An adhesion-switchable hydrogel dressing for painless dressing removal without secondary damage.

Hydrogels with strong adhesion to wet tissues are considered promising for wound dressings. However, the clinical application of adhesive hydrogel dressing remains a challenge due to the issues of secondary damage during dressing changes. Herein, we fabricated an adhesion-switchable hydrogel formed with poly(acrylamide)-co-poly(N-isopropyl acrylamide), quaternary ammonium chitosan and tannic acid. This hydrogel forms instant and robust adhesion to the skin at body temperature. However, as the temperature rises above the lower critical solution temperature (LCST), the hydrogel loses its adhesion towards the wound area due to the temperature-dependent volume phase transition of the copolymer, occurring around 45 °C. Consequently, the designed hydrogel can be easily detached from adhered tissues upon demand, providing a facile and effective method for painless dressing changes without secondary damage. This hydrogel holds great promise for long-term application in wound dressings.

Nanogalvanic Cells Release Highly Reactive Electrons in Tumors to Effectively Eliminate Tumors.

External stimuli triggering chemical reactions in cancer cells to generate highly reactive chemical species are very appealing for cancer therapy, in which external irradiation activating sensitizers to transfer energy or electrons to surrounding oxygen or other molecules is critical for generating cytotoxic reactive species. However, poor light penetration into tissue, low activity of sensitizers, and reliance on oxygen supply restrict the generation of cytotoxic chemical species in hypoxic tumors, which lowers the therapeutic efficacy. Here, this work presents galvanic cell nanomaterials that can directly release highly reactive electrons in tumors without external irradiation or photosensitizers. The released reactive electrons directly react with surrounding biomolecules such as proteins and DNA within tumors to destroy them or react with other surrounding (bio)molecules to yield cytotoxic chemical species to eliminate tumors independent of oxygen. Administering these nanogalvanic cells to mice results in almost complete remission of subcutaneous solid tumors and deep metastatic tumors. The results demonstrate that this strategy can further arouse an immune response even in a hypoxic environment. This method offers a promising approach to effectively eliminate tumors, similar to photodynamic therapy, but does not require oxygen or irradiation to activate photosensitizers.

Accumulation, translocation, metabolism and subcellular distribution of mandipropamid in cherry radish: A comparative study under hydroponic and soil-cultivated conditions.

The accumulation and transportation of pesticides in plants can provide valuable insights to assess potential risks and ensure food safety. The uptake and downward translocation of mandipropamid were examined in hydroponic and soil-cultivated cherry radishes. The uptake of mandipropamid in cherry radish was rapid (bioconcentration factors of 1.1-10.7), whereas the downward translocation was limited (translocation factors of 0.1-0.9). The subcellular distribution results indicated a predominant accumulation in solid fractions of cherry radish (proportions of 52.9-98.7%), potentially because of the hydrophobicity (log Kow of 3.2) of mandipropamid. Owing to the decrease in half-life (>10%), the cultivation of cherry radish enhanced the dissipation of mandipropamid in both nutrient solutions (without stereoselectivity) and soils (with stereoselectivity). In addition, eleven metabolites and three pathways are proposed. This study provides valuable insights for the varying extent of translocation and proper utilization and safety evaluation of mandipropamid in crops.

The fate and potential hazards of chlorfenapyr and one metabolite tralopyril in cabbages: A comprehensive investigation.

The potential hazards of chlorfenapyr warrant attention owing to its widespread application on vegetables. A comprehensive investigation of the fate of chlorfenapyr in the ecosystem is imperative. This paper presents a method for detecting chlorfenapyr and tralopyril in cabbages, which exhibits good linearity (determination coefficients > 0.99) and satisfactory recoveries (82.50 %-108.03 %). Chlorfenapyr residues in cabbages demonstrate a positive correlation with its application dose and time. Tralopyril can inhibit the dissipation of chlorfenapyr, as evidenced by the half-lives of 5.67-11.14 d (chlorfenapyr) and 6.91-14.77 d (total chlorfenapyr). The results of terminal residues (<2.0 mg/kg) and dietary risk assessment (<100 %) suggest preharvest intervals of 14 d (greenhouse) and 10 d (open-field). Additionally, the uptake of chlorfenapyr in cabbages is limited (translocation factor < 1), while the downward translocation predominantly occurs through phloem transport. The findings provide valuable insights for understanding the fate and potential risks of chlorfenapyr in cabbages.

