Covalent organic frameworks-derived carbon nanospheres based nanoplatform for tumor specific synergistic therapy via oxidative stress amplification and calcium overload.

Combinational therapy in cancer treatment that integrates the merits of different therapies is an effective approach to improve therapeutic outcomes. Herein, a simple nanoplatform (N-CNS-CaO2-HA/Ce6 NCs) that synergized chemodynamic therapy (CDT), photodynamic therapy (PDT), photothermal therapy (PTT), and Ca2+ interference therapy (CIT) has been developed to combat hypoxic tumors. With high photothermal effect, excellent peroxidase-like activity, and inherent mesoporous structure, N-doped carbon nanospheres (N-CNSs) were prepared via in situ pyrolysis of an established nanoscale covalent organic frameworks (COFs) precursor. These N-CNSs acted as PTT/CDT agents and carriers for the photosensitizer chlorin e6 (Ce6), thereby yielding a minimally invasive PDT/PTT/CDT synergistic therapy. Hyaluronic acid (HA)-modified CaO2 nanoparticles (CaO2-HA NPs) coated on the surface of the nanoplatform endowed the nanoplatform with O2/H2O2 self-supply capability to respond to and modulate the tumor microenvironment (TME), which greatly facilitated the tumor-specific performance of CDT and PDT. Moreover, the reactive oxygen species (ROS) produced during PDT and CDT enhanced the Ca2+ overloading due to CaO2 decomposition, amplifying the intracellular oxidative stress and leading to mitochondrial dysfunction. Notably, the HA molecules not only increased the cancer-targeting efficiency but also prevented CaO2 degradation during blood circulation, providing double insurance of tumor-selective CIT. Such a nanotherapeutic system possessed boosted antitumor efficacy with minimized systemic toxicity and showed great potential for treating hypoxic tumors.

CYP2C19-rs4986893 confers risk to major depressive disorder and bipolar disorder in the Han Chinese population whereas ABCB1-rs1045642 acts as a protective factor.

BACKGROUND: Genetic risks may predispose individuals to major mood disorders differently. This study investigated the gene polymorphisms of previously reported candidate genes for major depressive disorder (MDD) and bipolar disorder (BPD) in the Han Chinese population. METHODS: Twenty loci of 13 candidate genes were detected by MALDI-TOF mass spectrometry in 439 patients with MDD, 600 patients with BPD, and 464 healthy controls. The distribution of genotypes in alleles, Hardy-Weinberg equilibrium, and genetic association were analyzed using the PLINK software. The linkage of disequilibrium and haplotype analyses were performed using the Haploview software. RESULTS: Out of the 20 loci analyzed, CYP2C19-rs4986893, ABCB1-rs1045642, and SCN2A-rs17183814 passed Bonferroni correction; their statistical powers were > 55%. The minor allele frequencies (MAF) of CYP2C19-rs4986893 in the MDD group (0.0547) and BPD group (0.0533) were higher than that of the control group (0.0259, P < 0.05), leading to the odds ratios (ORs) of MDD (2.178) and BPD (2.122), respectively. In contrast, the lower MAFs of ABCB1-rs1045642 were observed in both MDD (0.3599, OR = 0.726) and BPD (0.3700, OR = 0.758) groups than controls (0.4364, P < 0.05). The MDD group had a higher MAF of SCN2A-rs17183814 than controls (0.1743 vs. 0.1207, OR = 1.538, P < 0.05). Moreover, a G-A haplotype composed by CYP2C19-rs4986893 and -rs4244285 was associated with BPD (OR = 1.361, P < 0.01), and the A-G haplotype increased the risks to both MDD (OR = 2.306, P < 0.01) and BPD (OR = 2.332, P < 0.001). The CYP2C19 intermediate metabolizer and poor metabolizer (IM&PM) status was related to the raised risk of both MDD (OR = 1.547, P < 0.01) and BPD (OR = 1.808, P < 0.001). CONCLUSION: Our data indicate that the impaired CYP2C19 metabolism caused by the haplotypes integrated by CYP2C19 alleles might confer the risk to MDD and BPD, whereas the ABCB1-rs1045642 T allele serves as a protective factor.

Metagenomic study of carbon metabolism in black soil microbial communities under lead-lanthanum stress.

