Browse Articles

Fluorescence tracking reveals CD8 T cell recruitment from lymph nodes to irradiated tumors and early activation via type I interferon 2260446

Abstract Introduction Radiation therapy is a potent local cancer treatment but depletes intratumoral CD8 T cells. Despite this, tumors rapidly refill with T cells post-treatment. The source and activation mechanisms of these repopulating T cells remain unclear. Understanding early recruitment and differentiation is critical to optimizing radiation-immunotherapy combinations. Methods We used Kaede photoconvertible mice to track CD8 T cells migrating from tumor-draining lymph nodes (TdLN) to irradiated tumors. Tumors were implanted subcutaneously and treated with CT-guided radiation (2—12Gy) using the SARRP. Photoconversion was performed by targeted 405nm light exposure to TdLN prior to radiation. CD8 T cell activation and phenotype were assessed by flow cytometry and scRNA-seq. Mechanistic studies used IFNAR1-/-, Sting-/-, and cGAS-/- mice, and adoptive transfer of antigen-specific 2C T cells. Fractionation effects and IFN signaling were evaluated using knockout models and RNA-seq datasets. Results TdLN-derived CD8 T cells preferentially migrated to irradiated tumors and rapidly upregulated CD69 independent of antigen specificity. Activation was mediated by type I IFN signaling triggered by cGAS in irradiated cancer cells. CD69 expression was dose-dependent and enriched in progenitor exhausted T cells. scRNA-seq revealed a shift toward stem-like and proliferating subsets post-radiation. Antigen-specific CD8 T cells also migrated and acquired exhaustion markers upon tumor entry, but their recruitment was not increased by radiation. Fractionated radiation (e.g., 2Gy ×3) induced similar CD69 upregulation at higher single doses. Conclusion Radiation induces early, non-specific activation of newly recruited CD8 T cells via type I IFN, shaping the tumor immune environment before antigen-specific expansion. These findings highlight the role of TdLN-derived T cells and suggest that radiation timing and dose critically influence immune synergy. Funding Source National Cancer Institute R01CA182311, R01CA244142, R01CA208644, 1R01CA293806-01A1, and the Providence Foundation Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

A Novel Flow Cytometry Array for High Throughput Detection of SARS-CoV-2 Antibodies 2257921

Abstract Introduction Coronavirus disease 2019 (COVID-19) that broke out at end of 2019 caused a global damage to both lives and economy. Although the U.S. Food and Drug Administration (FDA) has approved one antiviral treatment and authorized others for emergency use, there is no fully effective antiviral therapy for COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Assays detecting virus-specific immuno-globulins (Ig) or nucleic acids in large-scale epidemiological, vaccine, and drug development studies remain limited due to high costs, reagent accessibility, and cumbersome protocols. Methods A multiplex bead-based assay was developed to simultaneously detect human IgM, IgG, and IgA antibodies against the SARS-CoV-2 spike receptor binding domain (RBD) in serum using flow cytometry. Assay performance was evaluated for sensitivity, specificity, reproducibility, and cross-reactivity and compared to another immuno-assay platform. Results The assay enabled simultaneous measurement of three antibody isotypes across 624 samples within 2 h. Intra-plate coefficients of variation (CVs) ranged from 3.16 to 6.71%, and inter-plate CVs ranged from 3.33 to 5.49%, demonstrating high re-producibility. The platform also quantified background noise from nonspecific binding, facilitating straightforward data interpretation. Conclusion This novel, flexible multiplex bead-based assay utilizing a well-established platform provides a rapid and reproducible approach for detecting SARS-CoV-2-specific antibodies. Its high throughput capacity and low variability make it well suited for large-scale epidemiological, vaccine, and therapeutic studies. The platform’s adaptability further supports application to other infectious diseases, offering an ideal tool for broad immunological surveillance. Funding Source n/a Topic Categories Technological Innovations in Immunology (TECH)

