Theoretical Design of Strengthened Nanotwinned γ*-Boron.

The distinctive electron deficiency and unusual multicenter bonding situations of boron give rise to fascinating chemical complexity and imaginative structural polymorphism. Herein, we employ an independently developed method to construct the new twinned γ*-boron based on the well-known hardest elemental boron, γ-B28. Notably, the newly propounded γ*-boron phases exhibit considerably close energy levels with γ-B28 under ambient conditions. The simulated X-ray diffraction patterns of stable twinned structure present excellent agreement with experimental data. First-principles calculations reveal a 7.5% increase in the ideal Vickers shear strength of γ*-boron compared to γ-B28, attributed to diverse bond responses within the twinned slabs. The evaluated hardness of nanotwinned γ*-B reaches 59 GPa in consideration of the size hardening effect. Our research presents an efficient strategy for constructing new polymorphs of boron with improved mechanical properties and expands the knowledge about twinning structures of boron.

A novel model for predicting prognosis in patients with idiopathic pulmonary fibrosis based on endoplasmic reticulum stress-related genes.

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease of unknown pathogenic origin. Endoplasmic reticulum (ER) stress refers to the process by which cells take measures to ER function when the morphology and function of the reticulum are changed. Recent studies have demonstrated that the ER was involved in the evolution and progression of IPF. In this study, we obtained transcriptome data and relevant clinical information from the Gene Expression Omnibus database and conducted bioinformatics analysis. Among the 544 ER stress-related genes (ERSRGs), 78 were identified as differentially expressed genes (DEGs). These DEGs were primarily enriched in response to ER stress, protein binding, and protein processing. Two genes (HTRA2 and KTN1) were included for constructing an accurate molecular signature. The overall survival of patients was remarkably worse in the high-risk group than in the low-risk group. We further analyzed the difference in immune cells between high-risk and low-risk groups. M0 and M2 macrophages were significantly increased in the high-risk group. Our results suggested that ERSRGs might play a critical role in the development of IPF by regulating the immune microenvironment in the lungs, which provide new insights on predicting the prognosis of patients with IPF.

Responses of root-associated fungal community structure of mycorrhizal plants to nitrogen and/or phosphorus addition in a subtropical forest.

Root-associated fungi play a vital role in maintaining nutrient absorption and health of host plants. To compare the responses of root-associated fungal community structures to nitrogen (N) and/or phosphorus (P) additions across differential mycorrhizal types, we collected roots of nine plant species belonging to three mycorrhizal types (arbuscular mycorrhiza, ectomycorrhiza, and ericoid mycorrhiza) under control and N and/or P addition treatments from a subtropical forest, and detected the diversity and community composition of fungi inhabiting roots through the high-throughput sequencing technique. The results showed that root-associated fungal communities of all nine plant species were mainly composed of Basidiomycota and Ascomycota. The relative abundance of Ascomycota and Basidiomycota was significantly lower and higher under the P addition than that under control, respectively. The relative abundance of Ascomycota of ericoid mycorrhizal trees was significantly higher than those of arbuscular mycorrhizal and ectomycorrhizal trees, while the relative abundance of Basidiomycota was significantly lower than the other two mycorrhizal types. Compared with the control, P addition significantly reduced the α-diversity and changed community composition of root-associated fungi across different mycorrhizal plant types, while no effect of N addition or mycorrhizal type was observed. Compared with the control and N addition treatments, NP addition caused root-associated fungal communities of all plants becoming integrally divergent. In addition, the fungal communities of ectomycorrhizal mycorrhizal trees became apparently convergent in comparison with those of arbuscular and ericoid mycorrhizal trees under the NP addition. Collectively, our results highlighted that P was a critical factor influencing community structures of tree root-associated fungi in subtropical forest soils. This study would enhance our understanding of the responses and maintenance mechanisms of plant root-associated fungal diversity under global environmental changes in the subtropical region.

