Modeling Sialidosis with Neural Precursor Cells Derived from Patient-Derived Induced Pluripotent Stem Cells

Sialidosis, caused by a genetic deficiency of the lysosomal sialidase gene (NEU1), is a systemic disease involving various tissues and organs, including the nervous system. Understanding the neurological dysfunction and pathology associated with sialidosis remains a challenge, partially due to the lack of a human model system. In this study, we have generated two types of induced pluripotent stem cells (iPSCs) with sialidosis-specific NEU1^G227R and NEU1^V275A/R347Q mutations (sialidosis-iPSCs), and further differentiated them into neural precursor cells (iNPCs). Characterization of NEU1^G227R- and NEU1^V275A/R347Q- mutated iNPCs derived from sialidosis-iPSCs (sialidosis-iNPCs) validated that sialidosis-iNPCs faithfully recapitulate key disease-specific phenotypes, including reduced NEU1 activity and impaired lysosomal and autophagic function. In particular, these cells showed defective differentiation into oligodendrocytes and astrocytes, while their neuronal differentiation was not notably affected. Importantly, we found that the phenotypic defects of sialidosis-iNPCs, such as impaired differentiation capacity, could be effectively rescued by the induction of autophagy with rapamycin. Our results demonstrate the first use of a sialidosis-iNPC model with NEU1^G227R- and NEU1^V275A/R347Q- mutation(s) to study the neurological defects of sialidosis, particularly those related to a defective autophagy–lysosome pathway, and may help accelerate the development of new drugs and therapeutics to combat sialidosis and other LSDs.     

Environmental Enrichment Enhances Cav 2.1 Channel-Mediated Presynaptic Plasticity in Hypoxic–Ischemic Encephalopathy

Hypoxic–ischemic encephalopathy (HIE) is a devastating neonatal brain condition caused by lack of oxygen and limited blood flow. Environmental enrichment (EE) is a classic paradigm with a complex stimulation of physical, cognitive, and social components. EE can exert neuroplasticity and neuroprotective effects in immature brains. However, the exact mechanism of EE on the chronic condition of HIE remains unclear. HIE was induced by a permanent ligation of the right carotid artery, followed by an 8% O₂ hypoxic condition for 1 h. At 6 weeks of age, HIE mice were randomly assigned to either standard cages or EE cages. In the behavioral assessments, EE mice showed significantly improved motor performances in rotarod tests, ladder walking tests, and hanging wire tests, compared with HIE control mice. EE mice also significantly enhanced cognitive performances in Y-maze tests. Particularly, EE mice showed a significant increase in Ca_v 2.1 (P/Q type) and presynaptic proteins by molecular assessments, and a significant increase of Ca_v 2.1 in histological assessments of the cerebral cortex and hippocampus. These results indicate that EE can upregulate the expression of the Ca_v 2.1 channel and presynaptic proteins related to the synaptic vesicle cycle and neurotransmitter release, which may be responsible for motor and cognitive improvements in HIE.     

Tactile colour pictogram to improve artwork appreciation of people with visual impairments

A recent development in tactile technology enables an improvement in the appreciation of the visual arts for people with visual impairment (PVI). The tactile sense, in conjunction with, or a possibly as an alternative to, the auditory sense, would allow PVIs to approach artwork in a more self‐driven and engaging way that would be difficult to achieve with just an auditory stimulus. Tactile colour pictograms (TCPs), which are raised geometric patterns, are ideographic characters that are designed to enable PVIs to identify colours and interpret information by touch. In this article, three TCPs are introduced to code colours in the Munsell colour system. Each colour pattern consists of a basic cell size of 10 mm × 10 mm to represent the patterns consistently in terms of regular shape. Each TCP consists of basic geometric patterns that are combined to create primary, secondary, and tertiary colour pictograms of shapes indicating colour hue, intensity and lightness. Each TCP represents 29 colours including six hues; they were then further expanded to represent 53 colours. Two of them did not increase the cell size, the other increased the cell size 1.5 times for some colours, such as yellow‐orange, yellow, blue, and blue‐purple. Our proposed TCPs use a slightly larger cell size compared to most tactile patterns currently used to indicate colour, but code for more colours. With user experience and identification tests, conducted with 23 visually impaired adults, the effectiveness of the TCPs suggests that they were helpful for the participants.     

Progressive NO2 Sensors with Rapid Alarm and Persistent Memory-Type Responses for Wide-Range Sensing Using Antimony Triselenide Nanoflakes

Antimony triselenide (Sb₂Se₃) nanoflake-based nitrogen dioxide (NO₂) sensors exhibit a progressive bifunctional gas-sensing performance, with a rapid alarm for hazardous highly concentrated gases, and an advanced memory-type function for low-concentration (<1 ppm) monitoring repeated under potentially fatal exposure. Rectangular and cuboid shaped Sb₂Se₃ nanoflakes, comprising van der Waals planes with large surface areas and covalent bond planes with small areas, can rapidly detect a wide range of NO₂ gas concentrations from 0.1 to 100 ppm. These Sb₂Se₃ nanoflakes are found to be suitable for physisorption-based gas sensing owing to their anisotropic quasi-2D crystal structure with extremely enlarged van der Waals planes, where they are humidity-insensitive and consequently exhibit an extremely stable baseline current. The Sb₂Se₃ nanoflake sensor exhibits a room-temperature/low-voltage operation, which is noticeable owing to its low energy consumption and rapid response even under a NO₂ gas flow of only 1 ppm. As a result, the Sb₂Se₃ nanoflake sensor is suitable for the development of a rapid alarm system. Furthermore, the persistent gas-sensing conductivity of the sensor with a slow decaying current can enable the development of a progressive memory-type sensor that retains the previous signal under irregular gas injection at low concentrations.     

