Synthesis, radiolabeling, and evaluation of a potent ß-site APP cleaving enzyme (BACE1) inhibitor for PET imaging of BACE1 in vivo.

The ß-site APP-cleaving enzyme 1 (BACE1) plays important roles in the proteolytic processing of amyloid precursor protein, and can be regarded as an important target for the diagnosis and treatment of AD. This study aimed to report the synthesis and evaluation of an 18F-labeled 2-amino-3,4-dihydroquinazoline analog as a potential BACE1 radioligand. A fluoropropyl side chain was introduced to the phenyl of this 3,4-dihydroquinazoline scaffold to generate the radioligand. Our preliminary data indicated that although the 2-amino-3,4-dihydroquinazoline scaffold possessed favorable in-vitro properties as a PET ligand, its poor brain uptake hindered the in-vivo imaging of BACE1. Further investigation would be required to optimize the scaffold for the development of a blood-brain-barrier-permeable BACE1-targeted PET ligand.

Biogenic volatile organic compound emission patterns and secondary pollutant formation potentials of dominant greening trees in Chengdu, southwest China.

Integral to the urban ecosystem, greening trees provide many ecological benefits, but the active biogenic volatile organic compounds (BVOCs) they release contribute to the production of ozone and secondary organic aerosols, which harm ambient air quality. It is, therefore, necessary to understand the BVOC emission characteristics of dominant greening tree species and their relative contribution to secondary pollutants in various urban contexts. Consequently, this study utilized a dynamic enclosure system to collect BVOC samples of seven dominant greening tree species in urban Chengdu, Southwest China. Gas chromatography/mass spectrometry was used to analyze the BVOC components and standardized BVOC emission rates of each tree species were then calculated to assess their relative potential to form secondary pollutants. We found obvious differences in the composition of BVOCs emitted by each species. Ficus virens displayed a high isoprene emission rate at 31.472 µgC/(gdw (g dry weight)•hr), while Cinnamomum camphora emitted high volumes of D-Limonene at 93.574 µgC/(gdw•hr). In terms of the BVOC emission rates by leaf area, C. camphora had the highest emission rate of total BVOCs at 13,782.59 µgC/(m2•hr), followed by Cedrus deodara with 5466.86 µgC/(m2•hr). Ginkgo biloba and Osmanthus fragrans mainly emitted oxygenated VOCs with lower overall emission rates. The high BVOC emitters like F. virens, C. camphora, and Magnolia grandiflora have high potential for significantly contributing to environmental secondary pollutants, so should be cautiously considered for future planting. This study provides important implications for improving urban greening efforts for subtropical Chinese urban contexts, like Chengdu.

Antibacterial activity of ZnO quantum dots and its protective effects of chicks infected withSalmonella pullorum.

In light of emerging antibiotic resistance, synthesis of active, environmental friendly antimicrobial alternatives becomes increasingly necessary. In this study, ZnO quantum dots (ZnO QDs) were developed by the sol-gel method and characterized. The antibacterial activities of ZnO QDs againstEscherichia coli(E. coli),Staphylococcus aureus(S. aureus) andSalmonella Pullorum(S. Pullorum) were systematically investigated. Moreover, the protective effects of ZnO QDs on Salmonella-caused pullorosis in chicks were also explored. The results indicated that the size range of ZnO QDs was 3-6 nm. Antibacterial results showed that ZnO QDs treatment inhibited the growth ofE. coli,S. aureus, andS. Pullorumin the rate of 87.06 ± 0.98%, 94.75 ± 2.28%, and 85.55 ± 1.15%, respectively. Its excellent antibacterial property was manifested with the minimum inhibitory concentration of 0.7812, 0.0976, and 0.1953 mg ml-1, which may be attributed to the production of reactive oxygen species, the dissolution of Zn2+ions, and the loss of cell integrity. Furthermore, in thein vivotest, the ZnO QDs effectively reduced the mortality of chicks infected withS. Pullorumvia regulating the balance of the intestinal flora, protecting liver and intestine, and modulating the balance of antioxidation systems. This study reveals that ZnO QDs exerts remarkably antibacterial activityin vitroand anti-pullorosis effect in chicks.

