Physical effort modulates perceptual awareness judgment independent of level of processing.

Recent studies have emphasized the association between action and perceptual awareness, suggesting that action-related information can contribute to perceptual awareness. Given that the Level of Processing (LoP) hypothesis proposes that the emergence of awareness depends on the level of stimulus processing, the current study examines whether action impacts perceptual awareness across different processing levels. In Experiment 1, participants identified target stimuli's color (low-level task) or category (high-level task) via mouse clicks, followed by visual awareness ratings. Experiment 2 replicated the tasks using hand-grip dynamometers. Results from Experiment 1 support the LoP theory, showing a more gradual emergence of awareness for low-level features and a more dichotomous emergence for high-level features. In Experiment 2, higher reported visual awareness ratings were observed at greater physical effort, regardless of task type. These results suggest that action-related information influences reported awareness of stimuli in the same way at low- and high-level stimulus processing.

A novel and highly efficient AAV6 mutant.

Adeno-associated virus has been gaining prominence in its use as a highly secure virus gene vector with low immunogenicity in the field of human gene therapy. However, wild-type adeno-associated virus sometimes has low transduction efficiency for certain tissues or cells both in vivo and in vitro. Thus, achieving the desired level of expression often requires a large dose. Large doses of viral injection in clinical applications will not only trigger the body's immune response but will come at a high production cost. To improve the transduction efficiency of adeno-associated virus 6 (AAV6), we herein used fusion PCR to mutate a specific amino acid of the VP2 region of the wild-type AAV6 (AAV6-WT) and obtained AAV6-S663L, AAV6Y705 + 731F + T492A, AAV6Y705 + 731F + T492 V + S663 V and so on. We concluded that AAV6-S663L was the most efficient AAV6 mutant. When HEK293 cells were infected in vitro with a virus at a multiplicity of infection value of 1000, the transduction rate of AAV6-WT was only 43.8%, while that of AAV6-S663L was 83.9%. This highly efficient AAV6 mutant is highly significant for the future use of AAV6 in gene therapy.

Microstructured CNTs/Cellulose Aerogel for a Highly Sensitive Pressure Sensor.

Flexible sensors have been applied in human health monitoring and biomedical research, but producing high-performance piezoresistive sensors at low cost is still challenging. To address these shortcomings, we proposed a microstructured carbon nanotube (CNT)/cellulose aerogel-based pressure sensor. The sensor consists of three parts, i.e., cellulose/poly(vinyl alcohol)/CNT aerogel-based sensing layer and top and bottom thermoplastic polyurethane elastomer (TPU)/silver nanowire (Ag NW) nanofiber electrode. The aerogel is fabricated using a simple freeze-drying method and an easy electrospinning method to obtain the nanofiber-based electrode. Two TPU/Ag NW nanofiber electrodes sandwiched the aerogel with a microstructure in the middle. Benefiting from the microcone and micropore structures on the nanofiber electrode, the assembled sensors show a high sensitivity of 66.4 kPa-1, a significant detection boundary of 50 kPa, and an excellent response speed of 10 ms. The high sensing performance enables the sensor to monitor physiological signals, Morse code interactions, and gesture recognition. With the help of machine learning, the success rate of gesture recognition is as high as 98.8%. The preparation of this pressure sensor based on an aerogel shows excellent health and environmental monitoring potential as an artificial skin.

Hernandezine, a natural herbal alkaloid, ameliorates type 2 diabetes by activating AMPK in two mouse models.

BACKGROUND: AMP-activated protein kinase (AMPK) is an effective target for treating diabetes. However, successful drug development is delayed due to issues including toxicity. Plant-derived natural product AMPK activators have emerged as a new way to treat diabetes due to its potential low safety risks. Here, we studied the effect of hernandezine (HER), a natural product derived from Thalictrum, in activating AMPK and treating T2D in mouse models. METHOD: We tested HER in various cells and tissues, including primary hepatocytes, skeletal myotubes cell lines, as well as major metabolic tissues from diabetic (db/db) and diet-induced obesity (DIO) model mice. The effect of HER on glucose uptake via AMPK in vitro and in vivo was confirmed utilizing cell transfection and adenovirus interference analysis. Tissue staining assessed the effect of HER on adipogenesis. Real-time quantitative polymerase chain reaction (real-time PCR) was applied to verify the effect of HER on transcription factors. Western blot analysis was used to determine the activation of phosphorylated AMPK and ACC pathways. RESULTS: Biochemically, we found that HER prevented pAMPK from dephosphorylation to prolong its activity, disproving previous direct activation model and providing a new model to explain HER-mediated AMPK activation. HER could be orally delivered to animals and has a 3-fold long half-life in vivo as compared to metformin. Importantly, long-term oral HER treatment potently reduced body weight and blood glucose in both type 2 diabetes mullitus (T2DM) mouse models by increasing glucose disposal and reducing lipogenesis, and appeared not to induce cardiac hypertrophy. CONCLUSION: Natural product HER indirectly activates AMPK by suppressing its dephosphorylation. Oral HER effectively alleviated hyperglycemia and reduced body weight in T2D mouse models, appeared to have a low risk of causing cardiac hypertrophy, and might be a potential therapeutic option for T2DM.

A rAAV2/6 Mutant with Enhanced Targeting for Mouse Retinal Müller Cells.

Purpose: Adeno-associated virus vector (AAV) is the most accepted gene delivery vector for retinal gene therapy. Müller cells play an important role in maintaining homeostasis and neuronal structural integrity, stability and it has been found to be involved in many retinopathies. The aim of this study is to identify a rAAV2/6 mutant which has increased tropism for Müller cell of the mouse retina.Materials and Methods: Using amino acid mutagenesis, we created a rAAV2/6 capsid mutant, rAAV2/6-S663L. In vivo imaging and retinal flat mount were employed to analyze the gene expression of rAAV2/6-S663L and wt rAAV2/6 in mouse retinal tissue. Retinal tissue cryosection, immunohistochemistry (IHC), Müller cell-specific promoter-controlled gene expression, and double AAV fluorescent protein co-expression were performed to determine the targeting of rAAV2/6-S663L for mouse retinal Müller cells.Results: In vivo imaging, retinal flat mount and retinal tissue cryosection results showed that rAAV2/6-S663L and wt rAAV2/6 have different specific tropisms in mouse retina and rAAV2/6-S663L is more preferentially targeting Müller cells. Müller cell-specific promoter-controlled gene expression experiments and IHC test confirmed that rAAV2/6-S663L has a higher tendency to infect Müller cells than wt rAAV2/6. Co-infection of the mouse retina with one rAAV2/6-S663L expressing EGFP under the control of GFAP promoter and the other one expressing mCherry under the control of CMV promoter revealed co-expression of the two fluorescent proteins in Müller cells.Conclusions: The results confirmed that rAAV2/6-S663L has a higher tropism for Müller cells than wt rAAV2/6. Our findings could add a new useful tool for retinal disease gene therapy.