The functions and regulatory pathways of S100A8/A9 and its receptors in cancers

Inflammation primarily influences the initiation, progression, and deterioration of many human diseases, and immune cells are the principal forces that modulate the balance of inflammation by generating cytokines and chemokines to maintain physiological homeostasis or accelerate disease development. S100A8/A9, a heterodimer protein mainly generated by neutrophils, triggers many signal transduction pathways to mediate microtubule constitution and pathogen defense, as well as intricate procedures of cancer growth, metastasis, drug resistance, and prognosis. Its paired receptors, such as receptor for advanced glycation ends (RAGEs) and toll-like receptor 4 (TLR4), also have roles and effects within tumor cells, mainly involved with mitogen-activated protein kinases (MAPKs), NF-κB, phosphoinositide 3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR) and protein kinase C (PKC) activation. In the clinical setting, S100A8/A9 and its receptors can be used complementarily as efficient biomarkers for cancer diagnosis and treatment. This review comprehensively summarizes the biological functions of S100A8/A9 and its various receptors in tumor cells, in order to provide new insights and strategies targeting S100A8/A9 to promote novel diagnostic and therapeutic methods in cancers

Cyclizing-berberine A35 induces G2/M arrest and apoptosis by activating YAP phosphorylation (Ser127)

Abstract Background A35 is a novel synthetic cyclizing-berberine recently patented as an antitumor compound. Based on its dual targeting topoisomerase (top) activity, A35 might overcome the resistance of single-target top inhibitors and has no cardiac toxicity for not targeting top2β. In this study we further explored the biological effects and mechanisms of A35. Methods Antitumor activity of A35 was evaluated by SRB and colony formation assay. G2/M phase arrest (especially M) and first damage of M-phase cells were investigated by flow cytometry, cytogenetic analysis, immunofluorescence, co-immunoprecipitation and WB. The key role of phospho-YAP (Ser127) in decreasing YAP nuclear localization, subsequent G2/M arrest and proliferation inhibition were explored by YAP1−/− cells, mutated Ser127 YAP construct (Ser127A) and TUNEL. Results G2/M arrest induced by A35 was independent of p53. M phase cells at low dose were firstly damaged and most damaged-cells accumulated in M phase, and that was a result of preferring targeting top2α by A35, as top2α is essential to push M phase into next phase, and targeting top2α induced cells arrested at M phase. A35 decreased YAP1 nuclear localization by activating YAP phosphorylation (Ser127) which subsequently regulated the transcription of YAP target genes associated with growth and cycle regulation to induce G2/M arrest and growth inhibition. Conclusions Our studies suggested the mechanism of G2/M arrest induced by A35 and a novel role of YAP1 (Ser127) in G2/M arrest. As a dual topoisomerase inhibitor characterized by no cardiac toxicity, A35 is a promising topoisomerase anticancer agent and worthy of further development in future

Development Trend and Driving Factors of Agricultural Chemical Fertilizer Efficiency in China

In China, a high input of chemical fertilizers is currently required for a relatively low increase in agricultural production, and this has resulted in prominent nonpoint source pollution and problems related to the quality of agricultural products. These phenomena threaten China’s implementation of United Nations Sustainable Development Goal 2 (SDG-2). To explore agricultural chemical fertilizer efficiency and the factors driving the growth in chemical fertilizer use in China, as based on an international comparative analysis of China’s chemical fertilizer input, the development trend in the application level and the efficiency in the use of chemical fertilizer in China were subject to time series analysis, and the factors influencing change were identified and analyzed using the Logarithmic Mean Divisia Index (LMDI). The results show that: (1) The gap in agricultural chemical fertilizer efficiency is still large when comparing China with modern agricultural countries, and excessive fertilizer input is still a major problem. (2) The continuous growth in the total amount of chemical fertilizer applied in China during the past 18 years has contributed to the increase in chemical fertilizer application intensity, which provided a cumulative contribution of 85.52%, with smaller contributions from the planting structure and crop sown area. Based on the analysis of fertilizer application, the chemical fertilizer application intensity of the main grain crops was the most significant factor, accounting for about a 40.00% cumulative contribution. (3) Since 2015, the total amount of chemical fertilizers has been reduced through gradually improving the utilization rate of chemical fertilizers, reducing the application intensity of chemical fertilizers, and implementing the fallow rotation system and other measures. Of these, the reduction in application intensity was the most effective at reducing the overall amount of applied fertilizer. To meet the target for achieving sustainable agricultural development, China must still reduce its use of chemical fertilizers by at least 21.80 million tons. Based on the results of current measures and international experience, some suggestions for reducing fertilizer usage are provided

In Situ Determination of Bisphenol A in Beverage Using a Molybdenum Selenide/Reduced Graphene Oxide Nanoparticle Composite Modified Glassy Carbon Electrode

