A high-fidelity dual-channel fluorescence probe for benzoyl peroxide detection and toxicity early warning in food, zebrafish, and mice.

Benzoyl peroxide (BPO), as a widely used organic peroxide, has attracted widespread attention from all sectors of society for its environmental hazards and potential risks to human health. Herein, we employed a Förster resonance energy transfer (FRET) strategy to construct a novel ratiometric fluorescent probe CY-DCI for BPO detection in food, zebrafish, and mice. Specifically, a hemicyanine fluorophore and a dicyanoisophorone fluorophore were connected with a piperazine group as donor and acceptor, respectively, and an olefinic unsaturated bond as the reaction site. CY-DCI has favorable selectivity and an excellent detection limit as low as 58.1 nM, and the recovery rates for real-sample detection ranged from 95.8 % to 104 %, with relative standard deviations (RSD) less than 2.58 %. To further improve its practicality, silica gel plates and test strips containing CY-DCI (0-50 µM) were developed for naked-eye detection of BPO with satisfactory results. Additionally, this novel probe was then applied for ratiometric imaging of living zebrafish and mice and showed high ratiometric imaging resolution in the green and red channels, thus demonstrating its practical application for BPO detection and toxicity early warning in food and biosystems.

Construction of an effective near-infrared fluorescence "turn-on" probe for hydrogen sulfide detection and imaging in living inflammatory cell and zebrafish models.

Hydrogen sulfide (H2S) can act as a gaseous signaling mediator closely associated with inflammation development. In this work, we designed a fluorescence turn-on near-infrared (NIR) fluorescent probe CIT-H2S based on Intermolecular Charge Transfer (ICT) for the detection of H2S in living inflammatory cells and zebrafish. On this basis, a dicyanoisophorone fluorophore was chosen as the fluorescence signal reporting group of CIT-H2S, and an azide group was constructed as the recognition group of H2S. CIT-H2S is characterized by high selectivity and sensitivity for H2S over other interference species. The fluorescence intensity at 661 nm showed good linearity in the range of H2S concentration from 0 to 10 µM, with an excellent limit of detection (LOD) as low as 81.52 nM. Impressively, CIT-H2S has been visualized for detecting H2S in drug-induced inflammatory cell and zebrafish models, thus indicating that CIT-H2S is a robust tool with the ability to study the occurrence and development of hydrogen sulfide and inflammation.

The dissolution, reassembly and further clearance of amyloid-ß fibrils by tailor-designed dissociable nanosystem for Alzheimer's disease therapy.

The fibrillation of amyloid-ß (Aß) is the critical causal factor in Alzheimer's disease (AD), the dissolution and clearance of which are promising for AD therapy. Although many Aß inhibitors are developed, their low Aß-binding affinity results in unsatisfactory effect. To solve this challenge, the Aß sequence-matching strategy is proposed to tail-design dissociable nanosystem (B6-PNi NPs). Herein, B6-PNi NPs aim to improve Aß-binding affinity for effective dissolution of amyloid fibrils, as well as to interfere with the in vivo fate of amyloid for Aß clearance. Results show that B6-PNi NPs decompose into small nanostructures and expose Aß-binding sites in response to AD microenvironment, and then capture Aß via multiple interactions, including covalent linkage formed by nucleophilic substitution reaction. Such high Aß-binding affinity disassembles Aß fibrils into Aß monomers, and induces the reassembly of Aß&nanostructure composite, thereby promoting microglial Aß phogocytosis/clearance via Aß receptor-mediated endocytosis. After B6-PNi NPs treatment, the Aß burden, neuroinflammation and cognitive impairments are relieved in AD transgenic mice. This work provides the Aß sequence-matching strategy for Aß inhibitor design in AD treatment, showing meaningful insight in biomedicine.

Berbamine ameliorates DSS-induced colitis by inhibiting peptidyl-arginine deiminase 4-dependent neutrophil extracellular traps formation.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease with immune dysregulation affecting colon inflammatory response. Recent studies have highlighted that neutrophil extracellular traps (NETs) play an important role in the pathogenesis of UC. Berbamine (BBM), one of the bioactive ingredients extracted from Chinese herbal medicine Berberis vulgaris L, has attracted intensive attentions due to its significant anti-inflammatory activity and a marketing drug for treating leukemia in China. However, the exact role and potential molecular mechanism of BBM against UC remains elusive. In the present study, our results showed that BBM could markedly improve the pathological phenotype and the colon inflammation in mice with dextran sulfate sodium (DSS)-induced colitis. Then, comprehensive approaches combining network pharmacology and molecular docking analyses were employed to predict the therapeutic potential of BBM in treating UC by peptidyl-arginine deiminase 4 (PAD4), a crucial molecule involved in NETs formation. The molecular docking results showed BBM had a high affinity for PAD4 with a binding energy of -9.3 kcal/mol Moreover, PAD4 expression and NETs productions, including citrullination of histone H3 (Cit-H3), neutrophil elastase (NE), myeloperoxidase (MPO) in both neutrophils and colonic tissue were reduced after BBM administration. However, in the mice with DSS-induced colitis pretreated with GSK484, a PAD4-specific inhibitor, BBM could not further reduce disease related indexes, expression of PAD4 and NETs productions. Above all, the identification of PAD4 as a potential target for BBM to inhibit NETs formation in colitis provides novel insights into the development of BBM-derived drugs for the clinical management of UC.

