Virtual Water Scarcity Risk to the Global Trade System.

Local water scarcity risk (LWSR, meaning potential economic output losses in water-using sectors due to physical water scarcity) can be transmitted to downstream economies through the globalized supply chains. To understand the vulnerability of the global economy to water scarcity, we examine the impacts of local water scarcity risk on the global trade system from 1995 to 2009. We observe increasingly intensified geographical separation between physical water scarcity and production losses due to water scarcity. We identify top nation-sectors in virtual water scarcity risk (VWSR) exports (indicating local water scarcity risk in each nation transmitted to foreign nations through its exports), including agriculture and utilities in major economies such as China, India, Spain, France, and Turkey. These nation-sectors are critical to the resilience of the global economy to water scarcity. We also identify top nation-sectors in virtual water scarcity risk imports (indicating each nation's vulnerability to foreign water scarcity risk through the global trade system), highlighting their vulnerability to distant water scarcity. Our findings reveal the need for nations to collaboratively manage and conserve water resources, and lay the foundation for firms in high VWSR-importing sectors to develop strategies to mitigate such risk.

Income-Based Greenhouse Gas Emissions of Nations.

Accounting for greenhouse gas (GHG) emissions of nations is essential to understanding their importance to global climate change and help inform the policymaking on global GHG mitigation. Previous studies have made efforts to evaluate direct GHG emissions of nations (a.k.a. production-based accounting method) and GHG emissions caused by the final consumption of nations (a.k.a. consumption-based accounting method), but overlooked downstream GHG emissions enabled by primary inputs of individual nations and sectors (a.k.a. income-based accounting method). Here we show that the income-based accounting method reveals new GHG emission profiles for nations and sectors. The rapid development of mining industries drives income-based GHG emissions of resource-exporting nations (e.g., Australia, Canada, and Russia) during 1995-2009. Moreover, the rapid development of sectors producing basic materials and providing financial intermediation services drives income-based GHG emissions of developing nations (e.g., China, Indonesia, India, and Brazil) during this period. The income-based accounting can support supply side policy decisions and provide additional information for determining GHG emission quotas based on cumulative emissions of nations and designing policies for shared responsibilities.

Design, synthesis, and biological evaluation of RSL3-based GPX4 degraders with hydrophobic tags.

Ferroptosis is a new type of programmed cell death characterized by iron-dependent lipid peroxidation, during which glutathione peroxidase 4 (GPX4) plays an essential role and is well-recognized as a promising therapeutic target for cancer treatment. Although some GPX4 degradation molecules have been developed to induce ferroptosis, the discovery of GPX4 degraders with hydrophobic tagging (HyT) as an innovative approach is more challenging. Herein, we designed and synthesized a series of HyT degraders by linking the GPX4 inhibitor RSL3 with a hydrophobic and bulky group of adamantane. Among them, compound R8 is a potent degrader (DC50, 24h = 0.019 µM) which can effectively degrade GPX4 in a dose- and time-dependent manner. Furthermore, compound R8 exhibited superior in vitro antitumor potency against HT1080 and MDA-MB-231 cell lines with IC50 values of 24 nM and 32 nM respectively, which are 4 times more potent than parental compound RSL3. Mechanistic investigation evidenced that R8 consumes GPX4 protein mainly through the ubiquitin proteasome (UPS) and enables to induce the accumulation of LPO, thereby triggering ferroptosis. Our work presented the novel GPX4 degrader of R8 by HyT strategy, and provided a promising pathway of degradation agents for the treatment of ferroptosis relevant diseases.

An Anisotropic Peridynamic Model for Simulating Crack Propagation in Isotropic and Anisotropic Rocks.

In this work, we present a peridynamic-based simulation method for modeling quasi-static fracture propagation in isotropic and anisotropic rock within the framework of peridynamic least square minimization (PDLSM). The original isotropic elastic PDLSM is further extended to investigate fracture propagation in anisotropic materials in this study. The proposed AN-PDLSM model integrates an anisotropic model in fracture mechanics to analyze the failure process of anisotropic rocks. An important advancement in this research lies in the incorporation of the maximum energy release rate criterion (MERR) into the PDLSM framework for the first time. This enhancement enables accurately determining crack propagation and the associated crack angles. The proposed model utilizes the energy release rate calculated through the J-integral method to assess bond breakage, and it employs a mesh-independent, piecewise linear fracture model to describe crack propagation. The proposed method fully combines the merits of traditional fracture mechanics with the unique capabilities of peridynamics. To demonstrate the effectiveness of the proposed model, a simulation of fracture evolution in isotropic plates subjected to semi-circular bending tests is presented and compared with experimental results. It is shown that the proposed model accurately replicates fracture trajectories in isotropic specimens. In the context of anisotropic rock, the effect of a weak coefficient on crack morphology is discussed in order to obtain a suitable value. Additionally, the impact of bedding angles on fracture paths through our proposed model is also explored, revealing excellent agreement with experimental results. The findings in this research demonstrate that the proposed AN-PDLSM model is exceptionally proficient at capturing the intricate, oscillating crack paths observed in anisotropic rock materials.