Browse Articles

A Scoring System Using Visual and Artificial Intelligence Analysis Quantifies HEp-2 Cell Slide Quality for Optimal Antinuclear Antibody Testing 2253905

Abstract Introduction High-quality HEp-2 cell slides are essential for antinuclear autoantibodies (ANA) testing. However, there is currently no established method to quantify the substrate quality. This leads to subjective evaluation and affects the selection of high-quality HEp-2 cell slides. Our goal was to establish a method to thoroughly quantify HEp-2 cell slide quality and select the best HEp-2 cell slides for accurate and reliable ANA testing. Methods This study used both visual and Artificial Intelligence (AI) assisted image analysis methods to quantify the quality of HEp-2 slides based on a scoring system. The score system included cell distribution scores (density, aggregation, and separation); cell morphology scores (interphase/mitotic cell appearance, and nuclear/cytoplasmic ratio); mitotic cell scores; fluorescence scores; and pattern scores. Higher scores represent higher quality. dIFine M1® manual microscope, dIFine® automated microscope, Sebia ANA HEp-2 slides and another brand of HEp-2 slides from 2 different batches respectively, were used in the validation. Results Results from quantifying HEp-2 slide quality across different ANA patterns illustrate high agreement and accuracy between visual and AI-assisted analysis. Comparison of the total scores and the scores for each category can clearly differentiate the quality of HEp-2 cell slides and identify the substrate defects. Sebia ANA HEp-2 slides show significantly higher scores in all categories and present optimal quality for ANA testing. Conclusion This quantification scoring system demonstrates for the first time that a quantitative approach can be used to assess the quality of HEp-2 cells on ANA test slides. Thus, it is now possible to reliably select the best quality HEp-2 cell slides for ANA testing. Funding Source n/a Topic Categories Technological Innovations in Immunology (TECH)

Double positive (DP) developing thymocytes regulate the development of neuronal cell bodies within the thymus 2260542

Abstract Introduction Peripheral nervous system innervation of various organs has been associated with the development and maintenance of the immune system. Yet, the intricate details of thymic innervation remain less well-studied. Interestingly, various neurological insults including brain tumors, and neurotropic infections have been shown to have profound impacts on thymic size and cellularity and T cell development. Methods We used flow cytometry, confocal microscopy, neuro tracers, and genetic knockout mice to evaluate developing T cell-neuron interactions within the thymus. Results We have identified neuronal cell bodies within the thymus. These cells express neuronal markers such as NeuN and tyrosine hydroxylase and lack TEC identifiers, such as EpCAM, UEA-1, and Ly51. Thymic neurons can be infected with a neurotropic rabies vector, further cementing their neuronal identity. Considering the thymus consists mostly of T cells, we next investigated a potential interaction between T cells and thymic neurons. Interestingly, loss of T cell development results in a lack of thymic neuron development indicating T cell-neuron coregulation during development. However, thymic neurons can be recovered following a bone marrow transplant, suggesting the provision of a differentiation and/or survival signal for neurons provided by the developing T cells. Using knockout mice lacking the T cell lineage at various stages of development, we determined that TCR beta selection is required for the development of thymic neurons. Finally, we determined that a lack of transition from DN4 to DP severely diminishes the development of thymic neurons. Analysis of the publicly available bulk RNA-sequencing data comparing thymic DP to DN cell populations indicates the potential involvement of IL34 in neuronal development in the thymus. Conclusion We describe a novel population of neuronal cells within the thymus that interact with developing thymocytes to establish optimal thymic architecture. Funding Source NIH K99/R00 Topic Categories Neuroimmunology (NEUR)

Electrical Signals at the Subcellular Scale: How Electroactive Materials Regulate Stem Cell Fate