Gut bacteria-derived GABA promotes neonatal gut T cell immunity 2310019

Abstract Introduction Gut microbiota and derived metabolites are crucial for priming and maturation of postnatal intestinal immune responses and homeostasis. Our recent study shows age-dependent variations in the gut metabolome, including enrichment of the neurotransmitter γ-aminobutyric acid (GABA) in neonate. This coincides with the key “window of opportunity” for microbiota-driven immune programming. However, the regulation and immunomodulatory role of neonatal gut GABA remain unknown. My proposal aims to elucidate the role of GABA in regulating intestinal immune under homeostasis and in response to microbial colonization in the neonatal gut. Methods GABA quantification by mass spectrometry in intestinal tissue and luminal contents of pathogen-free(SPF) and germ-free(GF) mice. Oral gavage of GABA or vehicle (PBS) in neonates, followed by flow cytometry analysis of lamina propria (LP) immune cells. GABA-gavaged GF neonates were used to study its role in regulating immune response to microbial colonization. Mice with GABAA receptor ablation in CD4+ T cells(Gabrb3 cKO) were used to probe signaling specificity. Enteric Citrobacter rodentium infection was used to investigate how GABA affects neonatal gut immunity. Results GABA in the neonatal small intestine is mainly derived from the gut microbiome. In the SI LP of GABA-treated neonates, I observed increased numbers of T cells producing inflammatory cytokines IFNg and IL-17A, compared to vehicle-treated neonates. GABA-gavaged neonatal GF mice showed significant increases in antigen-presenting cells, neutrophils, and effector CD4+ T helper 17 (Th17) cells post-conventionalization. The SI LP of Gabrb3 cKO mice had a significant increase in Th17 cells, compared to littermate controls. GABA gavage in SPF neonates conferred enhanced immunity against C. rodentium infection. Conclusion My findings demonstrate that microbiome-derived GABA promotes Th17 responses to microbial colonization, and confers protection against bacterial pathogens during postnatal development. Funding Source N/A Topic Categories Mucosal and Regional Immunology (MUC)

Changes in Proxy Cerebral Perfusion in Infection-Associated Chronic llnesses 2259044

Abstract Introduction The Mucosal And systEmic Signatures Triggered by Responses to infectious Organisms (MAESTRO) Study aims to explore potential biomarkers to explain how infection-associated chronic illnesses (IACI) affect some patients but not others, and the different ways in which they do so. This information can guide further research into diagnosing, treating, and preventing IACIs. Methods The IACIs of focus are the long-lasting symptoms following acute infections of Borrelia burgdorferi and SARS-CoV-2, Long Lyme and Long COVID, respectively. Each participant contributes self-reported symptoms, surveys, tests for autonomic dysfunction, vital signs, reaction time tests, neurocognitive tests including eyetracking and electroencephalography (EEG) assessments, and various biological samples including blood, urine, sweat, throat swab, saliva, vaginal swab, and rectal swab. Throughout a study visit, an earpiece, Lumia, is used to measure blood flow to the brain and heart rate. Results During a NASA Lean Test, variations in proxy cerebral perfusion are compared to changes in traditional vital signs (blood pressure, heart rate, oxygen saturation) and observed physical signs and symptoms (blood pooling, lightheadedness, etc). Conclusion Analyses of these data may indicate a potential connection between autonomic function and proxy cerebral perfusion throughout various activities. Funding Source Fairbairn, NIH NIAID RO1 AI 178713-01, MLSC, Manton Topic Categories Neuroimmunology (NEUR)

Mechanisms Underlying LAG3 Immune Checkpoint Function 2330007

Abstract Introduction Immune checkpoint blockade was recognized with the 2018 Nobel Prize in Physiology or Medicine for its revolutionary impact on cancer therapy. LAG3 has emerged as a promising target in cancer immunotherapy, with the FDA approval of relatlimab establishing it as the third immune checkpoint blockade with demonstrated clinical efficacy. However, the molecular mechanisms underlying LAG3-mediated T cell inhibition remain incompletely understood. Methods We employed a multidisciplinary strategy to investigate LAG3 signaling, integrating site-directed mutagenesis, biochemical assays, and mass spectrometry. The functional consequences of LAG3 signaling were assessed through T cell proliferation and ELISA measurement of IL-2, while membrane binding properties were evaluated using FRET and NMR. Finally, these mechanistic insights were validated in a clinical context through analysis of single-cell RNA sequencing (scRNA-seq) and immunohistochemistry (IHC) data from patient cohorts treated with PD-1/LAG3 dual blockade. Results OUR RECENT STUDIES demonstrated that LAG3 undergoes robust non-K48-linked polyubiquitination upon ligand engagement, which promotes its inhibitory function through disruption of membrane binding by the juxtamembrane basic residue-rich sequence (Cell 2025). Building upon this foundation, our ongoing investigations are uncovering the downstream signaling mechanisms by which LAG3 suppresses T cell function. Through comprehensive proteomic analysis, we have identified novel LAG3-interacting proteins that mediate its immunosuppressive effects. Furthermore, we have discovered additional post-translational modifications on LAG3 that regulate its checkpoint activity in a context-dependent manner. Conclusion Collectively, our findings reveal a multi-layered regulatory network controlling LAG3 checkpoint signaling, which may provide new therapeutic opportunities for optimizing LAG3-targeted cancer immunotherapy. Funding Source n/a Topic Categories Tumor Immunology: Checkpoints, Prevention, and Treatment (TIPT)

