Developing a multifunctional material that combines fluorescence detection and adsorption removal of ethylenediamine (EDA) vapor would significantly mitigate its potential health risks. However, the existing materials can only achieve either detection or removal of EDA. Herein, we present a hydrogel sensor incorporating a sensing reagent (PTA), enabling simultaneous ratiometric sensing and efficient removal of EDA vapor. For practical use, this hydrogel sensor can be integrated into lab coats and protective masks, with changes in fluorescence color indicating whether EDA vapor concentrations exceed safe limits. Additionally, when integrated into an N95 mask, the hydrogel sensor effectively adsorbs and removes EDA vapor, thereby safeguarding human health. To facilitate practical use, we have developed an application program (app) called "WTU-color Reader", which can read the RGB values of fluorescence images from the hydrogel sensor, and accurately provide the concentrations of EDA vapor based on the input linear equation between B/R values with EDA levels.
Bioluminescence imaging (BLI) is widely used in preclinical biomedical research for noninvasive tracking of cell populations and biochemical events in vivo. With recent improvements in BLI brightness from the engineering of bioluminescent enzymes (luciferases) and substrates (luciferins), optimizing luciferin formulations to maximize delivery and minimize toxicity becomes important, especially for marine coelenterazine-type luciferins with limited solubility. Here, we complete the characterization of a previously reported NanoLuc substrate, designated cephalofurimazine-9 (CFz9), and optimize its formulation with water-soluble excipients. We report a pH-controlled formulation of CFz9 enabling high-dose delivery to achieve peak brightness comparable to other furimazine analogs both inside and outside the brain while reducing toxicity. Thus, an optimized CFz9 formulation improves the performance and tolerability of whole-animal BLI with NanoLuc-based reporters.
Traditional chemotherapy remains the main treatment option for cancer. However, drugs discovered through conventional targets are often accompanied by side effects and drug resistance, so more effective treatment options are urgently needed. Discovery of antitumor drugs targeting G-quadruplexes is an effective pathway. Here, a novel series of pyrazolo[4,3-c]quinolines as potential stabilizing ligands for c-MYC Pu27 and KRAS G-quadruplexes was synthesized. Compound PQ32 was observed to stabilize these G-quadruplexes with high ΔTm values. Biological investigations indicated that PQ32 inhibited tumor cell proliferation with an IC50 of ∼ 1.00 μM, arrested the cell cycle in the G2 phase, and caused cell apoptosis. Further studies revealed that PQ32 could inhibit the expression of c-MYC and KRAS genes. Xenograft animal model assay suggested that PQ32 effectively inhibited the tumor growth in mice with comparable activity to cisplatin. Thus, the interaction of quinoline-based ligands with multiple G-quadruplex DNA provides a promising target for anticancer therapeutic strategy.
The development of a bifunctional fluorescent probe for the simultaneous detection of SO2 and H2S in Chinese herbal medicines and living organisms is vital for human health. In this study, we present a novel fluorescent probe, TTP, which exhibits a fluorescence turn-on response to both SO2 and H2S through two independent fluorescent channels. Notably, this probe demonstrates a significant difference in response times for SO2 (10 s) and H2S (60 s), and the fluorescence response to one substance remains unaffected by the presence of the other, thus effectively eliminating the problem of signal crosstalk during the simultaneous detection. Integrating with a smartphone sensing platform, probe TTP realizes the convenient, rapid, quantitative, and on-site detection of SO2 and H2S in various Chinese herbal medicines. Additionally, TTP is suitable for the real-time monitoring of SO2 and H2S levels in living cells and zebrafish.
The accuracy of CH4 photoacoustic spectroscopy detection is greatly affected by the kinetic cooling effect of H2O and O2 in the air background. The lack of practical and convenient correction methods greatly limits the application of photoacoustic spectroscopy detection technology in CH4 monitoring. This study established a prediction algorithm for CH4 photoacoustic signals in the air background, and based on this, proposed a correction method for CH4 photoacoustic signals based on relative kinetic cooling coefficient. Inspired by the phenomenon that the resonance frequency of the photoacoustic cell in air mainly changes linearly with the O2 concentration, the correction method we proposed first estimates the O2 concentration through the change of the resonance frequency, and then calculates the H2O concentration in combination with the phase information, without the need to integrate additional H2O and O2 sensors in the volume-constrained photoacoustic cell. The established CH4 photoacoustic signal prediction algorithm takes into account the influence of O2 concentration on the resonance frequency, and can accurately predict the amplitude and phase of the CH4 photoacoustic signal in the air background. The relative error between the predicted results and the experimental results is less than 10%. The proposed correction method reduces the maximum value of the CH4 concentration prediction error from 91.50% to 27.35%, effectively improving the prediction accuracy of CH4 concentration and greatly improving the practicability of CH4 photoacoustic spectroscopy detection, providing strong support for the safe and stable operation of power equipment and natural gas monitoring. This method is expected to be extended to the photoacoustic spectroscopy detection applications of trace gases such as CO.