Environmental and occupational risk factors for COPD and its prevalence among miners worldwide: a Mendelian randomization and meta-analysis study.

Chronic obstructive pulmonary disease (COPD) is the third leading cause of death after cardiovascular disease and stroke, and its incidence is associated with genetic, environmental, and occupational factors. Miner is high-risk population for COPD, but the global prevalence of COPD in this group is inaccurate. In this study, the environmental and occupational risk factors for COPD were explored comprehensively with a two-sample Mendelian randomization study by combining genome-wide association data from two large global sample sizes of publicly available databases, UK Biobank (n = 503,317) and FinnGen (n = 193,638), as well as the prevalence of COPD among miners was investigated with meta-analysis followed a random-effects model including seven studies (16,033 miners in total). This study found that asthma, smoking, shift work, and workplace dust exposure may increase an individual's risk of COPD. The pooled prevalence of COPD among miners globally was 12% (95% CI: 8%, 18%), with higher prevalence of COPD among ex-smokers and dust-exposed individuals, and was significantly influenced by the method of diagnosis. Our findings suggest that there is currently a lack of practical criteria for diagnosing COPD in the physical examination and screening of miners. The actual prevalence of COPD may be underestimated due to the healthy worker effect and the phenomenon of job switching, and appropriate policies should be favored in the future to reduce the risk of COPD in miner.

Characteristics, sources and health risk assessment of trace metals and polycyclic aromatic hydrocarbons in PM2.5 from Hefei, China.

Trace metals (TRs) and polycyclic aromatic hydrocarbons (PAHs) are major toxic components of fine particulate matter (PM2.5) and related to various health adverse outcomes. The study aims to get a better understanding of the contents, sources and risks of PM2.5-bounded TRs and PAHs in Hefei, China, during the period of 2019-2021. We collected 504 samples and measured twelve TRs and sixteen priority PAHs by inductively coupled plasma mass spectrometry and high-performance liquid chromatography. The annual mass concentrations of PM2.5 was fluctuated in the year of 2019-2021 at 50.95, 47.48 and 59.38 µg/m3, with seasonal variations in rank order of winter > spring > autumn > summer. The median concentrations of PM2.5-bounded Æ©TRs and Æ©PAHs were also fluctuated, 132.85, 80.93 and 120.27 ng/m3 for Æ©TRs, 2.57, 5.85 and 2.97 ng/m3 for Æ©PAHs, in the year of 2019, 2020 and 2021, respectively. Seasonal variations of Æ©TRs and Æ©PAHs show the highest concentration in winter. Positive matrix factorization was used for identified pollution emission sources, and TRs mainly originated from coal combustion, traffic emission and fugitive dust, while PAHs stemmed from biomass, diesel, gasoline and coal combustion. Health risk assessment indicated that adults were more vulnerable than children, the carcinogenic risk assessment of As and Cr manifested a certain degree of cancer risk (1.0 × 10-6 < CR < 1.0 × 10-4) in adults group, and health risks of TRs were higher than PAHs in Hefei. These findings suggest that PM2.5-bounded TRs and PAHs should be considered when making emission control strategies for air pollution, and winter, combustion sources and adults should achieve more policy attention to decrease exposure risks in Hefei.

Response of gene abundance of ammonia-oxidizing microorganisms and denitrifying microorganisms to nitrogen and phosphorus addition in subtropical forest.