Pollution of soil environments with heavy metals (HMs) and rare earth elements (REEs) cannot be ignored. We aimed to determine the effects of lead combined with lanthanum (Pb-La) on microbial community structure, carbon metabolism, and differences in carbon source utilization in black soils using EcoPlates™ and a macrogenomic approach. We found that Pb and La contents and the microbial community structure together influence and shape the response of soil carbon metabolism to Pb-La. Compared with controls, microorganisms under pollution stress preferentially use phenolic and carboxylic acids as growth carbon sources. Under Pb-La stress, the relative abundance of Proteobacteria significantly increased, thereby selectively displacing heavy metal-sensitive phyla, such as Chloroflexi, Acidobacteria, and Thaumarchaeota. Altered functional potential of the microbial carbon cycle manifested as differences in carbon metabolism, methane metabolism, and carbon fixation pathways. Furthermore, an appropriate concentration of La can reduce the environmental toxicity of Pb, whereas a high concentration of La has synergistic toxicity with Pb. These findings have important implications for understanding the impact of HM-REE contamination in microbial communities and the functions associated with carbon metabolism in black soils.

Leymus chinensis resists degraded soil stress by modulating root exudate components to attract beneficial microorganisms.

Phytoremediation is an effective means to improve degraded soil nutrients and soil structure. Here, we investigated the remediation effects of Leymus chinensis on the physicochemical properties and structure of degraded soil after 3 years of cultivation and explored the bacterial and fungal drivers in root exudates by metabolomics and high-throughput sequencing. The results showed that root exudates increased soil organic matter (SOM), total nitrogen (TN), total phosphorus (TP) and soil aggregates, and organic acids in root exudates reduced pH and activated insoluble nutrients into forms that are available to plants, such as available nitrogen (NH4 +-N), nitrate nitrogen (NO3 --N), and available phosphorus (AP). The cultivation of L. chinensis restored the diversity and richness of soil microorganisms and recruited potential beneficial bacteria and fungi to resist degraded soil stress, and L. chinensis also regulated the abundances of organic acids, amino acids and fatty acids in root exudates to remediate degraded soils. Spearman correlation analysis indicated that glutaric acid, 3-hydroxybutyric acid and 4-methylcatechol in root exudates attracted Haliangium, Nitrospira and Mortierella to the rhizosphere and dispersed the relative abundance of the harmful microorganisms Fusicolla and Fusarium. Our results demonstrate that L. chinensis enhances soil fertility, improves soil structure, promotes microbial diversity and abundance, and recruits potentially beneficial microorganisms by modulating root exudate components.

Leymus chinensis Adapts to Degraded Soil Environments by Changing Metabolic Pathways and Root Exudate Components.

Phytoremediation is a promising remediation strategy for degraded soil restoration. Root exudates are the main carrier substances for information communication and energy transfer between plant roots and soil, which play non-negligible roles in the restoration process. This work investigated the adaptation of Leymus chinensis root exudates to different degraded levels of soil and the mechanism of rhizosphere restoration in a 3-year degraded soil field study. We found that the soil quality at each degradation level significantly increased, with the soil organic matter (SOM) content slightly increasing by 1.82%, moderately increasing by 3.27%, and severely increasing by 3.59%, and there were significant increases in the contents of available nutrients such as available phosphorus (AP), ammonia nitrogen (AN), and nitrate nitrogen (NN). The physiological activities indicated that root tissue cells also mobilize oxidative stress to respond to the soil environment pressure. A total of 473 main components were obtained from root exudates by gas chromatography-time-of-flight mass spectrometry (GC-TOFMS), including acids, alcohols, carbohydrates, and other major primary metabolites. OPLS-DA revealed that soil degradation exerted an important influence on the metabolic characteristics of root exudates, and the numbers of both up- and downregulated metabolic characteristic peaks increased with the increase in the degree of degradation. Forty-three metabolites underwent clear changes, including some defense-related metabolites and osmotic adjustment substances that were significantly changed. These changes mainly mobilized a series of lipid metabolism pathways to maintain the fluidity of membrane function and help plants adapt to unfavorable soil environmental conditions. The PPP energy metabolism pathway was mobilized in response to slight degradation, and TCA energy pathways responded to the environmental pressure of severe soil degradation.

