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Fifteen 1,2,4-triazole derivatives were synthesised in this study and their MIC values against Mycobacterium tuberculosis (Mtb) ranged from 2 to 32 μg/mL. Furthermore, their antimycobacterial activity was positively correlated with the KatG enzyme docking score. Among the 15 compounds, compound 4 showed the strongest bactericidal activity with an MIC of 2 μg/mL. The selectivity index of compound 4 is more than 10, indicating that the compound has low toxicity to animal cells and has the potential to become a drug. Molecular docking indicates that compound 4 can bind firmly to the Mtb KatG active site. The experimental results showed that compound 4 inhibited Mtb KatG and caused the accumulation of ROS in Mtb cells. We speculate that compound 4 causes the accumulation of ROS by inhibiting KatG, and ROS produces oxidative destruction, leading to the death of Mtb. This study provides a new idea for the development of novel anti-Mtb drugs. [ABSTRACT FROM AUTHOR]

This study aimed to observe the effects of puerarin on glycolysis and cisplatin sensitivity in oral squamous cell carcinoma (oSCC) cells and to explore the underlying mechanisms. CAL27 cells over- or under-expressing FBXW7 were treated with cisplatin or puerarin, and the levels of proteins involved in glycolysis as well as the activity of the respective enzymes were assessed. Glucose uptake and lactate production were also evaluated, and the IC50 value of cisplatin in CAL27 cells was determined. FBXW7 overexpression significantly downregulated HK2, PKM2, and LDH; suppressed the activity of the corresponding enzymes hexokinase, pyruvate kinase, and lactate dehydrogenase; as well as reduced glucose uptake and lactate production. FBXW7 overexpression was also associated with decreased mTOR phosphorylation and increased cisplatin sensitivity. These effects were partially antagonized by lactate or the mTOR agonist MHY1485. Puerarin suppressed glycolysis by reducing glucose uptake and lactate production, while it promoted cisplatin sensitivity and activated the FBXW7/mTOR signal pathway in a concentration-dependent manner. These effects were antagonized by FBXW7 downregulation or treatment with MHY1485. Our results suggest that FBXW7 improves cisplatin chemosensitivity and suppresses glycolysis in oSCC cells, indicating its promising potential as a target for puerarin to regulate the cisplatin sensitivity of oSCC cells. [ABSTRACT FROM AUTHOR]

The South China Uranium Province (SCUP) contains the largest number of discovered uranium deposits in China. This province includes seven uranium mineralization belts, at Wuyishan, Taoshan–Zhuguang, Chenzhou–Qinzhou, Gan–Hang, Xixia–Luzong, Mufushan–Hengshan, and Xuefengshan–Jiuwandashan. The uranium deposits can be classified according to their ore-hosting rocks into four general types: granite-, volcanic-, black-shale-, and sandstone-related. These uranium deposits crop out at the peripheries of Cretaceous–Neogene (K–N) redbed basins or are connected to the basins by NE–SW- to NNE–SSW-trending regional faults. Most of the volcanic-related uranium deposits were formed during the mid-Cretaceous (118 to 88 Ma); granite-related deposits have a wider range of ages from 124 to 11 Ma; the black-shale-related deposits have ages of 120 to 7 Ma; sandstone-related deposits yield ages of 111 to 22.5 Ma. As such, these four types of uranium deposits in South China have similar ages, irrespective of location, and are similar in age to K–N redbed basins in this region. δDVSMOW(fluid) and δ18OVSMOW(fluid) values of the volcanic-related uranium deposits generally range from – 105.9‰ to – 38.0‰ and – 11.1‰ to +5.3‰, respectively. The black-shale-related uranium deposits yield δDVSMOW(fluid) and δ18OVSMOW(fluid) values of – 74.5‰ to – 33.0‰ and – 4.4‰ to 9.3‰, respectively. However, the granite-related uranium deposits have a much wider range of δDVSMOW(fluid) and δ18OVSMOW(fluid) values from – 104.4‰ to – 23.1‰ and – 9.4‰ to +7.3‰, respectively. H–O isotopic compositions of the SCUP ore-forming fluids are similar to those of basinal fluids, again demonstrating the link between the uranium deposits and the basins. The spatial–temporal relationships and fluid isotopic similarities between the K–N basins and uranium mineralization indicate that the uranium deposits of the SCUP are genetically related to the K–N redbed basins, and are unconformity-related uranium deposits. [ABSTRACT FROM AUTHOR]

