Mechanism insight into the high-efficiency catalytic killing of E. coli by metal-phenolic network as a nanozyme.

Glutathione (GSH) as an antioxidant greatly attenuates the reactive oxygen species (ROS) treatment strategy based on peroxidase-activity nanozymes. Therefore, nanozymes with multiple properties that generate ROS and further GSH-depletion functions would be of great benefit to improve antimicrobial efficacy. Herein, focusing on the green, safe and abundant functional prospects of metal-phenolic networks (MPNs) and the strong prospect of biomedical applications, we have synthesized copper tannic acid (CuTA) nanozymes with dual functional properties similar to peroxidase-like activity and GSH depletion. CuTA can catalyze the decomposition of H2O2 to hydroxyl radicals (˙OH). In addition, CuTA nanozymes can efficiently deplete available GSH, thus enhancing ROS-mediated antimicrobial therapy. The antibacterial results show that CuTA has an excellent antibacterial effect against E. coli.

Effects of superfine grinding sweet potato leaf powders on physicochemical and structure properties of sweet potato starch noodles.

Sweet potato leaves (SPLs) containing abundant functional components are consumed primarily as fresh vegetables worldwide. This study investigated the physical properties of superfine grinding SPLs powder, and their effects on cooking, texture, and sensory properties, micro- and molecular structures of starch noodles were also explored. The results showed that the bulk and tapped density (from 0.34 to 0.28 g/mL3 and from 0.69 to 0.61 g/mL3), repose and slid angle (from 42.15 to 30.96° and from 48.67 to 22.00°), water-holding capacity and swelling capacity (from 8.66 to 4.94 g/g and from 10.03 to 7.77 mL/g) of SPLs powders were decreased with milling time increased. The cooking loss, swelling index, texture, and sensory properties of SPLs sweet potato starch noodles (SPLSNs) were improved as the particle size of SPLs decreased. XRD and FT-IR showed that SPLSNs contained less complete crystallites (from 28.85% to 14.19%) and lower proportion of crystalline region (R 1047/1017 from 0.96 to 0.81, R 1017/994 from 0.41 to 0.43). SEM revealed that SPLSNs exhibited fewer ordered arrays and smooth cross sections. Our findings provide a foundation for utilizing SPLs and developing functional starch noodles.

Impaired erythropoietin-producing hepatocellular B receptors signaling in the prefrontal cortex and hippocampus following maternal immune activation in male rats.

An environmental risk factor for schizophrenia (SZ) is maternal infection, which exerts longstanding effects on the neurodevelopment of offspring. Accumulating evidence suggests that synaptic disturbances may contribute to the pathology of the disease, but the underlying molecular mechanisms remain poorly understood. Erythropoietin-producing hepatocellular B (EphB) receptor signaling plays an important role in synaptic plasticity by regulating the formation and maturation of dendritic spines and regulating excitatory neurotransmission. We examined whether EphB receptors and downstream associated proteins are susceptible to environmental risk factors implicated in the etiology of synaptic disturbances in SZ. Using an established rodent model, which closely imitates the characteristics of SZ, we observed the behavioral performance and synaptic structure of male offspring in adolescence and early adulthood. We then analyzed the expression of EphB receptors and associated proteins in the prefrontal cortex and hippocampus. Maternal immune activation offspring showed significantly progressive cognitive impairment and pre-pulse inhibition deficits together with an increase in the expression of EphB2 receptors and NMDA receptor subunits. We also found changes in EphB receptor downstream signaling, in particular, a decrease in phospho-cofilin levels which may explain the reduced dendritic spine density. Besides, we found that the AMPA glutamate, another glutamate ionic receptor associated with cofilin, decreased significantly in maternal immune activation offspring. Thus, alterations in EphB signaling induced by immune activation during pregnancy may underlie disruptions in synaptic plasticity and function in the prefrontal cortex and hippocampus associated with behavioral and cognitive impairment. These findings may provide insight into the mechanisms underlying SZ.

pH-responsive dual-enzyme mimics based on hollow metal organic framework-derivatives ß-Co(OH)2 for multiple colorimetric assays.

