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Raman spectrum preprocessing method for automatic denoising and suppression of the fluorescent background. In this method, noise is reduced using wavelet transform, and a modified polynomial curve fitting method is implemented such that an algorithm can independently identify the optimal curve parameters for fluorescent background suppression. To address the problem of imbalanced datasets, the present study employed a synthetic minority oversampling technique to increase the volume of data in minority classes. This technique enables the prediction of pesticides that are otherwise difficult to detect, and the prediction accuracy is comparable to that of detection with large data volumes. The proposed convolutional neural network model was verified to accurately identify the type of single pesticides and composition of mixed pesticides. The prediction accuracy for mixed pesticides reached 99.1%., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Lipid droplets (LDs) are spherical organelles that localize in the cytosol of eukaryotic cells. Different proteins are embedded on the surface of LDs, so LDs play a vital role in the physiological activities of cells. The dysregulation of LDs is associated with various human diseases, such as diabetes and obesity. Therefore, it is essential to develop a fluorescent dye that labels LDs to detect and monitor illnesses. In this study, we developed the compound BDAA12C for staining LDs in cells. BDAA12C exhibits excellent LD specificity and low toxicity, enabling us to successfully stain and observe the fusion of LDs in A549 cancer cells. Furthermore, we also successfully distinguished A549 cancer cells and MRC-5 normal cells in a co-culture experiment and in normal and tumour tissues. Interestingly, we found different localizations of BDAA12C in well-fed and starved A549 cancer cells and consequently illustrated the transfer of fatty acids (FAs) from LDs to mitochondria to supply energy for β-oxidation upon starvation. Therefore, BDAA12C is a promising LD-targeted probe for cancer diagnosis and tracking lipid trafficking within cells., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:, (Copyright © 2024 Elsevier B.V. All rights reserved.)

The emergence of SARS-CoV-2 variants diminished the efficacy of current antiviral drugs and vaccines. Hence, identifying highly conserved sequences and potentially druggable pockets for drug development was a promising strategy against SARS-CoV-2 variants. In viral infection, the receptor-binding domain (RBD) proteins are essential in binding to the host receptor. Others, Heparan sulfate (HS), widely distributed on the surface of host cells, is thought to play a central role in the viral infection cycle of SARS-CoV-2. Therefore, it might be a reasonable strategy for antiviral drug design to interfere with the RBD in the HS binding site. In this study, we used computational approaches to analyze multiple sequences of coronaviruses and reveal important information about the binding of HS to RBD in the SARS-CoV-2 spike protein. Our results showed that the potential hot-spots, including R454 and E471, in RBD, exhibited strong interactions in the HS-RBD binding region. Therefore, we screened different compounds in the natural product database towards these hot-spots to find potential antiviral candidates using LibDock, Autodock vina and furthermore applying the MD simulation in AMBER20. The results showed three potential natural compounds, including Acetoside (ACE), Hyperoside (HYP), and Isoquercitrin (ISO), had a strong affinity to the RBD. Our results demonstrate a feasible approach to identify potential antiviral agents by evaluating the binding interaction between viral glycoproteins and host receptors. The present study provided the applications of the structure-based computational approach for designing and developing of new antiviral drugs against SARS-CoV-2 variants., (© 2024. The Author(s).)

Background: Osimertinib is the first-line therapy for patients with non-small cell lung cancer harboring epidermal growth factor receptor-activating alterations. Although osimertinib has been shown to elicit profound patient responses, cancer cells frequently develop additional alterations that sustain their proliferation capacity. This acquired resistance represents a substantial hurdle in precision medicine for patients with lung cancer., Methods: The biological and cellular properties of the G-quadruplex ligand BMVC-8C3O and its anticancer activities were evaluated in non-small cell lung carcinomas. In addition, combined treatment with BMVC-8C3O and osimertinib was evaluated for its effects on the growth of osimertinib-resistant tumors in vivo., Results: We demonstrate that BMVC-8C3O effectively suppresses c-FOS expression by stabilizing G-rich sequences located at the c-FOS promoter. The suppression c-FOS expression by BMVC-8C3O increases the sensitivity of acquired resistant cancer cells to osimertinib. Combining BMVC-8C3O and osimertinib has a synergistic effect in inhibiting the growth of acquired resistant cancers both in vitro and in mouse models. The combined inhibitory effect is not limited to BMVC-8C3O, either: several G-quadruplex ligands show varying levels of inhibition activity. We also show that simultaneous inhibition of both the c-FOS and PI3K/AKT pathways by BMVC-8C3O and osimertinib synergistically inhibits the growth of acquired resistant cancer cells., Conclusion: These findings unveil a synthetic lethal strategy to prevent and inhibit epidermal growth factor receptor-altered lung cancers with acquired osimertinib resistance. G-quadruplex ligands have the potential to be integrated into current osimertinib-based treatment regimens., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Chemical structures bearing a combination of aggregation-induced emission enhancement (AIEE) and intramolecular charge transfer (ICT) properties attracted the attention of many researchers. Recently, there is an increasing demand to pose tunable AIEE and ICT fluorophores that could present their conformation changes-related emission colors by adjusting the medium polarity. In this study, we designed and synthesized a series of 4-alkoxyphenyl-substituted 1,8-naphthalic anhydride derivatives NAxC using the Suzuki coupling reaction to construct donor-acceptor (D-A)-type fluorophores with alkoxyl substituents of varying carbon chain lengths (x = 1, 2, 4, 6, 12 in NAxC). To explain the observation that molecules with longer carbon chains revealed unusual fluorescence enhancement in water, we study the optical properties and evaluate their locally excited (LE) and ICT states by solvent effects combined with Lippert-Mataga plots. Then, we explored the self-assembly abilities of these molecules in water-organic (W/O) mixed solutions and observed the morphology of its nanostructure using a fluorescence microscope and SEM. The results show that NAxC, x = 4, 6, 12 show different degrees of self-assembly behaviors and corresponding aggregation-induced emission enhancement (AIEE) progresses. At the same time, different nanostructures and corresponding spectral changes can be obtained by adjusting the water ratio in the mixed solution. That is, NAxC compounds present different transitions between LE, ICT and AIEE based on the polarity, water ratio and time changes. We designed NAxC as the structure-activity relationship (SAR) of the surfactant to demonstrate that AIEE comes from the formation of micelle-like nanoaggregates, which causes a restriction of the transfer from the LE state to the ICT state, and micelle formation results in a blue-shift in emission and enhances the intensity in the aggregate state. Among them, NA12C is most likely to form micelles and the most obvious fluorescence enhancement, which will switch over time due to the nano-aggregation transition.

