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Background: Methyltransferase-like 3 (METTL3), a component of the N6-methyladenosine (m6A) methyltransferase family, exhibits significant expression in HEI-OC1 cells and cochlear explants. Aminoglycoside antibiotics, known for their ototoxic potential, frequently induce irreversible auditory damage in hair cells, predominantly through oxidative stress mechanisms. However, the specific role of METTL3 in kanamycin-induced hair cell loss remains unclear. Objective: This study aims to elucidate the mechanisms by which METTL3 contributes to kanamycin-induced ototoxicity. Methods and Results: In vivo experiments demonstrated a notable reduction in METTL3 expression within cochlear explants following kanamycin administration, concomitant with the formation of stress granules (SGs). Similarly, a 24-hour kanamycin treatment led to decreased METTL3 expression and induced SG formation both in HEI-OC1 cells and neonatal cochlear explants, corroborating the in vivo observations. Lentivirus-mediated transfection was employed to overexpress and knockdown METTL3 in HEI-OC1 cells. Knockdown of METTL3 resulted in increased reactive oxygen species (ROS) levels and apoptosis induced by kanamycin, while concurrently reducing SG formation. Conversely, overexpression of METTL3 attenuated ROS generation, decreased apoptosis rates, and promoted SG formation induced by kanamycin. Therefore, METTL3-mediated SG formation presents a promising target for mitigating kanamycin-induced ROS generation and the rate of apoptosis. Conclusion: This finding indicates that METTL3-mediated SG formation holds potential in mitigating kanamycin-induced impairments in cochlear hair cells by reducing ROS formation and apoptosis rates.
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Achieving large-area organic photovoltaic (OPV) modules with reasonable cost and performance is an important step toward commercialization. In this work, solution-processed conventional and inverted OPV modules with an area of 216 cm2 were fabricated by the blade coating method. Film uniformity was controlled by adjusting the fabrication parameters of the blade coating procedure. The influence of the concentration of the solutions of the interfacial materials on OPV module performance was investigated. For OPV modules based on the PM6:Y6 photoactive layer, a certificated power conversion efficiency (PCE) of 9.10% was achieved for the conventional OPV modules based on the TASiW-12 interfacial layer while a certificated PCE of 11.27% was achieved for the inverted OPV modules based on the polyethylenimine (PEI) interfacial layer. As for OPV modules based on a commercially available photoactive layer, PV-X Plus, a PCE of 8.52% was achieved in the inverted OPV modules. A halogen-free solvent, o-xylene, was used as the solvent for PV-X Plus, which makes the industrial production much more environmentally friendly.
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To answer the question of whether the same brain circuit(s) facilitates motor imagery (MI), motor execution (ME), and movement observation (MO), we conducted electroencephalography (EEG) experiment combining the three motor conditions in the same experimental runs. The EEG data were analyzed using two different independent component analysis (ICA) decomposition approaches: a single ICA decomposition on all EEG data combined and separate ICA decomposition on the EEG data obtained from the separate conditions. The results indicated that the separate ICA approach may provide a better fit to the EEG data obtained from the separate conditions to deliver specific independent right mu components with distinct topographies for each of the motor conditions. The topography of the MI condition covered the brain regions posterior to the central sulcus (P4 EEG channel); the ME condition covered the brain regions anterior to the central sulcus (C4 EEG channel), and the MO condition had broader coverage with the main activation in the premotor region (CP4 EEG channel). The source localization results also exhibited significant differences among the motor conditions. In addition, the result of single ICA decomposition resembled the result of separate ICA decomposition on the EEG data of ME with similar topographies and closely located EEG sources. This finding may further indicate that the result of single ICA decomposition may be dominated by the ME motor condition because it manifests higher data variance than the other two motor conditions.