A hollow metal organic framework derivative ß-Co(OH)2 has been prepared, which possesses oxidase and peroxidase-like activities. Oxidase-like activity is derived from the generation of free radicals, and peroxidase-like activity is related to the electron transfer process. Unlike other nanozymes with dual enzyme-like activities, ß-Co(OH)2 possesses pH-responsive enzyme-like activities, among which the ß-Co(OH)2 exhibits superior oxidase and peroxidase-like activities under pH of 4 and 6, respectively, which could avoid mutual interference between multiple enzymes. Based on the phenomenon that enzyme-like activities of ß-Co(OH)2 can catalyze colorless TMB to generate blue oxidized TMB (oxTMB) with absorption peak at 652 nm, the sensors integrating total antioxidant capacity and H2O2 quantification were developed. The oxidase-like activity-based colorimetric system has a sensitive response to ascorbic acid, Trolox, and gallic acid, in which the limit of detection for those antioxidant substances was 0.54 µM, 1.26 µM, and 14.34 µM, respectively. The sensors based on peroxidase-like activity had low limit of detection of 1.42 µM for H2O2 and a linear range of 5-1000 µM. The proposed method can be well applied to the detection of the total antioxidant capacity of kiwi, Vc tables, orange and tea extract with high accuracy, and H2O2 determination in milk and glucose detection in beverages with satisfactory recovery (within 97-106%).

Effect of three natural antioxidants on the structure and physicochemical properties of sweet potato starch noodles.

The study aimed to investigate the effect of three kinds of natural antioxidants (NAs), such as curcumin, tea polyphenols (TP), and lycopene, on sweet potato starch's structure and physicochemical properties of starch noodles. We found that the broken rates, iodine blue values, hardness, and chewiness of natural antioxidant starch noodles (NASN) were increased with the addition of the NAs. Additionally, the elasticity decreased with the addition of curcumin and lycopene, but it increased with the addition of TP. The cross-section structure of NASN obtained by scanning electron microscope (SEM) showed more holes appeared when adding NAs, and the additional amount had a pronounced effect on the microstructure of starch noodles (SN) regardless of the kind of NA added. The X-ray diffraction detection showed that some crystal forms were significantly damaged, and the addition of NAs affected the crystallization process of starch and produced a small proportion of new crystals in the NASNs. The protective effects of SN on NAs and their antioxidant capacities under dry and room temperature storage (DRTS) and wet and frozen storage (WFS) conditions were optimal as compared to those of flour noodles (FN). The results showed that adding NAs could improve the sensory quality and antioxidant function of starch noodles. In turn, the dense structure of starch noodles can also have a significant protective effect on antioxidants and their antioxidant activities, which is especially obvious under WFS conditions.

Synthesis and Biological Evaluation of Novel Phthalide Analogs-1,2,4-Oxadiazole Hybrids as Potential Anti-Inflammatory Agents.

A series of novel pathalide-1,2,4-oxadiazole analogs were synthesized for discovering novel anti-inflammatory agents. After the assessment of their cytotoxicity in vitro, all compounds had been screened for their anti-inflammatory activity by evaluating their inhibitory effect on LPS-induced NO production in RAW 264.7 macrophages. SARs had been concluded, and finally compound E13 was found to be the most potent compound. This compound could also significantly decrease the production of iNOS and COX-2. Preliminary mechanism studies indicated that compound E13 could inhibit the TLR4/NF-κB and ERK/p38 signaling pathways. These findings indicate that E13 holds great potential to be a lead compound for discovering novel anti-inflammatory drugs.

Immunity improvement and gut microbiota remodeling of mice by wheat germ globulin.

The wheat germ protein (WG) and it's proteolytic peptide have a variety of biological activities. Our previous work showed that WG could improve immunity of the immunosuppressive mice established by cyclophosphamide. However, in the healthy condition and normal diet, as a supplementary food, the effects of immunity improvement and gut microbiota remodeling by the wheat germ globulin has not been studied yet. Here, we reported that WG could improve the immunity and remodel the gut microbiota of the mice, as a potentially safe functional supplementary food for the first time. The increase of interleukin-6 (IL-6) and the decrease of tumor necrosis factor α (TNF-α) and interleukin-10 (IL-10) indicated that WG could enhance the levels of activated T cells and monocytes and anti-inflammatory ability, meanwhile, the significant increase of immunoglobin G (lgG) and the notable decrease of the immunoglobin M (lgM) and immunoglobin A (lgA) illustrated that WG could improve immunity by promoting the differentiation and maturation process of B cells, compared with the NC group (normal control group). 16S rRNA sequencing showed WG could remodel the gut microbiota. At the phylum level, the Bacteroidetes were reduced and Firmicutes were increased in WG group, compared with NC group. At the genus level, the SCFA producing genera of unclassified_f_Lachnospiraceae, Blautia and especially the Roseburia (increased more than threefold) increased notably. Further, the level changes of cytokines and immunoglobulins were associated with the gut microbiota. This work showed that WG could improve immunity and has potential application value as an immune-enhancing functional food.