Immiscible Metal‐Regulated Surface Segregation Enables Core–Shell Bi–PtMn Catalysts With Benchmark Performance in Direct Methanol Fuel Cells

ABSTRACT Although the Bi–Pt ensemble effect endows Bi–Pt‐based catalysts with remarkable CO tolerance in the methanol oxidation reaction (MOR), the lack of precise atomic‐level control over Bi–Pt surface structures leads to an intrinsic activity–selectivity trade‐off. Herein, we propose a facile immiscible‐metal‐induced surface‐segregation strategy to construct a core–shell Bi–PtMn catalyst that simultaneously achieves outstanding MOR performance and high selectivity toward the CO‐free pathway. Exploiting the immiscibility between Mn and Bi enables precise regulation of surface‐segregated Bi, leading to a well‐defined core–shell structure with an ordered L1 0 ‐PtMn core and a PtBi shell. The catalyst delivers benchmark mass activity of 61.81 A mg Pt −1 , 4.0 and 16.2 times that of Bi‐Pt and Pt/C, respectively. Furthermore, as a practical anodic electrocatalyst for direct methanol fuel cells, the catalyst achieves a peak power density of 294.21 mW cm −2 at an ultralow Pt loading of 0.5 mg Pt cm −2 . Mn lowers the barrier of the rate‐determining step by facilitating C─H bond cleavage, as corroborated by theoretical calculations and kinetic isotope effect (KIE) measurements. This work provides a design principle based on immiscible metal thermodynamics for atomic‐level surface engineering of electrocatalysts.

N‐Heterocycle‐Activated π‐Cooperative Coordination for Enhancing Structural Stability of Perovskite Solar Cells

ABSTRACT The chemistry of buried interfaces critically dictates the crystallization behavior of perovskite semiconductors in inverted perovskite solar cells, yet remains poorly controlled, giving rise to interfacial coordination disorder that disrupts the organization of self‐assembled monolayers (SAMs) during crystallization. Here, we report an N‐heterocycle‐activated coordination strategy that stabilizes SAM organization while enabling precise regulation of precursor chemistry and crystallization at SAM‐perovskite interfaces. Imidazolium‐derived molecules integrated into SAMs establish cooperative coordination interactions with neighbouring lead polyhalide species, thereby reshaping the local precursor environment and directing nucleation and crystal growth. This process gives rise to a π‐cooperative coordination interaction at the buried interface, which suppresses interfacial grooves and voids, reduces residual solvent–complex intermediates, and promotes the direct formation of phase‐pure α‐perovskite films. Devices based on this molecularly regulated interface achieve a power conversion efficiency of 26.83% and retain 93.8% of their initial efficiency after 936 h of continuous maximum power point operation. These results establish coordination‐mediated interfacial design as a molecular route to couple interfacial order with crystallization control in perovskite semiconductors.

Antibody glyco-optimization and site-specific conjugation enhance the immune-stimulating activity of antibody–TLR ligand conjugates

Doctor’s Dirty Little Secret — The Cost of Silence

DLGDFNet: a lung tumor image segmentation model based on local and global dual dynamic fusion

Overcoming age-related tumor progression using the HEPLISAV-B vaccine in combination with immunotherapies 2259634