Inflammation-induced subcutaneous neovascularization for the long-term survival of encapsulated islets without immunosuppression.

Cellular therapies for type-1 diabetes can leverage cell encapsulation to dispense with immunosuppression. However, encapsulated islet cells do not survive long, particularly when implanted in poorly vascularized subcutaneous sites. Here we show that the induction of neovascularization via temporary controlled inflammation through the implantation of a nylon catheter can be used to create a subcutaneous cavity that supports the transplantation and optimal function of a geometrically matching islet-encapsulation device consisting of a twisted nylon surgical thread coated with an islet-seeded alginate hydrogel. The neovascularized cavity led to the sustained reversal of diabetes, as we show in immunocompetent syngeneic, allogeneic and xenogeneic mouse models of diabetes, owing to increased oxygenation, physiological glucose responsiveness and islet survival, as indicated by a computational model of mass transport. The cavity also allowed for the in situ replacement of impaired devices, with prompt return to normoglycemia. Controlled inflammation-induced neovascularization is a scalable approach, as we show with a minipig model, and may facilitate the clinical translation of immunosuppression-free subcutaneous islet transplantation.

Enzyme Activity and Lipogenesis Inhibition by Fermented Grain Using Natural Enzymes.

This study aims to compare the effects of three enzyme-rich foods, including one fermented (grain enzyme) and two non-fermented foods (enzyme foods 1 and 2), by investigating their antioxidant, anti-inflammatory, and anti-adipogenic properties. Grain enzyme exhibited the highest radical scavenging activity and was rich in antioxidant components, including total polyphenol and total flavonoid contents. Grain enzyme and enzyme foods 1 and 2 inhibited nitric oxide production by 27, 34, and 17%, respectively, at a concentration of 200 µg/mL in LPS-stimulated macrophages. Among the tested enzymes, grain enzyme demonstrated the strongest inhibition on the expression of inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX-2), and interleukin (IL)-1ß, while Enzyme Food 2 exhibited the most significant suppression of IL-6 mRNA levels. Furthermore, Grain Enzyme demonstrated a stronger inhibitory effect compared to Enzyme Food 1 and 2. Grain Enzyme decreased the mRNA expression of peroxisome proliferator-activated receptor (PPAR)γ, CCAAT/enhancer-binding protein (C/EBP)α, and fatty acid-binding protein (FABP)4 by 28, 21, and 30%, respectively, at a concentration of 400 µg/mL. In summary, fermented grain enzymes outperformed non-fermented enzymes in suppressing inflammation and adipogenesis. This study highlights the anti-inflammatory and anti-adipogenic effects of grain enzyme, suggesting its potential as a valuable dietary supplement for managing metabolic disorders.

Co-delivery of a tumor microenvironment-responsive disulfiram prodrug and CuO2 nanoparticles for efficient cancer treatment.

Disulfiram (DSF) has been used as a hangover drug for more than seven decades and was found to have potential in cancer treatment, especially mediated by copper. However, the uncoordinated delivery of disulfiram with copper and the instability of disulfiram limit its further applications. Herein, we synthesize a DSF prodrug using a simple strategy that could be activated in a specific tumor microenvironment. Poly amino acids are used as a platform to bind the DSF prodrug through the B-N interaction and encapsulate CuO2 nanoparticles (NPs), obtaining a functional nanoplatform Cu@P-B. In the acidic tumor microenvironment, the loaded CuO2 NPs will produce Cu2+ and cause oxidative stress in cells. At the same time, the increased reactive oxygen species (ROS) will accelerate the release and activation of the DSF prodrug and further chelate the released Cu2+ to produce the noxious copper diethyldithiocarbamate complex, which causes cell apoptosis effectively. Cytotoxicity tests show that the DSF prodrug could effectively kill cancer cells with only a small amount of Cu2+ (0.18 µg mL-1), inhibiting the migration and invasion of tumor cells. In vitro and in vivo experiments have demonstrated that this functional nanoplatform could kill tumor cells effectively with limited toxic side effects, showing a new perspective in DSF prodrug design and cancer treatment.