Comparison of Two Different Natural Oil Body Emulsions: in vitro Gastrointestinal Digestion.

The surface compositions and structure of oil bodies (OBs) are dependent on the oil crop, and these factors affect in vitro gastrointestinal digestion behaviors. Herein, a comparative study was conducted to examine the in vitro gastrointestinal digestion characteristics of two natural emulsions prepared with soybean seeds and rapeseed OBs during gastrointestinal digestion process. The average particle size of soybean OBs and rapeseed OBs emulsions was 0.46 and 5.02 µm, respectively. The droplet size of soybean seed and rapeseed OBs emulsions was large with relatively low zeta-potentials at 30 min digestion time in simulated gastric fluid condition. The droplet size of two natural OBs emulsions decreased with increasing digestion time in simulated gastric fluid condition. The average droplet size of both emulsions gradually decreased with increasing digestion time in simulated intestinal fluid conditions. The zeta-potential of the two emulsions increased with increasing digestion time in simulated intestinal fluid conditions. The extent of free fatty acids of soybean OBs emulsions was significantly higher than rapeseed after 20 min digestion time in simulated intestinal fluid conditions. The obtained results suggested that plant OBs could be useful as natural emulsifiers in the development of functional food and achieve controlled release of bioactive compounds from emulsions during gastrointestinal digestion.

Effect of superfine grinding on physicochemical and antioxidant properties of soybean residue powder.

Soybean residue is an underutilized, nutrient-rich by-product of soybean processing. To enhance its value, we subjected soybean residue to superfine grinding and measured the resulting physiochemical properties and antioxidant activities. We prepared powders with particle sizes of 115.35, 77.93, 39.38, 25.01, and 20.44 µm. As particle size decreased, the surface area (from 96.46 to 198.32 m2/kg) and swelling capacity (from 2.05 to 10.62 ml/g) increased. Conversely, we observed decreases in the surface-number mean (from 23.07 to 11.20 µm), volume-surface mean (from 141.70 to 27.96 µm), angles of repose (from 48.30° to 31.46°), water holding capacity (from 7.86 to 4.39 g/g), and oil binding capacity (from 1.78 to 1.42 g/g). The water solubility index and antioxidant activity (reducing power and free radical scavenging activities of 2,2-diphenyl-1-picrylhydrazyl and 2,2'-azino-di-(3-ethylbenzthiazoline sulfonic acid)) improved as particle size decreased. In conclusion, superfine grinding improved some properties of soybean residue. Additionally, our findings provide theoretical support for using superfine grinding in industrial food applications.

Behavioral abnormalities and phosphorylation deficits of extracellular signal-regulated kinases 1 and 2 in rat offspring of the maternal immune activation model.

Extracellular signal-regulated kinase (ERK) signal transduction is known to be associated with neurogenesis and neuronal differentiation and as such may be related to the synaptic plasticity associated with cognitive function. Although antipsychotic drug studies have suggested a potential role for the ERK cascade in schizophrenia, the mechanistic basis is unknown. The maternal immune activation (MIA) rat model is a well-known to simulate many of the clinical symptoms of schizophrenia, including cognitive deficits, but a role in this model for dynamic changes in ERK has not been established. In this study, polyinosinic:polycytidylic acid was administered to rats intravenously at a dose of 10 mg/kg on embryonic day 9.5 to produce MIA. The effect of MIA on behavior and ERK phosphorylation within the prefrontal cortex and the hippocampus of adolescent and adult offspring were explored. We also examined neurofilaments, a marker of neurogenesis, which have been reported to be modulated by ERK signaling. The results demonstrate an age- and region-specific profile of ERK expression and phosphorylation and suggest possible relationships among ERK, neurofilament expression, and cognitive performance in schizophrenia.

