Category Archives: 研究發表

高雅婷副教授研究團隊發表研究成果於Phys Chem Chem Phys.

連結網址：https://pubmed.ncbi.nlm.nih.gov/41431324/

Abstract

Fatty acid photodecarboxylases (FAPs) utilize blue light to convert fatty acids into Cn-1 hydrocarbons and CO2, providing a sustainable route to photobiocatalytic fuel production. Despite increasing interest, substrate-dependent phenomena-such as binding affinity, initial electron-transfer (ET) dynamics, and the influence of residues near the FAD cofactor-remain insufficiently characterized. Here, we systematically analyzed substrate binding, substrate-to-product conversion, and initial ET dynamics for three fatty acids of varying chain lengths using two cosolvent buffer systems. Ethanol improved substrate solubility but increased enzyme flexibility, leading to an extended FAD-substrate distance (DFAD-substrate) and diminished fluorescence quenching. Fluorescence titrations revealed chain-length-dependent binding, with palmitic acid (C16) and arachidic acid (C20) exhibiting stronger binding than lauric acid (C12). A fluorometric assay enabled quantification of product formation and catalytic half-lives, revealing that the fastest turnover arises from binding competition between substrate and product. Time-resolved fluorescence measurements further demonstrate that ET rates increase with substrate chain length. Longer fatty acids position their carboxylate groups closer to the FAD cofactor, reducing DFAD-substrate and accelerating the initial ET step. Finally, targeted mutagenesis at residue N170-located adjacent to the isoalloxazine ring-shows that local active-site interactions strongly modulate the partitioning of the excited 1FAD* pathways, thereby tuning photocatalytic efficiency and photostability.

何信瑩教授研究團隊發表研究成果於Scientific Reports

連結網址：https://sciety.org/articles/activity/10.21203/rs.3.rs-7424363/v1?utm_source=sciety_labs_article_page

Abstract

Early diagnosis and treatment of postoperative infection (POI) are crucial for optimizing clinical outcomes. However, current POI prediction models remain unsatisfactory due to their limited interpretability and lack of personalized risk insights, restricting precise antibiotic use and personalized postoperative care strategies. This study aims to develop an interpretable model for predicting the individual POI risk within 30 days after liver resection. This retrospective study included 785 liver resection patients with 125 preoperative and early postoperative clinical factors. The dataset was divided into training (n = 551) and test (n = 234) sets in a 7:3 ratio. An interpretable evolutionary learning-driven method, EL-PIRLR, was proposed to develop a POI risk prediction model after liver resection. EL-PIRLR performs optimal feature selection in conjunction with an XGBoost classifier. EL-PIRLR identified 27 risk factors for modeling and achieved an accuracy of 87.50% and an AUC of 0.889 on the test set. Postoperative fever patterns, surgical difficulty, and the Charlson Comorbidity index emerged as crucial predictors of the POI risk. Using an uncertainty plot analysis, defining risk scores between 0.1 and 0.9 as the uncertainty region, EL-PIRLR achieved 92.05% accuracy for confidently predicted cases, covering 84.62% of the dataset. This demonstrates high reliability with a 98.70% negative predictive value in identifying non-infection patients. EL-PIRLR outperformed several state-of-the-art feature selection techniques and classification models. Precise POI prediction significantly impacts infection management and postoperative care. EL-PIRLR enhances the precision of hepatectomy POI risk prediction, facilitating personalized risk evaluations and aiding clinical decision-making.

李明家副教授研究團隊發表研究成果於JACS Au

連結網址：https://pubs.acs.org/doi/full/10.1021/jacsau.5c01533

Abstract

In this study, we introduce a system that is both nonconjugated and nonaromatic, specifically engineered to generate luminescence via cluster-triggered emission in its aggregated state. By integrating a chiral moiety, N-(tert-butoxycarbonyl)-cysteine methyl ester (cys) as a side group into a linear poly(methyl vinylsiloxane) (PMVS) backbone, we successfully achieved pronounced circularly polarized luminescence (CPL). The formation of the helical conformation was evaluated by vibrational circular dichroism (VCD) and electronic circular dichroism (ECD) spectroscopy. Furthermore, the 2D NMR analyses indicated that intramolecular hydrogen bonding significantly contributes to the stabilization of this structure, because of the intrinsic flexibility of the PMVS backbone, the resultant material demonstrates mechanically tunable CPL properties, underscoring its potential as a versatile chiroptical platform for material applications.

廖光文教授研究團隊發表研究成果於Molecular Medicine

連結網址：https://www.mdpi.com/2073-4468/14/4/106

Abstract

Background: PD-L1 immunotherapy plays a crucial role in cancer treatment, but PD-L1 peptide vaccines have low immunogenicity. A potent peptide derived from the spike protein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has a significant adjuvant effect, which may increase the immunogenicity of the PD-L1 peptide. This study evaluates whether the PD-L1-SARS peptide enhances PD-L1 immunotherapy and analyzes its potential synergistic effects with anti-PD-L1 antibodies.