Primary objective: Lipopolysaccharide (LPS) is known to alter the integrity of the blood-brain barrier (BBB) in sepsis, although the underlying mechanism remains unknown. The aim of this study was to elucidate the molecular mechanisms underlying disruption of the BBB in LPS-induced sepsis. Research design: Both in vitro and in vivo experiments were designed to test the role of AMP-activated protein kinase (AMPK) in LPS-induced BBB dysfunction. Methods and procedures: Human brain microvascular endothelial cells (HBMECs) were cultured. The protein expressions were detected by western blot. BBB integrity was determined by Evans Blue. Main outcomes and results: LPS (1 μg ml-1) dramatically increased the permeability of the BBB and the ROS productions, as well as reducing the expression levels of occludin and claudin-5 in cultured HBMECs. Inhibition of NAD(P)H oxidase by apocynin or up-regulation of AMPK reversed the LPS-induced abnormities in HBMECs. In LPS-induced sepsis in mice, it was found that LPS dramatically increased NAD(P)H oxidase protein expressions and ROS productions in the brain and disrupted BBB function assayed by Evans blue staining, which were abolished by AICAR treatment. Conclusions: It is concluded that AMPK activation improves the functions of the BBB impaired by LPS through suppression of NAD(P)H oxidase-derived ROS in mice. [ABSTRACT FROM AUTHOR]

A set of simple TLC and HPLC-PDA-MS methods were developed for detection of counterfeit herbal dietary supplements by the qualitative and quantitative analysis of eight phosphodiesterase type 5 inhibitors (PDE5-Is), sildenafil, hongdenafil, homosildenafil, hydroxyhomosildenafil, vardenafil, pseudovardenafil, tadalafil, and aminotadalafil. The analytical approach is simple for rapid screening with TLC and reliable with HPLC-PDA-MS. Good linearity (r2 > 0.999 over the concentration range of 8.1 to 211.2 μg/ml), sensitivity (limits of quantification 0.04-0.09 μg/ml), accuracy (97.03-101.25%), and precision (RSD (%) < 1.32%) were achieved for all analytes. The methods were applied for detection of 36 commercial herbal dietary supplements suspected containing PDE5-Is. In addition, the characteristic MS fragmentations of three main typical structures, sildenafil, vardenafil, and tadalafil, were discussed and summarized, which are very helpful in rapid screening identification and determination of suspected chemicals not claimed in herbal products. Results have demonstrated that established TLC and HPLC-PDA-MS methods are good confirmation and quantification test schemes for the eight target compounds. [ABSTRACT FROM AUTHOR]

A new natural coumarin, angepubebisin (1), and a new furan, angepubefurin (2), together with the five known compounds, umbelliferone, angelol B (3), ulopterol (4), peucedanol (5), and scopoletin, were isolated from the roots of Angelica pubescens Maxim. f. biserrata Shan et Yuan. The structures of angepubebisin (1) and known compounds were determined by spectroscopic methods, including IR, UV, EI-MS, HR-FTICR-MS, 1D-, and 2D-NMR spectral analyses, and angepubefurin (2) was determined by HR-FTICR-MS and X-ray diffraction analyses. [ABSTRACT FROM AUTHOR]

A novel gradient graphene composite composed of three-layers was fabricated by fused deposition modelling (FDM) with graphene oxide (RGO)/polylactic acid (PLA) as the printing filaments. Based on the analysis of the electromagnetic parameters of samples with different graphene contents, the thickness range of each functional layer was determined by the reflection loss model. The results show that when 5 wt%, 7 wt% and 8 wt% of graphene contents were selected as the three functional layers, the gradient structure absorber has better electromagnetic absorption effect than the homogeneous absorber. The sample achieving −8 dB broadband absorption in the X and Ku bands and a maximum absorption peak of −30 dB at 17 GHz for a 4 mm-thick composite absorber. The excellent microwave absorption ability could be attributed to the gradient distribution of graphene composites, which proper impedance matching, the substantial dielectric loss in graphene, the interfacial void, interfacial polarization loss. [ABSTRACT FROM AUTHOR]