Abstract Introduction As we age, the adaptive immune system declines due to factors such as reduced thymic cellularity, altered tissue architecture, decreased production of naïve T cells, and a limited repertoire of peripheral T cell receptors. Yet, most preclinical tumor models rely on young mice, overlooking the immunological decline that shapes therapeutic outcomes in older hosts. This gap limits translation of otherwise promising immunotherapies to the aging cancer population. To address this, we examined how age influences antitumor immunity and immune cell trafficking in a triple-negative breast cancer (TNBC) model treated with either intratumoral (i.t.) HEPLISAV-B (HEP B) vaccine or a combinatorial immunotherapy composed of i.t. HEP B vaccine, i.t. complexed IL-15, and intraperitoneal (i.p.) anti—PD-1. We hypothesized that treatment could reverse the effects of aging on tumorigenesis. Methods The TNBC cell line 4T1 expressing luciferase was used to establish tumors in young (6-8 weeks) and aged (24-26 weeks) female BALB/c mice. Mice were treated with i.t. injections of the HEP B vaccine or HEP B in combination with i.t. injections of IL-15 and i.p. injections of anti-PD-1. Tumor progression and survival were monitored. Flow cytometry quantified expression of trafficking receptors (CXCR4, B7). Results The HEP B vaccine and combination therapy induced complete tumor regression in 90% of young mice recipients (n = 10) and 60% of aged mice (n = 9) in a survival study out to 60 days. Aged mice showed faster tumor growth in controls but similar regression rates when treated. Aging altered the expression of key homing molecules on tumor-infiltrating CD8 T cells with decreased CXCR4 and elevated B7, suggesting impaired trafficking and retention. Changes in the CD4:CD8 T cell ratio were observed between groups. Conclusion Treatment with the HEP B vaccine or a combination therapy can overcome age-related hurdles in tumor regression. Funding Source Rush Philanthropy; Roumbas Estate Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

B Cell Activation Pathways Dictate the Effector Profile of Secreted IgG through Differential Fc Glycosylation 2257228

Abstract Introduction Glycosylation of IgG Fc is a critical modification, influencing IgG’s ability to bind to Fc receptors and complement, thereby defining its effector function. Despite this crucial role, mechanisms controlling the Fc glycosylation in B cells are poorly understood. Here, we sought to identify these mechanisms by mimicking T-cell-dependent and independent responses in vitro. Methods IgG+ memory B cells from healthy donors were stimulated to induce antibody-secreting cell differentiation. To define the upstream signals, IgG+ memory B cells were cultured via either T-cell-dependent (CD40L) or innate Toll-like receptor (TLR)-mediated pathways. IgG glycosylation was analyzed with Whole Immunoglobulin Glycoprofiling with Asymmetric Monitoring (WIgGWAM), a mass spectrometry method that analyzes glycan pairs on the intact Fc dimer. Results T-cell-dependent activation (CD40L) yielded IgG with significantly increased galactosylation and sialylation (glycans associated with anti-inflammatory activity) compared to TLR-mediated activation (R848 and CpG). Crucially, on asymmetrically glycosylated species, mono-sialylated Fc also differed significantly in its distribution between the T-cell-dependent and innate TLR activation conditions, revealing another layer of regulation. Conclusion B cell activation pathways represent a key checkpoint controlling IgG effector function. These findings suggest that T-cell-independent responses, which are prominent during active SLE and often driven by TLR engagement, may inherently generate more pro-inflammatory IgG characterized by reduced galactosylation and sialylation. Therapeutically manipulating specific B cell activation pathways represents a novel strategy to shape the IgG glycan profile towards a more anti-inflammatory state, offering a new approach to control antibody-mediated diseases. Funding Source This research was supported by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health under award number U19 AI144306 Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)

Cancer vaccine in combination with radiopharmaceutical therapy (RPT) upregulates type I interferon pathway in Ovalbumin-expressing tumor model 2254330

Abstract Introduction To enhance the efficacy of therapeutic cancer vaccines, combination strategies are needed to overcome mechanisms of immunoresistance. RPT, such as pan-cancer targeting 90Y-NM600, can act as an immunomodulating agent. We have previously found that cancer vaccines administered prior to RPT elicited greater anti-tumor response in murine models than if administered after RPT. Here, we investigated the mechanisms by which combination treatment of vaccine prior to RPT enhanced antitumor immunity using an ovalbumin-expressing tumor model. Methods 1x106 E.G7-OVA-PD-L1hi tumor cells were subcutaneously implanted in C57Bl/6 mice. 0.5x106 naïve OT-I CD8+ T cells were transferred to the tumor-bearing mice (day -3), followed by vaccination with OVA-encoding DNA plasmid (day -2), and low dose 90Y-NM600 injection (delivering 5Gy to the tumor; day 0). Tumors were collected 7- and 14-days post-RPT for transcriptomic analysis and flow cytometry. In a follow up study, mice were similarly treated, and concurrently treated or not with a STING antagonist H-151, and followed for changes in tumor growth. Results Combining tumor vaccine with RPT significantly upregulated genes associated with type I interferon pathway along with increased cytotoxic and CD8+ T cell scores. This finding aligned with increased infiltration of SIINFEKL-specific CD8+ T cells 7 days post-RPT. Genes associated with cytotoxicity significantly decreased 14 days post-RPT. Addition of H-151 did not affect tumor growth. Conclusion RPT enhanced the infiltration and functional activity of vaccine-activated tumor-specific CD8+ T cells, likely through STING-independent type I interferon signaling. Funding Source T32 CA009135 F31CA305954 P01 CA250972 Topic Categories Vaccines and Immunotherapy (VAC)

