GSK-3ß inhibition protects human nucleus pulposus cell against oxidative stress-inducing apoptosis through mitochondrial pathway.

BACKGROUND: Oxidative stress in the intervertebral disc leads to nucleus pulposus (NP) degeneration by inducing cell apoptosis. However, the molecular mechanisms underlying this process remain unclear. Increasing evidence indicates that GSK-3ß is related to cell apoptosis induced by oxidative stress. In this study, we explored whether GSK-3ß inhibition protects human NP cell against apoptosis under oxidative stress. METHODS AND RESULTS: Immunofluorescence staining was used to show the expression of GSK-3ß in human NP cells (NPCs). Flow cytometry, mitochondrial staining and western blot (WB) were used to detect apoptosis of treated NPCs, changes of mitochondrial membrane potential and the expression of mitochondrial apoptosis-related proteins using GSK-3ß specific inhibitor SB216763. Co-Immunoprecipitation (Co-IP) was used to demonstrate the interaction between GSK-3ß and Bcl-2. We delineated the protective effect of GSK-3ß specific inhibitor SB216763 on human NPCs apoptosis induced by oxidative stress in vitro. Further, we showed SB216763 exert the protective effect by preservation of the mitochondrial membrane potential and inhibition of caspase 3/7 activity during oxidative injury. The detailed mechanism underlying the antiapoptotic effect of GSK-3ß inhibition was also studied by analyzing mitochondrial apoptosis pathway in vitro. CONCLUSIONS: We concluded that the GSK-3ß inhibitor SB216763 protected mitochondrial membrane potential to delay nucleus pulposus cell apoptosis by inhibiting the interaction between GSK-3ß and Bcl-2 and subsequently reducing cytochrome c(Cyto-C) release and caspase-3 activation. Together, inhibition of GSK-3ß using SB216763 in NPCs may be a favorable therapeutic strategy to slow intervertebral disc degeneration.

The Water-Energy Nexus of Megacities Extends Beyond Geographic Boundaries: A Case of Beijing.

The water-energy nexus (WEN) is dynamic and complicated in megacities, most of which are challenged by water scarcity and the mandate to reduce energy consumption. A salient feature of water and energy services in megacities is that they are supported by a web of regional infrastructure, extending far beyond the geographic boundaries of the cities, resulting in a strong dependence on resources imported from outside. Understanding the WEN of megacities has implications not only for more efficient resource utilization but also for synergistic regional development and corporation. This study provides a quantitative assessment of the WEN of Beijing within and beyond its geographic boundaries. Results show that water for local internal energy production and transformation accounts for 220 million m3/year, or 5.6% of its total freshwater use in 2016, and the energy for local water abstraction, supply, and treatment is 3.06 billion kWh, accounting for 1.1% of its total energy consumption for the same year. The external water for "imported" energy is 290 million m3/year, 1.3 times of Beijing's freshwater use for internal energy. This means that more water for energy is consumed outside Beijing than that within Beijing. The energy for external water is negligible because the bulk of the water transfer into Beijing relies on gravity and because the energy for construction of the transfer infrastructure is not included. Analysis of the WEN revealed the contradiction between the two independently conceived policies of Beijing: to meet the "three-red-line" target in the water sector, recycled water and transferred water use will rise, making it more difficult to meet the carbon emission control targets. Therefore, adopting low energy intensity, nature-based water recycling is a wise policy choice.

[Application of high tibial osteotomy for chronic multi-ligament knee injury associated with lower extremity malalignment].

OBJECTIVE: To investigate the feasibility and effectiveness of high tibial osteotomy (HTO) in treatment of chronic multi-ligament knee injury (MLKI) associated with lower extremity malalignment. METHODS: A clinical data of 14 patients (14 knees) of chronic MLKI associated with lower extremity malalignment, who were treated with HTO between January 2016 and September 2020, was retrospectively analyzed. There were 10 males and 4 females, with an average age of 30.5 years (range, 22-48 years). The causes of injury included traffic accident in 8 cases, bruising by a heavy object in 3 cases, falling from height in 2 cases, and twisting in 1 case. According to Schenck classification of knee dislocation (KD), there were 4 cases of KD-Ⅰ [2 cases of anterior cruciate ligament (ACL) and posterolateral complex (PLC) injuries and 2 cases of posterior cruciate ligament (PCL) and PLC injuries], 7 cases of KD-Ⅲ (all of ACL, PCL, and PLC injuries), and 3 cases of KD-Ⅳ. The preoperative hip-knee-ankle angle (HKA) was (167.1±4.7)°, and the posterior tibial slope angle (PTSA) was (16.3±2.7)°. The knee joint was severely unstable and the patients could not stand and walk normally. Among them, 5 cases of medial compartment cartilage were severely worn out (3 cases of Kellgren-Lawrence grading Ⅱ, 2 cases of grading Ⅲ) causing pain. After admission, 2 cases of KD-Ⅰ underwent HTO and ligament reconstruction in the first stage, 1 case of KD-Ⅲ and 1 case of KD-Ⅳ underwent HTO in the first stage and ligament reconstruction in the second stage; the remaining 10 patients only underwent HTO. RESULTS: All patients were followed up 12-50 months, with an average of 30 months. The incisions healed by first intention after operation, and no complications such as infection and deep vein thrombosis of the lower extremities occurred. At 12 months after operation, knee range of extension was -5°-0° (mean, -1.2°) and range of flexion was 110°-140° (mean, 125.5°). The Lachman test was negative in 11 cases and positive in 3 cases. The posterior drawer test was negative in 9 cases and positive in 5 cases. The 0/30° varus stress test was negative in 10 cases and positive in 4 cases. The 0/30° valgus stress test was negative in 13 cases and positive in 1 case. The visual analogue scale (VAS) score was significantly lower than that before operation ( P<0.05), and the International Knee Documentation Committee (IKDC) score, Lysholm score, and Tegner score were all significantly higher than those before operation ( P<0.05). The X-ray film reexamination at 12 months after operation showed that the HKA was (178.2±3.8)° and the PTSA was (8.6±2.4)°, which were significantly different from those before operation ( P<0.05). All osteotomies achieved bone union, and the healing time was 3-11 months, with an average of 6.8 months. CONCLUSION: For chronic MLKI associated with lower extremity malalignment, HTO can restore normal lower extremity alignment and improve knee joint function, which is a feasible salvage operation.

