Carbonization of quercetin into nanogels: a leap in anticoagulant development.

Quercetin, a flavonoid abundantly found in onions, fruits, and vegetables, is recognized for its pharmacological potential, especially for its anticoagulant properties that work by inhibiting thrombin and coagulation factor Xa. However, its clinical application is limited due to poor water solubility and bioavailability. To address these limitations, we engineered carbonized nanogels derived from quercetin (CNGsQur) using controlled pyrolysis and polymerization techniques. This led to substantial improvements in its anticoagulation efficacy, water solubility, and biocompatibility. We generated a range of CNGsQur by subjecting quercetin to varying pyrolytic temperatures and then assessed their anticoagulation capacities both in vitro and in vivo. Coagulation metrics, including thrombin clotting time (TCT), activated partial thromboplastin time (aPTT), and prothrombin time (PT), along with a rat tail bleeding assay, were utilized to gauge the efficacy. CNGsQur showed a pronounced extension of coagulation time compared to uncarbonized quercetin. Specifically, CNGsQur synthesized at 270 °C (CNGsQur270) exhibited the most significant enhancement in TCT, with a binding affinity to thrombin exceeding 400 times that of quercetin. Moreover, variants synthesized at 310 °C (CNGsQur310) and 290 °C (CNGsQur290) showed the most substantial delays in PT and aPTT, respectively. Our findings indicate that the degree of carbonization significantly influences the transformation of quercetin into various CNGsQur forms, each affecting distinct coagulation pathways. Additionally, both intravenous and oral administrations of CNGsQur were found to extend rat tail bleeding times by up to fivefold. Our studies also demonstrate that CNGsQur270 effectively delays and even prevents FeCl3-induced vascular occlusion in a dose-dependent manner in mice. Thus, controlled pyrolysis offers an innovative approach for generating quercetin-derived CNGs with enhanced anticoagulation properties and water solubility, revealing the potential for synthesizing self-functional carbonized nanomaterials from other flavonoids for diverse biomedical applications.

Augmenting Neutrophil Extracellular Traps with Carbonized Polymer Dots: A Potential Treatment for Bacterial Sepsis.

Sepsis is a life-threatening condition that can progress to septic shock as the body's extreme response to pathogenesis damages its own vital organs. Staphylococcus aureus (S. aureus) accounts for 50% of nosocomial infections, which are clinically treated with antibiotics. However, methicillin-resistant strains (MRSA) have emerged and can withstand harsh antibiotic treatment. To address this problem, curcumin (CCM) is employed to prepare carbonized polymer dots (CPDs) through mild pyrolysis. Contrary to curcumin, the as-formed CCM-CPDs are highly biocompatible and soluble in aqueous solution. Most importantly, the CCM-CPDs induce the release of neutrophil extracellular traps (NETs) from the neutrophils, which entrap and eliminate microbes. In an MRSA-induced septic mouse model, it is observed that CCM-CPDs efficiently suppress bacterial colonization. Moreover, the intrinsic antioxidative, anti-inflammatory, and anticoagulation activities resulting from the preserved functional groups of the precursor molecule on the CCM-CPDs prevent progression to severe sepsis. As a result, infected mice treated with CCM-CPDs show a significant decrease in mortality even through oral administration. Histological staining indicates negligible organ damage in the MRSA-infected mice treated with CCM-CPDs. It is believed that the in vivo studies presented herein demonstrate that multifunctional therapeutic CPDs hold great potential against life-threatening infectious diseases.

Ultrahigh-Efficacy VEGF Neutralization Using Carbonized Nanodonuts: Implications for Intraocular Anti-Angiogenic Therapy.

