Abstract As water scarcity escalates globally, there is a growing focus on assessing its economic impact, both locally and through trade networks, defined as water scarcity risk (WSR). Given China's ...pivotal role as a top importer and exporter, coupled with significant spatial disparities in water scarcity across its provinces, understanding the spread of water scarcity risks within China and their interplay with global water dynamics is imperative yet relatively unexplored. This study constructs a nested Multi‐Regional Input‐Output (MRIO) model to evaluate water scarcity risk, connecting Chinese provinces with global counterparts. Notably, we integrate the spatial heterogeneity of environmental flow requirement as a vital criterion for long‐term sustainable water management in our assessment. Our findings reveal substantial economic impacts caused by water scarcity, with a global WSR valued at $11.1 trillion, of which $6.2 trillion is attributed to trade. Critical regions, sectors, and region‐sectors are identified, offering valuable insights for targeted interventions. This study presents a unique perspective on global water scarcity risk assessment at a higher resolution scale, laying the groundwork for the formulation of effective water scarcity risk mitigation strategies aligned with sustainable development goals, particularly SDG 6 and 8.
Spindle and kinetochore‑associated complex subunit 3 (SKA3) has recently been considered a key regulator of carcinogenesis. However, the connection between SKA3 and immune cell infiltration remains ...unknown.
The current study investigated the expression mode, prognostic effect, and functional role of SKA3 in different tumors, particularly bladder cancer using numerous databases, comprising TIMER, GEPIA, HPA, UALCAN, PrognoScan, and Kaplan-Meier Plotter. Differentially expressed gene and enrichment analyses were implemented on SKA3 using R packages "edgR" and "clusterProfiler". Immunohistochemistry was further used to validate the expression of SKA3 gene in bladder cancer. Following that, the relevance of SKA3 expression to immune infiltration level in bladder cancer was evaluated using TIMER.
Overall, the level of SKA3 expression in tumor tissue significantly increased than in normal tissue. In bladder cancer and other tumors, patients with high SKA3 expression levels had worse overall survival (OS) (p = 0.016), disease-specific survival (DSS) (p = 0.00004), and disease-free survival (DFS) (p = 0.032). Additionally, the major molecular functions for SKA3 included nuclear division, mitotic nuclear division, mitotic sister chromatid segregation, humoral immune response, and cell chemotaxis. Additionally, SKA3 expression was found to be positively associated with enhanced M2 macrophage and T helper (Th) 2 cell infiltration in bladder cancer.
Our study implies that SKA3 contributes to M2 macrophage and Th2 cell polarization by acting as an oncogene in bladder cancer. SKA3 might be a novel biomarker for evaluating prognosis and immune infiltration in bladder cancer.
Dysregulation of polyamine homeostasis strongly associates with human diseases. ATP13A2, which is mutated in juvenile-onset Parkinson's disease and autosomal recessive spastic paraplegia 78, is a ...transporter with a critical role in balancing the polyamine concentration between the lysosome and the cytosol. Here, to better understand human ATP13A2-mediated polyamine transport, we use single-particle cryo-electron microscopy to solve high-resolution structures of human ATP13A2 in six intermediate states, including the putative E2 structure for the P5 subfamily of the P-type ATPases. These structures comprise a nearly complete conformational cycle spanning the polyamine transport process and capture multiple substrate binding sites distributed along the transmembrane regions, suggesting a potential polyamine transport pathway. Integration of high-resolution structures, biochemical assays, and molecular dynamics simulations allows us to obtain a better understanding of the structural basis of how hATP13A2 transports polyamines, providing a mechanistic framework for ATP13A2-related diseases.
The COVID-19 pandemic has posed severe threats to global sustainable development. However, a comprehensive quantitative assessment of the impacts of COVID-19 on Sustainable Development Goals (SDGs) ...is still lacking. This research quantified the post-COVID-19 SDG progress from 2020 to 2024 using projected GDP growth and population and machine learning models including support vector machine, random forest, and extreme gradient boosting. The results show that the overall SDG performance declined by 7.7% in 2020 at the global scale, with 12 socioeconomic SDG performance decreasing by 3.0%–22.3% and 4 environmental SDG performance increasing by 1.6%–9.2%. By 2024, the progress of 12 SDGs will lag behind for one to eight years compared to their pre-COVID-19 trajectories, while extra time will be gained for 4 environment-related SDGs. Furthermore, the pandemic will cause more impacts on countries in emerging markets and developing economies than those on advanced economies, and the latter will recover more quickly to be closer to their pre-COVID-19 trajectories by 2024. Post-COVID-19 economic recovery should emphasize in areas that can help decouple economic growth from negative environmental impacts. The results can help government and non-state stakeholders identify critical areas for targeted policy to resume and speed up the progress to achieve SDGs by 2030.
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Abstract
Hundreds of indicators are available to monitor progress of countries and regions towards the Sustainable Development Goals (SDGs). However, the sheer number of indicators poses ...unprecedented challenges for data collection and compilation. Here we identify a subset of SDG indicators (principal indicators) that are relatively easy to collect data for and also are representative for all the indicators by considering the complex interrelationship among them. We find 147 principal indicators that can represent at least 90% of the annual variances of 351 SDG indicators in the past (2000–2017) and are expected to do so for the future (2018–2030) with the lowest difficulty of data collection. Our results can guide future investment in building the data infrastructure for SDG monitoring to give priorities to these principal indicators for global comparison.
