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.

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.

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.

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).

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.

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.

Effects of bok choy on the dissipation of dibutyl phthalate (DBP) in mollisol and its possible mechanisms of biochemistry and microorganisms.

Phytoremediation is an ecologically sustainable method for remediating contaminated soils, however, research on phytoremediation and its mechanisms are still rarely reported. The highest dibutyl phthalate (DBP) dissipation rate was 91% in 0-3mm bok choy rhizosphere via a 45-day rhizo-box experiment, and bok choy could regulate soil nutrients by increasing soil ammonia nitrogen (AN) and available phosphorus (AP). The biochemistry mechanism of interaction between dissolved organic matter (DOM) and DBP was also elucidated by various spectroscopy techniques. It was found that the alkyl ester in DBP produced the fastest response during the binding process, and the aromatic, hydroxyl and phenolic groups of the DOM humic-like substances preceded amide in DOM protein-like substance. It was found that DBP pollution reduced the Chao1 richness and Shannon index of bacteria in black soil via a pot experiment and high-throughput sequencing, which disturbed the metabolic activities and functional diversity of microorganisms in Mollisol. The microbial abundance increased in bok choy amendments, which has a specific microbial community structure and a high abundance of Actinobacteria and Acidobacteria. We concluded that some enriched genera were responsible for DBP dissipation, Alsobacter, Lacibacter, Myceligenerans, Schrenkiella parvula and Undibacterium. The findings of this study revealed that the possible biochemistry and microbial mechanisms of phytoremediation promoting the DBP dissipation in rhizosphere Mollisol and provided more useful information for phytoremediation of organic pollutants.

Metabolism of diethyl phthalate (DEP) and identification of degradation intermediates by Pseudomonas sp. DNE-S1.

A Pseudomonas sp. DNE-S1 (GenBank accession number MF803832), able to degrade DEP in a wide range of acid-base conditions, was isolated from landfill soil. The growth kinetics of DNE-S1 on DEP followed the inhibition model. Fe3+ could promote the degradation ability of DNE-S1 to DEP probably by over-expression of the gene phthalate dihydrodiol dehydrogenase (ophB) and phthalate dioxygenase ferredoxin reductase (ophA4). The degradation rate of DEP (500 mg L-1 at 12 h) increased by 14.5% in the presence of Fe3+. Cu2+, Zn2+, and Mn2+ showed an inhibiting effect on the degradation performance of the strain and could alter the cellular morphology, surface area and volume of DNE-S1. Three degradation intermediates, namely ethyl methyl phthalate (EMP), dimethyl phthalate (DMP), and phthalic acid (PA), were detected in the biodegradation of DEP, and the biochemical pathway of DEP degradation was proposed. This study provides new information on the biochemical pathways and the responsible genes involved in DEP degradation.

The drivers of bacterial community underlying biogeographical pattern in Mollisol area of China.

In order to better understand the composition and driving factors of the bacterial community in Mollisols, we selected 9 representative facility agricultural lands in Mollisol area of China for sampling, and described it on a larger spatial scale. Soil bacterial community structure in these 9 regions (determined by high-throughput sequencing analysis) showed significant differences at the genus level. The correlation between bacterial community composition and soil properties, contaminants and geographical latitude showed that the diversity of bacterial community was still strongly correlated with pH and SOM under the influence of phthalates (P < 0.05). Principal component Analysis (PCA) showed that soil properties (i.e. pH, organic matter, stacking density, the content of nitrogen, potassium, phosphorus) and PAEs level rather than geographic latitude were main drivers of differences in bacterial community structure. These factors account for 73.04% of the total variation of the bacterial community. Among them, PAEs act as a typical pollutant is the main factor driving the composition of bacterial community in facility agriculture Mollisols. This shows that PAEs is a potential pollution risk factor, which has important guiding significance for the sustainable and healthy development of agriculture in Mollisol area.

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.

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.

Competitive sorption of lead and methylene blue onto black soil and their interaction with dissolved organic matter using two-dimensional correlation analyses.

