The synapses between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) are the most vulnerable structures in the noise-exposed cochlea. Cochlear synaptopathy results from the disruption of ...these synapses following noise exposure and is considered the main cause of poor speech understanding in noisy environments, even when audiogram results are normal. Cochlear synaptopathy leads to the degeneration of SGNs if damaged IHC-SGN synapses are not promptly recovered. Oxidative stress plays a central role in the pathogenesis of cochlear synaptopathy. C-Phycocyanin (C-PC) has antioxidant and anti-inflammatory activities and is widely utilized in the food and drug industry. However, the effect of the C-PC on noise-induced cochlear damage is unknown. We first investigated the therapeutic effect of C-PC on noise-induced cochlear synaptopathy. In vitro experiments revealed that C-PC reduced the H
O
-induced generation of reactive oxygen species in HEI-OC1 auditory cells. H
O
-induced cytotoxicity in HEI-OC1 cells was reduced with C-PC treatment. After white noise exposure for 3 h at a sound pressure of 118 dB, the guinea pigs intratympanically administered 5 μg/mL C-PC exhibited greater wave I amplitudes in the auditory brainstem response, more IHC synaptic ribbons and more IHC-SGN synapses according to microscopic analysis than the saline-treated guinea pigs. Furthermore, the group treated with C-PC had less intense 4-hydroxynonenal and intercellular adhesion molecule-1 staining in the cochlea compared with the saline group. Our results suggest that C-PC improves cochlear synaptopathy by inhibiting noise-induced oxidative stress and the inflammatory response in the cochlea.
The improved split Hopkinson pressure bar (SHPB) was used to study the dynamic mechanical properties and failure characteristics of surrounding rock in deep rock mass engineering that is under high ...stress and affected by blasting excavation and other dynamic disturbances. In a three-dimensional high static load and frequent dynamic disturbance test, the preload high axial pressure and confining pressure are used to simulate the high crustal stress of deep rock, and the effect of small disturbances on the rock is simulated by the low impact load. The results show that there are two types of dynamic stress-strain curves of deep rock: an elastic-plastic curve and plastic-elastic-plastic curve. The curves consists of five parts: the compaction stage, micro-crack steady development stage, micro-crack unstable propagation stage, fatigue damage stage, and fatigue failure stage. Reductive phenomena of constringent strain after dynamic peak stress appear because of the different degrees of rock damage. Moreover, these phenomena include two conditions, namely, whether rebound occurs or not. The impact resistance of rock is strongest when the ratio of the confining pressure to axial pressure is optimal, and the dynamic average strength of rock and accumulative impact times decrease with the increase of the preloaded axial compression and increase with the increase of the preloaded confining pressure. Both the dynamic deformation modulus and dynamic peak stress decrease with the increase of the accumulative impact time, while the maximum strain and the dynamic peak strain increase. The corresponding rebound strain as a whole first increases and then decreases with the increasing impact times. For deep rock, tensile failure and single-bevel plane shear failure are the main failure modes, and pull-compression mixed friction failure is the auxiliary failure mode. Additionally, the lumpiness of broken rock decreases with the increase of the preloaded axial compression and increases with the increase of the preloaded confining pressure.
A salicylaldehyde Schiff base hybrid lead iodide perovskite SAPDPbI
3
(SAPD = 1-((2-hydroxybenzylidene)amino)pyridin-1-ium) was found to show a robust nonlinear optical response and large spontaneous ...polarization. We expect this work to inspire researchers to investigate the optical control of ferroelectricity in hybrid perovskites.
The first salicylaldehyde Schiff base organic-inorganic hybrid perovskite ferroelectric SAPDPbI
3
(SAPD = 1-((2-hydroxybenzylidene)amino)pyridin-1-ium) has been synthesized, which shows large spontaneous polarization and SHG response.
Over the past 50 years, 5-fluorouracil (5-FU) has played a critical role in the systemic chemotherapy of cancer patients. Bolus intravenous (IV) 5-FU infusion has been used due to the limitation of ...its extremely short half-life (10-15 min). This study used ultrasound (US) mediating 5-FU-loaded microbubbles (MBs) cavitation as a tool to increase local intratumoral 5-FU levels with a reduced dose of 5-FU (a single IV injection of 2.5 mg/kg instead of a single intraperitoneal injection of 25-200 mg/kg as used in previous studies in mice). The 5-FU-MBs were prepared with a 132 mg/mL albumin solution and a 0.30 mg/mL 5-FU solution. The diameters of the MBs and 5-FU-MBs were 1.24 ± 0.85 and 2.00 ± 0.53 µm (mean ± SEM), respectively, and the maximum loading efficiency of 5-FU on MBs was 19.04 ± 0.25%. In the in vitro study, the cell viabilities of 5-FU and 5-FU-MBs did not differ significantly, but compared with the 5-FU-MBs treatment-alone group, cell toxicity increased to 31% in the 5-FU-MBs + US group (p < 0.001). The biodistribution results indicated that the 5-FU levels of the tumors in small animals were significant higher for the 5-FU-MBs + US treatment than for either the 5-FU-MBs or 5-FU treatment with low 5-FU systemic treatment doses (2.5 mg/kg 5-FU IV). In small-animal treatment, 2.5 mg/kg 5-FU therapeutic IV doses injected into mice caused a more-significant reduction in tumor growth in the 5-FU-MBs + US group (65.9%) than in the control group after 34 days of treatment.
