Visualizing the crucial roles of plasma membrane and peroxynitrite during abdominal aortic aneurysm using two-photon fluorescence imaging.

Peroxynitrite (ONOO-) and cell plasma membrane (CPM) are two key factors in cell pyroptosis during the progression of abdominal aortic aneurysm (AAA). However, their combined temporal and spatial roles in initiating AAA pathogenesis remain unclear. Herein, we developed a two-photon fluorescence probe, BH-Vis, enabling real-time dynamic detection of CPM and ONOO- changes, and revealing their interplay in AAA. BH-Vis precisely targets CPM with reduced red fluorescence intensity correlating with diminished CPM tension. Concurrently, a blue shift of the fluorescence signal of BH-Vis occurs in response to ONOO- offering a reliable ratiometric detection mode with enhanced accuracy by minimizing external testing variables. More importantly, two photon confocal imaging with palmitic acid (PA) and ganglioside (GM1) manipulation, which modulating cell pyroptosis, showcases reliable fluorescence fluctuations. This groundbreaking application of BH-Vis in a mouse AAA model demonstrates its significant potential for accurately identifying cell pyroptosis levels during AAA development.

New materials-based on gelatin coordinated with zirconium or aluminum for ecological retanning.

Ecological retanning agent is an effective way to solve the pollution source of leather manufacturing industry. In this study, the gelatin from chrome-containing leather shavings in the leather industry was used to realize sustainable leather post-tanning. The gelatin hydrolysate (GH) coordinated with Zr4+ or Al3+ to prepare eco-friendly retanning agents GH-Zr and GH-Al. The successful coordination between GH and metal ions was characterized by FTIR and XPS. The retanning agents were characterized by FTIR curve-fitting and circular dichroism spectroscopy. The results showed that the conformation of the secondary structure of the polypeptide became ordered and stable after coordinating with the metal ions. The particle size and weight average molecular weight of the retanning agents were ~1700 nm and ~2100, respectively, measured by nanoparticle size analyzer and gel permeation chromatography (GPC). The retanning agents were applied to retanning of chrome tanned leather and glutaraldehyde tanned leather. The abundant free amino from retanning agents can consume the free formaldehyde. Meanwhile, retanning agents can effectively improve the multiple binding sites, resulting in favorable thickening rate (>110 %) and excellent dye and fatliquor absorption rate with ~99.91 % and ~93.18 %. Thus, this strategy can provide a viable choice for solid leather waste and sustainable development of the leather industry.

Fluorescence color change of supramolecular polymer networks controlled by crown ether-cation recognition.

We report a fluorescent supramolecular polymer networks (SPNs) system based on crown ether-cation recognition. The polymer side chains bear ammonium cations, which can be recognized by host molecules with a B15C5 unit and a quinoline group at each end. The quinoline group makes the host molecule exhibit blue fluorescence. After the formation of SPNs, the recognition of the crown ether-cation transforms the blue fluorescence into yellow fluorescence. The accompanying fluorescence color change during the formation of SPNs makes it with potential applications in the fields of display, printing, information storage, and bioimaging.

Development of de-novo coronavirus 3-chymotrypsin-like protease (3CLpro) inhibitors since COVID-19 outbreak: A strategy to tackle challenges of persistent virus infection.

Although no longer a public health emergency of international concern, COVID-19 remains a persistent and critical health concern. The development of effective antiviral drugs could serve as the ultimate piece of the puzzle to curbing this global crisis. 3-chymotrypsin-like protease (3CLpro), with its substrate specificity mirroring that of the main picornavirus 3C protease and conserved across various coronaviruses, emerges as an ideal candidate for broad-spectrum antiviral drug development. Moreover, it holds the potential as a reliable contingency option to combat emerging SARS-CoV-2 variants. In this light, the approved drugs, promising candidates, and de-novo small molecule therapeutics targeting 3CLpro since the COVID-19 outbreak in 2020 are discussed. Emphasizing the significance of diverse structural characteristics in inhibitors, be they peptidomimetic or nonpeptidic, with a shared mission to minimize the risk of cross-resistance. Moreover, the authors propose an innovative optimization strategy for 3CLpro reversible covalent PROTACs, optimizing pharmacodynamics and pharmacokinetics to better prepare for potential future viral outbreaks.