Synthesis and in vitro and in vivo anti-inflammatory activity of novel 4-ferrocenylchroman-2-one derivatives.

A series of novel 4-ferrocenylchroman-2-one derivatives were designed and synthesised to discover potent anti-inflammatory agents for treatment of arthritis. All the target compounds had been screened for their anti-inflammatory activity by evaluating the inhibition effect of LPS-induced NO production in RAW 264.7 macrophages. Among them, 4-ferrocenyl-3,4-dihydro-2H-benzo[g]chromen-2-one (3h) was found to be the most potent compound in inhibiting the productions of NO with low toxicity. This compound also exhibited significant inhibition of the productions of IL-6 and TNF-α in RAW 264.7 macrophages. Preliminary mechanism studies indicated that compound 3h could inhibit the activation of LPS-induced NF-κB and MAPKs signalling pathways. The in vivo anti-inflammatory effect of this compound was determined in the rat adjuvant-induced arthritis model.

Estrogen Receptor α (ERα)-targeting Compounds and Derivatives: Recent Advances in Structural Modification and Bioactivity.

Breast cancer is the most common cancer suffered by female, and the second highest cause of cancer-related death among women worldwide. At present, hormone therapy is still the main treatment route and can be divided into three main categories: selective estrogen receptor modulators (SERMs), selective estrogen receptor downregulators (SERDs), and aromatase inhibitors (AIs). However, breast cancer is difficult to cure even after several rounds of anti-estrogen therapy and most drugs have serious side-effects. Here, we review the literature published over the past five years regarding the isolation and synthesis of analogs and their derivatives.

Generation and Characterization of Induced Pluripotent Stem Cells from Mononuclear Cells in Schizophrenic Patients.

OBJECTIVE: Schizophrenia (SZ) is a mental disorder in which psychotic symptoms are the main problem. The pathogenesis of SZ is not fully understood, partly because of limitations in current disease models and technology. The development of induced pluripotent stem cell (iPSC) technology has opened up the possibility of elucidating disease mechanisms in neurodegenerative diseases. Here, we aimed to obtain iPSCs from peripheral blood mononuclear cells (PBMCs) of normal and schizophrenic individuals and analyze the inflammatory response in these iPSCs. MATERIALS AND METHODS: In this experimental study, we isolated PBMCs from whole blood of healthy individuals and SZ patients and reprogrammed them into iPSCs by transfection of recombinant lentiviruses that contained Yamanaka factors (Oct4, Sox2, Klf4 and c-Myc). We calculated the numbers of iPSC clones and stained them with alkaline phosphatase (ALP), Nanog, SSEA4, Nestin, Vimentin, and AFP to confirm their efficiency and pluripotency. The iPSCs were analyzed by real-time quantitative polymerase chain reaction (qRT-PCR) for the expressions of inflammatory factors. RESULTS: iPSCs from schizophrenic patients (SZ-iPSCs) exhibited typical morphology and highly expressed pluripotent markers. These iPSCs retained their normal karyotype and differentiated in vitro to form embryoid bodies (EBs) that expressed markers of all 3 germ layers. However, iPSCs from the SZ-iPSCs group had a weak capacity to differentiate into ectoderm compared to the normal iPSCs (Con-iPSC). An elevated, stronger inflammatory response existed in iPSCs from schizophrenic individuals. CONCLUSION: We successfully obtained iPSCs from PBMCs of schizophrenic patients without genetic operation and analyzed the expressions of pluripotent markers and inflammatory factors between the Con-iPSC and SZ-iPSC groups. Taken together, our results may assist to explain the pathogenesis of SZ and develop new strategies for clinical diagnosis and treatment.

Association of ARHGAP18 polymorphisms with schizophrenia in the Chinese-Han population.

