S-Nitrosylated CuS Hybrid Hydrogel Patches with Robust Antibacterial and Repair-Promoting Activity for Infected Wound Healing.

Development of wound dressing with robust antibacterial and repair-promoting activity has always been an urgent biomedical task during the past years. The therapeutic effect of current hydrogel dressings containing single bioactive agent like nanoparticle or gas is still unsatisfactory for the treatment of infected wound. Herein, a CuS/NO co-loaded hydrogel (CuS/NO Gel) is proposed, which is constructed by sequential polymerization, reduction, and S-nitrosylation of CuS hybrid hydrogel with disulfide bonds. These CuS/NO Gel patches show good mechanical stability, high photothermal activity and excellent biocompatibility. When being applied to treat infected wound, CuS/NO Gel can not only eliminate infection effectively by the synergistic effect of mild photothermal heating and boosted NO release in infection phase, but also promote vascularization and collagen deposition due to the synchronous supply of Cu ion nutrients and low concentration NO signaling molecules in wound repair phase. Compared to hydrogel dressings with individual active agent (CuS Gel or NO Gel), CuS/NO Gel exhibits better antibacterial and repair-promoting activity both in vitro and in vivo. Therefore, this CuS/NO Gel holds great promise in the future clinical treatment against infected wound.

Antibacterial, antioxidant and injectable hydrogels constructed using CuS and curcumin co-loaded micelles for NIR-enhanced infected wound healing.

Constructing antibacterial and antioxidant hydrogels is critical for treating infected full-thickness skin wounds. Herein, we report a co-encapsulation strategy to load CuS nanoparticles and hydrophobic antioxidant curcumin (cur) in aldehyde-terminated F127 micelles, which are then cross-linked with carboxymethyl chitosan through a Schiff base reaction to form a functional composite hydrogel (CF-CuS-cur). Apart from its suitable swelling and degradation behavior, good biocompatibility, and injectability for treating irregular wounds, the CF-CuS-cur hydrogel displayed excellent photothermal antibacterial ability under 1064 nm NIR laser irradiation, and antioxidant activity to protect cells from excessive oxidative stress. Using a full-thickness infected wound model, we demonstrated that the CF-CuS-cur hydrogel accelerated the wound healing process by effective sterilization and decreased inflammation, under synergistic action from CuS, curcumin and NIR irradiation. Histological and immunohistochemistry analysis further revealed the promoted skin attachments and regeneration, collagen deposition, neovascularization, and early transition to anti-inflammatory M2 macrophages, when the wounds were treated with the CF-CuS-cur hydrogel. This work demonstrates a facile strategy to construct functional hydrogels with NIR-enhanced antibacterial and antioxidant properties, which can be potentially applied as wound dressings for treating chronic wounds.

CuS Hybrid Hydrogel for Near-Infrared-Enhanced Infected Wound Healing: A Gelatin-Assisted Synthesis and Direct Incorporation Strategy.

Developing antibacterial hydrogels, with good mechanical strength and self-healing ability to resist bacterial invasion and accelerate skin regeneration, is critical for infected full-thickness skin wound treatment. Herein, we report a gelatin-assisted synthesis and direct incorporation strategy to construct a CuS hybrid hydrogel for infected wound healing applications. CuS nanodots (NDs) were synthesized directly inside a gelatin host matrix (Gel-CuS), and these tightly confined and evenly distributed CuS NDs displayed superb dispersibility and stability against oxidation. Gel-CuS was then used to crosslink with oxidized dextran (ODex) to form a Gel-CuS-8/ODex hydrogel (8 stands for the concentration of CuS, in mM) via a facile Schiff-base reaction, which exhibited improved mechanical properties, excellent adhesion and self-healing ability, suitable swelling and degradation behavior, and good biocompatibility. The Gel-CuS-8/ODex hydrogel can act as an efficient antibacterial agent due to its photothermal and photodynamic properties under a 1064 nm laser irradiation. Furthermore, in animal experiments, when being applied as wound dressing, the Gel-CuS-8/ODex hydrogel significantly promoted infected full-thickness cutaneous wound healing through improved epidermis and granulation tissue formation and accelerated generation of new blood vessels, hair follicles, and collagen deposition after proper near-infrared irradiation treatment. This work provides a promising strategy to synthesize functional inorganic nanomaterials tightly and evenly embedded inside modified natural hydrogel networks for wound healing applications.

Trend Feature Consistency Guided Deep Learning Method for Minor Fault Diagnosis.