We conducted a nitrogen (N) and phosphorus (P) addition experiment in Qianjiangyuan National Park in 2015, to investigate the response of ammonia-oxidizing microorganisms and denitrifying microorganisms. There were four treatments, including N addition (N), P addition (P), NP, and control (CK). Soil samples were collected in April (wet season) and November (dry season) of 2021. The abundance of amoA gene of ammonia-oxidizing microorganisms (i.e., ammonia-oxidizing archaea, AOA; ammonia-oxidizing bacteria, AOB; comammox) and denitrifying microbial genes (i.e., nirS, nirK, and nosZ) were determined using quantitative PCR approach. The results showed that soil pH was significantly decreased by long-term N addition, while soil ammonium and nitrate contents were significantly increased. Soil available P and total P contents were significantly increased with the long-term P addition. The addition of N (N and NP treatments) significantly increased the abundance of AOB-amoA gene in both seasons, and reached the highest in the N treatment around 8.30×107 copies·g-1 dry soil. The abundance of AOA-amoA gene was significantly higher in the NP treatment than that in CK, with the highest value around 1.17×109 copies·g-1 dry soil. There was no significant difference in N-related gene abundances between two seasons except for the abundance of comammox-amoA. Nitrogen addition exerted significant effect on the abundance of AOB-amoA, nirK and nosZ genes, especially in wet season. Phosphorus addition exerted significant effect on the abundance of AOA-amoA and AOB-amoA genes in both seasons, but did not affect denitrifying gene abundances. Soil pH, ammonium, nitrate, available P, and soil water contents were the main factors affecting the abundance of soil N-related functional genes. In summary, the response of soil ammonia-oxidizing microorganisms and denitrifying microorganisms was more sensitive to N addition than to P addition. These findings shed new light for evaluating soil nutrient availability as well as their response mechanism to global change in subtropical forests.

Evidence Based on an Integrative Analysis of Multi-Omics Data on METTL7A as a Molecular Marker in Pan-Cancer.

Methyltransferase-like protein 7A (METTL7A), an RNA N6-methyladenosine (m6A) methyltransferase, has attracted much attention as it has been found to be closely associated with various types of tumorigenesis and progression. This study provides a comprehensive assessment of METTL7A from a pan-cancer perspective using multi-omics data. The gene ontology enrichment analysis of METTL7A-binding proteins revealed a close association with methylation and lipid metabolism. We then explored the expression of METTL7A in normal tissues, cell lines, different subtypes and cancers, and found that METTL7A was differentially expressed in various cancer species, tumor molecular subtypes and immune subtypes. Evaluation of the diagnostic and prognostic value of METTL7A in pan-cancer revealed that METTL7A had high accuracy in tumor prediction. Moreover, the low expression of METTL7A significantly correlated with the poor prognosis, including kidney renal clear cell carcinoma (KIRC), mesothelioma and sarcoma, indicating that METTL7A could be a potential biomarker for tumor diagnosis and prognosis. We focused on KIRC after pre-screening and analyzed its expression and prognostic value in various clinical subgroups. We found that METTL7A was significantly related to tumor stage, metastasis stage, pathologic stage, primary therapy outcome, histologic grade and gender, and that low METTL7A expression was associated with poorer outcomes. Finally, we analyzed the immune infiltration and co-expressed genes of METTL7A as well as the differentially expressed genes in the high and low expression groups. In conclusion, METTL7A is a better molecular marker for pan-cancer diagnosis and prognosis and has high potential as a diagnostic and prognostic biomarker for KIRC.

Impaired autophagy-accelerated senescence of alveolar type II epithelial cells drives pulmonary fibrosis induced by single-walled carbon nanotubes.

BACKGROUND: The rapid increase in production and application of carbon nanotubes (CNTs) has led to wide public concerns in their potential risks to human health. Single-walled CNTs (SWCNTs), as an extensively applied type of CNTs, have shown strong capacity to induce pulmonary fibrosis in animal models, however, the intrinsic mechanisms remain uncertain. RESULTS: In vivo experiments, we showed that accelerated senescence of alveolar type II epithelial cells (AECIIs) was associated with pulmonary fibrosis in SWCNTs-exposed mice, as well as SWCNTs-induced fibrotic lungs exhibited impaired autophagic flux in AECIIs in a time dependent manner. In vitro, SWCNTs exposure resulted in profound dysfunctions of MLE-12 cells, characterized by impaired autophagic flux and accelerated cellular senescence. Furthermore, the conditioned medium from SWCNTs-exposed MLE-12 cells promoted fibroblast-myofibroblast transdifferentiation (FMT). Additionally, restoration of autophagy flux with rapamycin significantly alleviated SWCNTs-triggered senescence and subsequent FMT whereas inhibiting autophagy using 3-MA aggravated SWCNTs-triggered senescence in MLE-12 cells and FMT. CONCLUSION: SWCNTs trigger senescence of AECIIs by impairing autophagic flux mediated pulmonary fibrosis. The findings raise the possibility of senescence-related cytokines as potential biomarkers for the hazard of CNTs exposure and regulating autophagy as an appealing target to halt CNTs-induced development of pulmonary fibrosis.

