China’s declaration to the international community to peak CO
2
emissions before 2030 and achieve carbon neutrality before 2060 is of great significance in advancing the objectives of the Paris ...Agreement, and has a positive and far-reaching impact on China’s high-quality development. This paper expounds on responsibilities and ambitions in tackling climate change, analyzes the high-quality development opportunities brought about by CO
2
emissions peak and carbon neutrality, and discusses the net zero carbon emissions transformation in the new era of ecological civilization. This paper is of the view that development towards net zero carbon emissions provides a new impetus for building a Beautiful China, and promoting ecological civilization and green development. The essence of carbon neutrality should be correctly understood so that the world will work together to improve climate resilience. China should also deepen the understanding of the principles and methodologies of climate change economics.
Human hexokinase 2 is an essential regulator of glycolysis that couples metabolic and proliferative activities in cancer cells. The binding of hexokinase 2 to the outer membrane of mitochondria is ...critical for its oncogenic activity. However, the regulation of hexokinase 2 binding to mitochondria remains unclear. Here, we report that SUMOylation regulates the binding of hexokinase 2 to mitochondria. We find that hexokinase 2 can be SUMOylated at K315 and K492. SUMO-specific protease SENP1 mediates the de-SUMOylation of hexokinase 2. SUMO-defective hexokinase 2 preferably binds to mitochondria and enhances both glucose consumption and lactate production and decreases mitochondrial respiration in parallel. This metabolic reprogramming supports prostate cancer cell proliferation and protects cells from chemotherapy-induced cell apoptosis. Moreover, we demonstrate an inverse relationship between SENP1-hexokinase 2 axis and chemotherapy response in prostate cancer samples. Our data provide evidence for a previously uncovered posttranslational modification of hexokinase 2 in cancer cells, suggesting a potentially actionable strategy for preventing chemotherapy resistance in prostate cancer.
The “Proposals for Formulating the 14th Five-Year Plan (2021–2025) for National Economic and Social Development and the Long-Range Objectives Through the Year 2035” puts forth that there will be a ...fundamental improvement in the environment with the goal of building a Beautiful China basically. One of the key measurements of Beautiful China is carbon neutrality orientation. The task of achieving carbon neutrality is arduous, and the key difficulty of carbon neutrality lies in cities. The author believes there should be a timetable and a roadmap for carbon neutrality in cities. First, it is necessary to clarify the goal of achieving carbon emissions peak in the “14th Five-Year Plan”. Second, urban renewal, old city reconstruction and new infrastructure need to be incorporated into carbon constraints, so as to strictly prevent carbon locks, and fundamentally eliminate carbon demands. Third, the new construction, expansion or reconstruction of cities needs to be oriented by carbon neutrality.
International trade is characterized not only by the flow of capital and goods, but also by the energy and emissions embodied in goods during their production. This paper investigates the evolving ...role that Chinese trade is playing in the response to climate change by estimating the scale of emissions embodied in China's current trade pattern and demonstrating the magnitude of the difference between the emissions it produces (some of which are incurred to meet the consumption demands of the rest of the world) and the emissions embodied in the goods it consumes. Estimating China's emissions on a consumption rather than a production basis both lowers its responsibility for carbon-dioxide (CO2) emissions in 2006 from 5,500 to 3,840mtCO2 and reduces the growth rate of emissions from an average of 12.5 per cent p.a. to 8.7 per cent p.a. between 2001 and 2006. The analysis indicates that a reliable consumption-based accounting methodology is feasible and could improve our understanding of which actors and states are responsible for emissions. For example, recent emissions reductions by developed countries may lack credibility if production has merely been displaced to countries such as China. Moreover, in the current institutional context, production methodologies encourage leakages through trade that may do more to displace than to reduce emissions. Both equity and efficiency concerns therefore suggest that emissions embodied in trade should receive special attention in the distribution of post-Kyoto abatement burdens.
Neuroendocrine prostate cancer is one of the most aggressive subtypes of prostate tumor. Although much progress has been made in understanding the development of neuroendocrine prostate cancer, the ...cellular architecture associated with neuroendocrine differentiation in human prostate cancer remain incompletely understood. Here, we use single-cell RNA sequencing to profile the transcriptomes of 21,292 cells from needle biopsies of 6 castration-resistant prostate cancers. Our analyses reveal that all neuroendocrine tumor cells display a luminal-like epithelial phenotype. In particular, lineage trajectory analysis suggests that focal neuroendocrine differentiation exclusively originate from luminal-like malignant cells rather than basal compartment. Further tissue microarray analysis validates the generality of the luminal phenotype of neuroendocrine cells. Moreover, we uncover neuroendocrine differentiation-associated gene signatures that may help us to further explore other intrinsic molecular mechanisms deriving neuroendocrine prostate cancer. In summary, our single-cell study provides direct evidence into the cellular states underlying neuroendocrine transdifferentiation in human prostate cancer.