Methods: In vivo experiments compared prevention, therapy, and combination therapy using PD-L1 versus PD-L1-SARS peptides in mice. Cytokine multiplex arrays, ELISpot, and IHC were used to evaluate adjuvant effects. Molecular docking (hypothesis-generating), RNA-seq, and LC-MS/MS were used to explore putative mechanisms.

Results: The PD-L1-SARS peptide enhanced the Th1 immune response and increased CD8 and Th17 cell infiltration, effectively inhibiting tumor growth and liver metastasis. Additionally, it promoted M1 macrophage polarization and improved anti-PD-L1 antibody efficacy. Proteomics and bioinformatic analyses were consistent with IFN-γ-linked pathways, and an exploratory docking screen nominated candidate receptors/pathways potentially connecting the adjuvant motif to innate sensing.

Conclusions: Embedding a SARS-derived adjuvant-like motif within a PD-L1 peptide vaccine and delivering it in situ may re-condition the tumor microenvironment toward an immune-activating, Th1/Th17-biased state and complement PD-L1 blockade.

Keywords: Bioinformatics analysis; Melanoma; PD-L1; Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

廖光文教授研究團隊發表研究成果於Antibodies

連結網址：https://www.mdpi.com/2073-4468/14/4/106

Abstract

Background: Short peptide epitopes are valuable for mechanistic studies, yet their intrinsic low immunogenicity and lack of commercial antibodies hinder rapid antibody generation. Methods: We developed a reproducible, sequence-level workflow combining cross-species/structural triage, independent MHC-I/II prioritization, and conservative heteroclitic-style substitutions to enhance predicted MHC affinity while preserving native epitope features. Using visfatin as a model, two optimized fragments were conjugated to KLH and tested in mice for antibody titers, isotype profiles, and binding kinetics. Results: Mutant peptides improved MHC-binding prediction, elicited stronger antibody titers, and promoted isotype maturation (increased IgG1). Importantly, antibodies maintained measurable binding to wild-type sequences, indicating preserved cross-recognition. Similar effects were reproduced with additional antigens. Conclusions: This proof-of-concept study, based on small exploratory mouse cohorts (n = 3 per group), demonstrates that strategic, minimal sequence edits can significantly enhance peptide immunogenicity while preserving native epitope recognition. This streamlined workflow provides a low-barrier route to generate epitope-directed antibodies when commercial reagents are unavailable.

Keywords: peptide immunogenicity; sequence-level antigen engineering; conservative (heteroclitic) mutagenesis; cross-reactive antibodies

曾慶平教授研究團隊發表研究成果於International Journal of Molecular Sciences Macromolecules

連結網址：https://pubmed.ncbi.nlm.nih.gov/41241351/

Abstract

The immunoregulatory effects of probiotics have been widely studied, particularly in maintaining immune balance. Conventional in vitro functional screening of probiotics relies on fresh donor-derived primary immune cells, which often exhibit significant inter-individual and temporal variability, limiting reproducibility and interpretation. As an alternative, human-induced pluripotent stem cell (iPSC)-derived dendritic cells were co-cultured with five probiotic strains in the current study to evaluate their immunomodulatory interactions. To assess whether cytokines produced by probiotic-stimulated dendritic cells can influence T cell differentiation, human CD4+ T cells were exposed to the conditioned medium derived from co-cultures. Enzyme-linked immunosorbent assay results demonstrated that iPSC-derived dendritic cells secreted cytokines at distinct concentrations in response to different probiotic strains, suggesting that these cells can distinguish between different microbial stimuli, and supporting their use in functional probiotic screening. Among the five strains tested, Lactiplantibacillus plantarum LPA-56, Limosilactobacillus reuteri RU-23, and Lactobacillus fermentum Fem-99 induced cytokine production levels that promoted the differentiation of the human CD4+ T cells into regulatory T cells. These findings demonstrate that iPSC-derived dendritic cells have immunomodulatory potential, are reliable for in vitro screening of probiotics, and offer a promising strategy for selecting potent immunoregulatory probiotic candidates.

Keywords: CD4+ T cell; co-culture; dendritic cell; induced pluripotent stem cell; probiotic.

李宗夷教授研究團隊發表研究成果於Frontiers in Microbiology

連結網址：https://pubmed.ncbi.nlm.nih.gov/41395471/

Introduction: Systemic glucocorticoids (SG) are administered to quell hyper-inflammation in severe community acquired pneumonia (SCAP), yet trials report inconsistent efficacy and no mechanistic explanation.