Deep learning can be applied in the field of fault diagnosis without an accurate mechanism model. However, the accurate diagnosis of minor faults using deep learning is limited by the training sample size. In the case that only a small number of noise-polluted samples is available, it is crucial to design a new learning mechanism for the training of deep neural networks to make it more powerful in feature representation. The new learning mechanism for deep neural networks model is accomplished by designing a new loss function such that accurate feature representation driven by consistency of trend features and accurate fault classification driven by consistency of fault direction both can be secured. In such a way, a more robust and more reliable fault diagnosis model using deep neural networks can be established to effectively discriminate those faults with equal or similar membership values of fault classifiers, which is unavailable for traditional methods. Validation for gearbox fault diagnosis shows that 100 training samples polluted with strong noise are adequate for the proposed method to successfully train deep neural networks to achieve satisfactory fault diagnosis accuracy, while more than 1500 training samples are required for traditional methods to achieve comparative fault diagnosis accuracy.

Effects of High-Canolol Phenolic Extracts on Fragrant Rapeseed Oil Quality and Flavor Compounds during Frying.

Fragrant rapeseed oil (FRO) is a frying oil widely loved by consumers, but its quality deteriorates with increasing frying time. In this study, the effect of high-canolol phenolic extracts (HCP) on the physicochemical properties and flavor of FRO during frying was investigated. During frying, HCP significantly inhibited the increase in peroxide, acid, p-anisidine, and carbonyl values, as well as total polar compounds and degradation of unsaturated fatty acids. A total of 16 volatile flavor compounds that significantly contributed to the overall flavor of FRO were identified. HCP was effective in reducing the generation of off-flavors (hexanoic acid, nonanoic acid, etc.) and increased the level of pleasant deep-fried flavors (such as (E,E)-2,4-decadienal). Therefore, the application of HCP has a positive effect on protecting the quality and prolonging the usability of FRO.

Ball pen writing-without-ink: a truly simple and accessible method for sensitivity enhancement in lateral flow assays.

Lateral flow assays (LFAs), a popular point-of-care testing platform, have found widespread applications from laboratory to clinics. However, LFA-based testing is still subject to limited detection sensitivity, especially for classical gold nanoparticle-based LFAs. Inspired by traditional pen-based writing technologies, we developed a ball pen writing-without-ink method to amplify the detection signal of LFAs through controlling fluid flow rate. An enhancement of detection sensitivity by two times was obtained. Since the underlying mechanism of this method to improve detection sensitivity is to control the flow rate of the liquid on paper, it may be suitable for most paper-based platforms.

Novel Water-in-Oil Emulsions for Co-Loading Sialic Acid and Chitosan: Formulation, Characterization, and Stability Evaluation.

This study was designed to co-load sialic acid (SA) and chitosan in a water-in-oil (W/O) emulsion and investigated its characterization and stability. Emulsions were prepared using two different oils (olive oil and maize oil) and polyglycerol polyricinoleate (PGPR) alone or in combination with lecithin (LE) as emulsifiers. The results revealed that the aqueous phase of 5% (w/v) SA and 2% (w/v) chitosan could form a stable complex and make the aqueous phase into a transparent colloidal state. Increasing the concentration of PGPR and LE presented different effects on emulsion formation between olive oil-base and maize oil-base. Two stable W/O emulsions that were olive oil-based with 1.5% (w/v) PGPR+ 0.5% (w/v) LE and maize oil-based with 2% (w/v) PGPR+ 0% (w/v) LE were obtained. Initial droplet size distribution curves of the two stable emulsions displayed unimodal distribution, and the rheological curves displayed the characteristics of shear thinning and low static shear viscosity. Moreover, the storage stability showed that there was no significant change in droplet size distribution and Sauter mean diameter of the emulsions at room temperature (25 °C) for 30 days. These results indicated that the W/O emulsions could effectively co-load and protect sialic acid and chitosan and thus could be a novel method for increasing the stability of these water-soluble bioactive compounds.

Quantifying and Adjusting Plasmon-Driven Nano-Localized Temperature Field around Gold Nanorods for Nucleic Acids Amplification.

Fast nucleic acid (NA) amplification has found widespread biomedical applications, where high thermocycling rate is the key. The plasmon-driven nano-localized thermocycling around the gold nanorods (AuNRs) is a promising alternative, as the significantly reduced reaction volume enables a rapid temperature response. However, quantifying and adjusting the nano-localized temperature field remains challenging for now. Herein, a simple method is developed to quantify and adjust the nano-localized temperature field around AuNRs by combining experimental measurement and numerical simulation. An indirect method to measure the surface temperature of AuNRs is first developed by utilizing the temperature-dependent stability of Authiol bond. Meanwhile, the relationship of AuNRs' surface temperature with the AuNRs concentration and laser intensity, is also studied. In combination with thermal diffusion simulation, the nano-localized temperature field under the laser irradiation is obtained. The results show that the restricted reaction volume (≈aL level) enables ultrafast thermocycling rate (>104  °C s-1 ). At last, a duplex-specific nuclease (DSN)-mediated isothermal amplification is successfully demonstrated within the nano-localized temperature field. It is envisioned that the developed method for quantifying and adjusting the nano-localized temperature field around AuNRs is adaptive for various noble metal nanostructures and will facilitate the development of the biochemical reaction in the nano-localized environment.