This study proposes a flexible and stretchable 3D polymer film with photonic crystals for the visible detection of spoiled milk. Thermoplastic polyurethane (TPU) was used as the substrate for the photonic crystal structure. The back barrier layer with a regular array of nanohemispheres of anodic aluminum oxide film was used as a template for electroforming a nickel mold. The nanohemisphere array was then nanoimprinted onto the TPU substrate to form a strain-controllable photonic crystal (SCPC) structure on it. Food spoilage can be easily detected by the structural color change caused by the gas it produces. Experimental results confirmed that the structural color change of the fabricated SCPC TPU film occurred when the elongation (Δ L ) of the film reached 0.2 mm (1.2 %). Furthermore, spoiled milk detection experiments showed that the proposed SCPC TPU film is a highly intelligent and cost-effective biosensor for detecting spoiled food in a container., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2022 The Authors.)

It has been found that the direct/total bilirubin ratio (D/T-BIL) is related to the survival rate of COVID-19 pneumonia. The presence of an excessive amount of bilirubin in human blood also causes liver and neurological damage, leading to death. Therefore, upon considering the adverse impact of the presence of excessive bilirubin in human blood, it has become highly imperative to detect bilirubin in a fast and label-free manner. Herein, we designed and constructed a random-crossed-woodpile nanostructure from silver nanowires to form a 3-dimensional plasmonic hotspot-rich (3D-PHS) nanostructure and successfully used it to detect direct bilirubin (D-BIL) in human blood in a label-free manner. The 3D-PHS nanochip provides rich spatial hot spots that are simultaneously responsive to SERS and SPEF effects and consequently, successfully used to measure and characterize D-BIL with a detection limit of ∼10 nM, requiring only 10μL of human serum for rapid screening, which is the first time D-BIL has been detected in a clinically relevant range. This demonstrates a simple, label-free, pretreatment-free potential biosensing technology that can be used in health care units, and further, in the efficient detection of point-of-care testing with a portable spectrometer., (Copyright © 2022 Elsevier B.V. All rights reserved.)

(1) Background: Inexplicable low back and neck pain frequently results from spinal disc degeneration with an imbalanced intervertebral disc (IVD) cell homeostasis. We hypothesize that introducing MSC expressing a sustained cartilage-anabolic factor in the IVD may stimulate the mucoid materials secreted from the IVD cells, promote the MSC's chondrogenesis and maintain the hydration content providing mechanical strength to decelerate the disc degeneration progression; (2) Methods: This study expressed a cartilage-anabolic factor runx1 by a baculoviral vector (BV) transduced MSCs through a Cre/LoxP gene editing and recombination system for sustained recombinant runx1 transcription factor production. The Cre/LoxP BV modified MSCs were encapsulated by hyaluronan hydrogel, due to its' vital composition in ECM of a healthy disc and transplanted to a punctured coccygeal disc in rats through micro-injection, followed by X-ray radiography and histological analysis at the 4- and 12-weeks post-transplantation; (3) Results: Data reveals the Cre/LoxP BV system-mediated long-termed runx1 gene expression, possessing good biosafety characteristics in the in vitro cell transduction and in vivo MSCs transplantation, and maintained superior hydration content in the disc than that of mock transduced MSCs; (4) Conclusions: This proof-of-concept study fulfills the need of implanting therapeutic cells accompanied with microinjection in the disc, such as a discography and paves a road to manufacture composite hyaluronan, such as peptide modified hyaluronan as an MSC carrier for IVD regeneration in the future study.

Vertebral disc degenerative disease (DDD) affects millions of people worldwide and is a critical factor leading to low back and neck pain and consequent disability. Currently, no strategy has addressed curing DDD from fundamental aspects, because the pathological mechanism leading to DDD is still controversial. One possible mechanism points to the homeostatic status of extracellular matrix (ECM) anabolism, and catabolism in the disc may play a vital role in the disease's progression. If the damaged disc receives an abundant amount of cartilage, anabolic factors may stimulate the residual cells in the damaged disc to secrete the ECM and mitigate the degeneration process. To examine this hypothesis, a cartilage anabolic factor, Runx1, was expressed by mRNA through a sophisticated polyamine-based PEG-polyplex nanomicelle delivery system in the damaged disc in a rat model. The mRNA medicine and polyamine carrier have favorable safety characteristics and biocompatibility for regenerative medicine. The endocytosis of mRNA-loaded polyplex nanomicelles in vitro, mRNA delivery efficacy, hydration content, disc shrinkage, and ECM in the disc in vivo were also examined. The data revealed that the mRNA-loaded polyplex nanomicelle was promptly engulfed by cellular late endosome, then spread into the cytosol homogeneously at a rate of less than 20 min post-administration of the mRNA medicine. The mRNA expression persisted for at least 6-days post-injection in vivo. Furthermore, the Runx1 mRNA delivered by polyplex nanomicelles increased hydration content by ≈43% in the punctured disc at 4-weeks post-injection (wpi) compared with naked Runx1 mRNA administration. Meanwhile, the disc space and ECM production were also significantly ameliorated in the polyplex nanomicelle group. This study demonstrated that anabolic factor administration by polyplex nanomicelle-protected mRNA medicine, such as Runx1, plays a key role in alleviating the progress of DDD, which is an imbalance scenario of disc metabolism. This platform could be further developed as a promising strategy applied to regenerative medicine.

