The Effect of Endolymphatic Hydrops and Mannitol Dehydration Treatment on Guinea Pigs.

Background: Endolymphatic hydrops (EH) is considered as the pathological correlate of Menière's disease (MD) and cause of hearing loss. The mechanism of EH, remaining unrevealed, poses challenges for formalized clinical trials. Objective: This study aims to investigate the development of hearing loss, as well as the effect of dehydration treatment on EH animal models. Methods: In this study, different severity EH animal models were created. The laser Doppler vibrometer (LDV) and auditory brainstem responses (ABR) were used to study the effects of EH and the dehydration effects of mannitol. The LDV was used to measure the vibration of the round window membrane (RWM) reflecting the changes in inner ear impedance. ABR was used to evaluate the hearing changes. Furthermore, tissue section and scanning electron microscopy (SEM) observations were used to analyze the anatomical change to the cochlea and outer hair cells. Results: The RWM vibrations decreased with the severity of EH, indicating an increase in the cochlear impedance. The dehydration therapy lowered the impedance to restore acoustic transduction in EH 10- and 20-day animal models. Simultaneously, the ABR thresholds increased in EH models and were restored after dehydration. Moreover, a difference in the hearing was found between ABR and LDV results in severe EH animal models, and the dehydration therapy was less effective, indicating a sensorineural hearing loss (SNHL). Conclusion: Endolymphatic hydrops causes hearing loss by increasing the cochlear impedance in all tested groups, and mannitol dehydration is an effective therapy to restore hearing. However, SNHL occurs for the EH 30-day animal models, limiting the effectiveness of dehydration. Our results suggest the use of dehydrating agents in the early stage of EH.

Overexpression of Tripartite Motif-Containing 48 (TRIM48) Inhibits Growth of Human Glioblastoma Cells by Suppressing Extracellular Signal Regulated Kinase 1/2 (ERK1/2) Pathway.

BACKGROUND Herein, we found that tripartite motif-containing 48 (TRIM48) was reduced in human glioblastoma (GBM) cell lines. We investigated whether and how TRIM48 functions in human GBM in vitro. MATERIAL AND METHODS Human GBM cells (U87 MG and U138 MG) were infected with lentivirus to overexpress TRIM48, and 1 human GBM cell line (T98G) was infected with siRNAs to knock down TRIM48 expression. Techniques used included cell proliferation assay, measured by CCK-8 and BrdU-ELISA method, and cell cycle assay, determined using flow cytometry. Curcumin, a specific activator of extracellular signal regulated kinases (ERK1/2), or PD98059, a specific inhibitor of ERK1/2, was used to activate or block the ERK1/2 pathway, respectively. Expression of phosphorylated (p)-ERK1/2, and its downstream targets (Cyclin D1) were measured to assess the mechanism. RESULTS Our data suggest that overexpression of TRIM48 reduces the viability of U87 MG and U138 MG and leads to cell cycle arrest (in G0-G1 phase), which is associated with blockade of the ERK1/2 pathway and reduction of Cyclin D1. In contrast, knockdown of TRIM48 resulted in the opposite effects. Interestingly, the inhibitory effect of TRIM48 overexpression on human GBM cell growth and the inactivation of ERK1/2 were significantly alleviated with additional curcumin treatment, while it the promoted the effect of siTRIM48 on human GBM cell growth, and the activation of ERK1/2 was significantly alleviated with additional PD98059 treatment. CONCLUSIONS TRIM48 suppressed the growth of human GBM cell via the prevention of ERK1/2 activation.

Regulation effects of rosemary (Rosmarinus officinalis Linn.) on hepatic lipid metabolism in OA induced NAFLD rats.

Rosmarinus officinalis Linn. is a kind of medicinal and edible homologous plant, which is popular in the Mediterranean region with a significant effect on mind tranquilization, anti-oxidation, and metabolic improvement. However, the hypolipidemic effects and mechanism of rosemary ethanol extract (RO) and their metabolites are less known. In this study, the hypolipidemic effects of RO and its active compounds were clarified. The results showed that RO, rosmarinic acid (RA) and carnosic acid (CA) significantly reduced the contents of liver triglyceride (TG), total cholesterol (TC), free fatty acids (FFA) and improved cell hypertrophy, vacuolation, and cell necrosis in the liver of orotic acid induced non-alcoholic fatty liver disease (NAFLD) model rats. The mechanism and related pathways of RO and its main metabolites against lipid disorder were related to the up-regulation of the phosphorylation of adenosine 5'-monophosphate(AMP)-activated protein kinase (AMPK) and the inhibition of the sterol regulatory element binding protein-1c (SREBP-1c) cracking into the nucleus, following the down-regulation of fatty acid synthesis. In conclusion, our study demonstrates that RA and CA are active substances of RO, and provides scientific evidence to support functional food product development for improving NAFLD.