Evaporation-Induced Diffusion Acceleration in Liquid-Filled Porous Materials.

Liquid-filled porous materials exist widely in nature and engineering fields, with the diffusion of substances in them playing an important role in system functions. Although surface evaporation is often inevitable in practical scenarios, the evaporation effects on diffusion behavior in liquid-filled porous materials have not been well explored yet. In this work, we performed noninvasive diffusion imaging experiments to observe the diffusion process of erioglaucine disodium salt dye in a liquid-filled nitrocellulose membrane under a wide range of relative humidities (RHs). We found that evaporation can significantly accelerate the diffusion rate and alter concentration distribution compared with the case without evaporation. We explained the accelerated diffusion phenomenon by the mechanism that evaporation would induce a weak flow in liquid-filled porous materials, which leads to convective diffusion, i.e., evaporation-induced flow and diffusion (EIFD). Based on the EIFD mechanism, we proposed a convective diffusion model to quantitatively predict the diffusion process in liquid-filled porous materials under evaporation and experimentally validated the model. Introducing the dimensionless Peclet (P e) number to measure the relative contribution of the evaporation effect to pure molecular diffusion, we demonstrated that even at a high RH of 95%, where the evaporation effect is usually assumed negligible in common sense, the evaporation-induced diffusion still overwhelms the molecular diffusion. The flow velocity induced by evaporation in liquid-filled porous materials was found to be 0.4-5 µm/s, comparable to flow in many biological and biomedical systems. The present analysis may help to explain the driving mechanism of tissue perfusion and provide quantitative analysis or inspire new control methods of flow and material exchange in numerous cutting-edge technologies, such as paper-based diagnostics, hydrogel-based flexible electronics, evaporation-induced electricity generation, and seawater purification.

Cascade targeting tumor mitochondria with CuS nanoparticles for enhanced photothermal therapy in the second near-infrared window.

Photothermal therapy, assisted by local heat generation using photothermal nanoparticles (NPs), is an emerging strategy to treat tumors noninvasively. To improve treatment outcomes and to alleviate potential side effects on normal tissue cells, utilizing the optically transparent second near-infrared (NIR-II) window and actively targeting tumors are critical. Considering that mitochondria are heat sensitive and play an important role in the up-regulation of metabolic activity in tumor cells, herein we report a cascade targeting scheme that enables active photothermal ablation of tumor mitochondria. First, NIR-II absorbing CuS NPs were surface modified with the mitochondria targeting moiety (3-carboxypropyl) triphenylphosphonium bromide (TPP) and then shielded with CD44 targeting hyaluronic acid, which will only expose TPP upon reaching the tumor sites. This allowed over 90% CuS NP enrichment at tumor mitochondria, and as a result, significantly improved tumor cell photothermal ablation was observed at the cellular level. An in vivo study demonstrated enhanced tumor uptake and improved tumor growth suppression by using these cascade targeting CuS NPs as NIR-II photothermal agents.

Bistratal Au@Bi2S3 nanobones for excellent NIR-triggered/multimodal imaging-guided synergistic therapy for liver cancer.

To fabricate a highly biocompatible nanoplatform enabling synergistic therapy and real-time imaging, novel Au@Bi2S3 core shell nanobones (NBs) (Au@Bi2S3 NBs) with Au nanorods as cores were synthesized. The combination of Au nanorods with Bi2S3 film made the Au@Bi2S3 NBs exhibit ultrahigh photothermal (PT) conversion efficiency, remarkable photoacoustic (PA) imaging and high computed tomography (CT) performance; these Au@Bi2S3 NBs thus are a promising nanotheranostic agent for PT/PA/CT imaging. Subsequently, poly(N-vinylpyrrolidone)-modified Au@Bi2S3 NBs (Au@Bi2S3-PVP NBs) were successfully loaded with the anticancer drug doxorubicin (DOX), and a satisfactory pH sensitive release profile was achieved, thus revealing the great potential of Au@Bi2S3-PVP NBs in chemotherapy as a drug carrier to deliver DOX into cancer cells. Both in vitro and in vivo investigations demonstrated that the Au@Bi2S3-PVP NBs possessed multiple desired features for cancer therapy, including extremely low toxicity, good biocompatibility, high drug loading ability, precise tumor targeting and effective accumulation. Highly efficient ablation of the human liver cancer cell HepG2 was achieved through Au@Bi2S3-PVP NB-mediated photothermal therapy (PTT). As both a contrast enhancement probe and therapeutic agent, Au@Bi2S3-PVP NBs provided outstanding NIR-triggered multi-modal PT/PA/CT imaging-guided PTT and effectively inhibited the growth of HepG2 liver cancer cells via synergistic chemo/PT therapy.

