The AKT2/SIRT5/TFEB pathway as a potential therapeutic target in atrophic AMD.

Age-related macular degeneration (AMD), the leading cause of geriatric blindness, is a multi-factorial disease with retinal-pigmented epithelial (RPE) cell dysfunction as a central pathogenic driver. With RPE degeneration, lysosomal function is a core process that is disrupted. Transcription factors EB/E3 (TFEB/E3) tightly control lysosomal function; their disruption can cause aging disorders, such as AMD. Here, we show that induced pluripotent stem cells (iPSC)-derived RPE cells with the complement factor H variant [ CFH (Y402H)] have increased AKT2, which impairs TFEB/TFE3 nuclear translocation and lysosomal function. Increased AKT2 can inhibit PGC1α, which downregulates SIRT5, an AKT2 binding partner. SIRT5 and AKT2 co-regulate each other, thereby modulating TFEB-dependent lysosomal function in the RPE. Failure of the AKT2/SIRT5/TFEB pathway in the RPE induced abnormalities in the autophagy-lysosome cellular axis by upregulating secretory autophagy, thereby releasing a plethora of factors that likely contribute to drusen formation, a hallmark of AMD. Finally, overexpressing AKT2 in RPE cells in mice led to an AMD-like phenotype. Thus, targeting the AKT2/SIRT5/TFEB pathway could be a potential therapy for atrophic AMD.

Stable and Reversible Photoluminescence from GaN Nanowires in Solution Tuning by Ionic Concentration.

We report response of photoluminescence (PL) from GaN nanowires without protection in solutions. The distinct response is not only toward pH but toward ionic concentration under same pH. The nanowires appear to be highly stable under aqueous solution with high ionic concentration and low pH value down to 1. We show that the PL has a reversible interaction with various types of acidic and salt solutions. The quantum states of nanowires are exposed to the external environment and have a direct physical interaction which depends on the anions of the acids. As the ionic concentration increases, the PL intensity goes up or down depending on the chemical species. The response results from a competition of change in surface band bending and charge transfer to redox level in solution. That of GaN films is reported for comparison as the effect of surface band bending can be neglected so that there are only slight variations in PL intensity for GaN films. Additionally, such physical interaction does not impact on the PL peaks in acids and salts, whereas there is a red shift on PL when the nanowires are in basic solution, say NH4OH, due to chemical etching occurred on the nanowires.

Rapid SARS-CoV-2 Detection by Carbon Nanotube-Based Near-Infrared Nanosensors

To effectively track and eliminate COVID-19, it is critical to develop tools for rapid and accessible diagnosis of actively infected individuals. Here, we introduce a single-walled carbon nanotube (SWCNT)-based optical sensing approach towards these ends. We construct a nanosensor based on SWCNTs noncovalently functionalized with ACE2, a host protein with high binding affinity for the SARS-CoV-2 spike protein. Presence of the SARS-CoV-2 spike protein elicits a robust, two-fold nanosensor fluorescence increase within 90 min of spike protein exposure. We characterize the nanosensor stability and sensing mechanism, and passivate the nanosensor to preserve sensing response in saliva and viral transport medium. We further demonstrate that these ACE2-SWCNT nanosensors retain sensing capacity in a surface-immobilized format, exhibiting a 73% fluorescence turn-on response within 5 s of exposure to 35 mg/L SARS-CoV-2 virus-like particles. Our data demonstrate that ACE2-SWCNT nanosensors can be developed into an optical tool for rapid SARS-CoV-2 detection. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=86 SRC="FIGDIR/small/20223404v1_ufig1.gif" ALT="Figure 1"> View larger version (21K): org.highwire.dtl.DTLVardef@b78f2dorg.highwire.dtl.DTLVardef@118fdc8org.highwire.dtl.DTLVardef@1bd5e3corg.highwire.dtl.DTLVardef@175f6a8_HPS_FORMAT_FIGEXP M_FIG C_FIG

A 0.5-V multi-channel low-noise readout front-end for portable EEG acquisition.

This article presents a low-noise readout front-end suitable for Electroencephalogram (EEG) acquisition. The chip includes 8-channel fully-differential instrumentation amplifiers, utilizing chopper stabilization technique for reducing the flicker noise, each amplifier with a small Gm-C low-pass filter, a programmable gain amplifier, and a 10-bit successive approximation register (SAR) ADC with a detect logic for DAC switching. The chip is fabricated with the TSMC 90nm CMOS process. The low-noise readout front-end has simulated frequency response from 0.57 Hz to 213 Hz, programmable gain from 54.4 dB to 87.6 dB, integrated input-referred noise of 0.358 µVrms within EEG bandwidth, a noise efficiency factor (NEF) of 2.43, and a power efficiency factor (PEF) of 2.95. The overall system consumes 32.08 µW under 0.5-V supply.