Faculty Bibliography

INTRODUCTION/UNASSIGNED:Although hypoxic interventions are increasingly explored as non-pharmacological modulators of stress-related pathology, their ability to benefit PTSD remains poorly understood. We compared behavioural and molecular outcomes of three hypoxic regimes - intermittent normobaric hypoxia (IHT), hypobaric hypoxia (Bar), and chemical hypoxia (CH) via cobalt chloride (CoCl₂) - in rats with PTSD induced by single prolonged stress (SPS). METHODS/UNASSIGNED:= 105; eight groups) received one of the three treatments after control or SPS conditioning. Anxiety-like behaviour was assessed by Elevated Plus Maze (EPM), Open Field Test (OFT), and Dark-Light Box (DLB); HIF-1α, HIF-2α, HIF-3α, PACAP, and PAI-1 mRNA were quantified in the medial prefrontal cortex (mPFC) and hippocampus by real-time qPCR. RESULTS/UNASSIGNED:= 0.039); HIF-2α and HIF-3α showed a similar, non-significant upward trend (both ns after FDR correction, reflecting wide between-animal variability). Group means for all three HIF subunits converged toward the control range under all three interventions. HIF-3α responses to IHT or Bar were consistently blunted in PTSD animals across both regions, while PACAP was uniformly suppressed with stronger trauma-dependent attenuation under Bar. DISCUSSION/UNASSIGNED:As protein-level and canonical HIF target-gene readouts were not assessed, the reported transcript changes should be interpreted as a downstream feedback signature rather than a direct index of functional HIF activity. Hypoxic modality, not hypoxia per se, determines behavioural and molecular responses in PTSD; mild IHT uniquely normalised both in traumatised animals, supporting its development as a state-dependent non-pharmacological intervention for trauma-related conditions.

BACKGROUND AND STUDY AIMS/UNASSIGNED:Endoscopic ultrasound-guided gastroenterostomy (EUS-GE) is emerging as a minimally invasive alternative for benign gastric outlet obstruction (GOO). This study evaluated its safety, efficacy, and long-term outcomes. PATIENTS AND METHODS/UNASSIGNED:This international, multicenter retrospective study included 72 patients who underwent EUS-GE for benign GOO across 13 centers. Clinical success was defined as ability to tolerate solid food based on the GOO scoring system. Secondary outcomes included technical success and adverse events (AEs). RESULTS/UNASSIGNED:< 0.00001). Mean time to oral intake was 20.1 hours. AEs were mild,occurring in 6% intra-procedurally and 10% post-procedurally. Mean follow-up duration was 426.3 days. CONCLUSIONS/UNASSIGNED:EUS-GE demonstrates high technical and clinical success rates with a favorable safety profile for benign GOO, offering a promising alternative to traditional surgical approaches.

L-Glutamic acid (L-Glu) is central to carbon-nitrogen metabolism, yet its ability to improve starch quality by regulating grain metabolism and by directly modulating starch structure remains unclear. In this study, we integrated a field experiment with an in vitro experiment and combined untargeted metabolomics, microscopy, structural characterization, physicochemical and processing property analyses, and molecular dynamics simulations. It was found that under drought, L-Glu spraying reprogrammed the grain metabolome, with pathway enrichment in aminoacyl-tRNA biosynthesis and starch/sucrose metabolism. In vitro, L-Glu increased the full width at half maximum of the Raman band at 480 cm^-1 and altered the FTIR absorbance ratio of 1047/1022 cm^-1. L-Glu enhanced in vitro digestibility and reduced swelling power and paste transparency, while decreasing setback viscosity, suggesting a potential inhibition of short-term starch retrogradation; however, freeze-thaw stability was reduced. Microscopy revealed a more disordered gel network after L-Glu addition. Simulations showed that L-Glu formed 1.47-2.18 persistent hydrogen bonds with amylose chain per system and extensive hydrogen bonds with water.

Developing dry antimicrobial delivery systems that combine bioactive protection with biofilm-matrix disruption remains a major challenge. Building on a previously established protease-modulated pea protein isolate (PPI)-carvacrol nanoemulsion system, this study developed protease-assisted microcapsules designed to preserve carvacrol and promote the removal of preformed biofilms. Carvacrol-loaded nanoemulsions were prepared at pH 3.5, 7.0, and 10.0 and supplemented with pepsin or trypsin before spray-drying or freeze-drying with maltodextrin. Protease-specific interfacial modification markedly affected emulsion stability, powder structure, and encapsulation performance. At pH 7.0 and 10.0, trypsin reduced droplet size from 284.60 to 232.52 nm and from 149.13 to 140.38 nm, respectively. The resulting spray-dried microcapsules exhibited high encapsulation efficiency (>96%) and low surface carvacrol contents (0.95-1.24 mg/g). In contrast, pepsin caused pronounced destabilization under acidic conditions, particularly after freeze-drying, yielding porous powders with an encapsulation efficiency of 48.18% and a surface carvacrol content of 69.51 mg/g. Trypsin-assisted microcapsules achieved 90-99% removal of preformed Listeria innocua biofilm biomass within 1 h, whereas enzyme-free and pepsin-containing formulations generally remained below 40%. Microscopic observations confirmed extensive disruption and detachment of the biofilm structure. After one year at 4 °C, trypsin-loaded formulations retained high biofilm biomass removal activity (85-99% after 2 h). These findings demonstrate that protease-assisted microencapsulation can couple interfacial regulation during particle formation with enzyme-mediated biofilm-matrix disruption after rehydration, providing a sustainable carvacrol delivery platform with durable antibiofilm functionality.