Fluorometric dopamine assay based on an energy transfer system composed of aptamer-functionalized MoS2 quantum dots and MoS2 nanosheets.

The authors describe a fluorometric strategy for the determination of dopamine (DA). It is based on the use of aptamer-functionalized MoS2 quantum dots (QDs) and MoS2 nanosheets (NSs). The QDs and NSs were extensively characterized with regard to their physical and chemical properties using methods such as TEM, XRD, FT-IR, EDX and molecular spectroscopies. The aptamer against dopamine was labeled with QDs acting as the energy donor in an energy transfer system, while the NSs serve as the energy acceptor. Under the optimal conditions, the fluorescence (FL) intensity (best measured at excitation/emission peaks of 315/412 nm) increases with increasing DA concentration in the range from 0.1 nM to 1000 nM, with a lower detection limit of 45 pM. The method was successfully applied to the determination of DA in complex matrices. In our perception, the method has a wide scope in that it may be extended to other biomolecules for which respective aptamer are available. The QDs show excellent optical properties, good stability, low cytotoxicity, and may also be applied to fluorometric imaging of live cells. Graphical abstract A "turn-on" fluorometric aptasensor for the determination of dopamine (DA) was established based on aptamer-functionalized molybdenum disulfide quantum dots (MoS2 QDs) and MoS2 nanosheets. This assay exhibits high selectivity and sensitivity with a detection limit as low as 45 pM.

False human immunodeficiency virus test results associated with rheumatoid factors in rheumatoid arthritis.

OBJECTIVE: To investigate if immunological factors associated with rheumatoid arthritis (RA) affect the result of human immunodeficiency virus (HIV) screening by electrochemiluminescence immunoassay (ECLIA) and enzyme-linked immunosorbent assay (ELISA). METHODS: 100 RA cases were enrolled from January 2012 to February 2013 into this study. HIV screening was conducted with ECLIA detecting both HIV-1 p24 antigen, HIV-1 and HIV-2 antibodies, with ELISA and colloidal gold method detecting HIV-1 and HIV-2 antibodies. The samples producing positive results were submitted to the Center for Disease Control for confirmation using Western blotting method. The antibody titers of rheumatoid factors (RF) including RF-IgG, RF-IgM, RF-IgA, and CCP-IgG were analyzed by ELISA. RESULTS: The HIV positive-rate determined by ECLIA was significantly higher than that by ELISA and colloidal gold method (P<0.01). The false-positive rate of HIV screening was associated with antibody titers of RF-IgG, RF-IgM, RF-IgA, and CCP-IgG in RA (P<0.01). CONCLUSIONS: Immunological factors, including RF and anti-CCP antibody, may influence the screening of HIV by ECLIA, producing false-positive result.

The Study on the factors affecting transformation efficiency of E. coli competent cells.

The preparation of competent cell is the central step of bacteria transformation and has a great impact on transformation efficiency of nucleic acid. The aim of the research was to study the factors such as ionic species, strain types, plasmid concentration, ice-bath time and incubation time. The result shows that ionic species is fatal to the transformation efficiency, preparation of competent cells by monovalent ions (Li(+),Na(+),K(+)) and tervalent ion (Al(3+)) do not have capacity of transformation, preparation of competent cells by bivalent ion (Ba(2+),Ca(2+),Mn(2+),Mg(2+),Sr(2+)) has capacity of transformation. On the whole, the efficiency of Ca(2+) was found to be the optimum bivalent ion, following by Sr(2+),Mn(2+),Mg(2+),Ba(2+). On the other factors that affecting transformation efficiency, the transformation efficiency was the best when plasmid concentration was 100ng/mL, and ice-bath time should be controlled at about 30 min and incubate time selected as 60 min. Experiment of natural transformation later proves the existence of the phenomenon of natural transformation and it's also related to factors such as calcium chloride concentration, plasmid concentration and others.

Photothermal and ferroptosis synergistic therapy for liver cancer using iron-doped polydopamine nanozymes.

