Natural Flavonoid-Derived Enzyme Mimics DHKNase Balance the Two-Edged Reactive Oxygen Species Function for Wound Healing and Inflammatory Bowel Disease Therapy.

Rational regulation of reactive oxygen species (ROS) plays a vital importance in maintaining homeostasis of living biological systems. For ROS-related pathologies, chemotherapy technology derived from metal nanomaterials currently occupies a pivotal position. However, they suffer from inherent issues such as complicated synthesis, batch-to-batch variability, high cost, and potential biological toxicity caused by metal elements. Here, we reported for the first time that dual-action 3,5-dihydroxy-1-ketonaphthalene-structured small-molecule enzyme imitator (DHKNase) exhibited 2-edged ROS regulation, catering to the execution of physiology-beneficial ROS destiny among diverse pathologies in living systems. Based on this, DHKNase is validated to enable remarkable therapeutic effects in 2 classic disease models, including the pathogen-infected wound-healing model and the dextran sulfate sodium (DSS)-caused inflammatory bowel disease (IBD). This work provides a guiding landmark for developing novel natural small-molecule enzyme imitator and significantly expands their application potential in the biomedical field.

Microcapsules based on biological macromolecules for intestinal health: A review.

Intestinal dysfunction is becoming increasingly associated with neurological and endocrine issues, raising concerns about its impact on world health. With the introduction of several breakthrough technologies for detecting and treating intestinal illnesses, significant progress has been made in the previous few years. On the other hand, traditional intrusive diagnostic techniques are expensive and time-consuming. Furthermore, the efficacy of conventional drugs (not capsules) is reduced since they are more likely to degrade before reaching their target. In this context, microcapsules based on different types of biological macromolecules have been used to encapsulate active drugs and sensors to track intestinal ailments and address these issues. Several biomacromolecules/biomaterials (natural protein, alginate, chitosan, cellulose and RNA etc.) are widely used for make microcapsules for intestinal diseases, and can significantly improve the therapeutic effect and reduce adverse reactions. This article systematically summarizes microencapsulated based on biomacromolecules material for intestinal health control and efficacy enhancement. It also discusses the application and mechanism research of microencapsulated biomacromolecules drugs in reducing intestinal inflammation, in addition to covering the preparation techniques of microencapsulated drug delivery systems used for intestinal health. Microcapsule delivery systems' limits and potential applications for intestinal disease diagnosis, treatment, and surveillance were highlighted.

New Alkaloids and Steroids from Hydranth of Goniopora columna Corals and Their Inhibiting Lung Cancer Cell Activities.

A new alkaloids, aplysingoniopora A (1), and new configuration pregnane type steroid compound, 9,17-α-pregn-1,4,20-en-3-one (2), and two known pregnane type steroid compounds (3 and 4) were isolated from hydranth of Goniopora columna corals. The compounds structures and absolute configurations were determined by extensive spectroscopic analysis, MS data, single-crystal X-ray diffraction analysis and quantum chemical calculation. The anticancer effect of the compounds were explored in human non-small-cell lung cancer (NSCLC) A549 cell lines. As the results, the compound 3 and 4 induces toxicity and has proliferation inhibitory effects on A549 cells (IC50=58.99 µM and 58.77 µM, respectively) in vitro.

Chitosan-Se Engineered Nanomaterial Mitigates Salt Stress in Plants by Scavenging Reactive Oxygen Species.

Soil salinity seriously hinders the sustainable development of green agriculture. The emergence of engineered nanomaterials has revolutionized agricultural research, providing a new means to overcome the limitations associated with current abiotic stress management and achieve highly productive agriculture. Herein, we synthesized a brand-new engineered nanomaterial (Cs-Se NMs) through the Schiff base reaction of oxidized chitosan with selenocystamine hydrochloride to alleviate salt stress in plants. After the addition of 300 mg/L Cs-Se NMs, the activity of superoxide dismutase, catalase, and peroxidase in rice shoots increased to 3.19, 1.79, and 1.85 times those observed in the NaCl group, respectively. Meanwhile, the MDA levels decreased by 63.9%. Notably, Cs-Se NMs also raised the transcription of genes correlated with the oxidative stress response and MAPK signaling in the transcriptomic analysis. In addition, Cs-Se NMs augmented the abundance and variety of rhizobacteria and remodeled the microbial community structure. These results provide insights into applying engineered nanomaterials in sustainable agriculture.

Fluoride-activated photothermal system for promoting bacteria-infected wound healing.