Fluorescence lifetime imaging microscopy of a fluorescence probe, 3,6-bis(1-methyl-2-vinylpyridinium) carbazole diiodide (o-BMVC), provides an objective method for preoperative diagnosis of fine-needle aspiration (FNA) of thyroid nodules. The key of this o-BMVC test of FNA smears is the measurement of the digital number of o-BMVC foci in the nucleus. Thus, there are three categories classified in the o-BMVC test, which are nondiagnostic for unsatisfactory samples, benign for less numbers of o-BMVC foci, and malignant for more numbers of o-BMVC foci. The discrimination of indeterminate (including atypia, follicular neoplasm, suspicious) cytology into benign or malignant cases can reduce diagnostic uncertainty and benefit clinical decision making. This pilot study strongly suggests that the o-BMVC test is an invaluable method for diagnosing FNA samples. Particularly, the combination of FNA cytology and the o-BMVC test holds great promise to improve the efficacy of diagnosis and reduce the healthcare costs., (© 2021. The Author(s).)

Lysosomal adaptation is a cellular physiological process in which the number and function of lysosomes are regulated at the transcriptional and post-transcriptional levels in response to extracellular and/or intracellular cues or lysosomal damage. Imiquimod (IMQ), a synthetic toll-like receptor 7 ligand with hydrophobic and weak basic properties, exhibits both antitumor and antiviral activity against various skin malignancies as a clinical treatment. Interestingly, IMQ has been suggested to be highly concentrated in the lysosomes of plasmacytoid dendritic cells, indicating that IMQ could modulate lysosome function after sequestration in the lysosome. In this study, we found that IMQ not only induced lysosomal membrane permeabilization and dysfunction but also increased lysosome biogenesis to achieve lysosomal adaptation in cancer cells. IMQ-induced ROS production but not lysosomal sequestration of IMQ was the major cause of lysosomal adaptation. Moreover, IMQ-induced lysosomal adaptation occurred through lysosomal calcium ion release and activation of the calcineurin/TFEB axis to promote lysosome biogenesis. Finally, depletion of TFEB sensitized skin cancer cells to IMQ-induced apoptosis in vitro and in vivo. In summary, a disruption of lysosomal adaptation might represent a therapeutic strategy for synergistically enhancing the cytotoxicity of IMQ in skin cancer cells., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

The use of naturally occurring materials with antibacterial properties has gained a great interest in infected wound management. Despite being an abundant resource in Vietnam, chitosan and its derivatives have not yet been intensively explored for their potential in such application. Here, we utilized a local chitosan source to synthesize chitosan oligomers (OCS) using hydrogen peroxide (H 2 O 2 ) oxidation under the microwave irradiation method. The effects of H 2 O 2 concentration on the physicochemical properties of OCS were investigated through molecular weight, degree of deacetylation, and heavy metal contamination for optimization of OCS formulation. Then, the antibacterial inhibition was examined; the minimum inhibitory concentration and minimum bactericidal concentration (MIC and MBC) of OCS-based materials were determined against common skin-inhabitant pathogens. The results show that the local Vietnamese chitosan and its derivative OCS possessed high-yield purification while the molecular weight of OCS was inversely proportional and proportional to the concentration of H 2 O 2 , respectively. Further, the MIC and MBC of OCS ranged from 3.75 to less than 15 mg/mL and 7.5-15 mg/mL, respectively. Thus, OCS-based materials induce excellent antimicrobial properties and can be attractive for wound dressings and require further investigation.

In this manuscript, silver nanowire 3D random crossed-wire woodpile (3D-RCW) nanostructures were designed and prepared. The 3D-RCW provides rich "antenna" and "hot spot" effects that are responsive for surface-enhanced Raman scattering (SERS) effects and plasmon-enhanced fluorescence (PEF). The optimal construction mode for the 3D-RCW, based on the ratio of silver nanowire and control compound R6G, was explored and established for use in PEF and SERS analyses. We found that the RCW nanochip capable of emission and Raman-enhanced detections uses micro levels of analysis volumes. Consequently, and SERS and PEF of pesticides (thiram, carbaryl, paraquat, fipronil) were successfully measured and characterized, and their detection limits were within 5 μM~0.05 µM in 20 µL. We found that the designed 3D plasmon-enhanced platform cannot only collect the SERS of pesticides, but also enhance the fluorescence of a weak emitter (pesticides) by more than 1000-fold via excitation of the surface plasmon resonance, which can be used to extend the range of a fluorescence biosensor. More importantly, solid-state measurement using a 3D-RCW nanoplatform shows promising potential based on its dual applications in creating large SERS and PEF enhancements.

The major challenge in the fabrication of fluorescent silica nanoparticles (FSNs) based on dye-doped silica nanoparticles (DDSNs) is aggregation-caused fluorescence quenching. Here, we constructed an FSN based on a double emission enhancement (DEE) platform. A thio-reactive fluorescence turn-on molecule, N -butyl-4-(4-maleimidostyryl)-1,8-naphthalimide (CS), was bound to a silane coupling agent, (3-mercaptopropyl)-trimethoxysilane (MPTMS), and the product N -butyl-4-(3-(trimethoxysilyl-propylthio)styryl)-1,8-naphthalimide (CSP) was further used to fabricate a core-shell nanoparticle through the Stöber method. We concluded that the turn-on emission by CSP originated from the photoinduced electron transfer (PET) between the maleimide moiety and the CSP core scaffold, and the second emission enhancement was attributed to the aggregation-induced emission enhancement (AIEE) in CSP when encapsulated inside a core-shell nanoparticle. Thus, FSNs could be obtained through DEE based on a combination of PET and AIEE effects. Systematic investigations verified that the resulting FSNs showed the traditional solvent-independent and photostable optical properties. The results implied that the novel FSNs are suitable as biomarkers in living cells and function as fluorescent visualizing agents for intracellular imaging and drug carriers.