Near infrared in and out: Deep imaging for scrap leather induced autophagy in vivo by an ultrasensitive two-photon polarity probe.

As one of the important means for eukaryotic cells to maintain homeostasis, autophagy allows for transporting deformed biomacromolecules and damaged organelles to lysosome for digestion and degradation. The process of autophagy entails the merging of autophagosomes and lysosomes, culminating in the breakdown of biomacromolecules. This, in turn, leads to a change in lysosomal polarity. Therefore, fully understanding the changes of lysosomal polarity during autophagy is of significance to the study of membrane fluidity and enzymatic reaction. However, the shorter emission wavelength has greatly damaged the imaging depth, thus seriously limiting its biological application. Therefore, in this work, a near infrared in and out lysosome-targeted polarity-sensitive probe NCIC-Pola was developed. The fluorescence intensity of NCIC-Pola showed an approximate 1160-fold increase when the polarity decreased under two-photon excitation (TPE). In addition, the excellent fluorescence emission wavelength (692 nm) enabled the deep imaging analysis of scrap leather induced autophagy in vivo.

Efficient adsorption of low-concentration uranium from aqueous solutions by biomass composite aerogel.

The development of nuclear energy has led to the depletion of uranium resources and now presents the challenge of treating radioactive wastewater. Extracting uranium from seawater and nuclear wastewater has been identified as an effective strategy for addressing these issues. However, extracting uranium from nuclear wastewater and seawater is still extremely challenging. In this study, an amidoxime-modified feather keratin aerogel (FK-AO aerogel) was prepared using feather keratin for efficient uranium adsorption. The FK-AO aerogel showed an impressive adsorption capacity of 585.88 mg·g-1 in an 8 ppm uranium solution, with a calculated maximum adsorption capacity of 990.10 mg·g-1. Notably, the FK-AO aerogel demonstrated excellent selectivity for U(VI) in simulated seawater that contained coexisting heavy metal ions. In a uranium solution having a salinity of 35 g·L-1 and a concentration of 0.1-2 ppm, the FK-AO aerogel achieved a uranium removal rate of greater than 90 %, indicating its effectiveness in adsorbing uranium in environments having high salinity and low concentration. This suggests that FK-AO aerogel is an ideal adsorbent for extracting uranium from seawater and nuclear wastewater, and it is also expected that it could be used in industrial applications for extracting uranium from seawater.

Imaging of hypochlorous acid in mitochondria using an asymmetric near-infrared fluorescent probe with large Stokes shift.

Small-molecule near-infrared (NIR) imaging facilitates deep tissue penetration, low autofluorescence, non-invasive visualization, and a relatively simple operation. As such it has emerged as a popular technique for tracking biological species and events. However, the small Stokes shift of most NIR dyes often results in a low signal-to-noise ratio and self-quenching due to crosstalk between the excitation and emission spectra. With this research, we developed a NIR-based fluorescent probe WD-HOCl for hypochlorous acid (HOCl) detection using the NIR dye TJ730 as the fluorophore, which exhibits a large Stokes shift of 156 nm, with no crosstalk between the excitation and emission spectra. It contains acyl hydrazide as the responsive group and a pyridinium cation as the mitochondria-targeting group. The fluorescence intensity of WD-HOCl was enhanced by 30.1-fold after reacting with HOCl. Imaging studies performed using BV-2 cells indicated that WD-HOCl could be used for endogenous HOCl detection and imaging in living cells exposed to glucose and oxygen deprivation/reperfusion. Finally, we demonstrated that inhibiting the expression of NOX2 reduced the HOCl levels and the severity of oxidative stress during stroke in a mouse model.

Simultaneous tracking of autophagy and oxidative stress during stroke with an ICT-TBET integrated ratiometric two-photon platform.