ABSTRACT Electroactive materials have emerged as a pioneering frontier at the convergence of regenerative medicine and biomaterials science. Unlike conventional biochemical approaches, which often lack spatiotemporal precision, electroactive materials such as conductive polymers and piezoelectric nanostructures can mimic the native electrical microenvironment of tissues. By directly modulating subcellular electrical signals, including organelle membrane potential and ion dynamics (e.g., in mitochondria and endoplasmic reticulum), these materials present a paradigm shift in controlling stem cell fate. This review begins by outlining the classification of electroactive biomaterials and their mechanisms of generating electrical signals under external stimuli, highlighting their dynamic interactions with stem cells. It subsequently explores how material‐mediated electrical cues precisely modulate subcellular architecture and function, detailing key processes such as calcium oscillations regulated by membrane potential in endoplasmic reticulum and potential‐dependent regulation of mitochondrial redox homeostasis. This article further systematically evaluates the role of electroactive materials in guiding stem cell differentiation and reprogramming, while surveying their emerging applications in neural, bone, and cardiac tissue regeneration. Finally, it presents current challenges such as precise organelle targeting and long‐term electrical safety and suggests future directions, offering a theoretical and technological framework for developing electrically driven regenerative therapies.

Neuromorphic In‐Memory Computing for Marine Visual‐Auditory Perception

ABSTRACT The exploration of marine environments is crucial, yet the extreme conditions of the deep‐sea, combined with the segregated signal processing in current sensor technologies, lead to bulky systems, high energy consumption, and significant latency, which severely constrains the development of real‐time intelligent perception systems underwater. Herein, we developed a neuromorphic floating‐gate transistor (NFT) that integrates both electrical and optical memory functionalities, emulating simultaneously visual and auditory synaptic behaviors within a single unit, thus enabling in‐memory dual‐mode processing of visual‐auditory signals. Electrically, it achieves rapid switching (∼14 µs), high on/off ratio (10 6 ), and robust endurance (>10 4 cycles). This enables high‐accuracy (88%) classification of seafloor minerals and rocks via sonar echo processing using a convolutional neural network (CNN). Optically, the NFT exhibits tunable synaptic weight modulation from short‐term to long‐term plasticity under 405–808 nm laser pulses. Leveraging the low‐attenuation green‐light window in seawater, the system, combined with RGB denoising and green‐channel enhancement preprocessing, realizes 80% accuracy in marine biological image recognition. This synergistic electro‐optical in‐memory computing architecture provides an efficient, low‐power, and compact hardware solution for intelligent perception in complex underwater environments.

Individual skill differences and human AI interaction shape creative outcomes

Abstract This study investigates how individual differences in skill levels and human-AI interaction are associated with different creative outcomes, focusing on the cognitive, informative, and logical dimensions of interaction. Using quasi-experimental data, we explore how AI relates to creativity—specifically in terms of novelty and usefulness—across low-, medium-, and high-skill individuals. The findings reveal that logical interactions with AI are positively associated with both novelty and usefulness across all participants. Cognitive interactions are positively associated with novelty but not usefulness, while informative interactions are positively associated with usefulness but not novelty. Notably, medium-skill individuals achieve the highest creative performance overall, while low-skill individuals show the greatest potential for improvement through higher-quality AI interactions. These results highlight how individual differences and human-AI interactions are linked to different creative outcomes, offering insights into optimizing AI to enhance creativity for users with varying expertise.

Structural Rewiring of TCR Docking by Protective HLA Alleles Drive Treg-Mediated Tolerance in Type 1 Diabetes 2255268

Abstract Introduction Loss of immune tolerance to β-cell antigens, including insulin and GAD65, drives type 1 diabetes (T1D). MHC class II alleles shape T cell repertoires, with DR4/DQ8 conferring susceptibility and DR15/DQ6 protection in T1D. The mechanism by which protective alleles bias regulatory T cells (Treg) selection and function is unclear. We hypothesize that DR15/DQ6 promote tolerance by selecting Tregs with a distinct, regulation-favoring TCR recognition mode Methods To test this, we combined structural, biophysical, and repertoire analyses of human DR15-GAD65 and DQ6-insulin—specific TCRs. Mutagenesis mapped critical peptide residues mediating binding and signaling. In vivo, antigen-specific CD4+ Tregs were enumerated from NOD.FoxP3-eGFP mice by flow cytometry. Results Structural analysis of DR15—GAD65 Treg TCRs revealed a CDR3α-dominated, peptide-centric docking topology with minimal MHCβ engagement. A van der Waals clamp at GAD65 P5Y/P7W stabilized TCR—pMHC interactions and prolonged complex lifetime despite modest equilibrium affinity, establishing a kinetic signature of tolerogenic recognition. Alanine-scanning confirmed a flexible, low-constraint peptide footprint. For DQ6—InsB10-21 TCRs, mutagenesis and binding assays indicate a C-terminal-shifted docking mode, suggesting a recognition topology favoring regulatory engagement. To test whether these signatures are characteristic of peripherally induced Tregs (pTregs) under autoimmune pressure, insulin-specific CD4+ Tregs were enumerated from pancreatic lymph nodes and islets of NOD.FoxP3-eGFP mice via flow cytometry with Nrp-1. Single-cell RNA-seq will be used to define clonotypes and transcriptional programs, assessing whether this unconventional recognition are features of pTregs. Conclusion These findings establish a structural and kinetic blueprint for protective HLA—Treg interactions, highlighting unconventional TCR footprints as mechanistic features that may enforce peripheral tolerance in T1D. Funding Source n/a Topic Categories Basic Autoimmunity (BA)

