Homo-oxidized HSPB1 protects H9c2 cells against oxidative stress via activation of KEAP1/NRF2 signaling pathway

Summary: Several heat shock proteins are implicated in the endogenous cardioprotective mechanisms, but little is known about the role of heat shock protein beta-1 (HSPB1). This study aims to investigate the oxidation state and role of HSPB1 in cardiomyocytes undergoing oxidative stress and underlying mechanisms. Here, we demonstrate that hydrogen peroxide (H2O2) promotes the homo-oxidation of HSPB1. Cys137 residue of HSPB1 is not only required for it to protect cardiomyocytes against oxidative injury but also modulates its oxidation, phosphorylation at Ser15, and distribution to insoluble cell components after H2O2 treatment. Moreover, Cys137 residue is indispensable for HSPB1 to interact with KEAP1, thus regulating its oxidation and intracellular distribution, subsequently promoting the nuclear translocation of NRF2, and increasing the transcription of GLCM, HMOX1, and TXNRD1. Altogether, these findings provide evidence that Cys137 residue is indispensable for HSPB1 to maintain its redox state and antioxidant activity via activating KEAP1/NRF2 signaling cascade in cardiomyocytes

Xinmailong Attenuates Doxorubicin-Induced Lysosomal Dysfunction and Oxidative Stress in H9c2 Cells via HO-1

The clinical use of doxorubicin (DOX) is limited by its cardiotoxicity, which is closely associated with oxidative stress. Xinmailong (XML) is a bioactive peptide extracted from American cockroaches, which has been mainly applied to treat chronic heart failure in China. Our previous study showed that XML attenuates DOX-induced oxidative stress. However, the mechanism of XML in DOX-induced cardiotoxicity remains unclear. Heme oxygenase-1 (HO-1), an enzyme that is ubiquitously expressed in all cell types, has been found to take antioxidant effects in many cardiovascular diseases, and its expression is protectively upregulated under DOX treatment. Lysosome and autophagy are closely involved in oxidative stress as well. It is still unknown whether XML could attenuate doxorubicin-induced lysosomal dysfunction and oxidative stress in H9c2 cells via HO-1. Thus, this study was aimed at investigating the involvement of HO-1-mediated lysosomal function and autophagy flux in DOX-induced oxidative stress and cardiotoxicity in H9c2 cells. Our results showed that XML treatment markedly increased cell proliferation and SOD activity, improved lysosomal function, and ameliorated autophagy flux block in DOX-treated H9c2 cells. Furthermore, XML significantly increased HO-1 expression following DOX treatment. Importantly, HO-1-specific inhibitor (Znpp) or HO-1 siRNA could significantly attenuate the protective effects of XML against DOX-induced cell injury, oxidative stress, lysosomal dysfunction, and autophagy flux block. These results suggest that XML protects against DOX-induced cardiotoxicity through HO-1-mediated recovery of lysosomal function and autophagy flux and decreases oxidative stress, providing a novel mechanism responsible for the protection of XML against DOX-induced cardiomyopathy

Fabrication of flexible, all-reduced graphene oxide non-volatile memory devices

A flexible, all reduced graphene oxide non-volatile memory device, with lightly reduced GO as an active layer and highly reduced GO as both top and bottom electrodes, is fabricated by a full-solution process and its performance is characterized. It provides a convenient method to construct other all-carbon devices

HSPB1 Regulates Autophagy and Apoptosis in Vascular Smooth Muscle Cells in Arteriosclerosis Obliterans

Objective. Small heat shock protein-1 (HSPB1) is a small heat shock protein that participates in many cellular processes and alleviates stress-induced cell injury. Autophagy protects cells from many types of stress and plays a key role in preventing stress in arteriosclerosis obliterans (ASO). However, the roles of HSPB1 in autophagy and apoptosis in the context of ASO pathogenesis remain unclear. Methods. In vivo and in vitro studies were used to determine whether HSPB1 is associated with ASO progression. The expression of HSPB1 was measured in normal and sclerotic blood vessels. The role of HSPB1 and its potential downstream signaling pathway were determined in VSMCs by overexpressing and silencing HSPB1. Results. A total of 91 ASO patients admitted to and treated at our hospital from Sep. 2020 to Sep. 2021 were selected, and plasma HSPB1 expression was assessed. We divided the patients with ASO into the grade I (n=39), II (n=29), III (n=10), and IV (n=13) groups according to Fontaine’s classification. Plasma HSPB1 levels were markedly decreased in patients with grade III (n=10) and IV (n=13) ASO compared with patients with grade I ASO. Furthermore, HSPB1 expression was significantly decreased, and p62 and cleaved caspase-3 were increased in the sclerotic vasculature compared to the normal vasculature (p<0.05). Overexpression of HSPB1 promoted apoptosis of VSMCs following ox-LDL treatment. Knockdown of HSPB1 led to a marked increase in the expression of LC3II and Beclin-1 in ox-LDL-stimulated VSMCs, whereas knockdown of HSPB1 attenuated these changes (p<0.05). Importantly, overexpression of HSPB1 promoted the dephosphorylation of JNK in ox-LDL-stimulated VSMCs. Conversely, downregulation of HSPB1 induced the opposite change. Conclusion. Loss of HSPB1 promotes VSMC autophagy and inhibits VSMC apoptosis, which are associated with ASO. HSPB1 and its downstream signaling pathways could be potential therapeutic targets for ASO treatment