This paper describes the design of a deep-sea chemical data collector for a seafloor observatory network. The control system of the data collector comprises the main control unit, energy supply distribution unit, serial port expansion unit, condition monitoring, power supply switching unit, and communication unit. The functions of the data collector include self-inspection, diagnosis, and isolation. It also transmits the collected data and the monitoring data in the data collector cabin to the shore station management system in real-time. The data is transmitted through the secondary junction box and the photoelectric composite cable. The data collector also includes optical dissolved oxygen, deep-sea methane, chlorophyll, turbidity, and colored dissolved organic matter (CDOM) sensors. In January 2017, the data collector integrated with domestic chemical sensors was used for the sea trial, in Jiaozhou Bay, Qingdao. The experimental results demonstrate the reliability of the system and the data quality of all chemical parameters. [ABSTRACT FROM AUTHOR]

The Data Interpolation Empirical Orthogonal Functions (DINEOF) method is accurate in filling missing remote sensing datasets. This study used the Data-Interpolating Convolutional Auto-Encoder (DINCAE) method to reconstruct chlorophyll-a concentration (Chl-a) data from the Bohai and Yellow seas and compare it with DINEOF. The reconstruction power of the two methods was evaluated using cross-validation and in situ data, and the accuracy of both data validated by DINCAE was higher than that of DINEOF. The reconstruction results of the two methods were analysed from two perspectives: time and space scale. The reconstruction errors of DINCAE were lower than those of DINEOF at different temporal scales, and the temporal sensitivity of DINEOF was greater than that of DINCAE. DINCAE outperforms DINEOF in terms of controlling the small-scale features and Chl-a values. In terms of efficiency, DINCAE is five times faster than DINEOF for similar reconstruction conditions. [ABSTRACT FROM AUTHOR]

Drosophila melanogaster has been used as an in vivo model organism for the study of genetics and development since 100 years ago. Recently, the fruit fly Drosophila was also developed as an in vivo model organism for toxicology studies, in particular, the field of nanotoxicity. The incorporation of nanomaterials into consumer and biomedical products is a cause for concern as nanomaterials are often associated with toxicity in many in vitro studies. In vivo animal studies of the toxicity of nanomaterials with rodents and other mammals are, however, limited due to high operational cost and ethical objections. Hence, Drosophila, a genetically tractable organism with distinct developmental stages and short life cycle, serves as an ideal organism to study nanomaterial-mediated toxicity. This review discusses the basic biology of Drosophila, the toxicity of nanomaterials, as well as how the Drosophila model can be used to study the toxicity of various types of nanomaterials. [ABSTRACT FROM AUTHOR]

The title inorganic-organic hybrid material containing a mixed anion, [BzIQl]2[Zn(NCS)2Br2] (1) (BzIQl = benzyl isoquinolinium, NCS− = isothiocyanate), crystallizes with a benzyl isoquinolinium cation and half of a bis(bromo)-bis(isothiocyanate)zinc(II) anion in the asymmetric unit. It was characterized by elemental analysis, Fourier transform infrared spectroscopy (FTIR), ultraviolet-visible spectroscopy (UV-Vis), electrospray ionization mass spectrometry (ESI-MS), and powder and single crystal X-ray diffraction (PXRD and SC-XRD). The organic cation exhibits a Λ-shaped configuration in which two aromatic rings form an inclined dihedral angle of 90.12°. The ZnII ion in the anion is coordinated by two Br ions and two isothiocyanate ions, and two contiguous anions forms a dimer through S···Br interactions. The thermal stability of the hybrid crystal analyzed by thermogravimetric-differential thermal analysis (TG-DTA) reveals that the title crystal was stable up to 170 °C. The PXRD study confirms the phase purity of the crystalline sample. The band gap energy between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) explains the eventual charge transfer interaction that take place mainly between the anion and [BzIQl]+ cation, and the low value (0.46 ev) indicates the suitability of the crystal for optical application. The first hyperpolarizability predicted using density functional theory (DFT) is more than 720 times that of the reference potassium dihydrogen phosphate crystal (KDP). [ABSTRACT FROM AUTHOR]

Phytochemical investigation of 85% ethanol extracts from the roots of Aristolochia fangchi yielded a new aristolactam derivative named 6-methoxyl aristolactam I N-β-glucoside (1), together with four known compounds, aristolactam IVa (2), aristolactam I-β-d-glucoside (3), aristolactam I (4), and aristolactam-N-β-d-glucoside (5). Their structures were elucidated by spectral analysis. The cytotoxicity of the isolated compounds was also determined. [ABSTRACT FROM PUBLISHER]