Specific Bile Acids Elicit the Type-I Interferon Response Through the cGAS-STING Pathway 2329596

Abstract Introduction Bile acids are metabolites crucially involved in lipid metabolism and immune regulation. Despite the recent identification of enormous bile acids differing in composition, their biological functions and mechanistic underpinnings remain largely elusive. Methods In this study, we demonstrate that specific bile acids DCA, CDCA and LCA are capable of triggering the type-I interferon response (IFN-I) in various cells, including colonic epithelial cells, macrophages and fibroblasts. Genetic and pharmacologic analyses revealed that these three bile acids impinged on a common IFN-I-inducing cGAS-STING pathway, whose activation associated with the cytosolic release of mitochondrial DNAs. Phosphoproteomics indicated that DCA treatment led to a wide array of changes across numerous signaling pathways, including TBK1-IRF3, AKT-mTOR, PKA-BAD and CaMKII-NFAT. Results The downregulation of Bcl-2 abundance and BAD phosphorylation coincided with the formation of Bax/Bak foci on the mitochondrial membrane. Chemical blockade or genetic knockdown of Bax/Bak diminished DCA-induced Ifnb1 expression, revealing a crucial role of Bax/Bak pore in mtDNA release. The induction of the IFN-I response also depended on inter-organelle interactions among the endolysosome, ER and mitochondria, as cholesterol-dependent endocytosis and ER-derived calcium flux promoted DCA’s ability to induce the IFN-I response. Further, intraperitoneally administered DCA elicited the IFN-I response in various organs and tissues contingent on the STING pathway. Conclusion Together, these findings identify the cGAS-STING pathway as a mechanistic underpinning of specific bile acids and provide new insights into therapeutic interventions for bile acid-related pathologies. Funding Source The National Natural Science Foundation of China Topic Categories Immune Response Regulation: Molecular Mechanisms (IRM)

Characterizing the importance of the interaction between complement component C1q and the tumor microenvironment in colorectal cancer 2301362

Abstract Introduction Within the tumor microenvironment, C1q and its receptors (gC1qR and cC1qR) have been found to play both pro- and anti-tumorogenic roles. gC1qR secretion has been observed to act as a metastatic driver and play a role in tumor defense. The current study aims to understand the interactions of both membrane-localized and secreted C1q and C1qRs in the tumor microenvironment of colorectal cancer (CRC), as well as potential differences in these interactions between African American (AA) and Caucasian American (CA) cell lines. Methods Western Blot analysis revealed that both C1q and the C1qRs were expressed in all cell lines at both whole-cell and membrane levels, though the detection of C1q itself varied. This was performed alongside ELISA assays to quantitatively assess secretion of C1q and the C1qRs. gC1qR was demonstrated to be secreted into the extracellular environment by all four cell lines; C1q secretion was observed in small amounts. gC1qR secreted into the tumor microenvironment may compete with membrane-localized gC1qR for the binding of anti-gC1qR, potentially playing a protective role against immune-cell-expressed C1q. Cells from each line were treated with C1q, gC1qR, cC1qR, and the antibodies (α) to each, and MTT assays were used to study cell viability and proliferation. Results Increased dose of C1q was found to promote tumor cell proliferation in CRC, likely favoring the overexpression of C1q by other cell types within the microenvironment for growth. Cell lines from CAs produced pro-proliferative responses when treated with C1q. AA cell lines demonstrated greater sensitivity to treatment with αC1q. This was further supported by a significant drop in viability attributed to the inhibition of the receptor cC1qR using αcC1qR. Conclusion These findings point towards C1q and C1qRs as potential therapeutic targets in CRCs, and more in-depth studies into the role of these components are ongoing to further understand the mechanism by which they act within the tumor microenvironment. Funding Source NY State funds from the Associated Medical Schools of New York Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

