In situ spectroelectrochemical probing of CO redox landscape on copper single-crystal surfaces.

Electrochemical reduction of CO(2) to value-added chemicals and fuels is a promising strategy to sustain pressing renewable energy demands and to address climate change issues. Direct observation of reaction intermediates during the CO(2) reduction reaction will contribute to mechanistic understandings and thus promote the design of catalysts with the desired activity, selectivity, and stability. Herein, we combined in situ electrochemical shell-isolated nanoparticle-enhanced Raman spectroscopy and ab initio molecular dynamics calculations to investigate the CORR process on Cu single-crystal surfaces in various electrolytes. Competing redox pathways and coexistent intermediates of CO adsorption (*COatop and *CObridge), dimerization (protonated dimer *HOCCOH and its dehydrated *CCO), oxidation (*CO2- and *CO32-), and hydrogenation (*CHO), as well as Cu-Oad/Cu-OHad species at Cu-electrolyte interfaces, were simultaneously identified using in situ spectroscopy and further confirmed with isotope-labeling experiments. With AIMD simulations, we report accurate vibrational frequency assignments of these intermediates based on the calculated vibrational density of states and reveal the corresponding species in the electrochemical CO redox landscape on Cu surfaces. Our findings provide direct insights into key intermediates during the CO(2)RR and offer a full-spectroscopic tool (40-4,000 cm-1) for future mechanistic studies.

Biophilic Positive Carbon Dot Exerts Antifungal Activity and Augments Corneal Permeation for Fungal Keratitis.

Fungal keratitis (FK) is an infectious eye disease that poses a significant risk of blindness. However, the effectiveness of conventional antifungal drugs is limited due to the intrinsic ocular barrier that impedes drug absorption. There is an urgent need to develop new therapeutic strategies to effectively combat FK. Herein, we synthesized an ultrasmall positively charged carbon dot using a simple stage-melting method. The carbon dot can penetrate the corneal barrier by opening the tight junctions, allowing them to reach the lesion site and effectively kill the fungi. The results both in vitro and in vivo demonstrated that it exhibited good biocompatibility and antifungal activity, significantly improving the therapeutic effect in a mouse model of FK. Therefore, this biophilic ultrasmall size and positive carbon dot, characterized by its ability to penetrate the corneal barrier and its antifungal properties, may offer valuable insights into the design of effective ocular nanomedicines.

Diffusional Electron Transport Coupled to Thermodynamically Driven Electron Transfers in Redox-Conductive Multivariate Metal-Organic Frameworks.

The development of redox-conductive metal-organic frameworks (MOFs) and the fundamental understanding of charge propagation through these materials are central to their applications in energy storage, electronics, and catalysis. To answer some unresolved questions about diffusional electron hopping transport and redox conductivity, mixed-linker MOFs were constructed from two statistically distributed redox-active linkers, pyromellitic diimide bis-pyrazolate (PMDI) and naphthalene diimide bis-pyrazolate (NDI), and grown as crystalline thin films on conductive fluorine-doped tin oxide (FTO). Owing to the distinct redox properties of the linkers, four well-separated and reversible redox events are resolved by cyclic voltammetry, and the mixed-linker MOFs can exist in five discrete redox states. Each state is characterized by a unique spectroscopic signature, and the interconversions between the states can be followed spectroscopically under operando conditions. With the help of pulsed step-potential spectrochronoamperometry, two modes of electron propagation through the mixed-linker MOF are identified: diffusional electron hopping transport between linkers of the same type and a second channel that arises from thermodynamically driven electron transfers between linkers of different types. Corresponding to the four redox events of the mixed-linker MOFs, four distinct bell-shaped redox conductivity profiles are observed at a steady state. The magnitude of the maximum redox conductivity is evidenced to be dependent on the distance between redox hopping sites, analogous to the situation for apparent electron diffusion coefficients, Deapp, that are obtained in transient experiments. The design of mixed-linker redox-conductive MOFs and detailed studies of their charge transport properties present new opportunities for future applications of MOFs, in particular, within electrocatalysis.