Numerous developmental genes have been linked to schizophrenia (SZ) by case-control and genome-wide association studies, suggesting that neurodevelopmental disturbances are major pathogenic mechanisms. However, no neurodevelopmental deficit has been definitively linked to SZ occurrence, likely due to disease heterogeneity and the differential effects of various gene variants across ethnicities. Hence, it is critical to examine linkages in specific ethnic populations, such as Han Chinese. The newly identified RhoGAP ARHGAP18 is likely involved in neurodevelopment through regulation of RhoA/C. Here we describe four single nucleotide polymorphisms (SNPs) in ARHGAP18 associated with SZ across a cohort of >2000 cases and controls from the Han population. Two SNPs, rs7758025 and rs9483050, displayed significant differences between case and control groups both in genotype (P = 0.0002 and P = 7.54×10-6) and allelic frequencies (P = 4.36×10-5 and P = 5.98×10-7), respectively. The AG haplotype in rs7758025-rs9385502 was strongly associated with the occurrence of SZ (P = 0.0012, OR = 0.67, 95% CI = 0.48-0.93), an association that still held following a 1000-times random permutation test (P = 0.022). In an independently collected validation cohort, rs9483050 was the SNP most strongly associated with SZ. In addition, the allelic frequencies of rs12197901 remained associated with SZ in the combined cohort (P = 0.021), although not in the validation cohort alone (P = 0.251). Collectively, our data suggest the ARHGAP18 may confer vulnerability to SZ in the Chinese Han population, providing additional evidence for the involvement of neurodevelopmental dysfunction in the pathogenesis of schizophrenia.

Aquimarina aggregata sp. nov., isolated from seawater.

A novel Gram-stain-negative, agarolytic, rod-shaped, non-flagellated, strictly aerobic strain with gliding motility, designated RZW4-3-2T, was isolated from coastal seawater of the Yellow Sea in China (119.625° E 35.517° N). The organism grew optimally at 28 °C, at pH 7.0 and in the presence of 2.0-3.0 % (w/v) NaCl. The strain required seawater or artificial seawater for growth, and NaCl alone did not support growth. Strain RZW4-3-2T contained MK-6 as the major respiratory quinone and iso-C17 : 0 3-OH, iso-C15 : 0, iso-C15 : 1 G and iso-C15 : 0 3-OH as the dominant fatty acids. The polar lipids of strain RZW4-3-2T comprised phosphatidylethanolamine, five unknown phospholipids and one unknown lipid. The DNA G+C content of strain RZW4-3-2T was 32.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that the novel strain was related most closely to Aquimarina pacifica SW150T, Aquimarina macrocephali JCM 15542T and Aquimarina muelleri LMG 22569T with 98.1, 97.4 and 97.1 % sequence similarities, respectively. The estimated DNA-DNA hybridization values were 20.00±2.31 %, 20.70±2.33 % and 20.70±2.32 % between strain RZW4-3-2T and A. pacifica SW150T, A. macrocephali JCM 15542T and A. muelleri LMG 22569T, respectively. On the basis of results of polyphasic analyses, strain RZW4-3-2T represents a novel species of the genus Aquimarina, for which the name Aquimarinaaggregata sp. nov. is proposed. The type strain is RZW4-3-2T (=JCM 30824T=MCCC 1K00698T).

Analysis of pesticide residues in tobacco with online size exclusion chromatography with gas chromatography and tandem mass spectrometry.

An ultrasensitive method for the simultaneous analysis of pesticides residues in tobacco was developed with online size exclusion chromatography with gas chromatography and tandem mass spectrometry. Tobacco samples were extracted with the solvent mixture of cyclohexane and acetone (7:3, v/v) and centrifuged. Then, the supernatant liquors were injected directly into the online size exclusion chromatography with gas chromatography and tandem mass spectrometry without any other purification procedures after being filtered with a 0.22 µm organic phase filter. The matrix interferences were effectively removed and recoveries of most pesticides were in the range of 72-121%. Especially, for chlorothalonil, the analysis efficiency of this method was much more favorable than that of the general method, in which dispersive solid-phase extraction was used as an additional purified procedure. In addition, the limits of quantitation of this method were from 1 to 50 µg/kg. Therefore, a rapid, cost-effective, labor-saving method was proposed in the present work, which was suitable for the analysis of 41 pesticide residues in tobacco.

A Comparison of In-House Real-Time LAMP Assays with a Commercial Assay for the Detection of Pathogenic Bacteria.