CNPY2 controls Macrophage Metabolic Programming and Epigenetic Remodeling 2305267

Abstract Introduction Understanding the metabolic—epigenetic axis in macrophages is critical for human health. In cancer, metabolic and epigenetic reprogramming in tumor-associated macrophages (TAMs) can drive tumor-promoting phenotypes, aiding immune evasion and therapy resistance. However, the regulators linking these processes remain unclear. We previously found that Canopy homolog 2 (CNPY2) promotes chemical hepatocarcinogenesis by regulating macrophage cytokine production, migration, phagocytosis, and cytotoxicity. CNPY2 binds TLR4 and enhances NF-κB—dependent cytokine production in liver macrophages, thereby promoting DEN-induced HCC. Methods To investigate whether CNPY2 influences macrophage immunometabolism and associated chromatin modifications, we generated Cnpy2 knockout mice and used a carcinogen-induced liver cancer mouse model, combining with RNA-seq analysis, qRT-PCR and Western blotting. Results RNA-seq analysis revealed distinct transcriptional changes in metabolic pathways, including de novo lipogenesis, Fatty acid oxidation, and the TCA cycle between wild-type (WT) and Cnpy2-knockout (KO) liver macrophages. Gene-set enrichment analysis further showed altered expression of epigenetic regulators and histone modifying enzymes in Cnpy2-deficient macrophages. We then performed qPCR on selecting metabolic genes, confirming alterations of several RNA-seq-identified targets. Consistent with these findings, protein levels of metabolic enzymes, particularly in acetyl-coA pathway, were significantly increased in Cnpy2 KO liver macrophages. In addition, global histone H3 acetylation was also elevated in Cnpy2 KO liver macrophages compared with WT counterparts. Conclusion Our data suggest that CNPY2 plays a previously unrecognized role in coordinating macrophage metabolic programming and epigenetic regulation. These findings provide an initial framework for understanding how CNPY2 may integrate metabolic cues with chromatin state to shape macrophage function. Funding Source NCI R01CA270166 Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

PPARα modulation of lipid metabolism alters host defense and Staphylococcus aureus virulence during superinfection 2309857

Abstract Introduction Secondary bacterial superinfections following influenza remain a critical driver of respiratory mortality, particularly when caused by MRSA. While bioactive lipids are known regulators of inflammation, the molecular mechanisms linking lipid metabolism to compromised host defense remain incompletely understood. We investigated the role of PPARα, a nuclear receptor that regulates fatty acid oxidation, in shaping innate immune dysfunction during superinfection. Methods To investigate cellular mechanisms, hMDM and primary human neutrophils were treated with PPARα agonists and antagonists, followed by infection with MRSA. The accumulation of lipid droplets (LD) and the phagocytic activity were quantified using fluorescence microscopy. Additionally, to examine the in vivo transcriptional landscapes, single-cell RNA sequencing was performed on innate immune cells isolated from superinfected C57BL/6 mice, in comparison to PPARα-deficient (Ppara−/−) mice. Results Our research identifies a signaling pathway involving CYP450 and PPARα, in which eicosanoids induced by influenza trigger abnormal activation of PPARα. This creates a metabolic trade-off: the increased biogenesis of LD significantly suppresses phagocytosis and the ability to kill bacteria. We demonstrated that this lipid sequestration driven by PPARα diverts metabolic resources, which effectively impairs phagocytes and increases the burden of MRSA. Additionally, scRNA sequencing revealed a shift from pro-inflammatory to anti-inflammatory programs in wild-type mice compared to Ppara-/- mice, highlighting PPARα as a key factor contributing to susceptibility. Conclusion Collectively, these findings demonstrate that CYP450-mediated activation of PPARα functionally disrupts the neutrophil/monocyte axis by prioritizing lipid storage over pathogen elimination. Targeting this immunometabolic switch offers a novel therapeutic strategy to restore phagocytic competency and alleviate the severity of post-viral bacterial pneumonia. Funding Source N/A Topic Categories Mucosal and Regional Immunology (MUC)