With the rapid development in cell therapy and biopharmaceutical production in recent years, safe cryopreservation technologies are required to ensure product quality and safety. Dimethyl sulfoxide (DMSO), which is widely used as a conventional cryoprotectant, raises concerns owing to its cell permeability and consequent cytotoxicity. In this study, we focused on non-cell-permeable zwitterions that exhibit low cytotoxicity. We synthesised 21 zwitterions and systematically evaluated the relation between their molecular structures and cryoprotective effects. Elongation of the cationic side chain or spacer decreases the cryoprotective effects, which are associated with cytotoxicity and freezing of the unfrozen fraction. In contrast, ammonium/sulfonate-type zwitterions exhibited strong cryoprotective effects. This suggests their involvement in the modulation of membrane properties and the suppression of ice crystal formation. Notably, one of the synthesized ammonium/sulfonate-type zwitterions achieved cell recovery comparable with that of a commercial DMSO-containing cryoprotectant for human mesenchymal stem cells. This study deepens understanding of cryoprotective mechanisms based on the molecular design of zwitterions and provides guidelines for safe cellular cryoprotectants.

BACKGROUND/UNASSIGNED:The exponential expansion of biomedical literature has created an urgent need for efficient methods to recognize and extract population, intervention, comparison, and outcome (PICO) elements-the foundational elements of evidence-based medicine. OBJECTIVE/UNASSIGNED:This study systematically evaluated 2 complementary approaches for automating PICO recognition and extraction in medical literature: prompt engineering optimization and parameter-efficient fine-tuning (PEFT) of large language models (LLMs). METHODS/UNASSIGNED:We developed a dual-phase methodological framework: (1) systematic prompt optimization incorporating in-context learning, chain of thought (COT), and multipath reasoning strategies; and (2) PEFT of the LLM architecture using low-rank adaptation (LoRA), quantized LoRA, and freeze techniques. The PubMed-PICO and NICTA-PIBOSO benchmark datasets were used for recognition tasks, and the EBM-NLP dataset was used for extraction tasks. Performance metrics included precision, recall, and F1-score. F1-score was adopted as the major metric as it balances precision and recall. RESULTS/UNASSIGNED:For prompt engineering, COT achieved the overall best performance across both recognition and extraction tasks. For example, in the recognition task, COT obtained strong average F1-scores of 77.1% (SD 0.5%) for the population element and 84.5% (SD 0.4%) for the outcome element on PubMed-PICO. In the extraction task, COT achieved the highest average F1-score of 73.9% across 3 PICO elements (the population, intervention, and outcome elements) on EBM-NLP. These results suggest that, for smaller models such as those with 3B parameters, explicit step-by-step guidance in COT is more effective than more complex prompting strategies. In PEFT implementations, for example, LoRA achieved the best recognition performance (mean F1-score 91.7%, SD 0.3% for population) on PubMed-PICO, whereas quantized LoRA showed the best extraction capability (mean F1-score 79.3%, SD 0.5% for intervention) on EBM-NLP. Fine-tuned models achieved competitive performance across all datasets, with notable gains on NICTA-PIBOSO and EBM-NLP. PEFT further enhanced the model's overall performance compared with prompt engineering, with element-dependent differences across PICO categories. CONCLUSIONS/UNASSIGNED:Our findings indicate that LLMs can effectively automate PICO recognition and extraction through 2 complementary approaches. First, prompt engineering allows the model to perform tasks directly without altering its internal settings. Second, the PEFT method further unlocks their maximum performance potential by incorporating additional fine-tuning based on prompt engineering. This work makes significant advances and provides critical insights for optimizing methodological approaches in clinical applications related to or comprising PICO extraction and recognition tasks.

Decades of research on the developmental origins of health and disease highlight how prenatal and perinatal conditions are associated with long-term neurocognitive development. Exposures such as maternal stress, substance use, metabolic disorders, obstetric complications, low birthweight, and preterm birth have been linked to differences in brain, cognition, and mental health. Yet, most prior studies have been limited by small sample sizes, narrow exposure measures, or isolated outcomes. The Adolescent Brain Cognitive Development (ABCD) Study provides an unparalleled opportunity to overcome these limitations with nearly 12,000 children recruited at ages 9-10 across the United States, followed longitudinally with harmonized multimodal MRI, cognitive and behavioral testing, biospecimens, genetic data, and rich environmental measures in a diverse cohort. Retrospective caregiver reports provide key prenatal and perinatal information, which can be prospectively related to neurodevelopmental outcomes across adolescence. This review synthesizes findings from 111 ABCD-based studies published from 2017 to 2026. Results implicate maternal health conditions, substance use, birth outcomes, and cumulative adversity as being associated with variation in brain, cognitive, and behavioral development. Leveraging its size and diversity, ABCD has fostered advanced analytic approaches, such as multimodal integration of imaging and behavioral data, and longitudinal tracking of developmental trajectories, rarely possible elsewhere. While methodological challenges remain, including retrospective reporting and imaging site variability, ABCD offers unique opportunities to clarify pathways of vulnerability and resilience within an observational framework. Insights from this work can inform public health strategies and guide policies to reduce prenatal risks and strengthening early-life environments to optimize developmental outcomes.

