Brusatol Protects HepG2 Cells against Oxygen-Glucose Deprivation-Induced Injury via Inhibiting Mitochondrial Reactive Oxygen Species-Induced Oxidative Stress.

BACKGROUND: It has been reported that brusatol (BRU) reduces cellular reactive oxygen species (ROS) level under hypoxia; here the protective effect of BRU against oxygen-glucose deprivation/reoxygenation (OGD-R)-induced injury in HepG2 cells and against anoxia/reoxygenation (A/R)-induced injury in rat liver mitochondria was investigated. MATERIALS AND METHODS: OGD-R-induced HepG2 cell viability loss was detected by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide and trypan blue staining. Mitochondrial ROS level in HepG2 cells was measured by MitoSOX staining. The cellular malondialdehyde and adenosine triphosphate level was measured by commercial kits. The mitochondrial membrane potential in HepG2 cells was measured by JC-1 staining. The protein level was detected by Western blotting. Rat liver mitochondria were separated by differential centrifugation. A/R-induced injury in isolated rat liver mitochondria was established by using a Clark oxygen electrode. The ROS generation in isolated mitochondria was evaluated using Amplex red/horseradish peroxidase. RESULTS: BRU reduced mitochondrial ROS level and alleviated oxidative injury in HepG2 cells, thereby significantly inhibited OGD-R-induced cell death. During OGD-R, BRU improved mitochondrial function and inhibited the release of cytochrome c. Furthermore, BRU showed a clear protective effect against A/R-induced injury in isolated rat liver mitochondria. When isolated rat liver mitochondria were pretreated with BRU, A/R-induced ROS generation was significantly decreased, and mitochondrial respiratory dysfunction was ameliorated. CONCLUSIONS: BRU pretreatment attenuated OGD-R-induced injury in HepG2 cells and A/R-induced injury in isolated rat liver mitochondria by inhibiting mitochondrial ROS-induced oxidative stress.

Ammonia mediates mitochondrial uncoupling and promotes glycolysis via HIF-1 activation in human breast cancer MDA-MB-231 cells.

It has been reported that ammonia produced by glutaminolysis activates the HIF-1 pathway in several types of cancer cells, but the underlying mechanisms remain unclear. In this study, the effects of ammonia on the activation of HIF-1 pathway and glycolysis in MDA-MB-231 breast cancer cells were investigated and the underlying mechanisms involved were elucidated. The results showed that NH4Cl concentration-dependently increased the protein level of HIF-1α and enhanced the transactivation activity of HIF-1 in MDA-MB-231 cells. In addition, NH4Cl increased the expression of GluT1 and LDHA and promoted aerobic glycolysis by activating the HIF-1 pathway. Further study revealed that NH4Cl increased the mitochondrial ROS level and decreased the cellular Fe2+ level in MDA-MB-231 cells. Activation of the HIF-1 pathway induced by NH4Cl was inhibited by addition of the antioxidant NAC or the NADPH oxidase (NOX) inhibitor apocynin, indicating the involvement of the NOX-induced ROS generation. When MDA-MB-231 cells were treated with NH4Cl, the oxygen consumption of cells increased, followed by the decreased mitochondrial membrane potential and cellular ATP level, indicating the uncoupling of mitochondria. In conclusion, NH4Cl activated the HIF-1 signaling pathway and promoted aerobic glycolysis in MDA-MB-231 cells, likely through the promotion of mitochondrial ROS release and mitochondrial uncoupling.

Remote Health Management via WeChat to Improve the Quality of Life of Patients After PCI.

OBJECTIVES: The purpose of this research was to assess the effect of telehealth management via WeChat on improving the quality of life of patients after percutaneous coronary intervention (PCI). METHODS: In this study, we retrospectively collected the clinical data of 118 patients who underwent PCI and received remote health management from our hospital via WeChat from June 2021 to September 2021 (WeChat group). The clinical data of 114 patients who underwent PCI but did not receive remote health management from our hospital from September 2020 to December 2020 were also collected (conventional group). Anxiety, depression, and quality of life scale scores were compared between the 2 groups at 6 months postdischarge. RESULTS: Six months postdischarge, patients in the WeChat group had significantly lower Self-rating Anxiety Scale (SAS) (55.7 ± 7.2 vs 58.8 ± 6.4, P = .001) and Self-rating Depression Scale (SDS) (56.0 ± 5.9 vs 58.2 ± 6.2, P = .007) scores than did those in the conventional group. Compared to those in the conventional group, the patients in the WeChat group had significantly greater 6 months post-discharge The World Health Organization Quality of Life - BREF scores in the following domains: physical (14.3 ± 1.7 vs 13.1 ± 1.7, P < .001 psychological (15.2 ± 1.3 vs 13.5 ± 1.5, P < .001 social relationship (12.9 ± 1.7 vs 12.3 ± 1.8, P = .01) and environmental (12.7 ± 2.0 vs 12.0 ± 1.9, P = .006). CONCLUSION: The use of WeChat to carry out remote health management for patients who underwent PCI can be an effective way to provide high-quality hospital medical services to patients' families and can effectively alleviate patients' anxiety and depression and enhance their quality of life.