Ocular angiogenesis, associated with diseases such as retinopathy of prematurity and diabetic retinopathy, is a leading cause of irreversible vision loss. Herein, carbon nanodonuts (CNDs) with a donut-shaped structure are synthesized using sodium alginate (SA) and 1,8-diaminooctane (DAO) through a one-step thermal process. The formation of SA/DAO-CNDs occurs through a crosslinking reaction between SA and DAO, creating amide bonds followed by partial carbonization. In human retinal pigment epithelial cells exposed to H2 O2 or lipopolysaccharide, the SA/DAO-CNDs display a more than fivefold reduction in reactive oxygen species and proinflammatory cytokines, such as IL-6 and IL-1ß, when compared to carbonized nanomaterials produced exclusively from SA. Furthermore, the CNDs effectively inhibit vascular endothelial growth factor A-165 (VEGF-A165 )-induced cell migration and tube formation in human umbilical vein endothelial cells due to their strong affinity for VEGF-A165 , with a dissociation constant of 2.2 × 10-14  M, over 1600 times stronger than the commercial drug bevacizumab (Avastin). Trypsin digestion coupled with LC-MS/MS analysis reveals that VEGF-A165 interacts with SA/DAO-CNDs through its heparin-binding domain, leading to activity loss. The SA/DAO-CNDs demonstrate excellent biocompatibility and potent anti-angiogenic effects in chicken embryos and rabbit eyes. These findings suggest that SA/DAO-CNDs hold promise as a therapeutic agent for treating various angiogenesis-related ocular diseases.

NIR-activated quercetin-based nanogels embedded with CuS nanoclusters for the treatment of drug-resistant biofilms and accelerated chronic wound healing.

We have developed multifunctional nanogels with antimicrobial, antioxidant, and anti-inflammatory properties, facilitating rapid wound healing. To prepare the multifunctional nanogels, we utilized quercetin (Qu) and a mild carbonization process to form carbonized nanogels (CNGs). These CNGs possess excellent antioxidative and bacterial targeting properties. Subsequently, we utilized the Qu-CNGs as templates to prepare nanogels incorporating copper sulfide (CuS) nanoclusters, further enhancing their functionality. Notably, the CuS/Qu-CNGs nanocomposites demonstrated an exceptional minimum inhibitory concentration against tested bacteria, approximately 125-fold lower than monomeric Qu or Qu-CNGs. This enhanced antimicrobial effect was achieved by leveraging near-infrared II (NIR-II) light irradiation. Additionally, the CuS/Qu-CNGs exhibited efficient penetration into the extracellular biofilm matrix, eradicating methicillin-resistant Staphylococcus aureus-associated biofilms in diabetic mice wounds. Furthermore, the nanocomposites were found to suppress proinflammatory cytokines, such as IL-1ß, at the wound sites while regulating the expression of anti-inflammatory factors, including IL-10 and TGF-ß1, throughout the recovery process. The presence of CuS/Qu-CNGs promoted angiogenesis, epithelialization, and collagen synthesis, thereby accelerating wound healing. Our developed CuS/Qu-CNGs nanocomposites have great potential in addressing the challenges associated with delayed wound healing caused by microbial pathogenesis.

Synthesis of Fluorescent C-C Bonded Triazole-Purine Conjugates.

A design toward C-C bonded 2,6-bis(1H-1,2,3-triazol-4-yl)-9H-purine and 2-piperidinyl-6-(1H-1,2,3-triazol-4-yl)-9H-purine derivatives was established using the combination of Mitsunobu, Sonogashira, copper (I) catalyzed azide-alkyne cycloaddition, and SNAr reactions. 11 examples of 2,6-bistriazolylpurine and 14 examples of 2-piperidinyl-6-triazolylpurine intermediates were obtained, in 38-86% and 41-89% yields, respectively. Obtained triazole-purine conjugates expressed good fluorescent properties which were studied in the solution and in the thin layer film for the first time. Quantum yields reached up to 49% in DMSO for bistriazolylpurines and up to 81% in DCM and up to 95% in DMSO for monotriazolylpurines. Performed biological studies in mouse embryo fibroblast, human keratinocyte, and transgenic adenocarcinoma of the mouse prostate cell lines showed that most of obtained triazole-purine conjugates are not cytotoxic. The 50% cytotoxic concentration of the tested derivatives was in the range from 59.6 to 1528.7 µM.

