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Anti‐Freezing Fiber‐Shaped Iontronic Synapses With Ultralow Energy Consumption and High Rectification

ABSTRACT Fiber‐shaped iontronic synapses (FEISs) are emerging as promising building blocks for next‐generation wearable neuromorphic computing due to their ability to emulate biological signal transmission and plasticity. However, their practical application remains limited by poor environmental adaptability, high energy consumption, and inadequate rectification behavior. Herein, we report a FEIS with anti‑freezing capability that simultaneously achieves ultralow energy consumption and a high rectification ratio. The FEIS is constructed by directly assembling tetrachlorobenzoquinone and zinc hexacyanoferrate onto carbon nanotube fibers via π–π stacking, combined with a sucrose‐modified polyacrylamide hydrogel electrolyte that inhibits ice formation through hydrogen bond regulation. Our FEIS exhibits stable synaptic operation at −20°C, with an ultralow energy consumption of 17 fJ per synaptic event, and a high rectification ratio of 17.9, enabled by asymmetric Faradaic reactions and ionic relaxation kinetics. These characteristics enable the FEIS to achieve robust unidirectional information transmission and stable synaptic operation, even under cryogenic conditions. Furthermore, the FEIS demonstrates reliable operation in ionic logic circuits and robotic control systems, achieving 95.2%‐digit recognition accuracy at −20°C. This work expands the operational boundaries of flexible iontronic neuromorphic devices for applications in extreme environments.

Overcoming Raoult's Law via Ligand Field Polarization‐Mediated Interfacial Water Activation for High‐Performance Solar Evaporation

ABSTRACT In traditional saline water evaporation systems, water evaporation is severely suppressed by salt solute, which strictly follows Raoult's law and thus hinders the solar‐driven evaporation. Herein, a ligand field‐induced electrostatic polarization strategy is proposed to thermodynamically activate water molecules through disrupting the ideal solution behavior restricted by Raoult's law. By co‐coordinating Fe 3+ and Co 2+ within a sodium alginate hydrogel network, pronounced electron redistribution is induced in the polymer framework, generating a polarized coordination environment that disrupts the cooperative hydrogen‐bond network of water and thereby decreases the water vaporization enthalpy significantly. Combined with a biomimetic hierarchical hydrogel featuring a bubble‐channel and dual‐network architecture, the embedded microcavities substantially expand the active evaporation interface, while the bimetal‐regulated axial pumping and radial wetting dual‐network enables efficient water transport and localized heat management. Therefore, the optimized hydrogel achieves a high apparent evaporation rate of 5.82 kg m −2 h −1 under 1‐sun irradiation. Moreover, the atomically dispersed transition metal sites provide intrinsic catalytic activity for efficient degradation of organic pollutants. This work demonstrates an integrated strategy combining ligand field‐driven thermodynamic water activation with multiscale dual‐network engineering, offering a versatile platform for solar‐driven desalination and wastewater purification in both remote and off‐grid areas.

Stable and tunable expression of human peripheral myelin protein 22 in Rat Schwann cells

Optimizing the radiolytic degradation of aspirin and acetaminophen in aqueous solutions using a Rhodotron electron-beam accelerator and central composite design

A high fat diet exacerbates 5FU-induced intestinal mucositis and impairs the immune response in tumor-bearing mice 2331585