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•A novel tetracyclic aromatic lactam unit was firstly developed and used as π bridge for isomeric small-molecule donors.•Tetracyclic aromatic lactam-substituted tin-free donors ...(oPh2F, pPh2F) exhibited a broad bandgap and stong crystallinity.•oPh2F/pPh2F could regulate the crystallization kinetics and vertical phase separation of host system PM6:Y6.•Ternary devices PM6:pPh2F:Y6 achieved champion PCE of 18.4% with a synergistically improved all photovoltaic parameters.
Organic solar cells (OSCs) are rapidly developed for next-generation photovoltaic technologies due to low-cost and solution-processability etc. However, so far high-efficiency organic photovoltaic materials are typically prepared by multi-step Stille reactions, which are neither cost-efficient nor atom-economic, even raise safety concerns and incompatible with large-scale process. Large-scale industrial production of photovoltaic materials through simple, cost-effective, and green chemistry remains to be addressed. In this work, we present a case where two isomeric small-molecule donors based on polycyclic aromatic lactams (PAL) unit, named oPh2F and pPh2F with wide-bandgap and high-crystallinity, were designed and synthesized by atom-economic direct C-H activation strategy, modulates pre-aggregation and crystallization kinetics of host system PM6:Y6, induce distinct morphology evolution and effectively boost photovoltaic performance. The best power conversion efficiency (PCE) of 18.40 % for pPh2F-based ternary devices are found to be a fruit of improved light-harvesting ability, favorable vertical phase separation with enhanced crystallinity, the separated crystallization process of host materials and the higher and more balanced charge transport. To our knowledge, this study achieved the highest PCE among PM6:Y6-based ternary OSCs containing tin-free small-molecule donor, which not only highlights the great potential of PAL-based photovoltaic materials, but also promotes the integration of renewable energy with green chemistry.
Human multidrug resistance protein 4 (hMRP4, also known as ABCC4), with a representative topology of the MRP subfamily, translocates various substrates across the membrane and contributes to the ...development of multidrug resistance. However, the underlying transport mechanism of hMRP4 remains unclear due to a lack of high-resolution structures. Here, we use cryogenic electron microscopy (cryo-EM) to resolve its near-atomic structures in the apo inward-open and the ATP-bound outward-open states. We also capture the PGE1 substrate-bound structure and, importantly, the inhibitor-bound structure of hMRP4 in complex with sulindac, revealing that substrate and inhibitor compete for the same hydrophobic binding pocket although with different binding modes. Moreover, our cryo-EM structures, together with molecular dynamics simulations and biochemical assay, shed light on the structural basis of the substrate transport and inhibition mechanism, with implications for the development of hMRP4-targeted drugs.
The Mu Us Sandy Land is a key region of man-made desert control and farmland to forest (grass) return in China. Despite global change and the strong influence of human activities, the vegetation in ...this region has been significantly improved and restored. In this study, multisource remote sensing data and multiple indicators were used to quantitatively monitor and evaluate the vegetation restoration status in this area. The driving factors were also analysed. The results show that in the past 20 years, nearly the entire Mu Us Sandy Land significantly and substantively recovered. The regional fractional vegetation cover increased, with an average annual growth rate of 0.59% and obvious spatial heterogeneity. The nine most important driving factors could comprehensively account for 58.38% of the spatial distribution of the vegetation coverage. Factors such as land use and land cover, the aridity index, and gross domestic product had the most significant impact, followed by precipitation and temperature. The results confirmed that the vegetation was restored and improved in the Mu Us Sandy Land and determined the main driving factors, which is helpful for vegetation restoration and ecological improvement on sandy land similar to the Mu Us Sandy Land.
Paraneoplastic pemphigus (PNP) is an autoimmune bullous disease associated with underlying neoplasms and characterized by antibodies against desmoglein 3 (Dsg 3) and plakins. Autoantibodies against ...desmoglein 3 in sera of patients with PNP have been proven to cause acantholysis
in vivo
in neonatal mice. As a member of the plakin family, autoantibodies against desmoplakin were detected frequently by immunoprecipitation in the sera of PNP. The recombinant C-terminus of desmoplakin was expressed and purified to adsorb the specific autoantibodies against the C-terminus of desmoplakin.
In vitro
dispase-dependent keratinocyte dissociation assay and
in vivo
IgG passive transfer into neonatal mice assay were performed, followed by the electronic microscopy examination and TUNEL assay. We found that anti-C terminus of desmoplakin autoantibodies caused blisters and acantholysis in mice skin at a dose-dependent manner. Moreover, dissociated fragments were observed after incubation with the purified IgG against desmoplakin, compared with normal human IgG (
P
-value =0.0207). The electronic microscopy examination showed the disconnection of keratin intermediate filaments from desmosomes. Lastly, apoptosis of keratinocytes in the TUNEL assay was all detected in the skins of neonatal mice after injection of the anti-C terminus of desmoplakin autoantibodies. Taken together, the study suggests that autoantibodies against the C-terminus of desmoplakin might be pathogenic in PNP.
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