Hongtao Yu

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.

Distance dependent fluorescence quenching and mechanisms are studied on silver nanoparticle (AgNP) surface. The longer is the distance between fluorophore and AgNP surface, the less quenching. The relationship fits the quantum efficiency energy transfer equation where a Nanoparticle-Based Energy Transfer (NSET) quenching model dominates with the distance dependent factor of d^4.42 and an estimated NSET radius of 14.4 nm. Within 10 nm range, the quenching is a result of the combination of Forster Resonance Energy Transfer and NSET.

A total of 116 dust samples in downtown within the city wall were collected, and the spatial occurrence, source and health risk status of 19 trace metal/metalloids bound in street dusts (SDs) were systematically investigated. Geochemical maps, associations, risk models and indices were calculated to define levels of distribution, possible natural or anthropogenic sources, ecological and human health risks. It was found that the wide variations of these 19 trace metals would be observed in spatial maps, which indicated strongly anthropogenic activities inputs. Compared to the calculations of the potential ecological risk index of toxic trace metals, Pb (E_rⁱ = 20.32) ranked at the level of considerable ecological risk. The non-carcinogenic and carcinogenic risk from most trace metals exposed to children and adults were no significant health risks, except for the non-carcinogenic risk of Cr and As to children, and the carcinogenic risk of Cr to adults. The unacceptable risk locations were observed at traffic conjunctions, which should be given attention. The source apportionment results indicated that the trace metals/metalloids Co, Ga, Nb, As, Ni, and Y, coupled with main elements Al, K, Mg, Ca and Si, would possibly originate from “Soil Re-suspension”, whereas Fe, Cu, Rb, La, Ba, Mn, Ti, Ce and Zr were possibly derived from “Brake Wear”. As regards the Na, no valid assumption was formulated about the presence of this element in brake wear, while Cr, Sr, Zn were possibly associated with “Tire Wear”. Comparatively, V would be suggested as a representative source of fuel consumption, and Pb could possibly belong to “Traffic Pigment”. It was noted that the barbican city, surrounded by the Xi’an Ancient City Wall at 12 m high, would trap the trace metal emissions, and consequently increase the health risk for local residents.

Fluorescence titration of methylene blue, rhodamine B and rhodamine 6G (R6G) by silver nanoparticle (AgNP) all resulted in an initial steep quenching curve followed with a sharp turn and a much flatter quenching curve. At the turn, there are about 200,000 dye molecules per a single AgNP, signifying self-assembly of approximately 36-layers of dye molecules on the surface of the AgNP to form a micelle-like structure. These fluorescence-quenching curves fit to a mathematical model with an exponential term due to molecular self-assembly on AgNP surface, or we termed it “self-assembly shielding effect”, and a Stern-Volmer term (nanoparticle surface enhanced quenching). Such a “super-quenching” by AgNP can only be attributed to “pre-concentration” of the dye molecules on the nanoparticle surface that yields the formation of micelle-like self-assembly, resulting in great fluorescence quenching. Overall, the fluorescence quenching titration reveals three different types of interactions of dye molecules on AgNP surface: 1) self-assembly (methylene blue, rhodamine B and R6G), 2) absorption/tight interaction (tryptamine and fluorescein), and 3) loose interaction (eosin Y). We attribute the formation of micelle-like self-assembly of these three dye molecules on AgNP to their positive charge, possession of nitrogen atoms, and with relatively large and flat aromatic moieties.

With the growth of industry, the extensive use of lead, and urban expansion in Northwestern Valley Cities (NVC) China, there is probable reason for presuming an increasing risk of lead exposure. However, little is known about the lead exposure of children less than 6 years old in NVC. As a first investigation, this study uses a survey to systematically determine the influences of various risk factors within the family environment, parents’ background, children’s behavior, mother’s behavior during pregnancy, and parental perception about children’s blood lead (CBL). A total of 596 families were recruited from the general population in Urumqi, Lanzhou, Xining and Yan’an. Parents, and their children (<6 years old), were asked about the environment and behaviors which could possibly relate with lead exposure. The results indicated that in the typical NVC of China, children’s environment and behavior, parents’ education level, and mother’s pregnancy behavior, were associated with potential CBL. It was noted that not all parents in NVC China recognized the importance of children’s lead exposure. Therefore, children’s health care and medical screening campaigns need to be designed to improve family’s fundamental knowledge of lead hazards, associated health effects, and prevention in the NVC of China.