Mercury stress tolerance in wheat and maize is achieved by lignin accumulation controlled by nitric oxide.

Nitric oxide (NO) is an important phytohormone for plant adaptation to mercury (Hg) stress. The effect of Hg on lignin synthesis, NO production in leaf, sheath and root and their relationship were investigated in two members of the grass family - wheat and maize. Hg stress decreased growth and lignin contents, significantly affected phenylpropanoid and monolignol pathways (PAL, phenylalanine ammonia-lyase; 4-coumarate: CoA ligase, 4CL; cinnamyl alcohol dehydrogenase, CAD), with maize identified to be more sensitive to Hg stress than wheat. Among the tissue types, sheath encountered severe damage compared to leaves and roots. Hg translocation in maize was about twice that in wheat. Interestingly, total NO produced under Hg stress was significantly decreased compared to control, with maximum reduction of 43.4% and 42.9% in wheat and maize sheath, respectively. Regression analysis between lignin and NO contents or the activities of three enzymes including CAD, 4CL and PAL displayed the importance of NO contents, CAD, 4CL and PAL for lignin synthesis. Further, the gene expression profiles encoding CAD, 4CL and PAL provided support for the damaging effect of Hg on wheat sheath, and maize shoot. To validate NO potential to mitigate Hg toxicity in maize and wheat, NO donor and NO synthase inhibitor were supplemented along with Hg. The resulting phenotype, histochemical analysis and lignin contents showed that NO mitigated Hg toxicity by improving growth and lignin synthesis and accumulation. In summary, Hg sensitivity was higher in maize seedlings compared to wheat, which was associated with the lower lignin contents and reduced NO contents. External supplementation of NO is proposed as a sustainable approach to mitigate Hg toxicity in maize and wheat.

Interfacial compatibility critically controls Ru/TiO2 metal-support interaction modes in CO2 hydrogenation.

Supports can widely affect or even dominate the catalytic activity, selectivity, and stability of metal nanoparticles through various metal-support interactions (MSIs). However, underlying principles have not been fully understood yet, because MSIs are influenced by the composition, size, and facet of both metals and supports. Using Ru/TiO2 supported on rutile and anatase as model catalysts, we demonstrate that metal-support interfacial compatibility can critically control MSI modes and catalytic performances in CO2 hydrogenation. Annealing Ru/rutile-TiO2 in air can enhance CO2 conversion to methane resulting from enhanced interfacial coupling driven by matched lattices of RuOx with rutile-TiO2; annealing Ru/anatase-TiO2 in air decreases CO2 conversion and converts the product into CO owing to strong metal-support interaction (SMSI). Although rutile and anatase share the same chemical composition, we show that interfacial compatibility can basically modify metal-support coupling strength, catalyst morphology, surface atomic configuration, MSI mode, and catalytic performances of Ru/TiO2 in heterogeneous catalysis.

Suppressing Effect of Na+/Ca2+ Exchanger (NCX) Inhibitors on the Growth of Melanoma Cells.

