Double Cross-Linked Hydrogel Dressings Based on Triblock Copolymers Bearing Antifreezing, Antidrying, and Inherent Antibacterial Properties.

Bacterial infections typically invade the living tissue of wounds, thereby aggravating the inflammatory response, delaying wound healing, or causing further complications. In this paper, the antibacterial hydrogel (PNVBA) with antifreezing and antidrying properties was prepared by a two-step method using N-isopropylacrylamide (NIPAM), 1-butyl-3-vinylimidazolium bromide (VBIMBr), and 3-acrylamidophenylboronic acid (AAPBA). PNVBA hydrogels exhibited a high adsorption capacity of 280 mg·g-1 for bovine serum albumin (BSA) and can adhere to the surface of different materials through ion-dipole or hydrogen-bonding interactions. Meanwhile, the PNVBA hydrogels exhibited high viscoelasticity and good adhesion after freezing at -20 °C or heating at 70 °C for 24 h with a sterilizing rate of up to 98% against multidrug-resistant (MDR) Escherichia coli and methicillin-resistant Staphylococcus aureus (MRSA). Moreover, a survival rate of up to 90% after incubation with L929 cells over 24 h was observed. Therefore, this inherent antibacterial hydrogel can be used as an excellent alternative material for wound dressings.

A Coumarin-Hemicyanine Deep Red Dye with a Large Stokes Shift for the Fluorescence Detection and Naked-Eye Recognition of Cyanide.

In this study, we synthesized a coumarin-hemicyanine-based deep red fluorescent dye that exhibits an intramolecular charge transfer (ICT). The probe had a large Stokes shift of 287 nm and a large molar absorption coefficient (ε = 7.5 × 105 L·mol-1·cm-1) and is best described as a deep red luminescent fluorescent probe with λem = 667 nm. The color of probe W changed significantly when it encountered cyanide ions (CN-). The absorption peak (585 nm) decreased gradually, and the absorption peak (428 nm) increased gradually, so that cyanide (CN-) could be identified by the naked eye. Moreover, an obvious fluorescence change was evident before and after the reaction under irradiation using 365 nm UV light. The maximum emission peak (667 nm) decreased gradually, whilst the emission peak (495 nm) increased gradually, which allowed for the proportional fluorescence detection of cyanide (CN-). Using fluorescence spectrometry, the fluorescent probe W could linearly detect CN- over the concentration range of 1-9 µM (R2 = 9913, RSD = 0.534) with a detection limit of 0.24 µM. Using UV-Vis spectrophotometry, the linear detection range for CN- was found to be 1-27 µM (R2 = 0.99583, RSD = 0.675) with a detection limit of 0.13 µM. The sensing mechanism was confirmed by 1H NMR spectroscopic titrations, 13C NMR spectroscopy, X-ray crystallographic analysis and HRMS. The recognition and detection of CN- by probe W was characterized by a rapid response, high selectivity, and high sensitivity. Therefore, this probe provides a convenient, effective and economical method for synthesizing and detecting cyanide efficiently and sensitively.

Pyrene-Based Cationic Fluorophores with High Affinity for BF4-, PF6-, and ClO4- Anions: Detection and Removal.

Anions play an indispensable role in the balance and regulation of the ecological environment and human health; however, excess anions can cause serious ecological and environment problems. Therefore, the detection and removal of excess anions in aqueous solution is not only a technological problem but also crucial for environmental protection. Herein, a set of water-soluble pyrene-based cationic fluorophores were synthesized, which exhibit high sensitivity for the detection of the anions BF4-, PF6-, and ClO4- via electrostatic interactions. Such fluorescent probes exhibit "turn-on" emission characteristics even at low concentrations of anions due to anion-π+ interactions. Moreover, these fluorescence probes act as efficient precipitating agents for the removal of the BF4-, PF6-, and ClO4- anions from an aqueous environment. This work opens up new avenues for future research on pyrene-based fluorophores as turn-on fluorescence probes for anion detection and as excellent precipitating agents in environmental settings.

