Author Archives: yenchaohsu

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
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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.

林志生教授研究團隊發表研究成果於Bioresour Technol.
連結網址：https://pubmed.ncbi.nlm.nih.gov/38641299/

Abstract This study established and investigated continuous macular pigment (MP) production with a lutein (L):zeaxanthin (Z) ratio of 4-5:1 by an MP-rich Chlorella sp. CN6 mutant strain in a continuous microalgal culture module. Chlorella sp. CN6 was cultured in a four-stage module for 10 days. The microalgal culture volume increased to 200 L in the first stage (6 days). Biomass productivity increased to 0.931 g/L/day with continuous indoor white light irradiation during the second stage (3 days). MP content effectively increased to 8.29 mg/g upon continuous, indoor white light and blue light-emitting diode irradiation in the third stage (1 day), and the microalgal biomass and MP concentrations were 8.88 g/L and 73.6 mg/L in the fourth stage, respectively. Using a two-step MP extraction process, 80 % of the MP was recovered with a high purity of 93 %, and its L:Z ratio was 4-5:1.