Schisandra chinensis-derived gomisin C suppreses lipid accumulation by JAK2-STAT signaling in adipocyte.

Gomisin C is a lignan isolated from the fruit of Schisandra chinensis. The current study aimed to investigate the effect of gomisin C on lipid accumulation in adipocytes and its underlying mechanism. Gomisin C effectively inhibited lipid accumulation by downregulating adipogenic factors such as PPARγ and C/EBPα. Gomisin C-mediated suppression of lipid accumulation occurred in the early adipogenic stage; C/EBPß was downregulated by 55%, while KLF2 was upregulated by 1.5-fold. Gomisin C significantly reduced the production of reactive oxygen species but upregulated antioxidant enzymes, including catalase, SOD1, and Gpx at the mRNA level. Gomisin C regulated NRF2-KEAP1 pathway by increasing NRF2 and decreasing KEAP1, in protein abundance. Furthermore, gomisin C suppressed the JAK2-STAT signaling pathway by decreasing phosphorylation. Taken together, gomisin C reduced early adipogenesis and ROS production by inhibiting the JAK2-STAT signaling pathway but activating the NRF2-KEAP1 signaling pathway. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01263-8.

DPA-Zinc around Polyplexes Acts Like PEG to Reduce Protein Binding While Targeting Cancer Cells.

Gene therapy holds great promise as an effective treatment for many diseases of genetic origin. Gene therapy works by employing cationic polymers, liposomes, and nanoparticles to condense DNA into polyplexes via electronic interactions. Then, a therapeutic gene is introduced into target cells, thereby restoring or changing cellular function. However, gene transfection efficiency remains low in vivo due to high protein binding, poor targeting ability, and substantial endosomal entrapment. Artificial sheaths containing PEG, anions, or zwitterions can be introduced onto the surface of gene carriers to prevent interaction with proteins; however, they reduce the cellular uptake efficacy, endosomal escape, targeting ability, thereby, lowering gene transfection. Here, it is reported that linking dipicolylamine-zinc (DPA-Zn) ions onto polyplex nanoparticles can produce a strong hydration water layer around the polyplex, mimicking the function of PEGylation to reduce protein binding while targeting cancer cells, augmenting cellular uptake and endosomal escape. The polyplexes with a strong hydration water layer on the surface can achieve a high gene transfection even in a 50% serum environment. This strategy provides a new solution for preventing protein adsorption while improving cellular uptake and endosomal escape.

Dibenzoylmethane ameliorates adiposity-mediated neuroinflammatory response and inflammation-mediated neuronal cell death in mouse microglia and neuronal cells.

Dibenzoylmethane (DBM), a licorice-derived component, has numerous health benefits. The current study aimed to investigate the effect of DBM on adiposity-induced neuroinflammatory/oxidative response and microglial activation-induced neuronal cell damage. For this research, BV2 and HT22 cells were cultured using adipcyte- and microglia-conditioned media, respectively. DBM effectively suppressed lipopolysaccharide-induced productions in inducible nitric oxide synthase and cyclooxygenase2. Interleukin (IL)-6, monocyte chemoattractant protein-1, IL-1ß, and tumor necrosis factor-α levels were also downregulated by DBM. In adipocyte-conditioned medium (ACM)-cultured BV2 cells, DBM effectively decreased ACM-induced generation of nitric oxide, reactive oxygen species, and inflammatory cytokines by activating nuclear factor erythroid 2-related factor 2/heme oxygenase-1 signaling and reducing nuclear factor kappa-light-chain-enhancer of activated B cells. In BV2-conditioned medium (BVM)-cultured neuron cells, DBM recovered the BVM-induced reduction of neuronal cell viability, thereby regulating B-cell lymphoma 2 (BCL2), BCL2-associated X (BAX), and cleaved caspase-3 protein expression. Taken together, DBM suppressed adiposity-induced inflammation/oxidative responses and inflammation-induced neuronal cell death.