The role of calcium ion (Ca2+) signaling in tumorigenicity has received increasing attention in melanoma research. Previous Ca2+ signaling studies focused on Ca2+ entry routes, but rarely explored the role of Ca2+ extrusion. Functioning of the Na+/Ca2+ exchanger (NCX) on the plasma membrane is the major way of Ca2+ extrusion, but very few associations between NCX and melanoma have been reported. Here, we explored whether pharmacological modulation of the NCX could suppress melanoma and promise new therapeutic strategies. Methods included cell viability assay, Ca2+ imaging, immunoblotting, and cell death analysis. The NCX inhibitors SN-6 and YM-244769 were used to selectively block reverse operation of the NCX. Bepridil, KB-R7943, and CB-DMB blocked either reverse or forward NCX operation. We found that blocking the reverse NCX with SN-6 or YM-244769 (5-100 µM) did not affect melanoma cells or increase cytosolic Ca2+. Bepridil, KB-R7943, and CB-DMB all significantly suppressed melanoma cells with IC50 values of 3-20 µM. Bepridil and KB-R7943 elevated intracellular Ca2+ level of melanoma. Bepridil-induced melanoma cell death came from cell cycle arrest and enhanced apoptosis, which were all attenuated by the Ca2+ chelator BAPTA-AM. As compared with melanoma, normal melanocytes had lower NCX1 expression and were less sensitive to the cytotoxicity of bepridil. In conclusion, blockade of the forward but not the reverse NCX leads to Ca2+-related cell death in melanoma and the NCX is a potential drug target for cancer therapy.

Imaging asparaginyl endopeptidase (AEP) in the live brain as a biomarker for Alzheimer's disease.

BACKGROUND: Discovery of early-stage biomarkers is a long-sought goal of Alzheimer's disease (AD) diagnosis. Age is the greatest risk factor for most AD and accumulating evidence suggests that age-dependent elevation of asparaginyl endopeptidase (AEP) in the brain may represent a new biological marker for predicting AD. However, this speculation remains to be explored with an appropriate assay method because mammalian AEP exists in many organs and the level of AEP in body fluid isn't proportional to its concentration in brain parenchyma. To this end, we here modified gold nanoparticle (AuNPs) into an AEP-responsive imaging probe and choose transgenic APPswe/PS1dE9 (APP/PS1) mice as an animal model of AD. Our aim is to determine whether imaging of brain AEP can be used to predict AD pathology. RESULTS: This AEP-responsive imaging probe AuNPs-Cy5.5-A&C consisted of two particles, AuNPs-Cy5.5-AK and AuNPs-Cy5.5-CABT, which were respectively modified with Ala-Ala-Asn-Cys-Lys (AK) and 2-cyano-6-aminobenzothiazole (CABT). We showed that AuNPs-Cy5.5-A&C could be selectively activated by AEP to aggregate and emit strong fluorescence. Moreover, AuNPs-Cy5.5-A&C displayed a general applicability in various cell lines and its florescence intensity correlated well with AEP activity in these cells. In the brain of APP/PS1 transgenic mice , AEP activity was increased at an early disease stage of AD that precedes formation of senile plaques and cognitive impairment. Pharmacological inhibition of AEP with δ-secretase inhibitor 11 (10 mg kg-1, p.o.) reduced production of ß-amyloid (Aß) and ameliorated memory loss. Therefore, elevation of AEP is an early sign of AD onset. Finally, we showed that live animal imaging with this AEP-responsive probe could monitor the up-regulated AEP in the brain of APP/PS1 mice. CONCLUSIONS: The current work provided a proof of concept that assessment of brain AEP activity by in vivo imaging assay is a potential biomarker for early diagnosis of AD.

Perfluoro octanoic acid-modified magnetic hyperbranched polyamideamine as a sorbent for the extraction of fluorine-containing pesticides from water samples.

