Chemically diverse microtubule stabilizing agents initiate distinct mitotic defects and dysregulated expression of key mitotic kinases.

Microtubule stabilizers are some of the most successful drugs used in the treatment of adult solid tumors and yet the molecular events responsible for their antimitotic actions are not well defined. The mitotic events initiated by three structurally and biologically diverse microtubule stabilizers; taccalonolide AJ, laulimalide/fijianolide B and paclitaxel were studied. These microtubule stabilizers cause the formation of aberrant, but structurally distinct mitotic spindles leading to the hypothesis that they differentially affect mitotic signaling. Each microtubule stabilizer initiated different patterns of expression of key mitotic signaling proteins. Taccalonolide AJ causes centrosome separation and disjunction failure to a much greater extent than paclitaxel or laulimalide, which is consistent with the distinct defects in expression and activation of Plk1 and Eg5 caused by each stabilizer. Localization studies revealed that TPX2 and Aurora A are associated with each spindle aster formed by each stabilizer. This suggests a common mechanism of aster formation. However, taccalonolide AJ also causes pericentrin accumulation on every spindle aster. The presence of pericentrin at every spindle aster initiated by taccalonolide AJ might facilitate the maintenance and stability of the highly focused asters formed by this stabilizer. Laulimalide and paclitaxel cause completely different patterns of expression and activation of these proteins, as well as phenotypically different spindle phenotypes. Delineating how diverse microtubule stabilizers affect mitotic signaling pathways could identify key proteins involved in modulating sensitivity and resistance to the antimitotic actions of these compounds

Fracture toughness of the sidewall fluorinated carbon nanotube-epoxy interface

The effects ofﾠcarbon nanotubeﾠ(CNT)ﾠsidewall fluorination on theﾠinterfaceﾠtoughness of theﾠCNTﾠepoxyﾠinterfaceﾠhave been comprehensively investigated. Nanoscale quantitative single-CNT pull-out experiments have been conducted on individual fluorinatedﾠCNTsﾠembedded in an epoxy matrix,ﾠin situ, within aﾠscanning electron microscopeﾠ(SEM)ﾠusing an InSEMﾮﾠnanoindenter assisted micro-device. Equations that were derived using a continuum fracture mechanics model have been applied to compute theﾠinterfacialﾠfracture energy values for the system. Theﾠinterfacialﾠfracture energy values have also been independently computed by modeling the fluorinated graphene-epoxyﾠinterfaceﾠusingﾠmolecular dynamics simulationsﾠandﾠadhesionﾠmechanisms have been proposed

Research on grid based fire warning algorithm with YOLOv5s for palace buildings

In response to the early warning requirements of fire security technology in the Imperial Palace & large Ming and Qing ancient architectural complexes in China, a grid based fire warning algorithm is proposed by combining neural network YOLOv5s smoke detection technology. In this algorithm, the inverse proportional gridding algorithm based on building density is used to optimize the grid of buildings, and compared with the results of the equidistant grid algorithm, the risk distribution division is more detailed and reasonable. The smoke detection part uses YOLOv5s based smoke detection technology to detect the distribution of fire smoke in various areas, and the positioning of this area in the overall grid realized by the remote transmission module. With detection experiments on relevant datasets, the results show that its accuracy and mAP both reach 0.99. By utilizing the collaborative effect of inverse proportional gridding algorithm and smoke detection technology, a grid based visualization of smoke warning is achieved

One-pot melamine derived nitrogen doped magnetic carbon nanoadsorbents with enhanced chromium removal

Novel nitrogen doped magnetic carbons (NMC), in-situ synthesized through facile pyrolysis-carbonization processes using Fe(NO3)3 and melamine as precursors, were demonstrated as excellent nanoadsorbents to remove Cr(VI) effectively. The achieved removal capacity in both neutral and acidic solution was 29.4 and 2001.4 mg g−1 respectively, much higher than the reported adsorbents so far. The unprecedented high adsorption performance can be attributed to the incorporation of the nitrogen dopant, which increased the negative charge density on the surface of adsorbent and thereby enhanced the interaction between the adsorbents and Cr(VI) ions. The density functional theory (DFT) calculation demonstrated that the nitrogen dopants can decrease the adsorption energy between the Cr(VI) ions and NMC (−3.456 kJ mol−1), lower than the undoped sample (−3.344 kJ mol−1), which boosted the adsorption behavior. Chemical rather than physical adsorption was followed for these magnetic nanoadsorbents as revealed from the pseudo-second-order kinetic study. Furthermore, the NMC showed high stability with recycling tests for the Cr(VI) removal

Poly(vinylidene fluoride) derived fluorine-doped magnetic carbon nanoadsorbents for enhanced chromium removal

Newly designed fluorine-doped magnetic carbon (F-MC) was synthesized in situ though a facile one-step pyrolysis-carbonization method. Poly(vinylidene fluoride) (PVDF) served as the precursor for both carbon and fluorine. 2.5% F content with core-shell structure was obtained over F-MC, which was used as a adsorbent for the Cr(VI) removal. To our best knowledge, this is the first time to report that the fluorine doped material was applied for the Cr(VI) removal, demonstrating very high removal capacity (1423.4 mg g−1), higher than most reported adsorbents. The unexpected performance of F-MC can be attributed to the configuration of F dopants on the surface. The observed pseudo-second-order kinetic study indicated the dominance of chemical adsorption for this process. High stability of F-MC after 5 recycling test for the Cr(VI) removal was also observed, indicating that F-MC could be used as an excellent adsorbent for the toxic heavy metal removal from the wastewater