The present work is the first to study co-biosorption of Pb(II) and Sb(III) by a novel bacterium and its application strategy. The biosorption characteristics of Pb(II) and Sb(III) ions from aqueous solution using B. subtilis were investigated. Optimum pH, biomass dosage, contact time and temperature were determined to be 5.00, 6.00 mg/L, 45 min and 35 °C, respectively. Langmuir, Freundlich, Temkin and Dubinin-Radushkevich (D-R) models were applied to describe the biosorption isotherm of the metal ions by B. subtilis. Results showed that Langmuir model fitted the equilibrium data of Pb(II) better than others, while biosorption of Sb(III) obeyed the Freundlich model well. The biosorption capacity of B. subtilis biomass for Pb(II) and Sb(III) ions was found to be 17.34 ± 0.14 and 2.32 ± 0.30 mg/g, respectively. Kinetic data showed the biosorption process of Pb(II) and Sb(III) ions both followed the pseudo-second-order kinetic model, with R² ranging from 0.974 to 0.999 for Pb(II) and from 0.967 to 0.979 for Sb(III). The calculated thermodynamic parameters, negative ∆G and positive ∆H and ∆S values, indicated the biosorption of Pb(II) and Sb(III) ions onto B. subtilis biomass in water was feasible, endothermic, and spontaneous. Bacterial bioleaching experiment revealed B. subtilis can increase the mobility of Pb(II) and Sb(III) in polluted soil when pH was close to 6 at low temperature. Consequently, B. subtilis, as a cheap and original bacterial material, could be a promising biomass to remove Pb or isolate Sb from industrial wastewater and to assist phytoremediation of Pb and Sb from weak acid or near neutral pH polluted soils at low temperature.

Nanoparticles are used widely in our lives, but the understanding of their impacts on human and environmental health is still limited, at least due in part to the fact that nanoparticles are mixtures. This review describes that “nanotoxicity” is actually a test of the overall effect of a nanoparticle mixture: starting materials for nanoparticle preparation, surface coating agents, surface reaction-generated species, and transformed byproducts of the nanoparticle in biological and environmental media, as well as variations of the intrinsic nanoparticle structures.

The purpose of this study was to identify the concentration of multi-elements (MEs) in source water (surface and drinking water) and assess their quality for sustainability. A total of 161 water samples including 88 tap drinking waters (DW) and 73 surface waters (SW) were collected from five cities in Xi’an, Yan’an, Xining, Lanzhou, and Urumqi in northwestern China. Eighteen parameters including pH, electrical conductivity (EC), total organic carbon (TOC) total nitrogen (TN), chemical compositions of anions (F⁻, Cl⁻, NO₃⁻,HCO₃⁻, SO₄²⁻), cations (NH₄⁺, K⁺, Na⁺, Ca²⁺,Mg²⁺), and metals (lead (Pb), chromium (Cr), cadmium (Cd), copper (Cu)) were analyzed in the first time at the five cities . The results showed that pH values and concentrations of Cl⁻, SO₄²⁻, Na⁺, K⁺, Ca²⁺, Mg²⁺ and Cd, Cr, Cu in DW were within the permissible limits of the Chinese Drinking Water Quality Criteria, whereas the concentrations of other ions (F⁻, NO₃⁻, NH₄⁺ and Pb) exceeded their permissible values. In terms of the SW, the concentrations of F⁻, Cl⁻, NO₃⁻, SO₄²⁻ were over the third range threshold i.e., water suitable for fishing and swimming of the Surface Water Quality Standards in China. The spatial distributions of most MEs in source water are similar, and there was no clear variation for all ions and metals. The metals in DW may be caused by water pipes, faucets and their fittings. The noncarcinogenic risk of metals in DW for local children are in decreasing order Cr > Cd > Pb > Cu. The carcinogenic risk from Cr exposure was at the acceptable level according to threshold of USEPA. Although the comprehensive index of potential ecological assessment of Cr, Cd, Pb and Cu in SW ranked at low risk level and was in the order of Huang River in Xining > Peaceful Canal in Urumqi > Yan River in Yan’an > Yellow River in Lanzhou, their adverse effects to ecology and human health at a low concentration in local semi-arid and arid areas should not be ignored in the long run.