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Aluminum speciation identification reveals water interactions in silicoaluminophosphate zeolites
Water plays a crucial role in material development. As it is ubiquitous throughout zeolite generation and application, host–guest interaction between zeolite and water attracts broad interest, but mechanistic understanding remains fragmented. Here, advanced solid-state NMR techniques (2D 17 O SPAM-MQ, 27 Al{ 31 P} J -HMQC, 27 Al{ 29 Si} REDOR, and 1 H TQ-SQ NMR) combined with isotopic tracing and theoretical calculations determine water-induced octahedrally coordinated aluminum in silicoaluminophosphate molecular sieves (SAPOs) as an exclusive product of Al(OP) 4 units coordinated with two water molecules—a structure distinct from that in aluminosilicates. Based on the knowledge of aluminum speciation, we elucidate four water interaction mechanisms in SAPOs, including Brønsted-acid interaction, coordination, reversible/irreversible hydrolysis, and capillary condensation. Contrary to conventional wisdom attributing SAPO degradation to Al-O-P hydrolysis, we clarify that desilication dominates structural collapse, establishing Si environments as catalyst durability descriptors. These mechanistic insights decipher the nature of SAPO interacting with water and its fundamental differences from aluminosilicate zeolite.
Fate mapping of peripherally-derived macrophages after traumatic brain injury in mice reveals a long-lasting population with a distinct transcriptomic signature
Abstract Traumatic brain injury (TBI) is an environmental risk factor for dementia and long-term neurological deficits, posing a significant public health challenge. TBI-induced neuroinflammation involves both brain-resident microglia and peripheral monocyte-derived macrophages (MDMs). Previous research has shown that MDMs contribute to the development of long-term memory deficits, yet their long-term behavior following brain infiltration remains unclear. To address this, our study uses two complementary fate-mapping mouse lines, CCR2-creERT2 and Ms4a3-cre, for precise and lasting tracking of MDMs in vivo. Here we show that MDMs persist in the brain for at least 8 months post-TBI in both male and female mice. MDMs retain phagocytic activity for at least 30 days post-TBI, remain transcriptionally distinct from microglia, and display a gene expression profile associated with aging and disease. Moreover, we identify a core transcriptomic signature of MDMs shared across various mouse models and brain perturbations, which is also enriched in the brain myeloid cells of male subjects with TBI and Alzheimer’s disease patients. These findings enhance our understanding of MDMs' dynamics after TBI and inform future targeted myeloid-based therapies.
Two-Week Atrial Fibrillation Burden and Incident Heart Failure Among Older Individuals in the ARIC Study
Correction for Hoffmann et al., Cancer cells suppress NK cell activity by actin-driven polarization of inhibitory ligands to the immunological synapse
Scale-up of complex molecular reaction system by hybrid mechanistic modeling and deep transfer learning
Response by Boström and Yao to Letter Regarding Article, “Arterial-Lymphatic-Like Endothelial Cells Appear in Hereditary Hemorrhagic Telangiectasia 2 and Contribute to Vascular Leakage and Arteriovenous Malformations”
Uncovering cargo clients and accessory factors of AP-1 and AP-4 through vesicle proteomics
The trans -Golgi network (TGN) is a crucial sorting station in the secretory pathway, where adaptor protein (AP) complexes ensure selective cargo packaging into transport vesicles. However, the complete repertoire of cargoes and regulators associated with individual AP complexes remains poorly defined. Intriguingly, AP-4-mediated TGN export operates independently of clathrin, suggesting the involvement of uncharacterized accessory factors in vesicle biogenesis. To address these gaps, we developed an in vitro vesicle formation assay using wild-type HeLa cells or cells deficient in AP1γ1 or AP4ε, reconstituting their roles in packaging their known clients, Vangl2 and ATG9A, respectively. Coupling this assay with label-free quantitative mass spectrometry, we mapped distinct cargo profiles for AP-1 (which buds from the TGN and ARF1-positive endosomes) and AP-4, identifying the 45 kDa calcium-binding protein (CAB45) as an AP-1-dependent cargo and the Type-1 angiotensin II receptor-associated protein (ATRAP) as an AP-4-dependent cargo. Additionally, we uncovered PRRC1 and WDR44 as cytosolic regulators essential for AP-4-mediated TGN export. Our study advances the mechanistic understanding of AP-1 and AP-4 in secretory trafficking and provides a robust strategy to systematically identify cargo clients and accessory factors for specific adaptor complexes.
The dependence of children’s generalization on episodic memory varies with age and level of abstraction
Abstract Generalization extends learning from specific to new examples, whereas episodic memory preserves specific instances. Some models suggest generalization occurs by retrieving individual but related episodes, a pattern found in young adults. Children’s generalization of characteristics of individual people may rely instead on semantics. Here, we study generalizations across multiple levels of abstraction and characterize their contingency on episodic memory. Children (3-8 years, N = 121) watch animals find homes in different places. These events contain patterns of regularities linking different hierarchical levels of places and animal species. We assess children’s inferences about unstudied animal-place associations at various abstraction levels and memory precision for individual episodes. We find that lower-level generalization depends on memory of specific episodes, and the degree of dependence increases with age. In contrast, higher-level generalization is not statistically associated with episodic memory. This work shows that the contingency of generalization on memory specificity depends on age and level of abstraction.