Vapor–liquid–solid growth of endotaxial semiconductor nanowires

Free-standing and in-plane lateral nanowires (NWs) grown by the vapor–liquid–solid (VLS) process have been widely reported. Herein, we demonstrate that the VLS method can be extended to the synthesis of horizontally aligned semiconductor NWs embedded in substrates. Endotaxial SiGe NWs were grown in silicon substrates by tuning the directional movement of the catalyst in the substrates. The location of the SiGe NWs can be controlled by the SiO2 pattern on the silicon surface. By varying the growth conditions, the proportion of Ge in the obtained NWs can also be tuned. This approach opens up an opportunity for the spatial control of the NW growth in substrates and can potentially broaden the applications of NWs in new advanced fields

Coupling of NiFe Layered Double Hydroxides with Sulfides for Highly Efficient Urea Electrolysis and Hydrogen Evolution

Urea electrolysis is regarded as a prospective method for energy-saving hydrogen production. However, the practical application of this technology is limited by the lack of high-performance bifunctional catalysts for hydrogen evolution reaction (HER) and urea oxidation reaction (UOR). Herein, a heterostructure catalyst composed of NiFe layered double hydroxide (LDH) and sulfides (NiFe LDH-NiFeSx/NF) catalysts is prepared via a simple one-step hydrothermal approach. Remarkably, the prepared NiFe LDH-NiFeSx/NF required 138 mV and 1.34 V to achieve 10 mA cm&minus;2 for HER and UOR in 1 M KOH and 0.33 M urea, respectively. Furthermore, when NiFe LDH-NiFeSx/NF is used as a cathode for urea electrolysis, only 1.44 V is required at 10 mA cm&minus;2, which is much lower than the 1.53 V needed for overall water splitting

Layer thinning and etching of mechanically exfoliated MoS2 nanosheets by thermal annealing in air

A simple thermal annealing method for layer thinning and etching of mechanically exfoliated MoS2 nanosheets in air is reported. Using this method, single-layer (1L) MoS2 nanosheets are achieved after the thinning of MoS2 nanosheets from double-layer (2L) to quadri-layer (4L) at 330 °C. The as-prepared 1L MoS2 nanosheet shows comparable optical and electrical properties with the mechanically exfoliated, pristine one. In addition, for the first time, the MoS2 mesh with high-density of triangular pits is also fabricated at 330 °C, which might arise from the anisotropic etching of the active MoS2 edge sites. As a result of thermal annealing in air, the thinning of MoS2 nanosheet is possible due to its oxidation to form MoO3. Importantly, the MoO3 fragments on the top of thinned MoS2 layer induces the hole injection, resulting in the p-type channel in fabricated field-effect transistors

Preparation of MoS2-polyvinylpyrrolidone nanocomposites for flexible nonvolatile rewritable memory devices with reduced graphene oxide electrodes

A facile method for exfoliation and dispersion of molybdenum disulfide (MoS2) with the aid of polyvinylpyrrolidone (PVP) is proposed. The resultant PVP-coated MoS2 nanosheets, i.e., MoS2-PVP nanocomposites, are well dispersed in the low-boiling ethanol solvent, facilitating their thin film preparation and the device fabrication by solution processing technique. As a proof of concept, a flexible memory diode with the configuration of reduced graphene oxide (rGO)/MoS2-PVP/Al exhibited a typical bistable electrical switching and nonvolatile rewritable memory effect with the function of flash. These experimental results prove that the electrical transition is due to the charge trapping and detrapping behavior of MoS2 in the PVP dielectric material. This study paves a way of employing two-dimensional nanomaterials as both functional materials and conducting electrodes for the future flexible data storage

Insight into the mechanisms of therapeutic hypothermia for asphyxia cardiac arrest using a comprehensive approach of GC-MS/MS and UPLC-Q-TOF-MS/MS based on serum metabolomics

Cardiac arrest (CA) is a severe worldwide health problem. Therapeutic hypothermia is widely used to reduce the cardiac injury and improve the neurological outcomes after CA. However, a few studies have reported the changes of serum metabolic characteristics after CA. The healthy male New Zealand Rabbits successfully resuscitated from 10-min asphyxia-induced CA were divided randomly into the normothermia (NT) group and mild therapeutic hypothermia (HT) group. The sham group underwent sham-operation. Survival was recorded and neurological deficit score (NDS) was assessed. The serum non-targeted metabolomics were detected using ultra-high-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS/MS) at 15 min, 3 h, 6 h and 24 h after return of spontaneous circulation (ROSC). Our study showed that the heart rate (HR) significantly slowed down during 0.5–6 h post ROSC, consistent with the decreasing trend of body temperature in the HT group. Compared with the NT group, the levels of Lac and PCO2 at 24 h post ROSC were lower, while a significant increase in PO2 level at 24 h post ROSC was observed in the HT group. The survival rate of the HT group was significantly higher than that of the NT group, and NDS scores were remarkably increased at 24 h post ROSC in the NT group. Significant differences in metabolic profiles at 15 min, 3 h, 6 h and 24 h post ROSC were observed among the Sham, NT and HT groups. The differential metabolites detected by UPLC-Q-TOF-MS/MS and GC-MS/MS were screened for further study between every two groups (NT vs sham, HT vs sham and HT vs NT) at 15 min, 3 h, 6 h and 24 h post ROSC. Phenylalanine metabolism, alanine, aspartate and glutamate metabolism and tricarboxylic acid (TCA) cycle were enriched in NT vs sham, HT vs sham and HT vs NT respectively. Our study demonstrated that therapeutic hypothermia improves the survival and neurological outcomes in rabbit model of cardiac arrest, and firstly represents the dynamic metabolic changes in the hypothermia therapy for CA by comprehensive UPLC-Q-TOF-MS/MS- and GC-MS/MS-based metabolomics