As mainstream optical imaging electronic devices, image sensors are widely used in space missions under complex radiation environments. This study investigated the effects 60 and 10 MeV proton irradiations on dark current, dark signal non-uniformity (DSNU), and photon response non-uniformity (PRNU) for a commercial global shutter 8T complementary metal–oxide semiconductor (CMOS) image sensor. A fluence range from 9 × 109 p/cm2 to 7.26 × 1010 p/cm2 was considered. The total ionizing dose deposited reached 10 krad (Si), which significantly increased the dark current. DSNU and PRNU also followed a similar trend with an increase in the dose, which is based on the effects of the total dose and displacement damage. After irradiation, a TCAD simulation was conducted to identify the radiation-induced defects. The results showed that the trapped positive charges in the oxides, interface states in the Si/SiO2 interface, and bulk defects in a pinned photodiode depleted region significantly increased the dark current. The outcomes of this study form significant reference for advancements in radiation-hardened image sensor designs. [ABSTRACT FROM AUTHOR]

The land ice surface heights derived from Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) were assessed by comparing to the near-coincident measurements from the Airborne Topographic Mapper (ATM) Light Detection and Ranging (LiDAR) system during the 2018 Operation IceBridge mission in Antarctica. Over the marginal and interior Antarctic Ice Sheet, the ICESat-2 ice surface height was accurate to less than 14 cm, and remarkable correlations (R2 = 1) were found through the comparison to the ATM measurements. Centimetre-scale accuracy was seen for all ICESat-2 beams, ranging from −13 cm to −3 cm. The ICESat-2 land ice surface height performance was affected by the terrain conditions (i.e., surface roughness and slope); larger height differences could be seen when the surface roughness or slope values were higher as it becomes difficult for photons to accurately capture height distributions in areas with complex measurement geometry. No evident performance difference was found for the ICESat-2 beams; weak beams can still be used for height measurement. The fine spatial resolution and centimetre-scale accuracy of the ICESat-2 land ice elevation product make it one of the most suitable data sources for ice surface height measurements. [ABSTRACT FROM AUTHOR]

Aims: In this study, we prepared spirulina polysaccharides into spirulina polysaccharide-loaded nanoemulsions (SPS-NEs), and determined the antitumor effect of SPS-NEs, when combined with paclitaxel (PTX). Methods: SPS-NEs were prepared by a phase transformation method. The Characterisation and stability of SPS-NEs was measured. The antitumor effect of SPS-NEs combined with PTX was determined by S180 cells or RAW 264.7 macrophages and S180 tumour-bearing mice. Results: SPS-NEs were spherical and stable, the particle size of SPS-NEs was 84.6 ± 3.31 nm, PDI = 0.235 ± 0.02. PTX + SPS-NEs exhibited a much greater toxicity against RAW 264.7 cells than PTX. PTX + SPS-NEs increased the release of NO, IL-6 and TNF-α, and the expression of p-p65 NF-κB, p-I-κB, TLR4. In addition, PTX + SPS-NEs significantly inhibited tumour growth by 72.82% and increased the secretion of serum IL-2, TNF-α and IFN-γ. Conclusions: SPS-NEs can regulate immunity through TLR4/NF-κB signalling pathways, which enhances the anti-tumour effect of PTX. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is the leading cause of failure for breast cancer in the clinic. Thus far, polymer-lipid hybrid nanoparticles (PLN) loaded chemotherapeutic agents has been used to overcome MDR in breast cancer. In this study, we prepared psoralen polymer-lipid hybrid nanoparticles (PSO-PLN) to reverse drug resistant MCF-7/ADR cells in vitro and in vivo. PSO-PLN was prepared by the emulsification evaporation-low temperature solidification method. The formulation, water solubility and bioavailability, particle size, zeta potential and entrapment efficiency, and in vitro release experiments were optimized in order to improve the activity of PSO to reverse MDR. Optimal formulation: soybean phospholipids 50 mg, poly(lactic-co-glycolic) acid (PLGA) 15 mg, PSO 3 mg, and Tween-80 1%. The PSO-PLN possessed a round appearance, uniform size, exhibited no adhesion. The average particle size was 93.59 ± 2.87 nm, the dispersion co-efficient was 0.249 ± 0.06, the zeta potential was 25.47 ± 2.84 mV. In vitro analyses revealed that PSO resistance index was 3.2, and PSO-PLN resistance index was 5.6, indicating that PSO-PLN versus MCF-7/ADR reversal effect was significant. Moreover, PSO-PLN is somewhat targeted to the liver, and has an antitumor effect in the xenograft model of drug-resistant MCF-7/ADR cells. In conclusion, PSO-PLN not only reverses MDR but also improves therapeutic efficiency by enhancing sustained release of PSO. [ABSTRACT FROM AUTHOR]