Early administration of Wumei Wan inhibit myeloid-derived suppressor cells via PI3K/Akt pathway and amino acids metabolism to prevent colitis-associated colorectal cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Wumei Wan (WMW), a traditional Chinese medicine prescription, has been proved to be effective in treating Colitis-associated colorectal cancer (CAC), but it has not been proven to be effective in different stages of CAC. AIM OF THE STUDY: The purpose of our study is to investigate the therapeutic effect and mechanism of WMW on the progression of CAC. MATERIALS AND METHODS: Azioximethane (AOM) and dextran sulfate sodium (DSS) were used to treat mice for the purpose of establishing CAC models. WMW was administered in different stages of CAC. The presentative chemical components in WMW were confirmed by LC-MS/MS under the optimized conditions. The detection of inflammatory cytokines in the serum and colon of mice were estimated by qRT-PCR and ELISA. The changes of T cells and myeloid-derived suppressor cells (MDSCs) in each group were detected by flow cytometry. The metabolic components in serum of mice were detected by UPLC-MS/MS. Expression of genes and proteins were detected by eukaryotic transcriptomics and Western blot to explore the key pathway of WMW in preventing CAC. RESULTS: WMW had significant effect on inhibiting inflammatory responses and tumors during the early development stage of CAC when compared to other times. WMW increased the length of mice's colons, reduced the level of IL-1ß, IL-6, TNF-α in colon tissues, and effectively alleviated colonic inflammation, and improved the pathological damage of colon tissues. WMW could significantly reduce the infiltration of MDSCs in the spleen, increase CD4+ T cells and CD8+ T cells in the spleen of CAC mice, and effectively reform the immune microenvironment in CAC mice. Transcriptomics analysis revealed that 2204 genes had different patterns of overlap in the colon tissues of mice between control group, AOM + DSS group, and early administration of WMW group. And KEGG enrichment analysis showed that PI3K/Akt signaling pathway, ECM-receptor interaction, IL-17 signaling pathway, MAPK signaling pathway, pancreatic secretion, thermogenesis, and Rap1 signaling pathway were all involved. The serum metabolomics results of WMW showed that the metabolic compositions of the control group, AOM + DSS group and the early stage of WMW were different, and 42 differential metabolites with the opposite trends of changes were screened. The metabolic pathways mainly included pyrimidine metabolism, glycine, serine and threonine metabolism, tryptophan metabolism, and purine metabolism. And amino acids and related metabolites may play an important role in WMW prevention of CAC. CONCLUSION: WMW can effectively prevent the occurrence and development of CAC, especially in the initial stage. WMW can reduce the immune infiltration of MDSCs in the early stage. Early intervention of WMW can improve the metabolic disorder caused by AOM + DSS, especially correct the amino acid metabolism. PI3K/Akt signaling pathway was inhabited in early administration of WMW, which can regulate the amplification and function of MDSCs.

Development of a "Rigid-Flexible" Structure at the Interface Through Aramid Nanofibers@MXene to Enhance Mechanical Properties of Carbon Fiber/Polyamide Composites.

With the increasing development of nanomaterials, the construction of multiscale nanostructured interphase has emerged as a viable technique to reinforce carbon fiber-reinforced polymer composites. Here, "flexible" aramid nanofibers (ANFs) were first introduced on the surface of carbon fibers (CF) by electrophoretic deposition (EPD), and then "rigid" MXene sheets were grafted by ultrasonic impregnation. This feasible two-step treatment introduces a hierarchical "rigid-flexible" structure at the CF/polyamide (PA) interface. Results showed that this "rigid-flexible" multilayer structure improved the roughness, chemical bonding, mechanical interlocking, and wettability of CF/PA composites. At the same time, the modulus variation between the fiber and the matrix is significantly smoothed due to the increased thickness of the interfacial layer, increasing the payload transfer from the PA matrix to the fiber and decreasing the stress concentration. Compared to the desized CF, the interlaminar shear strength (ILSS) and tensile strength of the modified CF-ANF@MX0.2/PA composite increased by 50.02 and 36.11%, respectively. This innovative interfacial design and feasible treatment method facilitate the construction of firmly interacting interfacial layers in CF/PA composites, offering broad prospects for the production of high-performance CF/PA composites.

Neo-construction of a SO2-tunable near-infrared ratiometric fluorescent probe for high-fidelity diagnosis and evaluation hazards of Cd2+-induced liver injury.