Over recent years, fluorescent probes exhibiting simultaneous responses to multiple targets have been developed for in situ, real-time monitoring of cellular metabolism using two photon fluorescence sensing techniques due to numerous advantages including ease of operation, rapid reporting, high resolution, long visualization time and being non-invasive. However, due to interference from different fluorescence channels during simultaneous monitoring of multiple targets and the lack of ratiometric capability amongst the available probes, the accuracy in tracing metabolic processes has been restricted. With this research, using a through-bond energy transfer (TBET) mechanism, we designed a viscosity and peroxynitrite (ONOO-) mitochondria-targeting two-photon ratiometric fluorescent probe Mito-ONOO. Our results indicated that with decreasing levels of mitochondrial viscosity and increasing levels of ONOO-, the maximum of the emission wavelength of the probe shifted from 621 nm to 495 nm under 810 nm two-photon excitation. The baselines for the two emission peaks were significantly separated (Δλ = 126 nm), improving the resolution and reliability of bioimaging. Moreover, by ratiometric analysis during oxygen-glucose deprivation/reoxygenation (OGD/R, commonly used to simulate cell ischemia/reperfusion injury), the real-time visualization of the metabolic processes of autophagy and oxidative stress was possible. Our research indicated that during cellular oxygen-glucose deprivation/reoxygenation, cells produce ONOO-, causing cellular oxidative stress and cellular autophagy after 15 min, as such Mito-ONOO exhibits the potential for the monitoring and diagnosis of stroke, as well as providing insight into potential treatments, and drug design.

Gelatin from leather waste to tough biodegradable packaging film: One valuable recycling solution for waste gelatin from leather industry.

Large amount of gelatin can be extracted from the solid waste in leather industry. The advanced application of such gelatin is always desired by the leather industry, but remains challenging. Considering the urgent requirement of biodegradable plastic film, in this study, the gelatin extracted from waste skin scrap in the leather industry was used to fabricate a waste gelatin-based film with a high gelatin content, excellent mechanical performance, and autonomous biodegradability in natural soil. The film was prepared by introducing covalent bonds and metal-ligand bonds to the gelatin matrix. These covalent bonds, metal-ligand bonds, and inherent hydrogen bonds in the gelatin matrix serve as multiple sacrificial bonds for effective energy dissipation giving the waste gelatin-based film excellent mechanical parameters with the highest fracture stress of ≈ 32 MPa, maximum fracture strain of ≈1.25 mm/mm, and a high Young's modulus of ≈ 471 MPa, which are significantly higher than those of the original gelatin film (fracture stress ≈ 4 MPa, fracture strain ≈ 0.70 mm/mm, and Young's modulus ≈ 22 MPa). Owing to the water resistance of covalent bonds and metal-ligand bonds existed in gelatin matrix, the gelatin film possesses good water resistance. Additionally, after use, the fabricated film can completely biodegrade in natural soil in approximately 7 weeks. This strategy not only provides a valuable recycling solution for the gelatin from the unwelcome solid waste of the leather industry, but it also broadens the range of ecofriendly and cost effective biodegradable films available.

Near-infrared fluorescent probe for hydrogen sulfide: high-fidelity ferroptosis evaluation in vivo during stroke.

Ferroptosis is closely associated with cancer, neurodegenerative diseases and ischemia-reperfusion injury and the detection of its pathological process is very important for early disease diagnosis. Fluorescence based sensing technologies have become excellent tools due to the real-time detection of cellular physiological or pathological processes. However, to date the detection of ferroptosis using reducing substances as markers has not been achieved since the reducing substances are not only present at extremely low concentrations during ferroptosis but also play a key role in the further development of ferroptosis. Significantly, sensors for reducing substances usually consume reducing substances, instigating a redox imbalance, which further aggravates the progression of ferroptosis. In this work, a H2S triggered and H2S releasing near-infrared fluorescent probe (HL-H2S) was developed for the high-fidelity in situ imaging of ferroptosis. In the imaging process, HL-H2S consumes H2S and releases carbonyl sulfide, which is then catalyzed by carbonic anhydrase to produce H2S. Importantly, this strategy does not intensify ferroptosis since it avoids disruption of the redox homeostasis. Furthermore, using erastin as an inducer for ferroptosis, the observed trends for Fe2+, MDA, and GSH, indicate that the introduction of the HL-H2S probe does not exacerbate ferroptosis. In contrast, ferroptosis progression was significantly promoted when the release of H2S from HL-H2S was inhibited using AZ. These results indicate that the H2S triggered and H2S releasing fluorescent probe did not interfere with the progression of ferroptosis, thus enabling high-fidelity in situ imaging of ferroptosis.