Molecular detection of bacterial pathogens based on LAMP methods is a faster and simpler approach than conventional culture methods. Although different LAMP-based methods for pathogenic bacterial detection are available, a systematic comparison of these different LAMP assays has not been performed. In this paper, we compared 12 in-house real-time LAMP assays with a commercialized kit (Isothermal Master Mix) for the detection of Listeria monocytogenes, Salmonella spp, Staphylococcus aureus, Escherichia coli O157, E. coli O26, E. coli O45, E. coli O103, E. coli O111, E. coli O121, E. coli O145 and Streptococcus agalactiae. False-positive results were observed in all 12 in-house real-time LAMP assays, while all the negative controls of Isothermal Master Mix remained negative after amplification. The detection limit of Isothermal Master Mix for Listeria monocytogenes, Salmonella spp, Staphylococcus aureus, Escherichia coli O157, E. coli O26, E. coli O45, E. coli O103, E. coli O111, E. coli O121 and Streptococcus agalactiae was 1 pg, whereas the sensitivity of the commercialized kit for E. coli O145 was 100 pg. In conclusion, the 12 in-house real-time LAMP assays were impractical to use, while the commercialized kit Isothermal Master Mix was useful for the detection of most bacterial pathogens.

Simultaneous determination of herbicide residues in tobacco using ultraperformance convergence chromatography coupled with solid-phase extraction.

A time-saving and organic solvent efficient method to simultaneously determine six kinds of herbicide residues in tobacco using solid-phase extraction for sample clean-up and preconcentration and the highly sensitive ultraperformance convergence chromatography method was developed. Parameters for ultraperformance convergence chromatography, including the choice of stationary phase and modifiers, autobackpressure regulator pressure, column temperature, and the flow rate of mobile solvents, were optimized. The herbicide residues of napropamide, alachlor, quizalofop-ethyl, diphenamid, metolachlor, and clomazone in tobacco samples were successfully separated and detected at levels as low as 0.0043-0.0086 mg/kg within 5 min using a nonpolar high strength silica C18 selectivity for bases column and methanol as the cosolvent of the mobile phase of carbon dioxide (75-99.9%, v/v). Analysis of tobacco samples had recoveries of 69.8-95.0%, limit of quantitation of 0.0127-0.0245 mg/kg, limit of detection of 0.0043-0.0086 mg/kg, and correlation coefficient of >0.9990. Results support this method as an efficient alternative to current methodologies for the determination of herbicide residues in tobacco.

Association study of RELN polymorphisms with schizophrenia in Han Chinese population.

Schizophrenia (SZ) is a common and complex psychiatric disorder with a strong genetic component. Previous research suggests that mutations altering genes in neurodevelopmental pathways contribute to SZ. Reelin gene (RELN) maps to chromosome 7q22.1, the encoded protein plays a pivotal role in guiding neuronal migration, lamination and connection during embryonic brain development. Several reports had indicated that reduced RELN expression is associated with human mental illnesses such as SZ, mood disorders and autism. In this study, case-control association analyses were performed in the Han Chinese population to determine if the RELN gene is a susceptibility gene for SZ. Thirty-seven single nucleotide polymorphisms (SNPs) were genotyped in 528 paranoid SZ patients and 528 control subjects. A significant association was found between rs12705169 and SZ (p=0.001). Moreover, the haplotypes constructed from five SNPs showed significant differences between cases and controls (p=0.041). When subjects were divided by gender, rs12705169 remained significant difference only in females (OR=0.24, 95%CI=0.14-0.40 for CC and OR=0.40, 95%CI=0.27-0.58 for AC), both in the allele and genotype (p=0.0001 for both). This study describes a positive association between RELN and SZ in the Han Chinese population, and provides genetic evidence to support the gender difference of SZ.

2-[(5-Chloro-2-hy-droxy-benzyl-idene)amino]-3',6'-bis-(diethyl-amino)-spiro-[isoindoline-1,9'-xanthen]-3-one.

The title compound, C(35)H(35)ClN(4)O(3), resulted from a spiro-lactam ring closure of rhodamine B dye. The xanthene ring system is approximately planar [r.m.s. deviation = 0.050 (9) Šfor the xanthene ring]. The dihedral angles formed by the spiro-lactam and 5-chloro-2-hy-droxy-benzene rings with the xanthene ring system are 87.9 (7) and 79.1 (7)°, respectively.