Browse Articles

STING balances encephalopathy and neuroinflammation to polyomavirus infection 2260096

Abstract Introduction Type I interferons (IFN-Is) modulate the differentiation and recruitment of T cells. JC polyomavirus causes the often-fatal brain demyelinating disease, PML. Polyomavirus infection activates STING to produce IFN-Is in vitro, but STING’s effects in vivo on T cell expansion, entry, and function in the CNS are unknown. Methods Using mouse polyomavirus (MuPyV) CNS infection and STING-KO mice, we hypothesize that STING enhances MuPyV control and recruitment of functional T cells to the brain. Results Although MuPyV genome copies are equivalent, STING-KO mice developed severe ventriculomegaly and 40% lethality at day 60 post-infection. Virus-specific CD8+ and CD4+ T cells in STING-KO mice exhibit higher PD-1 levels and produce less IFN-γ after direct ex vivo virus peptide stimulation. To determine whether this effect is T cell—intrinsic or -extrinsic, we adoptively transferred wild-type CD45.1+ virus-specific CD8+ T cells into CD45.2+ wild-type or STING-KO mice. CD45.1+ donor T-cells upregulated PD-1 in STING-KO brains despite equivalent IFN-γ production after peptide stimulation, suggesting STING is acting extrinsic to T cells. T cell numbers in the brain during acute and persistent infection were similar in WT and STING-KO mice. Conclusion These findings suggest that STING is dispensable in controlling MuPyV levels or in recruiting T cells but is involved in mitigating neuroinflammation. Ongoing work aims to examine STING’s involvement in MuPyV-induced neuropathology and neuroinflammation. Funding Source F31 NINDS Topic Categories Neuroimmunology (NEUR)

Analysis of infection status and infection risk factors of caregivers of COVID-19 patients 2303403

Abstract Introduction Omicron infection often occurs in a family cluster, therefore, infection among caregivers of patients with COVID-19 is an important health concern. To explore the spread and risk factors of infection among caregivers of patients with COVID-19 and provide a theoretical basis for the scientific prevention and control of susceptible infections. Methods We recruited 66 caregivers of patients with COVID-19 who were admitted to the medicine department of Jilin Provincial Hospital of Hepatobiliary Diseases supported by the First Hospital of Jilin University. We analyzed the impact of age, sex, vaccination history, positive conversion time, and some basic disease on the occurrence of infection among caregivers. Results At one week after discharge of the admitted COVID-19 patients, 54 of the enrolled caregivers (including 22 males and 32 females) turned positive, while the remaining 12 did not. Among the patients with positive conversion, 79.63% had underlying diseases, 83.33% had positive conversion within 3 days after admission, and 46.30% had received the last vaccination more than 200 days. The positive conversion time, was significantly longer in women than in men. Additionally, the positive conversion time in those with underlying disease was longer than in those without. Conclusion An understanding of the prevalence and risk factors for secondary infection among caregivers of COVID-19 patients would be useful in developing strategies for the prevention of infection in the of COVID-19-susceptible population and help improve the monitoring of various susceptible factors. Funding Source n/a Topic Categories Translational and Interventional Immunology (TI)

Immune responsiveness influences Staphylococcus aureus persistence via citrate metabolic flux during prosthetic joint infection 2257191

