A self-cleaning photocatalytic membrane loaded with Bi2O2CO3/In(OH)3 S-scheme heterojunction composites for removing tetracycline from aqueous solutions.

Bi2O2CO3/In(OH)3 (BON) photocatalysts were synthesized by a one-pot method and loaded onto polyvinylidene fluoride (PVDF) membranes to obtain a Bi2O2CO3/In(OH)3/PVDF (BON-M) catalytic membrane system. The catalytic membranes demonstrated complete degradation of tetracycline within 40 min under visible light. They demonstrated robust photocatalytic activity across a broad pH range (5-11) and in the presence of coexisting ions. The membranes demonstrated excellent self-cleaning performance. Following exposure to light, the irreversible contamination decreased from 27.1% to 4.7% and the membrane's permeability was almost completely restored. Moreover, the charge transfer mechanism at the S-scheme heterojunction interface of BON was demonstrated by Density functional theory and in-situ X-ray Photoelectron Spectroscopy characterisation, and the active sites involved in tetracycline's degradation were identified. Meanwhile, the mechanism of the "anemone effect" of BON-M was demonstrated in conjunction with Electron paramagnetic resonance, and the intrinsic Some factors enhancing the membranes' photocatalytic activity are specified.

Protein engineering of multi-enzyme virus-like particle nanoreactors for enhanced chiral alcohol synthesis.

In the past decade, virus-like particles (VLPs) that can encapsulate single or multiple enzymes have been studied extensively as typical nanoreactors for biocatalysis in vitro, yet their catalytic efficiencies are usually inadequate for real applications. These biocatalytic nanoreactors should be engineered like their free-enzyme counterparts to improve their catalytic performance for potential applications. Herein we engineer biocatalytic VLPs for the enhanced synthesis of chiral alcohols. Different methods including directed evolution were applied to the entire bacteriophage P22 VLPs (except the coat protein), which encapsulated a carbonyl reductase from Scheffersomyces stipitis (SsCR) and a glucose dehydrogenase from Bacillus megaterium (BmGDH) in their capsids. The best variant, namely M5, showed an enhanced turnover frequency (TOF, min-1) up to 15-fold toward the majority of tested aromatic prochiral ketones, and gave up to 99% enantiomeric excess in the synthesis of chiral alcohol pharmaceutical intermediates. A comparison with the mutations of the free-enzyme counterparts showed that the same amino acid mutations led to different changes in the catalytic efficiencies of free and confined enzymes. Finally, the engineered M5 nanoreactor showed improved efficiency in the scale-up synthesis of chiral alcohols. The conversions of three substrates catalyzed by M5 were all higher than those catalyzed by the wild-type nanoreactor, demonstrating that enzyme-encapsulating VLPs can evolve to enhance their catalytic performance for potential applications.

Efficient Secretory Production of δ-Tocotrienol by Combining Pathway Modularization and Transportation Engineering.

The vitamin E component δ-tocotrienol has shown impressive activities in radioprotection, neuroprotection, and cholesterol reduction. Its production is limited by the low content in plants and difficulty in separation from other tocotrienols. Fermentative production using a microbial cell factory that exclusively produces and secretes δ-tocotrienol is a promising alternative approach. Assembly of the δ-tocotrienol synthetic pathway in Saccharomyces cerevisiae followed by comprehensive pathway engineering led to the production of 73.45 mg/L δ-tocotrienol. Subsequent addition of 2-hydroxypropyl-ß-cyclodextrin (CD) and overexpression of the transcription factor PDR1 significantly elevated δ-tocotrienol titer to 241.7 mg/L (63.65 mg/g dry cell weight) in shake flasks, with 30.4% secreted. By properly adding CD and the in situ extractant olive oil, 181.12 mg/L of δ-tocotrienol was collected as an extracellular product, accounting for 85.6% of the total δ-tocotrienol production. This process provides not only a promising δ-tocotrienol cell factory but also insights into yeast engineering toward secretory production of other terpenoids.

In Vivo Detection of Redox-Inactive Neurochemicals in the Rat Brain with an Ion Transfer Microsensor.