Efficacy of Dexmedetomidine Anesthesia plus Dorsal Penile Nerve Block in Pediatric Circumcision.

Objective: To assess the efficacy of dexmedetomidine anesthesia plus dorsal penile nerve block in pediatric circumcision. Methods: In this retrospective study, 80 children receiving circumcision in our hospital from February 2020 to February 2021 were recruited and assigned via different anesthesia methods at a ratio of 1 : 1 to receive dorsal penile nerve block plus dexmedetomidine anesthesia (combined anesthesia group) or only sevoflurane for total inhalational anesthesia (total anesthesia group). Traditional Chinese medicine (TCM) care was introduced to both groups of patients. Outcome measures included vital signs, operative indices, anesthesia effect, adverse reactions, parent satisfaction, and nursing satisfaction. Results: There were no significant differences in the heart rate, oxygen saturation, and mean arterial pressure between the two groups of children before anesthesia, after anesthesia, and during the awakening period (P > 0.05). Patients receiving combined anesthesia showed a shorter time lapse before the disappearance of eyelash reflex, longer time lapse before postoperative analgesic use, faster awakening, and shorter operation time and hospital stay versus those receiving total inhalational anesthesia alone (P > 0.05). The combined anesthesia resulted in a lower Induction Compliance Checklist (ICC) score, McGill score, and Richmond Agitation-Sedation Scale (RASS) score and a higher Ramsay score versus total anesthesia (P > 0.05). Patients receiving combined anesthesia showed a significantly lower incidence of adverse events (5.00% (2/40)) versus total inhalational anesthesia (62.50% (25/40)) (X 2 = 29.574, P > 0.05). The combined anesthesia group had a higher parent satisfaction (92.50% (37/40)) versus the total anesthesia group (75.00% (30/40)) (X 2 = 4.501, P > 0.05). A total of 80 questionnaires were distributed, with a 100% return rate and a 100% validity rate, and all 80 questionnaires scored 90 points or above. The families of children in both groups were satisfied with the quality of TCM care. Conclusion: The efficacy of dorsal penile nerve block plus dexmedetomidine anesthesia in pediatric circumcision is better than total inhalational anesthesia with sevoflurane.

An Eco-Friendly Acid Leaching Strategy for Dealkalization of Red Mud by Controlling Phase Transformation.

The alkaline components in red mud represent one of the crucial factors restricting its application, especially for the construction and building industry. The phase state of alkaline components has a significant influence on the dealkalization of red mud. In this work, an environmentally friendly acid leaching strategy is proposed by controlling the phase transformation of red mud during active roasting pretreatment. With a moderate roasting temperature, the alkaline component is prevented from converting into insoluble phases. After acid leaching with a low concentration of 0.1 M, a high dealkalization rate of 92.8% is obtained. Besides, the leachate is neutral (pH = 7) and the valuable metals in red mud are well preserved, manifesting a high selectivity and efficiency of diluted acid leaching. The calcination experiment further confirms the practicability of the strategy in the construction field, where the cementitious minerals can be formed in large quantities. Compared with the traditional acid leaching routes, the diluted acid leaching strategy in this work is acid saving with low valuable element consumption. Meanwhile, the secondary pollution issue can be alleviated. Hence, the findings in this work provide a feasible approach for the separation and recovery of alkali and resource utilization of red mud.

Mitochondria-targeting multifunctional nanoplatform for cascade phototherapy and hypoxia-activated chemotherapy.