Improving the Wear and Corrosion Resistance of Aeronautical Component Material by Laser Shock Processing: A Review.

Since the extreme service conditions, the serious failure problems caused by wear and corrosion are often encountered in the service process for aeronautical components. Laser shock processing (LSP) is a novel surface-strengthening technology to modify microstructures and induce beneficial compressive residual stress on the near-surface layer of metallic materials, thereby enhancing mechanical performances. In this work, the fundamental mechanism of LSP was summarized in detail. Several typical cases of applying LSP treatment to improve aeronautical components' wear and corrosion resistance were introduced. Since the stress effect generated by laser-induced plasma shock waves will lead to the gradient distribution of compressive residual stress, microhardness, and microstruture evolution. Due to the enhancement of microhardness and the introduction of beneficial compressive residual stress by LSP treatment, the wear resistance of aeronautical component materials is evidently improved. In addition, LSP can lead to grain refinement and crystal defect formation, which can increase the hot corrosion resistance of aeronautical component materials. This work will provide significant reference value and guiding significance for researchers to further explore the fundamental mechanism of LSP and the aspects of the aeronautical components' wear and corrosion resistance extension.

Environmental governance effects of local environmental protection expenditure in China.

China's economy is experiencing a rapid revival in the post Covid-19 era, while energy consumption is surging and environmental pressure is prominent. Environmental protection expenditure is an important means for local governments to improve environmental quality; it plays a crucial role in guiding market investment, providing environmental treatment funds and energy conservation and utilization. Based on a sample of 286 prefecture-level cities in China from 2007 to 2017, this study analyzes environmental governance effects of local environmental protection expenditure while considering the time duration, regional differences, and spatial spillover characteristics of industrial pollution emissions. The results reveal that local environmental protection expenditure could help reduce industrial pollution emissions in Chinese cities; however, the governance effects were heterogeneous in different clustering city groups. In addition, the effects of environmental protection expenditure at the neighborhood level varied greatly; the results showed that the stronger the spillover of pollutants, the more significant was the trans-regional governance effect of local environmental protection expenditure. Therefore, local governments should promote a cooperative mode of "joint prevention and control and cross-regional governance" when treating pollutants with strong spillover potential.

Microstructural Evolution and Surface Mechanical Properties of the Titanium Alloy Ti-13Nb-13Zr Subjected to Laser Shock Processing.

As a progressive surface-hardening technology, laser shock processing (LSP) can enhance the mechanical properties and extend fatigue life for metallic components through laser-generated high-pressure plasma shock waves. In this work, LSP was used to treat titanium alloy Ti-13Nb-13Zr experimental coupons, and the microstructural response and surface mechanical properties of the Ti-13Nb-13Zr experimental coupons were investigated. After the LSP treatment, the X-ray diffraction (XRD) peaks were shifted without any new phase formation. The surface roughness of the experimental coupons increased, which can be explained by the LSP-induced severe plastic deformation. The LSP treatment effectively enhanced the surface compressive residual stress of Ti-13Nb-13Zr. Meanwhile, the microhardness of the Ti-13Nb-13Zr was also obviously increased after the LSP treatment. The experimental results also showed that the number of shocks times is an important factor in the improvement of surface mechanical properties. LSP treatment with multiple shocks can lead to more severe plastic deformation. The surface roughness, surface compressive residual stress and microhardness of the Ti-13Nb-13Zr experimental coupons shocked three times are higher than those after one shock. What is more, grain refinement accounts for the mechanical properties' enhancements after the LSP treatment.

Pharmacological inhibition of mitochondrial division attenuates simulated high-altitude exposure-induced cerebral edema in mice: Involvement of inhibition of the NF-κB signaling pathway in glial cells.