Small molecules targeting G-quadruplexes (G4s) in viruses could inhibit viral proliferation. The 1a protein of cucumber mosaic virus (CMV) act as RNA-dependent RNA polymerase (RdRp) that plays a crucial role in regulating the replication of CMV. In this study, four putative G4 sequences (CMV PQS1-PQS4) in the genetic coding region of CMV 1a were identified, and three of them (PQS2, PQS3, and PQS4) were confirmed to fold into G4 structures. The G4-ligand, RHPS4, could bind to CMV PQS2 and PQS4 with a strong binding affinity and preferred to interact with the 3' terminal G-quartet surfaces of CMV PQS2, and 5' terminal of CMV PQS4. RHPS4 was also found to stabilize the CMV PQS2 and PQS4 G4s. Further studies revealed that RHPS4 exhibited an excellent anti-CMV activity. This study suggested that CMV PQS2 and PQS4 could be considered potential targets for screening viral inhibitors.
The application of solar thermal conversion is an effective means of utilizing solar energy. In this study, plain, honeycomb, and terry cotton fabrics are carbonized into carbon fiber fabrics at high temperatures, with subsequent Titanium nitride (TiN) modification. The dependence of the carbon fabric properties on structure is investigated. Fiber stability, high absorbance, and structural characteristics contribute to efficient performance in solar steam generation. The vertical loop array associated with the surface of the terry structure results in improved absorbance, limiting loss of TiN particles with a consequent enhancement of fiber photothermal conversion. The optimal TiN carbon fiber fabric (TiN CFF) based evaporator can achieve a water evaporation rate of 1.82 kg m-2 h-1 under one sun with up to 93.4% absorbance. Moreover, the fiber exhibits good cycling stability and seawater desalination performance. The synergism due to TiN modification and the terry fabric structure results in an efficient and low-cost evaporator preparation method, which can be effectively applied in photothermal conversion materials and seawater desalination. Plain, honeycomb, and terry cotton fabrics are carbonized into carbon fiber fabrics at high temperatures, with subsequent TiN modification. The synergism due to TiN modification and the terry fabric structure results in an efficient and low-cost evaporator preparation method, which can be effectively applied in photothermal conversion materials and seawater desalination.image
Microcracks on the surface and inside inevitably occur during processing and use. The use of photo -initiated, selfhealing, self -warning microcapsules to repair and monitor these microcracks is of practical importance to prolong the life of coated fabrics. In this work, the microcapsules (EP/FA/SiO 2 ) with SiO 2 as wall material, epoxy resin, fluorescent agent and cationic photoinitiator as core material were prepared using the interfacial in situ polymerization method. The self -healing self -warning PVC coated fabric was obtained by scraper coating method. The self -healing, self -warning and mechanical properties of the coated fabric were characterized. The results show that the microcapsules have an encapsulation efficiency of 79 % and a core -wall structure. The wall thickness is about 200 nm and the particle size is 1.7 mu m. The microcapsules have excellent thermal stability below 320 degrees C. The microcapsules have good dispersion in the PVC coating surface and the repair agent has good wettability in the PVC coating surface. When the cuts expand, the previously embedded microcapsules break open and release the fluorescent active ingredient and the repair agent of the capsule core. Under UV light irradiation, the scratches may show a yellow fluorescence to indicate the location of the damage to the coating. The repair agent (epoxy resin) fills the cuts and then polymerizes with the cationic photoinitiator under UV light. As the exposure time increases, the cut gradually narrows and the strength of the coated fabric increases. After 36 h of UV exposure, the cut disappears and the strength of the coated fabric is 742 N, reaching the strength (768 N) of the fabric before scratching. This indicates that the coated fabric has a good photo -initiated self -healing effect.