Tumor vaccines represent promising strategies for cancer immunotherapy. However, their application remains restricted in HER2-positive breast cancer due to poor immunogenicity and inefficient antigen presentation. Herein, a multitargeting HER2 nanoparticle vaccine, HER2_aHPF, is developed by co-displaying the HER2 extracellular domain and AE37 T-cell epitope on a Helicobacter pylori ferritin nanoparticle via SpyTag/SpyCatcher conjugation. The nanoparticle vaccine exhibits structural homogeneity, enhanced lymphatic drainage, and high stability during freeze-thaw cycles and long-term storage, with retained immunogenicity after repeated freeze-thaw treatment. WH peptide-mediated DC targeting, in combination with the ferritin scaffold, enhances antigen uptake and DC maturation. In BALB/c mice, CpG and fullerenol dual-adjuvanted HER2_aHPF elicits robust HER2-specific humoral and cellular immunity, characterized by high-titer antibodies, polyfunctional CD4⁺ and CD8⁺ T cells, and expanded effector-memory T cells. Prophylactic and therapeutic vaccination markedly inhibits primary tumor growth and lung metastasis in mouse and human HER2-positive 4T1 models. Mechanistically, HER2_aHPF reduces myeloid-derived suppressor cells and regulatory T cells, increases cytotoxic T-cell infiltration, and maintains a favorable in vivo safety profile. Combination with anti-PD-1 and anti-CD47 antibodies further enhances T-cell activity and tumor control, demonstrating strong synergy between active vaccination and dual immune checkpoint blockade. These findings establish HER2_aHPF as a versatile nanoparticle vaccine platform with clinical translation potential for HER2-positive cancer immunotherapy.

Freezing during Pavlovian fear conditioning is the most commonly used indicator of learned fear in rodents. Although freezing and its neural underpinnings have been widely studied, the field has largely ignored other potential indicators of learned fear. Darting, an escape-like conditioned fear response, occurs more frequently in females and is reliably predicted by a distinct behavioral phenotype: heightened shock response and decreased freezing compared to rodents that do not engage in darting. The experiments in this study sought to expand the field's understanding of conditioned fear by investigating the neural correlates of conditioned darting, focusing on the infralimbic cortex (IL) and longitudinal columns of the periaqueductal gray (PAG) due to their known roles in modulating defensive responses, including conditioned freezing. We find that fear conditioning elicits greater neural activity (measured by quantification of cFos expression) in the IL of females compared to males, but that IL activation corresponds to freezing only in Darters. We next used chemogenetic tools to excite or inhibit either the IL alone or IL-PAG projections prior to fear conditioning. IL manipulations in either direction reduced freezing in both males and females, while IL inhibition increased darting and shock response in females only, and the effects of circuit-specific manipulations were minimal. Together, our findings suggest a novel, role for the IL in driving defensive responses during fear conditioning that is not dependent on IL-PAG connectivity.

Environmental pollution, particularly water contamination, continues to be a critical global challenge, thereby necessitating the development of sustainable and high-efficiency catalytic systems for wastewater treatment. In this study, silver nanoparticles (AgNPs) were synthesized via a green chemistry approach and embedded on a biocomposite, cellulose-chitosan aerogel integrated with hydroxyapatite (HCCA) derived from Basa (Pangasius bocourti) fish bones. Notably, the synthesis route is straightforward, eco-friendly, and minimizes the use of hazardous chemicals. Durian shell (DS) extract was utilized as a natural reducing and stabilizing agent, while residual biomass was treated to obtain high-purity cellulose, highlighting the effective valorization of agricultural waste. The resulting HCCA aerogel biocomposite, fabricated through crosslinking and freeze-drying, exhibits high porosity (>97%) and ultralow density (about 0.03 g cm^-3), facilitating uniform dispersion and stabilization of AgNPs. The optimized 1.25Ag@HCCA sample achieved nearly complete conversion (about 99%) of p-nitrophenol (PNP) to p-aminophenol (PAP) within 15 minutes and retained approximately 98% efficiency after seven reuse cycles. Additionally, strong antibacterial activity against Escherichia coli and Salmonella paratyphi was observed. Overall, the Ag@HCCA sample demonstrates high potential as a multifunctional, sustainable material for wastewater treatment and waste valorization in circular economy applications.