Publications by authors named "Hung-Wing Li"

Penicillin G (PG) is a common antibiotic, and its accumulation in the environment can pose a threat to the ecological system and ultimately impact human health. Nanozymes have emerged as highly stable enzyme mimics that can be utilized as sensors to achieve the sensitive detection of specific antibiotics. Herein, we report on a dual single-atom Fe/Zn nanozyme (DSAzyme) synthesized from Fe-imidazole as the guest and zeolite imidazole framework-8 as the host.

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Alzheimer's disease (AD) is the most prevalent neurodegenerative disorder, characterized by the early presence of amyloid-β (Aβ) and hyperphosphorylated tau. Identifying the neuropathological changes preceding cognitive decline is crucial for early intervention. Axon initial segment (AIS) maintains the orderly structure of the axon and is responsible for initiating action potentials (APs).

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As a form of dementia, Alzheimer's disease (AD) suffers from no efficacious cure, yet AD treatment is still imperative, as it ameliorates the symptoms or prevents it from deteriorating or maintains the current status to the longest extent. The human brain is the most sensitive and complex organ in the body, which is protected by the blood-brain barrier (BBB). This yet induces the difficulty in curing AD as the drugs or nanomaterials that are much inhibited from reaching the lesion site.

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Extracellular clustering of amyloid-β (Aβ) and an impaired autophagy lysosomal pathway (ALP) are the hallmark features in the early stages of incurable Alzheimer's disease (AD). There is a pressing need to find or develop new small molecules for diagnostics and therapeutics for the early stages of AD. Herein, we report a small molecule, namely F-SLCOOH, which can bind and detect Aβ, Iowa mutation Aβ, Dutch mutation Aβ fibrils and oligomers exhibiting enhanced emission with high affinity.

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Significant advancements have been made in the application of chimeric antigen receptor (CAR)-T treatment for blood cancers during the previous ten years. However, its effectiveness in treating solid tumors is still lacking, necessitating the exploration of alternative immunotherapies that can overcome the significant challenges faced by current CAR-T cells. CAR-based immunotherapy against solid tumors shows promise with the emergence of macrophages, which possess robust phagocytic abilities, antigen-presenting functions, and the ability to modify the tumor microenvironment and stimulate adaptive responses.

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By combining exquisitely designed hairpins with the catalytic hairpin assembly (CHA) to form tripedal DNA walkers driven by enzyme, we constructed a 3D DNA walker with accordingly complementary hairpins attached on gold nanoparticles (AuNPs) and sensitive fluorescence sensing system for the sensitive detection of target miRNA-21 (miR-21). The presence of miR-21 triggers the CHA among three hairpins (HP1, HP2, and HP3), which lead to the formation of the tripedal DNA walkers. For the walking trajectories, FAM-labeled hairpins (HP4) were attached to the surface of AuNPs, the fluorescence of which was initially quenched due to its close proximity to AuNPs.

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Alzheimer's disease (AD) is a progressive and irreversible neurodegenerative disorder characterized by the synaptic and neuronal loss, which results in cognitive impairment in particular learning and memory. Currently, AD is incurable and no single confirmative test can clinically be used to diagnose AD. In light of the complex and multifactorial nature of AD etiology, the development of multifunctional/multi-target drugs that act on multiple pathological pathways and mechanisms shows great therapeutic potential for intervention of this devastating disease.

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Background: Biliary atresia (BA) is an infantile fibro-obstructive cholestatic disease with poor prognosis. An early diagnosis and timely Kasai portoenterostomy (KPE) improve clinical outcomes. Aggregation of amyloid-beta (Aβ) around hepatic bile ducts has been discovered as a factor for BA pathogenesis, yet whether plasma Aβ levels correlate with hepatic dysfunctions and could be a biomarker for BA remains unknown.

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Article Synopsis
  • Oxidative stress from reactive oxygen species (ROS) contributes to neurotoxicity in Alzheimer's disease (AD), but effective tools for detecting Aβ-induced ROS are lacking.
  • Researchers have developed the first Aβ-targeted fluorescent probe that can monitor the levels of Aβ-induced hydroxyl radical (HO) in real-time, showcasing a significant emission wavelength shift and high selectivity for Aβ.
  • This probe is biocompatible and can detect varying levels of Aβ-induced HO in neuronal cells and transgenic AD mice, aiding in the diagnosis and study of AD pathology.
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Current circulating tumor cells (CTCs) detection strategies based on surface epithelial markers suffer from low specificity in distinguishing between CTCs and epithelial cells in hematopoietic cell population. Tumor-associated miRNAs within CTCs are emerging as new biomarkers due to their high correlation with tumor development and progress. However, in-situ simultaneous analysis of multiple miRNAs in single CTC cell is still challenging.

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Article Synopsis
  • F-SLOH is a fluorescent probe that targets Aβ oligomers and shows promise in treating Alzheimer's disease (AD) by reducing harmful aggregates in mouse models.
  • It effectively lowers levels of Aβ oligomers, Tau aggregates, and related neuroinflammation while also improving cognitive function.
  • The compound works by activating a cellular pathway that promotes the clearance of toxic fragments associated with AD, indicating its potential as a therapeutic agent in the early stages of the disease.
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The study of metallopolymers with controllable helical sense remains in its infancy. We report arabinose-functionalized (Zn-salphen)-based conjugated polymers that display mirror-image circular dichroism spectra for L- and D-sugar sidechains respectively, signifying ordered (helical) coiling of the polymer backbone with opposite screw-sense preferences. The observation of different spectroscopic behavior and Cotton effects for a variety of solvents (in a reversible manner) and temperatures, ascribed to changes in the extent of intrachain (Zn⋅⋅⋅O(salphen) and π-stacking) interactions between Zn-salphen moieties, thus indicate the flexible, responsive and dynamic nature of the folded helical conformation in these systems.