One-Dimensional Deep Convolutional Neural Network for Mineral Classification from Raman Spectroscopy

Neural Processing Letters - Raman spectroscopy is often used for the composition determination and rapid classification of materials because it can reflect the molecular information of materials....     

ZnO·2.7Al2O3 nanocomposite with high optical transparency

Here we report a transparent dual-phase ZnO·2.7Al₂O₃ ceramic. The composite is pore-free and consists of thin nanosheets with a spinel phase and a hexagonal phase, while the two phases match closely in both lattice and refractive index. Such features result in excellent optical transmittance (maximum value >80% in the visible spectrum) at comparable phase volume. This work may provide a new thought for the rational structural design of optical nanocomposites.     

A Lane-Level Road Marking Map Using a Monocular Camera

The essential requirement for precise localization of a self-driving car is a lane-level map which includes road markings (RMs). Obviously, we can build the lane-level map by running a mobile mapping system (MMS) which is equipped with a high-end 3D LiDAR and a number of high-cost sensors. This approach, however, is highly expensive and ineffective since a single high-end MMS must visit every place for mapping. In this paper, a lane-level RM mapping system using a monocular camera is developed. The developed system can be considered as an alternative to expensive high-end MMS. The developed RM map includes the information of road lanes (RLs) and symbolic road markings (SRMs). First, to build a lane-level RM map, the RMs are segmented at pixel level through the deep learning network. The network is named RMNet. The segmented RMs are then gathered to build a lane-level RM map. Second, the lane-level map is improved through loop-closure detection and graph optimization. To train the RMNet and build a lane-level RM map, a new dataset named SeRM set is developed. The set is a large dataset for lane-level RM mapping and it includes a total of 25157 pixel-wise annotated images and 21000 position labeled images. Finally, the proposed lane-level map building method is applied to SeRM set and its validity is demonstrated through experimentation.      

Rheological phase reaction synthesis and electrochemical performance of LiFe2/3Mn1/3PO4/C cathode for lithium-ion batteries

LiFe_2/3Mn_1/3PO₄/C composite was prepared by the rheological phase reaction using LiH₂PO₄, Li₂CO₃, FePO₄, Mn(Ac)₂·4H₂O and ascorbic acid as starting materials. The crystal structure and morphology of as-synthesized sample were characterized by X-ray diffraction (XRD) and scanning electron microscopy (SEM). The analysis of XRD results showed that the obtained sample was single-phase with orthorhombic olivine-type structure (Pnma space group). SEM micrographs revealed that the sample was aggregates, with an irregular morphology. The initial discharge capacity was 166.9, 149.1, 139.6, 112.8, 82.93 mAh g^??1 at the rate of 0.1, 0.5, 1, 2, and 10 C, respectively. And when the rate was 0.1, 0.5, 1, 2, and 10 C, the capacity retention was 92.2%, 90%, 92.9%, 97.6%, 91.5% after 50, 100, 200, 200, 500 cycles, respectively.

     

Neoagarooligosaccharide Protects against Hepatic Fibrosis via Inhibition of TGF-β/Smad Signaling Pathway

Hepatic fibrosis occurs when liver tissue becomes scarred from repetitive liver injury and inflammatory responses; it can progress to cirrhosis and eventually to hepatocellular carcinoma. Previously, we reported that neoagarooligosaccharides (NAOs), produced by the hydrolysis of agar by β-agarases, have hepatoprotective effects against acetaminophen overdose-induced acute liver injury. However, the effect of NAOs on chronic liver injury, including hepatic fibrosis, has not yet been elucidated. Therefore, we examined whether NAOs protect against fibrogenesis in vitro and in vivo. NAOs ameliorated PAI-1, α-SMA, CTGF and fibronectin protein expression and decreased mRNA levels of fibrogenic genes in TGF-β-treated LX-2 cells. Furthermore, downstream of TGF-β, the Smad signaling pathway was inhibited by NAOs in LX-2 cells. Treatment with NAOs diminished the severity of hepatic injury, as evidenced by reduction in serum alanine aminotransferase and aspartate aminotransferase levels, in carbon tetrachloride (CCl₄)-induced liver fibrosis mouse models. Moreover, NAOs markedly blocked histopathological changes and collagen accumulation, as shown by H&E and Sirius red staining, respectively. Finally, NAOs antagonized the CCl₄-induced upregulation of the protein and mRNA levels of fibrogenic genes in the liver. In conclusion, our findings suggest that NAOs may be a promising candidate for the prevention and treatment of chronic liver injury via inhibition of the TGF-β/Smad signaling pathway.