Category Archives: 研究發表

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.

林志生教授研究團隊發表研究成果於Biosensors & Bioelectronics
連結網址： https://pubmed.ncbi.nlm.nih.gov/39102773/

Abstract
Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is
facilitated by its trimeric surface spike protein, which binds to the human angiotensin-
converting enzyme 2 (hACE2) receptor. This critical interaction facilitates viral entry
and is a primary target for therapeutic intervention against COVID-19. However, it is
difficult to fully optimize viral infection using existing protein-protein interaction
methods. Herein, we introduce a nano-luciferase binary technology (NanoBiT)-based
pseudoviral sensor designed to stimulate the dynamics of viral infection in both living
cells and animals. Infection progression can be dynamically visualized via a rapid
increase in luminescence within 3 h using an in vivo imaging system (IVIS).
Inhibition of viral infection by baicalein and baicalin was evaluated using a NanoBiT-
based pseudoviral sensor. These results indicate that the inhibitory efficacy of
baicalein was strengthened by targeting the spike protein, whereas baicalin targeted
the hACE2 protein. Additionally, under optimized conditions, baicalein and baicalin
provided a synergistic combination to inhibit pseudoviral infection. Live
bioluminescence imaging was used to evaluate the in vivo effects of baicalein and
baicalin treatment on LgBiT-hACE2 mice infected with the BA.2-SmBiT spike
pseudovirus. This innovative bioluminescent system functions as a sensitive and
early-stage quantitative viral transduction in vitro and in vivo. This platform provides
novel opportunities for studying the molecular biology of animal models.

林志生教授研究團隊發表研究成果於J Hazard Mater.

連結網址：https://pubmed.ncbi.nlm.nih.gov/39700942/

Abstract

Particulate matter 2.5 (PM2.5) pollution and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic are the greatest environmental health issues worldwide. Several statistics revealed the significant positive correlation between the morbidity of coronavirus disease-19 (COVID-19) and the levels of air pollution. Nevertheless, there is no direct experimental evidence to indicate the effect of PM2.5 exposure on SARS-CoV-2 infection. The objective of this study was to evaluate whether the infection of SARS-CoV-2 affected by PM2.5 through angiotensin-converting enzyme II (ACE2) expression enhances and investigate the function of ACE2 in lung injury induced by PM2.5. An animal model of PM2.5-induced lung injury was established using wild-type (WT, C57BL/6), human ACE2 transgenic (K18-hACE2 TG), and murine ACE2 gene knockout (mACE2 KO) mice. The results indicate that PM2.5 exposure facilitates SARS-CoV-2 infection through inducing ACE2 expression in vitro (10 μg/mL) and in vivo (6.25 mg/kg/day in 50 μL saline). The levels of ACE, inflammatory cytokines, and mitogen-activated protein kinase (MAPK) proteins in WT, K18-hACE TG and mACE2 KO mice were significantly increased after PM2.5 instillation. The severest PM2.5-induced lung damage was observed in mACE2 KO mice. In summary, ACE2 plays a double-edged sword role in lung injury, PM2.5 exposure contributed to SARS-CoV-2 infection through inducing ACE2 expression, but ACE2 also protected pulmonary inflammation from PM2.5 challenge. Keywords: Air pollution; Angiotensin converting enzyme II; Inflammation; Particulate matter 2.5; Severe acute respiratory syndrome coronavirus 2.

林志生教授研究團隊發表研究成果於Biosensors & Bioelectronics

連結網址：https://pubmed.ncbi.nlm.nih.gov/39102773/

Abstract

Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is facilitated by its trimeric surface spike protein, which binds to the human angiotensin-converting enzyme 2 (hACE2) receptor. This critical interaction facilitates viral entry and is a primary target for therapeutic intervention against COVID-19. However, it is difficult to fully optimize viral infection using existing protein-protein interaction methods. Herein, we introduce a nano-luciferase binary technology (NanoBiT)-based pseudoviral sensor designed to stimulate the dynamics of viral infection in both living cells and animals. Infection progression can be dynamically visualized via a rapid increase in luminescence within 3 h using an in vivo imaging system (IVIS). Inhibition of viral infection by baicalein and baicalin was evaluated using a NanoBiT-based pseudoviral sensor. These results indicate that the inhibitory efficacy of baicalein was strengthened by targeting the spike protein, whereas baicalin targeted the hACE2 protein. Additionally, under optimized conditions, baicalein and baicalin provided a synergistic combination to inhibit pseudoviral infection. Live bioluminescence imaging was used to evaluate the in vivo effects of baicalein and baicalin treatment on LgBiT-hACE2 mice infected with the BA.2-SmBiT spike pseudovirus. This innovative bioluminescent system functions as a sensitive and early-stage quantitative viral transduction in vitro and in vivo. This platform provides novel opportunities for studying the molecular biology of animal models.

李明家副教授研究團隊發表研究成果於ACS Macro Lett.

連結網址：https://pubs.acs.org/doi/full/10.1021/acsmacrolett.4c00122

Abstract We report the preparation of chiral silica using a linear polysiloxane main chain with a preferred-handed helical structure as the template. Poly(methylvinyl siloxane) (PMVS) with a cysteine derivative side chain designated as PMVS-Cys was prepared using anionic polymerization and an ene-thiol reaction. PMVS-Cys forms a helical conformation in both solution and film via hydrogen bonding between amide groups at side chains. The helical structure remains during the calcination process, resulting in silica with helical structure. The silica with a helical structure shows optical activity.