Abstract Introduction Obesity and cancer are among the largest public health burdens worldwide and research continues to demonstrate strong associations between them. Being overweight or obese increases the risk for all-cause and cancer-specific mortality and increases the risk for developing 13 different types of cancers. Chemotherapy-induced mucositis (CIM) affects as many as 90% of cancer patients undergoing treatment. One such drug used to target gastrointestinal cancers is 5-Fluorouracil (5FU), which causes GI distress, reduces quality of life, treatment tolerance, and survival. Diet has been shown to be a modifiable risk factor in diseases and cancers. A high fat diet (HFD) causes many health concerns, including detrimental effects on intestinal epithelium. The purpose of this study was to investigate whether a HFD exacerbates 5FU-induced mucositis in tumor-bearing mice. Methods C57BL/6 mice were given either a sham (Control) or 1 injection of MC38 (2x10^4) adenocarcinoma cells in the right hind flank, which caused cancerous growth at the injection site only. Mice were then given 3 cycles of chemotherapy (1 cycle: 5 injections of 5FU (35 mg/kg/d); 5d recovery), inducing intestinal mucositis, or PBS injections (Vehicle). Mice were euthanized, and samples were collected for downstream analysis. Results A HFD significantly (p < 0.05) exacerbated 5FU-induced symptomology (diarrhea, rectal bleeding, weight loss) and intestinal apoptosis (Bax), impaired intestinal inflammatory (IL-6, TNF α) and mucin (Muc2) gene expression, but did not exacerbate 5FU-induced villi or goblet cell loss. A HFD significantly increased the relative percent of immune cells in the colonic lamina propria, but significantly impaired myeloid-derived cells (neutrophiles, all/recruited macrophages, dendritic cells) compared to a lean diet. Conclusion We believe a HFD caused an inappropriately muted response following chemotherapy administration that likely contributed to worsened mucositis symptomology and disrupted intestinal gene expression. Funding Source F31AT012589 (BMB), F31CA278490 (TDC), F99CA294251 (TDC), K99CA27689 (BNV), U01CA272977 (EAM) Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)

Targeting NK Cell Trafficking and Function with Novel Oral Adjuvant to Enhance HIV Vaccine Efficacy 2306669

Abstract Introduction Though an effective HIV vaccine remains elusive, the ALVAC/gp120/alum regimen shows partial efficacy, mediated in part by antibody-dependent cell-mediated cytotoxicity of NK cells. NK cells play a dual role in vaccines: their cytokines support antibody responses, but their cytotoxicity can kill T follicular helper cells, impairing germinal center (GC) reactions and affinity maturation. Our prior work showed that an aryl hydrocarbon receptor (AHR) agonist as an oral adjuvant to ALVAC enhanced splenic NK cell memory and ADCC phenotypes, thought to improve vaccine efficacy. We investigated how this novel adjuvant affects NK cell phenotypes involved in antibody responses to further promote vaccine efficacy. Methods Twenty-four age-sex-matched C57BL/6 mice were randomized into four groups: ALVAC, I3C, ALVAC+I3C, and a PBS control. ALVAC-SIV was given intramuscularly at week 0, with an ALVAC-SIV/gp120/alum booster at week 2. Oral I3C was given daily. After sacrifice at week 4, lymphocytes from blood, bone marrow, lung, and spleen were analyzed via spectral flow cytometry. Group differences were assessed by Mann-Whitney U tests; phenotypic clusters by UMAP and FlowSOM; and polyfunctionality by SPICE. Results The oral adjuvant with ALVAC enriched CD62L+ NK cells in blood and bone marrow (p < 0.0001), associated with lymph node homing. The NK cells produced less granzyme B (p < 0.0001) but more TNFα and IL-1β (p < 0.01), consistent with B cell support. Polyfunctional analysis shows that these NK cells diversified into multi-cytokine-producing subsets. Together, these findings suggest that the adjuvant reprograms NK cells to promote GC responses and enhance vaccine-induced antibody protection. Conclusion This study demonstrates that our novel oral adjuvant reprograms NK cells to favor lymph node homing and cytokine-mediated B cell help, supporting GC responses essential for antibody maturation. These findings highlight the promise of AHR agonists as innovative adjuvants to enhance HIV vaccine efficacy. Funding Source NIAID/K22 AI127072 award to N.P.M.L Topic Categories Vaccines and Immunotherapy (VAC)

Exploring the role of complement in extracellular vesicle production: Insights into host-pathogen interactions 2258111

