Abstract
N-doping plays an irreplaceable role in controlling the electron concentration of organic semiconductors thus to improve performance of organic semiconductor devices. However, compared with ...many mature p-doping methods, n-doping of organic semiconductor is still of challenges. In particular, dopant stability/processability, counterion-semiconductor immiscibility and doping induced microstructure non-uniformity have restricted the application of n-doping in high-performance devices. Here, we report a computer-assisted screening approach to rationally design of a triaminomethane-type dopant, which exhibit extremely high stability and strong hydride donating property due to its thermally activated doping mechanism. This triaminomethane derivative shows excellent counterion-semiconductor miscibility (counter cations stay with the polymer side chains), high doping efficiency and uniformity. By using triaminomethane, we realize a record n-type conductivity of up to 21 S cm
−1
and power factors as high as 51 μW m
−1
K
−2
even in films with thicknesses over 10 μm, and we demonstrate the first reported all-polymer thermoelectric generator.
Excessive sodium intake is associated with nephrolithiasis, but the impact of sodium-deficient (SD) diets is unknown. Hence, we investigated the effects of short- and long-term SD diets on the ...expression of renal aquaporins and sodium transporters, and thus calcium oxalate (CaOx) crystal formation in hyperoxaluria rats. In a short-term sodium balance study, six male rats received drinking water and six received 0.75% ethylene glycol (EG) to induce hyperoxaluria. After a 30-day period of feeding on normal chow, both groups were treated with a normal-sodium diet for 5 days, followed by a sodium-free diet for the next 5 days. In a long-term SD study (42 days), four groups, induced with EG or not, were treated with normal-sodium water and sodium-free drinking water, alternately. Short-term sodium restriction in EG rats reversed the daily positive sodium balance, but progressively caused a negative cumulative water balance. In the long-term study, the abundant levels of of Na/H exchanger, thiazide-sensitive Na-Cl cotransporter, Na-K-ATPase, and aquaporins-1 from SD + EG rats were markedly reduced, corresponding to a decrease in Uosm, as compared to SD rats. Increased urine calcium, AP(CaOx)index, and renal CaOx deposition were also noted in SD + EG rats. Although the SD treatment reduced sodium excretion, it also increased urinary calcium and impaired renal function, ultimately causing the formation of more CaOx crystals.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Particulate matter 2.5 (PM2.5) is a risk factor for lung cancer. In this study, we investigated the molecular mechanisms of PM2.5 exposure on lung cancer progression. We found that short‐term ...exposure to PM2.5 for 24 h activated the EGFR pathway in lung cancer cells (EGFR wild‐type and mutant), while long‐term exposure of lung cancer cells to PM2.5 for 90 days persistently promoted EGFR activation, cell proliferation, anchorage‐independent growth, and tumor growth in a xenograft mouse model in EGFR‐driven H1975 cancer cells. We showed that PM2.5 activated AhR to translocate into the nucleus and promoted EGFR activation. AhR further interacted with the promoter of TMPRSS2, thereby upregulating TMPRSS2 and IL18 expression to promote cancer progression. Depletion of TMPRSS2 in lung cancer cells suppressed anchorage‐independent growth and xenograft tumor growth in mice. The expression levels of TMPRSS2 were found to correlate with nuclear AhR expression and with cancer stage in lung cancer patient tissue. Long‐term exposure to PM2.5 could promote tumor progression in lung cancer through activation of EGFR and AhR to enhance the TMPRSS2‐IL18 pathway.
Synopsis
PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18.
Exposure to PM2.5 activates EGFR pathway and promotes lung cancer progression.
Long‐term exposure to PM2.5 increases lung cancer cell proliferation, anchorage‐independent growth, and xenograft tumor growth in mice.
PM2.5 activates AhR to translocate into the nucleus and upregulates the expression of TMPRSS2.
Depletion of TMPRSS2 in lung cancer cells suppresses anchorage‐independent growth and xenograft tumor growth in mice.
TMPRSS2 upregulates IL I8 expression and promotes lung cancer progression.