A New Cationic Fluorescent Probe for HSO3- Based on Bisulfite Induced Aggregation Self-Assembly.

In comparison with the numerous studies that have centered on developing molecular frameworks for the functionalization of fluorescent materials, less research has addressed the influence of the side chains, despite such appendages contributing significantly to the properties and applications of fluorescent materials. In this work, a new series of cationic fluorescent probes with AIE characteristics have been developed, which exhibit unique sensitivity for charge-diffusion anions, namely HSO3-, via the interactions of ions and the cooperation of the controllable hydrophobicity. The impact of the alkyl chain length attached at the cationic probes suggested that the fluorescent intensity and sensitivity of the probes could be partially enhanced by adjusting their aggregation tendency through the action of the hydrophobic effect under aqueous conditions. DLS and SEM images indicated that different particle sizes and new morphologies of the probes were formed in the anion-recognition-triggered self-assembly process, which could be attributed to the composite effect of electrostatic actions, Van der Waals forces and π-π stacking.

Dynamic Coordination between a Triphenylamine-Functionalized Salicylaldehyde Schiff Base and a Copper(II) Ion.

The coordination between a ligand and a metal is a spontaneous and uncontrollable process. In this Article, we successfully observe the formation of metal coordination in a triphenylamine-functionalized salicylaldehyde Schiff base with a copper(II) ion. The ligand TPA-Py first reacts with Cu2+ in a stepwise process to afford the dynamic complex TPA-Py@Cu2+ ([ligand]:[Cu2+] = 1:1), which further reacts with an extra copper(II) ion to afford 2TPA-Py@4Cu2+ with the following stepwise (or cumulative) stability constants: K1 = 4.0694 × 103 and K2 = 1.0761 × 106, respectively. The entire metal coordination process can be visualized, and the coordination mode of the probe toward copper was further evaluated by ultraviolet-visible/fluorescence spectra, single-crystal X-ray diffraction, density functional theory calculations, high-resolution mass spectra, and nuclear magnetic resonance spectroscopic titrations. Compound TPA-Py exhibited excellent sensitivity and specificity toward copper(II) ions in THF/water media with a low limit of detection of 2.687 × 10-7 mol L-1. In addition, TPI-An-Py can be applied to the detection of Cu2+ in real samples with satisfactory recoveries in the range of 100-112% in lake water and 98-101% in tap water. This Article not only reports an excellent fluorescence probe for copper(II) ion detection but also presents an instance for more fully understanding the metal coordination process.

A Highly Selective Turn-On Fluorescent Probe for the Detection of Zinc.

A novel turn-on fluorescence probe L has been designed that exhibits high selectivity and sensitivity with a detection limit of 9.53 × 10-8 mol/L for the quantification of Zn2+. 1H-NMR spectroscopy and single crystal X-ray diffraction analysis revealed the unsymmetrical nature of the structure of the Schiff base probe L. An emission titration experiment in the presence of different molar fractions of Zn2+ was used to perform a Job's plot analysis. The results showed that the stoichiometric ratio of the complex formed by L and Zn2+ was 1:1. Moreover, the molecular structure of the mononuclear Cu complex reveals one ligand L coordinates with one Cu atom in the asymmetric unit. On adding CuCl2 to the ZnCl2/L system, a Cu-Zn complex was formed and a strong quenching behavior was observed, which inferred that the Cu2+ displaced Zn2+ to coordinate with the imine nitrogen atoms and hydroxyl oxygen atoms of probe L.

A 1-Hydroxy-2,4-Diformylnaphthalene-Based Fluorescent Probe and Its Detection of Sulfites/Bisulfite.

A novel 1-hydroxy-2,4-diformylnaphthalene-based fluorescent probe L was synthesized by a Knoevenagel reaction and exhibited excellent sensitivity and selectivity towards sulfite ions (SO32-) and bisulfite ions (HSO3-). The detection limits of the probe L were 0.24 µM using UV-Vis spectroscopy and 9.93 nM using fluorescence spectroscopy, respectively. Furthermore, the fluorescent probe L could be utilized for detection in real water samples with satisfactory recoveries in the range 99.20%~104.30% in lake water and 100.00%~104.80% in tap water by UV-Vis absorption spectrometry, and in the range 100.50%~108.60% in lake water and 102.70%~103.80% in tap water by fluorescence spectrophotometry.

