Monitoring the Mitochondrial Viscosity Changes During Cuproptosis with Iridium(III) Complex Probe <i>via</i> <i>In Situ</i> Phosphorescence Lifetime Imaging

Cuproptosis is a novel copper-dependent form of programmed cell death, displaying important regulatory functions in many human diseases, including cancer. However, the relationship between the changes in mitochondrial viscosity, a key factor associated with cellular malfunction, and cuproptosis is still unclear. Herein, we prepared a phosphorescent iridium (Ir) complex probe for precisely monitoring the changes of mitochondrial viscosity during cuprotosis via phosphorescence lifetime imaging. The Ir complex probe possessed microsecond lifetimes (up to 1 μs), which could be easily distinguished from cellular autofluorescence to improve the imaging contrast and sensitivity. Benefiting from the long phosphorescence lifetime, excellent viscosity selectivity, and mitochondrial targeting abilities, the Ir complex probe could monitor the increase in the mitochondrial viscosity during cuproptosis (from 46.8 to 68.9 cP) in a quantitative manner. Moreover, through in situ fluorescence imaging, the Ir complex probe successfully monitored the increase in viscosity in zebrafish treated with lipopolysaccharides or elescolomol-Cu2+, which were well-known cuproptosis inducers. We anticipate that this new Ir complex probe will be a useful tool for in-depth understanding of the biological effects of mitochondrial viscosity during cuproptosis

Multifunctional Mineral Hydrogels: Potential in Artificially Intelligent Skins and Drug Delivery

Hydrogels have received considerable attention due to their potential applications in the fields of drug delivery, tissue engineering, and stimuli-responsive devices. Nonetheless, it is still a great difficulty in designing hydrogels with multifunctional characteristics including excellent antibacterial activity and appropriate mechanical and remarkable sensing properties. In the present study, a novel type of organic–inorganic adhesive is demonstrated, which comprises inorganic matter of amorphous calcium phosphate particles and organic substances of poly­(acrylic acid) and chitosan. The hydrogel possesses excellent biocompatible and antibacterial activity, unique viscoelastic properties, high quantity of drug load, and remarkably sensitive pressure sensing, which have potential use as antibacterial biomaterials, artificially intelligent skins, and drug delivery carriers

An H₂S‑Regulated Artificial Nanochannel Fabricated by a Supramolecular Coordination Strategy

Hydrogen sulfide (H2S), as the third gasotransmitter, has an important impact on physiological and pathological activities. Herein, we fabricated an artificial nanochannel with a conductance value of 2.01 nS via a supramolecular coordination strategy. Benefiting from the unique H2S-mediated covalent reaction, the nanochannel biosensor could change from ON to OFF states with the addition of H2S. Furthermore, this nanochannel directed the ion transport, showing a high rectification ratio as well as gating ratio. Subsequently, theoretical simulations were conducted to help to reveal the possible mechanism of the functionalized nanochannel. This study can provide insights for better understanding the process of H2S-regulated biological channels and fabricating gas gated nanofluids

An H₂S‑Regulated Artificial Nanochannel Fabricated by a Supramolecular Coordination Strategy

Hydrogen sulfide (H2S), as the third gasotransmitter, has an important impact on physiological and pathological activities. Herein, we fabricated an artificial nanochannel with a conductance value of 2.01 nS via a supramolecular coordination strategy. Benefiting from the unique H2S-mediated covalent reaction, the nanochannel biosensor could change from ON to OFF states with the addition of H2S. Furthermore, this nanochannel directed the ion transport, showing a high rectification ratio as well as gating ratio. Subsequently, theoretical simulations were conducted to help to reveal the possible mechanism of the functionalized nanochannel. This study can provide insights for better understanding the process of H2S-regulated biological channels and fabricating gas gated nanofluids

DataSheet1_Synthesis and Discovery of Schiff Base Bearing Furopyrimidinone for Selective Recognition of Zn2+ and its Applications in Cell Imaging and Detection of Cu2+.docx

A simplefuro [2,3-d]pyrimidinone-based Schiff base FPS was synthesized via aza-Wittig reaction and structure elucidation was carried out by spectroscopic studies FT-IR, 1H NMR, and 13C NMR and mass spectrometry. FPS showed weak fluorescence emission in methanol and the selectivity of FPS to different metal ions (Mn2+, Ca2+, Fe2+, Fe3+, Mg2+, Al3+, Ba2+, Ag+, Co2+, Na+, K+, Cu2+, Zn2+, Pb2+, Bi3+) were studied by absorption and fluorescence titration. The results show that FPS has selective fluorescence sensing behavior for Zn2+ ions and the limit of detection (LOD) was calculated to be 1.19 × 10–8 mol/L. Moreover, FPS-Zn2+ acts as a metal based highly selective and sensitive new chemosensor for Cu2+ ions and the LOD was calculated to be 2.25 × 10–7 mol/L. In accordance with the results and theoretical calculations, we suspected that the binding mechanisms of FPS to Zn2+ and Cu2+ were assigned to be the cooperative interaction of Zn2+(Cu2+)-N.</p

Visual and Rapid Detection of Nerve Agent Mimics in Gas and Solution Phase by a Simple Fluorescent Probe