ROS-responsive celastrol-nanomedicine alleviates inflammation for dry eye disease.

Dry eye disease (DED) is a major global eye disease leading to severe eye discomfort and even vision impairment. The incidence of DED has been gradually increasing with the high frequency of use of electronic devices. It has been demonstrated that celastrol (Cel) has excellent therapeutic efficacy in ocular disorders. However, the poor water solubility and short half-life of Cel limit its further therapeutic applications. In this work, a reactive oxygen species (ROS) sensitive polymeric micelle was fabricated for Cel delivery. The micelles improve the solubility of Cel, and the resulting Cel loaded micelles exhibit an enhanced intervention effect for DED. Thein vitroresults demonstrated that Cel-nanomedicine had a marked ROS responsive release behavior. The results ofin vitroandin vivoexperiments demonstrated that Cel has excellent biological activities to alleviate inflammation in DED by inhibiting TLR4 signaling activation and reducing pro-inflammatory cytokine expression. Therefore, the Cel nanomedicine can effectively eliminate ocular inflammation, promote corneal epithelial repair, and restore the number of goblet cells and tear secretion, providing a new option for the treatment of DED.

Dual-ROS-scavenging and dual-lingering nanozyme-based eye drops alleviate dry eye disease.

Efficiently removing excess reactive oxygen species (ROS) generated by various factors on the ocular surface is a promising strategy for preventing the development of dry eye disease (DED). The currently available eye drops for DED treatment are palliative, short-lived and frequently administered due to the short precorneal residence time. Here, we developed nanozyme-based eye drops for DED by exploiting borate-mediated dynamic covalent complexation between n-FeZIF-8 nanozymes (n-Z(Fe)) and poly(vinyl alcohol) (PVA) to overcome these problems. The resultant formulation (PBnZ), which has dual-ROS scavenging abilities and prolonged corneal retention can effectively reduce oxidative stress, thereby providing an excellent preventive effect to alleviate DED. In vitro and in vivo experiments revealed that PBnZ could eliminate excess ROS through both its multienzyme-like activity and the ROS-scavenging activity of borate bonds. The positively charged nanozyme-based eye drops displayed a longer precorneal residence time due to physical adhesion and the dynamic borate bonds between phenyboronic acid and PVA or o-diol with mucin. The in vivo results showed that eye drops could effectively alleviate DED. These dual-function PBnZ nanozyme-based eye drops can provide insights into the development of novel treatment strategies for DED and other ROS-mediated inflammatory diseases and a rationale for the application of nanomaterials in clinical settings.

Pantoprazole suppresses carcinogenesis and growth of hepatocellular carcinoma by inhibiting glycolysis and Na+/H+ exchange.

Hepatocellular carcinoma (HCC) is one of the deadliest cancers. The prevention and therapy for this deadly disease remain a global medical challenge. In this study, we investigated the effect of pantoprazole (PPZ) on the carcinogenesis and growth of HCC. Both diethylnitrosamine (DEN) plus CCl4-induced and DEN plus high fat diet (HFD)-induced HCC models in mice were established. Cytokines and cell proliferation-associated gene in the liver tissues of mice and HCC cells were analyzed. Cellular glycolysis and Na+/H+ exchange activity were measured. The preventive administration of pantoprazole (PPZ) at a clinically relevant low dose markedly suppressed HCC carcinogenesis in both DEN plus CCl4-induced and HFD-induced murine HCC models, whereas the therapeutic administration of PPZ at the dose suppressed the growth of HCC. In the liver tissues of PPZ-treated mice, inflammatory cytokines, IL1, CXCL1, CXCL5, CXCL9, CXCL10, CCL2, CCL5, CCL6, CCL7, CCL20, and CCL22, were reduced. The administration of CXCL1, CXCL5, CCL2, or CCL20 all reversed PPZ-suppressed DEN plus CCL4-induced HCC carcinogenesis in mice. PPZ inhibited the expressions of CCNA2, CCNB2, CCNE2, CDC25C, CDCA5, CDK1, CDK2, TOP2A, TTK, AURKA, and BIRC5 in HCC cells. Further results showed that PPZ reduced the production of these inflammatory cytokines and the expression of these cell proliferation-associated genes through the inhibition of glycolysis and Na+/H+ exchange. In conclusion, PPZ suppresses the carcinogenesis and growth of HCC, which is related to inhibiting the production of inflammatory cytokines and the expression of cell proliferation-associated genes in the liver through the inhibition of glycolysis and Na+/H+ exchange.