Abstract Introduction Prosthetic joint infection (PJI) is a complication following arthroplasty that occurs in 1-3% of patients, with ∼50% of cases caused by Staphylococcus aureus (S. aureus) that forms biofilm. Biofilms are difficult to eradicate due to their recalcitrance to antibiotics and immune-mediated clearance, resulting in chronic symptoms that are debilitating for PJI patients. Bacterial-derived metabolites play a central role in biofilm infection, where several tricarboxylic acid cycle (TCA) intermediates are key for biofilm development. However, little information is available regarding how leukocytes influence S. aureus TCA cycle activity and resultant adaptations by the bacteria, which can inform future therapeutic targets to promote biofilm clearance. Methods S. aureus strains lacking the TCA cycle enzymes, citrate synthase (ΔgltA), aconitase (ΔacnA), isocitrate dehydrogenase (Δicd), and a double mutant lacking citrate synthesis and transport (ΔgltA/ΔcitM) were assessed for intracellular survival in macrophages (Mϕs) and a mouse model of PJI. Results Both ΔacnA and Δicd had increased survival within Mϕs at 4 h; however, this was transient, with intracellular burdens reaching that of WT S. aureus by 24 h. The early survival advantage of α”acnA and α”icd strains was partially driven by mitochondrial reactive oxygen species (mtROS), since the mtROS inhibitor MitoTEMPO negated this phenotype. In a mouse model of PJI, bacterial burden was significantly decreased with α”gltA compared to WT at day 7 post-infection. This difference was transient, as no changes in biofilm burden were observed at day 14. However, the ΔgltA/ΔcitM strain displayed reduced bacterial burden at day 14. Conclusion Citrate synthesis is important for early biofilm infection; however, S. aureus employs compensatory mechanisms such as citrate import to overcome TCA cycle loss. Future studies will explore how leukocytes reprogram S. aureus TCA cycle activity and how S. aureus adapts to immune pressure. Funding Source UNMC Fellowship; UNMC Neuroimmunology of Disease Training Program T32 Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

Sequential interactions with distinct DC subsets direct CD4 T helper cell differentiation 2257528

Abstract Introduction Naïve CD4T cells differentiate into distinct T helper (Th) subsets depending on the type of dendritic cell (DC) presenting antigen. While different DC subsets are thought to present antigen to CD4T cells with distict spatiotemporal dynamics in lymph nodes (LNs), how these DC—T cell interactions are spatially and temporally organized and how they instruct Th differentiation remain incompletely understood. We previously showed that CD301b+ DCs, a major subset of migratory cDC2s, are strategically positioned near high endothelial venules at the T cell—B cell border in antigen-draining LNs. There, they engage incoming naïve polyclonal CD4T cells irrespective of the immunization context, facilitating efficient repertoire scanning and robust expansion of antigen-specific clones. Upon cognate interaction, CD301b+ cDC2s upregulate IL-2, which enhances IL-2 receptor signaling in CD4 cells to promote Th2 differentiation while suppressing the T follicular helper (Tfh) program. Methods To define the temporal and subset-specific contributions of DCs, we immunize mice subcutaneously with soluble OVA plus either a Th1- or Th2-polarizing adjuvant, followed by adoptive transfer of OVA-specific OT-II CD4 T cells. Results Here we show that OT-II cells undergo multiple waves of TCR activation during priming. The first wave, mediated by CD301b+ cDC2s shortly after LN entry, is characterized by ERK-dominant TCR signaling, leading to optimal IRF4 induction. The second wave, occurring at later stages, is primarily driven by cDC1s and marked by strong activation of proximal TCR signaling components. Functionally, depletion of CD301b+ DC abrogated Th2 differentiation without affecting Th1 development, whereas cDC1 depletion significantly impair Th1 differentiation. Conclusion These findings support a model in which distinct DC subsets provide non-redundant, temporally coordinated cues to antigen-specific CD4 T cells, directing Th fate specification through sequential interactions. Funding Source NIH Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)

Interfacial‐Electronegativity‐Induced Near‐Surface Tetrahedral Reconstruction Enables One‐Step Upcycling of Spent LiFePO ₄ for High‐Rate and Long‐Life Pouch Cells