Progesterone attenuates Aß25-35-induced neuronal toxicity by activating the Ras signalling pathway through progesterone receptor membrane component 1.

AIMS: Progesterone receptor membrane component 1 (PGRMC1) has been reported to mediate the neuroprotective effect of progesterone, but the exact mechanism has not been elucidated. Therefore, the purpose of this study was to investigate the signalling pathway downstream of PGRMC1 in progesterone-induced neuroprotection. Recognition of the mechanism of progesterone opens novel perspectives for the treatment of diseases of the nervous system. MAIN METHODS: The PGRMC1 protein level was knocked down in rat primary cortical neurons, and Aß25-35 was used to establish an Alzheimer's disease cell model. The neuroprotective effect of progesterone was assessed by Hoechst 33258 staining and a cell counting kit-8 (CCK-8) assay. Then, proteomic and bioinformatic methods were used to analyse the proteins altered in response to PGRMC1 silencing to identify target proteins and signalling pathways involved in PGRMC1-mediated progesterone-induced neuroprotection. These findings were further verified by using signalling pathway inhibitors and western blotting. KEY FINDINGS: The neuroprotective effect of progesterone was significantly attenuated with PGRMC1 silencing. The expression of many proteins in the Ras signalling pathway was significantly changed in response to PGRMC1 silencing. FTI-277 inhibited progesterone-induced neuroprotection. Progesterone increased the expression of total Ras and Grb2. SIGNIFICANCE: These findings provide new perspectives for understanding the mechanism of and role of PGRMC1 in progesterone-induced neuroprotection. The Ras signalling pathway is the signalling pathway downstream of PGRMC1 in the mediation of progesterone-induced neuroprotection.

The role of reactive oxygen species in tumor treatment.

Reactive oxygen species (ROS) are by-products of aerobic metabolism and can also act as signaling molecules to participate in multiple regulation of biological and physiological processes. The occurrence, growth and metastasis of tumors, and even the apoptosis, necrosis and autophagy of tumor cells are all closely related to ROS. However, ROS levels in the body are usually maintained at a stable status. ROS produced by oxidative stress can cause damage to cell lipids, protein and DNA. In recent years, ROS have achieved satisfactory results on the treatment of tumors. Therefore, this review summarizes some research results of tumor treatments from the perspective of ROS in recent years, and analyzes how to achieve the mechanism of inhibition and treatment of tumors by ROS or how to affect the tumor microenvironment by influencing ROS. At the same time, the detection methods of ROS, problems encountered in the research process and solutions are also summarized. The purpose of this review is to provide a clearer understanding of the ROS role in tumor treatment, so that researchers might have more inspiration and thoughts for cancer prevention and treatment in the next stage.

Effects of progesterone on glucose uptake in neurons of Alzheimer's disease animals and cell models.

AIMS: Alzheimer's disease (AD) is closely related to abnormal glucose metabolism in the central nervous system. Progesterone has been shown to have obvious neuroprotective effects in the pathogenesis of AD, but the specific mechanism has not been fully elucidated. Therefore, the purpose of this study was to investigate the effect of progesterone on the glucose metabolism of neurons in amyloid precursor protein (APP)/presenilin 1 (PS1) mice and Aß-induced AD cell model. MATERIALS AND METHODS: APP/PS1 mice were treated with 40 mg/kg progesterone for 40 days and primary cultured cortical neurons were treated with 1 µM progesterone for 48 h.Then behavior tests,2-NBDG glucose uptake tests and the protein levels of glucose transporter 3 (GLUT3), GLUT4, cAMP-response element binding protein (CREB) and proliferator-activated receptor γ (PPARγ) were examined. KEY FINDINGS: Progesterone increased the expression levels of GLUT3 and GLUT4 in the cortex of APP/PS1 mice, accompanied by an improvement in learning and memory. Progesterone increased the levels of CREB and PPARγ in the cerebral cortex of APP/PS1 mice. In vitro, progesterone increased glucose uptake in primary cultured cortical neurons, this effect was blocked by the progesterone receptor membrane component 1 (PGRMC1)-specific blocker AG205 but not by the progesterone receptor (PR)-specific blocker RU486. Meanwhile, progesterone increased the expression of GLUT3, GLUT4, CREB and PPARγ, and AG205 blocked this effect. SIGNIFICANCE: These results confirm that progesterone significantly improves the glucose metabolism of neurons.One of the mechanisms of this effect is that progesterone upregulates protein expression of GLUT3 and GLUT4 through pathways PGRMC1/CREB/GLUT3 and PGRMC1/PPARγ/GLUT4.