Response by Zweck and Møller to Letter Regarding Article, “Microaxial Flow Pump Use and Renal Outcomes in Infarct-Related Cardiogenic Shock: A Secondary Analysis of the DanGer Shock Trial”
Correction for Gilboa et al., Measurement of α-synuclein as protein cargo in plasma extracellular vesicles
Nonlocality-enabled photonic analogies of parallel spaces, wormholes and multiple realities
Incorporating Management of Clonal Hematopoiesis of Indeterminate Potential Into Cardiovascular Practice
Correction for Zhao et al., Blood–labyrinth barrier damage mediated by granzymes from cytotoxic lymphocytes results in hearing loss in systemic lupus erythematosus
HCS-3DX, a next-generation AI-driven automated 3D-oid high-content screening system
Self-Reported Race as a Determinant of Differential Methylation in Peripheral Artery Disease
Ultrasmall inorganic nanoparticles repair damaged meningeal lymphatic vessels to boost Parkinson’s disease therapy
Meningeal lymphatic vessels (MLVs) have been identified to associate with various neurological diseases, such as traumatic brain injury (TBI), Alzheimer’s disease (AD), Parkinson’s disease, multiple sclerosis, and brain tumors. Damage to MLVs can exacerbate the pathological progression of these diseases and significantly impede therapeutic efficacy. Therefore, targeted repair of the damaged MLVs has emerged as an innovative strategy for treating these central nervous system (CNS) diseases. In this study, we find that inorganic Cu 2− x Se nanoparticles, rather than conventional endogenous vascular endothelial growth factor-C (VEGF-C), can repair the damaged MLVs to restore their structure and functions. These nanoparticles not only promote the growth and development of lymphatic vessels but also enhance the drainage capacity of impaired MLVs, thereby facilitating the transport of immune cells and macromolecules through these vessels. Unlike the conventional repair of damaged MLVs, this is an instance where inorganic nanoparticles have been explored to stimulate the expression of VEGF-C and its receptor VEGFR3, thereby promoting the structural and functional recovery of these vessels. The enhanced drainage function of MLVs mediated by Cu 2− x Se nanoparticles significantly alleviates the symptoms of pre-formed fibrils (PFFs)-induced Parkinson’s disease in mice. Collectively, our findings demonstrate that inorganic nanoparticles can promote the growth and development of meningeal lymphatics like VEGF-C, providing a cost-effective and innovative strategy for repairing damaged MLVs to boost the therapeutic efficacy of CNS diseases.
High-strength, multi-mode processable bamboo molecular bioplastic enabled by solvent-shaping regulation
Cannabis Use Linked to Substantial Heart Risks
Climate change intensifies plant–pollinator mismatch and increases secondary extinction risk for plants in northern latitudes
Climate change is altering the timing of species’ life-cycle events (i.e., phenology), but the rates of phenological shifts vary across taxa. These mismatches in phenological response may disrupt interactions between interdependent species, such as plants and their pollinators, which may lead to reduced plant reproduction via pollen limitation and thus contribute to secondary extinction risks for plants. However, secondary extinction risk is rarely assessed under future climate-change scenarios. Here, we used ca. 15,000 crowdsourced specimen records of Viola species and their solitary bee pollinators, spanning 120 y across the eastern United States, and integrated climate data, phenological information, and species distribution models to quantify the risk of secondary plant extinction associated with phenological mismatch with their bee pollinators. We further examined geographical patterns in secondary extinction risk for plants and explored how their interactions between plants and generalist versus specialist pollinators influence such risk. Secondary local extinction risk of Viola spp. increases with latitude, indicating that future climate change will pose a greater threat to plant–bee pollinator networks at northern latitudes. Additionally, the sensitivity of secondary local extinction risk to phenological mismatch with both generalist and specialist bee pollinators varies by latitude, with specialist bees showing a sharper decline at higher latitudes. Our findings demonstrate that existing conservation priorities based solely on primary extinction risk directly caused by climate change may be insufficient to support self-sustaining populations of plants. Thus, incorporating secondary extinction risk resulting from ecological mismatches between plants and pollinators into future global conservation frameworks should be carefully considered.
A histomorphological atlas of resected mesothelioma discovered by self-supervised learning from 3446 whole-slide images
Abstract Mesothelioma is a highly lethal and poorly biologically understood disease which presents diagnostic challenges due to its morphological complexity. This study uses self-supervised AI (Artificial Intelligence) to map the histomorphological landscape of the disease. The resulting atlas consists of recurrent patterns identified from 3446 Hematoxylin and Eosin (H&E) stained images scanned from resected tumour slides. These patterns generate highly interpretable predictions, achieving state-of-the-art performance with 0.65 concordance index (c-index) for outcomes and 88% AUC in subtyping. Their clinical relevance is endorsed by comprehensive human pathological assessment. Furthermore, we characterise the molecular underpinnings of these diverse, meaningful, predictive patterns. Our approach both improves diagnosis and deepens our understanding of mesothelioma biology, highlighting the power of this self-learning method in clinical applications and scientific discovery.