ABSTRACT Direct upcycling of spent lithium iron phosphate (S‐LFP) into high‐rate cathodes is highly desirable yet remains challenging. While conventional solid‐state sintering can repair bulk lattice defects, it is intrinsically limited in reconstructing localized near‐surface tetrahedral distortions, which critically impede 1D [010] Li + diffusion under high‐rate conditions. Herein, we propose a novel electronegative‐heterointerface‐enhanced solid‐state sintering for one‐step upcycling S‐LFP into high‐rate pouch‐cell cathodes. In this approach, S‐LFP nanoparticles are in situ encapsulated by highly electronegative heterointerfaces through temperature‐controlled solid‐state sintering, which finely modulates Fe d‐band/O p‐band hybridization, engineers O 1 ─O 2 ─O 3 ─O 3 tetrahedra, and accelerates Li + near‐surface migration. Consequently, regenerated LFP exhibits record‐high rate capability (125.0 and 70.0 mA h g −1 at 5 C and 30 C, respectively) and superior cycling stability (91.2% after 400 cycles at 5 C), significantly outperforming both conventional sintering paradigms and commercial counterparts by ∼100% at high rates. Moreover, regenerated Ah‐level pouch cells retain 82.9% of their 1 C capacity at 5 C and deliver 88.0% capacity retention even after 1000 cycles, simultaneously achieving high power and energy densities that surpass those of commercial LFP (C‐LFP) and demonstrating strong practical viability by successfully powering unmanned aerial vehicles. This work elucidates the fundamental correlation between electronegative heterointerfaces and tetrahedral framework for high‐rate LFP.

A Biomimetic Single‐Atom Nanozyme With a Substrate Pocket for Accurate and Continuous Sweat Glucose Monitoring

ABSTRACT Wearable non‐invasive glucose sensors are revolutionizing diabetic management by enabling real‐time monitoring and personalized care. However, their widespread adoption has been limited by the intrinsic instability and high cost of natural glucose oxidase (GOx). Although nanozymes offer a more robust alternative, their lack of substrate specificity is a major challenge. Herein, a manganese‐based tannic acid single‐atom nanozyme (TA‐Mn SA) with a dual biomimetic architecture was developed. It features atomically dispersed Mn catalytic sites embedded within a tannic acid‐derived molecular pocket tailored for selective glucose recognition. This engineered enzyme mimic exhibits exceptional catalytic efficiency and substrate selectivity. The origin of this selectivity and the catalytic cycle were elucidated through both experimental data and density functional theory calculations. When integrated into a wearable sweat sensor, the TA‐Mn SA nanozyme reliably tracked blood glucose levels in human trials, capturing personalized metabolic dynamics during fasting, feeding, and exercise. This design is inherently compatible with scalable, low‐cost manufacturing, paving the way for a new era of accessible continuous glucose monitoring.

Oncogenic KRAS represses the dependence receptor UNC5C via ERK2-FOS signaling in non-small cell lung cancer

Cognitive neuroscience-inspired multimodal perceptual fusion framework for enhanced mixed reality environments: a deep learning approach

Development of an ultra-high-plex immunofluorescence assay to investigate the tumor-immune microenvironment on the CellScape platform with EpicIF 2309991

Abstract Introduction Spatial biology has transformed cancer immunology, but single-cell in-situ proteomic data remain challenging to acquire. To streamline spatial proteomic assay development we developed EpicIF™, a proprietary signal removal chemistry for the CellScape platform for precise spatial phenotyping (PSP). We previously demonstrated that EpicIF efficiently eliminates fluorophores between imaging cycles while preserving tissue morphology and antigenicity. Here we demonstrate how EpicIF, with key enhancements to the CellScape platform, enable ultra-high-plex PSP to study the tumor immune microenvironment (TIME). Methods To test the feasibility of an ultra-high-plex spatial assay on CellScape, we subjected tissue to 50 EpicIF signal removal cycles and then applied a small 30-plex antibody panel to image protein markers and compared their staining to known expression patterns. We then developed a 100-plex panel to profile the TIME with commercially sourced fluorophore-conjugated antibodies targeting various immune phenotypes, signaling pathways, and tissue architecture. Downstream analysis was performed to highlight spatial phenotypes within the TIME. Results Following 50 rounds of EpicIF-based signal removal we found signal reduction in only 2 out of 30 markers from our representative panel, suggesting a marginal effect on antigenicity and high likelihood of success for an ultra-high-plex assay. We then successfully applied our 100-plex panel to additional tumor tissues, enabling deep phenotyping of the TIME. Conclusion Key enhancements in imaging throughput and stability across long assays on the CellScape, along with EpicIF technology, establish a new benchmark for rapid, reliable, and ultra-high-plex spatial proteomic studies of the TIME. Funding Source N/A Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