Chemical nerve agents are highly toxic organophosphorus compounds that are easy to obtain and can be utilized by terrorists to threaten homeland security and human safety. Those organophosphorus nerve agents contain nucleophilic ability that can react with acetylcholinesterase leading to muscular paralysis and human death. Therefore, there is great importance to explore a reliable and simple method to detect chemical nerve agents. Herein, the o-phenylenediamine-linked dansyl chloride as a colorimetric and fluorescent probe has been prepared to detect specific chemical nerve agent stimulants in the solution and vapor phase. The o-phenylenediamine unit serves as a detection site that can react with diethyl chlorophosphate (DCP) in a rapid response within 2 min. A satisfied relationship line was obtained between fluorescent intensity and the concentration of DCP in the range of 0–90 μM. In the optimized conditions, we conducted the fluorescent titration to measure the limits of detection (0.082 μM) with the fluorescent enhancement up to 18-fold. Fluorescence titration and NMR studies were also conducted to explore the detection mechanism, indicating that the formation of phosphate ester causes the intensity of fluorescent change during the PET process. Finally, probe 1 coated with the paper test is utilized to detect DCP vapor and solution by the naked eye. We expect that this probe may give some admiration to design the small molecule organic probe and applied in the selectivity detection of chemical nerve agents

Rapid Fabrication of Porous Photothermal Hydrogel Coating for Efficient Solar-Driven Water Purification

Cost management and scalable fabrication without sacrificing the purification performance are two critical issues that should be addressed before the practical commercial application of solar-driven evaporators. To address this challenge, we report a porous photothermal hydrogel coating prepared by mixing the raw materials of sawdust (SD), carbon nanotubes (CNTs), and poly­(vinyl alcohol) (PVA), which was applied to undergo a blading–drying–rehydration process to prepare the evaporator. In the coating, the crystallized PVA gives the coating a solid skeleton and the sawdust endows the coating with a loose structure to sufficiently enhance the water transportation capacity. As a result, the evaporator coated with the hydrogel coating displays a high water transport rate and efficient evaporation performance along with excellent mechanical properties and stability. Water migrates vertically upward 5 cm within 4 minutes. The compressive stress of the rehydrated hydrogel coating reaches as high as 14.28 MPa under 80% strain. The water evaporation rate of the hydrogel coating-based evaporator reaches 1.833 kg m–2 h–1 corresponding to an energy efficiency of 83.29% under 1 sun irradiation. What is more, the hydrogel coating retains its excellent evaporation performance and stability after immersion in acid or alkali solution, ultrasound treatment, and long-time immersion in water. Under outdoor conditions, the water evaporation rate of the hydrogel coating-based evaporator is about 5.69 times higher than that of pure water. This study proposes a rapid, cost-effective, and scalable strategy for preparing a high-performance photothermal hydrogel coating that will find sustainable and practical application in solar-driven water purification

Structure-Based Design and Synthesis of Novel Dual-Target Inhibitors against Cyanobacterial Fructose-1,6-Bisphosphate Aldolase and Fructose-1,6-Bisphosphatase

Cyanobacteria class II fructose-1,6-bisphoshate aldolase (Cy-FBA-II) and cyanobacteria fructose-1,6-bisphosphatase (Cy-FBPase) are two neighboring key regulatory enzymes in the Calvin cycle of the cyanobacteria photosynthesis system. Each of them might be taken as a potential target for designing novel inhibitors to chemically control harmful algal blooms (HABs). In the present paper, a series of novel inhibitors were rationally designed, synthesized, and optimized based upon the structural and interactional information of both Cy-FBA-II and Cy-FBPase, and their inhibitory activities were examined in vitro and in vivo. The experimental results showed that compounds L19e–L19g exhibited moderate inhibitory activities (IC50 = 28.1–103.2 μM) against both Cy-FBA-II and Cy-FBPase; compounds L19a–L19d, L19h, L20a–L20d exhibited high Cy-FBA-II inhibitory activities (IC50 = 2.3–16.9 μM) and moderate Cy-FBPase inhibitory activities (IC50 = 31.5–141.2 μM); however, compounds L20e–L20h could potently inhibit both Cy-FBA-II and Cy-FBPase with IC50 values less than 30 μM, which demonstrated more or less dual-target inhibitor’s feature. Moreover, most of them exhibited potent algicide activity (EC50 = 0.8–22.3 ppm) against cyanobacteria Synechocystis sp. PCC 6803

Structure-Guided Discovery of the Novel Covalent Allosteric Site and Covalent Inhibitors of Fructose-1,6-Bisphosphate Aldolase to Overcome the Azole Resistance of Candidiasis

Fructose-1,6-bisphosphate aldolase (FBA) represents an attractive new antifungal target. Here, we employed a structure-based optimization strategy to discover a novel covalent binding site (C292 site) and the first-in-class covalent allosteric inhibitors of FBA from Candida albicans (CaFBA). Site-directed mutagenesis, liquid chromatography–mass spectrometry, and the crystallographic structures of APO–CaFBA, CaFBA–G3P, and C157S–2a4 revealed that S268 is an essential pharmacophore for the catalytic activity of CaFBA, and L288 is an allosteric regulation switch for CaFBA. Furthermore, most of the CaFBA covalent inhibitors exhibited good inhibitory activity against azole-resistant C. albicans, and compound 2a11 can inhibit the growth of azole-resistant strains 103 with the MIC80 of 1 μg/mL. Collectively, this work identifies a new covalent allosteric site of CaFBA and discovers the first generation of covalent inhibitors for fungal FBA with potent inhibitory activity against resistant fungi, establishing a structural foundation and providing a promising strategy for the design of potent antifungal drugs