In Situ Hybridization of Polymeric Curcumin to Arginine-Derived Carbon Quantum Dots for Synergistic Treatment of Bacterial Infections.

Effective infectious keratitis treatment must eliminate the pathogen, reduce the inflammatory response, and prevent persistent damage to the cornea. Infectious keratitis is generally treated with broad-spectrum antibiotics; however, they have the risk of causing corneal epithelial cell damage and drug resistance. In this study, we prepared a nanocomposite (Arg-CQDs/pCur) from arginine (Arg)-derived carbon quantum dots (Arg-CQDs) and polymeric curcumin (pCur). Partial carbonization of arginine hydrochloride in the solid state by mild pyrolysis resulted in the formation of CQDs, which exhibited enhanced antibacterial activity. pCur was formed by the polymerization of curcumin, and further crosslinking reduced its cytotoxicity and improved antioxidative, anti-inflammatory, and pro-proliferative activities. The pCur in situ conjugated with Arg-CQDs to form the Arg-CQDs/pCur nanocomposite, which showed a minimum inhibitory concentration of ca. 10 µg mL-1, which was >100-fold and >15-fold lower than that of the precursor arginine and curcumin, respectively, against Staphylococcus aureus, Escherichia coli, and Pseudomonas aeruginosa. The Arg-CQDs/pCur nanocomposite with combined antibacterial, antioxidative, anti-inflammatory, pro-proliferative properties, and long-term retention on cornea enabled synergistic treatment of bacterial keratitis. In a rat model, it can effectively treat P. aeruginosa-induced bacterial keratitis at a concentration 4000-fold lower than the commercially used drug, Sulmezole eye drops. Arg-CQDs/pCur nanocomposites have great potential for application in antibacterial and anti-inflammatory nanoformulations for clinical use to treat infectious diseases.

Synthesis of novel Type-II MnNb2O6/g-C3N4 Mott-Schottky heterojunction photocatalyst: Excellent photocatalytic performance and degradation mechanism of fluoroquinolone-based antibiotics.

Fluoroquinolone antibiotics have been encountered in aquatic environments in quantities giving rise to significant concern recently. To cope with this problem, it is necessary to design a semiconductor photocatalyst having excellent photocatalytic efficiency to eliminate the antibiotics. The heterojunction is a likely situate where the efficiency of relevant photocatalyst can be strengthened. In this study, the performance of MnNb2O6/g-C3N4 (MNO/g-CN) composites in the photocatalytic degradation of ciprofloxacin (CIP) and tetracycline-HCl (TCH) antibiotics was explored. Enhanced photocatalytic activity of MNO/g-CN was found to be owing to electron's shifting between the MNO, and g-CN sheets, which promotes the formation of photo-generated e⁻/h⁺ pairs. This shows a low-waste, high-performance material exists to eradicate CIP and TCH from wastewater. Further, the structural, photochemical and light interacted properties of the MNO/g-CN photocatalyst, prepared by solvothermal method and sonication, were described using photochemical, physiochemical and electrochemical approaches. The synthesized photocatalyst owes its particular efficiency to its methodical photo-degradation of CIP and TC using visible light. The optimum composite 15% MNO/g-CN evinced the greatest photocatalytic efficiency with CIP and TCH photo-degradation of 94.10%, and 98.50%, respectively, and degradation mechanism were investigated using LC-MS spectroscopy. The suitable photocatalytic activity is ascribed to lower the recombination's rate of e⁻/h⁺ pairs. The scavenging evaluations proved that the h+ and •O2- were two major photoactive species accomplishing the CIP and TCH photodegradation over MNO/g-CN under visible region. Our findings pave the way for the construction of efficient binary photocatalysts for antibiotic restitution.

