphate glucuronosyltransferase 2B7 (UGT2B7). In this study, we seek to evaluate the effects of genetic polymorphisms of the UGT2B7 gene on serum VPA concentrations in epileptic children comedicated with lamotrigine (LTG). METHODS: We recruited 166 Chinese children with epilepsy who were treated with VPA in combination with LTG. Serum VPA and LTG concentrations were measured by fluorescence polarization immunoassay and high performance liquid chromatography, respectively. The UGT2B7 -161C > T in the 5'-upstream regions and 211 G > T, 372A > G, 735A > G, and 802C > T in the coding regions were genotyped using polymerase chain reaction amplification followed by direct automated DNA sequencing. RESULTS: Our data show that patients carrying the variant UGT2B7 -161C > T or 802C > T genotypes had significantly higher adjusted VPA concentrations than those carrying the wild-type genotypes. The significant associations were potentiated after adjusted by age and adjusted LTG concentration. However, no associations were detected between the other studied UGT2B7 genotypes and adjusted VPA concentrations, even after adjusting by age and comedication. CONCLUSIONS: These results suggest that the UGT2B7 -161C > T or 802C > T mutations affect VPA pharmacokinetics, which are potentially enhanced by age and concomitant LTG administration. These findings provide a potential mechanism underlying interindividual variation in the disposition of VPA in combination with LTG.

Influence of valproic acid concentration and polymorphism of UGT1A4*3, UGT2B7 -161C > T and UGT2B7*2 on serum concentration of lamotrigine in Chinese epileptic children.

PURPOSE: To investigate the impact of valproic acid (VPA) and genetic polymorphism of the major metabolizing enzyme (UGT1A4, UGT2B7) of lamotrigine (LTG) and VPA on LTG concentration in Chinese epileptic children. METHODS: Three single nucleotide polymorphisms (UGT1A4*3, UGT2B7 -161C > T and UGT2B7*2) were analyzed by polymerase chain reaction-restriction fragment length polymorphism or direct DNA sequencing. The concentrations of LTG and VPA were measured by high-performance liquid chromatography (HPLC) and fluorescence polarization immunoassay, respectively. The adjusted concentration of LTG was defined as the concentration-to-dose-ratio (CDRLTG). Data analysis was performed using IBM SPSS Statistics 21.0. RESULTS: A total of 56 patients treated with LTG as monotherapy and 158 patients treated with LTG plus VPA were included in this study. In the polytherapy group, LTG concentration showed a good linear relationship with gender, age, daily LTG dose, VPA concentration, and UGT1A4*3 polymorphism, but had no relationship with the polymorphism of UGT2B7 -161C > T or UGT2B7*2. Moreover, LTG concentration and CDRLTG for the UGT1A4*3 were higher compared to UGT1A4*1 (LTG: 7.24 ± 3.51 vs 5.26 ± 3.27 µg/mL, p = 0.001; CDRLTG: 2.75 ± 1.02 vs 2.14 ± 0.96 µg/mL per mg/kg, p < 0.001, respectively). In the monotherapy group, there was no statistical difference between UGT1A4*3 and UGT1A4*1 in LTG concentration or CDRLTG. The patients in the polytherapy group were divided into two subgroups according to VPA concentration (lower/higher: 10-50/50-125 µg/mL). CDRLTG values of the patients carrying the UGT1A4*3 genotype were higher compared to UGT1A4*1*1 (2.86 ± 1.03 vs 2.22 ± 0.94 µg/mL per mg/kg, p = 0.001) only when the VPA concentration was higher. CONCLUSIONS: UGT1A4*3 polymorphism had an effect on LTG concentration only with VPA co-administration, and the effect was remarkable when VPA concentration was higher.

Effects of UGT1A4 genetic polymorphisms on serum lamotrigine concentrations in Chinese children with epilepsy.

Lamotrigine (LTG) is widely used in the treatment of children with epilepsy. Genetic polymorphisms in genes encoding drug-metabolizing enzymes may be an important source of interindividual variability in LTG metabolism. The aim of this study was to evaluate the effects of genetic polymorphisms of uridine diphosphate glucuronosyltransferase (UGT) 1A4 (UGT1A4) gene on LTG serum concentrations in children with epilepsy. The UGT1A4 142T > G in the coding regions and -219C > T/-163G > A in the 5'-upstream regions were genotyped using polymerase chain reaction amplification followed by direct automated DNA sequencing in 148 patients treated with polytherapy with LTG and valproic acid (VPA). Our data showed that patients carrying the variant UGT1A4 -219C > T/-163G > A genotypes or alleles had significantly higher adjusted LTG concentrations than those carrying the wild-type genotypes or alleles. However, the significant association was abrogated after adjusted by age, body weight, and adjusted VPA concentration. No associations were detected between the UGT1A4 142T > G genotypes or alleles and adjusted LTG concentrations. Taken together, these results suggest that the -219C > T/-163G > A mutations in the 5'-upstream regions of the UGT1A4 gene affect LTG pharmacokinetics, with which is potentially interfered by age, body weight, and concomitant VPA administration.