Dipyridamole as a Potential NEK7—NLRP3 Inflammasome Modulator in Adult Onset Still’s Disease and Pre Myelodysplastic Syndrome 2216232

Abstract Introduction Dipyridamole, a phosphodiesterase inhibitor used for stroke prevention, has emerging evidence as an NLRP3 inflammasome inhibitor. Because NEK7—NLRP3 interactions drive IL-1β/IL-18 release in autoinflammatory disease and may accelerate clonal myeloid evolution, we investigated whether low-dose dipyridamole could modulate inflammasome activity in a patient with adult-onset Still’s disease (AOSD) overlap and pre-MDS features. Methods A patient with CAPS/AOSD overlap, germline TP53 loss, and early marrow abnormalities was treated with dipyridamole 25 mg twice daily. Biomarkers including ferritin, VEGF, and lipid profiles were tracked over two years. Cytokine panels, bone marrow immunohistochemistry, and genetic data were used to correlate clinical and molecular findings. Results Dipyridamole restored VEGF expression, which had been undetectable, normalized ferritin after two years of elevation, and stabilized lipid abnormalities resistant to prior IL-1 blockade. Inflammatory symptoms improved in parallel with biomarker correction. Mechanistic correlations included increased intracellular cAMP, reduced NF-κB priming, attenuation of mitochondrial ROS, and disruption of NEK7—NLRP3 binding, consistent with published models. Biomarker shifts suggested improved macrophage function and reduced IL-1β/IL-18 activity. Conclusion This case shows that dipyridamole, a widely used cardiovascular agent, can function as an NEK7—NLRP3 inflammasome modulator in human disease. By restoring VEGF, ferritin, and lipid balance, dipyridamole reduced systemic inflammation in a patient at risk for myeloid transformation. These findings support further study of biomarker-guided dipyridamole therapy in autoinflammatory conditions with hematologic involvement. Funding Source N/A Topic Categories Immune Mechanisms of Human Disease (HUM)

Aged lymph node stromal microenvironment as a driver of immune function decline 2257900

Abstract Introduction Immune system undergo profound age-associated changes underlying impaired immune function in response to infections, malignancies, and vaccines. While cell-intrinsic changes in lymphocyte are well recognized, emerging evidence indicates that degenerative changes in secondary lymphoid organs (SLO) microenvironment decisively contribute to immune decline. Methods To define the molecular basis of these changes, we performed transcriptomic profiling and functional validation of non-hematopoietic lymph node stromal cells (LNSCs), which regulate lymphocyte homeostasis and orchestrate immune responses. Results Aging induces coordinated metabolic defects in fibroblastic reticular cells, a major stromal cell subtype, characterized by reduced expression of amino acid transporters and mitochondrial phosphate and ATP/ADP carriers. These alterations coincided with a metabolic shift from oxidative phosphorylation (OXPHOS) to glycolysis, accompanied by mitochondrial dysfunction and a reduction in their ability to maintain T cells. Functionally, aged LNSCs exhibited impaired proliferation and expansion of the reticular network during West Nile virus and herpes simplex virus type 1 infections, resulting in diminished and hypofunctional antigen-specific CD8+ T cell responses. Restoring mitochondrial quality through mitophagy induction enhanced the ability of aged LNSCs to support naïve T cells in vitro. Ongoing studies aim to identify upstream cues driving these stromal metabolic defects and to leverage FRC-specific genetic models to dissect their role in functional immune decline with age. Conclusion Together, these results suggest that age-related mitochondrial and metabolic changes in the lymph node stromal microenvironment contribute to T cell immune function. Funding Source n/a Topic Categories Lymphocyte Differentiation and Peripheral Maintenance (LYM)