Cadmium-contaminated water and food are seriously hazardous to the human health, especially liver injury. To understand the entanglement relationship between cadmium ion (Cd2+)-induced liver injury and the biomarker sulfur dioxide (SO2), a reliable bioanalytical tool is urgently needed, detecting SO2 to diagnose and evaluate the extent of liver injury in vivo. Herein, based on the Förster resonance energy transfer (FRET) mechanism, a novel SO2-tunable NIR ratiometric fluorescent probe (SMP) was developed, it was used to diagnose and treat liver injury induced by Cd2+ in biosystems. Specifically, it was constructed by conjugating a NIR dicyanoisophorone with a NIR benzopyranate as the donor and acceptor, respectively, and the ratiometric response of SO2- regulated by the Michael addition reaction. In addition, SMP exhibits rapid reaction time (<15 s), two well-resolved emission peaks (68 nm) with less cross-talk between channels for high imaging resolution, superior selectivity, and low limit of detection (LOD=80.3 nM) for SO2 detection. Impressively, SMP has been successfully used for intracellular ratiometric imaging of Cd2+-induced SO2 and diagnostic and therapeutic evaluation in liver injury mice models with satisfactory results. Therefore, SMP may provide a powerful molecular tool for revealing the occurrence and development relationship between SO2 and Cd2+-induced liver injury. ENVIRONMENTAL IMPLICATION: Cadmium ions are one of the well-known toxic environmental pollutants, which are enriched in the human body through inhalation of cadmium-contaminated air or from the food chain, leading to damage in various organs, especially liver injury. Therefore, we developed a novel fluorescent probe that can specifically detect SO2 in Cd2+-induced liver injury, which is critically important for the diagnosis and evaluation of Cd2+-induced liver injury diseases. The specific detection of SO2 of this probe has been successfully demonstrated in live HepG2 cells and Cd2+-induced liver injury mice.

Molecular engineering of a new method for effective removal of cadmium from water.

Cadmium (Cd) is a widespread and highly toxic environmental pollutant, seriously threatening animal and plant growth. Therefore, monitoring and employing robust tools to enrich and remove Cd from the environment is a major challenge. In this work, by conjugating a fluorescent indicator (CCP) with a functionalized glass slide, a special composite material (CCPB) was constructed to enrich, remove, and monitor Cd2+ in water rapidly. Then Cd2+ could be effectively eluted by immersing the Cd-enriched CCPB in an ethylenediaminetetraacetic acid (EDTA) solution. With this, the CCPB was continuously reused. Its recovery of Cd2+was above and below 100 % after multiple uses by flame atomic absorption spectrometry (FAAS), which was excellent for practical use in enriching and removing Cd2+ in real aqueous samples. Therefore, CCPB is an ideal material for monitoring, enriching, and removing Cd2+ in wastewater, providing a robust tool for future practical applications of Cd enrichment and removal in the environment.

Activatable fluorescent probes for early diagnosis and evaluation of liver injury.

With the increase in people's living standards, the number of patients suffering from liver injury keeps on increasing. Traditional diagnostic methods can no longer meet the needs of early and accurate diagnosis due to their limitations in application. However, fluorescent probes based on different fluorophores and nanomaterials have been gradually lighting up medical research due to their unique properties, such as high specificity and non-invasiveness. In addition, accurate identification of the different types of liver injury biomarkers can significantly improve the level of early diagnosis. Therefore, this review reviews the fluorescent probes used in the detection of biomarkers of liver injury over recent years and briefly summarizes the corresponding biomarkers of different types of liver injury. Impressively, this review also lists the structures and the response mechanisms of the different probes, and concludes with an outlook, suggesting directions in which improvements can be made. Finally, we hope that this review will contribute to the further development of fluorescent probes for the early diagnosis and assessment of liver injury.

Advances in the study of antisense long­stranded non­coding RNAs in tumors (Review).

Long­stranded non­coding RNAs (lncRNAs) are RNAs that consist of >200 nucleotides. The majority of lncRNAs do not encode proteins but have been revealed to mediate a variety of important physiological functions. Antisense­lncRNAs (AS­lncRNAs) are transcribed from the opposite strand of a protein or non­protein coding gene as part of the antisense strand of the coding gene. AS­lncRNAs can serve an important role in the tumorigenesis, prognosis, metastasis and drug resistance of a number of malignancies. This has been reported to be exerted through various mechanisms, such as endogenous competition, promoter interactions, direct interactions with mRNAs, acting as 'scaffolds' to regulate mRNA half­life, interactions with 5­untranslated regions and regulation of sense mRNAs. AS­lncRNAs have been found to either inhibit or promote tumor aggressiveness by regulating cell proliferation, energy metabolism, inflammation, inflammatory­carcinoma transformation, invasion, migration and angiogenesis. In addition, accumulating evidence has documented that AS­lncRNAs can regulate tumor therapy resistance. Therefore, targeting aberrantly expressed AS­lncRNAs for cancer treatment may prove to be a promising approach to reverse therapy resistance. In the present review, research advances on the role of AS­lncRNAs in tumor occurrence and development were summarized, with the aim of providing novel ideas for further research in this field.