This study proposes to develop a dual-acting antibacterial film of porous chitosan (Cs) embedded with small molecular compound, which possesses photosensitive characteristics with bactericidal efficacy, to promote the accelerated recovery of infectious wounds. The Cs/small molecular compound (Cs-cpd.2) dressing was prepared using the freeze-drying method. Characterization of the synthesized Cs-cpd.2 indicated that it has high porosity and moisture absorption effect, hence enhancing the absorption of wound exudate. Experimental results showed that Cs-cpd.2 dressing has good bactericidal and bacteriostatic effects on Staphylococcus aureus under visible-light irradiation and has antibacterial effect in the dark. It was also found that the small molecular compound does not have cytotoxicity at a dose of 0-5 μM. Furthermore, Cs-cpd.2 that contained small molecular compound with a concentration of 0.3-1 μM has positive effect on both the cell viability rate and cell proliferation rate of human fibroblast CG1639. Cs-cpd.2 can significantly promote cell proliferation when the small molecular compound and the basic fibroblast growth factor bFGF were added together. Therefore, the proposed Cs-cpd.2 dressing is feasible for photodynamic therapy (PDT) and clinical wound dressing applications., Competing Interests: No potential conflict of interest was reported by the authors., (© 2020 The Author(s). Published by National Institute for Materials Science in partnership with Taylor & Francis Group.)

The potent DNA-binding compound triaminotriazine-acridine conjugate (Z1) functions by targeting T:T mismatches in CTG trinucleotide repeats that are responsible for causing neurological diseases such as myotonic dystrophy type 1, but its binding mechanism remains unclear. We solved a crystal structure of Z1 in a complex with DNA containing three consecutive CTG repeats with three T:T mismatches. Crystallographic studies revealed that direct intercalation of two Z1 molecules at both ends of the CTG repeat induces thymine base flipping and DNA backbone deformation to form a four-way junction. The core of the complex unexpectedly adopts a U-shaped head-to-head topology to form a crossover of each chain at the junction site. The crossover junction is held together by two stacked G:C pairs at the central core that rotate with respect to each other in an X-shape to form two nonplanar minor-groove-aligned G·C·G·C tetrads. Two stacked G:C pairs on both sides of the center core are involved in the formation of pseudo-continuous duplex DNA. Four metal-mediated base pairs are observed between the N7 atoms of G and Co II , an interaction that strongly preserves the central junction site. Beyond revealing a new type of ligand-induced, four-way junction, these observations enhance our understanding of the specific supramolecular chemistry of Z1 that is essential for the formation of a noncanonical DNA superstructure. The structural features described here serve as a foundation for the design of new sequence-specific ligands targeting mismatches in the repeat-associated structures.

A detection and degradation platform was developed to optically quantify the 6-enolate, 8-keto-dG, an important tautomer of mitochondrial mutated DNA 8-oxo-dG. We first found that 6-enolate, 8-keto-dG offers particular fluorescence emission under the conditions between pH ∼ 7 and ∼11. Thus, a mitochondria-targeting photosensitizer NV-12P was prepared to offer simultaneously photoinduced electron transfer and fluorescence resonance energy transfer (FRET) with 6-enolate, 8-keto-dG. Furthermore, NV-12P can also generate a reactive oxygen species to degrade 6-enolate, 8-keto-dG under irradiation conditions. This is the first publication about optical characterization, concentration detection and photodegradation of 6-enolate, 8-keto-dG, either in biological or in vitro applications.

Using time-gated fluorescence lifetime imaging microscopy, significantly more signals from 3,6-bis(1-methyl-2-vinyl-pyridinium) carbazole diiodide (o-BMVC) foci, characterized by the longer fluorescent decay time of o-BMVC, were detected in six types of cancer cells than in three types of normal cells. Accumulating evidence suggested that the o-BMVC foci are mainly the G-quadruplex foci. The large contrast in the number of o-BMVC foci can be considered as a common signature to distinguish cancer cells from normal cells. Further study of tissue biopsy showed that the o-BMVC test provides a high accuracy for clinical detection of head and neck cancers.

Melanogenesis is a complex physiological mechanism involving various paracrine factors. Skin cells such as keratinocytes, fibroblasts, and melanocytes communicate with one another through secreted regulators, thereby regulating the melanocytes' bio-functions. The stem cell factor (SCF) is a paracrine factor produced by fibroblasts, and its receptor, c-kit, is expressed on melanocytes. Binding of SCF to c-kit activates autophosphorylation and tyrosine kinase to switch on its signal transmission. SCF inhibition does not suppress fibroblast proliferation in MTT assay, and SCF silencing induced mRNA expressions of paracrine factor genes, HGF , NRG-1 , and CRH in qPCR results. Following UVB stimulation, gene expressions of HGF , NRG , and CRH were higher than homeostasis; in particular, HGF exhibited the highest correlation with SCF variations. We detected fibroblasts regulated SCF in an autocrine-dependent manner, and the conditioned medium obtained from fibroblast culture was applied to treat melanocytes. Melanogenesis-related genes, tyrosinase and pmel17 , were upregulated under conditioned mediums with SCF silencing and exposed to UVB treatments. Melanin quantities in the melanocytes had clearly increased in the pigment content assay. In conclusion, SCF silencing causes variations in both fibroblast paracrine factors and melanocyte melanogenesis, and the differences in gene expressions were observed following UVB exposure.

Traditional fluorogens with aggregation-induced emission (AIEgens) generally exhibit strong luminescence with monotonous wavelengths in the aggregated state, whereas apparent solvatochromic emission intensities and wavelengths (shift) are observed in molecules with twisted intramolecular charge transfer (TICT) characteristic molecules. Herein, we develop a platform to construct strong luminescent nanoparticles with tunable emission colors based on a TICT-AIEgen, 3,6-divinylaryl-substituted carbazole (C12P). Also based on the same molecule, through different nanoparticle fabrication approaches, fluorescent nanoparticles with different emission colors were obtained. A detailed analysis reveals that AIE and TICT characteristics play different roles in nanoparticle emission, with AIE primarily controlling the emission intensity while TICT is more involved in manipulating the emission wavelengths. Applications of the as-prepared nanoparticles in cell imaging were preliminarily demonstrated.

In this study, a nanoimprinting method was introduced to fabricate polycarbonate films with transparent and flexible photonic crystal (FPC) structures. The fabricated flexible polymer films display a full-color grating because of the nanohemispherical structures on the surface. Through the Bragg diffraction formula, it was confirmed that the FPC polymer films transfer a part of the light energy to the second-order diffraction spectrum. Furthermore, the full-color grating properties can be modulated through geometric deformation because of the film's elasticity. Additionally, anticounterfeiting features were also successfully achieved when the polymer films were either engraved with drawings and bent or patterned with fluorophores, which can be revealed under ultraviolet light. The most important aspect of this research is that the preparation of this FPC-structured polymer film is inexpensive and convenient, enabling the mass production of a new generation of smart materials.