Phloretin Inhibits Quorum Sensing and Biofilm Formation in Serratia marcescens.

This study investigated the antivirulence capacity and mechanism of apple-skin-derived phloretin against Serratia marcescens NJ01, a vegetable spoilage bacterium. At 0.5 to 2 mg/mL doses, phloretin considerably inhibited the secretion of acyl homoserine lactones (AHLs), indicating that phloretin disrupted quorum sensing (QS) in S. marcescens NJ01. The dysfunction of QS resulted in reduced biofilms and the decreased production of protease, prodigiosin, extracellular polysaccharides (EPSs), and swimming and swarming motilities. Dysfunctional QS also weakened the activity of antioxidant enzymes and improved oxidative injury. The improved oxidative injury changed the composition of the membrane, improved membrane permeability, and eventually increased the susceptibility of biofilm cells to amikacin, netilmicin, and imipenem. The disrupted QS and enhanced oxidative stress also caused disorders of amino acid metabolism, energy metabolism, and nucleic acid metabolism, and ultimately attenuated the ability of S. marcescens NJ01 to induce spoilage. Our results indicated that phloretin can act as a potent drug to defend against spoilage by S. marcescens.

Organic Polymer Dots Photocatalyze CO2 Reduction in Aqueous Solution.

Developing low-cost and efficient photocatalysts to convert CO2 into valuable fuels is desirable to realize a carbon-neutral society. In this work, we report that polymer dots (Pdots) of poly[(9,9'-dioctylfluorenyl-2,7-diyl)-co-(1,4-benzo-thiadiazole)] (PFBT), without adding any extra co-catalyst, can photocatalyze reduction of CO2 into CO in aqueous solution, rendering a CO production rate of 57 µmol g-1 h-1 with a detectable selectivity of up to 100 %. After 5 cycles of CO2 re-purging experiments, no distinct decline in CO amount and reaction rate was observed, indicating the promising photocatalytic stability of PFBT Pdots in the photocatalytic CO2 reduction reaction. A mechanistic study reveals that photoexcited PFBT Pdots are reduced by sacrificial donor first, then the reduced PFBT Pdots can bind CO2 and reduce it into CO via their intrinsic active sites. This work highlights the application of organic Pdots for CO2 reduction in aqueous solution, which therefore provides a strategy to develop highly efficient and environmentally friendly nanoparticulate photocatalysts for CO2 reduction.

Syntheses of Polypeptides and Their Biomedical Application for Anti-Tumor Drug Delivery.

Polypeptides have attracted considerable attention in recent decades due to their inherent biodegradability and biocompatibility. This mini-review focuses on various ways to synthesize polypeptides, as well as on their biomedical applications as anti-tumor drug carriers over the past five years. Various approaches to preparing polypeptides are summarized, including solid phase peptide synthesis, recombinant DNA techniques, and the polymerization of activated amino acid monomers. More details on the polymerization of specifically activated amino acid monomers, such as amino acid N-carboxyanhydrides (NCAs), amino acid N-thiocarboxyanhydrides (NTAs), and N-phenoxycarbonyl amino acids (NPCs), are introduced. Some stimuli-responsive polypeptide-based drug delivery systems that can undergo different transitions, including stability, surface, and size transition, to realize a better anti-tumor effect, are elaborated upon. Finally, the challenges and opportunities in this field are briefly discussed.

MXene-based hybrid system exhibits excellent synergistic antibiosis.