This study investigated the competitive sorption of black soil to adsorb Pb(II) and methylene blue (MB) from multi-contaminated soils. According to the experimental data, the process of adsorption can be clearly explained by pseudo-second-order kinetic equation. Both single and binary systems of the adsorption isotherms had a good fit with Langmuir models. The maximal adsorption abilities of Pb(II) and MB acquired from binary systems sorption were attenuated compared to those from the single system (Pb(II): 77.70 > 65.96 mg g-1; MB: 242.31 > 222.36 mg g-1). Pb(II) and MB can inhibit each other's sorption ability. A combination of three-dimensional excitation-emission matrix (3D-EEM), synchronous fluorescence spectra as well as two-dimensional correlation spectroscopy (2D-COS) were employed to determine the binding of dissolved organic matter (DOM) for Pb(II) and MB during soil sorption process. As a result, 3D-EEM implicated that the two main composes of DOM were humic acid-like substances and the fluorescence of DOM specimens were gradually diminished with increasing concentrations of Pb(II) and MB. According to synchronous fluorescence spectra, static quenching of Pb(II) and MB mainly led to fluorescence quenching. Specifically, fluorescence-2D-COS implicated that Pb(II) and MB bound to fluorescence in the following sequence: the earlier occurrence of the humic-like fraction compared to that of protein-like fraction. FTIR-2D-COS results concluded that the structural change sequence of DOM by Pb(II) binding followed the order: 1700＞863＞1332＞1529＞1200＞1086 cm-1 and the sequence of the MB binding affinities followed the order: 1520＞1399＞1345＞1152＞1602＞993＞881 cm-1. These findings would be beneficial to understand the mechanism of adsorb multi-component systems and have the potential to contribute significance to the interaction mechanism of multi-component with soil DOM at the molecular level.

How do root exudates of bok choy promote dibutyl phthalate adsorption on mollisol?

This study investigates the interaction between the bok choy root exudates and dibutyl phthalate (DBP) onto mollisol during the adsorption. The result elucidated that the adsorption reached equilibrium within 12 h, the adsorption capacity of rhizosphere mollisol containing root exudates and ordinary mollisol were 243.46 mg kg-1 and 281.95 mg kg-1, separately. The adsorption kinetics and isotherm model followed the pseudo-second order and the Frendlish model, respectively, which hinted that the adsorption process was multi-layer heterogeneous chemisorption. We characterized the root exudates and analyzed its effects on soil physical and chemical properties and structure. The result revealed that the root exudates contained hydrocarbons, sulfur compounds and acids. Root exudates made the dissolved organic matter (DOM) dissolution from soil and the increase of organic matter, which might be one of the reasons that root exudates promote DBP adsorption on mollisol. We selected three-dimensional excitation-emission matrix (3D-EEM), synchronous fluorescence and Fourier transform infrared spectroscopy (FTIR) to analyze the interactions between root exudates and DBP, DOM and DBP, respectively. Fluorescence spectrum revealed that the main component of root exudates was protein, for DOM was humic acid, the fluorescence of root exudates and DOM gradually disappeared with the increase of DBP concentration. FTIR revealed that -COO in root exudates and -CH2 in DOM respectively reacted with DBP. The results of this study are of great importance to reveal that the root exudates are significant in the environmental behavior of DBP adsorption on mollisol, and also provide more useful information for phytoremediation of organic pollutants in the mollisol.

Dysregulated Serum MicroRNA Expression Profile and Potential Biomarkers in Hepatitis C Virus-infected Patients.

