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Abstract Continued warming trends lead to an increasing risk of exposure to extreme heatwaves, which threaten the health of urban residents, especially the ageing population. Here, we project the spatiotemporal trend of future exposure risk across 9188 global urban settlements between 2020 and 2100 under the shared socioeconomic pathway (SSP) 2-4.5 and SSP5-8.5 scenarios. Results show that urban heatwave exposure risk increases by 619% and 1740% for SSP2-4.5 and SSP5-8.5, respectively, and by 1642% to 5529% for the elderly. Notably, 69% of the elderly exposure risk comes from middle-income countries, where the increasing trend on the regional average is 1.2 times higher than that of high-income countries. There is an increasing trend towards greater concentration on large cities, especially in low- and lower-middle-income countries. In high-income countries, climate effects contribute 39% to 58% of increasing exposure for elderly individuals, whereas ageing effects play more prominent role in lower-income countries. This emphasizes the disproportionately higher heat-related burden for elderly individuals and inequitable trends in lower income countries. Understanding the vulnerable and priority regions in future heatwave exposure will inform adaptation strategies to support urban climate-resilient development.

Context Paclitaxel (PTX) leads to chemotherapy brain (chemo-brain) which is characterised by cognitive impairment. It has been reported that necroptosis is associated with cognitive impairment in some neurodegenerative diseases, but it is not clear whether it is related to the development of chemo-brain.Objective To investigate the role of necroptosis and related changes in PTX-induced cognitive impairment.Materials and methods C57bl/6n mice were randomly divided into five groups: control, vehicle, and different concentrations of PTX (6, 8, 10 mg/kg). Two additional groups received pre-treatment with Gdcl3 or PBS through Intracerebroventricular (ICV) injection before PTX-treatment. Cognitive function, necroptosis, synaptic plasticity and microglia polarisation were analysed.Results PTX (10 mg/kg) induced significant cognitive impairment, accompanied by changes in synaptic plasticity, including decreased density of PSD95 (0.65-fold), BDNF (0.44-fold) and dendritic spines (0.57-fold). PTX induced necroptosis of 53.41% (RIP3) and 61.91% (MLKL) in hippocampal neurons, with high expression of RIP3 (1.58-fold) compared with the control group. MLKL (1.87-fold) exhibited the same trend, reaching a peak on the 14th day. The increased expression of iNOS (1.63-fold) and inflammatory factors such as TNF-α (1.85-fold) and IL-β (1.89-fold) compared to the control group suggests that M1 polarisation of microglia is involved in the process of cognitive impairment. Pre-treatment with Gdcl3 effectively reduced the number of microglia (0.50-fold), inhibited the release of TNF-α (0.73-fold) and IL-β (0.56-fold), and improved cognitive impairment.Conclusion We established a stable animal model of PTX-induced cognitive impairment and explored the underlying pathophysiological mechanism. These findings can guide the future treatment of chemo-brain.

Measurement(s) population Technology Type(s) location-based big data Factor Type(s) spatial region Sample Characteristic - Environment spatial region Sample Characteristic - Location China

Abstract In this era of drastic global change, the Anthropocene, carbon neutrality and sustainable development have become common twenty-first century human challenges and goals. Large-scale urbanization is indicative of human activities and provides an important impetus for environmental changes; therefore, cities have become an important stage in which to promote a more sustainable future development of human society. However, current researchers study urbanization issues based on the perspectives and tools of their respective disciplines; therefore, a holistic and comprehensive understanding of urbanization is lacking due to the insufficient integration of multidisciplinary study perspectives. We explored the construction of interdisciplinary computable sustainable urbanization and introduces a conceptual framework for interdisciplinary urbanization, as scientific computing supports and integrates the natural sciences and humanities to simulate urban evolution and further observe, explain, and optimize human and environment interactions in urban areas. We advocated for the establishment of major international research programs and organizations in the field of sustainable urbanization, and the cultivation of talented young professionals with broad-ranging interdisciplinary interests. Expectantly, we hope a livable planet in the Anthropocene era could be created by developing sustainable urbanization and achieving carbon neutrality.

Metal–N–C single‐atom catalysts, mostly prepared from pyrolysis of metal‐organic precursors, are widely used in heterogeneous electrocatalysis. Since metal sites with diverse local structures coexist in this type of material and it is challenging to characterize the local structure, a reliable structure–property relationship is difficult to establish. Conjugated macrocyclic complexes adsorbed on carbon support are well‐defined models to mimic the single‐atom catalysts. Metal–N4 site with four electroneutral pyridine‐type ligands embedded in a graphene layer is the most commonly proposed structure of the active site of single‐atom catalysts, but its molecular counterpart has not been reported. In this work, we synthesized the conjugated macrocyclic complexes with a metal center (Co, Fe, or Ni) coordinated with four electroneutral pyridinic ligands as model catalysts for CO2 electroreduction. For comparison, the complexes with anionic quadri‐pyridine macrocyclic ligand were also prepared. The Co complex with the electroneutral ligand expressed a turnover frequency of CO formation more than an order of magnitude higher than that of the Co complex with the anionic ligand. Constrained ab initio molecular dynamics simulations based on the well‐defined structures of the model catalysts indicate that the Co complex with the electroneutral ligand possesses a stronger ability to mediate electron transfer from carbon to CO2. [ABSTRACT FROM AUTHOR]

Objective: Network pharmacology was utilized to explore the mechanism of Guanxinning (GXN) tablet for the treatment of stable coronary artery disease (SCAD). Materials and Methods: First, active ingredients and therapeutic targets were predicted by databases and gene chip. Then, we constructed the compound-target (C-T) network and target-disease (T-D) network to screen hub compounds and therapeutic targets based on contribution index (CI), degree, closeness, betweenness, and coreness in the networks. Enrichment analysis was performed on hub therapeutic targets, and finally, the verification of hub ingredients and hub therapeutic targets was performed through molecular docking. Results: With “oral bioavailability ≥30%, druglikeness ≥0.18, and half-life ≥4 h” as screening conditions, 58 active ingredients were obtained. Seven hundred and seventeen compound targets and 636 SCAD targets were retrieved using databases and gene chip, and the intersection of both (139 targets) was defined as therapeutic targets. According to CI, degree, betweenness, closeness, and coreness, 2 hub compounds and 13 hub therapeutic targets were chosen from the C-T network and T-D network, respectively. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that GXN treated SCAD from several aspects including inflammatory reaction, oxidative stress, nutritional metabolism, blood pressure regulation, ventricular remodeling, vascular smooth muscle proliferation, angiogenesis, and platelet aggregation. Tissue enrichment analysis revealed that the therapeutic targets were enriched in multiple organs and tissues. The excellent binding force between the hub compounds and hub therapeutic targets was verified by molecular docking. Conclusions: The treatment of SCAD by GXN has the characteristics of multiple ingredients, multiple targets, and multiple approaches. Consequently, it may theoretically treat SCAD from multiple angles and levels.