AAV-mediated Gene Therapy for Hereditary Deafness: Progress and Perspectives.

Hereditary deafness is the most prevalent sensory deficit disorder, with over 100 identified deafness-related genes. Clinical treatment options are currently limited to external devices like hearing aids and cochlear implants. Gene therapy has shown promising results in various genetic disorders and has emerged as a potential treatment for hereditary deafness.

AAV-mediated Gene Cocktails Enhance Supporting Cell Reprogramming and Hair Cell Regeneration.

Mammalian cochlear hair cells (HCs) are essential for hearing, and damage to HCs results in severe hearing impairment. Damaged HCs can be regenerated by neighboring supporting cells (SCs), thus the functional regeneration of HCs is the main goal for the restoration of auditory function in vivo. Here, cochlear SC trans-differentiation into outer and inner HC by the induced expression of the key transcription factors Atoh1 and its co-regulators Gfi1, Pou4f3, and Six1 (GPAS), which are necessary for SCs that are destined for HC development and maturation via the AAV-ie targeting the inner ear stem cells are successfully achieved.

Eggshell membrane powder reinforces adhesive polysaccharide hydrogels for wound repair.

Multifunctional polysaccharide hydrogels with strong tissue adhesion, and antimicrobial and hemostatic properties are attractive wound healing materials. In this study, a chitosan-based hydrogel (HCS) was designed, and its properties were enhanced by incorporating oxidized eggshell membrane (OEM). Hydrogel characterization and testing results showed that the hydrogel had excellent antimicrobial properties, cytocompatibility, satisfactory adhesion properties on common substrates, and wet-state adhesion capacity.

Pcolce2 overexpression promotes supporting cell reprogramming in the neonatal mouse cochlea.

Hair cell (HC) damage is a leading cause of sensorineural hearing loss, and in mammals supporting cells (SCs) are unable to divide and regenerate HCs after birth spontaneously. Procollagen C-endopeptidase enhancer 2 (Pcolce2), which encodes a glycoprotein that acts as a functional procollagen C protease enhancer, was screened as a candidate regulator of SC plasticity in our previous study. In the current study, we used adeno-associated virus (AAV)-ie (a newly developed adeno-associated virus that targets SCs) to overexpress Pcolce2 in SCs.

AAV-mediated Gpm6b expression supports hair cell reprogramming.

Irreversible damage to hair cells (HCs) in the cochlea leads to hearing loss. Cochlear supporting cells (SCs) in the murine cochlea have the potential to differentiate into HCs. Neuron membrane glycoprotein M6B (Gpm6b) as a four-transmembrane protein is a potential regulator of HC regeneration according to our previous research.

Critical role of TPRN rings in the stereocilia for hearing.

Inner ear hair cells detect sound vibration through the deflection of mechanosensory stereocilia. Cytoplasmic protein TPRN has been shown to localize at the taper region of the stereocilia, and mutations in TPRN cause hereditary hearing loss through an unknown mechanism. Here, using biochemistry and dual stimulated emission depletion microscopy imaging, we show that the TPRN, together with its binding proteins CLIC5 and PTPRQ, forms concentric rings in the taper region of stereocilia.

Dual-bioactive molecules loaded aligned core-shell microfibers for tendon tissue engineering.

Development of a controlled delivery ultrafine fibrous system with two bioactive molecules is required to stimulate tendon healing in different phase. In this study, we used emulsion stable jet electrospinning to fabricate aligned poly(L-lactic acid) (PLLA) based ultrafine fibers with two small bioactive molecules of L-Arginine (Arg) and low molecular weight hyaluronic acid (HA). The results demonstrated that the aligned Arg/HA/PLLA microfibrous scaffold showed core-shell structure and allowed sequential release of Arg and HA due to their different electric charge.

Rps14 upregulation promotes inner ear progenitor proliferation and hair cell regeneration in the neonatal mouse cochlea.

Sensorineural hearing loss a result from hair cell damage, which is irreversible in mammals owing to the lack of hair cell regeneration, but recent researches have shown that Lgr5 supporting cells are progenitors capable of regenerating hair cells. RPS14 (ribosomal protein S14) is a 40S ribosomal subunit component and is associated with erythrocyte differentiation, and in this study, we used a novel adeno-associated virus-inner ear system to upregulate Rps14 expression in cultured hair cell progenitors and observed an enhancement on their ability to proliferate and differentiate into hair cells. Similarly, Rps14 overexpression in the mice cochlea could promote supporting cells proliferation by activating the Wnt signalling pathway.

AAV-Net1 facilitates the trans-differentiation of supporting cells into hair cells in the murine cochlea.

Mechanosensitive hair cells (HCs) in the cochlear sensory epithelium are critical for sound detection and transduction. Mammalian HCs in the cochlea undergo cytogenesis during embryonic development, and irreversible damage to hair cells postnatally is a major cause of deafness. During the development of the organ of Corti, HCs and supporting cells (SCs) originate from the same precursors.

Hierarchical Network Enabled Flexible Textile Pressure Sensor with Ultrabroad Response Range and High-Temperature Resistance.

Thin, lightweight, and flexible textile pressure sensors with the ability to detect the full range of faint pressure (<100 Pa), low pressure (≈KPa) and high pressure (≈MPa) are in significant demand to meet the requirements for applications in daily activities and more meaningfully in some harsh environments, such as high temperature and high pressure. However, it is still a significant challenge to fulfill these requirements simultaneously in a single pressure sensor. Herein, a high-performance pressure sensor enabled by polyimide fiber fabric with functionalized carbon-nanotube (PI/FCNT) is obtained via a facile electrophoretic deposition (EPD) approach.

Isolation and characterization of antioxidative monoterpenes from Cynanchum atratum roots.

One novel monoterpene rhamnoside (1) and 7 known monoterpenes (2-8) were isolated from the ethanol extract of Cynanchum atratum for the first time. Their structures were identified by comprehensive spectroscopic data analysis such as nuclear magnetic resonance, high-resolution electrospray ionization mass spectra, optical rotatory dispersion, and acid hydrolysis. In the subsequent antioxidant assay, compound 8 exhibited obvious 2,2-diphenyl-2-picrylhydrazyl hydrate radical scavenging activity.

Two new iridoid glycosides from Gardeniae Fructus.

Two new iridoid glycosides, genipin 1,10-di-O-α-l-rhamnoside (1) and genipin 1,10-di-O-β-d-xylopyranoside (2), along with thirteen known compounds (3-15) were isolated from Gardeniae Fructus. Their structures were elucidated by physical data analyses such as NMR, UV, IR, HR-ESI-MS, as well as chemical hydrolysis. All compounds were tested for their tyrosinase inhibitory and antioxidant activities.

High-performance x-ray source based on graphene oxide-coated CuS nanowires grown on copper film.

Full static x-ray computed tomography (CT) technology has enabled higher precision and resolution imaging and has been applied in many applications such as diagnostic medical imaging, industrial inspection and security screening. In this technique, the x-ray source section is mainly composed of a thermionic cathode and electron beam scanning system. However, they have several shortcomings such as limited scanning angle, long response time and large volume.

Highly Sensitive and Wide Linear-Response Pressure Sensors Featuring Zero Standby Power Consumption under Bending Conditions.

The ability of a flexible pressure sensor to possess zero power consumption in standby mode, high sensitivity, and wide linear-response range is critical in real flexible matrix-based scenes. However, when the conventional flexible pressure sensors are attached on a curved surface, a pseudosignal response is generated because of the normal stress, resulting in a short linear-response range. Here, a flexible piezoresistive pressure sensor with high performance, zero standby power consumption is demonstrated.