Easy Access to Diverse Multiblock Copolymers with On-Demand Blocks via Thioester-Relayed In-Chain Cascade Copolymerization.

Multiblock copolymers are envisioned as promising materials with enhanced properties and functionality compared with their diblock/triblock counterparts. However, the current approaches can construct multiblock copolymers with a limited number of blocks but tedious procedures. Here, we report a thioester-relayed in-chain cascade copolymerization strategy for the easy preparation of multiblock copolymers with on-demand blocks, in which thioester groups with on-demand numbers are built in the polymer backbone by controlled/living polymerizations. These thioester groups further serve as the in-chain initiating centers to trigger the acyl group transfer ring-opening polymerization of episulfides independently and concurrently to extend the polymer backbone into multiblock structures. The compositions, number of blocks, and block degree of polymerization can be easily regulated. This strategy can offer easy access to a library of multiblock copolymers with ≈100 blocks in only 2 to 4 steps.

Influence of Additive N2 on O2 Plasma Ashing Process in Inductively Coupled Plasma.

One of the cleaning processes in semiconductor fabrication is the ashing process using oxygen plasma, which has been normally used N2 gas as additive gas to increase the ashing rate, and it is known that the ashing rate is strongly related to the concentration of oxygen radicals measured OES. However, by performing a comprehensive experiment of the O2 plasma ashing process in various N2/O2 mixing ratios and RF powers, our investigation revealed that the tendency of the density measured using only OES did not exactly match the ashing rate. This problematic issue can be solved by considering the plasma parameter, such as electron density. This study can suggest a method inferring the exact maximum condition of the ashing rate based on the plasma diagnostics such as OES, Langmuir probe, and cutoff probe, which might be useful for the next-generation plasma process.

Biodegradable hydrogels with photodynamic antibacterial activity promote wound healing and mitigate scar formation.

Bacterial proliferation and the disordered extracellular matrix (ECM) at the wound site are the major reasons for delayed healing and abnormal scarring. The development of new multifunctional dressing materials that can effectively prevent scar formation without delaying wound healing remains a challenge. In this study, we construct a verteporfin-loaded biodegradable hydrogel (VP-gel) using hyaluronic acid and thiol-terminated 4-arm polyethylene glycol (PEG). The injectable VP-gel sustainably releases small doses of verteporfin in the wound microenvironment that generates reactive oxygen species (ROS) under red light irradiation to kill bacteria efficiently. Importantly, the sustained release of VP could also regulate TGF-ß family-induced cellular responses and the downstream signaling molecule Smad2 in fibroblasts to reduce myofibroblast differentiation, promoting ECM reconstruction and scarless wound healing. Immunohistochemical examination of wound healing and histomorphology in a mouse full-thickness wound model demonstrates excellent acceleration effects of VP-gel for infected wound healing. Therefore, VP-gel with anti-scarring and antibacterial activity, as well as enhanced infection wound healing ability shows great potential in the clinical treatment of scar healing for infected wounds.

Development of a High-Linearity Voltage and Current Probe with a Floating Toroidal Coil: Principle, Demonstration, Design Optimization, and Evaluation.

As the conventional voltage and current (VI) probes widely used in plasma diagnostics have separate voltage and current sensors, crosstalk between the sensors leads to degradation of measurement linearity, which is related to practical accuracy. Here, we propose a VI probe with a floating toroidal coil that plays both roles of a voltage and current sensor and is thus free from crosstalk. The operation principle and optimization conditions of the VI probe are demonstrated and established via three-dimensional electromagnetic wave simulation. Based on the optimization results, the proposed VI probe is fabricated and calibrated for the root-mean-square (RMS) voltage and current with a high-voltage probe and a vector network analyzer. Then, it is evaluated through a comparison with a commercial VI probe, with the results demonstrating that the fabricated VI probe achieved a slightly higher linearity than the commercial probe: R2 of 0.9967 and 0.9938 for RMS voltage and current, respectively. The proposed VI probe is believed to be applicable to plasma diagnostics as well as process monitoring with higher accuracy.

