Three two-dimensional donor-acceptor conjugated copolymers consisting of a benzo1,2-b:4,5-
'dithiophene derivative and thieno3,2-
thiophene with a conjugated side chain were designed and synthesized ...for use in bulk heterojunction (BHJ) or nonfullerene polymer solar cells (PSCs). Through attaching various acceptor end groups to the conjugated side chain on the thieno3,2-
thiophene moiety, the electronic, photophysical, and morphological properties of these copolymers were significantly affected. It was found that the intermolecular charge transfer interactions were enhanced with the increase in the acceptor strength on the thieno3,2-
thiophene moiety. Moreover, a better microphase separation was obtained in the copolymer: PC
BM or ITIC blend films when a strong acceptor end group on the thieno3,2-
thiophene moiety was used. As a result, BHJ PSCs based on copolymer:PC
BM blend films as active layers exhibited power conversion efficiencies from 2.82% to 4.41%, while those of nonfullerene copolymer:ITIC-based inverted PSCs ranged from 6.09% to 7.25%. These results indicate the side-chain engineering on the end groups of thieno3,2-
thiophene unit through a vinyl bridge linkage is an effective way to adjust the photophysical properties of polymers and morphology of blend films, and also have a significant influence on devices performance.
Alzheimer's disease (AD) is the most common cause of dementia in late life. It is difficult to precisely diagnose AD at early stages, making biomarker search essential for further developments. The ...objective of this study was to identify protein biomarkers associated with aluminum ions toxicity (AD-like toxicity) in a human neuroblastoma cell model, SH-SY5Y and assess potential prevention by NAP (NAPVSIPQ). Complete proteomic techniques were implemented. Four proteins were identified as up-regulated with aluminum ion treatment, CBP80/20-dependent translation initiation factor (CTIF), Early endosome antigen 1 (EEA1), Leucine-rich repeat neuronal protein 4 (LRRN4) and Phosphatidylinositol 3-kinase regulatory subunit beta (PI3KR2). Of these four proteins, EEA1 and PI3KR2 were down-regulated after NAP-induced neuroprotective activity in neuroblastoma cells. Thus, aluminum ions may increase the risk for neurotoxicity in AD, and the use of NAP is suggested as a treatment to provide additional protection against the effects of aluminum ions, via EEA1 and PI3KR2, associated with sorting and processing of the AD amyloid precursor protein (APP) through the endosomal system.
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•The aluminum ion-induced accumulation of β-amyloid1–42 which may cause risk of AD.•ADNP level may serve as a new and direct therapeutic indicator for NAP treatment.•NAP may effect the mTOR pathway, which is responsible for the proliferation and for survival of the majority of cell.
We are developing time-of-flight (TOF) multi-gap Resistive Plate Chambers (MRPCs) which perform both timing and hit position measurements, the TOF-tracker MRPC, for muon detection to measure ...exclusive Drell–Yan reaction (π−p→γ∗n→μ+μ−n) at J-PARC’s hadron hall. Here we report on the development of a prototype TOF-tracker MRPC with a sensitive area of 500×1000mm2 and its performance in an electron-positron particle beam at the SPring-8 synchrotron in Japan.
•Development of the muon detector for both timing and hit position measurements.•Beam test for examination of the basic performance the muon detector.•Achievement of a time resolution of 100 ps.
Left ventricular hypertrophy (LVH) in hypertension has prognostic significance on cardiovascular mortality and morbidity. Recently, we have shown that n-butylidenephthalide (BP) improves human ...adipose-derived stem cell (hADSC) engraftment via attenuated reactive oxygen species (ROS) production. This prompted us to investigate whether remote transplantation of BP-pretreated hADSCs confers attenuated LVH at an established phase of hypertension. Male spontaneously hypertensive rats (SHRs) aged 12 weeks were randomly allocated to receive right hamstring injection of vehicle, clinical-grade hADSCs, and BP-preconditioned hADSCs for 8 weeks. As compared with untreated SHRs, naïve hADSCs decreased the ratio of LV weight to tibia, cardiomyocyte cell size, and collagen deposition independent of hemodynamic changes. These changes were accompanied by attenuated myocardial ROS production and increased p-STAT3 levels. Compared with naïve hADSCs, BP-preconditioned hADSCs provided a further decrease of ROS and LVH and an increase of local hADSC engraftment, STAT3 phosphorylation, STAT3 activity, STAT3 nuclear translocation, myocardial IL-10 levels, and the percentage of M2 macrophage infiltration. SIN-1 or S3I-201 reversed the effects of BP-preconditioned ADSCs increase on myocardial IL-10 levels. Furthermore, SIN-1 abolished the phosphorylation of STAT3, whereas superoxide levels were not affected following the inhibition of STAT3. Our results highlighted the feasibility of remote transplantation of hADSCs can be considered as an alternative procedure to reverse cardiac hypertrophy even at an established phase of hypertension. BP-pretreated hADSCs polarize macrophages into M2 immunoregulatory cells more efficiently than naïve hADSCs via ROS/STAT3 pathway.