In the human body, carboxylesterases (CEs) play crucial roles in xenobiotic metabolism and lipid homeostasis. But abnormal expression of CEs is highly associated with some diseases, such as hyperlipidemia, diabetes, and liver cancer. Therefore, it is of great importance to develop an efficient tool for the accurate detection of CEs in living organisms. Herein, an innovative near-infrared (NIR) fluorescent probe, TTAP−AB, was designed for CE detection based on the aggregation-induced emission (AIE) mechanism. This probe exhibits rapid response (2 min), excellent sensitivity (limit of detection = 8.14 × 10−6 U/mL), and high selectivity to CEs. Additionally, owing to its good biocompatibility, the TTAP−AB probe enables the monitoring of dynamic changes in CE levels under drug-induced modulation in living cells and zebrafish. More importantly, the TTAP−AB probe was successfully employed to image liver tumors and assist in tumor resection through the real-time monitoring of CEs, indicating that TTAP−AB is promising to guide liver cancer surgery. Therefore, the TTAP−AB probe can not only enrich the strategies for CE detection in biological systems but also has great potential for some clinical imaging applications, including medical diagnosis, preclinical research, and imaging-guided surgery.
Abstract Non-invasive imaging methods for tracking gene expression, cell growth and migration and other biological events in vivo are indispensable tools for biomedical studies. Bioluminescence imaging (BLI) can achieve sensitive detection with low background in vivo, which is desirable for body imaging of small animals. Yet, BLI in the central nervous system (CNS) is challenging because many luciferase substrates show limited permeability of the blood-brain-barrier (BBB). To address this issue, we developed a family of new brain-permeant NanoLuc (NLuc) substrates, cephalofurimazine (CFz). CFz family paired with Antares, a fusion of CyOFP and NLuc that emits orange light instead of blue, produces an order of magnitude more signal from the brain than the standard combination of D-luciferin with firefly luciferase and matches the peak output of AkaLumine with AkaLuc but without the need of ATP. One of the substrates in the family, CFz-9, not only produces outstanding signal as other CFz substrates when paired with Antares, but also is able to be formulated into lyophilized cake that can be reconstituted in aqueous buffers for i.p. injections. Toxicity studies demonstrate that CFz-9 and its reconstituted solutions are non-toxic to mice and thus multiple injections are allowed. Citation Format: Chao Gao, Yichi Su, Yan Wu, Connor Fitzgerald, Tetsuo H. Uyeda, Hui Wang, Thomas A. Kirkland, Michael Z. Lin, Wenhui Zhou. Brain permeable bioluminescent substrates for NanoLuc based reporters [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4146.
The coronavirus SARS-CoV-2 continues to spread worldwide. Dozens of compounds have been discovered based on the structure of viral proteins. However, the candidate drugs are still some distance away from clinical use. It is worth exploring new targets for drug discovery against the virus. RNA structures are expected to play a regulatory role in the life cycle of RNA viruses and to provide novel drug targets. Recently, G-quadruplex (G4) has been reported as a promising therapeutic target against SARS-CoV-2. This study identified nine putative G4 sequences (PQSs) that fold into parallel G4 structures in the SARS-CoV-2 genome, five of which are located in the ORF1ab, S, and N genes and are regulated by the presence of potassium. G4s in the ORF1ab and S genes repressed RNA synthesis and gene expression with a differentiated response to G4 ligands. Four classic G4 ligands bound to the G4s in vitro, among which NMM and TMPyP4 exhibited efficient antiviral activity against SARS-CoV-2 in host cells. This demonstrates the potential of G4 ligands to inhibit the replication of SARS-CoV-2 in cells, suggesting that G4s hold promise as potential antiviral therapeutic targets.