Abstract Introduction Increased intravascular coagulation is a molecular hallmark of sepsis and we showed that extracellular vesicles (EVs) from human neutrophils challenged with bacteria activate the coagulation cascade. Discovery of the EV biogenesis pathway may lead to the ability to interfere with EV production and reduce coagulation. Methods To investigate the mechanism of EV biogenesis, we performed proteomics on three EV subsets: those produced spontaneously, in response to fMLF, and after staphylococcal challenge. After protein abundances were normalized, we compared fold changes between subsets. We validated the proteomic results with immunoblotting. The role of nSmase was evaluated using GW4869, an nSmase inhibitor. Results Although the production of some neutrophil EV subsets relies on membrane curvature caused by neutral sphingomyelinase (nSmase), the production of EVs in response to staphylococcal challenge was nSmase-independent. Annexins and proteins involved in the formation of the membrane attack complex (C5b-9) were enriched in EVs produced after staphylococcal challenge. Conclusion Based on these results, we propose that complement-mediated bystander activation produces membrane damage, which initiates Annexin-mediated repair and EV production. To test this, we opsonized bacteria with C9-sufficient or deficient serum, and measured production of EVs by monitoring Flotillin-1. In the absence of C9, less Flotillin-1 was observed compared to the control. These data suggest a role for complement in EV production. Funding Source The Frost Fund in the Cal Poly Bailey College of Science and Mathematics Topic Categories Innate Immune Responses and Host Defense: Cellular Mechanisms (INC)

CUE-401 is a Novel TGF-beta/IL-2 Fusion Protein that Induces Selective Expansion of Functional, Stable FOXP3+ Tregs for Treatment of Autoimmunity 2255949

Abstract Introduction Regulatory T cells (Tregs) are critical for maintaining peripheral tolerance and immune homeostasis, making them attractive therapeutic targets for treating autoimmune and inflammatory diseases. Efforts to expand Tregs in patients have focused on delivering IL-2 to promote expansion of existing FOXP3+ Tregs. In contrast, CUE-401 was designed to combine novel attenuated variants of TGFb and IL-2 into a single fusion protein, thus delivering the two key signals that are required for conversion of effector T cells into induced Tregs (iTregs) while also promoting expansion of existing Tregs. In the context of autoimmunity or GVHD, where TCR stimulation is provided by autoantigens or alloantigens, respectively, the ability of CUE-401 to convert autoreactive CD4+ T cells into iTregs as they become activated may provide significant advantages for the treatment of patients with these diseases. Methods CUE-401 activity was tested in vitro in human healthy donor PBMCs and in vivo in models of xenogeneic GVHD and EAE. Treg frequency and phenotypes were assessed by flow cytometry. Results CUE-401 induces and expands highly functional and stable Tregs. In vivo, CUE-401 induces highly selective Treg expansion across mice, rats, and non-human primates at dose levels that are safe and that provide significant therapeutic benefit in multiple disease models, including xenogeneic GVHD and EAE. CUE-401 treatment significantly delays disease onset in EAE and GVHD while reducing effector T cell responses and expanding Tregs that are able to migrate to inflamed tissues and limit diverse types of inflammatory responses, including TH17 and TH1 responses. Conclusion Together, these results demonstrate that CUE-401 induces functional, stable Tregs and promotes control of diverse inflammatory responses, supporting the therapeutic potential of CUE-401 to restore immune balance for the treatment of autoimmune and inflammatory diseases. Funding Source n/a Topic Categories Therapeutic Approaches to Autoimmunity (THER)

The Prevalence and Significance of Established Cancer Stem Cell Biomarkers in Follicular Lymphoma Patients 2260603