Electrochemical tracking of redox-inactive neurochemicals remain a challenge due to chemical inertness, almost no Faraday electron transfer for these species, and the complex brain atmosphere. In this work, we demonstrate a low-cost, simple-making liquid/liquid interface microsensor (LLIM) to monitor redox-inactive neurochemicals in the rat brain. Taking choline (Ch) as an example, based on the difference in solvation energies of Ch in cerebrospinal fluid (aqueous phase) and 1,2-dichloroethane (1,2-DCE; organic phase), Ch is recognized in the specific ion-transfer potential and distinctive ion-transfer current signals. The LLIM has an excellent response to Ch with good linearity and selectivity, and the detection limit is 0.37 µM. The LLIM can monitor the dynamics of Ch in the cortex of the rat brain by both local microinfusion and intraperitoneal injection of Ch. This work first demonstrates that the LLIM can be successfully applied in the brain and obtain electrochemical signals in such a sophisticated system, allowing one new perspective of sensing at the liquid/liquid interface for nonelectrically active substances in vivo to understand the physiological function of the brain.

Effect of Graphene Oxide on Mechanical Properties and Durability of Ultra-High-Performance Concrete Prepared from Recycled Sand.

Ultra-high-performance concrete (UHPC) has been used as an advanced construction material in civil engineering because of its excellent mechanical properties and durability. However, with the depletion of the raw material (river sand) used for preparing UHPC, it is imperative to find a replacement material. Recycled sand is an alternative raw material for preparing UHPC, but it degrades the performance. In this study, we investigated the use of graphene oxide (GO) as an additive for enhancing the properties of UHPC prepared from recycled sand. The primary objective was to investigate the effects of GO on the mechanical properties and durability of the UHPC at different concentrations. Additionally, the impact of the GO additive on the microstructure of the UHPC prepared from recycled sand was analysed at different mixing concentrations. The addition of GO resulted in the following: (1) The porosity of the UHPC prepared from recycled sand was reduced by 4.45-11.35%; (2) the compressive strength, flexural strength, splitting tensile strength, and elastic modulus of the UHPC prepared from recycled sand were enhanced by 8.24-16.83%, 11.26-26.62%, 15.63-29.54%, and 5.84-12.25%, respectively; (3) the resistance of the UHPC to penetration of chloride ions increased, and the freeze-thaw resistance improved; (4) the optimum mixing concentration of GO in the UHPC was determined to be 0.05 wt.%, according to a comprehensive analysis of its effects on the microstructure, mechanical properties, and durability of the UHPC. The findings of this study provide important guidance for the utilisation of recycled sand resources.

Zwitterionic Polydopamine Engineered Interface for In Vivo Sensing with High Biocompatibility.

Electrochemical sensing performance is often compromised by electrode biofouling (e.g., proteins nonspecific binding) in complex biological fluids; however, the design and construction of a robust biointerface remains a great challenge. Herein, inspired by nature, we demonstrate a robust polydopamine-engineered biointerfacing, to tailing zwitterionic molecules (i.e., sulfobetaine methacrylate, SBMA) through Michael Addition. The SBMA-PDA biointerface can resist proteins nonspecific binding in complex biological fluids while enhancing interfacial electron transfer and electrochemical stability of the electrode. In addition, this sensing interface can be integrated with tissue-implantable electrode for in vivo analysis with improved sensing performance, preserving ca. 92.0% of the initial sensitivity after 2 h of implantation in brain tissue, showing low acute neuroinflammatory responses and good stability both in normal and in Parkinson's disease (PD) rat brain tissue.

Mechanical Properties and Environmental Evaluation of Ultra-High-Performance Concrete with Aeolian Sand.

Ultra-high-performance concrete (UHPC) has received increasing attention in recent years due to its remarkable ductility, durability, and mechanical properties. However, the manufacture of UHPC can cause serious environmental issues. This work addresses the feasibility of using aeolian sand to produce UHPC, and the mix design, environmental impact, and mechanical characterization of UHPC are investigated. We designed the mix proportions of the UHPC according to the modified Andreasen and Andersen particle packing model. We studied the workability, microstructure, porosity, mechanical performance, and environmental impact of UHPC with three different water/binder ratios. The following findings were noted: (1) the compressive strength, flexural strength, and Young's modulus of the designed UHPC samples were in the ranges of 163.9-207.0 MPa, 18.0-32.2 MPa, and 49.3-58.9 GPa, respectively; (2) the compressive strength, flexural strength, and Young's modulus of the UHPC increased with a decrease in water/binder ratio and an increase in the steel fibre content; (3) the compressive strength-Young's modulus correlation of the UHPC could be described by an exponential formula; (4) the environmental impact of UHPC can be improved by decreasing its water/binder ratio. These findings suggest that it is possible to use aeolian sand to manufacture UHPC, and this study promotes the application of aeolian sand for this purpose.