As a common disinfectant and an essential reactive oxygen species (ROS), hypochlorite (ClO−) plays vital roles in both water treatment and cell metabolism, but its abnormal level can cause serious harm to human health. Therefore, quantifying ClO− level in drinking water and living organisms is extremely significant. Herein, we decorated different cationic heterocycles on phenothiazine core to construct three fluorescent probes for ClO−. According to the results, only benzothiazolium moiety reasonably adjusted the electron cloud density at sulphur atom of phenothiazine core for the specific oxidation with ClO−, thus endowing the prepared probe PT-BT with a perfect selectivity for ClO−. Meanwhile, PT-BT exhibited a low detection limit (38 nM) and a fast response (within 20 s) toward ClO−. Furthermore, this probe was utilized to fabricate a ready-to-use test strip, which could quantitatively measure ClO− level in real water samples by a portable smartphone sensing platform. Notably, PT-BT targeted mitochondria efficiently, and successfully visualized endogenous ClO− in living cells and zebrafish larvae. Especially, PT-BT was able to monitor the dynamic change of ClO− level in inflammatory mice. These results strongly manifested that probe PT-BT was a promising tool for detecting ClO− in drinking water and living organisms.
Hypochlorite (ClO−) and viscosity both affect the physiological state of mitochondria, and their abnormal levels are closely related to many common diseases. Therefore, it is vitally important to develop mitochondria-targeting fluorescent probes for the dual sensing of ClO− and viscosity. Herein, we have explored a new fluorescent probe, XTAP–Bn, which responds sensitively to ClO− and viscosity with off–on fluorescence changes at 558 and 765 nm, respectively. Because the emission wavelength gap is more than 200 nm, XTAP–Bn can effectively eliminate the signal crosstalk during the simultaneous detection of ClO− and viscosity. In addition, XTAP–Bn has several advantages, including high selectivity, rapid response, good water solubility, low cytotoxicity, and excellent mitochondrial-targeting ability. More importantly, probe XTAP–Bn is successfully employed to monitor the dynamic change in ClO− and viscosity levels in the mitochondria of living cells and zebrafish. This study not only provides a reliable tool for identifying mitochondrial dysfunction but also offers a potential approach for the early diagnosis of mitochondrial-related diseases.
The self-warning and thermal-induced self-healing microcapsules were fabricated by the interfacial in situ polymerization process, which consists of SiO2 as the shell material and epoxy resin, a thermal initiator, and a fluorescent agent as the core materials. The squeegee coating method was used to prepare the self-healing self-warning PVC-coated fabric. The microcapsules have a core-shell structure with an average particle size of 1.5 mu m and a high sphericity with a coverage rate of 77% and excellent thermal stability below 320 degrees C. The PVC coating agent has good wettability with the microcapsules with a contact angle of 34.6 +/- 0.9 degrees. When cracks appear on the surface of the coated fabric containing microcapsules, the fluorescent agent and repair agent (epoxy resin and thermal initiator) will then flow out from the broken microcapsules and fill the cracks owing to the great wettability of the PVC coating agent with a contact angle of 44.2 +/- 1.1 degrees. Under UV light, the cut displays a yellow fluorescence line, indicating the location of the damage. After filling the cracks, the epoxy resin polymerizes with the thermal initiator at 120 degrees C. When the heating time reaches 6 h, the cuts in the fabric are healed, and the strength of the coated fabric reaches 699 N, thereby matching the original strength of 713 N before cutting.
Hydrogen peroxide (H2O2) is a significant reactive oxygen species (ROS) that mainly produced in cell mitochondria, and its physiological concentration is crucial to human health. Till now, a plenty of reaction-based fluorescent probes have been explored for H2O2 detection. Unfortunately, due to the low reactivity with H2O2 under physiological pH, the poor selectivity and weak sensitivity are regarded as the major problems for these probes. To bridge this gap, we employ the oxidative cleavage of alkene as a novel sensing strategy for H2O2, and successfully construct a mitochondria-targeted fluorescent probe TBBP-Pro. In this probe, 4-(1-cyanovinyl)-pyridinium moiety not only acts as a specific response site for H2O2, but also targets cell mitochondria efficiently. Comparing with previous H2O2 probes, TBBP-Pro exhibits the advantages of high selectivity, excellent sensitivity (LOD = 47 nM) and fast response (within 5 min) toward H2O2. In addition, TBBP-Pro successfully images endogenous H2O2 in living HepG2 cells and zebrafish. More importantly, TBBP-Pro has been applied in monitoring the dynamic change of H2O2 level for the diagnosis and treatment of ulcerative colitis mice. This oxidative cleavage reaction of alkene provides a new sensing platform for H2O2 with superior selectivity and sensitivity to more favorably apply in living systems.