Synthesis, Crystal Structure and Bioactivity of Phenazine-1-carboxylic Acylhydrazone Derivatives.

A phenazine-1-carboxylic acid intermediate was synthesized from the reaction of aniline and 2-bromo-3-nitro-benzoic acid. It was then esterified and reacted with hydrazine hydrate to afford phenazine-1-carboxylic hydrazine. Finally, 10 new hydrazone compounds 3a-3j were obtained by the condensation reaction of phenazine-1-carboxylic acid hydrazide and the respective aldehyde-containing compound. The structures were characterized by 1H and 13C NMR spectroscopy, MS and single crystal X-ray diffraction. The antitumor activity of the target compounds in vitro (HeLa and A549) was determined by thiazolyl blue tetrazolium bromide. The results showed that compound (E)-N'-(2-hydroxy-4-(2-(piperidine-1-yl) ethoxy) benzyl) phenazine-1-carbonyl hydrazide 3d exhibited good cytotoxic activity.

A Simple Turn-off Schiff Base Fluorescent Sensor for Copper (II) Ion and Its Application in Water Analysis.

An aniline-functionalized naphthalene dialdehyde Schiff base fluorescent probe L with aggregation-induced enhanced emission (AIEE) characteristics was synthesized via a simple one-step condensation reaction and exhibited excellent sensitivity and selectivity towards copper(II) ions in aqueous media with a fluorescence " turn-off " phenomenon. The detection limit of the probe is 1.64 × 10-8 mol·L-1. Furthermore, according to the results of the UV-vis/fluorescence titrations, Job's plot method and 1H-NMR titrations, a 1:2 stoichiometry was identified. The binding constant between L and Cu2+ was calculated to be Ka = 1.222 × 103. In addition, the AIEE fluorescent probe L could be applied to detection in real water samples with satisfactory recoveries in the range 99.10-102.90% in lake water and 98.49-102.37% in tap water.

Multinuclear Alkali Metal Complexes of a Triphenylene-Based Hexamine and the Transmetalation to Tris(N-heterocyclic tetrylenes) (Ge, Sn, Pb).

A C3-symmetric hexamine (LH6) based on the triphenylene and ortho-phenylenediamine (PDAH2) skeletons has been synthesized, and was partially or fully deprotonated upon treatment with alkali metal agents to afford amino-amido or diamido coordination sites. Four alkali metal complexes, the dinuclear [Na2(LH4)(DME)5] (1) and [K2(LH4)(DME)4] (2), trinuclear [K3(LH3)(DME)6] (3), and hexanuclear [Li6(L)(DME)6] (4), were obtained and used in transmetalation/ligand exchange with other metals. The hexalithium salt of the fully deprotonated ligand, [Li6L], reacted with heavier group 14 element halides to yield three tris(N-heterocyclic tetrylenes), the germylene [Ge3(L)] (5), stannylene [Sn3(L)] (6), and plumbylene [Pb3(L)] (7). The synthesis and crystal and electronic structures of these compounds are reported.

Study on the host-guest interactions between tetramethyl cucurbit[6]uril and 2-heterocyclic-substituted benzimidazoles.

Cucurbit[n]urils (Q[n]s) are a class of supramolecular host compounds with hydrophilic carbonyl ports and hydrophobic cavities, which can selectively form host-guest inclusion complexes with guest molecules to change the properties of guest molecules. In this paper, tetramethyl cucurbit[6]uril (TMeQ[6]) was used as the host and three 2-heterocyclic substituted benzimidazole derivatives as the guests, and their modes of interaction were investigated using X-ray crystallography, 1H NMR spectrometry, and other analytical techniques. The results showed that TMeQ[6] formed a 1 : 1 host-guest inclusion complex with three guest molecules, and the binding process between them was mainly enthalpy-driven. The X-ray diffraction analysis indicated that the main driving forces for the formation of these three inclusion complexes included hydrogen bonding interactions and ion dipole interactions. There are two modes of interaction between G3 and TMeQ[6] in the liquid phase, indicating that the benzimidazole ring and heterocyclic substituents on the guest molecule compete with the cavity of TMeQ[6]. Besides, the addition of TMeQ[6] significantly enhanced the fluorescence of these guests and slightly improved their solubility.