Abstract Introduction Follicular lymphoma (FL), the most common form of non-Hodgkin’s lymphoma, is frequently indolent but has a high risk for multiple relapses. Despite therapeutic advances, 45% of relapsed patients have a reported median survival of 1-2 years and account for up to one third of lymphoma-related deaths. Cancer stem cells (CSCs) with self-renewal ability are thought to be responsible for tumor progression and chemo resistance. Here we investigated the prevalence and significance of CSCs biomarkers in FL patients (pts). Methods AI software Deep6 and Slicer Dicer were used for query building in EPIC (ICD-10 code: C82.9), resulting in 105 FL pts with available lymph node biopsy blocks. Demographic and clinicopathological characteristics of these FL pts were collected. FFPE blocks from 59 FL pts were collected and used to create tissue microarray slides (TMA). H&E staining and IHC staining of FL cells (CD20) and CSCs (ABCG2, Ki67, and OCT3/4) were performed. Frequency of CSCs was analyzed using HALO® software. All results were divided and compared in 2 groups: FL pts with short-term survival (less than 5 years) and long-term survival (more than 20 years). Unpaired Student’s t-test was used for statistical analysis in these groups. Results There were 26 (44.1%) pts with short-term survival and 33 (55.9%) FL pts with long-term survival in our studied patients. There was no difference in the frequencies of CD20+ cells in the short-term and long-term survival groups (p > 0.05). However, a significant increase in the frequencies of single CSC markers (ABCG2, Ki67, or OCT3/4) as well as CSC combination markers (ABCG2+Ki67+OCT3/4+) was found in the short-term survival group compared to the long-term group (all with p values < 0.05). Conclusion Short-term survival FL pts demonstrated higher expression of CSC markers in their lymph node biopsies, indicating their prognostic value in distinguishing FL patients at the highest risk of disease and worse outcome, and providing a guide for more effective therapy in FL. Funding Source Ladies Leukemia League Topic Categories Tumor Immunology: Cellular Responses and Tumor Microevironment (TIME)

Development of a Novel Mucosal Vaccine Against Clostridium difficile 2261214

Abstract Introduction C. difficile (CD) is the leading cause of antibiotic-associated diarrhea and colitis. Vaccines for CD infection (CDI) have failed in Phase III trials as although serum antibodies induced by systemic immunization can neutralize CD toxins, these vaccines do not impact bacterial colonization and transmission. As such, our lab aims to develop a mucosal vaccine that can neutralize CD toxins, TcdA and TcdB, at mucosal surfaces, while also protecting from bacterial colonization and transmission. We hypothesize that a mucosal vaccine inducing mucosal IgA antibodies against TcdA and TcdB, as well as antibody against surface layer protein (SLP), would prevent bacterial colonization and eliminate a major cause of hospital-acquired infection. Methods We used papilloma-like particles as a mucosal vector to package plasmids encoding TcdA, TcdB, and SLP to form pseudoviruses as the mucosal vaccine. Mice were immunized orally and then tested for production of serum IgG and intestinal/fecal IgA against TcdA, TcdB and SLP, with detection being done by ELISA. Results We found the vaccine induced a significant amount of serum IgG and intestinal IgA antibody against TcdA, TcdB, and SLP. We also challenged mice after oral immunization with the vaccine, and found the mice were protected against weight loss and diarrhea. Fecal CD CFU were also greatly reduced in the immunized mice as compared to unimmunized control mice. Conclusion Our preliminary results indicate that this strategy is warranted for further development of an effective mucosal CD vaccine and can potentially be applied to the development of other mucosal vaccines. Funding Source NIH Topic Categories Vaccines and Immunotherapy (VAC)

Monitoring antigen-specific T cell responses to B. burgdorferi 2253490

Abstract Introduction Despite decades of research into Borrelia burgdorferi immunopathogenesis, less is known about antigen-specific T cell responses to this bacterial pathogen than the role of antibodies. Studying antigen-specific T cell responses to B. burgdorferi has been challenging due to the relatively few immunological tools available. Methods To address this, we have engineered B. burgdorferi to express a well-characterized CD4+ T cell epitope from chicken ovalbumin (Bb-OVA). Using adoptively transferred OVA-specific T cells from OT-II TCR transgenic mice, we show that these OVA-specific T cells proliferate during infection in an antigen-specific manner in response to Bb-OVA but not Bb-control. Using a variety of markers, we have characterized these antigen-specific T cells during various stages of infection, and the sites to which OVA-specific cells migrate. Results While polarization of OVA- specific T cells driven by natural infection do not provide robust protection, we show that reprograming OVA-specific T cells in vitro to different T-helper polarizations before adoptive transfer can reduce bacterial burden and immunopathology in vivo. Conclusion Taken together, our data demonstrate that although T cells are misprogrammed during natural infection, one can overcome this by reprogramming T cells towards alternative polarizations to reduce burden and immunopathology (eg. carditis and arthritis). Understanding the basis of these mechanisms is key to well-informed vaccine design that, with the help of adjuvants which can polarize T cells towards different subsets, will elicit strong T cell responses to confer long-lasting protection. Funding Source n/a Topic Categories Microbial, Parasitic, and Fungal Immunology (MPF)