Perfluoro octanoic acid was modified on the surface of magnetic hyperbranched polyamideamine by acid amine condensation. The morphology and chemical composition of perfluoro octanoic acid-modified magnetic hyperbranched polyamideamine was characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, zeta potential, particle size analysis, Brunauer-Emmett-Teller measurement, and X-ray photoelectron spectroscopy. Perfluoro octanoic acid-modified magnetic hyperbranched polyamideamine was applied in magnetic solid phase extraction for the separation and enrichment of four fluorine-containing pesticides (indoxacarb, metaflumizone, cyflumetofen, and cyhalothrin). The magnetic solid phase extraction method based on perfluoro octanoic acid-modified magnetic hyperbranched polyamideamine has low method detection limits (0.30-0.49 µg/L), a satisfactory coefficient of determination (0.9995-0.9999), wide linear ranges (2.5-250 µg/L), and good repeatability (intraday: 2.6-4.7%; interday: 1.1-7.9%). The enrichment factors and extraction efficiences varied from 55 to 76 and 69 to 96%, respectively. The sorbent-to-sorbent reproducibility was in the range of 3.2-7.6%, indicating that the synthesis of the sorbent was reliable. For the detection of actual water samples, the relative recoveries were in the range from 80.1 to 114.4% with relative standard deviations less than 9.6%. The calculation results of quantum chemistry calculations showed that after the modification of perfluoro octanoic acid, the interaction between the sorbent and four fluorine-containing pesticides was stronger.

1-Octyl-3-methylimidazolium hexafluorophosphate-functionalised magnetic poly ß-cyclodextrin for magnetic solid-phase extraction ofpyrethroids from tea infusions.

In this study, a novel sorbent, 1-octyl-3-methylimidazolium hexafluorophosphate functionalised magnetic poly ß-cyclodextrin, was successfully synthesised and applied to magnetic solid-phase extraction for the determination of pyrethroids in tea infusions. The sorbent was characterised by transmission electron microscopy, energy-dispersive spectroscopy, Fourier transform infrared spectroscopy, X-ray photoelectron spectroscopy, vibrating sample magnetometer and Brunauer-Emmett-Teller measurement. All factors affecting extraction efficiency, such as sorbent amount, extraction time, ionic strength and desorption conditions, were optimised individually. Under the chosen conditions, wide linearity (2.5-500 µg L-1) with determination coefficients ranging from 0.9995 to 0.9999, low limits of detection of 0.32-0.54 µg L-1 and good precision (intra-day: 2.6-7.0%; inter-day: 3.5-7.6%) were achieved for four pyrethroids in tea infusions. The relative recoveries of target analytes in real tea infusion samples were from 70% to 101% with relative standard deviations lower than 9.1%. We conclude that the proposed method is promising in the detection of pyrethroids in tea infusions.

Use of 1-octyl-3-methylimidazole hexafluorophosphate modified magnetic hyperbranched polyamideamine as sorbent for the extraction of pyrethroid insecticides from tea infusion.

Magnetic hyperbranched polyamideamine was carboxylated using succinic anhydride and modified further with 1-octyl-3-methylimidazole hexafluorophosphate successively. The morphology and chemical composition of the prepared material was characterized by transmission electron microscopy, scanning electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller measurement, X-ray photoelectron spectroscopy, etc. 1-Octyl-3-methylimidazole hexafluorophosphate modified magnetic hyperbranched polyamideamine was used as sorbent in the magnetic solid-phase extraction for the separation and enrichment of five pyrethroid insecticides from tea infusion. The magnetic solid-phase extraction method proposed in this article has low method detection limits (0.53-0.71 ng/mL), acceptable coefficient of determination (0.9992-0.9998), wide linear ranges (2.5-500.0 ng/mL), and good repeatability (intraday: 1.2-6.3%; interday: 1.6-5.4%). In the detection of five pyrethroid insecticides in tea infusion, relative recoveries were in the range from 87.7 to 114.7% with satisfactory relative standard deviations (0.2-7.4%). With the aid of quantum chemistry calculations, the interaction energy between the sorbent and five pyrethroid insecticides was calculated, which proved the necessity of the modification of 1-octyl-3-methylimidazole hexafluorophosphate.