Although photothermal therapy (PTT) employing nanozymes has shown excellent antibacterial potential, excessive heating generally harms host cells and hinders recovery. Herein, we report an innovative technique for acquiring the programmed temperature by managing the catalytic activity of nanozymes. The photothermal system of CeO2 + F- + TMB can obtain precise photothermal temperature by adjusting the concentration of fluoride ions under near-infrared irradiation. At the optimized photothermal temperature, the photothermal system affords fine photothermal antibacterial treatment with high-efficiency antibacterial effects against Staphylococcus aureus and Escherichia coli in vitro. In vivo wound healing experiments confirm that the system can effectively promote fibroblast proliferation, angiogenesis and collagen deposition with remarkable wound healing efficiency. This strategy offers a novel design concept for creating a new generation of PTT and opens the way for the creation of alternative antibiotics.

Smart G-quadruplex hydrogels: From preparations to comprehensive applications.

In recent years, the accelerated development of G-quadruplexes and hydrogels has driven the development of intelligent biomaterials. Based on the excellent biocompatibility and special biological functions of G-quadruplexes, and the hydrophilicity, high-water retention, high water content, flexibility and excellent biodegradability of hydrogels, G-quadruplex hydrogels are widely used in various fields by combining the dual advantages of G-quadruplexes and hydrogels. Here, we provide a systematic and comprehensive classification of G-quadruplex hydrogels in terms of preparation strategies and applications. This paper reveals how G-quadruplex hydrogels skillfully utilize the special biological functions of G-quadruplexes and the skeleton structure of hydrogels, and expounds its applications in the fields of biomedicine, biocatalysis, biosensing and biomaterials. In addition, we deeply analyze the challenges in preparation, applications, stability and safety of G-quadruplex hydrogels, as well as potential future development directions.

Engineering a Red Fluorescent Protein Chromophore for Visualization of RNA G-Quadruplexes.

Synthetic red fluorescent protein (RFP) chromophores have emerged as valuable tools for biological imaging and therapeutic applications, but their application in the visualization of endogenous RNA G-quadruplexes (G4s) in living cells has been rarely reported so far. Here, by integrating the group of the excellent G4 dye ThT, we modulate RFP chromophores to create a novel fluorescent probe DEBIT with red emission. DEBIT selectively recognizes the G4 structure with the advantage of strong binding affinity, high selectivity, and excellent photostability. Using DEBIT as a fluorescent indicator, the real-time monitoring of RNA G4 in biological systems can be achieved. In summary, our work expands the application of synthetic RFP chromophores and provides an essential dye category to the classical G4 probes.

Nanozyme-based dual-signal sensing system for colorimetric and photothermal detection of AChE activity in the blood of liver-injured mice.

Acetylcholinesterase (AChE), a crucial enzyme related to liver function, is involved in numerous physiological processes such as neurotransmission and muscular contraction. The currently reported techniques for detecting AChE mainly rely on a single signal output, limiting their high-accuracy quantification. The few reported dual-signal assays are challenging to implement in dual-signal point-of-care testing (POCT) because of the need for large instruments, costly modifications, and trained operators. Herein, we report a colorimetric and photothermal dual-signal POCT sensing platform based on CeO2-TMB (3,3',5,5'-tetramethylbenzidine) for the visualization of AChE activity in liver-injured mice. The method compensates for the false positives of a single signal and realizes the rapid, low-cost portable detection of AChE. More importantly, the CeO2-TMB sensing platform enables the diagnosis of liver injury and provides an effective tool for studying liver disease in basic medicine and clinical applications. Rapid colorimetric and photothermal biosensor for sensitive detection of acetylcholinesterase (I) and acetylcholinesterase levels in mouse serum (II).

FeOOH nanosheet assisted metal ion coordination with porphyrins for rapid detection and removal of cadmium ions in water.

Excessive cadmium ions in water bodies pose a severe challenge to ecology and human health, and the development of cadmium metal ion sensors is imperative. Here, we showed a dual-signal sensor based on colorimetry and fluorescence that was self-assembled from FeOOH nanosheets and TMPyP4. This nanocomposite enabled quick, selective cadmium ion detection. The Soret band at 442 nm in the UV absorption spectrum represented the coordination of cadmium ions with FeOOH@TMPyP4, and the absorbance increased linearly with increasing cadmium ion concentration (R2 = 0.989 and linear range: 0.5-10 µM). In the presence of FeOOH nanosheets, the coordination of cadmium ions with FeOOH@TMPyP4 took only 70 min, and the detection limit of cadmium ions was as low as 0.24 µM. In addition, Cd2+ could be effectively removed from the nanocomposite due to its easy separation from water. This research developed a simple and efficient approach for detecting and removing heavy metal ions from water bodies.