To achieve carbon neutrality, it is necessary to grasp the essence of carbon neutrality. This paper looks into a few fundamental issues of carbon neutrality, and provides an in-depth analysis from ...the perspectives of environmental sustainability, technological innovation, economic viability, energy security, and international cooperation. It is shown that efforts for carbon neutrality need to focus on the key carbon dioxide (CO
2
) emissions from fossil fuel combustion. Fossil energy is considered to play a role as a short-term “ballast stone”, but its attributes decide that it can hardly lead to a sustainable future, and its phasing-out is inevitable. Disruptive zero-carbon energy production and revolutionary technological innovation in its consumption are accelerating that phasing-out process; the zero-carbon-oriented carbon neutrality goal is growing more resilient to market headwinds and releasing momentum for high-quality development. Carbon capture and carbon sinks are indispensable, but they are unable to provide a satisfactory path to carbon neutrality. Carbon neutrality requires substantial capital investment, which can be provided by zero-carbon products with ever-increasing market competitiveness. Investment in high carbon fossil fuel industry can be risky. High carbon lock-in not only increases the difficulty of carbon neutrality, but also intensifies the risk of energy security, and it is difficult to avoid the risk of market crowding-out, resulting in huge amounts of capital waste. Consequently, decarbonization is the trend of the times, giving an edge on seeking international justice and a louder voice in the international community, and also the focus of market competitiveness. However, the target year for carbon neutrality in China is before 2060, indicating that carbon neutrality is not a short-term goal. Therefore, it is impossible and unnecessary to have it realized overnight. The opportunity of carbon neutrality should be well taken for quality growth of the economy and enhancement of people’s well-being. Carbon neutrality is a long-term process which calls for thorough plans and step-by-step actions. It is also evident that along with energy revolution, carbon neutrality also brings revolutionary transformation of relations of production and development paradigm.
Solar radiation modification, particularly stratospheric aerosol injection, holds the potential to reduce the impacts of climate change on sustainable development, yet could itself generate negative ...impacts and is subject to intense scholarly debate based on relatively little evidence. Based on expert elicitation involving over 30 individuals with backgrounds across the domains of the United Nations’ Sustainable Development Goals (SDGs), we identify a broad range of potential implications of solar radiation modification for the SDGs. Depending on design and application scenarios, applications could potentially assist in the pursuit of several of the goals by limiting temperature rise and limiting acceleration in atmospheric water cycles as well as extreme weather events. However, by adding to particulates, introducing an additional layer of complexity and potential for conflict in global governance, as well as otherwise altering planetary environments, they might also detract from the pursuit of SDGs and introduce novel risks. The overall impact of solar radiation modification on sustainable development is currently highly uncertain and dependent on climate change mitigation pathways and governance. We identify key areas for further transdisciplinary research the pursuit of which might reduce some uncertainty and help inform emerging governance processes.
Mechanisms driving the progression of castration-resistant prostate cancer are believed to relate substantially to the tumor microenvironment. However, the cross-talks between tumor epithelial cell, ...stromal cells, and immune cells are yet to be fully elucidated. The present study aims to determine the role of chemokine and neutrophil derived cytokine paracrine axis in mediating the interaction between tumor cells, stromal myofibroblasts, and neutrophils in the tumor microenvironment of prostate cancer.
To identify myofibroblasts and neutrophil derived specific proteins affecting progression of prostate cancer, bioinformatics analyses were firstly performed in independent human prostate cancer gene expression data sets from the GEO data bank. Expression of stromal myofibroblasts secretory chemokine CXCL1 and neutrophil derived cytokine LCN2 was evaluated in prostate tissues via immunohistochemistry assay. We further investigated the effect of CXCL1 and LCN2 on prostate cancer using in vivo and in vitro models, and explored the underlying signal transduction pathways.
A CXCL1-LCN2 paracrine network was confirmed in prostate cancer tissue samples, which was correlated with the biochemical recurrence of prostate cancer. Of note, CXCL1-LCN2 axis activates Src signaling, triggers the epithelial-mesenchymal transition (EMT), consequently promotes the migration of prostate cancer cells, leading to enhanced tumor metastasis.
Our findings may provide enhanced insight into the interactions of carcinoma-stromal cells and immune cells linked to prostate cancer progression, wherein CXCL1-LCN2 axis is a key contributor to prostate cancer cells migration. These data indicate tumor microenvironment and Src signaling pathway may be potential therapeutic targets of prostate cancer treatment.
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