Aggregation-Induced Emission Photosensitizer with Ag(I)-π Interaction-Enhanced Reactive Oxygen Species for Eliminating Multidrug Resistant Bacteria.

Multidrug-resistant (MDR) bacteria pose serious threats to public health due to the lack of effective and biocompatible drugs to kill MDR bacteria. Photodynamic antibacterial therapy has been widely studied due to its low induction of resistance. However, photosensitizers that can efficiently generate reactive oxygen species (ROS) through both type I and type II mechanisms and that have the capability of multiple modes of action are rarely reported. Addressing this issue, we developed a near-infrared-emitting triphenylamine indole iodoethane (TTII) and its silver(I) self-assembled (TTIIS) aggregation-induced emission (AIE) photosensitizer for multimode bacterial infection therapy. TTII can efficiently produce both Type I ROS •OH and Type II ROS 1O2. Interestingly, the Ag(I)-π interaction contributed in TTIIS efficiency promotion of the generation of 1O2. Moreover, by releasing Ag+, TTIIS enabled photodynamic-Ag(I) dual-mode sterilization. As a result, TTIIS achieved an effective enhancement of antibacterial activity, with a 1-2-fold boost against multidrug-resistant Escherichia coli (MDR E. coli). Both TTII and TTIIS at a concentration as low as 0.55 µg mL-1 can kill more than 98% of methicillin resistant Staphylococcus aureus (MRSA) on MRSA-infected full-thickness defect wounds of a mouse, and both TTII and TTIIS were effective in eliminating the bacteria and promoting wound healing.

Protein Palmitoylation Modification During Viral Infection and Detection Methods of Palmitoylated Proteins.

Protein palmitoylation-a lipid modification in which one or more cysteine thiols on a substrate protein are modified to form a thioester with a palmitoyl group-is a significant post-translational biological process. This process regulates the trafficking, subcellular localization, and stability of different proteins in cells. Since palmitoylation participates in various biological processes, it is related to the occurrence and development of multiple diseases. It has been well evidenced that the proteins whose functions are palmitoylation-dependent or directly involved in key proteins' palmitoylation/depalmitoylation cycle may be a potential source of novel therapeutic drugs for the related diseases. Many researchers have reported palmitoylation of proteins, which are crucial for host-virus interactions during viral infection. Quite a few explorations have focused on figuring out whether targeting the acylation of viral or host proteins might be a strategy to combat viral diseases. All these remarkable achievements in protein palmitoylation have been made to technological advances. This paper gives an overview of protein palmitoylation modification during viral infection and the methods for palmitoylated protein detection. Future challenges and potential developments are proposed.

A Turn-On Fluorescent Chemosensor for Cyanide Ion Detection in Real Water Samples.

We have designed and synthesized a novel simple colorimetric fluorescent probe with aggregation-induced emission (AIE) properties. Probe 5-(4-(diphenylamine)phenyl) thiophen-2-formaldehyde W exhibited a turn-on fluorescent response to cyanide ion (CN-), which induces distinct visual color changes. Probe W exhibited a highly selective and sensitive ratiometric fluorescence response for the detection of CN- over a wide pH range (4-11) and in the presence of common interferents. The linear detection of CN- over the concentration range of 4.00-38.00 µM (R 2 = 0.9916, RSD = 0.02) was monitored by UV-Vis absorption spectrometry (UV-Vis) with the limit of detection determined to be 0.48 µM. The linear detection of CN- over the concentration range of 8.00-38.00 µM was examined by fluorescence spectrophotometry (R 2 = 0.99086, RSD = 0.031), and the detection limit was found to be 68.00 nM. The sensing mechanisms were confirmed by 1H NMR spectroscopic titrations, X-ray crystallographic analysis, and HRMS. Importantly, probe W was found to show rapid response, high selectivity, and sensitivity for cyanide anions in real water samples, over the range of 100.17∼100.86% in artificial lake water and 100.54∼101.64% in running water by UV-Vis absorption spectrometry, and over the range of 99.42∼100.71% in artificial lake water and 100.59∼101.17% in running water by fluorescence spectrophotometry. Importantly, this work provides a simple and effective approach which uses an economically cheap and uncomplicated synthetic route for the selective, sensitive, and quantitative detection of CN- ions in systems relevant to the environment and health.