Despite considerable progress has been achieved in hypoxia-associated anti-tumor therapy, the efficacy of utilizing hypoxia-activated prodrugs alone is not satisfied owing to the inadequate hypoxia within the tumor regions. In this work, a mitochondrial targeted nanoplatform integrating photodynamic therapy, photothermal therapy and hypoxia-activated chemotherapy has been developed to synergistically treat cancer and maximize the therapeutic window. Polydopamine coated hollow copper sulfide nanoparticles were used as the photothermal nanoagents and thermosensitive drug carriers for loading the hypoxia-activated prodrug, TH302, in our study. Chlorin e6 (Ce6) and triphenyl phosphonium (TPP) were conjugated onto the surface of the nanoplatform. Under the action of TPP, the obtained nanoplatform preferentially accumulated in mitochondria to restore the drug activity and avoid drug resistance. Using 660 nm laser to excite Ce6 can generate ROS and simultaneously exacerbate the cellular hypoxia. While under the irradiation of 808 nm laser, the nanoplatform produced local heat which can increase the release of TH302 in tumor cells, ablate cancer cells as well as intensify the tumor hypoxia levels. The aggravated tumor hypoxia then significantly boosted the anti-tumor efficiency of TH302. Both in vitro and in vivo studies demonstrated the greatly improved anti-cancer activity compared to conventional hypoxia-associated chemotherapy. This work highlights the potential of using a combination of hypoxia-activated prodrugs plus phototherapy for synergistic cancer treatment.

Ion channel-targeting near-infrared photothermal switch with synergistic effect for specific cancer therapy.

Despite significant achievement in chemotherapy, the off-target actions and low pharmaceutical selectivity of the therapeutic agents still limit their clinical efficacy. Herein, a multifunctional nanoplatform which integrates chemotherapy, chemodynamic therapy (CDT) and photoactivation of TRPV1 channels has been successfully established for specific cancer therapy. Polydopamine (PDA) coated hollow prussian blue nanocages (hPBNCs) are used as the photothermal switches and drug carriers for loading chemotherapeutic drug, doxorubicin (Dox). Conjugating with the TRPV1 antibodies enables the nanoplatform to bind specifically to TRPV1 channels on the plasma membrane of the TRPV1-positive cancer cells and then activate them by local heating upon NIR irradiation, leading to the over-influx of Ca2+. Critically, the laser irradiation can be carefully controlled to not only open the TRPV1 channels but also avoid burning of tumors by hyperthermia. Moreover, the exposed hPBNCs in the acidic tumor cells can decompose endogenous H2O2 into ˙OH by Fenton reaction to realize CDT, which further aggravates cancer cell apoptosis. Together with the chemotherapy caused by Dox, our nanoplatform displays an enhanced anticancer effect both in vitro and in vivo. Our work provides a powerful means for site-specific cancer synergetic therapy with high spatial and temporal resolution.

Chiral FexCuySe nanoparticles as peroxidase mimics for colorimetric detection of 3, 4-dihydroxy-phenylalanine enantiomers.

L-3,4-dihydroxy-phenylalanine (L-dopa) is the most widely used drug in Parkinson's disease treatment. However, development of cost-effective and high-throughput sensors to accurate enantioselective discrimination of L-dopa and D-dopa remains challenging to date. Herein, on the basis of the peroxidase-mimic activity of chiral FexCuySe nanoparticles, we demonstrated a novel colorimetric sensor for determination of chiral dopa. The surface chiral ligand, L/D-histidine (L/D-His), endowed the nanozymes with enantioselectivity in catalyzing the oxidation of dopa enantiomers. According to the values ofkcat/Km, the efficiency of L-His modified nanoparticles (L-FexCuySe NPs) towards L-dopa was 1.56 times higher than that of D-dopa. While, D-His can facilely reverse the preference of the nanozyme to D-dopa. On the basis of high catalytic activity and enantioselectivity of L-FexCuySe NPs in oxidation of L-dopa, the L-FexCuySe NPs-based system can be utilized for detection of L-dopa. The linear ranges for L-dopa determination were 5µM-0.125 mM and 0.125 mM-1 mM with a detection limit of 1.02µM. Critically, the developed sensor has been successfully applied in the quality control of clinical used L-dopa tablets. Our work sheds light on developing simple and sensitive chiral nanomaterials-based sensors for drug analysis.

Large Amino Acid Mimicking Selenium-Doped Carbon Quantum Dots for Multi-Target Therapy of Alzheimer's Disease.