Patients with triple-negative breast cancer have few therapeutic strategy options. In this study, we investigated the effect of isoliquiritigenin (ISL) on the proliferation of triple-negative breast ...cancer cells. We found that treatment with ISL inhibited triple-negative breast cancer cell line (MDA-MB-231) cell growth and increased cytotoxicity. ISL reduced cell cycle progression through the reduction of cyclin D1 protein expression and increased the sub-G1 phase population. The ISL-induced apoptotic cell population was observed by flow cytometry analysis. The expression of Bcl-2 protein was reduced by ISL treatment, whereas the Bax protein level increased; subsequently, the downstream signaling molecules caspase-3 and poly ADP-ribose polymerase (PARP) were activated. Moreover, ISL reduced the expression of total and phosphorylated mammalian target of rapamycin (mTOR), ULK1, and cathepsin B, whereas the expression of autophagic-associated proteins p62, Beclin1, and LC3 was increased. The decreased cathepsin B cause the p62 accumulation to induce caspase-8 mediated apoptosis. In vivo studies further showed that preventive treatment with ISL could inhibit breast cancer growth and induce apoptotic and autophagic-mediated apoptosis cell death. Taken together, ISL exerts an effect on the inhibition of triple-negative MDA-MB-231 breast cancer cell growth through autophagy-mediated apoptosis. Therefore, future studies of ISL as a supplement or alternative therapeutic agent for clinical trials against breast cancer are warranted.
Herein, three benzodithiophene (BDT)-based conjugated polymers, PBDTT-FBT, P3TBDT-FBT, and PTBOT-FBT, with gradually increased biaxially-extended side-chain conjugation are synthesized. The increase ...in the side-chain conjugated plane is revealed to enhance the π-π* transition and intramolecular charge transfer (ICT) of the polymer to result in improved absorption at near-ultraviolet region. Besides, the electron-withdrawing ability of the large side-chain conjugation effectively downshifts the energy levels of the derived polymer. Through providing complementary absorption spectra and suitable cascade energy levels, PTBOT-FBT with the largest side-chain conjugation is demonstrated as an effective third photoactive component for both fullerene and non-fullerene-acceptor (NFA) binary bulk-heterojunction (BHJ) systems, which enables a respective improvement of 2.5% and 11.8% in PCE of the studied fullerene- and NFA-based ternary solar cell devices. Moreover, it is found that the ternary NFA-based BHJ film exhibits a more favorable morphology after adding PTBOT-FBT as compared to the fullerene-based film, suggesting the higher tolerance of the polymers with bulky sidechains in the NFA system.
Three benzoditiophene (BDT)-based conjugated polymers with gradually increased biaxially-extended side-chain conjugation are synthesized in this study. The increase in the side-chain conjugated plane is revealed to enhance the π-π* transition and intramolecular charge transfer (ICT) of the polymer to result in improved absorption at near-ultraviolet region. Besides, the electron-withdrawing ability of the large side-chain conjugation effectively downshifts the energy levels of the derived polymer. Display omitted
•PTBOT-FBT with biaxially-extended side-chains was synthesized, possessing broad UV-vis absorption/deep-lying energy levels.•PTBOT-FBT serves an efficient third component for fullerene- and non-fullerene-acceptor (NFA) bulk-heterojunction systems.•It enables a respective improvement of 2.5% and 11.8% in efficiency for the studied fullerene- and NFA-based solar cells.•Out results suggest the rigid and amorphous polymers, like PTBOT-FBT, have a better compatibility with NFA than fullerene.
Aeromonas aquariorum, a recently described species, is associated with a variety of human diseases. We present here the first genome sequence of A. aquariorum strain AAk1, which was isolated as the ...sole pathogen from the blood of a patient with septicemia and necrotizing fasciitis.