PHGDH regulates dendritic cell immune crosstalk 2267410

Abstract Introduction Conventional dendritic cells (cDCs) play a unique role in immunoregulation and antigen presentation, which is fundamental to protective immunity and is implicated in various autoimmune pathologies. Accordingly, cDCs are targeted in autoimmune and cancer immunotherapies. However, leveraging their full therapeutic potential is limited by an incomplete mechanistic understanding of cDC functions. Methods We used transcriptomic, metabolomic, and immunophenotyping analyses on both in vivo and in vitro cDCs to investigate molecular regulators of cDC immune maturation and T cell stimulation. Results These analyses identified phosphoglycerate dehydrogenase (PHGDH) as a key modulator of cDC immune functions. Loss of PHGDH limits cDC maturation and weakens their ability to prime potent effector CD8+ T cell responses. We show that PHGDH regulates cDC function through a non-canonical mechanism involving remodeling of interactions with bystander cells, such as T cells. Conclusion Our findings identify PHGDH as a critical immunomodulator of cDCs and highlight its potential as a therapeutic target for autoimmune diseases through modulation of cDC-mediated immune crosstalk. Funding Source n/a Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)

Differentiation, programming, and (dys)functions of cytotoxic CD4 T cells in acute and chronic viral infection 2257364

Abstract Introduction Killing of virus infected cells is associated with CD8 cytotoxic T lymphocytes (CTL) and NK cells; however, CD4 T cells can also exhibit cytotoxic properties. In response to viral infections and cancers, cells downregulate MHC-I but maintain MHC-II, thereby preventing CD8-CTL killing and enabling CD4-CTL targeting. Further, CD8-CTL are functionally exhausted during chronic infections, limiting their ability to kill and providing a potential role for CD4-CTL in controlling infection. Immune activity and effector cell differentiation mediated by antigen presenting cells (APC) can also potentially be modulated by CD4-CTL targeting. We have identified cytotoxic activity as a main CD4 T cell function restored by anti-PD-L1 during chronic LCMV infection. Conversely, the role of CD4-CTL in acute infections is unclear. Methods We used two strains of Lymphocytic choriomeningitis virus (LCMV), Armstrong and Clone 13, to study the role of cytotoxic CD4 in acute and chronic viral infections in mice. Results In acute lymphocytic choriomeningitis virus (LCMV) infection, we demonstrate that CD4-CTL are restricted to the Th1 subset, are associated with the highest level of metabolic and functional activation, and have a distinct transcriptional and epigenetic profile compared to non-CTL Th1 cells. Interestingly, the initial CD4-CTL response forms the basis for maintaining long-term CD4 CTL-reactivatable memory following rechallenge. In vivo, CD4-CTL target B cells via MHC-II in a perforin-dependent manner, and we are exploring a potential role of CD4-CTL to tune B cell immunity and enable a focused immune response. Interestingly, during chronic LCMV infection, alterations in transcriptional programming restrict the induction of CD4-CTL, despite the presence of Th1 cells, underpinning a previously unrecognized quality of CD4 T cell exhaustion. Conclusion Together, my findings provide fundamental insights into the role of CD4-CTL in shaping the antiviral immune response in both acute and chronic infection. Funding Source n/a Topic Categories Viral Immunology (VIR)

CD1-Mediated Lipid Antigen Presentation Orchestrates Neuroinflammation in Alzheimer’s Disease 2259966