Multi-target intervention and synergistic treatment are critical for the drug development of Alzheimer's disease (AD) due to its complex and multifactional nature. Oxidative stress and amyloid ß peptides (Aß) accumulation have been recognized as therapeutic targets for AD. Herein, with ability to inhibit Aß aggregation and the broad-spectrum antioxidant properties, the large amino acid mimicking selenium-doped carbon quantum dots (SeCQDs) are presented as novel nanoagents for multi-target therapy of AD. Compared with the precursor, selenocystine, SeCQDs which maintain the intrinsic properties of both selenium and carbon quantum dots (CQDs) possess good biocompatibility and a remarkable ROS-scavenging activity. Moreover, the functionalized α-carboxyl and amino groups on edge of SeCQDs can trigger multivalent interactions with Aß, leading to the ability of SeCQDs to inhibit Aß aggregation. In vivo study demonstrated that SeCQDs can significantly ameliorate the Aß induced memory deficits, reduce Aß accumulation and inhibit neuron degeneration in AD model rats. The versatility of functionalization and potential ability to cross the blood-brain barrier (BBB) make SeCQDs as prospective nanodrugs for treating AD.

Colorimetric determination of amyloid-ß peptide using MOF-derived nanozyme based on porous ZnO-Co3O4 nanocages.

A sensitive and rapid colorimetric biosensor has been developed for determination of amyloid-ß peptide (Aß) and study of amyloidogenesis based on the high peroxidase-like activity of porous bimetallic ZnO-Co3O4 nanocages (NCs). Due to the high binding ability of Aß monomer to ZnO-Co3O4 NCs, the catalytic activity of ZnO-Co3O4 NCs can be significantly suppressed by Aß monomer. This finding forms the basis for a colorimetric assay for Aß monomer detection. The detection limit for Aß monomer is 3.5 nM with a linear range of 5 to 150 nM (R2 = 0.997). The system was successfully applied to the determination of Aß monomer in rat cerebrospinal fluid. Critically, the different inhibition effects of monomeric and aggregated Aß species on the catalytic activity of ZnO-Co3O4 NCs enabled the sensor to be used for tracking the dynamic progress of Aß aggregation and screening Aß inhibitors. Compared with the commonly used thioflavin T fluorescence assay, this method provided higher sensitivity to the formation of Aß oligomer at the very early assembly stage. Our assay shows potential application in early diagnosis and therapy of Alzheimer's disease (AD).

8-Hydroxyquinoline functionalized covalent organic framework as a pH sensitive carrier for drug delivery.

A porous 8-hydroxyquinoline functionalized organic covalent framework (named COF-HQ) was synthesized. The as-prepared COF-HQ showed stable crystal structure, suitable pore size, excellent dispersibility in physiological solution and pH sensitivity, which would be employed as a potential nanocarrier for drug transport and controlled release. The drug loading experiment with 5-Fluorouracil (5-FU) as the model molecule proved that the drug loading capacity of COF-HQ was significantly improved due to the introduction of quinoline groups. The drug release profiles of 5-FU from 5-FU loaded COF-HQ (termed 5-FU@COF-HQ) under different pH showed that its release was controlled by pH owing to the pH sensitivity of conjugated nitrogen atoms from quinoline groups and CN. The in vitro hemolysis and in vivo biocompatibility experiments further verified the good biocompatibility of COF-HQ. Importantly, 5-FU@COF-HQ-treated B16F10 cell-induced tumor models showed that 5-FU@COF-HQ displayed enhanced anti-tumor efficacy than other groups. These results suggested that the drug-loading COF-HQ delivery system showed the potential for effective cancer therapy with advantages of high drug loading, good biocompatibility and the pH-sensitive release of the tumor microenvironment. Overall, our research provided a new functionalized COF-HQ drug delivery system, which further expanded the application of COFs as carriers in the field of cancer treatment.

ATP induced alteration in the peroxidase-like properties of hollow Prussian blue nanocubes: a platform for alkaline phosphatase detection.

Breaking the pH limitation of the enzyme-like activity of nanomaterials is of great importance for extending their applications in environmental and biomedical fields. Herein, to mimic the role of histidine residues in horseradish peroxidase (HRP), adenosine 5'-triphosphate (ATP) is reported to improve the peroxidase-like activity of hollow Prussian blue nanocubes (hPBNCs). Due to the inherited porous structures, hPBNCs can expose all the binding sites as far as possible to ATP to significantly amplify their catalytic activity and broaden their applicable pH range up to pH 12. Introduction of ATP provides the possibility of realizing efficient catalytic reactions under alkaline conditions. Upon binding with hPBNCs, ATP can enhance the stability of hPBNCs, increase the affinities of the catalysts towards substrates and improve the conductivity of hPBNCs as well as change the decomposed product from H2O2. Moreover, on the basis of the different catalytic activities of hPBNCs towards ATP, adenosine 5'-diphosphate and adenosine 5'-monophosphate, hPBNCs-ATP is utilized to construct a novel colorimetric sensor for the detection of alkaline phosphatase (ALP) activity in biological fluids, which is significantly important for the clinical diagnosis of ALP-related diseases.