PM2.5 promotes lung cancer progression through activation of the AhR‐TMPRSS2‐IL18.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Pulmonary artery hypertension (PAH) pathology involves extracellular matrix (ECM) remodeling in cardiac tissues, thus promoting cardiac fibrosis progression. miR-29a-3p reportedly inhibits lung ...progression and liver fibrosis by regulating ECM protein expression; however, its role in PAH-induced fibrosis remains unclear. In this study, we aimed to investigate the role of miR-29a-3p in cardiac fibrosis progression in PAH and its influence on ECM protein thrombospondin-2 (THBS2) expression. The diagnostic and prognostic values of miR-29a-3p and THBS2 in PAH were evaluated. The expressions and effects of miR-29a-3p and THBS2 were assessed in cell culture, monocrotaline-induced PAH mouse model, and patients with PAH. The levels of circulating miR-29a-3p and THBS2 in patients and mice with PAH decreased and increased, respectively. miR-29a-3p directly targets THBS2 and regulates THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis. The circulating levels of miR-29a-3p and THBS2 were correlated with PAH diagnostic parameters, suggesting their independent prognostic value. miR-29a-3p targeted THBS2 expression via a direct anti-fibrotic effect on PAH-induced cardiac fibrosis, indicating miR-29a-3p acts as a messenger with promising therapeutic effects.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The role of miRNAs in cancer and their possible function as therapeutic agents are interesting and needed further investigation. The miR-26a-5p had been demonstrated as a tumor suppressor in various ...cancers. However, the importance of miR-26a-5p regulation in upper tract urothelial carcinoma (UTUC) remains unclear. Here, we aimed to explore the miR-26a-5p expression in UTUC tissues and to identify its regulatory targets and signal network involved in UTUC tumorigenesis. The miR-26a-5p expression was validated by quantitative real-time polymerase chain reaction (qPCR) using renal pelvis tissue samples from 22 patients who were diagnosed with UTUC and 64 cases of renal pelvis tissue microarray using in situ hybridization staining. BFTC-909 UTUC cells were used to examine the effects of miR-26a-5p genetic delivery on proliferation, migration and expression of epithelial-to-mesenchymal transition (EMT) markers. MiR-26a-5p was significantly down-regulated in UTUC tumors compared to adjacent normal tissue and was decreased with histological grades. Moreover, restoration of miR-26a-5p showed inhibition effects on proliferation and migration of BFTC-909 cells. In addition, miR-26a-5p delivery regulated the EMT marker expression and inhibited WNT5A/β-catenin signaling and expression of downstream molecules including NF-κB and MMP-9 in BFTC-909 cells. This study demonstrated that miR-26a-5p restoration may reverse EMT process and regulate WNT5A/β-catenin signaling in UTUC cells. Further studies warranted to explore the potential roles in biomarkers for diagnostics and prognosis, as well as novel therapeutics targets for UTUC treatment.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Molecular doping plays an important role in the modification of carrier density of organic semiconductors thus enhancing their optoelectronic performance. However, efficient n‐doping remains ...challenging, especially owing to the lack of strongly reducing and air‐stable n‐dopants. Herein, an N‐heterocyclic carbene (NHC) precursor, DMImC, is developed as a thermally activated n‐dopant with the excellent stability in air. Its thermolysis in situ regenerates free NHC and subsequently dopes typical organic semiconductors. In sequentially doped FBDPPV films, DMImC does not disturb the π–π packing of the polymer and achieves good miscibility with the polymer. As a result, a high electrical conductivity of up to 8.4 S cm−1 is obtained. Additionally, the thermally activated doping and the excellent air stability permit DMImC to be noninteractively co‐processed with polymers in air. Our results reveal that DMImC can be served as an efficient n‐dopant suitable for various organic semiconductors.
Based on N‐heterocyclic carbene, a thermally activated n‐dopant with excellent air stability and high n‐doping efficacy is developed. It can regenerate N‐heterocyclic carbene in situ by decarboxylation for the subsequent n‐doping. The thermally activated n‐doping increases the air stability of n‐dopants and permits n‐dopants to be co‐processed with polymer FBDPPV noninteractively before heating in air.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Background An unscheduled return visit (URV) to the emergency department (ED) within 72-h is an indicator of ED performance. An unscheduled return revisit (URV) within 72-h was used to monitor ...adverse events and medical errors in a hospital quality improvement program. The study explores the potential factors that contribute to URV to the ED within 72-h and the unscheduled return revisit admission (URVA) in adults below 50 years old. Methods The case-control study enrolled 9483 URV patients during 2015-2020 in National Cheng-Kung University Hospital. URVA and URV non-admission (URVNA) patients were analyzed. The Gini impurity index was calculated by decision tree (DT) to split the variables capable of partitioning the groups into URVA and URVNA. Logistic regression is applied to calculate the odds ratio (OR) of candidate variables. The alpha level was set at 0.05. Results Among patients under the age of 50, the percentage of females in URVNA was 55.05%, while in URVA it was 53.25%. Furthermore, the average age of URVA patients was 38.20 + or - 8.10, which is higher than the average age of 35.19 + or - 8.65 observed in URVNA. The Charlson Comorbidity Index (CCI) of the URVA patients (1.59 + or - 1.00) was significantly higher than that of the URVNA patients (1.22 + or - 0.64). The diastolic blood pressure (DBP) of the URVA patients was 85.29 + or - 16.22, which was lower than that of the URVNA (82.89 + or - 17.29). Severe triage of URVA patients is 21.1%, which is higher than the 9.7% of URVNA patients. The decision tree suggests that the factors associated with URVA are "severe triage," "CCI higher than 2," "DBP less than 86.5 mmHg," and "age older than 34 years". These risk factors were verified by logistic regression and the OR of CCI was 2.42 (1.50-3.90), the OR of age was 1.84 (1.50-2.27), the OR of DBP less than 86.5 was 0.71 (0.58-0.86), and the OR of severe triage was 2.35 (1.83-3.03). Conclusions The results provide physicians with a reference for discharging patients and could help ED physicians reduce the cognitive burden associated with the diagnostic errors and stress. Keywords: Charlson comorbidity index, Emergency department, Unscheduled revisit, Admission