Dual-emissive carbonized polymer dots for the ratiometric fluorescence imaging of singlet oxygen in living cells.

Singlet oxygen (1O2) is a type of reactive oxygen species (ROS), playing a vital role in the physiological and pathophysiological processes. Specific probes for monitoring intracellular 1O2 still remain challenging. In this study, we develop a ratiometric fluorescent probe for the real-time intracellular detection of 1O2 using o-phenylenediamine-derived carbonized polymer dots (o-PD CPDs). The o-PD CPDs possessing dual-excitation-emission properties (blue and yellow fluorescence) were successfully synthesized in a two-phase system (water/acetonitrile) using an ionic liquid tetrabutylammonium hexafluorophosphate as a supporting electrolyte through the electrolysis of o-PD. The o-PD CPDs can act as a photosensitizer to produce 1O2 upon white LED irradiation, in turn, the generated 1O2 selectively quenches the yellow emission of the o-PD CPDs. This quenching behavior is ascribed to the specific cycloaddition reaction between 1O2 and alkene groups in the polymer scaffolds on o-PD CPDs. The interior carbon core can be a reliable internal standard since its blue fluorescence intensity remains unchanged in the presence of 1O2. The ratiometric response of o-PD CPDs is selective toward 1O2 against other ROS species. The developed o-PD CPDs have been successfully applied to monitor the 1O2 level in the intracellular environment. Furthermore, in the inflammatory neutrophil cell model, o-PD CPDs can also detect the 1O2 and other ROS species such as hypochlorous acid after phorbol 12-myristate 13-acetate (PMA)-induced inflammation. Through the dual-channel fluorescence imaging, the ratiometric response of o-PD CPDs shows great potential for detecting endogenous and stimulating 1O2in vivo.

Photoswitchable carbon-dot liposomes mediate catalytic cascade reactions for amplified dynamic treatment of tumor cells.

Most biochemical reactions that occur in living organisms are catalyzed by a series of enzymes and proceed in a tightly controlled manner. The development of artificial enzyme cascades that resemble multienzyme complexes in nature is of current interest due to their potential in various applications. In this study, a nanozyme based on photoswitchable carbon-dot liposomes (CDsomes) was developed for use in programmable catalytic cascade reactions. These CDsomes prepared from triolein are amphiphilic and self-assemble into liposome-like structures in an aqueous environment. CDsomes feature excitation-dependent photoluminescence and, notably, can undergo reversible switching between a fluorescent on-state and nonfluorescent off-state under different wavelengths of light irradiation. This switching ability enables the CDsomes to exert photocatalytic oxidase- and peroxidase-like activities in their on- (bright) and off- (dark) states, respectively, resulting in the conversion of oxygen molecules into hydrogen peroxide (H2O2), followed by the generation of active hydroxyl radicals (OH). The two steps of oxygen activation can be precisely controlled in a sequential manner by photoirradiation at different wavelengths. Catalytic reversibility also enables the CDsomes to produce sufficient reactive oxygen species (ROS) to effectively kill tumor cells. Our results reveal that CDsomes is a promising photo-cycling nanozyme for precise tumor phototherapy through regulated programmable cascade reactions.

Pulsed laser irradiation induces the generation of alloy cluster ions for the screening of protease activity.