OBJECTIVES: Circulating microRNAs (miRNAs) play critical roles in pathogen-host interactions. Aberrant miRNA expression profiles might have specific characteristics for virus strains, and could serve as noninvasive biomarkers for screening and diagnosing infectious diseases. In this study, we aimed to find new potential miRNA biomarkers of hepatitis C virus (HCV) infection. METHODS: Expression levels of broad-spectrum miRNAs in serum samples from 10 patients with HCV viremia and 10 healthy volunteers were analyzed using miRNA PCR arrays. Subsequently, the differential expression of four selected miRNAs (miR-122, miR-134, miR-424-3p, and miR-629-5p) was verified by qRT-PCR in the serum of 39 patients compared with that in 29 healthy controls. Receiver operating characteristic (ROC) curve analysis was performed to evaluate their potential for the diagnosis of HCV infection. RESULTS: miRNA PCR array assays revealed differential expression of 106 miRNAs in sera of HCV patients compared with that in healthy controls. Serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p were well identified. The ROC curves showed that miR-122, miR-134, miR-424-3p, and miR-629-5p could distinguish HCV patients with preferable sensitivity and specificity. In addition, Correlation analysis indicated serum miR-122 expression was positive correlation with ALT/AST levels. Functional analysis of target proteins of these miRNAs indicated the involvement of viral replication, inflammation, and cell proliferation. CONCLUSION: HCV patients have a broad 'fingerprint' profile with dysregulated serum miRNAs compared with that in healthy controls. Among these, serum hsa-miR-122, miR-134, miR-424-3p, and miR-629-5p are identified as promising indication factors of the serum miRNA profile of HCV infection. Particularly, miR-122 could be one of serum biomarkers for early pathological process of HCV. However, more miRNA biomarkers and biological functions of these miRNAs require further investigation.

Preparation, characterization, and evaluation of dipfluzine-benzoic acid co-crystals with improved physicochemical properties.

PURPOSE: To prepare and characterize the co-crystal of dipfluzine and benzoic acid. To investigate the feasibility of the co-crystal for improving solubility and a faster dissolution rate in vitro and evaluate the bioavailability and tissue distribution of co-crystal in vivo. METHODS: A novel dipfluzine-benzoic acid co-crystal prepared using the solvent-assisted co-grinding and the solvent ultrasonic methods were identified and characterized by powder X-ray diffraction (PXRD), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA), as well as Raman, solid-state nuclear magnetic resonance (ssNMR), and terahertz (THz) spectroscopy. Pharmacokinetics and tissue distribution were tested in vivo using murine models. Statistics analysis for dissolution data of co-crystal in vitro and animal experiment data in vivo were evaluated using t-test. RESULTS: Results of PXRD and DSC identified the dipfluzine-benzoic acid co-crystals were formed with a molar ratio of 1:2. The IR, Raman, and ssNMR spectra verified the formation of O-H · · · O and O-H · · · F hydrogen bonds. The complex constant, K, was evaluated to be 10(9) orders of magnitude with Δ r G < 0. The co-crystal solubility, the rate of drug dissolution and the relative bioavailability were approximately 500 times, five times and double that of dipfluzine, respectively. Increased solubility of co-crystal did not reduce distribution in the brain; the mean concentrations in the brain increased, but the differences had no statistic significance (p > 0.05). CONCLUSIONS: The co-crystal of dipfluzine-benzoic acid improved the physicochemical properties of dipfluzine, such as solubility and dissolution rate. Furthermore, the increased relative bioavailability of co-crystal indicated the potential use in further clinical study.

Decolorization of methyl orange by green rusts with hydrogen peroxide at neutral pH.

Heterogeneous Fenton-like processes using green rusts (GRs) with hydrogen peroxide (H2O2) were studied to decolorize methyl orange (MO) in aqueous solution at an initial pH of 7.0. In this study, two types of crystal structure for GRs, the hydroxycarbonate GR(CO3(2-)) (GR1) and the hydroxysulphate GR(SO4(2-)) (GR2), were synthesized by partial oxidation of Fe(OH)2 suspension under light irradiation and distinguished by X-ray diffraction (XRD) due to different characteristic peaks. In oxidation reactions, decolorization rate of MO, bubbling air through the solution, was about 65% (experiment B), whereas, it was up to 95% in the presence of H2O2 (experiment C) within 60 min. The comparative tests of GR1 and GR2 show that the reduction capability of GR2 is stronger than GR1, which may be due to Fe(II) content and interlayer anions. XRD analysis and Fourier transform infrared spectroscopy revealed that the oxidation end products of GR2 were mainly a poorly crystallized mixture of magnetite (Fe3O4) and hydroxy ferric oxide (FeOOH). However, when GR was immediately oxidized, the weakly crystallized goethite (α-FeOOH) and lepidocrocite (γ-FeOOH) were formed for O2 and H2O2, respectively. Based on the intermediates obtained, a probable decolorization mechanism has been proposed.

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.

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.

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.