ABHD16A Negatively Regulates the Palmitoylation and Antiviral Function of IFITM Proteins.

Interferon-inducible transmembrane (IFITM) proteins are small homologous proteins that are encoded by the interferon-stimulated genes (ISGs), which can be strongly induced by interferon (IFN) and provide resistance to invasion by a variety of viral pathogens. However, the exact molecular mechanisms underlying this function have remained elusive. The antiviral activity of IFITMs from different species depends on S-palmitoylation at conserved cysteine residues. However, specific enzymes involved in the dynamic palmitoylation cycle of IFITMs, especially depalmitoylase, have not yet been reported. Here, we demonstrate that α/-hydrolase domain-containing 16A (ABHD16A) is a depalmitoylase and a negative regulator of IFITM protein that can catalyze the depalmitoyl reaction of S-palmitoylated IFITM proteins, thereby decreasing their antiviral activities on RNA viruses. Using the acyl-PEGyl exchange gel shift (APEGS) assay, we identified ABHD16A proteins from humans, pigs, and mice that can directly participate in the palmitoylation/depalmitoylation cycles of IFITMs in the constructed abhd16a-/- cells and ABHD16A-overexpressing cells. Furthermore, we showed that ABHD16A functions as a regulator of subcellular localization of IFITM proteins and is related to the immune system. It is tempting to suggest that pharmacological intervention in IFITMs and ABHD16A can be achieved either through controlling their expression or regulating their activity, thereby providing a broad-spectrum therapeutic strategy for animal viral diseases. IMPORTANCE IFITM protein is the cells first line of antiviral defense that blocks early stages of viral replication; the underlying mechanism might be associated with the proper distribution in cells. The palmitoylation/depalmitoylation cycle can dynamically regulate protein localization, stability, and function. This work is the first one that found the critical enzyme that participates in the palmitoylation/depalmitoylation cycle of IFITM, and this type of palmitoyl loss may be an essential regulation mode for balancing the antiviral functions of the IFN pathway. These findings imply that the pharmacological intervention in IFITM and ABHD16A, either through controlling their expression or regulating their activities, could provide a broad-spectrum therapeutic strategy for animal viral diseases and complications linked to interferon elevation.

Inflammasome Inhibition Prevents Motor Deficit and Cerebellar Degeneration Induced by Chronic Methamphetamine Administration.

Methamphetamine (METH), a psychostimulant, has the potential to cause neurodegeneration by targeting the cerebrum and cerebellum. It has been suggested that the NLRP3 inflammasome may be responsible for the neurotoxicity caused by METH. However, the role of NLRP3 in METH-induced cerebellar Purkinje cell (PC) degeneration and the underlying mechanism remain elusive. This study aims to determine the consequences of NLRP3 modulation and the underlying mechanism of chronic METH-induced cerebellar PC degeneration. In METH mice models, increased NLRP3 expression, PC degeneration, myelin sheath destruction, axon degeneration, glial cell activation, and motor coordination impairment were observed. Using the NLRP3 inhibitor MCC950, we found that inhibiting NLRP3 alleviated the above-mentioned motor deficits and cerebellar pathologies. Furthermore, decreased mature IL-1ß expression mediated by Caspase 1 in the cerebellum may be associated with the neuroprotective effects of NLRP3 inflammasome inhibition. Collectively, these findings suggest that mature IL-1ß secretion mediated by NLRP3-ASC-Caspase 1 may be a critical step in METH-induced cerebellar degeneration and highlight the neuroprotective properties of inflammasome inhibition in cerebellar degeneration.