Complete metabolic study by dibutyl phthalate degrading Pseudomonas sp. DNB-S1.

The primary purpose of this study was to systematically explore the complete metabolic pathway and tolerance mechanism of strain DNB-S1 to dibutyl phthalate (DBP), and the effect of DBP on energy metabolism of DNB-S1. Here, DNB-S1, a strain of Pseudomonas sp. that was highly effective in degrading DBP, was identified, and differentially expressed metabolites and metabolic networks of DBP were studied. The results showed that the differentially expressed metabolites were mainly aromatic compounds and lipid compounds, with only a few toxic intermediate metabolites. It speculated that phthalic acid, salicylic acid, 3-hydroxybenzoate acid, 3-Carboxy-cis, cis-muconate, fumarypyravate were intermediate metabolites of DBP. Their up-regulation indicated that there were two metabolic pathways in the degradation of DBP (protocatechuate pathway and gentisate pathway), which had been verified by peak changes at 290 nm, 320 nm, 330 nm, and 375 nm in the enzymatic method. Also, aspartate, GSH, and other metabolites were up-regulation, indicating that DNB-S1 had a high tolerance to DBP and maintained cell homeostasis, which was also one of the essential reasons to ensure the efficient degradation of DBP. Altogether, this study firstly proposed two pathways to degrade DBP and comprehensively explored the effect of DBP on the metabolic function of DNB-S1, which enriched the study of microbial metabolism of organic pollutants, and which provided a basis for the application of metabolomics.

Expanded mesoporous silica-encapsulated ultrasmall Pt nanoclusters as artificial enzymes for tracking hydrogen peroxide secretion from live cells.

Design of synthetic structures that possess the similar functions to natural enzymes held great promise in environmental detection and biomedical application. Herein, a new concept for the fabrication of solid-supported catalysts as peroxidase mimic have been proposed to realize high-catalytic activity and stability by utilizing expanded mesoporous silica (EMSN)-encapsulated Pt nanoclusters. Compared with PtNCs, the introduction of amino group modified EMSN would enrich H2O2 on the surface of PtNCs and increase the catalytic sites for H2O2 decomposition, which gave rise to the higher catalytic activity of EMSN-PtNCs over a broad pH range, especially in weakly acidic and neural solutions. This would facilitate their applications for real-time monitoring the secretion of H2O2 from living cancer cells stimulated by various anticancer drugs. Our findings not only pave the way to use porous matrix as the structural component for the design of the biomimetic catalysts, but also provide a simple and reliable platform to monitor H2O2 released from living cells in real time, which holds great potential for elucidating the biological roles of H2O2 and underlying molecular mechanisms of drug cytotoxicity as well as drug therapeutic effects.

A nickel-cobalt bimetallic phosphide nanocage as an efficient electrocatalyst for nonenzymatic sensing of glucose.

The authors describe Ni-Co bimetal phosphide (NiCoP) nanocages that exhibit enhanced electrocatalytic performance toward glucose oxidation. The nanocages offer an appealing architecture, large specific area, and good accessibility for the analyte glucose. When placed on a glassy carbon electrode, the sensor exhibits attractive figures of merit for sensing glucose in 0.1 M NaOH solution including (a) a wide linear range (0.005-7 mM), (b) a low determination limit (0.36 µM), (c) high sensitivity (6115 µA•µM-1•cm-2), (d) a relatively low working potential (0.50 V vs. Ag/AgCl), and (e) good selectivity, reproducibility, and stability. The sensor is successfully applied to the determination of glucose in human serum samples. Graphical abstractSchematic representation of a glassy carbon electrode modified with Ni-Co bimetal phosphide (NiCoP) nanocage. NiCoP nanocage exhibits excellent electrocatalytic activity toward glucose oxidation. NiCoP nanocage is applied in a sensitive non-enzymatic glucose sensor.