A cost-effective o-toulidine-based Schiff base as an efficient sorbent for metal ion uptake from aqueous and soil samples: Synthesis, antimicrobial, and acute toxicity analyses

Heavy metals create serious health problems, so the practical implementation and development of low-cost sorbent materials to remove heavy metals from the ecosystem is a worldwide issue. The purpose of this study is to find a low-cost ligand that has the potential to adsorb heavy metals from aqueous and soil samples and also has biological potential. For this, a Schiff base, dimeric o-toluidine (SBL), has been synthesized through condensation, characterized by spectroscopic analysis, and had its biological activities measured. We also studied its adsorption efficiency through a batch technique to remove Zn(II), Co(II), and Cu(II) from aqueous and soil samples under different conditions such as metal ion concentration, pH, contact time, and SBL concentration. The adsorption potential of SBL was analyzed by the Langmuir and Freundlich adsorption isotherms. The values of correlation coefficients revealed that the Freundlich isotherm elucidated results that were more appropriable than the Langmuir model. Adsorption equilibrium was established in 90 min for aqueous samples and in 1,440 min for soil samples. For the maximum adsorption of all metals, the optimum pH was 8, and it showed a capacity to remove 77 to 95 percent of metals from the samples. The maximum adsorption capacity (qmax) of SBL were 75.75, 62.50, and 9.17 mg g-1 in the case of Cu(II), Zn(II), and Co(II) ions, respectively, from aqueous samples and 10.95, 64.10, and 88.49 mg g-1 in the case of Zn(II), Cu (II), and Co(II), respectively, from soil samples. The effectiveness of SBL in the sorption of the selected metals was found to be Cu+2 > Zn+2 > Co+2 for aqueous samples and Co+2 > Cu+2 > Zn+2 for soil samples. The antimicrobial activity of SBL was also investigated. The results revealed that SBL showed moderate inhibitory activity against Staphylococcus dysentria, C. albican, and Aspergillus niger, whereas it exhibited weak activity against S. aureus, P. aureginosa, K. pneumoniae, P. vulgaris, and E.coli when compared to Fluconazole and Ciprofloxacin as the standard. Acute toxicity of the synthesized compound was measured through its daily oral administration with various doses ranging from 0.1 to 1,000 mg/kg of the mice’s body weights. Even at the dose of 1,000 mg/kg, the SBL showed no mortality or any type of general behavioral change in the treated mice. Based on preparation cost, metal removal capacity, toxicity, and antimicrobial activities, SBL is an excellent sorbent and should be studied at pilot scale levels

Taccalonolides: A Novel Class of Microtubule-Stabilizing Anticancer Agents

Microtubule stabilizing agents, such as paclitaxel, docetaxel, and cabazitaxel have been among the most used chemotherapeutic agents in the last decades for the treatment of a wide range of cancers in the clinic. One of the concerns that limit their use in clinical practice is their intrinsic and acquired drug resistance, which is common to most anti-cancer chemotherapeutics. Taccalonolides are a new class of microtubule stabilizers isolated from the roots of a few species in the genus of Tacca. In early studies, taccalonolides demonstrated different effects on interphase and mitotic microtubules from those of paclitaxel and laulimalide suggesting a unique mechanism of action. This prompts the exploration of new taccalonolides with various functionalities through the identification of minor constituents of natural origin and semi-synthesis. The experiments on the new highly potent taccalonolides indicated that taccalonolides possessed a unique mechanism of covalently binding to the microtubule. An X-ray diffraction analysis of a crystal of taccalonolides AJ binding to tubulin indicated that the covalent binding site is at β-tubulin D226. Taccalonolides circumvent all three mechanisms of taxane drug resistance both in vitro and in vivo. To improve the activity, the structure modification through semi-synthesis was conducted and the structure-activity relationships (SARs) was analyzed based on natural and semi-synthetical taccalonolides. The C22–C23 epoxide can significantly increase the antiproliferation potency of taccalonolides due to the covalent link of C22 and the carboxylic group of D226. Great progress has been seen in the last few years in the understanding of the mechanism of this class of microtube-stabilizing agents. This review summarizes the structure diversity, structure-activity relationships (SARs), mechanism of action, and in vivo activities of taccalonolides

Cloud Longwave Scattering Effect and Its Impact on Climate Simulation

The cloud longwave (LW) scattering effect has been ignored in most current climate models. To investigate its climate impact, we apply an eight-stream DIScrete Ordinates Radiative Transfer (DISORT) scheme to include the cloud LW scattering in the General circulation model version of the LongWave Rapid Radiative Transfer Model (RRTMG_LW) and the Community Atmospheric Model Version 5 (CAM5). Results from the standalone RRTMG_LW and from diagnostic runs of CAM5 (no climate feedback) show that the cloud LW scattering reduces the upward flux at the top of the atmosphere and leads to an extra warming effect in the atmosphere. In the interactive runs with climate feedback included in CAM5, the cloud LW scattering effect is amplified by the water vapor-temperature feedback in a warmer atmosphere and has substantial influences on cloud fraction and specific humidity. The thermodynamic feedbacks are more significant in the northern hemisphere and the resulting meridional temperature gradient is different between the two hemispheres, which strengthens the southern branch of Hadley circulation, and modulates the westerly jet near 50° S and the upper part of Walker circulation. Our study concludes that the cloud LW scattering effect could have complex impacts on the global energy budget and shall be properly treated in future climate models