Observation of macrophage autophagy in the healing of diabetic ulcers via a lysosome-targeting polarity-specific two-photon probe.

As a disease with high incidence, mutilation, and fatality rates, diabetic ulcers (DUs) have become a difficult and complicated disease of widely concern in recent years due to the unclear healing mechanism. The main reason for the delayed healing in DU patients is the unduly long chronic inflammation window, and the polarization state of macrophages plays a key role in this process. Since autophagy is believed to be closely related to the polarization trend of macrophages, recent studies have shown that autophagy is closely related to the healing of DU. To this end, a lysosome-targeting polarity-sensitive probe, XZTU-VIS, was developed to monitor the changes in lysosomal polarity, thereby assessing the autophagy of macrophages in mice suffering from DU. The experimental results showed that under two-photon fluorescence microscopy, the green channel fluorescence signal of XZTU-VIS decreased significantly during autophagy. In the meantime, DU models established using BV-2 cells and mice showed a process that could cause inflammation and the release of ROS, thereby inducing autophagy.

From Structure Modification to Drug Launch: A Systematic Review of the Ongoing Development of Cyclin-Dependent Kinase Inhibitors for Multiple Cancer Therapy.

Herein, we discuss more than 50 cyclin-dependent kinase (CDK) inhibitors that have been approved or have undergone clinical trials and their therapeutic application in multiple cancers. This review discusses the design strategies, structure-activity relationships, and efficacy performances of these selective or nonselective CDK inhibitors. The theoretical basis of early broad-spectrum CDK inhibitors is similar to the scope of chemotherapy, but because their toxicity is greater than the benefit, there is no clinical therapeutic window. The notion that selective CDK inhibitors have a safer therapeutic potential than pan-CDK inhibitors has been widely recognized during the research process. Four CDK4/6 inhibitors have been approved for the treatment of breast cancer or for prophylactic administration during chemotherapy to protect bone marrow and immune system function. Furthermore, the emerging strategies in the field of CDK inhibitors are summarized briefly, and CDKs continue to be widely pursued as emerging anticancer drug targets for drug discovery.

Waste feather fiber based high extraction capacity bio-adsorbent for sustainable uranium extraction from seawater.

Recycling uranium from seawater is of great significance to the development of nuclear industry. However, due to high salinity and low uranium concentration in seawater, there are still many challenges in current seawater uranium extraction technology. In this study, waste feather fibers (FF) were used as raw materials to develop a phosphonate-functionalized feather fiber (FF-PT). The study on the adsorption performance shows that FF-PT have good adsorption and recycling performance for uranium. The study on the adsorption performance shows that FF-PT have good adsorption and recycling performance for uranium. The adsorption capacity reaches up to 342.5 mg·g-1 in the 8 ppm uranium solution, and service life of at least 10 cycles were obtained. In addition, in the environment with high salinity and the coexistence of metal competitive ions, FF-PT also shows excellent selectivity, and it can reach 3.22 mg·g-1 adsorption capacity after immersed in natural seawater for 30 days. Combined with the results of economic analysis, we believe that the FF-PT has broad application prospects in the industrialized uranium extraction from seawater.

Bio-templated synthesis of porous silica nano adsorbents to wastewater treatment inspired by a circular economy.