A cobalt corrole/carbon nanotube enables simultaneous electrochemical monitoring of oxygen and ascorbic acid in the rat brain.

It is of interest to in vivo monitor the co-dynamics of different substances. However, the tracking of multiple species is still challenging. In this work, we demonstrate an in vivo electrochemical method by using multi-potential step amperometry to in vivo detect ascorbic acid (AA) and oxygen (O2) simultaneously. In order to achieve good selectivity and high sensitivity for both AA and O2, we design a cobalt corrole [Co(tpfc)(py)2] (tpfc = 5,10,15-tris(penta-fluorophenyl) corrole, py = pyridine, denoted as Co-TPFC) and carbon nanotube nanocomposite to modify a carbon fiber microelectrode (Co-TPFC/MWNT/CFE). This Co-TPFC/MWNT/CFE exhibits excellent electrocatalytic properties towards the reduction of O2 preceding a 4e process and facilitates the oxidation of AA at low potential in the physiological environment. Based on this, we realize simultaneous detection of AA and O2 using two-potential steps (one cathodic (-0.2 V) and the other anodic (+0.05 V)) with 1 second step time. Both in vitro and in vivo experiments proved the feasibility of this method. This demonstrated strategy is useful for us to understand various physiological and pathological processes associated with O2 and AA co-dynamics, and also provides an idea for detecting multiple substances simultaneously.

Low-Fouling Nanoporous Conductive Polymer-Coated Microelectrode for In Vivo Monitoring of Dopamine in the Rat Brain.

In vivo electrochemistry with a carbon-fiber electrode (CFE) is the most useful method for tracking neurochemicals in specific brain regions due to its high spatiotemporal resolution. However, CFE is inevitably subject to surface biofouling that leads to a decrease in sensitivity. Here, we develop a polytannic acid (PTA)-doped nanoporous conductive polyaniline (PANI) membrane-coated CFE to minimize biofouling-induced negative effects for in vivo analysis. The as-prepared PTA-PANI-coated CFE shows excellent antifouling property and enrichment capacity toward electrochemical measurement of dopamine (DA) in physiological pH. The PTA-PANI-coated CFE can in vivo monitor the release of DA induced by electrical stimulation and exhibits almost the same sensitivity in the postcalibration (Spost) and the precalibration (Spre; Spost/Spre = 0.90). We believe this conductive nanoporous membrane-coated CFE offers a new platform for in vivo measurement, which would help probe brain chemistry.

Collision of Aptamer/Pt Nanoparticles Enables Label-Free Amperometric Detection of Protein in Rat Brain.

Single particle collision is emerging as a powerful and sensitive technique for analyzing small molecules, however, its application in biomacromolecules detection, for example, protein, in complex biological environments is still challenging. Here, we present the first demonstration on the single particle collision that can be developed for the detection of platelet-derived growth factor (PDGF), an important protein involved in the central nervous system in living rat brain. The system features Pt nanoparticles (PtNPs) conjugated with the PDGF recognition aptamer, suppressing the electrocatalytic collision of PtNPs toward the oxidation of hydrazine. In the presence of PDGF, the stronger binding between targeted protein and the aptamer disrupts the aptamer/PtNPs conjugates, recovering the electrocatalytic performance of PtNPs, and allowing quantitative, selective, and highly sensitive detection of PDGF in cerebrospinal fluid of rat brain.

Nanoskiving fabrication of size-controlled Au nanowire electrodes for electroanalysis.

Nanoskiving, benefiting from its simple operation and high reproducibility, is a promising method to fabricate nanometer-size electrodes. In this work, we report the fabrication of Au nanowire electrodes with different shapes and well-controlled sizes through nanoskiving. Au nanowire block electrodes, membrane electrodes and tip electrodes are prepared with good reproducibility. Steady-state cyclic voltammograms (CVs) demonstrate that all these electrodes behave well as nanoband ultramicroelectrodes. A fast heterogeneous electron transfer rate constant can be extracted reliably from steady-state CVs at various size Au nanowire block electrodes by the Koutecký-Levich (K-L) method. The Au nanowire membrane electrodes demonstrate good sensitivity toward the oxidation of catecholamine and could monitor catecholamine released from rat adrenal chromaffin cells stimulated by high K+.

Observing Single Hollow Porous Carbon Catalyst Collisions for Oxygen Reduction at Gold Nanoband Electrode.