Novel Mouse Models Allow Selective Labelling and Depletion of Perinatal and Adult-derived Regulatory T Cells 2257791

Abstract Introduction Regulatory T cells (Tregs) that develop during the perinatal period (2-3 weeks after birth) are believed to be distinct from adult-derived Tregs. Previous approaches to selectively label perinatal versus adult derived Tregs have used Foxp3-GFP-Cre-ERT2 x R26YFP mice. This approach has two critical drawbacks: limited labeling of perinatal Tregs due to tamoxifen (TAM) toxicity, and failure to discriminate perinatal versus adult-derived Tregs later in life. Methods We developed two novel mouse models that overcome these limitations: Rag-Rox-cre-Rox x CAGS-DREERT2 x Foxp3-iDTR mice, in which developing Tregs express GFP until TAM is added, and Rag-Rox-STOP-Rox-Cre x CAGS-DREERT2 x Foxp3-iDTR mice, in which developing Tregs are GFP- until TAM administration. This allows us to selectively identify and delete Tregs that developed during the perinatal versus adult time frames. Results We used Rag-Rox-cre-Rox x CAGS-DREERT2 x Foxp3-iDTR mice to track the persistence of perinatal Tregs in tissues. At 15 weeks of age virtually all newly generated Tregs in the thymus were adult derived. In contrast, ∼21% of splenic Tregs were perinatally derived. Higher percentages of Tregs in the lungs (49.8%), small intestine (34.2%), meninges (39.9%), skin (63.7%) and liver (25.7%) were perinatal Tregs. By examining perinatal Tregs in the blood at 11 and 18 weeks after birth we noted that the percentage of perinatal Tregs did decay with time, albeit quite slowly (3.5%/week). We are currently examining how the TCR repertoire and suppressive capacity of perinatal versus adult Tregs differ. Finally, by depleting perinatal Tregs with DT in older mice we can test their function at homeostasis and during inflammatory conditions such as EAE. Conclusion We developed two novel and complementary mouse models that can selectively label and deplete perinatal or adult derived Tregs. These models will allow us to determine the distribution, persistence, and function of perinatal Tregs throughout life. Funding Source n/a Topic Categories Hematopoiesis and Immune System Development (HEM)

Bioinspired Photodetectors: From Nature to Advanced Applications

ABSTRACT Bioinspired photodetectors (BPDs) have achieved unprecedented advancements in dynamic regulation, energy efficiency, environmental adaptability, and multifunctional integration by emulating biological vision mechanisms. These devices ingeniously leverage nature‐optimized strategies, such as the dynamic adaptation of human vision, the wide‐field imaging capability of insect compound eyes, and the superior light‐harvesting efficiency of plant photosynthetic systems, thereby opening new pathways for next‐generation photodetection technologies. This review establishes a comprehensive theoretical framework that links biological inspiration to the advancement of photodetectors. It systematically examines the design principles, performance evaluation, material selection, fabrication techniques, recent progress, and cutting‐edge applications of BPDs, while also providing a critical assessment of current challenges and future prospects. By synergistically integrating fundamental biological insights with practical engineering solutions, this work aims to analyze the current state of BPDs research and explore future directions, ultimately heralding a new era for intelligent, efficient, and multifunctional optoelectronic systems.

Intimate Interaction Between Nucleic Acid and Conjugated Polymers in Organic Electrochemical Transistors Enables Ultrasensitive Biomarker Detection

ABSTRACT Ultrasensitive biosensors are crucial for pandemic prevention and healthcare monitoring. The interactions between biomolecules and functional materials, such as metals and semiconductors, have led to the development of highly sensitive biosensors. Organic semiconductors, known for their unique mixed ion and electronic conduction properties in aqueous solutions, show promise in these applications. However, the interactions between organic semiconductors and biomolecules remain poorly understood. In this study, we investigate the interaction between nucleic acid and a conjugate polymer by analyzing the performance of organic electrochemical transistors (OECTs). For the first time, we demonstrate that negatively charged ribonucleic acid (RNA) can interact with the conjugate polymer, leading to a decrease in the volumetric capacitance of the polymer channel in aqueous solutions. Based on this effect, OECTs are employed to detect various RNA biomarkers with high sensitivity, achieving multiplexed and selective detections of multiple RNA biomarkers at a low detection limit down to 10 −17  M. This portable biosensing platform can facilitate rapid, low‐cost and point‐of‐care diagnostics for various diseases.