CD14 directs Fas-mediated apoptosis in dendritic cells to restrain neutrophil-driven psoriatic inflammation 2266853

Abstract Introduction Immune cell turnover is vital for resolving chronic inflammation like psoriasis, which is driven by DCs. CD14, known as a TLR4 co-receptor for activation, was hypothesized to be a molecular switch, coupling pro-apoptotic Fas signaling to immune resolution. This study defines CD14’s cell-type-specific role in regulating Fas-mediated DC apoptosis and its impact on psoriatic inflammation and neutrophil recruitment. Methods Psoriasis was induced using the IMQ mouse model; severity and neutrophil infiltration were quantified. Conditional Knockout (CKO) models achieved cell-type-specific CD14 deletion in dDCs, LCs, and Mφs. Mechanistic analysis included Caspase-8 quantification in murine skin lesion protein extracts. Signaling redirection was confirmed via NF-κB p65 nuclear translocation and chemokine expression (Cxcl1, Cxcl2) after Fas ligation. Results CD14 expression inversely correlated with disease severity and neutrophil infiltration. CKO analysis confirmed a dermal DC-specific role: CD14 deficiency only in dDCs (dDC-CKO) exacerbated inflammation and led to a massive influx of neutrophils. CD14 was critical for promoting caspase-8-dependent Fas signaling, enabling DC apoptosis. In CD14-deficient dDCs, the Fas signal was redirected toward pro-inflammatory NF-κB pathways, amplifying the inflammatory loop via robust chemokine expression. Conclusion CD14 acts as a critical, dDC-specific molecular switch, balancing inflammation and resolution. It facilitates caspase-8 activation, driving efficient Fas-mediated DC apoptotic clearance. In its absence, the Fas signal is corrupted, activating NF-κB, which sustains inflammation by amplifying neutrophil recruitment and exacerbating pathology. This reveals a novel CD14 role in coupling apoptotic turnover to immune resolution, positioning it as a selective therapeutic target for chronic skin inflammation. Funding Source This study was supported by National Research Foundation of Korea (NRF) grants funded by the Ministry of Science and ICT (2023R1A2C2002522 to Y.J.; and 2021R1A5A2030333 to Y.K., Y.L., S.R., B.O., I.H., H.K., and Y.J.) and by the Ministry of Education (RS-2024-00411734 to K.N.). Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

B7 co-stimulation antagonizes RORγt+ regulatory T cells and tolerance to gut microbiota 2254003

Abstract Introduction Regulatory T (Treg) cells recognizing dietary or microbiota-derived antigens express RORγt and are essential for intestinal immune tolerance. A recent paradigm-shifting finding revealed that these cells require major histocompatibility complex class II (MHCII) on RORγt+ antigen-presenting cells (APCs) to provide signal one. Here, we evaluated signal two and found that broad blockade of co-stimulatory molecules B7-1 (CD80) and B7-2 (CD86) unexpectedly provoked the expansion of microbiota-specific RORγt+ Treg cells. Methods Cutting-edge transgenic, knockout, and adoptive-transfer mouse models were employed to define how the induction of RORγt+ Treg cells is regulated by MHCII (signal one) from RORγt+ APCs and B7 co-stimulation (signal two) from non-RORγt+ APCs to maintain immune tolerance to gut microbiota. Flow cytometry, ex vivo T cell differentiation, histology, and colitis models induced by Helicobacter hepaticus plus anti—IL-10R antibody, combined with co-stimulation blockade and CTLA4-Ig treatment, were integrated to dissect the interplay between RORγt+ APCs and RORγt+ Tregs. Results Mechanistically, B7/CD28-dependent Akt signaling antagonizes the core transcriptional program of RORγt+ Treg cells through the Forkhead box protein O1 (Foxo1) pathway. The expansion of RORγt+ Tregs was recapitulated by CTLA4-Ig but required MHCII (signal one) on RORγt+ APCs together with inhibition of B7 co-stimulation (signal two) from non-RORγt+ APCs. CTLA4-Ig treatment during pathobiont colonization and IL-10R blockade restored microbiota-specific RORγt+ Treg generation and protected against experimental colitis, reducing IL-17+ and TNF+ T cells. Conclusion These results mechanistically define that B7 co-stimulation limits microbiota-specific RORγt+ Treg cells, while identifying CTLA4-Ig as an approach to enhance immune tolerance and reduce inflammatory cytokines in the intestine when acting in concert with RORγt+ APCs, provoking a novel therapeutic strategy for patients with chronic intestinal inflammation. Funding Source NIH/NCI - K99CA290052 Topic Categories Mucosal and Regional Immunology (MUC)