Pharmacological inhibition of asparaginyl endopeptidase by δ-secretase inhibitor 11 mitigates Alzheimer's disease-related pathologies in a senescence-accelerated mouse model.

BACKGROUND: Currently, there is no cure for Alzheimer's disease (AD). Therapeutics that can modify the early stage of AD are urgently needed. Recent studies have shown that the pathogenesis of AD is closely regulated by an endo/lysosomal asparaginyl endopeptidase (AEP). Inhibition of AEP has been reported to prevent neural degeneration in transgenic mouse models of AD. However, more than 90% of AD cases are age-related sporadic AD rather than hereditary AD. The therapeutic efficacy of AEP inhibition in ageing-associated sporadic AD remains unknown. METHODS: The senescence-accelerated mouse prone 8 (SAMP8) was chosen as an approximate model of sporadic AD and treated with a selective AEP inhibitor,: δ-secretase inhibitor 11. Activation of AEP was determined by enzymatic activity assay. Concentration of soluble amyloid ß (Aß) in the brain was determined by ELISA. Morris water maze test was performed to assess the learning and memory-related cognitive ability. Pathological changes in the brain were explored by morphological and western blot analyses. RESULTS: The enzymatic activity of AEP in the SAMP8 mouse brain was significantly higher than that in the age-matched SAMR1 mice. The half maximal inhibitory concentration (IC50) for δ-secretase inhibitor 11 to inhibit AEP in vitro is was around 150 nM. Chronic treatment with δ-secretase inhibitor 11 markedly decreased the brain AEP activity, reduced the generation of Aß1-40/42 and ameliorated memory loss. The inhibition of AEP with this reagent not only reduced the AEP-cleaved tau fragments and tau hyperphosphorylation, but also attenuated neuroinflammation in the form of microglial activation. Moreover, treatment with δ-secretase inhibitor 11 prevented the synaptic loss and alleviated dendritic disruption in SAMP8 mouse brain. CONCLUSIONS: Pharmacological inhibition of AEP can intervene and prevent AD-like pathological progress in the model of sporadic AD. The up-regulated AEP in the brain could be a promising target for early treatment of AD. The δ-secretase inhibitor 11 can be used as a lead compound for translational development of AD treatment.

Hyperbranched aromatic polyamide modified magnetic nanoparticles for the extraction of benzoylurea insecticides.

Herein, a novel hyperbranched aromatic polyamide-coated magnetic sorbent was prepared by in situ polymerization on the surface of amino-functionalized Fe3 O4 nanoparticles. The magnetic sorbent was characterized by transmission electron microscopy, Fourier transform infrared spectroscopy, elemental analysis, Brunauer-Emmett-Teller measurement, and X-ray photoelectron spectroscopy, etc. The new magnetic sorbent was used in the magnetic solid-phase extraction for the detection of seven benzoylurea insecticides. Under optimum conditions, low method detection limits (0.56-1.20 ng/mL), acceptable coefficient of determination (0.9967-0.9996), wide linear ranges (2.5-500.0 ng/mL), and good repeatability (intraday: 2.0-7.3%; interday: 1.9-9.2%) were achieved. The magnetic solid-phase extraction method based on the new magnetic sorbent showed good reliability in the analysis of seven benzoylurea insecticides in real water samples, as the relative recoveries were in the range from 80.1 to 116.3% with satisfactory RSDs (0.1-9.8%). By means of density functional theory and semiempirical quantum mechanical, the binding configuration and interaction energy of hyperbranched aromatic polyamide and benzoylurea insecticides were calculated. The result of theoretical calculation revealed that the adsorption of benzoylurea insecticides by hyperbranched aromatic polyamide was derived from hydrogen bonding and π-π stacking. The contribution of π-π stacking was greater than that of hydrogen bond, which was confirmed by energy decomposition analysis.