MXenes are a group of inorganic two-dimensional (2D) nanomaterial, and have raised significant interests in biomedical areas. Ti3C2Tx, as an important member of MXene family, is widely studied because of its biodegradability and low-cytotoxicity. However, their single antibacterial mechanism and poor stability in aqueous solution need to be improved, especially for the antimicrobial applications. In this work, a MXene-based hybrid antibacterial system (M-HAS) was developed and its synergistic antibacterial activity was investigated. In the M-HAS, 2D few-layer Ti3C2Tx(FL-Ti3C2Tx) was modified with hydrophilic polymers and thereby used as carriers for silver nanoparticles (Ag NPs). By assembling these two substrates, photodynamic performance of the prepared system is significantly improved with a large amount of reactive oxygen species produced under 660 nm laser. Antibacterial effects of the M-HAS are enhanced by over 4 times with irradiation. In another word, the developed hybrid system displays excellent photodynamic antibacterial synergistic properties. This work takes advantage of the photodynamic properties of each component in the M-HAS to achieve efficient antibacterial activity and proposes an innovative approach to develop the 2D FL-Ti3C2Tx-based antibacterial platform.

Celastrol-based nanomedicine promotes corneal allograft survival.

Effectively promoting corneal allograft survival remains a challenge in corneal transplantation. The emerging therapeutic agents with high pharmacological activities and their appropriate administration routes provide attractive solutions. In the present study, a celastrol-loaded positive nanomedicine (CPNM) was developed to enhance corneal penetration and to promote corneal allograft survival. The in vitro, in vivo and ex vivo results demonstrated the good performance of CPNM prolonging the retention time on ocular surface and opening the tight junction in cornea, which resulted in enhanced corneal permeability of celastrol. Both in vitro and in vivo results demonstrated that celastrol inhibited the recruitment of M1 macrophage and the expression of TLR4 in corneal allografts through the TLR4/MyD88/NF-κB pathway, thereby significantly decreasing secretion of multiple pro-inflammatory cytokines to promote corneal allograft survival. This is the first celastrol-based topical instillation against corneal allograft rejection to provide treatment more potent than conventional eye drops for ocular anterior segment diseases.

Inflammation-Targeted Celastrol Nanodrug Attenuates Collagen-Induced Arthritis through NF-κB and Notch1 Pathways.

Rheumatoid arthritis (RA) is a systemic inflammatory disorder which can cause bone and cartilage damage leading to disability, yet the treatment remains unsatisfactory nowadays. Celastrol (Cel) has shown antirheumatic activity against RA. However, the frequent parenteral delivery and poor water solubility of Cel restrict its further therapeutic applications. Here, aiming at effectively overcoming the poor water solubility and short half-life of Cel to boost its beneficial effects for treating RA, we developed a polymeric micelle for Cel delivery based on a reactive oxygen species (ROS) sensitive polymer. Our results demonstrated that Cel may inhibit the repolarization of macrophages toward the pro-inflammatory M1 pheno-type via regulating the NF-κB and Notch1 pathways, which resulted in significantly decreased secretion of multiple pro-inflammatory cytokines to suppress the RA progression. Consequently, the Cel-loaded micelle effectively alleviated the major RA-associated symptoms including articular scores, ankle thickness, synovial inflammation, bone erosion, and cartilage degradation.

Hematite Photoanodes for Water Oxidation: Electronic Transitions, Carrier Dynamics, and Surface Energetics.

We review the current understanding of charge carriers in model hematite photoanodes at different stages. The origin of charge carriers is discussed based on the electronic structure and absorption features, highlighting the controversial assignment of the electronic transitions near the absorption edge. Next, the dynamic evolution of charge carriers is analyzed both on the ultrafast and on the surface reaction timescales, with special emphasis on the arguable spectroscopic assignment of electrons/holes and their kinetics. Further, the competitive charge transfer centers at the solid-liquid interface are reviewed, and the chemical nature of relevant surface states is updated. Finally, an overview on the function of widely employed surface cocatalysts is given to illustrate the complex influence of physiochemical modifications on the charge carrier dynamics. The understanding of charge carriers from their origin all the way to their interfacial transfer is vital for the future of photoanode design.