Identification of functional noncoding variants regulating Fc gamma receptor expression in human natural killer cells 2260713

Abstract Introduction Antibody-dependent cellular cytotoxicity (ADCC) is an important effector mechanism through which antibody-based therapies drive target cell clearance. Natural Killer (NK) cells mediate ADCC through Fc gamma receptor IIIa (FcγRIIIa) expressed on their surface, with variation in receptor abundance affecting cytotoxic activity and treatment efficacy. While coding polymorphisms in FcγR genes have been linked to altered receptor function, genome-wide association studies (GWAS) have also associated variation in noncoding regions of the low-affinity FcγR cluster with complex disease and treatment outcomes. However, the functional impact of these noncoding variants remains largely uncharacterized. Here, we aim to investigate noncoding variants in the Fc region with allele-specific protein binding that may influence receptor abundance and modulate NK cell-mediated ADCC. Methods To identify functional variants in the Fc region, we screened an oligonucleotide library containing sequences from 4,323 single nucleotide polymorphisms (SNPs) using high-throughput Regulatory Element Sequencing (Reel-seq). Unlike GWAS, which identifies context-specific associations, Reel-seq is an unbiased assay that detects allele-specific protein-DNA interactions through electrophoresis mobility shift assays (EMSA). This allows for the identification of variants with potential regulatory activity based on direct protein binding. Results Using Reel-seq, we identified a set of functional SNPs in human NK cell lines (NK-92, NKL). Ongoing work aims to attribute these variants to differences in FcγR expression and to map regions of regulatory activity within Fc that may influence receptor abundance. Conclusion Altogether, this work will define regulatory variants affecting FcγR abundance, with implications for antibody-based therapies. Funding Source National Institutes of Health Grant #1R01AI187318-01, North Carolina State University College of Veterinary Medicine Topic Categories Innate Immune Responses and Host Defense: Molecular Mechanisms (INM)

A Bifunctional Colloidal Quantum Dot Diode for Nanosecond Short‐Wave Infrared Detection and Emission

ABSTRACT Short‐wave infrared (SWIR) technologies are vital for optical communication, all‐weather imaging, and advanced spectroscopy. Using a single diode for light detection and emission can reduce device footprints, lower cost and enable fast, bidirectional communication. However, dual detection/emission operation often involves incompatible choices of material and stack design, which result in devices with inferior performance. Here, we introduce a bifunctional PbS QD diode stack that achieves, for the first time, nanosecond‐fast photodetection and emission in a single SWIR device. Using thin active layers with high charge‐carrier mobility and compact geometries, we demonstrate a record 2 ns response in photodiode (QDPD) mode and 11.7 ns rise time/6.5 ns fall time in light‐emitting diode (QDLED) mode. This high‐speed operation is combined with a 49% external quantum efficiency (EQE) and 2.6 × 10 1 2  cm·Hz 0 . 5 ·W − 1 detectivity for QDPD operation, while the QDLED reaches 8.1% EQE. These high‐speed, compact devices unify imaging and detection with a single, CMOS‐compatible platform, and set the stage for integrated SWIR photonics and bidirectional optical interconnects. This work demonstrates the potential of QDs to unify imaging, detection, and communication in a single materials platform.