An innovative nanozyme, iron-doped polydopamine (Fe-PDA), which integrates iron ions into a PDA matrix, conferred peroxidase-mimetic activity and achieved a substantial photothermal conversion efficiency of 43.5 %. Fe-PDA mediated the catalysis of H2O2 to produce toxic hydroxyl radicals (•OH), thereby facilitating lipid peroxidation in tumour cells and inducing ferroptosis. Downregulation of solute carrier family 7 no. 11 (SLC7A11) and solute carrier family 3 no. 2 (SLC3A2) in System Xc- resulted in decreased intracellular glutathione (GSH) production and inactivation of the nuclear factor erythroid 2-related factor 2 (NRF2)-glutathione peroxidase 4 (GPX4) pathway, contributing to ferroptosis. Moreover, the application of photothermal therapy (PTT) enhanced the effectiveness of chemodynamic therapy (CDT), accelerating the Fenton reaction for targeted tumour eradication while sparing adjacent non-cancerous tissues. In vivo experiments revealed that Fe-PDA significantly hampered tumour progression in mice, emphasizing the potential of the dual-modality treatment combining CDT and PTT for future clinical oncology applications.

An efficient ratiometric fluorescence and colorimetric dual-mode probe for convenient determination of nitrite in real samples and E. coli.

Developing an effective and convenient nitrite detection method is indispensable in food safety, environmental monitoring, clinical diagnosis of diseases, and many other areas. Herein, a dicyanoisophorone derivative, TMN-NH2 with large Stokes shift and near-infrared (NIR) emission, was proposed as a ratiometric fluorescence and colorimetric dual-mode probe for the rapid determination of NO2- in acidic media, showing excellent selectivity and high sensitivity. The sensing mechanism is based on the diazotization of TMN-NH2 with NO2- and subsequent diazonium salt hydrolysis to form a hydroxyl-substituted product (TMN-OH). Under the optimized conditions of reaction and detection, a new quantitative analysis method based on TMN-NH2 was established for NO2- detection, exhibiting good linear relationships to NO2- in the range of 0.5 to 15 µM with practical detection limits of 26.6 nM and 17.6 nM for the colorimetric and fluorescent readout, respectively. The quantitative detection of NO2- in real samples demonstrated satisfactory recoveries and repeatability. Moreover, TMN-NH2 was successfully applied for monitoring NO2- in Escherichia coli by confocal fluorescence imaging.

Preparation and characterization of EDTAD-modified magnetic-Fe3O4 chitosan composite: application of comparative adsorption of dye wastewater with magnetic chitosan.

Ethylenediaminetetraacetic dianhydride (EDTAD)-modified magnetic-Fe3O4 chitosan (EMC), prepared using the cross-link agent glutaraldehyde and chemicals Fe3O4, chitosan, and EDTAD, was used to compare the adsorption of methylene blue (MB) with magnetic chitosan (MC). The composite structure was confirmed by multiple characterization techniques, including scanning electron microscopy (SEM), X-ray powder diffraction, Fourier transform infrared spectroscopy (FTIR), and potentiometric titration methods. The characterization results suggest that Fe3O4 particles successfully bound on the surface of chitosan, and the EDTAD thoroughly modified the MC. Furthermore, EMC had more amino, carboxyl, and hydroxy groups than typical MC. Adsorption conditions, such as pH values, initial concentrations of MB, reaction temperature, and contact time were systematically examined. In comparison, the maximum adsorption capacity of EMC was approximately twice as much as that of MC. The recovery efficiency for EMC was >80% using 0.1 M HCl as an eluent solution. Therefore, the results reported herein indicate that EMC is very attractive and imply a practical application for dye wastewater treatment.

Degradation of tetracycline and sulfadiazine during continuous thermophilic composting of pig manure and sawdust.