Water is an indispensable substance in human life activities. However, due to industrial discharge problems, water resources are polluted, so there is an urgent need for material and technology for wastewater treatment. This paper presents an innovative synthesis of porous silica microspheres (PSM) from a biomass template material (fish skin collagen) to treat protein from wastewater. The collagen from the biomass template was rich in amino, carboxyl, and hydroxyl groups that effectively controlled the hydrolysis rate of tetraethyl orthosilicate (TEOS) and promoted the synthesis of structured PSM. X-ray photoelectron spectroscopy (XPS), X-ray powder diffraction (XRD), nitrogen sorption isotherms measurements, scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were utilized to characterize the chemical composition, crystalline structure, and pore architecture of the synthesized PSM. The characterization results confirmed that the PSM were spherical with the microporous and mesoporous structure in shape and approximately 400 nm in size. Moreover, the pore size could be tuned by addition of mesitylene (TMB). The large number of silicon hydroxyl groups on the PSM surface effectively bound proteins in wastewater and greatly improved the overall absorption rate. The PSM adsorption capacity for lysozyme (LZ) was 49.5 mg/g, and the adsorption behavior was well described by a pseudo-second-order kinetic model and the Langmuir model. Most importantly, the PSM effectively removed protein from actual industrial wastewater, thereby realizing a high value-added utilization of wastewater pollutants.

A dual lock-and-key two photon fluorescence probe in response to hydrogen peroxide and viscosity: Application in cellular imaging and inflammation therapy.

Here, a dual lock-and-key fluorescence probe was developed for visualizing the inflammatory process in myocardial H9C2 cells. The probe possessed two-photon properties, viscosity sensitivity, and hydrogen peroxide (H2O2) responsiveness. A thiocarbamate spacer between fluorophore and H2O2 responsive unit enabled the release of carbonyl sulfide (COS). This rapidly converts to the anti-inflammatory hydrogen sulfide (H2S) by the ubiquitous enzyme carbon anhydrase. The probe displayed a dual response towards hydrogen peroxide and viscosity in vitro. No obvious fluorescence changes were observed towards either hydrogen peroxide or viscosity alone. In cellular experiments, the probe demonstrated good biocompatibility, low toxicity, and was shown responses towards exogenous and endogenous hydrogen peroxide under viscosity conditions. LPS induced cell inflammation showed it was able to effectively alleviate the inflammation-caused damage by releasing H2S and eliminating H2O2. The new protocol demonstrates its promising to achieve diagnosis and treatment of cellular inflammatory process.

Recyclable polyurethane foam loaded with carboxymethyl chitosan for adsorption of methylene blue.

Novel composite foam (CMCTS-PUF-s) was prepared by immobilizing carboxymethyl chitosan (CMCTS) on polyurethane foam (PUF) in which amino groups in CMCTS reacted with isocyanate groups in polyurethane prepolymer. The adsorption capacity of the optimal composite foam (CMCTS-PUF-5) reached to 118.2 mg/g with 5% CMCTS loading. The removal rate to methylene blue (MB) was up to 97.1%, which was obviously higher than 18.9% of PUF. After recycling for five times, the removal rate still reached 83.2%, which strongly proved the excellent reusability of immobilizing CMCTS modified PUF. The characterization results of FTIR and TG showed that CMCTS was well loaded on PUF by covalent bond. The Young's modulus and tensile strength of CMCTS-PUF-5 were increased by 252% and 97% compared with that of PUF. MIP characterization result showed the porosity of CMCTS-PUF-5 was 73.99% and the pore sizes were mainly distributed between 50 and 150 µm, which provide sufficient diffusion channels and active sites for MB dyes. The adsorption kinetics and isotherm proved pseudo-second-order kinetic model and Langmuir isotherm model could well describe the adsorption process of CMCTS-PUF-5. Therefore, CMCTS-PUF-s presents excellent recoverability, high stability and attractive adsorption efficiency, shows the potential application in future treatment of dye wastewater.

An ultrasensitive polarity-specific two-photon probe for revealing autophagy in live cells during scrap leather-induced neuroinflammation process.