Hollow Prussian Blue nanocubes as peroxidase mimetic and enzyme carriers for colorimetric determination of ethanol.

The peroxidase-like activity of hollow Prussian Blue nanocubes (hPBNCs) is used, in combination with the enzyme alcohol oxidase (AOx), in a colorimetric ethanol assay. Different from other nanozymes, the large cavity structure of the hPBNCs provides a larger surface and more binding sites for AOx to be bound on their surface or in the pores. This extremely enhances the sensitivity of the assay system. In the presence of ethanol, AOx is capable of catalyzing the oxidation of alcohols to aldehydes, accompanied by the generation of hydrogen peroxide (H2O2). The hPBNCs act as peroxidase mimics and then can catalyze the oxidation of 3,3'5,5'-tetramethylbenzidine (TMB) by H2O2, resulting in a color change of the solution from colorless to blue with a strong absorption at 652 nm. The lower detection limit for ethanol is 1.41 µg∙mL-1. Due to the high catalytic activity of hPBNCs in weakly acidic and neutral solutions, the system was successfully applied to the determination of ethanol in mice blood. This is critically important for studying the alcohol consumption and monitoring the ethanol toxicokinetics. Graphical abstract Schematic representation of hollow Prussian Blue nanocubes (hPBNCs) used as both a peroxidase mimetic and as a carrier for alcohol oxidase. Utilizing hPBNCs along with the ethanol conversion enzyme, a sensitive colorimetric assay for ethanol was developed and applied to blood samples with satisfactory results.

Targeted acetylcholinesterase-responsive drug carriers with long duration of drug action and reduced hepatotoxicity.

PURPOSE: Acetylcholinesterase (AChE) plays a critical role in the transmission of nerve impulse at the cholinergic synapses. Design and synthesis of AChE inhibitors that increase the cholinergic transmission by blocking the degradation of acetylcholine can serve as a strategy for the treatment of AChE-associated disease. Herein, an operational targeted drug delivery platform based on AChE-responsive system has been presented by combining the unique properties of enzyme-controlled mesoporous silica nanoparticles (MSN) with clinical-used AChE inhibitor. METHODS: Functionalized MSNs were synthesized by liquid phase method and characterized by using different analytical methods. The biocompatibility and cytotoxicity of MSNs were determined by hemolysis experiment and MTT assay, respectively. Comparison of AChE activity between drug-loading system and inhibitor was developed with kits and by ELISA method. The efficacy of drug-loaded nanocarriers was investigated in a mouse model. RESULTS: Compared with AChE inhibitor itself, the inhibition efficiency of this drug delivery system was strongly dependent on the concentration of AChE. Only AChE with high concentration could cause the opening of pores in the MSN, leading to the controlled release of AChE inhibitor in disease condition. Critically, the drug delivery system can not only exhibit long duration of drug action on AChE inhibition but also reduce the hepatotoxicity in vivo. CONCLUSION: In summary, AChE-responsive drug release systems have been far less explored. Our results would shed lights on the design of enzyme controlled-release multifunctional system for enzyme-associated disease treatment.

A non-enzymatic amperometric glucose sensor based on the use of graphene frameworks-promoted ultrafine platinum nanoparticles.

Ultrafine platinum nanoparticles are grown on a 3D graphene framework (GF-Pt) via a hydrothermal method. The material, when placed on a glassy carbon electrode (GCE), displays enhanced electrocatalytic activity towards glucose oxidation. This is assumed to be the result of the numerous easily accessible active sites, an enlarged electrochemically active area, and the presence of multiple electron/ion transport channels. The modified GCE can be operated at a low potential (- 0.15 V vs. Ag/AgCl) has linear responses in the 0.1 µM - 0.01 mM and 0.01 mM - 20 mM glucose concentration range, and a 30 nM detection limit. It was applied to the rapid determination of glucose in human serum samples. Graphical abstract Schematic presentation of a glassy carbon electrode modified with ultrafine Pt nanoparticles grown on a graphene framework (GFs-Pt). GFs-Pt presents enhanced electrocatalytic activity towards glucose oxidation. GFs-Pt is used in a sensitive non-enzymatic amperometric glucose sensor.