Hepatitis B virus promotes hepatocellular carcinogenesis by activating IL-6-dependent tumor-macrophage crosstalk and M2-like macrophage polarization

CBCT-based submandibular fossa depth classification and panoramic fractal dimension analysis in the posterior mandible

CpG-Adjuvanted Heplisav-B Induces Strong Th1-Biased Innate Responses Compared to Alum-Adjuvanted HBV Vaccines in PLWH 2308661

Abstract Introduction Alum-adjuvanted HBV vaccines such as Engerix-B offer limited protection for people living with HIV (PLWH), achieving only 35—70% seroprotection (as defined by HBsAb titers ≥10 mIU/mL). While Heplisav-B’s CpG 1018 adjuvant improves immunogenicity in PLWH, its mechanisms for overcoming HIV-related immune dysfunction are not yet defined. Methods We performed multiplex cytokine/chemokine profiling assays and high-dimensional flow cytometry, including markers to interrogate cellular metabolism, to characterize early innate responses 24 hours after the first dose of Engerix-B or Heplisav-B in PLWH who were non-responders to prior HBV vaccination. Results Heplisav-B induced robust early innate activation, characterized by significantly elevated IP-10, MCP-2, and IFN-γ versus baseline, consistent with Th1-skewed inflammatory profile that was not observed following Engerix-B vaccination. Heplisav-B produced an increased frequency of B cells following vaccination, but the cellular immunometabolic expression profiles were otherwise not significantly different between the two vaccines 24 hours after vaccination. This suggests that global immune cell proportions were largely maintained despite differences in cytokine induction. However, 24-hour cytokine levels predictive of seroprotection were distinct between vaccines, with low IL-17A production following Heplisav-B and low IL-2 and IL-4 production following Engerix-B being the strongest predictors of antibody responses. Conclusion Heplisav-B induces stronger Th1-skewed innate responses and increased B cell frequency than Engerix-B in PLWH within the first 24 hours of vaccination, while overall cellular composition and activation remain largely preserved. These findings provide mechanistic insight into how TLR9-targeting adjuvants can enhance vaccine immunogenicity in immunocompromised populations and suggest that response to the two vaccines may be driven through different innate immune pathways. Funding Source NIH/NIAID R01AI186730 Topic Categories Vaccines and Immunotherapy (VAC)

Low CD21 identifies germinal center B cells failing antigen-driven positive selection destined for removal by FAS 2307103

Abstract Introduction Germinal centers (GC) drive affinity maturation of antibody responses. GC B cells lacking FAS death receptor escape affinity-based selection and persist despite carrying non-competitive low-affinity BCRs. It remains unclear how these FAS-deficient GC B cells can capture sufficient antigen to present to CD4+ follicular T cells and persist in competition against other high-affinity GC B cells. Defining how these low-affinity GC B cells persist within the competitive GC microenvironment may reveal additional mechanisms that enforce typical affinity-matured GC B cell responses. Methods Using adoptive transfer of FAS-deficient B cells possessing a starting specificity for hen egg lysozyme (Fas-/-.SWHEL B cells), we perform a series of single cell-omics and in vivo experiments to characterise the GC B cells that accumulate in FAS-deficient responses following immunisation. Results We find FAS-deficient GC B cells that escape affinity maturation display low surface CD21 and high B220 (CD21lo). Using this definition, we also identify rare, non-affinity matured CD21lo GC B cells in wild-type responses. Unlike their affinity-matured CD21+ GC B cell counterparts, CD21lo GC B cells are dark zone enriched, express low levels of surface BCR and show diverse variable immunoglobulin gene somatic hypermutations. Despite low affinities for foreign antigen, FAS-deficient CD21lo GC B cells are highly proliferative and depend on T cell signals. Transcriptomic profiling finds evidence of an analogous CD21lo population in human GCs. Conclusion Our findings suggest GC B cells enriched for reduced antigen reactivity that still receive follicular T cell help transition into CD21loB220hi GC B cells. These non-affinity matured CD21lo GC B cells normally fail to accumulate in typical GC responses due to FAS-mediated removal. As such, FAS serves as an additional checkpoint for GC B cells failing antigen-driven positive selection in the GC. Funding Source n/a Topic Categories Immune Response Regulation: Cellular Mechanisms (IRC)