Pulsed laser irradiation can cause the fragmentation of nanoparticles, which generates cluster ions. This allows nanoparticles to be adopted as mass tag/signal amplifiers in laser desorption/ionization mass spectrometry (LDI-MS) bioassays. Herein, we demonstrate the potential of using the signal from alloy cluster ions in bioassays through a fibrin clot model to determine the activity of thrombin. A mixed solution of silver and gold nanoparticles functionalized with fibrinogen (Fg‒Ag NPs/Fg‒Au NPs) treated with thrombin can form clots composed of aggregated fibrin-Au NPs/Ag NPs. These clots analyzed with LDI-MS are noted to form intense Ag-Au alloy cluster ions, especially [Ag2Au]+, which were used to detect thrombin concentration with a dynamic range of 2.5-50 pM in human plasma. This sensing platform was further employed for the screening of direct thrombin inhibitors. This work developed a novel bioassay utilizing metallic gas-phase reactions generated from pulsed laser irradiation of aggregated nanoparticles to monitor enzymatic activity and to screen inhibitors. We believe that LDS-MS can serve as a new platform for gas-phase reaction-based bioassays.

Synthesis and in situ sulfidation of molybdenum carbide MXene using fluorine-free etchant for electrocatalytic hydrogen evolution reactions.

Synthesizing MXenes from Mn+1AXn (MAX) phases using hazardous hydrogen fluoride is a common and effective method. However, fluorine termination on the basal planes and edges of the resulting MXenes is undesirable for the electrocatalytic hydrogen evolution reaction (HER), while oxygen (O), hydroxyl (OH), and sulfur (S) termination favors this reaction. Herein, we unveil a simple fluorine-free exfoliation and two-step vulcanization method for synthesizing molybdenum sulfide-modified molybdenum carbide (MoS2/Mo2CTx MXene, T = OH, O, S) for the HER in alkaline medium. Microwave-assisted hydrothermal treatment of the MAX phase (Mo3AlC2) with sodium hydroxide-sodium sulfide as an etching solution and thioacetamide as a source of sulfide ions enabled the selective dissolution of the aluminum (Al) layer and sulfidation of the surface Mo atoms to form amorphous MoS2. Thus, the vulcanization of Mo2CTx MXene resulted in the formation of MoS2/Mo2CTx MXene. The MoS2 formed on the surface of Mo2CTx provided enhanced stability by preventing oxidation. MoS2/Mo2CTx exhibited enhanced electrocatalytic activity toward the HER, mainly due to the O, OH, and amorphous MoS2 functionalities. The MoS2 sites on the surface exhibited an overpotential of 110 ± 7 mV at a current density of 10 mA cm-2 as a result of enhanced charge transfer and mass transfer. Thus, the sulfidation method demonstrated herein is capable of producing amorphous MoS2 structures on Mo2CTx MXene, which could be applied for the surface modification of other molybdenum-based nanomaterials or electrocatalysts to improve stability and enhance electrocatalytic activity.

Recent progress in nanomaterial-functionalized membranes for removal of pollutants.

Membrane technology has gained tremendous attention for removing pollutants from wastewater, mainly due to their affordable capital cost, miniature equipment size, low energy consumption, and high efficiency even for the pollutants present in lower concentrations. In this paper, we review the literature to summarize the progress of nanomaterial-modified membranes for wastewater treatment applications. Introduction of nanomaterial in the polymeric matrix influences membrane properties such as surface roughness, hydrophobicity, porosity, and fouling resistance. This review also covers the importance of functionalization strategies to prepare thin-film nanocomposite hybrid membranes and their effect on eliminating pollutants. Systematic discussion regarding the impact of the nanomaterials incorporated within membrane, toward the recovery of various pollutants such as metal ions, organic compounds, dyes, and microbes. Successful examples are provided to show the potential of nanomaterial-functionalized membranes for regeneration of wastewater. In the end, future prospects are discussed to develop nanomaterial-based membrane technology.

Self-redox reaction driven in situ formation of Cu2O/Ti3C2Tx nanosheets boost the photocatalytic eradication of multi-drug resistant bacteria from infected wound.

