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Excitotoxicity is classically attributed to Ca influx through NMDA receptors (NMDAr), leading to production of nitric oxide by neuronal nitric oxide synthase and superoxide by mitochondria, which react to form highly cytotoxic peroxynitrite. More recent observations warrant revision of the classic view and help to explain some otherwise puzzling aspects of excitotoxic cell injury. Studies using pharmacological and genetic approaches show that superoxide produced by NMDAr activation originates primarily from NADPH oxidase rather than from mitochondria. As NADPH oxidase is localized to the plasma membrane, this also provides an explanation for the extracellular release of superoxide and cell-to-cell \"spread\" of excitotoxic injury observed and . The signaling pathway linking NMDAr to NADPH oxidase involves Ca influx, phosphoinositol-3-kinase, and protein kinase Cζ, and interventions at any of these steps can prevent superoxide production and excitotoxic injury. Ca influx specifically through NMDAr is normally required to induce excitotoxicity, through a mechanism presumed to involve privileged Ca access to local signaling domains. However, experiments using selective blockade of the NMDAr ion channel and artificial reconstitution of Ca by other routes indicate that the special effects of NMDAr activation are attributable instead to concurrent non-ionotropic NMDAr signaling by agonist binding to NMDAr. The non-ionotropic signaling driving NADPH oxidase activation is mediated in part by phosphoinositol-3-kinase binding to the C-terminal domain of GluN2B receptor subunits. These more recently identified aspects of excitotoxicity expand our appreciation of the complexity of excitotoxic processes and suggest novel approaches for limiting neuronal injury.

Linear transportation infrastructure significantly contributes to biodiversity loss and habitat fragmentation. This study evaluates the impact of the G331 tourist highway on wildlife in the Changbai Mountain region using an integrated multi-model framework. The InVEST 3.14.1 model assessed the habitat quality, while MaxENT v3.4.4 identified the habitat’s suitability for mammals, birds, and amphibians. Ecological source areas were derived by overlaying high-suitability and high-quality zones. A comprehensive resistance surface was constructed, and the Linkage Mapper toolbox identified potential ecological corridors, pinch points, and barrier points. Results reveal significant spatial conflicts between the highway and wildlife networks, with 16 ecological conflict points identified. The “common key area” that is critical for all three species groups covers only 1.2% of the total key area but holds the highest conservation value. This integrated framework not only diagnoses ecological impacts but also generates a prioritized spatial decision-support tool for conservation planning, demonstrating a replicable approach for assessing linear infrastructure in similar ecologically sensitive regions.

Three-dimensional (3D) bioprinting is an emerging technology that is widely used in regenerative medicine. With the continuous development of the technology, it has attracted great attention and demonstrated promising prospects in ophthalmologic applications. In this paper, we review the three main types of 3D bioprinting technologies: Vat polymerizationbased bioprinting, extrusion-based bioprinting, and jetting-based bioprinting. We also present in this review the analysis of the usage of both natural and synthesized hydrogels as well as the types of cells adopted for bioinks. Cornea and retina are the two main types of ocular tissues developed in bioprinting, while other device and implants were also developed for the ocular disease treatment. We also summarize the advantages and limitations as well as the future prospects of the current bioprinting technologies based on systematic reviews.

NMDA receptors (NMDARs) are crucial for excitatory synaptic transmission and synaptic plasticity. The number and subunit composition of synaptic NMDARs are tightly controlled by neuronal activity and sensory experience, but the molecular mechanism mediating NMDAR trafficking remains poorly understood. Here, we report that RIM1, with a well-established role in presynaptic vesicle release, also localizes postsynaptically in the mouse hippocampus. Postsynaptic RIM1 in hippocampal CA1 region is required for basal NMDAR-, but not AMPA receptor (AMPAR)-, mediated synaptic responses, and contributes to synaptic plasticity and hippocampus-dependent memory. Moreover, RIM1 levels in hippocampal neurons influence both the constitutive and regulated NMDAR trafficking, without affecting constitutive AMPAR trafficking. We further demonstrate that RIM1 binds to Rab11 via its N terminus, and knockdown of RIM1 impairs membrane insertion of Rab11-positive recycling endosomes containing NMDARs. Together, these results identify a RIM1-dependent mechanism critical for modulating synaptic function by facilitating membrane delivery of recycling NMDARs. Rab3-interacting molecules (RIMs) are a key component of the presynaptic active zone that regulate neurotransmitter release. Here, the authors show that RIM1 also has postsynaptic function to organize NMDA receptors and synaptic response.