Dual-signal output paper sensor based on coordinative self-assembly biomimetic nanozyme for point-of-care detection of biomarker.

Paper-based point-of-care (POC) devices exhibit the advantages of simplicity, rapidity, trim sizes, and low cost, which are of particular importance for food safety, biological analysis, and medical diagnosis. However, the materials utilized to make paper-based POC rarely produce multiple signals, hampering further applications in diverse situations. Herein, we present an appealing approach, namely Colorimetric-Temperature Dual-Signal Output Sensor (CTDSS), and construct a CTDSS based on coordinative self-assembly biomimetic nanozymes Fe-GMP-L-His CPNs as a proof of concept. These CPNs mimic the structure of horseradish peroxidase (HRP), in which Fe (II) is the center, nucleotide GMP and histidine are chosen as ligands to simulate metal coordination of the pyrrole ring and protein function in HRP, respectively. This strategy allows CPNs to show an excellent peroxidase-like activity, efficiently converting H2O2 into •OH and oxidizing TMB to generate colorimetric-temperature dual-signal. As a proof-of-concept application, we exploited cholesterol as the target and successfully applied this CTDSS to detect cholesterol, displaying extraordinary features of rapidity, dramatic specificity, and high sensitivity. By utilizing the colorimetric test strip and temperature discoloration sticker, the paper-based POC tools were constructed to visualize the target. Meanwhile, two proposed test strip POC devices generating different signal outputs exhibited remarkable feasibility and were further employed to detect cholesterol in human serum. We anticipate that this CTDSS platform will inspire innovative concepts for future portable detection tools.

Nanotechnology for research and treatment of the intestine.

The establishment of intestinal in vitro models is crucial for elucidating intestinal cell-microbe intrinsic connections and interaction mechanisms to advance normalized intestinal diagnosis and precision therapy. This review discusses the application of nanomaterials in mucosal therapy and mechanism research in combination with the study of nanoscaffold in vitro models of the gut. By reviewing the original properties of nanomaterials synthesized by different physicochemical principles and modifying the original properties, the contribution of nanomaterials to solving the problems of short survival period, low cell differentiation rate, and poor reduction ability in traditional intestinal models is explored. According to nanomaterials' different diagnostic mediators and therapeutic targets, the current diagnostic principles in inflammatory bowel disease, intestinal cancer, and other diseases are summarized inductively. In addition, the mechanism of action of nanomedicines in repairing mucosa, inhibiting inflammation, and alleviating the disease process is also discussed. Through such systematic elaboration, it offers a basis for nanomaterials to help advance in vitro research on the intestine and provide precision treatments in the clinic.

When AIE meets enzymes.

With the rapid development of physiopathology and the surge in demand for comprehension of micro-scale physiological events, AIE-based bio-probes are found superior in presenting precise and practical results in enzyme imaging and analysis with a high signal-to-noise ratio and non-destructive operation. By delivering enzyme-responding "light-up" fluorescence signals, the visual and real-time tracking of the distribution and activity of intracellular enzymes is accomplished with AIE-based bio-probes. In particular, by combining with modern nano-encapsulation technologies, AIE-based compounds can realize the simultaneous diagnosis and treatment of specific diseases that are difficult to deal with through traditional strategies. This review summarizes and generalizes the typical AIE-based bio-probes reported recently based on the AIE mechanisms of solubility changes, excited-state intramolecular proton transfer (ESIPT), electrostatic interactions, and hydrophobic interactions, expounding their great values in the bio-sensing and bio-medicine field. Advanced enzyme detection and estimation, cell identification, disease diagnosis, and controlled drug release are demonstrated with high confidence and reproducibility. Through the in-depth analysis of these bio-probes' design and working principles, currently existing drawbacks and further future directions are subsequently proposed to promote a more prosperous development of AIE-based enzyme probes.

Fluorescence thermometers: intermediation of fundamental temperature and light.

The rapid advancement of thermal materials and fluorescence spectroscopy has extensively promoted the development of micro-scale fluorescence thermometry in recent years. Based on their advantages of fast response, high sensitivity, simple operation, high spatial resolution, and non-destructive detection, fluorescence thermometers have become powerful analysis tools used to sense temperature fluctuations through fluorescent signals, especially to accurately capture living cells via fluorescent signals and local temperature variations in living bodies, thus providing the most direct means for the in-depth understanding of biological processes in cells. Herein, we systematically categorize the currently reported fluorescence thermometers based on the aspects of fluorescence intensity and wavelength, reveal the intrinsic relationship between fluorescence (intensity and wavelength) and temperature response, expound the applications of fluorescence thermometers in the fields of chemical sensing and biomedicine, and analyze the challenges faced by current fluorescence thermometers based on fundamental problems and practical applications simultaneously, thus highlighting the future directions of fluorescence thermometers.

