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Neutrophil gelatinase-associated lipocalin (Ngal) is a biomarker for acute and chronic renal injuries, including polycystic kidney disease (PKD). However, the effect of Ngal on PKD progression remains unexplored. To study this, we generated 3 strains of mice with different expression levels of Ngal within an established PKD model (Pkd1L3/L3): Pkd1L3/L3 (with endogenous Ngal), Pkd1L3/L3; NgalTg/Tg (with endogenous and overexpression of exogenous kidney-specific Ngal) and Pkd1L3/L3; Ngal-/- mice (with Ngal deficiency). Knockout of endogenous Ngal had no effect on phenotypes, cystic progression, or survival of the PKD mice. However, the transgenic mice had a significantly longer lifespan, smaller (but not fewer) renal cysts, and less interstitial fibrosis than the mice without or with endogenous Ngal. Western-blot analyses showed significant increases in Ngal and cleaved caspase-3 and decreases in α-smooth muscle actin, hypoxia-inducible factor 1-α, pro-caspase 3, proliferating cell nuclear antigen, Akt, mammalian target of rapamycin, and S6 Kinase in the transgenic mice as compared with the other 2 strains of PKD mice. Thus, overexpression of exogenous kidney-specific Ngal reduced cystic progression and prolonged the lifespan in PKD mice, was associated with reductions in interstitial fibrosis and proliferation, and augmented apoptosis.

In this paper, a cross-domain integration system composed of a gene transfer technique with a pre-clinical trial, an on-chip circuit design, an off-chip hardware with peripheral unit integration, and a custom software is presented. Opsin protein-gene transfer is successfully conducted to demonstrate that gene transfer treatment with optical stimulation has several benefits compared with electrical treatment. The proposed wireless programmable stimulating system on chip (WPSSoC) is composed of two sensing channels combined with a decimation filter to acquire intracranial electroencephalography (iEEG), an epilepsy detection unit (EDU), a stimulator with a waveform controller, and an ultra-low-power embedded transceiver. The equivalent sample rate of sensed data is 375 samples/s with 16-bit output data. The performance of intermodulation distortion with a third order (IMD3) is approximately 68 dB. The EDU extracts approximate entropy (ApEn) and spectrum bins for the classifier. The stimulator with controller features on the waveform-adjustable function to provide 0-510 μA of electrical stimulation and 0-50 mW of optical stimulation. The proposed transceiver is implemented with a 2.45 GHz on-off keying (OOK) carrier frequency. Transmitter and receiver front-ends perform at 50.6 and 12.7 pJ/bit of energy per bit, respectively. Power consumption and area of WPSSoC are about 1 mW and 13.67 mm2 in a 0.18 μm process, respectively. Circuits of each part are integrated in a 4.3 cm × 2 cm printed circuit board. The shrunk device is verified with Thy1-ChR2-YFP gene transfer in C57BL/6 mice by using a custom software which is used to provide commands and monitor iEEG.