Stressful life events are important risk factors in the development of adolescent depression. Executive function is significant in the stress–depression link. However, it is not clear whether there is a specific effect for subcomponents of executive function (working memory, inhibition, and shifting). Therefore, the present study recruited 213 adolescents (mean age (Mage) = 15.19 years, SD = 1.27, range = 12.00–18.00 years, and 53.00% girls) and measured their perceived stress using the questionnaire of the Adolescent Self-Rating Life Events Checklist, working memory ability by two-back tasks, inhibition ability by Stroop tasks, and shifting ability by Wisconsin Card-Sorting tasks. Results showed that stressful life events positively correlated with adolescents’ depression, while stressful life events negatively linked with working memory and inhibition. Depression was negatively associated with working memory and inhibition. No significant correlation was found between shifting and either stressful life events or depression. Mediation analyses revealed that working memory and inhibition mediated the link between stressful life events and adolescent depression, while shifting did not show a mediating effect. Our findings provide further evidence for the precise effect of executive function in the stress–depression link, implicating that different subcomponents should be considered to provide targeted intervention to alleviate adolescents’ depressive symptoms.

In the adult mouse hippocampus, NMDA receptors (NMDARs) of CA1 neurons play an important role in the synaptic plasticity. The location of NMDARs can determine their roles in the induction of long-term potentiation (LTP). However, the extrasynaptic NMDARs (ES-NMDARs) dependent LTP haven’t been reported. Here, through the use of a 5-Hz stimulation and MK-801 (an irreversible antagonist of NMDARs) in the CA1 neurons of adult mice hippocampal slices, synaptic NMDARs were selectively inhibited and NMDAR-mediated excitatory postsynaptic currents were not recovered. We found that a robust LTP was induced by 3-train 100-Hz stimulation when the synaptic NMDARs and extrasynaptic NR2B containing NMDARs were blocked, but not in the any of the following conditions: blocking of all NMDARs (synaptic and extrasynaptic), blocking of the synaptic NMDARs, and blocking of the synaptic NMDARs and extrasynaptic NR2A-containing NMDARs. The results indicate that this LTP is ES-NMDARs dependent, and NR2B-containing ES-NMDARs modulates the threshold of LTP induction.

Skin necrosis is the most common complication in total auricular reconstruction, which is mainly induced by vascular compromise and local stress concentration of the overlying skin. Previous studies generally emphasized the increase in the skin flap blood supply, while few reports considered the mechanical factors. However, skin injury is inevitable due to uneasily altered loads generated by the intraoperative continuous negative suction and uneven cartilage framework structure. Herein, this study aims to attain the stable design protocol of the ear cartilage framework to decrease mechanical damage and the incidence of skin necrosis. Finite element analysis was initially utilized to simulate the reconstructive process while the shape optimization technique was then adopted to optimize the three-pretested shape of the hollows inside the scapha and fossa triangularis under negative suction pressure. Finally, the optimal results would be output automatically to meet clinical requirement. Guided by the results of FE-based shape optimization, the optimum framework with the smallest holes inside the scapha and fossa triangularis was derived. Subsequent finite element analysis results also demonstrated the displacement and stress of the post-optimized model were declined 64.9 and 40.1%, respectively. The following clinical study was performed to reveal that this new design reported lower rates of skin necrosis decrease to 5.08%, as well as the cartilage disclosure decreased sharply from 14.2 to 3.39% compared to the conventional method. Both the biomechanical analysis and the clinical study confirmed that the novel design framework could effectively reduce the rates of skin necrosis, which shows important clinical significance for protecting against skin necrosis.