During composting, the thermophilic phase resulted in high degradation of antibiotics in the composting mass; thus temperature is considered as the major factor for degradation of antibiotics. Therefore, to achieve complete removal of antibiotics, the effect of continuous thermophilic composting on the degradation of antibiotics and their effect on antibiotic resistant bacteria in the pig manure were evaluated. Pig manure was mixed with sawdust, spiked with tetracycline (10 and 100 mg/kg) and sulfadiazine (2 and 20mg/kg) on dry weight (DW) basis and composted at 55 degrees C for six weeks. Based on the organic decomposition, the antibiotics did not affect the composting process significantly, but negatively influenced the bacterial population. Tetracycline clearly exhibited a negative but marginal influence on carbon decomposition at 100 mg/kg level. The bacterial population initially decreased steeply approximately 2 logs and slowly increased thereafter. Sulfadiazine and tetracycline resistant bacterial populations were stable/marginally increased after an initial decrease of about 2 or 3-5 logs, respectively. Sulfadiazine was not detectable after three days; whereas, approximately 8% of tetracycline was detected after 42 days of composting with a t(1/2) of approximately 11 days, irrespective of the initial concentration. The presence of tetracycline in the compost after 42 days of thermophilic composting indicates the involvement of a mesophilic microbial-mediated degradation; however, further studies are required to confirm the direct microbial involvement in the degradation of antibiotics.

[Research on the relationship between combined detection of RF and CCP and Chinese medical syndrome patterns of RA].

OBJECTIVE: To study the objective diagnostic mechanisms on Chinese medical (CM) syndrome patterns of rheumatoid arthritis (RA), and to research different titers of rheumatoid factor (RF)/citrullinated protein antibody (CCP) in CM syndrome patterns of RA. METHODS: Totally 230 early RA patients were assigned to five CM syndrome pattern groups, i.e., the dampness-heat blockage group (50 cases), the cold-dampness blockage group (50 cases), the Shen-qi deficiency-cold group (50 cases), the Gan-Shen yin deficiency group (40 cases), and the blood stasis blockage group (40 cases). Another 100 healthy subjects were recruited as the healthy control group. RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody were detected and compared. RESULTS: The titers of RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody were higher in all groups than in the healthy control groups (P < 0.01). As for the 5 groups, RF-IGM, RF-IGA,RF-IGG, and anti-CCP antibody were higher in the RA active stage than in the nonactive stage. They were higher in the dampness-heat blockage group in the RA active stage than in the Shen-qi deficiency-cold group, the Gan-shen yin deficiency group, and the blood stasis blockage group. CONCLUSION: Titers of RF-IGM, RF-IGA, RF-IGG, and anti-CCP antibody could be taken as judging indicators for differentiating objective lab indices of CM syndromes and assessing the active stage of RA.

Two new species of the pseudoscorpion genus Stenohya (Pseudoscorpiones: Neobisiidae) from Guangxi Zhuang Autonomous Region, China.

Two new pseudoscorpion species, Stenohya dongtianensis sp. nov. and S. jiahensis sp. nov., from Guangxi Zhuang Autonomous Region, are described and illustrated. An identification key is provided for all known representatives of the genus Stenohya from China.

Formation pathways of aldehydes from heated cooking oils.

Cooking emissions account for a major fraction of urban volatile organic compounds and organic aerosol. Aldehyde species, in particular, are important exposure hazards in indoor residential and occupational environments, and precursors to particulate matter and ozone formation in outdoor air. Formation pathways of aldehydes from oils that lead to their emissions are not well understood. In this work, we investigate the underlying mechanisms involved in the formation of aldehydes from heated cooking oil emissions, through studying how antioxidants and oil composition modulate oxidation chemistry. Our results demonstrate that gaseous emissions are driven by radical-mediated autoxidation reactions in cooking oil, and the composition of cooking oils strongly influences the reaction mechanisms. Antioxidants have a dual effect on aldehyde emissions depending on the rates of radical propagation reactions. We propose a mechanistic framework that can be used to understand and predict cooking emissions under different cooking conditions. Our results highlight the need to understand the rates and mechanisms of autoxidation and other reactions in cooking oils in order to accurately predict the gas- and particle-phase emissions from food cooking in urban atmospheres.

Antioxidant and hypoglycemic activity of tea polysaccharides with different degrees of fermentation.

