PTEN alleviates maladaptive repair of renal tubular epithelial cells by restoring CHMP2A-mediated phagosome closure.

Phosphatase and Tensin Homolog on chromosome Ten (PTEN) has emerged as a key protein that governs the response to kidney injury. Notably, renal adaptive repair is important for preventing acute kidney injury (AKI) to chronic kidney disease (CKD) transition. To test the role of PTEN in renal repair after acute injury, we constructed a mouse model that overexpresses PTEN in renal proximal tubular cells (RPTC) by crossing PTENfl-stop-fl mice with Ggt1-Cre mice. Mass spectrometry-based proteomics was performed after subjecting these mice to ischemia/reperfusion (I/R). We found that PTEN was downregulated in renal tubular cells in mice and cultured HK-2 cells subjected to renal maladaptive repair induced by I/R. Renal expression of PTEN negatively correlated with NGAL and fibrotic markers. RPTC-specific PTEN overexpression relieved I/R-induced maladaptive repair, as indicated by alleviative tubular cell damage, apoptosis, and subsequent renal fibrosis. Mass spectrometry analysis revealed that differentially expressed proteins in RPTC-specific PTEN overexpression mice subjected to I/R were significantly enriched in phagosome, PI3K/Akt, and HIF-1 signaling pathway and found significant upregulation of CHMP2A, an autophagy-related protein. PTEN deficiency downregulated CHMP2A and inhibited phagosome closure and autolysosome formation, which aggravated cell injury and apoptosis after I/R. PTEN overexpression had the opposite effect. Notably, the beneficial effect of PTEN overexpression on autophagy flux and cell damage was abolished when CHMP2A was silenced. Collectively, our study suggests that PTEN relieved renal maladaptive repair in terms of cell damage, apoptosis, and renal fibrosis by upregulating CHMP2A-mediated phagosome closure, suggesting that PTEN/CHMP2A may serve as a novel therapeutic target for the AKI to CKD transition.

PTEN protects kidney against acute kidney injury by alleviating apoptosis and promoting autophagy via regulating HIF1-α and mTOR through PI3K/Akt pathway.

Phosphatase and tensin homolog (PTEN) deleted on human chromosome 10 is a tumor suppressor with bispecific phosphatase activity, which is often involved in the study of energy metabolism and tumorigenesis. PTEN is recently reported to participate in the process of acute injury. However, the mechanism of PTEN in Ischemia-Reperfusion Injury (IRI) has not yet been clearly elucidated. In this study, mice with bilateral renal artery ischemia-reperfusion and HK-2 cells with hypoxia/reoxygenation (H/R) were used as acute kidney injury models. We demonstrated that PTEN was downregulated in IRI-induced kidney as well as in H/R-induced HK-2 cells. By silencing and overexpressing PTEN with si-PTEN RNA and PHBLV-CMV-PTEN-flag lentivirus before H/R, we found that PTEN protected HK-2 cells against H/R-induced injury reflected by the change in cell activity and the release of LDH. Furthermore, we inhibited HIF1-α with PX-478 and inactivated mTOR with Rapamycin before the silence of PTEN in H/R model. Our data indicated that the renoprotective effect of PTEN worked via PI3K/Akt/mTOR pathway and PI3K/Akt/HIF1-α pathway, hence alleviating apoptosis and improving autophagy respectively. Our findings provide valuable insights into the molecular mechanism underlying renoprotection of PTEN on autophagy and apoptosis induced by renal IRI, which offers a novel therapeutic target for the treatment of AKI.

Flexible Hybrid Photo-Thermoelectric Generator Based on Single Thermoelectric Effect for Simultaneously Harvesting Thermal and Radiation Energies.

Wearable electronic devices have great potential in the fields of the Internet of Things (IoT), sports and entertainment, and healthcare, and they are essential in advancing the development of next-generation electronic information technology. However, conventional lithium batteries, which are currently the main power supply of wearable electronic devices, have some critical issues, such as frequent charging, environmental pollution, and no surface adaptability, which limit the further development of wearable electronic devices. To address these challenges, we present a flexible hybrid photothermoelectric generator (PTEG) with a simple structure composed of a thermoelectric generator (TEG) and a light-to-thermal conversion layer to simultaneously harvest thermal and radiation energies based on a single working mechanism. The mature mass-fabrication technology of screen printing was applied to successively prepare n-type (i.e., Bi2Te2.7Se0.3) and p-type (i.e., Sb2Te3) thermoelectric inks atop a polyimide substrate to form the TEG with a serpentine thermocouple chain, which was further covered by a light-to-thermal conversion layer to constitute the PTEG. The resulting PTEG with five pairs of thermocouples generated a direct-current output of 82.4 mV at a temperature difference of 50 °C and a direct-current output of 41.2 mV under 20 mW/cm2 infrared radiation. Meanwhile, the remarkable mechanical reliability and output stability were experimentally demonstrated through a systematic test, which indicated the feasibility and potential of the developed PTEG as a reliable power source. In addition, as desirable application prototypes, the fabricated PTEGs have been successfully demonstrated to harvest biothermal energy and infrared radiation to drive portable electronic devices (e.g., a calculator and a clock). Hybrid energy harvesting technology based on a simple structure may provide a new solution to current power supply issues of wearable electronic device.

Perturbation Analysis of Nonlinearity in Radio-Frequency Bulk Acoustic Wave Resonators Using the Mass-Spring Model.

This article describes derivation of an equivalent circuit for nonlinear responses in film bulk acoustic resonators from the first-order perturbation analysis using the piezoelectric constitutive equations with the h -form. For simplicity, electrodes and piezoelectric layers are considered as mass and spring, respectively, in the derivation. Then, it is demonstrated that the second- and third-order harmonic responses can be simulated well by the circuit. In addition, nonlinearity in the Si substrate is also taken into account and its impact is discussed. It is also discussed how the frequency dependences vary with the nonlinearity mechanisms as a finding from the derived equivalent circuit.

Concentric Split Aluminum with Silicon-Aluminum Nitride Annular Rings Resonators.

This paper presents a novel approach of annular concentric split rings microelectromechanical resonators with tether configuration to reduce anchor loss and gives very high-quality factor (Q) 2.97 Million based on FEA (Finite Element Analysis) simulation. The operating frequencies of these resonators are 188.55 MHz to 188.62 MHz. When the proposed SR (square rectangle) hole shaped one dimensional phononic crystal (1D PnC), and two dimensional phononic crystal (2D PnC) structure consist of very wide and complete band gaps is applied to novel design rings MEMS resonators, the quality factor (Q) further improved to 19.7 Million and 1750 Million, respectively, by using the finite element method. It is also observed that band gaps become closer by reducing the value of filling fraction, and proposed SR PnC gives extensive peak attenuation. Moreover, harmonic response of ring resonator is verified by the perfect match layers (PML) technique surrounded by resonators with varying width 1.5λ, and 3λ effectively reduce the vibration displacement.