Large projected increases in forest disturbance pose a major threat to future wood fiber supply and carbon sequestration in the cold-limited, Canadian boreal forest ecosystem. Given the large sensitivity of tree growth to temperature, warming-induced increases in forest productivity have the potential to reduce these threats, but research efforts to date have yielded contradictory results attributed to limited data availability, methodological biases, and regional variability in forest dynamics. Here, we apply a machine learning algorithm to an unprecedented network of over 1 million tree growth records (1958 to 2018) from 20,089 permanent sample plots distributed across both Canada and the United States, spanning a 16.5 °C climatic gradient. Fitted models were then used to project the near-term (2050 s time period) growth of the six most abundant tree species in the Canadian boreal forest. Our results reveal a large, positive effect of increasing thermal energy on tree growth for most of the target species, leading to 20.5 to 22.7% projected gains in growth with climate change under RCP 4.5 and 8.5. The magnitude of these gains, which peak in the colder and wetter regions of the boreal forest, suggests that warming-induced growth increases should no longer be considered marginal but may in fact significantly offset some of the negative impacts of projected increases in drought and wildfire on wood supply and carbon sequestration and have major implications on ecological forecasts and the global economy.

Carbon and pollution reduction are highly synergistic elements of green development, and the detailed derivation of the synergistic relationship is urgently needed. Based on the research perspective of coupling coordination, this paper firstly bases on the research perspective of coupling synergy, takes 30 provinces in China as the research object from 2011 to 2022, and constructs a coupling coordination degree model to measure the synergistic effect of pollution reduction and carbon reduction; secondly, kernel density and Dagum coefficient are used to analyze the spatial and temporal characteristics, spatial differences and sources of differences in the synergistic effects of pollution reduction and carbon reduction in China as a whole, in the three major regions and in each province; finally, the Moran index is applied to test the spatial agglomeration characteristics of the synergistic effect of pollution reduction and carbon reduction, and the spatial panel model is applied to test its β-convergence. The study shows that (1) during the study period, the level of synergistic effect on carbon reduction in China changed from good coordination to good coordination, and the synergistic effect in the western region was significantly better than that in the eastern and central regions; (2) the synergistic effect of pollution reduction and carbon reduction in China as a whole and the three regions showed obvious spatial differences, but the differences were gradually narrowing, and the supervariable density was the dominant factor of the overall differences; (3) as a whole, the synergistic effect of pollution reduction and carbon reduction among provinces has a spatial agglomeration effect, and the level of synergistic effect of pollution reduction and carbon reduction across the country and east and west regions has a significant absolute β convergence trend, while there is a significant conditional β convergence trend across the country and the three major regions, and the eastern and central regions with a low synergy level have a higher convergence rate, indicating that as time goes by, under the influence of various factors, the synergistic effect will converge to the steady state level. The purpose of this paper is to analyze the spatial patterns and regional differences in the synergistic effects of pollution reduction and carbon reduction in Chinese provinces and also to provide a quantitative basis for the full implementation of the synergistic regulation of pollution reduction and carbon reduction.

The geography of film is an interdisciplinary field of geography and communication. Understanding the spatial and temporal characteristics of the global box office scale represented by the G20 is important for expanding the research scope of film geography focusing on “space” and promoting the development of film industries around the world. This paper studies the spatial and temporal characteristics and influencing factors of G20 box office revenues 2003–2019 using the Theil coefficient, spatial analysis, and a panel vector auto-regressive model. According to the research: (1) the distribution of the top box office revenues within the G20 is obvious; the scale differences among these countries are gradually decreasing and the scale differences between China and the United States are the most significant; (2) the box office differences of the G20 are gradually decreasing; the Asian movie market represented by China and South Korea is developing rapidly; (3) from the perspective of the transfer of movie box office scale types within a Markov Chain, the number of countries in type II and III is the largest and the transfer among different types is mainly to high-level types; and (4) the factors influencing the box office of G20 movies are the number of screens, per capita gross national income, the working-age population, and GDP, respectively.