A GaN metal-insulator-semiconductor-high electron mobility transistor (HEMT) using hybrid ferroelectric charge trap gate stack (FEG-HEMT) is demonstrated for normally-OFF operation. The ferroelectric ...(FE) polarization increases the number of trapped charges in the HfON charge trapping layer, leading to high positive threshold voltage (V th ) shift for the normally-OFF device. Besides, under the positive bias temperature instability (PBTI) test, the internal electric field induced by FE polarization causes smoother slope of the conduction band in FE gate stack, resulting in better V th stability. With the proposed hybrid FE charge trap gate stack, the device exhibits a high V th of +2.71 V at I Dh = 1μA/mm, a high maximum current density of 820 mA/mm and low on-resistance (R ON ) of 11.1 Ω · mm. The FE device also shows good V th -temperature stability compared to the non-FE device results. Besides, a high current device with 40 A is also fabricated in this letter to demonstrate the feasibility of the proposed FEG-HEMT device for high power device application.
The incidence of human papillomavirus (HPV) positive oropharyngeal cancer (OPC) is rising but HPV negative OPC is decreasing in Western countries. In Taiwan, the incidence of HPV negative OPC is ...common but the incidence of HPV positive OPC remains unknown. The objective of this study is to estimate the incidence trend and the survival of HPV positive OPC in Taiwan.
Between 1999 and 2014, primary tumor tissues from 425 incident OPCs were obtained from 5 medical centers in Taiwan. 408 OPCs were evaluated by the EasyChip HPV genotyping (King-Car, I-Lan, Taiwan) and 369 OPCs by p16 staining. The clinical data were retrospectively obtained from the medical records.
In our study, 29% of OPCs were HPV positive. The percentage of HPV positive OPC was stable from 1999 to 2014 (25% (1999-2002), 30% (2003-2006), 30% (2007-2010), 29% (2011-2014)). The estimated crude incidence rate of HPV positive OPC increased significantly from 0.62 (1999-2002), 1.06 (2003-2006), 1.52 (2007-2010) to 1.74 (2011-2014) per 100,000 person-year. The sensitivity and specificity of p16 staining for positive HPV infection were 92% and 91%, respectively. The 5-year overall survival rates for patients with HPV positive OPC and with HPV negative OPC were 67.8% and 49.0%, respectively (HR = 0.52 (0.35-0.76), p = 0.0005). Patients with HPV positive OPC but no betel nut/cigarette exposure had the best overall survival (5-year: 88.2%, p < 0.0001). Patients with HPV negative OPC and betel nut/cigarette exposure had the worst overall survival (5-year: 46.6%, p < 0.0001). Patients with HPV positive OPC but also with betel nut/cigarette exposure had poorer 5-year overall survival (48.3%, p < 0.01).
The incidence of HPV positive OPC is increasing along with HPV negative OPC, which leads to stably low percentage of HPV positive OPC in Taiwan. HPV positive OPC may become an important head and neck cancer when the incidence of HPV negative OPC declines in the near future. P16 is a useful surrogate marker for HPV infection in OPC and a good prognostic indicator for treatment outcome of OPC. Patients with HPV positive OPC but no betel nut/cigarette exposure has an excellent prognosis. Betel nut/cigarette exposure significantly worsens the prognosis of HPV positive OPC.
Background
Benefited from advances in technology, virtual reality (VR) has been widely applied to learning content in operational training as well as hands‐on courses. However, most current studies ...tend to evaluate learning effectiveness in this application, and few were focused on how learners can be benefited from transferring the knowledge learned to real‐world field performance. Moreover, in application‐oriented hands‐on courses such as embedded electronic circuits, to our best knowledge, none were presented in interactive learning materials with the combination of VR and neither were the understanding of the changes in cognition, learning anxiety, and learning confidence during the learning process.
Method and Objective
We combine VR technology with hands‐on tasks to design a VR‐based embedded electronic circuit learning system. We conduct a quasi‐experiment to investigate differences in knowledge, comprehension, and application levels in different learning environments, and to assess learning performance, learning anxiety, and learning confidence levels when applying the knowledge learned to real‐world hands‐on tasks.
Results
Groups that receive VR‐mediated training exhibit superior knowledge, comprehension, and application levels. In addition, learners with higher levels of knowledge and application exhibit lower learning anxiety and higher learning confidence during practical application tasks.
Conclusions
We investigate the learning outcomes of learners on practical hands‐on tasks after VR‐mediated learning. To improve the learning experience and performance for learners in an embedded electronic circuit course, we discuss the learning performance in terms of the knowledge and concepts learned in the VR environment and transferred to the real world. The results show that learners achieve better cognitive levels in the learning process through the VR system described here. Better performance on hands‐on tasks was also obtained as well as low anxiety and high confidence levels.
Lay Description
What Is Already Known about this Topic
Multimedia learning materials are important for improving hands‐on practical ability.