A water-soluble pH sensor, 2-(6-(4-aminostyryl)-1,3-dioxo-1H-benzo[de]isoquinolin-2(3H)-yl)-N, N-dimethylethanamine (ADA), was synthesized based on the molecular design of photoinduced electron transfer (PET) and intramolecular charge transfer (ICT). The fluorescence emission response against a pH value is in the range 3-6, which is suitable for labelling intracellular pH-dependent microenvironments. After biological evolution, ADA is more than a pH biosensor because it is also an endocytosis pathway tracking biosensor that labels endosomes, late endosomes, and lysosome pH gradients. From this, the emissive aggregates of ADA and protonated-ADA in these organs were evaluated to explore how this probe stresses emission colour change to cause these unique cellular images.

The microvascular network is a simple but critical system that is responsible for a range of important biological mechanisms in the bodies of all animals. The ability to generate a functional microvessel not only makes it possible to engineer vital tissue of considerable size but also serves as a platform for biomedical studies. However, most of the current methods for generating microvessel networks in vitro use rectangular channels which cannot represent real vessels in vivo and have dead zones at their corners, hence hindering the circulation of culture medium. We propose a scaffold-wrapping method which enables fabrication of a customized microvascular network in vitro in a more biomimetic way. By integrating microelectromechanical techniques with thermal reflow, we designed and fabricated a microscale hemi-cylindrical photoresist template. A replica mold of polydimethylsiloxane, produced by casting, was then used to generate cylindrical scaffolds with biodegradable poly(lactide-co-glycolide) (PLGA). Human umbilical vein endothelial cells were seeded on both sides of the PLGA scaffold and cultured using a traditional approach. The expression of endothelial cell marker CD31 and intercellular junction vascular endothelial cadherin on the cultured cell demonstrated the potential of generating a microvascular network with a degradable cylindrical scaffold. Our method allows cells to be cultured on a scaffold using a conventional culture approach and monitors cell conditions continuously. We hope our cell-covered scaffold can serve as a framework for building large tissues or can be used as the core of a vascular chip for in vitro circulation studies.

This manuscript describes the preparation of water soluble aggregation-induced emission enhancement (AIEE)-based fluorescent organic nanoparticles (FONs). The fluorescence diversity of the FONs was investigated in the presence of silver nanowires. We observed that the emission of the FONs can be enhanced by mixing with the nanowires, which is believed to originate from resonance between the emission of the FONs and the surface plasmon resonances of the metal surface. That is, the AIEE phenomenon was promoted according to the metal-enhanced fluorescence (MEF) mechanism that can be used to build up a novel double emission enhancement (DEE) platform and to extend the range of AIEE applications. The systemic fluorescence enhancement, lifetime and photostability were measured and the AIEE-MEF evaluation and the interaction between the FONs and nanowires were discussed based on the obtained spectral data and SEM and fluorescent microscopy images.

Tiny bubbles readily stick onto substrates owing to contact angle hysteresis (CAH). Nevertheless, they can slide slowly on a tilted surface with ultralow CAH because capillarity is overcome by buoyancy. It is surprising to observe experimentally that bubbles of 3-15 μL (diameter 1.79-3.06 mm) slide beneath a tilted superhydrophobic surface at a vertical ascent rate faster than that of freely rising ones of high Reynold numbers ≈O(10 2 ). As the tilting angle increases, the drag coefficient remains essentially the same as that of a freely rising bubble, but the frontal area of the flat bubble rises monotonically. Nonetheless, the frontal area of the sliding bubble always stays much smaller than that of a freely rising bubble. Consequently, the small drag force associated with the sliding bubbles is attributed to their substantially small frontal areas on superhydrophobic surfaces.

The enzyme kinetic in a biochemical reaction is critical to scientific research and drug discovery but can hardly be determined experimentally from enzyme assays. In this work, a charge-current transducer (a transistor) is proposed to evaluate the status of biochemical reaction by monitoring the electrical charge changes. Using the malate-aspartate shuttle as an example, a thin-film transistor (TFT)-based biosensor with an extended gold pad is demonstrated to detect the biochemical reaction between NADH and NAD+. The drain current change indicates the status of chemical equilibrium and stoichiometry., Competing Interests: The authors have declared that no competing interests exist.

Unlike traditional binary nanostructures that construct chemotherapy drugs and photodynamic therapy photosensitizers, we introduce a molecule with a chemo-photodynamic dual therapy function. A water-soluble aggregation-induced emission enhancement (AIEE) fluorogen, NV-12P, was designed and synthesized based on asymmetric 1,6-disubstituted naphthalene and can generate particular reactive oxygen species to undergo type I photodynamic therapy under irradiation. Furthermore, this compound can specifically localize in mitochondria and, after biological evaluation, can cause mitochondrial dysfunction and potent cytotoxicity to cancer cells but not normal cells. We conclude that this compound is a potential dual-toxic efficacy molecule because it exhibits selective dark cytotoxicity and efficient photodamage in cancer cells. Additionally, we also supported the optimal combinational treatment course for the best chemo-phototherapy efficacy.

The encounter of a nanodrop with a trench on a hysteresis-free surface is explored by many-body dissipative particle dynamics to show the effect of surface roughness on droplet wetting. A free nanodrop exhibits Brownian motion and the diffusivity decays exponentially with the liquid-solid contact area. In contrast, as the nanodrop sits on a trench, its random motion is constrained. Work must be done to overcome the energy barriers for the transition between free and trapped states. The potential energy landscape is thus constructed based on the force-displacement plot. It is shown that the trench acts as a hydrophobic blemish for capture but like a hydrophilic blemish for escape. A drop always breaks up after detachment from a hydrophilic trench. Therefore, the drop tends to bypass a small trench when it meets one. The macroscopic experiments are performed by fabricating liquid-infused surfaces with extremely low contact angle hysteresis. The experimental observations agree qualitatively with simulation outcomes.