Molecular Chelating‐Clamp Strategy Using Dithiol Antidotes Enables Efficient and Stable Inorganic Perovskite Solar Cells

ABSTRACT The photovoltaic performance and stability of all‐inorganic perovskites are critically compromised by halide vacancy defects and concomitant ion migration, both arising from their intrinsically soft lattice and mixed ionic‐electronic character. To simultaneously address both issues, we introduce sodium 2,3‐dimercapto‐1‐propanesulfonate (DPS), a sulfonated thiol molecule that acts as a multifunctional chelating clamp. Unlike conventional monodentate passivators, DPS employs a bidentate chelation strategy: its two thiol groups coordinatively bind to undercoordinated Pb 2+ sites, forming a stable five‐membered ring. The flexible three‐carbon linker enables conformational adaptation to heterogeneous grain‐boundary microenvironments, while the sulfonate group provides electrostatic anchoring and spatial orientation, guiding the thiol moieties toward targeted defect sites. Moreover, DPS retards the crystallization kinetics during film annealing, resulting in enlarged grains, reduced residual strain, and enhanced film homogeneity. This synergistic integration of molecular adaptability, chelate‐based defect passivation, and crystallization regulation yields CsPbI 3‐x Br x perovskite films with lower trap density, prolonged carrier lifetime, and favorable energy alignment. Consequently, solar cells incorporating DPS achieve a champion power conversion efficiency of 22.28%, among the highest for all‐inorganic perovskite devices, alongside substantially enhanced operational and environmental stability. The strategy underscores the potential of tailored molecular design for enabling efficient and stable perovskite photovoltaics with straightforward processability.

NiMo Dual‐Atom Dimers on Pd Nanosheets for Selective C─H and C─C Bond Cleavage of Ethylene Glycol From Waste Plastics

ABSTRACT Herein, we report the CO gas–mediated synthesis of palladium nanosheets (PdNS) as the first palladene support for atomically dispersed dimer catalysts. We further present the first report of NiMo dual‐atom dimer immobilization on PdNS (NiMo‐DA/PdNS) using rapid CO 2 laser irradiation within 10 min. The NiMo‐DA/PdNS platform exhibits enhanced ethylene glycol (EG) oxidation reaction (EGOR) activity with potential‐dependent product selectivity. At 1.0 V vs. RHE, glycolate (C2 product from selective C─H bond cleavage) was obtained with a Faradaic efficiency (FE) of 81% and a yield rate (YR) of 1.14 mmol h −1 cm −2 . At 1.6 V vs. RHE, formate (C1 product from C─C bond cleavage) was selectively produced with an FE of 77.9% and a YR of 0.39 mmol h −1  cm −2 . Theoretical calculations further corroborate these performance trends and elucidate the mechanism that C─C bond scission is facilitated by electron transfer to the catalyst surface at higher potentials, lowering the reaction free energy and enhancing C1 formation. This study demonstrates concurrent high selectivity toward both glycolate and formate while efficiently recovering high‐purity terephthalic acid (TPA) monomers from polyethylene terephthalate (PET) hydrolysate electrolysis over 50 h, highlighting the practical potential of atomically engineered catalysts with real‐world PET upcycling.

Incidence of mother-to-child transmission of hepatitis B virus and associated factors in Addis Ababa, Ethiopia: a prospective cohort study

Iron overload induces intestinal macrophage dysfunction and promotes enteric infection in hemochromatosis 2255857

Abstract Introduction Hemochromatosis is an iron overload (IO) disorder that causes multi-organ damage, immune dysfunction, and increased susceptibility to enteric infections. There have been numerous case studies reporting septic-like outcomes for hemochromatosis patients infected with Gram-negative, enteric Yersiniae. However, the impact of hemochromatosis on intestinal immunity and its role in exacerbating infection remains unclear. Methods Our lab has established a mouse model in which C57BL/6 mice are fed a high-iron diet for four weeks, resulting in elevated serum iron, transferrin saturation, ferritin levels, tissue iron deposition, and heightened susceptibility to Yersinia enterocolitica (Ye) infection. Results During intestinal inflammation, the monocyte-macrophage differentiation process is stalled, leading to the accumulation of monocytes and immature intestinal macrophages (IMs). Immature IMs fail to differentiate into highly phagocytic, reparative, mature IMs seen at homeostasis, but instead remain highly responsive to pattern recognition receptor stimulation and are potent producers of inflammatory cytokines. I have observed that increasing iron levels elevate CCL2 levels in the serum and intestine, leading to increased monocyte mobilization and intestinal infiltration. In IO mice, the intestine contains more inflammatory monocytes and immature IMs, along with elevated levels of TNF-a, IL-1B, and IL-6 cytokines, which are known to be produced by these cell types. This phenotype is dependent on both high iron and CCR2 signaling and is exacerbated following Ye infection. Conclusion My data indicate that the CCL2/CCR2 axis has a detrimental role during Ye infection in IO mice, as disruption of this axis significantly improves animal survival. I hypothesize that IO-induced inflammation and CCL2/CCR2 signaling stalls the monocyte-macrophage differentiation process in the intestine, resulting in the accumulation of immature, inflammatory IMs that contribute to mortality during Ye infection. Funding Source NIAID R01AI162670 Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

