Quantitative determination of pyriproxyfen and its metabolite residues in bee products of China using a modified QuEChERS approach with UPLC-MS/MS.

Given the key role of bees as indicators for environmental assessment, residues in bees and bee products have attracted great interest. In this regard, an improved, highly sensitive method for quantifying the insecticide pyriproxyfen and its four metabolites (4'-OH-Pyr, DPH-Pyr, 2-OH-PY, 4'-OH-POP) in honeybees, larvae, and bee products (honey, pollen, royal jelly and wax) should be established. For this purpose, we used ultra-performance liquid chromatography coupled with triple-quadrupole mass spectrometry for rapid quantification (≤5 min). Recoveries for various matrices ranged from 73.77% to 114.97%, with satisfactory intra-day and inter-day precision (relative standard deviations of 0.03-8.61% and 0.10-7.25%, respectively). The results demonstrated excellent linearity (R2 > 0.9903) with a limit of quantification of 1 µg/kg for six different matrices. We collected and analyzed 597 samples (honey, bees and wax) from four major beekeeping areas in China. Only 47 of these samples contained residues of pyriproxyfen and two of its metabolites (2-OH-PY, 4'-OH-Pyr), and high levels of contamination were found in bee samples (2-739 µg/kg), with substantive accumulation in wax (levels were 9.49% higher than in other samples). The result demonstrate that the method provides a reliable and convenient means of monitoring pyriproxyfen and its metabolites in bee products for better product quality, human health, and international commercial competition and also lays a foundation for risk assessment of potential pyriproxyfen contamination in China.

Modulating Hypoxia via Nanomaterials Chemistry for Efficient Treatment of Solid Tumors.

The common existence of hypoxia in solid tumors has been heavily researched because it renders tumors more resistant to most standard therapeutic methods, such as radiotherapy (RT), chemotherapy, and photodynamic therapy (PDT), and is associated with a more malignant phenotype and poor survival in patients with tumors. The development of hypoxia modulation methods for advanced therapeutic activity is therefore of great interest but remains a considerable challenge. Since the significant development of nanotechnology and nanomedicine, functionalized nanomaterials can be exploited as adjuvant "drugs" for these oxygen-dependent standard therapies or as hypoxia initiators for advanced new therapies to solid tumors. In this Account, we summarize our recent studies on the design and synthesis of nanomaterials with a set of desired chemistry benefits achievable by modulating hypoxia, suggesting a valid therapeutic option for tumors. The investigated strategies can be categorized into three groups: The first strategy is based on countering hypoxia. Considering that O2 deficiency is the major obstacle for the oxygen-dependent therapies, we initially developed methods to supply O2 by taking advantage of the hypoxia-responsive properties of nano-MnO2 or nanomaterials' photothermal effects for increased intratumoral blood flow. The second approach is to disregard hypoxia. Possible benefits of nanoagents include reducing/eliminating reliance on O2 or making O2 replacements as adjuvants to standard therapies. To this end, we investigated a nano-upconversion/scintillator with the capacity toup-/down-convert near-infrared light (NIR)/X-ray to luminescence in the ultraviolet/visible region fortype-I PDT with minimized oxygen-tension dependency or developed Fe-based nanomaterials for chemodynamic therapy (CDT) without external energy and oxygen participation for efficient free radical killing of deep tumors. The third strategy involves exploiting hypoxia. The unique biological characteristics of hypoxia are exploited to activate nanoagents for new therapies. To address the discrepancy between the nanoagents' demand and supply within the hypoxia region, a smart "molecule-nano" medicine that stays small-molecule-like in the bloodstream and turns into self-assembled nanovesicles after entry into the hypoxia region was constructed for hypoxia-adaptive photothermal therapy (PTT). In addition to traditional anti-angiogenesis therapy, we prepared Mg2Si nanoparticles by a special self-propagating high-temperature synthesis approach. These nanoparticles can directly remove the intratumoral oxygen via the oxidation reactions of Mg2Si and later efficiently block the rapid reoxygenation via tumor blood vessels by the resultant SiO2 microsheets for cancer starvation therapy. Taken together, these findings indicate that nanomaterials will assume a valuable role for anticancer exploration based on either their properties to make up oxygen deficiency or the use of hypoxia for therapeutic applications.

Application of the combination index (CI)-isobologram equation to research the toxicological interactions of clothianidin, thiamethoxam, and dinotefuran in honeybee, Apis mellifera.

Due to complex pest control scenarios and the needs of agricultural production, different neonicotinoids may be used in certain agricultural applications. Consequently, honeybees may be exposed to these substances through distribution throughout plant tissues via the vascular system through several pathways, such as surface water, the exudates excreted from plants, and air pollution via drift of dust as well as contaminated pollen and nectar. In the current study, the single and combined toxicity of clothianidin, dinotefuran, and thiamethoxam to honeybees was examined after 48 h exposure by the acute oral method and combination index (CI)-isobologram equation. At the 48 h interval, our results showed that 1) the order of toxicities for the single insecticides was ranked as clothianidin > thiamethoxam > dinotefuran and that 2) all binary and ternary combinations showed synergism or additive effect at the effect (fa) 0.5. Therefore, our results not only provided meaningful guidelines in evaluating the safety risk of the mixtures of the three neonicotinoids towards honeybees but also suggested that there is a significant interest in the study of mixture toxicities of neonicotinoids against honeybees because risk assessment of neonicotinoids against honeybees conducted only in individual insecticides may underestimate the realistic toxicity.