Public anxiety through various stages of COVID-19 coping: Evidence from China.

As countries underwent the initiation, peak, post-peak, and early vaccination stages of COVID-19, the changing risk perception, coping behaviors and corresponding psychological stress experienced by the public over time was rarely reported. We conducted a national scale panel study using social-psychological data collected from 5,983 questionnaires to investigate the interactions between anxiety level, risk perception and coping behavior during different stages of COVID-19 in China. We found that sustained perceiving worries of being infected, first due to domestic and then global pandemic, contributed to the persistent high proportion of respondents with anxiety disorders which even gradually increased over time (56.1% during initiation to 60.4% during early vaccination). Gender was the strongest predictor of anxiety at all stages, with females having less confidence in COVID-19 control and always suffering from much higher anxiety levels than males even during the post peak stage. Excessive protective behavior and frequency of access to COVID-related news also contributed to public anxiety. Additionally, public risk perception was significantly associated with their willingness to vaccinate. The findings verify the feasibility of taking stage-specific and gender-based risk communication strategies to alleviate the pandemic-related public anxiety and promote vaccination by influencing public risk perception and guiding coping behaviors.

Changes of public risk perception in China: 2008-2018.

This paper characterizes the risk acceptance of the Chinese public based on a psychometric paradigm and documents its change by conducting a nationally representative longitudinal survey spanning 10 years. We explore key factors that influence the acceptance of seven typical risks: drinking water pollution, interior decoration, electromagnetic radiation, air pollution, chemical plants, public transportation, and natural hazards, reflecting the general and referential changes in risk perception. The results show a general decrease in the acceptance of all of these risks in the examined decade, especially in economically developed areas. Different types of risk perception varied, but environmental risks had similar trends of perception. The perceived benefits from these risks and local GDP had the greatest impact on risk acceptance. The interaction between the changing perspectives of the emerging middle class and the evolving hazard risk landscape may be the reasons for the reduction in risk acceptance. The main findings offer insights for effective risk education and communication as well as sustainable risk management strategy.

Reducing hazard vulnerability: towards a common approach between disaster risk reduction and climate adaptation.

Over the past few decades, four distinct and largely independent research and policy communities--disaster risk reduction, climate change adaptation, environmental management and poverty reduction--have been actively engaged in reducing socio-economic vulnerability to natural hazards. However, despite the significant efforts of these communities, the vulnerability of many individuals and communities to natural hazards continues to increase considerably. In particular, it is hydro-meteorological hazards that affect an increasing number of people and cause increasingly large economic losses. Arising from the realisation that these four communities have been largely working in isolation and enjoyed only limited success in reducing vulnerability, there is an emerging perceived need to strengthen significantly collaboration and to facilitate learning and information exchange between them. This article examines key communalities and differences between the climate change adaptation and disaster risk reduction communities, and proposes three exercises that would help to structure a multi-community dialogue and learning process.

Reducing hazard vulnerability: towards a common approach between disaster risk reduction and climate adaptation

Over the past few decades, four distinct and largely independent research and policy communitiesùdisaster risk reduction, climate change adaptation, environmental management and poverty reductionùhave been actively engaged in reducing socio-economic vulnerability to natural hazards. However, despite the significant efforts of these communities, the vulnerability of many individuals and communities to natural hazards continues to increase considerably. In particular, it is hydrometeorological hazards that affect an increasing number of people and cause increasingly large economic losses. Arising from the realisation that these four communities have been largely working in isolation and enjoyed only limited success in reducing vulnerability, there is an emerging perceived need to strengthen significantly collaboration and to facilitate learning and information exchange between them. This article examines key communalities and differences between the climate change adaptation and disaster risk reduction communities, and proposes three exercises that would help to structure a multi-community dialogue and learning process. (AU)