Phosphonium-based deep eutectic solvent coupled with vortex-assisted liquid-liquid microextraction for the determination of benzoylurea insecticides in olive oil.

In this study, a novel method using a phosphonium-based deep eutectic solvent coupled with vortex-assisted liquid-liquid microextraction was investigated for the enrichment and separation of five benzoylurea insecticides in olive oil. The experimental factors affecting the extraction efficiency, including the extractant type, deep eutectic solvent volume, extraction time, and extraction mode, were optimized. Under optimal conditions, good linearity was observed for all target analytes, with correlation coefficients (r) ranging from 0.9971 to 0.9998; the limits of detection were in the range of 1.5 to 7.5 µg/L, and the recoveries of analytes using the proposed method ranged between 66.9 and 111.0%. The simple, rapid, and effective method was successfully applied for detecting target analytes in olive oil sample.

The Effect of Rotigotine Extended-Release Microspheres Alone or With Celecoxib on the Inflammatory Pain.

Clinical trials of rotigotine extended-release microspheres (RTGT-MS), which provides a sustained release of rotigotine for near 2 weeks in vivo, have been conducted in the treatment of Parkinson's disease (PD). This study was to investigate the analgesic effect of RTGT-MS, and to know whether RTGT-MS have synergistic interaction with non-steroidal anti-inflammatory drug, celecoxib. The inflammatory pain model of rats was prepared by carrageenan-induced paw edema. The thermal and mechanical stimuli were applied and the hindpaw withdrawal latency (HWL) response was evaluated. Treatment with RTGT-MS increased the HWL in a dose-dependent manner. The ED50 of RTGT-MS was 24.68 ± 1.02 mg/kg. Isobolographic analysis shows that the combination of RTGT-MS and celecoxib resulted in a synergistic antinociceptive effect. Further results demonstrated that antinociceptive effect of RTGT-MS was accompanied with that PKA, cAMP, COX-2, and PGE2 levels were decreased. Chlorpromazine, a dopamine receptor blocker, not only weakened the analgesic effect of RTGT-MS, but also increased the levels of cAMP, PKA, COX-2, and PGE2. These findings provide a rationale for the combination of RTGT-MS and celecoxib in the treatment of PD, which may reduce the dose of celecoxib, thereby lowering the incidence of adverse effects and improving the pain management in PD patients.

Dispersive micro-solid phase extraction based on a graphene/polydopamine composite for the detection of pyrethroids in water samples.

In this study, a simple, rapid, precise, and environmentally friendly microextraction named dispersive micro-solid phase extraction based on a graphene/polydopamine composite as a sorbent was investigated for the analysis of four pyrethroids (fenpropathrin, cyhalothrin, etofenprox and bifenthrin) in water samples. The graphene/polydopamine composite was successfully synthesized using a one-step method, and was characterized by scanning electron microscopy, transmission electron microscopy, energy-dispersive spectroscopy and X-ray photoelectron spectroscopy. The simplicity and rapidity of dispersive micro-solid phase extraction and the high surface area and adsorptivity of the graphene/polydopamine composite were combined in the proposed method. Several main parameters, including the amount of the sorbent, extraction time, ionic strength and desorption conditions, were independently optimized and the results were compared to find the best extraction setup for dispersive micro-solid phase extraction. Under the optimal conditions, good linearity was observed for all the target analytes, with the coefficient of determination ranging from 0.9997 to 0.9999. The extraction recoveries obtained using the proposed method ranged from 76.81% to 85.29%, and the limits of detection varied from 1.5 to 3 µg L-1. In addition, the relative standard deviation values for the intra-day precision were between 0.41% and 3.00%, while the inter-day precision showed relative standard deviation values ranging from 1.61% to 5.59%. Overall, the figures of merit of the entire procedure showed that this technique could produce satisfactory results in the detection of pyrethroids in water samples or other organic pollutants in the future.