Spatial proximity sequencing maps developmental dynamics in the Germinal Center 2332687

Abstract Introduction Spatial profiling of proteins and protein interactions is essential for understanding immune responses, yet existing methods cannot simultaneously measure protein complexes in situ. We developed Spatial Proximity-Sequencing (Sprox-seq), a multi-omic technique that simultaneously profiles proteins, protein complexes, and mRNAs with spatial resolution in intact tissues. Methods Sprox-seq integrates proximity ligation assay with spatial transcriptomics on the 10x Visium platform. Antibody-oligonucleotide conjugate pairs targeting 32 proteins were applied to human tonsil sections. Upon spatial proximity, probes ligate to generate PLA products captured alongside mRNAs via spatial barcodes. Fisher’s Exact Test and fractional overlap analysis were used to identify and quantify protein complexes. Results We profiled 32 proteins, 528 pairwise interactions, and thousands of mRNAs across human tonsil germinal centers. Protein interaction networks revealed higher complexity in the Light zone compared to Dark zone, consistent with B cell selection dynamics. Trajectories inferred from protein interactions uncovered a B cell state transition distinct from that inferred by RNA. We identified spatially enriched complexes including CD19-CD21, CD21-CD35, and directly captured VLA-4—VCAM1 mediated B cell-FDC interactions in the Light zone. Conclusion Sprox-seq enables simultaneous spatial profiling of transcriptomes, proteomes, and interactomes, revealing protein interaction dynamics during B cell state transition that cannot be inferred from RNA or protein expression alone. This technology provides new insights into cell-cell communication in immune tissues. Funding Source NIH grants AI175371, R35GM148231, and GM127527 (S.T.), P. Allen Distinguished Investigator Award (S.T), and Chan-Zuckerbeg Chicago Biohub Investigator Award (S.T. and M. R. C.). Topic Categories Technological Innovations in Immunology (TECH)

GNTI-932: A Targeted, Scalable, and Hypoimmune Allogeneic Engineered Treg therapy for the treatment of Inflammatory Bowel Disease 2251383

Abstract Introduction Autologous polyclonal regulatory T cell (Treg) therapies hold promise for treating autoimmune and inflammatory bowel disease (IBD), but face challenges with specificity, stability, cost, long manufacturing times, inconsistent quality, and logistical complexity. Allogeneic approaches can overcome some of these barriers but introduce risks of immune rejection and graft-versus-host disease. Methods To address this, we developed GNTI-932, a precision-engineered, allogeneic, gut-targeted Treg therapy. GNTI-932 integrates four innovations: gut-specific targeting via synthetic binding receptors; stable Treg phenotype by FOXP3 overexpression in bulk CD4+ T cells; a rapamycin-inducible IL-2 signaling complex (CISC) supporting in vivo stability and purity; and immune evasive engineering (IEE) combining HLA class I/II knockout with a proprietary NK cell inhibitor to prevent rejection. Results In vitro, GNTI-932 showed a characteristic Treg phenotype (CD25, CTLA-4, LAP, GARP), suppressed effector CD4+ T cells, secreted no proinflammatory cytokines, and resisted allo-rejection. In vivo, murine surrogates localized to inflamed gut, minimized off-target trafficking, improved survival, reduced inflammation and restored mucosal integrity. GNTI-932 also persisted beyond 80 days, enabled by IEE. Conclusion GNTI-932 is a novel, hypoimmune, antigen-specific, off-the-shelf immunotherapy for restoring tolerance in IBD, designed to be scalable and affordable for widespread use. Funding Source Bristol Myers Squibb provided initial funding. Topic Categories Therapeutic Approaches to Autoimmunity (THER)