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Encéfalo , Electroencefalografía , Encéfalo/fisiología , Mapeo Encefálico/métodos , Electroencefalografía/métodos , Imágenes en Psicoterapia , Imaginación , MovimientoRESUMEN
Motor imagery (MI) has been widely used to operate brain-computer interface (BCI) systems for rehabilitation and some life assistive devices. However, the current performance of an MI-based BCI cannot fully meet the needs of its in-field applications. Most of the BCIs utilizing a generalized feature for all participants have been found to greatly hamper the efficacy of the BCI system. Hence, some attempts have made on the exploration of subject-dependent parameters, but it remains challenging to enhance BCI performance as expected. To this end, in this study, we used the independent component analysis (ICA), which has been proved capable of isolating the pure motor-related component from non-motor-related brain processes and artifacts and extracting the common motor-related component across MI, motor execution (ME), and motor observation (MO) conditions. Then, a sliding window approach was used to detect significant mu-suppression from the baseline using the electroencephalographic (EEG) alpha power time course and, thus, the success rate of the mu-suppression detection could be assessed on a single-trial basis. By comparing the success rates using different parameters, we further quantified the extent of the improvement in each motor condition to evaluate the effectiveness of both generalized and individualized parameters. The results showed that in ME condition, the success rate under individualized latency and that under generalized latency was 90.0% and 77.75%, respectively; in MI condition, the success rate was 74.14% for individual latency and 58.47% for generalized latency, and in MO condition, the success rate was 67.89% and 61.26% for individual and generalized latency, respectively. As can be seen, the success rate in each motor condition was significantly improved by utilizing an individualized latency compared to that using the generalized latency. Moreover, the comparison of the individualized window latencies for the mu-suppression detection across different runs of the same participant as well as across different participants showed that the window latency was significantly more consistent in the intra-subject than in the inter-subject settings. As a result, we proposed that individualizing the latency for detecting the mu-suppression feature for each participant might be a promising attempt to improve the MI-based BCI performance.
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OBJECTIVE: To investigate the effect of losartan on the expression of monocyte chemoattractant protein-1 (MCP1) and transforming growth factor-ß(1) (TGF-ß(1)) in the kidney of rats with unilateral urethral obstruction (UUO) and evaluate protective effect of losartan against reanal interstitial fibrosis. METHODS: Rat models of UUO were treated with losartan at the routine dose, high dose, and very high dose (50, 200, and 500 mg/kg daily, respectively), and saline was given to UUO model rats and rats with sham operation. At 7, 14, and 21 days, the tail cuff blood pressure (TCP), 24-h urine protein (Upro), serum Scr, BUN, K(+), percentage of renal damage and renal interstitial fibrosis (%INT) were measured in the rats. MCP1 protein in the renal tissues was detected using immunohistochemistry, and MCP1 and TGF-ß(1) mRNA expressions were assayed using RT-PCR. RESULTS: As the UUO prolonged, Upro, TCP, tubular damage, %INT, and MCP1 and TGF-ß(1) mRNA expressions all increased significantly (P<0.05). High and very high doses of losartan, compared with the routine dose, obviously reversed these changes. CONCLUSION: High-dose losartan can effectively control blood pressure, reduce renal damage and fibrosis, and inhibit MCP1 and TGF-ß(1) expression in rats with UUO, and at a very high dose, losartan can more effectively reduce 24-h Upro than the high-dose group. High and very high doses of losartan offer better protective effect on the kidney in rats with UUO.
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Quimiocina CCL2/metabolismo , Riñón/metabolismo , Losartán/farmacología , Factor de Crecimiento Transformador beta1/metabolismo , Obstrucción Ureteral/tratamiento farmacológico , Animales , Fibrosis/etiología , Fibrosis/prevención & control , Riñón/patología , Masculino , Ratas , Ratas Sprague-Dawley , Obstrucción Ureteral/complicacionesRESUMEN
OBJECTIVE: To study the diagnostic values of detection of glutamic acid decarboxylase antibody (GAD-Ab) for latent autoimmune diabetes in adults (LADA). METHOD: The clinical characteristics, body mass index (BMI), serum C-peptide levels, and HbAIC were compared between the 12 type 2 diabetic patients positive and 86 negative for GAD-Ab. RESULTS: The mean age, BMI, fasting and postprandial 2 h C-peptide levels in GAD-Ab-positive group were lower than those of GAD-Ab-negative group. The frequency of insulin use and prevalence of ketosis were higher in GAD-Ab-positive group than in GAD-Ab-negative group. CONCLUSIONS: The diagnosis of LADA can be established according to GAD-Ab-positivity, clinical characteristics and islet function. Patients with LADA should receive insulin therapy as early as possible to protect the residue islet B cells, reduce the occurrence of ketosis, and prevent diabetic complications of the eye, kidney and nerves.