Nanodrops on smooth or patterned rough surfaces are explored by many-body dissipative particle dynamics to demonstrate the influence of surface roughness on droplet wetting. On a smooth surface, nanodrops exhibit the random motion and contact angle hysteresis is absent. The diffusivity decays as the intrinsic contact angle (θ_{Y}) decreases. On a rough surface, the contact line is pinned and the most stable contact angle (θ_{Y}^{'}) is acquired. The extent of contact angle hysteresis (Δθ) is determined by two approaches, which resemble the inflation-deflation method and inclined plane method for experiments. The hysteresis loop is acquired and both approaches yield consistent results. The influences of wettability and surface roughness on θ_{Y}^{'} and Δθ are examined. θ_{Y}^{'} deviates from that estimated by the Wenzel or Cassie-Baxter models. This consequence can be explained by the extent of impregnation, which varies with the groove position and wettability. Moreover, contact angle hysteresis depends more on the groove width than the depth.

A sensing platform, combined amino acid labeling kit and a double-generation gold nanoparticle (DG-AuNP) chip, was designed to prove the existence of weak but crucial binding between the DV (dengue virus) and its CLEC5A receptor. At first, we have designed a kit combining the novel fluorescence turn-on sensors for lysine, arginine and cysteine amino acids. Advantages of this kit are that emission on-off switching can increase the signal-to-noise ratio and the virus must be fluorescently labelled with sufficient numbers of fluorophores because the lysine, arginine and cysteine residues of viral proteins are labelled simultaneously. Consequently, this kit can be used to light-on single DV spot both in solution and in cell under fluorescence microscopy. Second, the labeling kit was used to examine the DV binding to the CLEC5A-coated DG-AuNP chip. Based on our study, the double-generation gold nanoparticle construction of chip can support more coating areas for receptor CLEC5A and then, support more binding opportunities for DV. Meanwhile, the grooves between nanohemispheres will provide the extra driving force for DV stacking. We try to give a proof that this sensing platform is very useful for detection of weak binding mechanism., (Copyright © 2015 Elsevier B.V. All rights reserved.)

G-quadruplex (G4) is a promising target for anti-cancer treatment. In this paper, we provide the first evidence supporting the presence of G4 in the mitochondrial DNA (mtDNA) of live cells. The molecular engineering of a fluorescent G4 ligand, 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC), can change its major cellular localization from the nucleus to the mitochondria in cancer cells, while remaining primarily in the cytoplasm of normal cells. A number of BMVC derivatives with sufficient mitochondrial uptake can induce cancer cell death without damaging normal cells. Fluorescence studies of these anti-cancer agents in live cells and in isolated mitochondria from HeLa cells have demonstrated that their major target is mtDNA. In this study, we use fluorescence lifetime imaging microscopy to verify the existence of mtDNA G4s in live cells. Bioactivity studies indicate that interactions between these anti-cancer agents and mtDNA G4 can suppress mitochondrial gene expression. This work underlines the importance of fluorescence in the monitoring of drug-target interactions in cells and illustrates the emerging development of drugs in which mtDNA G4 is the primary target., (© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.)

The stability of air pockets formed in grooves on a surface is relevant to contact angle hysteresis of droplet wetting and it is investigated by imbibition experiments and surface evolver (SE) simulations. Liquid drops of different wettabilities are placed atop a conical hole on a polymethyl methacrylate (PMMA) substrate. The stability of the air pocket depends on surface wettability. Four kinds of imbibition behaviors ranging from wetting to nonwetting are observed. The imbibition pathway for the kinetically unstable air pocket is observed by using the olive oil droplet. It involves an inward flow of a thin liquid film along the wall of the hole. The accumulation of liquid at the bottom leads to the rise of the air bubble. The energy-barrier profile associated with the imbibition pathway acquired by SE simulations is able to interpret the outcome of imbibition. The advancing and receding contact angles of various liquids on a PMMA substrate with drilled holes are also determined. Their wetting behaviors can be categorized into three types. Our experimental results for substrates with or without fluorination are in good agreement with the theory based on the stability of air pockets.

The self-coating process of solid particles over a liquid drop is important for the formation of a liquid marble. Generally, some external forces such as rolling or flipping are used to cover a drop by small particles. In this work, it is observed that flaky copper powders can spontaneously spread over the planar water surface and form a dense flat cluster with a fractal dimension of 2. Moreover, flaky copper powders can cover the water pendant and sessile drops spontaneously and rapidly. This powder-coated drop can roll on an inclined plane at a relatively high speed. However, spontaneous self-coating disappears for spheroidal copper powders. To explain our observations, the shape factors of particles are introduced into the spreading coefficient S for powders on the liquid surface. The flaky powders have the lowest shape factors and therefore spontaneous self-coating formation, with S > 0.

Compelling evidence suggests that formation of guanine-quadruplex (G4) can protect the integrity of chromosome ends in eukaryotes, and regulate the activity of some gene promoters. In addition, G4 may be a novel therapeutic target. Thus, a number of ligands have been synthesized to stabilize G4. However, skepticism lingers over the existence of G4 in cells, as well as its biological function. The molecule 3,6-bis(1-methyl-4-vinylpyridium) carbazole diiodide (BMVC) can be used not only as a fluorescent probe to map endogenous and exogenous G4 in live cells, but also as therapeutic agent that arrests cancer growth by inhibiting telomerase activity and regulating gene expression. Thus, the fluorescence of a G4 anti-cancer agent is an invaluable tool to detect G4 in cells, investigate ligand-G4 interaction in live cells, examine the biological function of G4, and guide the development of new fluorescent anti-cancer agents.

The nanostructure can collapse due to elasto-capillary interactions. On the basis of free energy analysis for three cases, the contact between double beams can be induced by equilibrium contact or instability. In the former mechanism, the beam contact can be achieved by a gradual increase of deformation with increasing the liquid volume. In the latter mechanism, a sudden rise of deformation occurs due to the divergence of the Laplace pressure as the liquid volume exceeds a critical value. For the case of free-fixed beams, the collapse phase diagram is obtained in the structure aspect ratio-liquid volume plane. The collapse by equilibrium contact occurs for a large aspect ratio but that by instability happens for a small aspect ratio. For the case of fixed-fixed beams, the collapse can occur at the midpoint of two beams by instability.