Development of the Measurement of Lateral Electron Density (MOLE) Probe Applicable to Low-Pressure Plasma Diagnostics.

As the importance of measuring electron density has become more significant in the material fabrication industry, various related plasma monitoring tools have been introduced. In this paper, the development of a microwave probe, called the measurement of lateral electron density (MOLE) probe, is reported. The basic properties of the MOLE probe are analyzed via three-dimensional electromagnetic wave simulation, with simulation results showing that the probe estimates electron density by measuring the surface wave resonance frequency from the reflection microwave frequency spectrum (S11). Furthermore, an experimental demonstration on a chamber wall measuring lateral electron density is conducted by comparing the developed probe with the cutoff probe, a precise electron density measurement tool. Based on both simulation and experiment results, the MOLE probe is shown to be a useful instrument to monitor lateral electron density.

Integrating Au and ZnO nanoparticles onto graphene nanosheet for enhanced sonodynamic therapy.

Sonodynamic therapy has attracted widespread attention for cancer treatment because of its noninvasiveness and high tissue-penetration ability. Generally, ultrasound irradiation of sonosensitizers produces separated electrons (e-) and holes (h+), which inhibits cancer by producing reactive oxygen species (ROS). However, the separated electrons (e-) and holes (h+) could easily recombine, lowering the yield of ROS and hindering the application of sonodynamic therapy (SDT). Herein, we present a highly efficient sonosensitizer system for enhanced sonodynamic therapy built on reduced graphene oxide (rGO) nanosheets, bridged ZnO and Au nanoparticles, coated with polyvinyl pyrrolidone (PVP). The ultrasound irradiation activates ZnO nanoparticles to generate separated electron-hole (e--h+) pairs, and the rGO nanosheets facilitate electron transfer from ZnO to Au nanoparticles because of the narrow band gap of rGO, which could efficiently restrain the recombination of the e--h+ pairs, thereby significantly augmenting the production of ROS to kill cancer cells, such as U373MG, HeLa, and CT26 cells. Moreover, rGO nanosheets integrated with Au nanoparticles could catalyze the endogenous decomposition of H2O2 into O2, which can alleviate hypoxic tumor microenvironment (TME). Therefore, the rational design of Au-rGO-ZnO@PVP nanomaterials can not only improve the efficiency of sonodynamic therapy, but also mitigate the hypoxic tumor microenvironment, which would provide a new perspective in the development of efficient sonosensitizers. Electronic Supplementary Material: Supplementary material (the UV-vis-NIR absorption spectra of the DPBF and the RhB, biological effect assessment of the Au-rGO-ZnO@PVP, and the inhibition rate of tumor under different treatments during the animal study) is available in the online version of this article at 10.1007/s12274-022-4599-5.

Tumor Microenvironment Triggered the In Situ Synthesis of an Excellent Sonosensitizer in Tumor for Sonodynamic Therapy.

An ultrasound-triggered sonodynamic therapy has shown great promise for cancer therapy. However, its clinical applications are very limited because the traditional sonosensitizers tend to suffer from very poor efficiency combined with low retention in cancer cells and low tumor selectivity. Therefore, sonosensitizers with higher effectivity, higher tumor cell retention, and higher tumor cell specificity are highly required. Herein, we constructed a Ti2C(OH)X nanosheet, which was a poor sonosensitizer but had a long circulation in the blood system. However, it was very interesting to find that the tumor microenvironment could in situ turn Ti2C(OH)X nanosheet into a novel and excellent sonosensitizer with a nanofiber structure in tumors, exhibiting excellent ability to generate reactive oxygen species (ROS) under ultrasound. Moreover, the nanofiber structure made it very difficult to get out of cancer cells, highly enhancing the retention of the sonosensitizer in the tumor, thereby enabling it to effectively and selectively kill cancer cells in vivo. Our findings demonstrate that the strategy of the tumor microenvironment triggering the in situ synthesis of an effective sonosensitizer in tumor provided a promising means to simultaneously increase the efficiency, sonosensitizer retention in cancer cells, and cancer selectivity, thereby effectively killing cancer cells but causing little damage to healthy tissues via the sonodynamic therapy.