Multimedia learning materials are already being used to promote learning effectiveness and outcomes.
There is a significant impact on learning anxiety and learning confidence in the cognitive process.
What this Paper Adds
Embedded electronic circuits course presented by IVR reduces learning anxiety and increases learning confidence in the hands‐on practical task.
Through IVR learning, students can construct their knowledge better and be able to perform better in hands‐on tasks.
Implications for Practice and/or Policy
We show the effectiveness of a hands‐on embedded electronic circuit course when transferring and applying knowledge to real‐world hands‐on tasks after learning in a virtual environment.
Learners exhibit better performance on practical hands‐on tasks, as well as lower anxiety and higher confidence levels.
Future work could explore adaptive factors by learners such as feedback and prompts given by learners in the VR learning environment to better understand the changes and effects in learners' cognitive processes.
What Are the 1 or 2 Major Takeaways from the Study
According to these results, the combination of IVR in hands‐on courses is an effective learning method, which can effectively improve students' knowledge, comprehension, and application ability.
We reveal the potential for hands‐on embedded courses to outperform traditional lecture courses through VR learning. Learners exhibit higher confidence and lower anxiety in the process of hands‐on practice.
Abstract Deregulated microRNAs and their roles in cancer development have attracted much attention. Although miR-133a has been shown to be important in osteogenesis, its roles in osteosarcoma ...carcinogenesis and progression remain unknown. Hence, we focused on the expression and mechanisms of miR-133a in osteosarcoma development in this study. We found that miR-133a was downregulated in osteosarcoma cell lines and primary human osteosarcoma tissues, and its decrease was significantly correlated with tumor progression and prognosis of the patients. Functional studies revealed that restoration of miR-133a could reduce cell proliferation, promote cell apoptosis, and suppress tumorigenicity in osteosarcoma cell lines. Furthermore, bioinformatic prediction and experimental validation were applied to identify target genes of miR-133a, and the results revealed that the anti-tumor effect of miR-133a was probably due to targeting and repressing of Bcl-xL and Mcl-1 expression. Taken together, our data elucidate the roles of miR-133a in osteosarcoma pathogenesis and implicate its potential in cancer therapy.
MicroRNA-208a (mir-208a) is essential for cardiac hypertrophy and fibrosis. Endoglin, a co-receptor of transforming growth factor-β is also essential for cardiac fibrosis. Endoglin has been shown to ...be a target of mir-208a in the in vitro mechanical stress model. Volume overload can lead to heart failure and cardiac fibrosis. The role of mir-208a and endoglin in volume overload heart failure is well known. We sought to investigate the mechanism of regulation of mir-208a and endoglin in volume overload-induced heart failure. Aorta-caval (AV) shunt was performed in adult Sprague-Dawley rats to induce volume overload. Heart weight and heart weight/body weight ratio significantly increased in AV shunt animals. AV shunt significantly increased left ventricular end-diastolic dimension as compared to sham group. Mir-208a was significantly induced by AV shunt from 3 to 14 days. Endoglin, myosin heavy chain-β and brain natriuretic peptide were significantly induced by AV shunt from 3 to 14 days. Overexpression of mir-208a in the sham group without AV shunt significantly increased endoglin expression similar to the AV shunt group. Antagomir-208a attenuated the endoglin expression induced by AV shunt. Pretreatment with atorvastatin also attenuated the endoglin expression induced by AV shunt. AV shunt significantly increased myocardial fibrosis as compared to sham group. Overexpression of mir-208a in the sham group significantly increased myocardial fibrosis. Antagomir-208a and atorvastatin significantly attenuated the myocardial fibrosis induced by AV shunt. In conclusion, mir-208a increased endoglin expression to induce myocardial fibrosis in volume overloaded heart failure. Treatment with atorvastatin can attenuate the myocardial fibrosis induced by volume overload through inhibition of endoglin expression.
As a natural sesquiterpene compound with numerous biological activities, patchoulol has extensive applications in the cosmetic industry and potential usage in pharmaceuticals. Although several ...patchoulol-producing microbial strains have been constructed, the low productivity still hampers large-scale fermentation. Escherichia coli possesses the ease of genetic manipulation and simple nutritional requirements and does not comprise competing pathways for the farnesyl diphosphate (FPP) precursor, showing its potential for patchoulol biosynthesis. Here, combinatorial strategies were applied to produce patchoulol in E. coli. The initial strain was constructed, and it produced 14 mg/L patchoulol after fermentation optimization. Patchoulol synthase (PTS) was engineered by semirational design, resulting in improved substrate binding affinity and a patchoulol titer of 40.3 mg/L; the patchoulol titer reached 66.2 mg/L after fusing of PTS with FPP synthase. To further improve the patchoulol production, the genome of an efficient chassis strain was engineered by deleting the competitive routes for acetate, lactate, ethanol, and succinate synthesis and cumulatively enhancing the expression of efflux transporters, which improved patchoulol production to 338.6 mg/L. When tested in a bioreactor, the patchoulol titer and productivity were further improved to 970.1 mg/L and 199 mg/L/d, respectively, and were among the highest levels reported using mineral salt medium.
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