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.
李孟學助理教授研究團隊發表研究成果於Talanta.
連結網址：https://pubmed.ncbi.nlm.nih.gov/41418617/
Abstract
Immunoassays are indispensable tools in biomedical research and diagnostics, but conventional approaches such as ELISA demand large sample volumes and long assay times, making them unsuitable for precious biological fluids like single-embryo culture medium (ECM). Here we present a novel mechanical buoyant microsphere immunoassay platform that enables reliable analysis of microliter-scale samples. Buoyant hollow glass microspheres (40-60 μm) serve as the reaction carriers, passively aggregating by buoyancy for extraction and sequential transfer across reagent droplets. Through a droplet-based design, in which droplets are stabilized on hydrophilic traps patterned on a hydrophobic surface, each assay requires only 2 μL of sample. By using a custom quantification chip to standardize the microsphere number to 25, the system achieved high reproducibility (coefficients of variation, CV values < 10 %) and enhanced fluorescence signals. The assay demonstrated a limit of detection (LOD) below 0.4 pg/mL for human IL-1β. Importantly, with a wind-assisted mixing module, biomolecular interactions were accelerated and the total assay time was reduced to about 18 min. Validation with single-embryo ECM from a mouse model, followed by embryo transfer and implantation assessment, further demonstrated feasibility for embryo-related biomarker studies. Overall, this platform provides a rapid, sensitive, and automation-ready solution optimized for low-volume samples, with strong potential for non-invasive embryo assessment and broader biomedical applications.
陳誼如教授研究團隊發表研究成果於 Molecular Therapy
連結網址：
https://www.sciencedirect.com/science/article/abs/pii/S1525001625008135?via%3Dihub
Abstract
Pancreatic ductal adenocarcinoma (PDAC) remains highly lethal due to its aggressive nature and resistance to chemotherapy. Immunotherapies have shown promise in various cancers but are limited in PDAC due to poor drug penetration through dense stroma and systemic toxicities. Herein, we developed a stroma-targeted gene delivery platform for efficient immunogene therapy in PDAC. Using an in vitro-in vivo phage display screening approach, we identified the LQT peptide, which selectively binds to fibronectin 1 (FN1) in pancreatic stellate cells (PSCs), key mediators of PDAC stroma. We then engineered a lipid-dendrimer-CaP (LDCP) nanoparticle functionalized with the LQT peptide for targeted gene delivery of interleukin-2 (IL-2) plasmid DNA (pDNA). This design improves delivery to PSCs, enhances nanoparticle accumulation and penetration in PDAC, and facilitates endosomal escape and effective nuclear entry through its pH-responsive calcium phosphate core and thymine-capped polyamidoamine (PAMAM) dendrimers. The production of IL-2 significantly amplifies CD8 T cell infiltration and activation, counteracting the immunosuppressive microenvironment. When combined with checkpoint inhibitors such as anti-PD-1 antibodies or costimulatory molecules like OX40 ligand (OX40L), this gene therapy strategy leads to substantial suppression of PDAC progression. This stroma-targeted immunogene therapy shows significant promise as a safe and effective approach for PDAC treatment.
羅惟正教授研究團隊發表研究成果於 Nature Communications
連結網址：
https://www.nature.com/articles/s41467-025-63757-9
Abstract
The flood of protein structural Big Data is coming. With the belief that biotech researchers deserve powerful analysis engines to overcome the challenge of rapidly increasing computational demands, we are devoted to developing efficient protein structural alignment search algorithms to assist researchers as they push the frontiers of biological sciences and technology. Here, we present SARST2, an algorithm that integrates primary, secondary, and tertiary structural features with evolutionary statistics to perform accurate and rapid alignments. In large-scale benchmarks, SARST2 outperforms state-of-the-art methods in accuracy, while completing AlphaFold Database searches significantly faster and with substantially less memory than BLAST and Foldseek. It employs a filter-and-refine strategy enhanced by machine learning, a diagonal shortcut for word-matching, a weighted contact number-based scoring scheme, and a variable gap penalty based on substitution entropy. SARST2, implemented in Golang as standalone programs available at https://10lab.ceb.nycu.edu.tw/sarst2 and https://github.com/NYCU-10lab/sarst, enables massive database searches using even ordinary personal computers.
中文簡介
蛋白質的功能取決於其結構，解析結構有助人們了解功能形成之機制，研發蛋白質藥物與仿生分子材料。然而，結構解析困難，2020年之前，已知的上億筆蛋白質序列中，僅有十數萬筆結構確知。2020年, Google-DeepMind 發表了精準結構預測演算法AlphaFold2, 並宣告將對當時兩億多筆序列做預測。本實驗室意識到，蛋白質結構資料將暴增千倍，比對分析會非常耗時，於是著手研發高效能結構比對搜尋平行運算方法，協助國際蛋白質科研團隊解決龐大計算壓力。我們的SARST2演算法，效能不僅數百至數萬倍高於早年方法，更能在個人電腦上以三分鐘完成兩億多筆AlphaFold資料庫的比對搜尋，且僅用極少資源。相同任務，近年知名的平行運算方法Foldseek需要六倍時間、四十倍記憶體及三倍磁碟空間。感謝國科會、教育部及母院工程生物科學學院於各方面的支持，本團隊將持續努力推廣平行運算技術於蛋白質結構分析之應用，盼推助臺灣在高通量運算領域引領國際。
黃兆祺教授研究團隊發表研究成果於 ADVANCED MATERIALS
連結網址：
https://advanced.onlinelibrary.wiley.com/doi/10.1002/adma.202500650
Abstract
Electronic signaling and microRNA (miRNA) regulation play pivotal roles in determining neuronal cell fate and promoting brain recovery. Despite this, clinical advancements are hindered by the limited availability of tools for spatiotemporal electrical signaling and non-viral gene modulation in neurons in vivo. In this study, a conductive granular scaffold (cGRAS) that doubles as an antenna and neuronal gene delivery agent for targeted miRNA regulation of nerve repair in traumatic brain injury (TBI) is developed. The inherent features of granular scaffolds reduce the inflammation and glial scarring in TBI by mitigating activated microglia and stellate cells. Upon irradiation with an external alternating magnetic field (AMF), the “electromagnetic messenger” induces electrical stimulation to restore brain function and promotes temporal electroporation. This process, together with mechanotransduction capability of cGRAS, enhances the delivery and formation of miRNA sponges both in vitro and in vivo, thereby reducing the overexpression of miR6263, which is significantly upregulated upon neuronal injury. In the whole brain imaging analysis, suppression of inflammation, angiogenesis around the TBI cavity, and infiltration of newborn neurons in the injured area are observed after in situ magnetoelectric formation of miRNA sponges and wireless electric stimulus, leading to improved brain function and behavioral recovery. Overall, this cGRAS represents a potentially innovative and versatile tool for clinical neuronal regeneration engineering.