The developmental potential within pluripotent cells in the canonical model is restricted to embryonic tissues, whereas totipotent cells can differentiate into both embryonic and extraembryonic ...tissues. Currently, the ability to culture in vitro totipotent cells possessing molecular and functional features like those of an early embryo in vivo has been a challenge. Recently, it was reported that treatment with a single spliceosome inhibitor, pladienolide B (plaB), can successfully reprogram mouse pluripotent stem cells into totipotent blastomere-like cells (TBLCs) in vitro. The TBLCs exhibited totipotency transcriptionally and acquired expanded developmental potential with the ability to yield various embryonic and extraembryonic tissues that may be employed as novel mouse developmental cell models. However, it is disputed whether TBLCs are 'true' totipotent stem cells equivalent to in vivo two-cell stage embryos. To address this question, single-cell RNA sequencing was applied to TBLCs and cells from early mouse embryonic developmental stages and the data were integrated using canonical correlation analyses. Differential expression analyses were performed between TBLCs and multi-embryonic cell stages to identify differentially expressed genes. Remarkably, a subpopulation within the TBLCs population expressed a high level of the totipotent-related genes
and displayed transcriptomic features similar to mouse two-cell stage embryonic cells. This study underscores the subtle differences between in vitro derived TBLCs and in vivo mouse early developmental cell stages at the single-cell transcriptomic level. Our study has identified a new experimental model for stem cell biology, namely 'cluster 3', as a subpopulation of TBLCs that can be molecularly defined as near totipotent cells.
Episodic migraine (EM) may evolve into the more disabling chronic migraine (CM, monthly migraine days ≥ 8 and headache days ≥ 15) with unknown mechanism. Aiming to elucidate the pathophysiology of CM ...and its relationship with EM, this study characterized the visual cortical responses in CM and EM. Neuromagnetic visual-evoked responses to left-hemifield checkerboard reversals were obtained in patients with EM (interictal or ictal states), CM (interictal) and age-matched controls. For each subject, the 1500 evoked responses were sequentially divided into 30 blocks and percentage changes of P100m amplitude in blocks 2, 9, 16, 23, and 30 compared to the first block were computed to assess habituation. At the end of visual stimulation (block 30), P100m amplitude was decreased (habituated) in the controls (n=32) (35.2±2.6nAm vs. 41.9±2.7, p=0.005) but increased (potentiated) in the interictal state of EM (n=29) (39.7±3.8 vs. 33.5±3.0, p=0.007). In CM (n=25), P100m was habituated (46.5±2.9 vs. 51.6±3.7, p=0.013) but higher at the initial block than in those of the interictal state of EM (p=0.001). These CM features also characterized the P100m in the ictal state of EM (n=9). There was no difference of P100m between CM and ictal state of EM. In conclusion, patients with CM demonstrate a persistent ictal-like excitability pattern of the visual cortex between migraine attacks which may implicate central inhibitory dysfunction.
A new category of cefepime susceptibility, susceptible dose dependent (SDD), for Enterobacteriaceae, has been suggested to maximize its clinical use. However, clinical evidence supporting such a ...therapeutic strategy is limited. A retrospective study of 305 adults with monomicrobial Enterobacter cloacae bacteremia at a medical center from 2008 to 2012 was conducted. The patients definitively treated with in vitro active cefepime (cases) were compared with those treated with a carbapenem (controls) to assess therapeutic effectiveness. The 30-day crude mortality rate is the primary endpoint, and clinical prognostic factors are assessed. Of 144 patients receiving definitive cefepime or carbapenem therapy, there were no significant differences in terms of age, sex, comorbidity, source of bacteremia, disease severity, or 30-day mortality (26.4% versus 22.2%; P = 0.7) among those treated with cefepime (n = 72) or a carbapenem (n = 72). In the multivariate analysis, the presence of critical illness, rapidly fatal underlying disease, extended-spectrum beta-lactamase (ESBL) producers, and cefepime-SDD (cefepime MIC, 4 to 8 μg/ml) isolates was independently associated with 30-day mortality. Moreover, those infected by cefepime-SDD isolates with definitive cefepime therapy had a higher mortality rate than those treated with a carbapenem (5/7 71.4%, versus 2/11 18.2%; P = 0.045). Cefepime is one of the therapeutic alternatives for cefepime-susceptible E. cloacae bacteremia but is inefficient for cases of cefepime-SDD E. cloacae bacteremia compared with carbapenem therapy.
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