The development of the first miniaturized parallel acoustic delay line (PADL) probe for handheld photoacoustic tomography (PAT) is reported. Using fused-silica optical fibers with low acoustic attenuation, we constructed two arrays of eight PADLs. Precision laser micromachining was conducted to produce robust and accurate mechanical support and alignment structures for the PADLs, with minimal acoustic distortion and interchannel coupling. The 16 optical-fiber PADLs, each with a different time delay, were arranged to form one input port and two output ports. A handheld PADL probe was constructed using two single-element transducers and two data acquisition channels (equal to a channel reduction ratio of 8∶1). Photoacoustic (PA) images of a black-ink target embedded in an optically scattering phantom were successfully acquired. After traveling through the PADLs, the eight channels of differently time-delayed PA signals reached each single-element ultrasonic transducer in a designated nonoverlapping time series, allowing clear signal separation for PA image reconstruction. Our results show that the PADL technique and the handheld probe can potentially enable real-time PAT, while significantly reducing the complexity and cost of the ultrasound receiver system.

A new class of near-infrared (NIR)-absorptive (>900 nm) photosensitizer based on a phenothiazinium scaffold is reported. The stable solid compound, o-DAP, the oxidative form of 3,7-bis(4-methylaminophenyl)-10H-phenothiazine, can generate reactive oxygen species (ROS, singlet oxygen and superoxide) under appropriate irradiation conditions. After biologically evaluating the intracellular uptake, localization, and phototoxicity of this compound, it was concluded that o-DAP is photostable and a potential selective photodynamic therapy (PDT) agent under either NIR or white light irradiation because its photodamage is more efficient in cancer cells than in normal cells and is without significant dark toxicity. This is very rare for photosensitizers in PDT applications., (© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We introduce a new class of photostable, efficient photosensitizers based on boron-dipyrromethene (BODIPY) derivatives that can generate singlet oxygen and superoxide simultaneously under irradiation. First, we report the synthesis and design of how to control the generation of a specifically substituted position of BODIPY. Second, after biologically evaluating the uptake, localization and phototoxicity in cell lines, we conclude that 2,6-di-anisole substituted BODIPY is a potentially selective photodynamic therapy candidate because its photodamage is more efficient in cancer cells than in normal cells without significant dark toxicity.

We introduce a new class of photostable, efficient photosensitizers based on boron-dipyrromethene (BODIPY) derivatives that can generate singlet oxygen and super oxide simultaneously under irradiation. For compound preparation, appropriate regulation of the reaction conditions and control of specifically substituted BODIPY derivatives have been achieved. After biologically evaluating the intracellular uptake, localization, and phototoxicity of the compounds, we conclude that 3,5-dianiline-substituted BODIPY is a potentially selective photodynamic therapy candidate because its photodamage is more efficient in cancer cells than in normal cells, without apparent dark toxicity. Furthermore, direct comparison of photodamage efficacy revealed that our compound has better efficacy than Foscan and nearly equal efficacy to that of methylene blue.

The patch described in this paper combines the principles of wet adhesion, which is a widely adopted biological adhesion system in nature, with transdermal drug delivery. A biologically inspired micropillar patch was fabricated that is self-adhesive, reusable, and can sustain a controlled drug release. We successfully preloaded the commercial non-steroidal anti-inflammatory generic drug unguents indomethacin, ketoprofen, diclofenac sodium and etofenamate into a polydimethylsiloxane elastomeric matrix and fabricated drug-containing micropillar patches. When examining the drug release kinetics and friction of the patches, we observed that these drug unguents can be released calculably and regularly for several days. Additionally, the drug unguents released from the patch to its attached surface are critical to increase the strength of the patch's adhesion, which is based on capillary attractive forces and is inspired by beetle feet. Here, we create a novel system combining biomimetics and drug delivery that can be modified for use across the biomedical and engineering spectra. Motivation: the objective of the present study was to characterize a micropillar PDMS patch that was inspired by a beetle's wet adhesion as a platform for conducting in vitro release studies. Commercially available non-steroid anti-inflammatory drugs (NSAIDs) were used as the model drugs for our delivery systems. An emphasis was put on quantitatively evaluating the drug release and friction manifestation of these patches.

The importance of guanine-quadruplex (G4) is not only in protecting the ends of chromosomes for human telomeres but also in regulating gene expression for several gene promoters. However, the existence of G4 structures in living cells is still in debate. A fluorescent probe, 3,6-bis(1-methyl-2-vinylpyridinium) carbazole diiodide (o-BMVC), for differentiating G4 structures from duplexes is characterized. o-BMVC has a large contrast in fluorescence decay time, binding affinity, and fluorescent intensity between G4 structures and duplexes, which makes it a good candidate for probing G4 DNA structures. The fluorescence decay time of o-BMVC upon interaction with G4 structures of telomeric G-rich sequences is ∼2.8  ns and that of interaction with the duplex structure of a calf thymus is ∼1.2  ns. By analyzing its fluorescence decay time and histogram, we were able to detect one G4 out of 1000 duplexes in vitro. Furthermore, by using fluorescence lifetime imaging microscopy, we demonstrated an innovative methodology for visualizing the localization of G4 structures as well as mapping the localization of different G4 structures in living cells.

Understanding of principles governing selective and sensitive cancer targeting is critical for development of chemicals for cancer diagnostics and treatment. We determined the underlying mechanisms of how a novel fluorescent small organic molecule, 3,6-bis(1-methyl-4-vinylpyridinium)carbazole diiodide (BMVC), selectively labels cancer cells but not normal cells. We show that BMVC is retained in the lysosomes of normal cells. In cancer cells, BMVC escapes lysosomal retention and localizes to the mitochondria or to the nucleus, where DNA-binding dramatically increases BMVC fluorescence intensity, allowing it to light up only cancer cells. Structure-function analyses of BMVC derivatives show that hydrogen-bonding capacity is a key determinant of lysosomal retention in normal cells, whereas lipophilicity directs these derivatives to the mitochondria or the nucleus in cancer cells. In addition, drug-resistant cancer cells preferentially retain BMVC in their lysosomes compared to drug-sensitive cancer cells, and BMVC can be released from drug-resistant lysosomes using lysosomotropic agents. Our results further our understanding of how properties of cellular organelles differ between normal and cancer cells, which can be exploited for diagnostic and/or therapeutic use. We also provide physiochemical design principles for selective targeting of small molecules to different organelles. Moreover, our results suggest that agents which can increase lysosomal membrane permeability may re-sensitize drug-resistant cancer cells to chemotherapeutic agents.