Hospitals and Laboratories on Paper-Based Sensors: A Mini Review.

With characters of low cost, portability, easy disposal, and high accuracy, as well as bulky reduced laboratory equipment, paper-based sensors are getting increasing attention for reliable indoor/outdoor onsite detection with nonexpert operation. They have become powerful analysis tools in trace detection with ultra-low detection limits and extremely high accuracy, resulting in their great popularity in medical detection, environmental inspection, and other applications. Herein, we summarize and generalize the recently reported paper-based sensors based on their application for mechanics, biomolecules, food safety, and environmental inspection. Based on the biological, physical, and chemical analytes-sensitive electrical or optical signals, extensive detections of a large number of factors such as humidity, pressure, nucleic acid, protein, sugar, biomarkers, metal ions, and organic/inorganic chemical substances have been reported via paper-based sensors. Challenges faced by the current paper-based sensors from the fundamental problems and practical applications are subsequently analyzed; thus, the future directions of paper-based sensors are specified for their rapid handheld testing.

Lighting up the Native Viral RNA Genome with a Fluorogenic Probe for the Live-Cell Visualization of Virus Infection.

RNA viruses represent a major global health threat, and the visualization of their RNA genome in infected cells is essential for virological research and clinical diagnosis. Due to the lack of chemical toolkits for the live-cell imaging of viral RNA genomes, especially native viral genomes without labeling and genetic modification, studies on native virus infection at the single-live-cell level are challenging. Herein, taking hepatitis C virus (HCV) as a representative RNA virus, we propose that the innate noncanonical G-quadruplex (G4) structure of viral RNA can serve as a specific imaging target and report a new benzothiazole-based G4-targeted fluorescence light-up probe, ThT-NE, for the direct visualization of the native RNA genome of HCV in living host cells. We demonstrate the use of the ThT-NE probe for several previously intractable applications, including the sensitive detection of individual virus-infected cells by small-molecule staining, real-time monitoring of the subcellular distribution of the viral RNA genome in live cells, and continuous live-cell tracking of the infection and propagation of clinically isolated native HCV. The fluorogenic-probe-based viral RNA light-up system opens up a promising chemical strategy for cutting-edge live-cell viral analysis, providing a potentially powerful tool for viral biology, medical diagnosis, and drug development.

Engineering of Nucleic Acids and Synthetic Cofactors as Holo Sensors for Probing Signaling Molecules in the Cellular Membrane Microenvironment.

The comprehensive understanding of the mechanisms underlying the interaction of cells with their membrane microenvironment is of great value for fundamental biological research; however, tracking biomolecules on cell surfaces with high temporal and spatial resolution remains a challenge. Herein, a modular strategy is presented for the construction of cell surface DNA-based sensors by engineering DNA motifs and synthetic cofactors. In this strategy, a stimuli-reactive organic molecule is employed as the cofactor for the DNA motif, and the self-assembly of them forms a FRET-based holo DNA-based sensor. With the use of the DNA-based sensors, the versatility of this modular strategy has been demonstrated in the ratiometric imaging of the cellular extrusion process of endogenous signaling molecules, including sulfur dioxide derivatives and nitric oxide.

DNA mimics of red fluorescent proteins (RFP) based on G-quadruplex-confined synthetic RFP chromophores.

Red fluorescent proteins (RFPs) have emerged as valuable biological markers for biomolecule imaging in living systems. Developing artificial fluorogenic systems that mimic RFPs remains an unmet challenge. Here, we describe the design and synthesis of six new chromophores analogous to the chromophores in RFPs. We demonstrate, for the first time, that encapsulating RFP chromophore analogues in canonical DNA G-quadruplexes (G4) can activate bright fluorescence spanning red and far-red spectral regions (Em = 583-668 nm) that nearly match the entire RFP palette. Theoretical calculations and molecular dynamics simulations reveal that DNA G4 greatly restricts radiationless deactivation of chromophores induced by a twisted intramolecular charge transfer (TICT). These DNA mimics of RFP exhibit attractive photophysical properties comparable or superior to natural RFPs, including high quantum yield, large Stokes shifts, excellent anti-photobleaching properties, and two-photon fluorescence. Moreover, these RFP chromophore analogues are a novel and distinctive type of topology-selective G4 probe specific to parallel G4 conformation. The DNA mimics of RFP have been further exploited for imaging of target proteins. Using cancer-specific cell membrane biomarkers as targets, long-term real-time monitoring in single live cell and two-photon fluorescence imaging in tissue sections have been achieved without the need for genetic coding.