Synthesis of Poly(thioester sulfonamide)s via the Ring-Opening Copolymerization of Cyclic Thioanhydride with N-Sulfonyl Aziridine Using Mild Phosphazene Base.

Providing access to diverse polymer structures is highly desirable, which helps to explore new polymer materials. Poly(thioester sulfonamide)s, combining both the advantages of thioesters and amides, however, are rarely available in polymer chemistry. Here, the ring-opening copolymerization (ROCOP) of cyclic thioanhydride with N-sulfonyl aziridine using mild phosphazene base, resulting in well-defined poly(thioester sulfonamide)s with highly alternative structures, high yields, and controlled molecular weights, is reported. Additionally, benefiting from the mild catalytic process, this ROCOP can be combined with ROCOP of N-sulfonyl aziridines with cyclic anhydrides to produce novel block copolymers.

Simultaneous nanocatalytic surface activation of pollutants and oxidants for highly efficient water decontamination.

Removal of organic micropollutants from water through advanced oxidation processes (AOPs) is hampered by the excessive input of energy and/or chemicals as well as the large amounts of residuals resulting from incomplete mineralization. Herein, we report a new water purification paradigm, the direct oxidative transfer process (DOTP), which enables complete, highly efficient decontamination at very low dosage of oxidants. DOTP differs fundamentally from AOPs and adsorption in its pollutant removal behavior and mechanisms. In DOTP, the nanocatalyst can interact with persulfate to activate the pollutants by lowering their reductive potential energy, which triggers a non-decomposing oxidative transfer of pollutants from the bulk solution to the nanocatalyst surface. By leveraging the activation, stabilization, and accumulation functions of the heterogeneous catalyst, the DOTP can occur spontaneously on the nanocatalyst surface to enable complete removal of pollutants. The process is found to occur for diverse pollutants, oxidants, and nanocatalysts, including various low-cost catalysts. Significantly, DOTP requires no external energy input, has low oxidant consumption, produces no residual byproducts, and performs robustly in real environmental matrices. These favorable features render DOTP an extremely promising nanotechnology platform for water purification.

Cyclic topology enhances the killing activity of polycations against planktonic and biofilm bacteria.

Bacterial biofilms, as a fortress to protect bacteria, enhance resistance to antibiotics because of their limited penetration, which has become a major threat to current anti-infective therapy. Antimicrobial polycations have received wide attention to kill planktonic bacteria because of their unique antimicrobial mechanism without drug resistance but it is still hard to kill the bacteria in the deep of the biofilm. Unlike linear polymers, the cyclic topology has been demonstrated with enhanced penetration in tissues, which is attributed to the lack of end groups, constrained conformation and a smaller hydrodynamic volume, opening a new sight of polycations in the antibacterial application against biofilms. Here, polycations with different topologies including linear and cyclic polycations were synthesized and their killing activity against planktonic and biofilm bacteria was studied. The experimental results showed the enhanced antibacterial activity of cyclic polycations for planktonic bacteria, which is presumably attributed to their smaller hydrodynamic volume, higher local density of positive charge and more interactions between cation units and the bacterial membrane than their linear analogues. Besides, cyclic polycations exhibit enhanced killing effect for biofilm bacteria and inhibition effect for biofilms with 5-7 times and 2-3 times enhancements than the linear polycations, respectively. Furthermore, an Escherichia coli infection model on mice was established and the therapeutic effects of cyclic and linear polycations were evaluated. Compared with the linear polycations, the cyclic polycations exhibited enhanced antibacterial activity with an ∼4 times increase, promoting the healing of the infected wounds. This work provides a new perspective in the development of antimicrobial polycations, which are promising therapeutic agents to kill planktonic and biofilm bacteria without drug resistance.