Multidrug resistance (MDR) is the leading cause of failure for breast cancer in the clinic. Thus far, polymer-lipid hybrid nanoparticles (PLN) loaded chemotherapeutic agents has been used to overcome MDR in breast cancer. In this study, we prepared psoralen polymer-lipid hybrid nanoparticles (PSO-PLN) to reverse drug resistant MCF-7/ADR cells in vitro and in vivo. PSO-PLN was prepared by the emulsification evaporation-low temperature solidification method. The formulation, water solubility and bioavailability, particle size, zeta potential and entrapment efficiency, and in vitro release experiments were optimized in order to improve the activity of PSO to reverse MDR. Optimal formulation: soybean phospholipids 50 mg, poly(lactic-co-glycolic) acid (PLGA) 15 mg, PSO 3 mg, and Tween-80 1%. The PSO-PLN possessed a round appearance, uniform size, exhibited no adhesion. The average particle size was 93.59 ± 2.87 nm, the dispersion co-efficient was 0.249 ± 0.06, the zeta potential was 25.47 ± 2.84 mV. In vitro analyses revealed that PSO resistance index was 3.2, and PSO-PLN resistance index was 5.6, indicating that PSO-PLN versus MCF-7/ADR reversal effect was significant. Moreover, PSO-PLN is somewhat targeted to the liver, and has an antitumor effect in the xenograft model of drug-resistant MCF-7/ADR cells. In conclusion, PSO-PLN not only reverses MDR but also improves therapeutic efficiency by enhancing sustained release of PSO. [ABSTRACT FROM AUTHOR]

Objective:The purpose of this study was to compare clinical features, long-term surgical outcomes between patients with idiopathic and tumor-related trigeminal neuralgia (TN), and to identify factors associated with the maintenance of permanent pain-free state. Methods:Between January 2003 and December 2013, 360 patients with idiopathic TN and 39 patients with tumor-related TN who had undergone microsurgery were retrospectively studied. Kaplan–Meier survival curves were generated and compared by Log-rank test, and the possible prognostic factors were analyzed by the Cox proportional-hazards regression. Results:Patients with tumor-related TN exhibited a younger age of pain onset (46.28 ± 18.18y vs. 53.03 ± 11.90y,p = .006), a briefer symptom duration (3.20 ± 4.38y vs. 7.01 ± 6.04y,p = .000), and much more preoperative neuropathic deficits (61.54%% vs. 24.17%%,p = .000), as compared with patients with idiopathic TN. Using Kaplan–Meier analysis, we found microsurgery was effective in 72.3% of patients with idiopathic TN, and in 86.4% of cases with tumor-related TN at six years follow-up postoperatively. Prognostic analysis suggested that a clear-cut neurovascular compression in patients with idiopathic TN (HR = 3.098, 95%CI: 1.800–5.311;p = .000) and total tumor removal in patients with tumor secondary TN (HR = 7.662, 95%CI: 0.098–36.574;p = .044) were positively correlated with excellent long-term outcomes. Conclusions:The occurrences of TN at younger age, a shorter duration and preponderance of preclinical neuropathic symptoms are the characteristics of TN patients secondary to intracranial tumor, in contrast to patients with TN caused by a compressed vessel. Microsurgery is an effective and safe treatment modality for TN regardless of the disease etiology, the involvement of a clear-cut vascular offender and total tumor resection are the most important predictors of excellent outcome for microsurgery in idiopathic and tumor-related TN patients, respectively. [ABSTRACT FROM PUBLISHER]

Breast cancer is a serious threat to women's health, because multidrug resistance (MDR) has hampered treatment and prognosis. Nanodelivery of anticancer agents is a new technology to be exploited in the treatment of patients, because it bypasses multispecific drug efflux transporters such as P-glycoprotein (ABCB1), multidrug resistance protein-1 (MRP1, ABCC1) and breast cancer resistance protein (BCRP, ABCG2). Drugs can be delivered to tumor tissue by passive and active tumor targeting strategies, which may reduce or reverse drug resistance. This review will mainly focus on MDR-associated proteins, as well as various nanoparticle formulations developed to overcome MDR in breast cancer. [ABSTRACT FROM AUTHOR]