Four polysaccharides (GTPS, OTPS, BTPS and DTPS) were extracted from green tea, oolong tea, black tea and dark tea respectively. The physical and chemical properties, antioxidant and hypoglycemic activities were studied. Structural analysis showed that these tea polysaccharides were glycoprotein complexes, and there were significant differences in microstructure, protein, total sugar and uronic acid content. They were all composed of multiple monosaccharides and different molar ratios. In terms of antioxidant activity, completely fermented BTPS and DTPS had higher activity. Regarding to hypoglycemic effects, BTPS showed higher α-glucosidase inhibitory activity in vitro. And in the treatment of type 2 diabetes mice, Oral BTPS significantly controlled the levels of blood glucose, TG, TC, LDL-C, Cr, UREA, ALT and AST in diabetic mice, and improved insulin resistance. Histopathological observation further confirmed that BTPS can alleviate liver injury caused by hyperglycemia and hyperlipidemia. Data showed that BTPS significantly improved hyperglycemia and liver function in diabetic mice.

Synthesis, radiolabeling, and evaluation of a (4-quinolinoyl)glycyl-2-cyanopyrrolidine analogue for fibroblast activation protein (FAP) PET imaging.

Fibroblast activation protein (FAP) is regarded as a promising target for the diagnosis and treatment of tumors as it was overexpressed in cancer-associated fibroblasts. FAP inhibitors bearing a quinoline scaffold have been proven to show high affinity against FAP in vitro and in vivo, and the scaffold has been radio-labeled for the imaging and treatment of FAP-positive tumors. However, currently available FAP imaging agents both contain chelator groups to enable radio-metal labeling, making those tracers more hydrophilic and not suitable for the imaging of lesions in the brain. Herein, we report the synthesis, radio-labeling, and evaluation of a 18F-labeled quinoline analogue ([18F]3) as a potential FAP-targeted PET tracer, which holds the potential to be blood-brain barrier-permeable. [18F]3 was obtained by one-step radio-synthesis via a copper-mediated SNAR reaction from a corresponding boronic ester precursor. [18F]3 showed moderate lipophilicity with a log D 7.4 value of 1.11. In cell experiments, [18F]3 showed selective accumulation in A549-FAP and U87 cell lines and can be effectively blocked by the pre-treatment of a cold reference standard. Biodistribution studies indicated that [18F]3 was mainly excreted by hepatic clearance and urinary excretion, and it may be due to its moderate lipophilicity. In vivo PET imaging studies indicated [18F]3 showed selective accumulation in FAP-positive tumors, and specific binding was confirmed by blocking studies. However, low brain uptake was observed in biodistribution and PET imaging studies. Although our preliminary data indicated that [18F]3 holds the potential to be developed as a blood-brain barrier penetrable FAP-targeted PET tracer, its low brain uptake limits its application in the detection of brain lesions. Herein, we report the synthesis and evaluation of [18F]3 as a novel small-molecule FAPI-targeted PET tracer, and our results suggest further structural optimizations would be needed to develop a BBB-permeable PET tracer with this scaffold.

Five new troglobitic species of Tyrannochthonius (Arachnida, Pseudoscorpiones, Chthoniidae) from the Yunnan, Guizhou and Sichuan Provinces, China.

Five new species of the genus Tyrannochthonius Chamberlin, 1929 are described from caves in the provinces of Yunnan (T.huilongshanensis sp. nov., T.xinzhaiensis sp. nov., and T.yamuhensis sp. nov.), Guizhou (T.dongjiensis sp. nov.), and Sichuan (T.huaerensis sp. nov.). An identification key is provided for all known representatives of the genus Tyrannochthonius from China.

Cave-inhabiting Cheliferidae (Arachnida, Pseudoscorpiones) from Thailand, with description of four new species of Metachelifer Redikorzev.

Four new species of the genus Metachelifer Redikorzev, 1938 are described from caves in the provinces of Tak (M.takensis sp. nov. and M.thailandicus sp. nov.), Chiangmai (M.mahnerti sp. nov.), and Nakhon Ratchasima (M.cheni sp. nov.). An identification key is provided to all known world representatives of the genus Metachelifer.

A polysaccharide from Lycium barbarum L.: Structure and protective effects against oxidative stress and high-glucose-induced apoptosis in ARPE-19 cells.