Low and high dose methamphetamine differentially regulate synaptic structural plasticity in cortex and hippocampus.

Psychostimulants, such as methamphetamine (METH) can induce structural remodeling of synapses by remodeling presynaptic and postsynaptic morphology. Escalating or long-lasting high dose METH accounts for neurodegeneration by targeting multiple neurotransmitters. However, the effects of low dose METH on synaptic structure and the modulation mechanism remain elusive. This study aims to assess the effects of low dose (2 mg/kg) and high dose (10 mg/kg) of METH on synaptic structure alternation in hippocampus and prefrontal cortex (PFC) and to reveal the underlying mechanism involved in the process. Low dose METH promoted spine formation, synaptic number increase, post-synaptic density length elongation, and memory function. High dose of METH induced synaptic degeneration, neuronal number loss and memory impairment. Moreover, high dose, but not low dose, of METH caused gliosis in PFC and hippocampus. Mechanism-wise, low dose METH inactivated ras-related C3 botulinum toxin substrate 1 (Rac1) and activated cell division control protein 42 homolog (Cdc42); whereas high dose METH inactivated Cdc42 and activated Rac1. We provided evidence that low and high doses of METH differentially regulate synaptic plasticity in cortex and hippocampus.

Design and Fabrication of the Evolved Zeolitic Imidazolate Framework-Modified Polylactic Acid Nonwoven Fabric for Efficient Oil/Water Separation.

Design of durable and recyclable superhydrophobic materials for oil/water separation is a major concern in the field of wastewater treatment. Functionalization of a biodegradable matrix with controllable grown crystals brings out a new research perspective. In this study, multiscale zeolitic imidazolate frameworks (ZIFs) were grown and decorated on a polylactic acid (PLA) nonwoven fabric (NWF) to construct a superhydrophobic material by an in situ growth method and a spraying process. The stable superhydrophobic layer contains two kinds of ZIF crystals showing microscale flake-like structures and nanoscale particles. The morphology and surface energy of such a hierarchically structured ZIF-modified PLANWF is controllable by the adjustment of experimental parameters. The as-prepared PLA hybrid materials exhibit high separation efficiency and recyclability as for water-nitromethane and water-toluene mixtures. Based on the wetting envelopes of the ZIF-modified PLA material, its separation performance for various oil/water mixtures can be preliminarily assessed before the application.

S-palmitoylation of swine interferon-inducible transmembrane protein is essential for its anti-JEV activity.

Japanese encephalitis virus (JEV) is an infectious pathogen spreading in a wide range of vertebrate species. Pigs are amplifying hosts of JEV and thought to be maintained in nature predominantly by avian-mosquito cycles. In the innate immune system, interferon-inducible transmembrane protein (IFITM) is a small transmembrane protein family and has been identified as the first line of defense against a broad range of RNA virus invasion. In this paper, we found that swine IFITM (sIFITM) could restrict the replication of both JEV vaccine strain and wild strain NJ-2008. The cysteine S-palmitoylation modification of sIFITM plays important roles in their anti-JEV effects and intracellular distributions. Our findings show the anti-JEV activities of swine interferon-inducible transmembrane proteins and broaden the antiviral spectrum of IFITM protein family. The preliminary exploration of S-palmitoylation modification of sIFITM may contribute to understanding of the antiviral molecular mechanism of sIFITM.

Stabilization of Grignard reagents by a pillar[5]arene host - Schlenk equilibria and Grignard reactions.

Grignard reagents (RMgX) are widely used in organic synthesis. However, these highly reactive compounds are supplied in inflammable solvents, which causes extra complexity in their transportation. Herein we report that Grignard reagents with linear alkyl chains can be entrapped and stabilized by the macrocyclic host pillar[5]arene while preserving their reactivity.