High-altitude cerebral edema (HACE) is the severe type of acute mountain sickness, which is still lack of effective therapy. This study investigated for the first time the protective effect of mitochondrial division inhibitor-1 (mdivi-1) against cerebral edema induced by simulated high-altitude exposure in mice. It was found that mdivi-1 effectively inhibited phosphorylation of dynamin-related protein-1 (Drp1), reduced expression of AQP4, decreased secretion of IL-6 and TNF-α, and alleviated cerebral edema in mice. In primary cultured astrocytes or microglia, mdivi-1 significantly decreased the hypoxia-induced Drp1 phosphorylation and mitochondrial fragmentation, inhibited the activation of the NF-κB signaling pathway, reduced the secretion of IL-6 and TNF-α. In addition, mdivi-1 inhibited mitochondrial reactive oxygen species (ROS) generation induced by hypoxia in both astrocytes and microglia. When astrocytes were treated with the conditioned medium of microglia exposed to hypoxia (H-MCM), the protein levels of p-Drp1, p-p65, and AQP4 as well as the mRNA levels of IL-6, TNF-α, and IL-1ß in astrocytes were increased. When the mitochondrial components in H-MCM were removed, the influence of microglia on astrocytes under hypoxia was significantly alleviated. Treated with mdivi-1, the integrity of mitochondria released from microglia induced by hypoxia were significantly improved. In conclusion, pharmacological inhibition of mitochondrial division by mdivi-1 alleviated cerebral edema induced by simulated high-altitude exposure in mice. Inhibition of ROS/NF-κB signaling pathway may contribute to the protective effect of mdivi-1. Under hypoxic conditions, mdivi-1 may attenuate the activation of astrocytes by reducing the release of damaged mitochondria from microglia.

Intermittent hypoxia preconditioning protects WRL68 cells against oxidative injury: Involvement of the PINK1/Parkin-mediated mitophagy regulated by nuclear respiratory factor 1.

The protective effect of intermittent hypoxia (IH) preconditioning against oxidative injury in hepatic cells was investigated and the involvement of the PINK1/Parkin-mediated mitophagy regulated by nuclear respiratory factor 1 (NRF-1) was evaluated. The results showed that IH preconditioning protected HepG2 cells against oxygen and glucose deprivation/reperfusion (OGD/Rep)-induced injury and protected WRL68 cells against H2O2 or AMA-induced oxidative injury. IH preconditioning up-regulated the protein level of NRF-1, PINK1, Parkin, and LC3 II, promoted the recruitment of the cytosolic Parkin, indicating the initiation of the PINK1/Parkin-mediated mitophagy in WRL68 cells. When NRF-1 was down-regulated by NRF-1 specific shRNA, the protein level of PINK1 and Parkin as well as the mitophagy level were significantly decreased. After IH preconditioning, the protein level of PINK1 and the recruitment of Parkin in CCCP-treated group were significantly higher than that of the control group, indicating the increased mitophagy capacity. And the increased mitophagy capacity induced by IH preconditioning was also reduced by down-regulation of NRF-1. Furthermore, the protective effect of IH preconditioning against H2O2-induced oxidative injury in WRL68 cells was inhibited when NRF-1 or PINK1 was down-regulated by specific shRNA. Mitochondrial ROS generation may be responsible for the increased expression of NRF-1 induced by IH preconditioning. In conclusion, the PINK1/Parkin-mediated mitophagy regulated by NRF-1 was involved in IH preconditioning-induced protective effect against oxidative cellular injury in hepatic cells.

Measuring China's regional inclusive green growth.

In response to the increasing pressure of global resource management and environmental issues and a slowdown in the related economic growth, China has proposed an inclusive green growth strategy based on coordination between society, the economy, and the environment. The alignment of resources with the socio-economic development goals is a key issue that must be addressed for inclusive green growth. A comprehensive directional distance function and slacks-based measure model are proposed to evaluate the inclusive green growth levels of 285 cities in China from 2003 to 2015. The Luenberger indicator is used to decompose the drivers of inclusive green growth. Our research shows that the main obstacle to China's inclusive green growth is the magnitude of technical change, which is not aligned with China's green development level. Hence, it is necessary to coordinate overall inclusive green growth levels using both technical and regional aspects. This research provides a reference not only for China's economic green development, but also for that of developing countries, enabling the coordination of economic development and environmental resource protection.

Positive regulation of human PINK1 and Parkin gene expression by nuclear respiratory factor 1.