The evaluation of single carbon particle catalysts is critical to better understand the relationship between structure and properties. Here, we use an electrochemical collision method to study the electrocatalytic behaviour of single hollow porous carbon catalyst on gold nanoband electrodes (AuNBE). We observed the catalytic current of oxygen reduction of single carbon particle and quantified the contribution of the porous structure to the catalytic performance. We find that the meso/microporous and hollow structures contribute to the electrocatalytic current. Our research provides direct evidence that the hollow/porous structures improve the electrocatalytic performance.

A mixed-ion strategy to construct CNT-decorated Co/N-doped hollow carbon for enhanced oxygen reduction.

A mixed-ion strategy to achieve carbon nanotube-decorated Co/N-doped hollow carbon hybrids (CNTs-Co/NHC) is developed by precisely controlling the Co2+/Zn2+ molar ratio in the ZIFs-CoxZn1-x precursor. The optimized CNTs-Co/NHC-0.23 catalyst shows outstanding catalytic activity and durability for the oxygen reduction reaction (ORR) and outperformed commercial Pt/C.

Co@C Nanoparticle Embedded Hierarchically Porous N-Doped Hollow Carbon for Efficient Oxygen Reduction.

The rational construction of highly active and stable non-noble metal electrocatalysts for the oxygen reduction reaction (ORR) is an ongoing challenge for practical applications of catalysts. Here, we report a novel nanostructured hollow N-doped carbon hybrid through pyrolysis of silica@CoZn-coordinated zeolitic imidazolate frameworks. The carbon layer encased cobalt nanoparticles were embedded in the hierarchically porous carbon catalyst (Co@C-HN-hC). Profiting from the synergistic effect between highly active Co@C NPs and HN-hC, the Co@C-HN-hC catalyst exhibited remarkable catalytic performances as compared to porous N-doped hollow carbon (N-hC) and N-doped carbon encased Co NPs (Co@N-C). The electrochemical measurements show that the performances of the Co@C-HN-hC catalyst is close to that of the Pt/C catalysts, along with an excellent stability and durability in the ORR process. This study provides a guideline for controllable design of carbon-based ORR catalysts for substituting noble metal catalysts.

Discovery, design and synthesis of 6H-anthra[1,9-cd]isoxazol-6-one scaffold as G9a inhibitor through a combination of shape-based virtual screening and structure-based molecular modification.

Protein lysine methyltransferase G9a is widely considered as an appealing antineoplastic target. Herein we present an integrated workflow combining shape-based virtual screening and structure-based molecular modification for the identification of novel G9a inhibitors. The shape-based similarity screening through ROCS overlay on the basis of the structure of UNC0638 was performed to identify CPUY074001 contained a 6H-anthra[1,9-cd]isoxazol-6-one scaffold as a hit. Analysis of the binding mode of CPUY074001 with G9a and 3D-QSAR results, two series compounds were designed and synthesized. The derivatives were confirmed to be active by in vitro assay and the SAR was explored by docking stimulations. Besides, several analogues showed acceptable anti-proliferative effects against several cancer cell lines. Among them, CPUY074020 displayed potent dual G9a inhibitory activity and anti-proliferative activity. Furthermore, CPUY074020 induced cell apoptosis in a dose-dependent manner and displayed a significant decrease in dimethylation of H3K9. Simultaneously, CPUY074020 showed reasonable in vivo PK properties. Altogether, our workflow supplied a high efficient strategy in the identification of novel G9a inhibitors. Compounds reported here can serve as promising leads for further study.

Graphene oxide supported rhombic dodecahedral Cu2O nanocrystals for the detection of carcinoembryonic antigen.

In this work, a simple electrochemical immunosensor was developed for the detection of carcinoembryonic antigen (CEA) based on rhombic dodecahedral Cu2O nanocrystals-graphene oxide-gold nanoparticles (rCu2O-GO-AuNPs). GO as the template and surfactant resulting in rCu2O exhibit improved rhombic dodecahedral structure uniformity and excellent electrochemical performance. Moreover, GO was found to be able to effectively improve the long stability of rCu2O on the electrode response. Under optimal conditions, the immunosensor showed a low limit of detection (0.004 ng ml(-1)) and a large linear range (0.01-120 ng ml(-1)). This work presents a potential alternative for the diagnostic applications of GO-supported special morphology materials in biomedicine and biosensors.

A sandwich-type electrochemical immunosensor for carcinoembryonic antigen based on signal amplification strategy of optimized ferrocene functionalized Fe3O4@SiO2 as labels.