A polarity-sensitive fluorescence probe AMN was developed to demonstrate the role of autophagy inhibitory drugs in the process of leather residue-induced neuroinflammation, promoting the knowledge of the relationship between autophagy and neuroinflammation. AMN showed a turn-on fluorescent signal in the process of autophagy inhibition via two-photon confocal imaging, which is different from the current popular autophagy probes. Therefore, AMN can offer high-sensitive imaging analysis of the autophagy inhibition process to better understand the role of autophagy in the process of neuroinflammation. The model of scrap leather-induced neuroinflammation using PC12 cells demonstrated that neuroinflammation can induce autophagy by releasing reactive oxygen species (ROS), and autophagy can alleviate neuroinflammation significantly via ROS scavenging.

Observation of inflammation-induced mitophagy during stroke by a mitochondria-targeting two-photon ratiometric probe.

This study reports the development of a new, pH-sensitive, mitochondria-targeting two-photon ratiometric probe (Mito-BNO) for real-time tracking of mitophagy, a process that can be accelerated in brain tissue during stroke. Mito-BNO shows excellent capability for mitochondrial localisation (Pearson's correlation coefficient, r = 0.91), and can also effectively distinguish mitochondria from other subcellular organelles such as lysosomes and the endoplasmic reticulum (r = 0.40 and r = 0.33, respectively). Meanwhile, a rewarding pKa value (5.23 ± 0.03) and the pH reversibility suggest that Mito-BNO can track mitophagy in real time via confocal imaging. Most importantly, the relationship between mitophagy and neuroinflammation during stroke has been successfully demonstrated by evaluating the fluorescence of PC12 cells stained with Mito-BNO during an oxygen-glucose deprivation/reperfusion (OGD/R) process with and without anti-inflammatory treatment. The results indicate that the occurrence of mitophagy during stroke is caused by oxidative stress induced by neuroinflammation. This study will help further understanding stroke pathogenesis, can provide potential new targets for early diagnosis and treatment, and can also help to develop therapeutic drugs for stroke.

RNA-dependent RNA polymerase (RdRp) inhibitors: The current landscape and repurposing for the COVID-19 pandemic.

The widespread nature of several viruses is greatly credited to their rapidly altering RNA genomes that enable the infection to persist despite challenges presented by host cells. Within the RNA genome of infections is RNA-dependent RNA polymerase (RdRp), which is an essential enzyme that helps in RNA synthesis by catalysing the RNA template-dependent development of phosphodiester bonds. Therefore, RdRp is an important therapeutic target in RNA virus-caused diseases, including SARS-CoV-2. In this review, we describe the promising RdRp inhibitors that have been launched or are currently in clinical studies for the treatment of RNA virus infections. Structurally, nucleoside inhibitors (NIs) bind to the RdRp protein at the enzyme active site, and nonnucleoside inhibitors (NNIs) bind to the RdRp protein at allosteric sites. By reviewing these inhibitors, more precise guidelines for the development of more promising anti-RNA virus drugs should be set, and due to the current health emergency, they will eventually be used for COVID-19 treatment.

Esculin and ferric citrate-incorporated sturgeon skin gelatine as an antioxidant film for food packaging to prevent Enterococcus faecalis contamination.

Herein, a sturgeon skin gelatine film combined with esculin and ferric citrate was developed as an edible food packaging material to prevent Enterococcus faecalis (E. faecalis) contamination. E. faecalis is able to hydrolyse esculin in the film, and then the hydrolysed product, esculetin, combines with ferric citrate to form a brown-black phenol iron complex. This phenomenon can be observed easily after 48 h of contamination under visible light, and it can be determined under 365 nm ultraviolet light with high sensitivity. With the addition of esculin and ferric citrate, the film showed better mechanical properties and water vapour permeability than those of the unmodified gelatine. When an increased amount of esculin was added, an increase in thermal stability, antioxidant activity, and antioxidant stability of the film was observed. These physicochemical characteristics are beneficial for developing a packaging material for food storage that mitigates foodborne illness caused by E. faecalis.