Previous studies have demonstrated that two Parkinson'sdisease-associatedgenes PINK1 and Parkin play a key role in mitochondrial quality control. But until now, the transcriptional regulation of these two genes under normal physiological conditions are not well understood. In this study, the transcriptional regulation of PINK1 and Parkin genes by nuclear respiratory factor 1 (NRF-1) and its effect on PINK1/Parkin-mediated mitophagy were studied. The NRF-1 binding sites in the promoter regions of human PINK1 and Parkin genes were analyzed by JASPER software and were confirmed by chromatin immunoprecipitation (ChIP) assay. The transcriptional activities and the expressions of PINK1 and Parkin genes were positively regulated by NRF-1 in HEK293T cells and in SH-SY5Y cells. Furthermore, NRF-1 over-expression (OE) up-regulated the protein level of full-length PINK1 in CCCP-treated cells, indicating the enhanced PINK1/Parkin-mediated mitophagy. When NRF-1 expression was transient orstableknockdown, the CCCP-induced mitophagy was alleviated as characterized by the reduced protein level of full-length PINK1, the declined ratio of LC3 II to LC3 I, and the decreasedratioof Mt-keimafluorescenceintensityexcited at 552 nm to that excited at 488 nm. In conclusion, NRF-1 has a positive regulatory effect on the transcription of PINK1 and Parkin genes, and involves in mitochondrial quality control through regulating PINK1/Parkin-mediated mitophagy.

Cleistanthin A inhibits the invasion of MDA-MB-231 human breast cancer cells: involvement of the ß-catenin pathway.

BACKGROUND: Cleistanthin A (CleA), a natural diphyllin glycoside, has been shown to suppress the invasion of cancer cells, but the underlying mechanisms remain unclear. Here, the inhibitory effect of CleA on the invasion of MDA-MB-231 human breast cancer cells was investigated, and the mechanisms involved were clarified. METHODS: Cell viability was studied by MTT assay. The migration and invasion of MDA-MB-231 cells were assessed by wound healing assay and transwell assay, respectively. The enzymatic activity of matrix metalloproteinases (MMPs) was detected by gelatin zymography. mRNA and protein levels were detected by qRT-PCR and Western blotting, respectively. Nuclear translocation of ß-catenin was observed by immunofluorescence and detected by Western blotting. RESULTS: CleA effectively inhibited the migration and invasion of MDA-MB-231 cells and suppressed the expression and activation of MMP-2/9. Moreover, the expression and nuclear translocation of ß-catenin were reduced by CleA treatment, as well as transcription of the Cyclin D1 and c-myc genes. In addition, the inhibitory effect of CleA on the ß-catenin pathway was attributed to the promotion of ß-catenin degradation by inhibition of GSK3ß phosphorylation. When the phosphorylation of GSK3ß was induced by LiCl, the inhibitory effect of CleA on the ß-catenin pathway and the invasion of MDA-MB-231 cells were almost reversed. CONCLUSION: CleA suppressed the invasion of MDA-MB-231 cells, likely through the ß-catenin pathway.

[Mechanical properties of 3D-printed titanium mesh and its biocompatibility in vitro].

PURPOSE: To compare the mechanical properties of 3D-printed titanium meshes and pre-shaped titanium meshes, and to evaluate the effects of 3D-printed titanium meshes on cell proliferation and differentiation. METHODS: 3D- printed titanium meshes were produced and prepared with laser printing machine. The mechanical properties were analyzed by static tension and compression load test. Bone marrow mesenchymal stem cells (BMSCs) were extracted from 4-week-old male SD rats. BMSCs were co-cultured with 3D-printed titanium meshes of different apertures. Cell counting kit-8 (CCK-8) assay was used to detect cell proliferation. Alkaline phosphatase (ALP) activity assay was used to test ALP activity. The expression of related osteogenic genes was tested by real-time PCR. The adhesion and growth of BMSCs were investigated by scanning electron microscopy (SEM) and living / dead cell staining. SPSS 22.0 software package was used for statistical analysis of the results. RESULTS: The results of 3D-printing Ti-meshes tension and compression loading experiment were excellent. The 3D-printing Ti-meshes showed no inhibitory effects on cell proliferation, survival and adhesion, but had a positive effect on osteogenesis of BMSCs. CONCLUSIONS: The mechanical properties of 3D-printed Ti-meshes are excellent. The 3D-printed Ti-meshes have good biocompatibility.