王雲銘教授研究團隊發表研究成果於 Biosensors and Bioelectronics
連結網址：https://www.sciencedirect.com/science/article/pii/S0956566324011205
Abstract
Anti-mullerian hormone (AMH) detection receives much attention since it is used as an ideal biomarker for quantitative assessment of ovarian reserve. The present study proposed a first report on the use of MOF-on-MOF as an electrochemical sensor for recognizing AMH in buffer and serum media. The MOF-on-MOF, MIL-88 B@UiO66NH2 was synthesized by the internal extended growth method (IEGM) involving MIL-88 B on UiO66NH2 by in situ method for the first time. MOF matrix could be established to form a three-dimensional (3D) core-shell hybrid unit using MOFs with distinct characteristics. The morphology, structural characteristics, and electrochemical performance of MIL-88 B@UiO66NH2 were studied. It was successfully used for AMH sensing to demonstrate the detection performance of the internal extended growth method (IEGM) grown MIL-88 B@UiO66NH2 made immunosensor. The electrochemical results indicated that MOF-on-MOF exhibited linear EIS response for AMH concentration varying from 100 ng/mL to 1 fg/mL. Further, the immunosensor displayed high specificity and sensitivity for AMH detection. The fabricated sensor attained a remarkable limit of detection (LOD) of 1.07 fg/mL and 0.82 fg/mL, when studied in PBS and 10% serum buffer media, respectively. The biosensor achieved the limit of quantification (LOQ) of 3.25 fg/mL and 2.5 fg/mL, respectively, when analyzed in PBS buffer and 10% serum buffer. The significant results emphasized that the fabricated biosensor holds a promising potential to act as an appropriate tool for rapid assessment of AMH levels.
蘇昱誠副教授研究團隊發表研究成果於ACS Nano
連結網址： https://pubmed.ncbi.nlm.nih.gov/39749925/
Abstract
The blood-brain barrier (BBB) remains a major obstacle for effective delivery of
therapeutics to treat central nervous system (CNS) disorders. Although transferrin
receptor (TfR)-mediated transcytosis is widely employed for brain drug delivery, the
inefficient release of therapeutic payload hinders their efficacy from crossing the
BBB. Here, we developed a pH-responsive anti-polyethylene glycol (PEG) × anti-TfR
bispecific antibody (pH-PEG engagerTfR) that can complex with PEGylated
nanomedicine at physiological pH to trigger TfR-mediated transcytosis in the brain
microvascular endothelial cells, while rapidly dissociating from PEGylated
nanomedicine at acidic endosomes for efficient release of PEGylated nanomedicine to
cross the BBB. The pH-PEG engagerTfR significantly increased the accumulation of
PEGylated nanomedicine in the mouse brain compared to wild-type PEG engagerTfR
(WT-PEG engagerTfR). pH-PEG engagerTfR-decorated PEGylated liposomal
doxorubicin exhibited an enhanced antitumor effect and extended survival in a human
glioblastoma (GBM) orthotopic xenograft mice model. Conditional release of
PEGylated nanomedicine during BBB-related receptor-mediated transcytosis by pH-
PEG engagerTfR is promising for enhanced brain drug delivery to treat CNS
disorders.
王雲銘教授研究團隊發表研究成果於 Sensors and Actuators Reports
連結網址https://www.sciencedirect.com/science/article/pii/S2666053924000870?via%3Dihu
b
Abstract
Clinical diagnosis of diseases like cancer, requires rapid and ultrasensitive
screening methods. β-galactosidase (β-gal) is a glycoside hydrolase enzyme,
that is upregulated in senescent cells and primary ovarian cancer cells. It is
considered a significant biomarker for cellular senescence and primary
ovarian cancers. The current study demonstrates the designing of a bimetallic
metal-organic framework, (Fe, Cu)-MOF-919, as an ultrasensitive
electrochemical immunosensor for investigating ꞵ-galactosidase (β-gal)
enzyme on screen-printed carbon electrodes (SPCE) using electrochemical
impedance spectroscopy (EIS) in human oral cancer plasma samples. The
sensor exhibited a linear response in a wide concentration of β-gal ranging
from 10 fg/mL to 1 ng/mL with a limit of detection (LOD) of 4.79 fg/mL and a
limit of quantification (LOQ) of 14.53 fg/mL. Furthermore, the sensor
confirmed outstanding selectivity and sensitivity against biologically
significant interfering molecules. Analyses of β-gal in human oral cancer
samples also demonstrated the potential of β-gal for clinical diagnosis. The
sensing approach holds substantial clinical relevance by being a promising
option for designing latent biosensors.