Near-Infrared Electron Acceptors with Fluorinated Regioisomeric Backbone for Highly Efficient Polymer Solar Cells.

Solar photon-to-electron conversion with polymer solar cells (PSCs) has experienced rapid development in the recent few years. Even so, the exploration of molecules and devices in efficiently converting near-infrared (NIR) photons into electrons remains critical, yet challenging. Herein presented is a family of near-infrared nonfullerene acceptors (NIR NFAs, T1-T4) with fluorinated regioisomeric A-Aπ-D-Aπ-A backbones for constructing efficient single-junction and tandem PSCs with photon response up to 1000 nm. It is found that the tuning of the regioisomeric bridge (Aπ) and fluoro (F)-substituents on a molecular skeleton strongly influences the backbone conformation and conjugation, leading to the optimized optoelectronic and stable stacking of resultant NFAs, which eventually impacts the performance of derived PSCs. In PSCs, the proximal NFAs with varied F-atoms (T1-T3) mostly outperform than that of distal NFA (T4). Notably, single-junction PSC with PTB7-Th:T2 blend can reach 10.87% power conversion efficiency (PCE), after implementing a solvent additive to improve blend morphology. Moreover, efficient tandem PSCs are fabricated through integrating such NIR cells with mediate bandgap nonfullerene-based subcells, to achieve a PCE of 14.64%. The results reveal the structural design of organic semiconductor and device with improved photovoltaic performance.

A Low-Temperature, Solution-Processable Organic Electron-Transporting Layer Based on Planar Coronene for High-performance Conventional Perovskite Solar Cells.

A low-temperature, solution-processable organic electron-transporting material (ETM) is successfully developed for efficient conventional n-i-p perovskite solar cells (PVSCs). This ETM can show a high efficiency over 17% on rigid device and 14.2% on flexible PVSC. To the best of our knowledge, this efficiency is among the highest values reported for flexible n-i-p PVSCs with negligible hysteresis thus far.

Pyrene and diketopyrrolopyrrole-based oligomers synthesized via direct arylation for OSC applications.

In this report, an atom efficient and facile synthetic strategy for accessing multi-diketopyrrolopyrrole (DPP)-based oligomers used in solution-processed organic field effect transistors (OFETs) and organic solar cells (OSCs) has been developed. The DPP units were successfully installed onto benzene and pyrene cores via palladium-catalyzed dehydrohalogenative coupling of mono-capped DPPs with multi-bromo-benzene or -pyrene (direct arylation), affording four oligomer small molecules (SMs 1-4) containing bis-, tri-, tri-, and tetra-DPP, respectively, in high yields of 78-96%. All the designed linear or branched DPP-based oligomers exhibit broad light absorptions, narrow band-gaps (1.60-1.73 eV), deep highest occupied molecular orbital (HOMO) levels (-5.26∼-5.18 eV), and good thermal stability (Td=390-401 °C). OFETs based on SMs 1-4 showed hole mobilities of 0.0033, 0.0056, 0.0005, and 0.0026 cm2 V(-1) s(-1), respectively. OSCs based on SMs 1-4 under one sun achieved power conversion efficiencies of 3.00%, 3.71%, 2.47%, and 1.86% accordingly, along with high open-circuit voltages of 0.86-0.94 V. For OSC devices of SM 1, SM 3, and SM 4, the solvent CHCl3 was solely employed to the formation of active layers; neither high boiling point additives nor annealing post-treatment was needed. Such a simple process benefits the large-scale production of OSCs via roll to roll technology.

A direct arylation-derived DPP-based small molecule for solution-processed organic solar cells.

A diketo-pyrrolo-pyrrole (DPP) oligomer containing three DPP cores (Ph4Th4(DPP)3) was synthesized via direct arylation of C-H bonds (DACH). Ph4Th4(DPP)3 has good solubility in many organic solvents, and shows a broad absorption band from the visible to near-infrared region as well as a field-effect hole mobility as high as 0.006 cm(2) V(-1) s(-1). Solution-processed bulk heterojunction organic solar cells based on blends of Ph4Th4(DPP)3 as electron donor and fullerene derivative as electron acceptor were fabricated. An optimized power conversion efficiency of 3.76% with a high open-circuit voltage of 0.85 V was achieved after finely tuning the morphology by changing the blend ratio and by adding additives. These results indicate that DACH is an effective way to produce π-conjugated oligomers for organic solar cells.