Monascus spp., a fungus of medicine food homology, produces various beneficial secondary metabolites such as monacolin K (MK) during fermentation. In this study, the mixed fermentation of Monascus with rice, Pueraria, and yam has been systematically investigated. Single-factor and response surface methodology (RSM) were carried out to maximize MK content, and the optimized fermentation results showed that the content of MK reached 1.40 +/- 0.04 mg/g. The optimal fermentation process determined the ratio of 8: 1: 1 for rice, Pueraria, and yam, respectively, the inoculation amount was 106 spores/mL, fermentation time was 15 days. Further analysis of the content of active substance in the fermentation process revealed that the beta-glycosidase activity increased, the amylase enzyme activity decreased, the dioscin content decreased by 19.5%, and the diosgenin content increased by 175%, suggesting that there was a dynamic equilibrium relationship among the changes of active substances. This study aims at provide a basis and reference for the research of Monascus fermented foods by medicine food homology raw materials.
Monascus red pigments (MRPs) are mainly used as natural food colorants; however, their application is limited due to their poor stability. To expand their areas of application, we investigated the binding constants and capacity of MRPs to whey protein isolate (WPI) and whey protein hydrolysate (WPH) and calculated the surface hydrophobicities of WPI and WPH. MRPs were combined with WPI and WPH at a hydrolysis degree (DH) of 0.5% to form the complexes (DH = 0.0%) and (DH = 0.5%), respectively. Subsequently, the structural characteristics of complex (DH = 0.5%) and WPI were characterized and the color retention rates of both complexes and MRPs were investigated under different pretreatment conditions. The results showed that the maximum binding constant of WPI with MRPs was 0.670 ± 0.06 U−1 and the maximum binding capacity was 180 U/g. Furthermore, the thermal degradation of complex (DH = 0.0%), complex (DH = 0.5%), and MRPs in a water bath at 50–100 °C followed a first-order kinetic model. Thus, the interaction of WPI with MRPs could alter the protein conformation of WPI and effectively protect the stability of MRPs.
Hydrogen peroxide (H2O2) is a significant reactive oxygen species (ROS) mainly produced in mitochondria, and it plays crucial roles in many physiological processes. Till now, a plenty of fluorescent probes relying on various organic reactions have been explored for H2O2. However, these probes still suffered from some problems, including the interference from ONOO- and ClO-, unsatisfying limit of detection (LOD > 100 nM), long response time (over 30 min) and lacking mitochondria-targeting ability. Herein, we employ the oxidative cleavage reaction of alkene as a novel sensing strategy, and successfully construct a turn-on fluorescent probe TBBP-Pro for detecting H2O2 in biological system. In this probe, the cyanovinyl-pyridinium moiety not only acts as a specific response site for H2O2, but also targets mitochondria efficiently. Comparing with previous H2O2 probes, TBBP-Pro possesses the advantages of high selectivity, excellent sensitivity (LOD = 47 nM) and fast response (within 5 min) toward H2O2. Additionally, TBBP-Pro successfully visualizes the endogenous H2O2 in mitochondria of HepG2 cells and zebrafish larvae. More importantly, TBBP-Pro is promising to monitor the dynamic change of H2O2 level for the diagnosis and treatment of inflammatory mice
Bisulfite (HSO3-), as a preservative, is commonly used in food production and storage, whereas its excessive addition will cause some serious illness to humans. Therefore, it is urgent to develop a convenient method for the quantitative detection of HSO3- in food samples. In this work, a novel conjugated polymer-based ratiometric fluorescent probe PFTQ has been synthesized. In probe PFTQ, the electron-deficient C=C bond conjugated with quinolinium moiety specifically reacts with nucleophile HSO3- by 1,2-addition reaction, consequently causing the emission to be changed from red to steelblue. Meanwhile, the signal of fluorescence color can be converted into the digital values by our smartphone optical platform, and a linear relationship of RGB ratio (B/R) with HSO3- concentration is established. The fluorescence sensing is completed within 6 min, and the detection limit is calculated to be 106 nM. Finally, this sensing platform achieves the quantitative detection of HSO3- in crystal sugar, red wine and beer samples with high accuracy.
The assembly of cyclopentazolate (cyclo-N5−) anions with counterions has thrived in recent years owing to the potential of cyclo-N5− anions as high energy density materials. However, high-valence metal pentazolates are...