Protective Role of Interferon Omega in Human Airway Epithelium During Human Metapneumovirus Infection 2258656

Abstract Introduction Human Metapneumovirus (HMPV) remains one of the leading causes of lower respiratory tract infections and hospitalization, particularly in infants. Currently, there is no vaccine or specific antiviral treatment for HMPV, making it crucial to explore antiviral therapy against this virus. Interferons (IFNs) are antiviral cytokines with potential clinical use. Previous work in our lab showed differential IFN responses between adult and pediatric epithelial cells after HMPV infection, where we observed that IFN-omega (IFN-ω), a type-I IFN, was the prominent IFN induced in pediatric epithelium. However, the antiviral effect of IFN-ω during HMPV infection is largely unknown. In this work, we investigated the susceptibility of HMPV infection to IFN-ω. Methods We employed a physiological 3D organotypic culture model of infection using normal human bronchial epithelial (NHBE) cells from pediatric donors, differentiated in an air-liquid interface (ALI) culture system. We used CRISPR-Cas9 and RNAi molecular techniques to investigate the mechanism of induction of IFN-ω and the mechanism by which IFN-ω exerts its antiviral effects during HMPV infection. Results Our results show that the induction of IFN-ω after HMPV infection is through a mechanism that involves the activation of Retinoic acid-inducible gene-I (RIG-I), and that IFN-ω significantly reduced HMPV infection through the induction of interferon-stimulated genes (ISGs) that block the further replication of HMPV without inducing a pro-inflammatory response. Conclusion These novel findings demonstrate the potential of IFN-ω as a modulator of epithelial antiviral responses and inflammation against HMPV infection, supporting its further evaluation as a therapeutic candidate for HMPV and other human respiratory viral infections. Funding Source Supported by the National Institute of General Medical Sciences (5P20GM130555) from the NIH, Louisiana State University, School of Veterinary Medicine Bridge Funding Grant Topic Categories Viral Immunology (VIR)

The cognitive, technological, and pedagogical dimensions of declining attention spans in educational contexts 2256287

Abstract Introduction Recently, educators have observed a notable decline in students’ attention spans in classrooms, raising concerns about the effectiveness of traditional teaching methods. This trend results from various factors, including widespread use of digital technology, increased multitasking, and evolving cognitive habits driven by fast-paced media consumption. Methods We at Chicago State University used appropriate surveillance methods, such as direct observation, digital monitoring, biometric sensors, and self-reporting tools. Ensured ethical practices by obtaining informed consent, protecting privacy, and maintaining transparency. Used tools such as LMS analytics, screen-monitoring software, and video analysis platforms to collect data. Analyzed the data using qualitative or quantitative methods. Results Studies show that students’ average attention span has decreased significantly, with many struggling to focus for more than 10—15 minutes during lectures. This change creates challenges for retaining knowledge, critical thinking, and engaging meaningfully with academic material. The widespread use of smartphones and other digital devices has fostered a culture of constant stimulation and instant gratification, which sharply contrasts with the sustained focus required in academic settings. Additionally, the rise of social media and short-form content platforms has conditioned students to expect quick information, making traditional lecture formats seem dull or unengaging. Conclusion This study proposes new strategies for curriculum design, instructional strategies, and classroom management. Emerging solutions should include integrating active learning techniques, gamification, and technology-enhanced instruction to re-engage students and promote deeper learning. Ultimately, addressing the issue of shrinking attention spans requires a multifaceted approach that balances the demands of modern digital culture with evidence-based educational practices. Funding Source n/a Topic Categories Immunology Education and Communication (EDU)