Infection history shapes envelope-specific IgG repertoires with convergent neutralization from multiple lineages in secondary dengue 2259474

Abstract Introduction Dengue virus (DENV1-4) infects an estimated 400 million people annually. Severe disease is often linked to antibody-dependent enhancement (ADE) during secondary infection, whereby cross-reactive, non-neutralizing antibodies facilitate viral entry. While primary infection elicits protective serotype-specific and enhancing cross-reactive antibodies, secondary infection is thought to elicit broadly neutralizing antibodies that confer heterotypic protection. However, it remains unknown whether post-secondary plasma neutralization is driven by a few dominant clonotypes or distributed across diverse broadly neutralizing lineages. Methods We applied high-resolution proteomic analysis of DENV envelope (E) dimer-specific circulating immunoglobulin (IgG) at post-secondary late convalescence (4-6 months post-illness) to quantitatively profile the plasma antibody repertoire with monoclonal resolution in participants of a pediatric hospital-based study in Nicaraguan (N = 3 DENV2, N = 4 DENV3). Recombinant monoclonal antibodies (mAbs) were constructed from the most abundant serological lineages for epitope mapping and neutralization assays. Results Across five donors, >87% of E-specific IgG lineages were cross-reactive and >67% neutralized at least two serotypes. Of these, 64% cross-neutralized DENV1-4 with geometric mean NT50 values between 0.19 — 1.4 µg/mL. Analysis of abundant IgG lineages from two donors, either secondary DENV2 or DENV3 infection, revealed distinct epitope profiles on the E dimer despite similar cross-neutralizing activity. Conclusion Our findings demonstrate functional convergence to DENV cross-neutralization despite divergent epitope profiles in donors with different secondary DENV infection histories. Together, this suggests that DENV cross-neutralizing antibodies are abundant in post-secondary plasma, and that there are several mechanisms and lineages that enable broad neutralization of DENV1-4. Funding Source National Institute of Health R21AI176011 and National Institute of Allergy and Infectious Disease P01AI106695 Topic Categories Viral Immunology (VIR)

A Novel Nanoparticle Strategy to Deliver Locally High Concentrations of Active Vitamin D and Retinoic Acid to Enhance Gut Immune Tolerance 2259162

Abstract Introduction Despite promises in treating many diseases, active vitamin D and retinoic acid (RA) face a formidable barrier in clinical application due to severe side effects associated with the systemic high concentrations usually required for therapeutic efficacy. We recently propose that de novo synthesis of locally high concentrations of these two molecules is a potential solution because of their short half-lives, which can prevent systemic concentration surges while still maintaining therapeutic concentrations locally. Methods We previously evaluated one strategy that overexpressed two physiological enzymes in activated dendritic cells (DCs): the 1alpha-hydroxylase that synthesizes active vitamin D, and the retinaldehyde dehydrogenase 2 (RALDH2) that synthesizes RA. We showed that the engineered DCs, when injected, homed to peripheral lymphoid tissues and de novo synthesized locally high concentrations of the two molecules without significant side effects, leading to robust suppression of experimental colitis by augmenting the induction of gut-homing CD4 Treg, consistent with other reports that active vitamin D at high concentrations induces regulatory molecules (Foxp3 and IL-10) and RA gut-homing receptors. However, DC-based therapy entails technological challenges and high costs. Here, we report a novel engineered nanoparticles that deliver the genes of 1apha-hydroxylase and RALDH2 specifically to DCs in vivo. Results Our data showed that intravenous injections of the engineered nanoparticles significantly upregulated the expression of 1apha-hydroxylase and RALDH2 and increased the local concentrations of these two molecules in tissues. In vitro, the nanoparticle-loaded DCs programmed gut-homing CD4 Treg and suppressed the proliferation of autologous CD4 T cells. Conclusion Our data suggests that such engineered nanoparticles are a potential cure for intestinal inflammation, e.g., canine inflammatory bowel disease. Funding Source n/a Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)

Gene-Specific Rewiring of Type I Interferon Responses by Staphylococcus aureus 2329926