Crystallinity and crystal orientation have a predominant impact on a materials’ semiconducting properties, thus it is essential to manipulate the microstructure arrangements for desired ...semiconducting device performance. Here, ultra‐uniform hole‐transporting material (HTM) by self‐assembling COOH‐functionalized P3HT (P3HT‐COOH) is fabricated, on which near single crystal quality perovskite thin film can be grown. In particular, the self‐assembly approach facilitates the P3HT‐COOH molecules to form an ordered and homogeneous monolayer on top of the indium tin oxide (ITO) electrode facilitate the perovskite crystalline film growth with high quality and preferred orientations. After detailed spectroscopy and device characterizations, it is found that the carboxylic acid anchoring groups can down‐shift the work function and passivate the ITO surface, retarding the interface carrier recombination. As a result, the device made with the self‐assembled HTM show high open‐circuit voltage over 1.10 V and extend the lifetime over 4,300 h when storing at 30% relative humidity. Moreover, the cell works efficiently under much reduced light power, making it useful as power source under dim‐light conditions. The demonstration suggests a new facile way of fabricating monolayer HTM for high efficiency perovskite devices, as well as the interconnecting layer needed for tandem cell.
Self‐assembled P3HT‐COOH is an excellent hole extraction layer to fabricate robust, high‐performance, and extremely reproducible perovskite solar cells. The well‐aligned self‐assembled P3HT‐COOH generates a dipole layer between indium tin oxide and perovskite, substantially retarding interface charge recombination and producing highly sensitive devices to dim light. The enhanced crystallinity and preferred out‐of‐plane orientation play a key role to suppress the device degradation process.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The TAR DNA-binding protein of 43kDa (TDP-43) has been identified as the main component of amyotrophic lateral sclerosis (ALS) cytoplasmic inclusions. The link between this proteinopathy and TDP-43′s ...intrinsically disordered C-terminal domain is well known, but recently also, this domain has been shown to be involved in the formation of the membraneless organelles that mediate TDP-43′s functions. The mechanisms that underpin the liquid-liquid phase separation (LLPS) of these membraneless organelles undergo remain elusive. Crucially though, these factors may be the key to understanding the delicate balance between TDP-43′s physiological and pathological functions. In this study, we used nuclear magnetic resonance spectroscopy and optical methods to demonstrate that an α-helical component in the centre (residues 320–340) of the C-terminal domain is related to the protein's self-association and LLPS. Systematically analysing ALS-related TDP-43 mutants (G298S, M337V, and Q331K) in different buffer conditions at different temperatures, we prove that this phase separation is driven by hydrophobic interactions but is inhibited by electrostatic repulsion. Based on these findings, we rationally introduced a mutant, W334G, and demonstrate that this mutant disrupts LLPS without disturbing this α-helical propensity. This tryptophan may serve as a key residue in this protein's LLPS.
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•Liquid-liquid phase separation (LLPS) of TDP-43C-terminal domain is characterized.•LLPS of this protein is induced at a low temperature without salt or RNA.•Hydrophobicity is the main force driving the formation of LLPS.•Tryptophan-334 is a key residue for LLPS.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
Summary
The increased expression of programmed death‐ligands 1 and 2 (PD‐L1 and PD‐L2, respectively) on tumour cells contributes to immune evasion, suggesting that these proteins are attractive ...therapeutic targets. This study aimed to evaluate the validity of cerebrospinal fluid (CSF) soluble PD‐L1 (sPD‐L1) and soluble PD‐L2 (sPD‐L2) as biomarkers for primary central nervous system lymphoma (PCNSL). We determined the CSF concentrations of sPD‐L1 and sPD‐L2 in 46 patients with PCNSL using enzyme‐linked immunosorbent assays (ELISAs). A control group comprised 153 patients with other brain tumours, inflammatory/infectious status, or neurodegenerative diseases. Only CSF sPD‐L1 levels were significantly higher in patients with PCNSL relative to the controls. CSF sPD‐L1 also exhibited superior overall discrimination performance compared to CSF sPD‐L2 in diagnosing PCNSL. Compared with patients with PCNSL with low CSF sPD‐L1 levels, more patients with high levels had high serum lactate dehydrogenase levels, leptomeningeal involvement, and deep‐brain involvement. Furthermore, CSF sPD‐L1 could predict poor survival in PCNSL but CSF sPD‐L2 could not. Intriguingly, CSF sPD‐L1 levels were correlated with disease status and their dynamic changes post treatment could predict time to relapse. In conclusion, this study identified CSF sPD‐L1 as a promising prognostic biomarker, indicating a therapeutic potential of PD‐L1 blockade in PCNSL.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
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