Abstract Introduction Neuroinflammation is a hallmark of neurodegeneration, yet its origins remain unclear in Alzheimer’s disease (AD). The brain’s lipid abundance and the ability of CD1 molecules to present lipid antigens to natural killer T (NKT) cells suggest a lipid-immune axis that could sustain inflammation. While CD1-NKT activity is implicated in several neuroinflammatory diseases, such as multiple sclerosis and Lewy body dementia, its role in AD is largely unexplored. Therefore, we asked whether AD-driven lipid changes activate CD1-dependent antigen presentation in glia and thereby sustain neuroinflammation. Methods 1. human iPSC-derived glia exposed to inflammatory cues, 2. transgenic AD mouse models, and 3. lipidomics to profile CD1 ligands and the “CD1 lipidome” under AD-relevant conditions. We used immunostaining for CD1, NKT, and LD quantification, and targeted mass spectrometry for lipidomics Results 1. Plaque proximal astrocytes in AD mice show higher CD1d than non-AD. 2. hiPSC-derived microglia upregulate CD1 under inflammation. 3. Preliminary lipidomics reveal shifts in glial LD composition in AD brain, with enrichment of candidate glycolipid/phospholipid species under inflammation. Conclusion Our data support a previously underappreciated lipid-immune axis in AD where glial lipid remodeling coincides with CD1-NKT pathway engagement. CD1-mediated lipid antigen presentation offers a mechanistic link between altered brain lipids and neuroinflammation in AD, nominating therapeutic targets along the CD1-NKT axis. Funding Source National Institute of Health, Indiana Clinical & Translational Science Institute, National Institute of Mental Health, National Center for Advancing Translational Sciences, Stark Neurosciences Research Institute, the Indiana Alzheimer Disease Center, Eli Lilly and Company. Topic Categories Classical and Non-Classical Antigen Presenting Cells (APC)

Dysbiosis drives allergic inflammation independent of IL-33/ST2 signaling 2260035

Abstract Introduction The IL-1 family cytokine IL-33 plays a role in many inflammatory diseases including atherosclerosis, fibrosis, COPD, and asthma. As a pleotropic alarmin, IL-33 is an innate mediator of Th2 immunity and a coveted clinical target. However, while a-IL-33 therapeutics have advanced to clinical trials none have been efficacious enough for regulatory approval. Hence, the incomplete understanding of contextual IL-33 function is a detriment to its therapeutic use. In the literature, mice lacking IL-33 (IL-33-/-) or ST2 (ST2-/-) exhibit a reduced response to allergen, demonstrating the necessity of IL-33/ST2 signaling. Paradoxically, ST2-/- mice in our studies respond to allergen comparably to controls, indicating that alternative pathways to inflammation can be sufficient. These data led us to the intriguing hypothesis that the environment can drive IL-33/ST2-independent inflammation, perhaps via the microbiome. Methods A house dust mite model of acute allergic inflammation was used to compare the allergic responses of ST2-/- mice from two facilities, A and B, quantified by flow cytometry and histology. Antibiotic depletion was performed to test the effect of the microbiome. Results Our data show that ST2-/- mice from Facility A exhibit an increased inflammatory response compared to those from Facility B, supporting an environmental effect. Excitingly, while inflammatory responses of WT and ST2-/- mice in Facility B were unaffected by microbiome depletion, the regimen resulted in a marked decrease in Th2 responses from Facility A ST2-/- mice. Conclusion Together, these data demonstrate that IL-33/ST2 signaling is only necessary to generate allergic inflammation in some environmental contexts, and that IL-33/ST2-independent allergic pathways are upregulated in a microbiome-dependent manner. By discerning the role of the microbiome in driving alternative pathways to allergic activation, the relationship between the environment and innate signaling can be better understood in broader disease contexts. Funding Source Immunology Training Grant- 5T32AI007496-28 Topic Categories Mucosal and Regional Immunology (MUC)

Anti-tumor activity of CTLA4-blockade-sensitive and insensitive CD8 T cells recognising the same low affinity neoepitope (IC50 for Kd 11,987 nM) 2304523