Dynamic Role of Cluster Cocatalysts on Molecular Photoanodes for Water Oxidation.

While loading of cocatalysts is one of the most widely investigated strategies to promote the efficiency of photoelectrodes, the understanding of their functionality remains controversial. We established new hybrid molecular photoanodes with cobalt-based molecular cubane cocatalysts on hematite as a model system. Photoelectrochemical and rate law analyses revealed an interesting functionality transition of the {Co(II)4O4}-type cocatalysts. Their role changed from predominant hole reservoirs to catalytic centers upon modulation of the applied bias. Kinetic analysis of the photoelectrochemical processes indicated that this observed transition arises from the dynamic equilibria of photogenerated surface charge carriers. Most importantly, we confirmed this functional transition of the cocatalysts and the related kinetic properties for several cobalt-based molecular and heterogeneous catalysts, indicating wide applicability of the derived trends. Additionally, complementary analytical characterizations show that a transformation of the applied molecular species occurs at higher applied bias, pointing to a dynamic interplay connecting molecular and heterogeneous catalysis. Our insights promote the essential understanding of efficient (molecular) cocatalyzed photoelectrode systems to design tailor-made hybrid devices for a wide range of catalytic applications.

Synthesis of Ag/rGO composite materials with antibacterial activities using facile and rapid microwave-assisted green route.

The present paper represents a facile and rapid synthesis of silver-reduced graphene oxide Ag/rGO (Ag/reduced graphite oxides) composites with the help of microwave irradiation. This is a rapid green route requiring power microwave irradiation only 400 W(30 s) and 200 W (60 s) for the uniform Ag nanoparticles with average diameter of ~10 nm embedded on rGO sheets. In the microwave irradiation process, rGO samples absorb electromagnetic energy to be heated rapidly due to their intrinsic dielectric and conductive losses. Local hot sheets appear in aqueous solution, facilitating homogeneous nucleation, as well as the grain growth of Ag crystallites throughout the rGO sheets. The obtained Ag/rGO composites exhibited significant antibacterial property towards Gram-negative bacteria (E. coli and P. aeruginosa), Gram-positive bacteria (S. aureus and Enterococcus), and white rot fungus. The minimum bactericidal concentration of the Ag /rGO nanocomposite against E. coli was about 1 µg/mL. Strong interaction between Ag/rGO composites and bacteria contributed to the totally non-activity of bacteria. We designed Ag/rGO nanocomposite with excellent antibacterial activities by facile andrapid microwave-assisted green route. In Ag/rGO nanocomposite, the morphology and size distributions of Ag particles anchored on the rGO sheets can controlled via the microwave irradiation power and time. The results suggested that in the microwave field, GO reduced into unique rGO sheets and uniform AgNPs with average size of 12 nm can be decorated on rGO sheets at 30 s and at 200 W, respectively. we successfully demonstrated small silver particles anchored on graphene displayed great antibacterial activities against Gram-negative bacteria (E. coli and P. aeruginosa), Gram-positive bacteria (S. aureus and Enterococcus) and white rot fungus. Ag/rGO nanocomposites may have potential applications as antibacterial agent for daily life.

Probing the Microporous Structure of Silica Shell Via Aggregation-Induced Emission in Au(I)-Thiolate@SiO2 Nanoparticle.

An efficient method to investigate the window size of the silica shell generated via the classical Stöber method is reported by making use of the unique aggregation-induced emission property of Au(I)-thiolate complexes, which can precisely probe the porosity of the silica shell in Au(I)-thiolate@SiO2 nanoparticles.

Tuning the Accessibility and Activity of Au25 (SR)18 Nanocluster Catalysts through Ligand Engineering.

In this work, the effects of thiolate ligands (-SR, e.g., chain length and functional moiety) on the accessibility and catalytic activity of thiolate-protected gold nanoclusters (e.g., Au25 (SR)18 ) for 4-nitrophenol hydrogenation is reported. The data suggest that Au25 (SR)18 bearing a shorter alkyl chain shows a better accessibility to the substrates (shown by shorter induction time, t0 ) and a higher catalytic activity (shown by higher apparent reaction rate constant, kapp ). The functional moiety of the ligands is another determinant factor, which clearly suggests that ligand engineering of Au25 (SR)18 would be an efficient platform for fine-tuning its catalytic properties.