Due to the endocrine disturbing effects of bisphenol A (BPA) on organisms, rapid detection has become one of the most important techniques for monitoring its levels in the aqueous solutions associated with plastics and human beings. In this paper, a glassy carbon electrode (GCE) modified with molybdenum selenide/reduced graphene oxide (MoSe2/rGO) was fabricated for in situ determination of bisphenol A in several beverages. The surface area of the electrode dramatically increases due to the existence of ultra-thin nanosheets in a flower-like structure of MoSe2. Adding phosphotungstic acid in the electrolyte can significantly enhance the repeatability (RSD = 0.4%) and reproducibility (RSD = 2.2%) of the electrode. Under the optimized condition (pH = 6.5), the linear range of BPA was from 0.1 μM–100 μM and the detection limit was 0.015 μM (S/N = 3). When using the as-prepared electrode for analyzing BPA in beverage samples without any pretreatments, the recoveries ranged from 98–107%, and the concentrations were from below the detection limit to 1.7 μM, indicating its potential prospect for routine analysis of BPA

Fast searching measurement of absolute displacement based on submicron-aperture fiber point-diffraction interferometer

The submicron-aperture fiber point-diffraction interferometer (SFPDI) can be applied to realize the measurement of three-dimensional absolute displacement within large range, in which the performance of point-diffraction wavefront and numerical iterative algorithm for displacement reconstruction determines the achievable measurement accuracy, reliability and efficiency of the system. A method based on fast searching particle swarm optimization (FS-PSO) algorithm is proposed to realize the rapid measurement of three-dimensional absolute displacement. Based on the SFPDI with two submicron-aperture fiber pairs, FS-PSO method and the corresponding model of the SFPDI, the measurement accuracy, reliability and efficiency of the SFPDI system are significantly improved, making it more feasible for practical application. The effect of point-diffraction wavefront error on the measurement is analyzed. The error of point-diffraction wavefront obtained in the experiment is in the order of 1x10(-4). (the wavelength. is 532 nm), and the corresponding displacement measurement error is smaller than 0.03 mu m. Both the numerical simulation and comparison experiments have been carried out to demonstrate the accuracy and feasibility of the proposed SFPDI system, high measurement accuracy in the order of 0.1 mu m, convergence rate (similar to 90.0%) and efficiency have been realized with the proposed method, providing a feasible way to measure three-dimensional absolute displacement in the case of no guide rail.Zhejiang Provincial Natural Science Foundation of China [LY17E050014, LY13E060006, Q14E060016]; National Natural Science Foundation of China (NSFC) [11404312, 51476154, 51404223, 51375467]; Zhejiang Key Discipline of Instrument Science and Technology [JL150508, JL150502]; Guangxi Key Laboratory of Automatic Detecting Technology and Instruments [YQ15204]; Guangxi Colleges and Universities Key Laboratory of Optoelectronic Information Processing [KFJJ2014-03]This item from the UA Faculty Publications collection is made available by the University of Arizona with support from the University of Arizona Libraries. If you have questions, please contact us at [email protected]

Synthesis and biological evaluation of 12-N-p-chlorobenzyl sophoridinol derivatives as a novel family of anticancer agents

Taking 12-N-p-chlorobenzyl sophoridinol 2 as a lead, a series of novel sophoridinic derivatives with various 3′-substituents at the 11–side chain were synthesized and evaluated for their anticancer activity from sophoridine (1), a natural antitumor medicine. Among them, the sophoridinic ketones 5a–b, alkenes 7a–b and sophoridinic amines 14a–b displayed reasonable antiproliferative activity with IC50 values ranging from 3.8 to 5.4 μmol/L. Especially, compounds 5a and 7b exhibited an equipotency in both adriamycin (AMD)-susceptible and resistant MCF-7 breast carcinoma cells, indicating a different mechanism from AMD. The primary mechanism of action of 5a was to arrest the cell cycle at the G0/G1 phase, consistent with that of parent compound 1. Thus, we consider 12-chlorobenzyl sophoridinic derivatives with a tricyclic scaffold to be a new class of promising antitumor agents with an advantage of inhibiting drug-resistant cancer cells

Contamination Status, Environmental Factor and Risk Assessment of Polychlorinated Biphenyls and Hexachlorobutadiene in Greenhouse and Open-Field Agricultural Soils across China

With the popularization and high-intensity utilization of greenhouse cultivation for crops growth, the pollution of greenhouse soils has been of concern. Therefore, a national-scale survey was conducted to investigate the contamination status, sources, influence factors and the risks of polychlorinated biphenyls (PCBs) and hexachlorobutadiene (HCBD) in greenhouse and nearby open-field soils. Contents of PCBs ranged from Pseudomonas as the PCBs-degrader in open-field soils. Although the higher values of mean contents were found in greenhouses, the health risks of ΣPCBs in open-field soils were higher than in greenhouse soils due to the higher percentages of high-toxicity PCBs, especially the carcinogenic risks to children (>10−6). This study provided a full insight on the contamination status and risks of PCBs and HCBD when guiding greenhouse agriculture activities