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Despite the wide use of magnetic resonance imaging (MRI) as a clinical diagnostic tool, there are still no clinically approved MRI contrast agents that can be applied for cerebral Alzheimer's disease (AD) biomarker imaging. We report here the design and development of the first amyloid-β (Aβ)-targeted, blood-brain barrier (BBB) penetrable theranostic Gd(DOTA)-cyanine dyad, which was synthesized by the conjugation of Gd(DOTA) complex and carbazole-based cyanine dye by the copper(I)-catalyzed azide-alkyne cycloaddition click reaction for imaging of Aβ and in AD mouse models. This dyad, as a multimodal probe, possesses desirable multifunctional properties, including good biocompatibility, low cytotoxicity, high Aβ selectivity, strong fluorescence enhancement upon binding with Aβ species, good paramagnetic properties, high stability, good BBB penetrability, and fast elimination from the mouse.

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To enable the early detection and intervention of Alzheimer's disease (AD), it is highly desirable to develop novel theranostic agents for simultaneous detection of toxic and pathogenic amyloid-β (Aβ) oligomers in vivo and attenuation of Aβ-induced toxicity. Herein, we report a new series of oligomeric Aβ targeted near infrared (NIR) emissive dibutylnaphthylamine-based cyanine probes for in vivo and ex vivo imaging of Aβ in AD mouse model. These new fluorophores exhibited strong solvatochromism and a large bathochromic shift of the emission spectrum upon binding with Aβ species, giving rise to advantageous NIR emission.

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Deposition and aggregation of β-amyloid (Aβ) peptides are demonstrated to be closely related to the pathogenesis of Alzheimer's disease (AD). Development of functional molecules capable of visualizing Aβ aggregates with nanoscale resolution and even modulating Aβ assembly has attracted great attention recently. In this work, we use monocyanine fluorophore as the lead structure to develop a set of deep red carbazole-based cyanine molecules, which can specifically bind with Aβ fibril electrostatic and van der Waals interactions.

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With the globalization of food and its complicated networking system, a wide range of food contaminants is introduced into the food system which may happen accidentally, intentionally, or naturally. This situation has made food safety a critical global concern nowadays and urged the need for effective technologies capable of dealing with the detection of food contaminants as efficiently as possible. Hence, Surface-enhanced Raman spectroscopy (SERS) has been taken as one of the primary choices for this case, due to its extremely high sensitivity, rapidity, and fingerprinting interpretation capabilities which account for its competency to detect a molecule up to a single level.

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A sandwich-type surface-enhanced Raman scattering (SERS) sensor using dual aptamers and gold-enhanced Raman signal probes has been successfully constructed for the detection of tumor-derived extracellular vesicles. The simple and sensitive sensor has the capability to detect tumor extracellular vesicles in 10-fold diluted human serum samples.

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Article Synopsis
  • Metal nanoclusters, particularly protein-templated gold nanoclusters (AuNCs), are important in research due to their unique properties useful for applications in catalysis, electronics, and medicine.
  • AuNCs are fluorescent materials characterized by good solubility, stability, and biocompatibility, making them versatile for modification and diverse applications.
  • The review discusses the synthesis, properties, and potential uses of AuNCs, with an emphasis on how modifying natural proteins and enzymes can enhance their fluorescence and expand their roles in analytical, biomedical, and food science fields.
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A fluorescence method based on functionalized magnetic nanoparticles (FMNPs) and hybridization chain reaction (HCR) is developed for the enzyme-free amplified determination of thrombin. In the proposed design, aptamer against thrombin was hybridized with the capture DNA-modified magnetic nanoparticles to yield the FMNPs. In the presence of thrombin, aptamers are released due to the specific and high-affinity binding between thrombin and its aptamer.

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The self-aggregation of amyloid-β peptides into soluble oligomers and then into insoluble fibril-associated amyloid plaques is a key event in the progression of Alzheimer's disease (AD). The imaging of Aβ aggregates in the brain is a powerful and practical approach for the diagnosis and progression monitoring of AD and the evaluation of the effectiveness of novel therapies for this devastating disease. Near-infrared (NIR) imaging is a sensitive and noninvasive method to detect and visualize Aβ aggregates in vivo because of its good penetration depth and low autofluorescence of biological substances.

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Herein, a simple enzyme-free method based on the seesaw-gate-driven isothermal signal amplification strategy was developed for nucleic acid detection. In this method, a partially complementary double-stranded beacon was designed, after the addition of ssDNA or RNA of target sequence, the fluorescence signal was restored through a toehold-mediated strand displacement process, followed by a seesaw-like reaction with the aid of an auxiliary strand with the same length of the toehold domain. Liberation of the target would initiate the next round of seesaw reaction to achieve recycling amplification of the fluorescence signal.

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Peroxynitrite (ONOO) plays a crucial role in the regulation of diverse pathophysiological processes, and high level of ONOO is profound association with numerous diseases. Herein, we developed an anthraquinone-based fluorescent probe L for ONOO determination by a new recognition mechanism: amido oxidized nitroso-group by ONOO. Probe L with amine-based recognition receptor is more selective to ONOO than other reactive oxygen species, including HO and ClO.

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