An Effective Design of Electrically Conducting Thin-Film Composite (TFC) Membranes for Bio and Organic Fouling Control in Forward Osmosis (FO).

The organic foulants and bacteria in secondary wastewater treatment can seriously impair the membrane performance in a water treatment plant. The embedded electrode approach using an externally applied potential to repel organic foulants and inhibit bacterial adhesion can effectively reduce the frequency of membrane replacement. Electrode embedment in membranes is often carried out by dispensing a conductor (e.g., carbon nanotubes, or CNTs) in the membrane substrate, which gives rise to two problems: the leaching-out of the conductor and a percolation-limited membrane conductivity that results in an added energy cost. This study presents a facile method for the embedment of a continuous electrode in thin-film composite (TFC) forward osmosis (FO) membranes. Specifically, a conducting porous carbon paper is used as the understructure for the formation of a membrane substrate by the classical phase inversion process. The carbon paper and the membrane substrate polymer form an interpenetrating structure with good stability and low electrical resistance (only about 1Ω/□). The membrane-electrode assembly was deployed as the cathode of an electrochemical cell, and showed good resistance to organic and microbial fouling with the imposition of a 2.0 V DC voltage. The carbon paper-based FO TFC membranes also possess good mechanical stability for practical use.

Ultrasound-responsive microbubbles for sonography-guided siRNA delivery.

RNA interfering is a gene therapeutic approach of great potential for cancer. However, tumor-targeted delivery of small interfering RNA (siRNA) solely based on the enhanced permeability and retention effect of nanocarriers is often insufficient. To address this challenge, siRNA encapsulated ultrasound-responsive microbubble (MB) was developed from polymeric siRNA micelles and liposomal MBs using hetero-assembling strategy. 1MHz low-frequency ultrasound exposure of the tumor site after intratumoral injection of XIAP siRNA/MBs led to enhanced permeability for much more siRNA delivery into deep tumor regions. Significant improvement of XIAP gene silencing and cleaved caspase-3 activation was achieved, resulting in good therapeutic effect on human cervical cancer xenograft model in nude mice. Moreover, real-time US monitoring of the tumor was also possible using the siRNA/MBs as a contrast agent during the therapeutic process. These results show that the multi-functional siRNA/MBs are a promising theranostic system for cancer gene therapy.

Combination of siRNA-directed Kras oncogene silencing and arsenic-induced apoptosis using a nanomedicine strategy for the effective treatment of pancreatic cancer.

The synergetic inhibitory effects on human pancreatic cancer by nanoparticle-mediated siRNA and arsenic therapy were investigated both in vitro and in vivo. Poly(ethylene glycol)-block-poly(L-lysine) were prepared to form siRNA-complexed polyplex and poly(ethylene glycol)-block-poly(DL-lactide) were prepared to form arsenic-encapsulated vesicle, respectively. Down-regulation of the mutant Kras gene by siRNA caused defective abilities of proliferation, clonal formation, migration, and invasion of pancreatic cancer cells, as well as cell cycle arrest at the G0/G1 phase, which substantially enhanced the apoptosis-inducing effect of arsenic administration. Consequently, co-administration of the two nanomedicines encapsulating siRNA or arsenic showed ideal tumor growth inhibition both in vitro and in vivo as a result of synergistic effect of the siRNA-directed Kras oncogene silencing and arsenic-induced cell apoptosis. These results suggest that the combination of mutant Kras gene silencing and arsenic therapy using nanoparticle-mediated delivery strategy is promising for pancreatic cancer treatment. FROM THE CLINICAL EDITOR: Treatment of pancreatic cancer remains a major challenge. These authors demonstrate a method that combines a siRNA-based Kras silencing with arsenic delivery to pancreatic cancer cells using nanoparticles, resulting in enhanced apoptosis induction in the treated cells.