Abstract Introduction The binding affinities of tumor-controlling neoepitopes for MHCI span a broad range (8 nM—40,000 nM), with the overwhelming majority of them exhibiting low to ultra-low affinities (see Srivastava 2024 J. Clinical Investigation for review). Since low-affinity neoepitope—MHCI complexes are unstable, conventional MHCI tetramers cannot be generated. Here, we have engineered single-chain trimers (SCT) in which the neoepitope is linked to the MHCI α-chain and β2-microglobulin via peptide linkers within a single genetic construct and examined the functional activity of tetramer-reactive CD8 T cells. Methods SCT-based tetramers were generated and CD8 T cells recognizing them were adoptively transferred of into mice with pre-existing tumors. Results CD8 T cells from un-immunized mice or mice immunized with the ccdc85cMUT neoepitope, were stained with the SCT-tetramer described. Unexpectedly, we detected ccdc85cMUT-Kd specific CD8 T cells in both groups of mice although the number of tetramer-reactive cells was statistically significantly higher in mice immunized with ccdc85cMUT-pulsed BMDCs than in mice immunized with un-pulsed BMDCs in independent experiments. The efficacy of tetramer-reactive cells was tested by adoptively transferring the cells into mice bearing ∼5mm diameter Meth A tumors. Tetramer-reactive CD8 T cells from immunized mice mediated excellent tumor control while those from un-immunized mice did not, except in mice treated with CTLA4 blockade. Conclusion We report here the first identification of antigen-specific CD8 T cells recognising a neoepitope with low affinity for MHCI. Our observations also suggest the existence of two populations of ccdc85cMUT-reactive CD8 T cells, one that exists even in un-immunized mice where it is under Treg control, and the other that exists only in immunized mice where it is not under such control. These findings have implications for the intersection between neoepitope-elicited cancer immunity and autoimmunity. Funding Source n/a Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Vasoactive intestinal peptide stimulates B cell maturation and class switch recombination 2257501

Abstract Introduction Neuropeptides released from sensory neurons or neuroendocrine cells impact immune responses to pulmonary bacterial infection. We identified that in response to priming and infection with Streptococcus pneumoniae, pulmonary sensory neurons preferentially release vasoactive intestinal peptide (VIP), which stimulates IgG production. Methods To determine how vasoactive intestinal peptide (VIP) acts on antibody-secreting cells, we cultured naïve B cells with or without VIP in TLR or TLR+BCR stimulation media for 96 hours, sampling media and cells every 24 hours. Results In both media, VIP increased the number of isotype-switched (IgD-IgM-) differentiated and stimulated (Irf4+ Irf8+) B cells after 72 and 96 hours of culture. Additionally, the activation of these cells increased as Stat3 levels rose more with VIP. CD138+ Blimp+ plasma cells were increased with VIP, and the proportion of Stat3+ activated plasma cells was also increased. Isotyping analysis showed that IgG2a, IgG2b and IgG3 were consistently upregulated with VIP in both media after 96 hours. Finally, key enzymes involved in class switch recombination, AID, Rag1 and Rag2 were upregulated in both media with VIP. Conclusion The interrelated processes of B-cell maturation and class switch recombination are accelerated in the presence of VIP. This work is funded by NIH R01HL176463-01A1. Funding Source NIH/NHLBI Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)

Dynamic nutrient sensing in plasma cells licenses immunoglobulin A secretion 2257718

Abstract Introduction Dietary cues modulate immunoglobulin A (IgA) production, thus impacting gut homeostasis and response to pathogens. However, molecular processes integrating nutrient sensing and translating it into specific downstream signaling for antibody secretion remain poorly understood. Methods To study the intrinsic pathways regulating IgA secretion, we isolated plasma cells from both mucosal and non-mucosal tissues, focusing on two metabolic pathways known to be upregulated in IgA-secreting plasma cells: the intracellular cholesterol sensor Sterol Regulatory Element-Binding Protein 2 (SREBP2) and the mammalian target of rapamycin complex 1 (mTORC1). We then used in vitro-differentiated plasma cells to test whether depleting SREBP2–either genetically or pharmacologically–affects IgA secretion, using the ELISPOT assay for measurement. Finally, we employ conditional knockout mice lacking SREBP2 and mTORC1 specifically in plasma cells to study their function in antibody secretion in vivo. Results Here, we identified that both SREBP2 and mTORC1 work synergistically as metabolic checkpoints controlling IgA plasma cell secretion. SREBP2 regulates B lymphocyte-induced maturation protein-1 (Blimp-1) in response to cholesterol metabolites, while mTORC1 amplifies SREBP2 activation through direct phosphorylation. Screening for mTORC1 agonists revealed alanine as the dominant amino acid enhancing IgA, but not IgG, secretion, an effect independent of anatomical location and conserved in human plasma cells. Finally, alanine supplementation enhances protective, antigen-specific IgA to oral immunization and infection. Conclusion Our work elucidates metabolic processes required for integrating nutrients in plasma cells and has implications for developing therapeutics that modulate IgA production. Funding Source The American Association of Immunologists; NIH Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)

