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A hybrid energy-efficient, area-efficient, low-complexity switching scheme in SAR ADC for biosensor applications is proposed. This scheme is a combination of the monotonic technique, the MSB capacitor-splitting technique, and a new switching method. The MSB capacitor-splitting technique, as well as the reference voltage Vaq allow for more options for reference voltage conversion, resulting in higher area savings and higher energy efficiency. In a capacitor array, the circuit performs unilateral switching during all comparisons except for the second and last two comparisons, reducing the difficulty in designing the drive circuit. The proposed switching scheme saves 98.4% of the switching energy and reduces the number of unit capacitors by 87.5% compared to a conventional scheme. Furthermore, the SAR ADC employs low-noise and low-power dynamic comparators utilizing multi-clock control, low-sampling error-sampling switches based on the bootstrap technique, and dynamic SAR logic. The simulation results demonstrated that the proposed SAR ADC achieves 61.51 dB SNDR, 79.21 dB SFDR and consumes 0.278 μW of power in a 180 nm process with a 1 V power supply, a full swing input signal frequency of 23.33 kHz, and a sampling rate of 100 kS/s. [ABSTRACT FROM AUTHOR]

Metastasis associated lung adenocarcinoma transcript 1( MALAT1) is a long non-coding RNA, broadly expressed in mammalian tissues including kidney and up-regulated in a variety of cancer cells. To date, its functions in podocytes are largely unknown. β-catenin is a key mediator in the canonical and non-canonical Wnt signalling pathway; its aberrant expression promotes podocyte malfunction and albuminuria, and contributes to kidney fibrosis. In this study, we found that MALAT1 levels were increased in kidney cortices from C57 BL/6 mice with streptozocin ( STZ)-induced diabetic nephropathy, and dynamically regulated in cultured mouse podocytes stimulated with high glucose, which showed a trend from rise to decline. The decline of MALAT1 levels was accompanied with β-catenin translocation to the nuclei and enhanced expression of serine/arginine splicing factor 1 ( SRSF1), a MALAT1 RNA-binding protein. Further we showed early interference with MALAT1 si RNA partially restored podocytes function and prohibited β-catenin nuclear accumulation and SRSF1 overexpression. Intriguingly, we showed that β-catenin was involved in MALAT1 transcription by binding to the promotor region of MALAT1; β-catenin knock-down also decreased MALAT1 levels, suggesting a novel feedback regulation between MALAT1 and β-catenin. Notably, β-catenin deletion had limited effects on SRSF1 expression, demonstrating β-catenin might serve as a downstream signal of SRSF1. These findings provided evidence for a pivotal role of MALAT1 in diabetic nephropathy and high glucose-induced podocyte damage. [ABSTRACT FROM AUTHOR]

Fyn, a member of the Src family of tyrosine kinases, is a key regulator in cytoskeletal remodeling in a variety of cell types. Recent studies have demonstrated that Fyn is responsible for nephrin tyrosine phosphorylation, which will result in polymerization of actin filaments and podocyte damage. Thus detailed involvement of Fyn in podocytes is to be elucidated. In this study, we investigated the potential role of Fyn/ROCK signaling and its interactions with paxillin. Our results presented that high glucose led to filamentous actin (F-actin) rearrangement in podocytes, accompanied by paxillin phosphorylation and increased cell motility, during which Fyn and ROCK were markedly activated. Gene knockdown of Fyn by siRNA showed a reversal effect on high glucose-induced podocyte damage and ROCK activation; however, inhibition of ROCK had no significant effects on Fyn phosphorylation. These observations demonstrate that in vitro Fyn mediates high glucose-induced actin cytoskeleton remodeling of podocytes via promoting ROCK activation and paxillin phosphorylation. [ABSTRACT FROM AUTHOR]