Abstract Introduction Staphylococcus aureus is a Gram-positive pathogen that is a major cause of soft tissue and bloodstream infections in humans. Previous studies have shown that S. aureus triggers myeloid cell-driven innate immune activation including inflammatory signaling and type I interferon (IFN) responses; however, the role type I IFNs remains controversial. Methods Primary human CD14+ monocytes were purified from PBMCs of healthy donors using anti-CD14 magnetic beads. Monocytes were infected with various doses of S. aureus and harvested for RT-qPCR, Western blotting, and integrated bulk RNA sequencing, ATAC-seq and CUT&RUN. Results We observed a dose-dependent dichotomous regulation of the IFN response, which was induced by low doses and suppressed at high doses of S. aureus. Only a subset of interferon-stimulated genes (ISGs) was induced despite intact IFNβ production following S. aureus infection. Intriguingly, S. aureus selectively abrogated the activation and nuclear translocation of STAT1, while activation and nuclear translocation of the other ISGF3 components STAT2 and IRF9 were preserved. Furthermore, RNA profiling revealed a disparate regulation of gene expression, with a distinct subset of genes exhibiting significantly enhanced expression upon combined S. aureus and IFNβ treatment. Epigenomic profiling showed a complete repression of chromatin accessibility as well as STAT1 binding at a subset of ISG loci upon S. aureus infection, whereas another subset of ISGs displayed increased chromatin accessibility and transcriptional activation upon infection. Conclusion Our findings suggest that S. aureus alters activation of the canonical type I IFN-mediated Jak-STAT pathway through suppression of STAT1 activation and altering chromatin remodeling . This change in signaling is associated with gene-specific reprogramming of the type I IFN response by S. aureus that may alter the host response to this pathogen in a context-dependent manner and contribute to difficulty in clearing S. aureus infection. Funding Source n/a Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

Hydrogen Bond Networks for Stable and Sustainable Production of Hydrogen From Seawater via Contact‐Electro‐Catalysis

ABSTRACT Hydrogen production from seawater offers a sustainable pathway to obtain clean energy while alleviating the shortage of freshwater resources. However, the corrosive marine environment presents a significant challenge for conventional metal‐based catalysts. Here, we propose a contact‐electro‐catalysis (CEC) strategy that employs nonmetallic fluorinated SiO 2 (F‐SiO 2 ) for effectively extracting hydrogen from seawater by mechanical agitations. In contrast to conventional fluorocarbon polymers that can hardly be electrified by contact with ionic liquids, F‐SiO 2 group could still maintain high CE performance and thus exhibit 2.91 times higher H 2 yield. Mechanistic investigations reveal that ion exclusion by hydrogen bond networks at F‐SiO 2 /water interface should be the dominant reason for such performance enhancement. In practical applications using real seawater from Bohai sea, the F‐SiO 2 ‐based CEC delivers a stable hydrogen yield during a continuous ultrasonication for 1000 h. We expect this strategy could not only provide a sustainable platform for in situ hydrogen production from seawater by utilizing unlimited mechanical energy in the ocean, but also enable a feasible route for improving the liquid‐solid contact‐electrification (CE) especially under high salinity conditions.

Engineering Polarons for Circumventing Energy Gap Law: Nd‐doped CdTe Quantum Dots With High‐efficiency Emission at 1730 nm for NIR‐IIb/c Bioimaging

ABSTRACT Despite widespread attention in near‐infrared IIb/c (NIR‐IIb/c, 1500–2000 nm) fluorescence for deep‐tissue bioimaging, the development of NIR‐IIb/c emissive materials with high photoluminescence quantum yield (PLQY) remains hindered by the energy gap law (EG law). Herein, we propose a polaron engineering strategy to circumvent the EG law via accelerating the radiative recombination rate by 150‐fold through increased charge localization. By incorporating Nd 3+ into CdTe quantum dot lattice, we achieved broadband NIR‐IIb/c emission peak at 1730 nm, with PLQY of 11.34 ± 0.79% in aqueous solution and a Stokes shift exceeding 900 nm. We demonstrate Nd 3+ substitution introduces beneficial defects that perturb electronic structure and local symmetry. Upon 808 nm excitation, these defects trap photoexcited carriers, inducing lattice distortions and strong electron‐phonon coupling, which leads to the formation of polarons with high NIR‐II emission efficiency. The resulting QDs enable clinical‐grade NIR‐II imaging via dual modes, including low‐power (10 mW cm − 2 ) real‐time deep‐tissue imaging and white‐light‐activatable fluorescence‐guided surgery navigation. This study provides a promising approach to bypass the EG law, offering a pathway toward highly emissive emitters in the NIR regime.