An Efficient and Durable Low‐Iridium Catalyst Enabled by a Potential‐Triggered Dual‐Pathway Mechanism for Acidic Water Oxidation

ABSTRACT Addressing the activity‐durability trade‐off of low‐iridium anode catalysts remains a key challenge for acidic oxygen evolution reaction (OER) in proton exchange membrane water electrolysis (PEMWE). Herein, we develop a three‐dimensional ordered macroporous (3DOM) Cr─Ir solid solution oxide to regulate intersite oxygen intermediate reactivity for efficient and durable acidic water oxidation. Solid solution formation, together with the ordered macroporous architecture, creates electronically and geometrically coupled Cr─Ir dual sites that enable a potential‐triggered coupling between the conventional adsorption evolution mechanism (AEM) and the oxide pathway mechanism (OPM). Beyond the AEM pathway involving *OOH intermediates at Ir sites, anodic polarization activates surface Cr─OH species into Cr─O moieties that cooperate with adjacent Ir─O species to promote intersite O─O coupling, thereby preserving the structural robustness associated with AEM while harnessing the activity advantage of OPM. As a result, Cr 0.72 Ir 0.28 O x achieves an overpotential of 254 mV at 10 mA cm −2 in acidic electrolyte and sustains stable PEMWE operation for over 2000 h at current densities up to 3.0 A cm −2 at an Ir loading of 0.36 mg Ir  cm −2 . This work establishes pathway coupling through architectural engineering as a viable design strategy for practical low‐iridium PEMWE catalysts, advancing sustainable hydrogen energy technologies.

From Preinstalled AIEgens to In Situ–Generated AIE Motifs: Photo−Triggered Dynamic C = S Bond Formation in Polymers for 4D Luminescence Encryption

ABSTRACT Achieving aggregation‐induced emission (AIE) in polymers via in situ, real‐time generation of chemically explicit emissive motifs, while simultaneously enabling programmable 4D (time‐/sequence‐dependent) luminescence, remains challenging. Herein, we report a facile platform that converts nonemissive polymer precursors into AIE‐active materials through photo‐triggered radical reactions that dynamically construct thiocarbonyl (C = S) motifs in polymer backbones. Two kinetically programmable modules are established by molecular design: Switch 1 affords a metastable C = S motif with reversible write–read–erase behavior, and can further evolve into a stabilized thiobenzophenone‐like state under prolonged irradiation; Switch 2 yields a more stable C = S motif featuring delayed‐write and write–fix characteristics. Spectroscopic evidence supports the radical pathway and reversible/stable C = S formation. By substituent engineering of diphenylmethane‐derived cores and sulfur‐containing groups, the emission is rationally tuned across the full visible range, supported by quantum‐chemical simulations correlating color with frontier‐orbital gaps. Leveraging orthogonal control of activation and erasure kinetics via photoinitiators and oxygen‐free atmospheres, we demonstrate two modes of 4D fluorescence encryption with time‐gated decryption and time‐window decoding. This work shifts AIE polymer design from “preinstalled AIEgens” to writable covalent emissive motifs, providing a scalable strategy for smart luminescent coatings and advanced information‐security materials.

Phospholipase Cβ regulates negative associative memory through calcium dependent and independent mechanisms

Thermal regulation and electrical performance improvement of solar panels using magnetically assisted nanofluid flow