The liquid drop captured at the capillary end, which is observed in capillary valve and pendant drop technique, is investigated theoretically and experimentally. Because of contact line pinning of the lower meniscus, the lower contact angle is able to rise from the intrinsic contact angle (θ*) so that the external force acting on the drop can be balanced by the capillary force. In the absence of contact angle hysteresis (CAH), the upper contact angle remains at θ*. However, in the presence of CAH, the upper contact angle can descend to provide more capillary force. The coupling between the lower and upper contact angles determines the equilibrium shape of the captured drop. In a capillary valve, the pinned contact line can move across the edge as the pressure difference exceeds the valving pressure, which depends on the geometrical characteristic and wetting property of the valve opening. When CAH is considered, the valving pressure is elevated because the capillary force is enhanced by the receding contact angle. For a pendant drop under gravity, the maximal capillary force is achieved as the lower contact angle reaches 180° in the absence of CAH. However, in the presence of CAH, four regimes can be identified by three critical drop volumes. The lower contact angle can exceed 180°, and therefore the drop takes on the shape of a light bulb, which does not exist in the absence of CAH. The comparisons between Surface Evolver simulations and experiments are quite well.

The G-quadruplex structures in the telomere of a chromosome can not only protect the internal chromosome sequences by preventing the improper activation of DNA-damage-response pathways but also become targets for cancer treatments. In this manuscript, we wish to prove the existence of G-quadruplex structure formation, rather than G-quadruplex sequence, in chromosome of human cancer cells. Based on our studies, the fluorescent mapping of G-quadruplex structures in the chromosome is possible with the combination of G-quadruplex targeting fluorophore (BMVC, 3, 6-bis-(1-methyl-4-vinylpyridinium)-carbazole diiodide) and duplex-binding fluorophores (Hoechst or propidium iodide). By means of an applicable incubation time between cell cycle period and proper staining procedure to the chromosome, FRET (fluorescence resonance energy transfer) between G-quadruplex targeting fluorophore and duplex-binding fluorophore can increase the signal contrast of the fluorescent color and the fluorescent mapping of quadruplex structures can be easily observed using fluorescence microscopy. These observations are further supported by basic spectral analysis, titration binding assay, gel electrophoresis binding competition assay and confocal microscopy., (Copyright © 2013 Elsevier B.V. All rights reserved.)

A liquid drop trapped in a microchannel, in which both contact angle (wettability) and opening angle (geometry) can vary with position, is investigated based on the minimization of free energy. The calculus of variation yields the Young-Laplace equation and its further integration leads to the general force balance. The equilibrium position of the trapped drop is determined by the balance between the area-mean capillary force and the area-mean hydrostatic pressure difference. Trapped liquid drops in truncated cones and hyperboloids are studied to elucidate our theory. As the volume of the drop trapped in the hydrophilic cones is increased, four regimes separated by three critical volumes are identified. The drop is either trapped at the narrow end or away from the cone top. The solution at the cone top satisfies the force balance by adjusting the upper contact angle, which is experimentally observed and verified by Surface Evolver (SE) simulations. Multiple stable states can exist in a particular regime. The hyperboloid tube in which the opening angle varies with position is also considered. As the gravitational strength is increased in hydrophilic hyperboloid, four regimes separated by three critical gravitational strengths are identified. The drop is either trapped near the neck or below the neck. Unlike hydrophilic cones, the drop stays near the neck of the hyperboloid due to varying opening angles. Multiple stable states are also observed. For both cone and hyperboloid, hydrophobic cases are studied as well and all theoretical solutions of the force balance agree well with SE simulation outcomes.

A binary molecule can self-assemble to form fluorescent organic nanoparticles (FONs) based on the Aggregation-Induced Emission Enhancement (AIEE) property and subsequently, presents an efficient fluorescence resonance energy transfer (FRET) to generate singlet oxygen under linear and nonlinear light sources. Biologically, this FON-photosensitizer is much more phototoxic to cancer cells than to normal cells without significant dark toxicity. Eventually, a new approach, called FON FRET-PDT or AIEE FRET-PDT, to promote the PDT effect is expected.

In this paper, we present the design, fabrication and testing of novel micromachined silicon-based acoustic delay lines. The acoustic properties of different silicon delay line structures have been characterized. Based on the experiment results, two different acoustic delay line systems (parallel and serial) have been successfully demonstrated to create controlled time delays in multiple channels of ultrasound signals. The time-delayed ultrasound signals are received with a single-element ultrasound transducer in a time-serial manner. This unique capability could be used to merge multiple signal channels, thereby enabling new ultrasound receiver designs with potentially less complexity and lower cost.

We have applied a fluorescent molecule 3,6-bis(1-methyl-4-vinylpyridinium) carbazole diiodide (BMVC) for tumor targeting and treatment. In this study, we investigated the photo-induced antitumor effect of BMVC. In vitro cell line studies showed that BMVC significantly killed TC-1 tumor cells at light dose greater than 40 J/cm(2). The fluorescence of BMVC in the tumor peaked at 3 hours and then gradually decreased to reach the control level after 24 hours. In vivo tumor treatment studies showed BMVC plus light irradiation (iPDT) significantly inhibited the tumor growth. At day 24 after tumor implantation, tumor volume was measured to be 225 ± 79 mm(3), 2542 ± 181 mm(3), 1533 ± 766 mm(3), and 1317 ± 108 mm(3) in the iPDT, control, light-only, and BMVC-only groups, respectively. Immunohistochemistry studies showed the microvascular density was significantly lower in the iPDT group. Taken together, our results demonstrated that BMVC may be a potent tumor-specific photosensitizer (PS) for PDT.