Lycium barbarum polysaccharides (LBPs) are beneficial for vision; however, relevant research has mainly focused on entire crude polysaccharides, with the basis and exact structure of the polysaccharide rarely explored. In this study, LICP009-3F-2a, a novel polysaccharide from Lycium barbarum L., was separated and then purified using anion-exchange and size-exclusion chromatography. Structural characteristics were investigated using chemical and spectroscopic methods, which revealed that LICP009-3F-2a has an Mw of 13720 Da and is an acidic heteropolysaccharide composed of rhamnose (39.1%), arabinose (7.4%), galactose (22.5%), glucose (8.3%), galacturonic acid (13.7%), and glucuronic acid (4.0%). Linkage and NMR data revealed that LICP009-3F-2a has the following backbone: →2)-α-L-Rha-(1 â†’ 2,4)-α-L-Rha-(1 â†’ 4)-α-D-GalAp-(1 â†’ 3,6)-ß-D-Galp-(1 â†’ 3,6)-ß-D-Galp-(1 â†’ 6)-ß-D-Galp-(1→, with three main branches, including: α-L-Araf-(1 â†’ 5)-α-L-Araf-(1 â†’ 6)-ß-D-Glcp-(1 â†’ 2,4)-α-L-Rha-(1→, ß-D-Glcp-(1 â†’ 4)-ß-D-Glcp-(1 â†’ 3,6)-ß-D-Galp-(1→, and ß-D-Galp-(1 â†’ 3)-ß-D-Galp-(1 â†’ 3,6)-ß-D-Galp-(1 â†’ . Differential scanning colorimetry and thermogravimetric analysis showed that LICP009-3F-2a is thermally stable, while X-ray diffractometry showed that LICP009-3F-2a has a semi-crystalline structure. In addition, LICP009-3F-2a protects ARPE-19 cells from H2O2-induced oxidative damage by regulating the expression of antioxidant SOD1 and CAT enzymes and down-regulating MMP2 expression. Moreover, LICP009-3F-2a promotes the proliferation of ARPE-19 cells in a concentration-dependent manner, and protects ARPE-19 cells from hyperglycemia by inhibiting apoptosis.

In vivo PET Imaging of EGFR Expression: An Overview of Radiolabeled EGFR TKIs.

With the development of epidermal growth factor receptor (EGFR)-based tyrosine kinase inhibitors (TKIs) and their applications in the clinic, non-small-cell lung cancer (NSCLC) treatment has entered a new era, and a great number of patients have benefited. However, there still exist other subgroups of patients who may not benefit from EGFR TKIs, although EGFR mutation is the main driving mutation that leads to NSCLC. To identify potential NSCLC responders for TKI therapy and to detect EGFR status in vivo, noninvasive technology, such as TKI PET imaging, has been developed in recent years, and a great number of tyrosine kinase-targeted PET tracers have been reported. The visualization and quantification of EGFR expression in vivo by PET would provide the most important information for personalizing NSCLC therapy and prediction of response in clinical. This article reviews the progress of small molecular tyrosine kinase-targeted PET tracers and their applications in preclinical experiments and clinical studies. The current limitations and future development of these tracers are also briefly discussed.

Positron emission tomography imaging of lung cancer: An overview of alternative positron emission tomography tracers beyond F18 fluorodeoxyglucose.

Lung cancer has been the leading cause of cancer-related mortality in China in recent decades. Positron emission tomography-computer tomography (PET/CT) has been established in the diagnosis of lung cancer. 18F-FDG is the most widely used PET tracer in foci diagnosis, tumor staging, treatment planning, and prognosis assessment by monitoring abnormally exuberant glucose metabolism in tumors. However, with the increasing knowledge on tumor heterogeneity and biological characteristics in lung cancer, a variety of novel radiotracers beyond 18F-FDG for PET imaging have been developed. For example, PET tracers that target cellular proliferation, amino acid metabolism and transportation, tumor hypoxia, angiogenesis, pulmonary NETs and other targets, such as tyrosine kinases and cancer-associated fibroblasts, have been reported, evaluated in animal models or under clinical investigations in recent years and play increasing roles in lung cancer diagnosis. Thus, we perform a comprehensive literature review of the radiopharmaceuticals and recent progress in PET tracers for the study of lung cancer biological characteristics beyond glucose metabolism.