BACKGROUND: MXenes with interesting optical and electrical properties have been attractive in biomedical applications such as antibacterial and anticancer agents, but their low photogeneration efficiency of reactive oxygen species (ROS) and poor stability are major concerns against microbial resistance. METHODS: Water-dispersible single layer Ti3C2Tx-based MXene through etching tightly stacked MAX phase precursor using a minimally intensive layer delamination method. After addition of Cu(II) ions, the adsorbed Cu(II) ions underwent self-redox reactions with the surface oxygenated moieties of MXene, leading to in situ formation of Cu2O species to yield Cu2O/Ti3C2Tx nanosheets (heterostructures). RESULTS: Under NIR irradiation, the Cu2O enhanced generation of electron-hole pairs, which boosted the photocatalytic production of superoxide and subsequent transformation into hydrogen peroxide. Broad-spectrum antimicrobial performance of Cu2O/Ti3C2Tx nanosheets with sharp edges is attributed to the direct contact-induced membrane disruption, localized photothermal therapy, and in situ generated cytotoxic free radicals. The minimum inhibitory concentration of Cu2O/Ti3C2Tx nanosheets reduced at least tenfold upon NIR laser irradiation compared to pristine Cu2O/Ti3C2Tx nanosheets. The Cu2O/Ti3C2Tx nanosheets were topically administrated on the methicillin-resistant Staphylococcus aureus (MRSA) infected wounds on diabetic mice. CONCLUSION: Upon NIR illumination, Cu2O/Ti3C2Tx nanosheets eradicated MRSA and their associated biofilm to promote wound healing. The Cu2O/Ti3C2Tx nanosheets with superior catalytic and photothermal properties have a great scope as an effective antimicrobial modality for the treatment of infected wounds.

Evaluation of chemotherapeutic response in living cells using subcellular Organelle‒Selective amphipathic carbon dots.

Monitoring of structural changes in subcellular organelles is critical to evaluate the chemotherapeutic response of cells. However, commercial organelle selective fluorophores are easily photobleached, and thus are unsuitable for real-time and long-term observation. We have developed photostable carbon-dot liposomes (CDsomes)-based fluorophores for organellar and suborganellar imaging to circumvent these issues. The CDs synthesized through a mild pyrolysis/hydrolysis process exhibit amphipathic nature and underwent self-assembly to form liposome-like structures (CDsomes). The controlled hydrophilicity or hydrophobicity-guided preparation of CDsomes are used to selectively and rapidly (<1 min) stain nucleolus, cytoplasm, and membrane. In addition, the CDsomes offer universal high-contrast staining not only in fixed cells but also in living cells, allowing real-time observation and morphological identification in the specimen. The as-prepared CDsomes exhibit excitation-dependent fluorescence, and are much more stable under photoirradiation (e.g., ultraviolet light) than traditional subcellular dyes. Interestingly, the CDsomes can be transferred to daughter cells by diluting the particles, enabling multigenerational tracking of suborganelle for up to six generations, without interrupting the staining pattern. Therefore, we believe that the ultra-photostable CDsomes with high biocompatibility, and long-term suborganellar imaging capabilities, hold a great potential for screening and evaluating therapeutic performance of various chemotherapeutic drugs.

Carbon dots with polarity-tunable characteristics for the selective detection of sodium copper chlorophyllin and copper ions.

Compared to water-soluble carbon dots (CDs) the properties and applications of hydrophobic CDs are rarely addressed. In this study, a one-pot, simple chemical oxidation approach has been applied to synthesize hydrophobic carbon dots (TO-CDs) at room temperature from triolein (TO) in concentrated sulfuric acid solution. Sodium copper chlorophyllin (SCC) quenches the fluorescence of TO-CDs by a photoinduced electron transfer process. Upon excitation at 400 nm, the fluorescence intensity of TO-CDs probe at 500 nm shows a linear response against the SCC concentration ranging from 1.0 to 10 µM, with a limit of detection (LOD) of 0.61 µM. Quantitation of SCC in flavored drinks shows percentage recovery (%R) vaues of 98-103% and relative standard deviation (RSD) values less than 6.5%. The hydrophobic TO-CDs can be converted into hydrophilic TO-CDs through hydrolysis in NaOH solution. The presence of sulfonyl groups on the hydrophilic TO-CDs enhances the coordination ability of the CDs toward Cu2+ ions, leading to fluorescence quenching which allows for the detection of Cu2+ ions with LOD of 0.21 µM and a linear range of 0.5-10 µM. The hydrophilic TO-CD probe possesses high selectivity toward Cu2+ ions (tolerance at least ten-fold comparative to other metal ions). The assay has been validated with the analysis of spiked soil samples, with %R values of Cu concentration of 97.8-99.0% and RSDs below 2.0%. The surface tunable CD probes demonstrate their potential for the rapid screening of Cu2+ ions in environmental samples and SCC in foods.