Methods: We enrolled 200 ventilated SCAP patients, whom received hydrocortisone within 48 h of ICU admission, and generated longitudinal lower-airway microbiome profiles by 16S rRNA amplicon and metagenomic sequencing on ICU Days 1, 3 and 7. Compositional data were integrated with clinical variables through a fully reproducible bioinformatics analysis workflow.

Results: Baseline community structures did not differ between SG and control cohorts, but by Day 7 survivors exhibited enrichment of Actinobacteria and Gammaproteobacteria whereas non-survivors accumulated Alphaproteobacteria and Campylobacteria. A random-forest model restricted to Bacilli and Alphaproteobacteria achieved AUROC = 0.89 (sensitivity 0.83, specificity 0.81) on a patient-held-out test set, significantly outperforming conventional severity indices like APACHE II, SOFA and mNUTRIC scores.

Discussion: Collectively, our results demonstrate that SG therapy imposes reproducible ecological pressures on the lung microbiome and that a two-feature microbial fingerprint can forecast treatment success with single-sample resolution. These findings show that SG therapy actively reshapes the respiratory ecosystem and that lightweight microbiome-aware machine learning can stratify treatment response, offering a tractable path toward precision corticosteroid stewardship.

Keywords: gut-lung axis; lung microbiome; machine learning; severe community-acquired pneumonia (SCAP); systemic glucocorticoids response.

柯泰名副教授研究團隊發表研究成果於Clinical and Translational Medicine

連結網址：https://pubmed.ncbi.nlm.nih.gov/41249858/

In summary, we identified a novel circulating skinhoming CD4+ T cell subset, CLA+ CTSW+ T cells, that may drive psoriasis relapse by persisting in circulation, exhibiting cytotoxicity, and engaging pathogenic immune cells via MIF and PGE2/EP2 signalling, promoting a proinflammatory, Th17-skewed milieu (Figure S10). These results provide potential targets for psoriasis relapse prevention.

尤禎祥教授研究團隊發表研究成果於Journal of Organic Chemistry

連結網址：https://pubmed.ncbi.nlm.nih.gov/41059733/

Abstract

The phosphine-catalyzed [3 + 2] cycloaddition of allenoates with enones provides an efficient route to five-membered carbocycles and exhibits regioselectivity that depends on the substituents of the substrates. To elucidate the origin of the substituent effects, density functional theory calculations and kinetic modeling are performed on the reactions of unsubstituted/substituted allenoates (2/8) with arylideneoxindoles (e-iii). Nucleophilic attack of PPh3 on the allenoate generates interconvertible Z-, E-, and twisted adducts: the former two participate in regioselective [3 + 2] cyclization. For 2, the major γ-regioisomeric product forms via the E-adduct. Kinetic modeling predicts an α:γ ratio of 1:99, consistent with the experimentally observed 10:90 selectivity. By contrast, the reaction of 8 yields the α-regioisomer via the Z-adduct. The computed isomer ratio of 99:1 agrees with the experimental value of >95:5. The switch in regioselectivity is attributed to the interplay between electronic and steric effects. Secondary orbital interactions favor the γ-[3 + 2] pathway. Substituent-induced steric hindrance is found to elevate the activation barriers to cyclization, thereby shifting the kinetic regime toward Curtin-Hammett control and modulating regioselectivity. These findings highlight the pivotal role of adduct dynamics in phosphine catalysis and clarify the conditions under which Curtin-Hammett control governs product selectivity.

莊碧簪副教授研究團隊發表研究成果於iScience.

連結網址：https://www.cell.com/iscience/fulltext/S2589-0042(26)00187-2

Abstract

Fragile X-associated tremor/ataxia syndrome (FXTAS) is caused by CGG repeat expansions in FMR1, leading to RNA toxicity and toxic FMRpolyG peptide from abnormal translation. Using a Caenorhabditis elegans model, we generated single-copy insertions of the human FMR1 5’ UTR containing 0, 16, or 99 CGG repeats under a pan-neuronal promoter. Worms expressing 99 CGG repeats showed impaired motility, altered neuronal morphology, and disrupted miRNA homeostasis. Co-expression of PASH-1, the C. elegans ortholog of a miRNA-processing DGCR8 sequestered in FXTAS, mitigated both RNA- and peptide-mediated toxicity, restoring locomotion, neuronal structure, and miRNA regulation balance. Removing FMRpolyG improved movement by ∼50%, suggesting RNA toxicity is primary pathogenesis. Glial 99 CGG expression altered nearby neuronal cilia, disrupting olfaction without affecting movement, revealing non-cell-autonomous toxicity. These findings establish the protective role of PASH-1 against CGG-induced neurotoxicity and underscore C. elegans as a model for dissecting FXTAS mechanisms and exploring therapeutic strategies.