A sandwich-type electrochemical immunosensor was developed for sensitive detection of carcinoembryonic antigen (CEA) by using ferroferric oxide@silica-amino groups (Fe3O4@SiO2-NH2) as carriers and gold nanoparticles-graphene oxide (GO-AuNPs) as platform. The Fe3O4@SiO2-NH2 surface was used as linked reagents for co-immobilization of ferrocenecarboxylic acid (Fc-COOH) and secondary anti-CEA (Ab2) to prepare the signal probe, and it also could hasten the decomposition of hydrogen peroxide (H2O2) to amplify signals. Differential pulse voltammetry (DPV) was successfully used to quantify CEA. Under the optimized conditions, the designed immunosensor shows an excellent analytical performance wide dynamic response range of CEA concentration from 0.001 ng mL(-1) to 80 ng mL(-1) with a relatively low detection limit of 0.0002 ng mL(-1) (S/N=3), and high specificity and good reproducibility. The proposed immunosensor was successfully used to determine CEA in spiked human serum samples.

An electrochemical immunosensor for simultaneous point-of-care cancer markers based on the host-guest inclusion of ß-cyclodextrin-graphene oxide.

A novel electrochemical immunosensor was developed for the simultaneous detection of alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) using Cu2O-graphene oxide-ß-cyclodextrin (Cu2O-GO-CD) and ß-cyclodextrin-graphene oxide-ferrocenecarboxylic acid (GO-CD-Fc-COOH) as the distinguishable signal probe, and graphene oxide-gold nanoparticles (GO-AuNPs) as the sensor platform. GO-CD displayed excellent solubility in water and rich capture capability to Fc-COOH and the secondary antibody. The proposed immunosensor exhibited an excellent electrochemical performance. The linear ranges were from 0.001 ng mL-1 to 80 ng mL-1 for AFP and CEA with a detection limit of 0.0002 ng mL-1 for AFP and 0.0001 ng mL-1 for CEA. With the merits of acceptable stability, high sensitivity, a wide linear range and a low detection limit, the proposed immunosensor showed great potential for the simultaneous detection of multi-analytes in clinical diagnosis.

Novel 5-carboxy-8-HQ based histone demethylase JMJD2A inhibitors: introduction of an additional carboxyl group at the C-2 position of quinoline.

A series of JMJD2A inhibitors had been designed by analyzing the binding mode of 5-carboxy-8-hydroxyquinoline (5-carboxy-8-HQ) with JMJD2A. The inhibitory activity of the synthesized compounds against JMJD2A was determined, followed by docking simulations to understand the structure-activity relationships. Compounds with potent JMJD2A inhibitory activity demonstrated outstanding selectivity for JMJD2A over PHD2. Several potent compounds were selected to evaluate their anti-proliferative activity on tumor cell lines. Among them, compound 6p displayed the best anti-proliferative activity. Based on these in vitro biological data, seven compounds were chosen to determine their physicochemical properties. Compound 6p displayed good aqueous solubility and better permeability than 5-carboxy-8-HQ. Our data recognized that compound 6p could be considered as a starting point for development of new JmjC inhibitors.

The discovery of novel histone lysine methyltransferase G9a inhibitors (part 1): molecular design based on a series of substituted 2,4-diamino-7- aminoalkoxyquinazoline by molecular-docking-guided 3D quantitative structure-activity relationship studies.

Protein lysine methyltransferase G9a, which catalyzes methylation of lysine 9 of histone H3 (H3K9) and lysine 373 (K373) of p53, is overexpressed in human cancers. This suggests that small molecular inhibitors of G9a might be attractive antitumor agents. Herein we report our efforts on the design of novel G9a inhibitor based on the 3D quantitative structure-activity relationship (3D-QSAR) analysis of a series of 2,4-diamino-7-aminoalkoxyquinazolineas G9a inhibitors. The 3D-QSAR model was generated from 47 compounds using docking based molecular alignment. The best predictions were obtained with CoMFA standard model (q2 =0.700, r2 = 0.952) and CoMSIA model combined with steric, electrostatic, hydrophobic, hydrogen bond donor and acceptor fields (q2 = 0.724, r2 =0.960). The structural requirements for substituted 2,4-diamino-7-aminoalkoxyquinazoline for G9a inhibitory activity can be obtained by analysing the COMSIA plots. Based on the information, six novel follow-up analogs were designed.