Multifunctional carbonized nanogels to treat lethal acute hepatopancreatic necrosis disease.

BACKGROUND: Shrimp aquaculture has suffered huge economic losses over the past decade due to the outbreak of acute hepatopancreatic necrosis disease (AHPND), which is mainly caused by the bacteria Vibrio parahaemolyticus (V. parahaemolyticus) with the virulence pVA1 plasmid, which encodes a secretory photorhabdus insect-related (Pir) toxin composed of PirA and PirB proteins. The Pir toxin mainly attacks the hepatopancreas, a major metabolic organ in shrimp, thereby causing necrosis and loss of function. The pandemic of antibiotic-resistant strains makes the impact worse. METHODS: Mild pyrolysis of a mixture of polysaccharide dextran 70 and the crosslinker 1,8-diaminooctane at 180 â„ƒ for 3 h to form carbonized nanogels (DAO/DEX-CNGs) through controlled cross-linking and carbonization. The multifunctional therapeutic CNGs inherit nanogel-like structures and functional groups from their precursor molecules. RESULTS: DAO/DEX-CNGs manifest broad-spectrum antibacterial activity against Vibrio parahaemolyticus responsible for AHPND and even multiple drug-resistant strains. The polymer-like structures and functional groups on graphitic-carbon within the CNGs exhibit multiple treatment effects, including disruption of bacterial membranes, elevating bacterial oxidative stress, and neutralization of PirAB toxins. The inhibition of Vibrio in the midgut of infected shrimp, protection of hepatopancreas tissue from Pir toxin, and suppressing overstimulation of the immune system in severe V. parahaemolyticus infection, revealing that CNGs can effectively guard shrimp from Vibrio invasion. Moreover, shrimps fed with DAO/DEX-CNGs were carefully examined, such as the expression of the immune-related genes, hepatopancreas biopsy, and intestinal microbiota. Few adverse effects on shrimps were observed. CONCLUSION: Our work proposes brand-new applications of multifunctional carbon-based nanomaterials as efficient anti-Vibrio agents in the aquatic industry that hold great potential as feed additives to reduce antibiotic overuse in aquaculture.

Catalytic and photoresponsive BiZ/CuxS heterojunctions with surface vacancies for the treatment of multidrug-resistant clinical biofilm-associated infections.

We report a one-pot facile synthesis of highly photoresponsive bovine serum albumin (BSA) templated bismuth-copper sulfide nanocomposites (BSA-BiZ/CuxS NCs, where BiZ represents in situ formed Bi2S3 and bismuth oxysulfides (BOS)). As-formed surface vacancies and BiZ/CuxS heterojunctions impart superior catalytic, photodynamic and photothermal properties. Upon near-infrared (NIR) irradiation, the BSA-BiZ/CuxS NCs exhibit broad-spectrum antibacterial activity, not only against standard multidrug-resistant (MDR) bacterial strains but also against clinically isolated MDR bacteria and their associated biofilms. The minimum inhibitory concentration of BSA-BiZ/CuxS NCs is 14-fold lower than that of BSA-CuxS NCs because their multiple heterojunctions and vacancies facilitated an amplified phototherapeutic response. As-prepared BSA-BiZ/CuxS NCs exhibited substantial biofilm inhibition (90%) and eradication (>75%) efficiency under NIR irradiation. Furthermore, MRSA-infected diabetic mice were immensely treated with BSA-BiZ/CuxS NCs coupled with NIR irradiation by destroying the mature biofilm on the wound site, which accelerated the wound healing process via collagen synthesis and epithelialization. We demonstrate that BSA-BiZ/CuxS NCs with superior antimicrobial activity and high biocompatibility hold great potential as an effective photosensitive agent for the treatment of biofilm-associated infections.

Electrocatalytic CuBr@CuO nanoparticles based salivary glucose probes.

Highly electrocatalytic cuprous halide/copper oxide nanoparticles (CuX@CunO NPs; X = Cl, Br or I; n = 1 or 2) have been fabricated on copper foils for sensitive detection of glucose. Formation of CuX@CunO NPs involves two steps- in situ electrochemical deposition of CuX on the foil and then conversion of CuX to CunO. The deposited CuX converts to CunO, leading to the generation of abundant oxygen vacancies in the CuO lattice, enhancing the number of catalytically active sites, and improving the charge transfer efficiency. Among the as-prepared electrodes, CuBr@CuO NP ones provide the highest electrocatalytic activity toward the oxidation of glucose. The electrode provides electrocatalytic activity toward the oxidation of glucose at a low overpotential of 0.25 V (vs. SCE), which is lower than that (0.40 V) of unmodified copper electrodes. The generated anodic current is proportional to glucose concentration in an alkaline medium, with a good linear range from 5.0 µM to 3.51 mM (R2 = 0.995). Its reliability has been validated by detecting the glucose concentration in saliva samples at different time intervals after a meal. The results are in good correlation with the blood glucose level determined by using a commercial blood glucose meter. Our CuBr@CuO NP electrode possesses great potential for monitoring salivary glucose to achieve the purpose of noninvasive glucose monitoring for patients with diabetes in the future.

Silver oxide model surface improves computational simulation of surface-enhanced Raman spectroscopy on silver nanoparticles.

Surface-enhanced Raman spectroscopy (SERS) coupled with density functional theory (DFT) computations can characterise the adsorption orientation of a molecule on a nanoparticle surface. When using DFT to simulate SERS on a silver surface, one typically employs an atom (Ag), ion (Ag+), or cluster (Agx or Agx+) as the model surface. Here, by examining the nucleobase 2,6-diaminopurine (2,6-DAP) and then generalising our strategy to three other molecules, we show that employing silver oxide (Ag2O) as the model surface can quantitatively improve the accuracy of simulated SERS.

CD28 engagement inhibits CD73-mediated regulatory activity of CD8+ T cells.

CD28 is required for T cell activation as well as the generation of CD4+Foxp3+ Treg. It is unclear, however, how CD28 costimulation affects the development of CD8+ T cell suppressive function. Here, by use of Hepa1.6.gp33 in vitro killing assay and B16.gp33 tumor mouse model we demonstrate that CD28 engagement during TCR ligation prevents CD8+ T cells from becoming suppressive. Interestingly, our results showed that ectonucleotidase CD73 expression on CD8+ T cells is upregulated in the absence of CD28 costimulation. In both murine and human tumor-bearing hosts, CD73 is upregulated on CD28-CD8+ T cells that infiltrate the solid tumor. UPLC-MS/MS analysis revealed that CD8+ T cells activation without CD28 costimulation produces elevated levels of adenosine and that CD73 mediates its production. Adenosine receptor antagonists block CD73-mediated suppression. Our data support the notion that CD28 costimulation inhibits CD73 upregulation and thereby prevents CD8+ T cells from becoming suppressive. This study uncovers a previously unidentified role for CD28 costimulation in CD8+ T cell activation and suggests that the CD28 costimulatory pathway can be a potential target for cancer immunotherapy.