Mechanism of Rotenone Toxicity against Plutella xylostella: New Perspective from a Spatial Metabolomics and Lipidomics Study.

The botanical pesticide rotenone can effectively control target pest Plutella xylostella, yet insights into in situ metabolic regulation of P. xylostella toward rotenone remain limited. Herein, we demonstrated metabolic expression levels and spatial distribution of rotenone-treated P. xylostella using spatial metabolomics and lipidomics. Specifically, rotenone significantly affected purine and amino acid metabolisms, indicating that adenosine monophosphate and inosine were distributed in the whole body of P. xylostella with elevated levels, while guanosine 5'-monophosphate and tryptophan were significantly downregulated. Spatial lipidomics results indicated that rotenone may significantly destroy glycerophospholipids in cell membranes of P. xylostella, inhibit fatty acid biosynthesis, and consume diacylglycerol to enhance fat oxidation. These findings revealed that high toxicity of rotenone toward P. xylostella may be ascribed to negative effects on energy production and amino acid synthesis and damage to cell membranes, providing guidelines for the toxicity mechanism of rotenone on target pests and rational development of botanical pesticide candidates.

Insights into the degradation and toxicity difference mechanism of neonicotinoid pesticides in honeybees by mass spectrometry imaging.

Honeybees are essential for the pollination of a wide variety of crops and flowering plants, whereas they are confronting decline around the world due to the overuse of pesticides, especially neonicotinoids. The mechanism behind the negative impacts of neonicotinoids on honeybees has attracted considerable interest, yet it remains unknown due to the limited insights into the spatiotemporal distribution of pesticides in honeybees. Herein, we demonstrated the use of matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) for the spatiotemporal visualization of neonicotinoids, such as N-nitroguanidine (dinotefuran) and N-cyanoamidine (acetamiprid) compounds, administered by oral application or direct contact, in the whole-body section of honeybees. The MSI results revealed that both dinotefuran and acetamiprid can quickly penetrate various biological barriers and distribute within the whole-body section of honeybees, but acetamiprid can be degraded much faster than dinotefuran. The degradation rate of acetamiprid is significantly decreased when piperonyl butoxide (PBO) is applied, whereas that of dinotefuran remains almost unchanged. These two factors might contribute to the fact that dinotefuran affords a higher toxicity to honeybees than acetamiprid. Moreover, the toxicity and degradation rate of acetamiprid can be affected by co-application with tebuconazole. Taken together, the results presented here indicate that the discrepant toxicity between dinotefuran and acetamiprid does not lie in the difference in their penetration of various biological barriers of honeybees, but in the degradation rate of neonicotinoid pesticides within honeybee tissues. Moreover, new perspectives are given to better understand the causes of the current decline in honeybee populations posed by insecticides, providing guidelines for the precise use of conventional agrochemicals and the rational design of novel pesticide candidates.

Rapid structural discrimination of IgG antibodies by multicharge-state collision-induced unfolding.

Immunoglobulin G (IgG) antibodies are an important class of biotherapeutics that target various diseases, such as cancers, neurodegenerative disorders, and autoimmune diseases, yet rapid discrimination of IgG antibodies remains a great challenge due to heterogeneity, flexibility, and large size. Herein, we demonstrate a simplified multicharge-state collision-induced unfolding (CIU) method for rapid differentiation of four IgG isotypes that differ in terms of the numbers and patterns of disulfide bonds, bypassing tedious single charge-state selection in advance. The results presented herein reveal that gas-phase unfolding behaviors have a strong dependence on charge states outside IgG surfaces; therefore, multicharge-state CIU analysis of IgG subtypes could offer a great opportunity to gain deeper insights into their gas-phase structural differentiation. The full discrimination of IgG antibody isoforms that possess different disulfide bond numbers and even subtle disulfide bonding patterns can be achieved based on their charge-dependent gas-phase unfolding behaviors and root-mean square deviation in CIU difference spectra. Taken together, the incorporation of all charge states observed in a native ion mobility-mass spectrometry (IM-MS) experiment to CIU analysis could make this strategy sensitive to more subtle structural discrepancies, facilitating the rapid discrimination and evaluation of innovative structurally similar biotherapeutic candidates with unexplored functions.

Research on 5-fluorouracil as a drug carrier materials with its in vitro release properties on organic modified magadiite.

The magadiite (MAG) was modified by cetyltrimethyl ammonium-Bromide (CTAB) and then further modified by Chitosan (CS) which is called organic modified-magadiite as magadiite-cetyltrimethyl ammonium bromide (MAG-CTAB) and magadiite-cetyltrimethyl ammonium bromide-Chitosan (MAG-CTAB-CS), respectively, in this research study. The MAG, MAG-CTAB, and MAG-CTAB-CS were used as 5-Fluorouracil (5-FU) drug carrier materials; the drug carrier's materials were marked as magadiite-5-Fluorouracil (MAG/5-FU), magadiite-cetyltrimethyl ammonium bromide-5-Fluorouracil (MAG-CTAB/5-FU), and magadiite-cetyltrimethyl ammonium bromide-Chitosan (MAG-CTAB-CS/5-FU). X-ray diffraction(XRD, Flourier transform infrared spectrometry (FTIR) and scanning electron microscopy (SEM) results were shown that 5-Fluorouracil was combined with carrier materials through physical apparent adsorption, ion exchange, chemical bond, hydrogen bond, and electrostatic interaction. The drug carriers in vitro release behavior in simulated gastric fluids (SGF，pH = 1.35) and intestinal fluids (SIF，pH = 7.40) were investigated. The drug loading capacity and accumulated release ration were as follows the order: MAG-CTAB-CS/5-FU > MAG-CTAB/5-FU > MAG/5-FU. The drug loading capacity of MAG-CTAB-CS/5-FU was 162.29 mg/g, 48 h later the drug accumulated release ratio was 61.24%, and the release amount was 97.52 mg/g for 24 h. Korsmeyer-Peppas model and First order model were found to be suitable to describe the vitro release behavior of 5-Fluorouracil. This would be an economically viable and efficient method for the preparation of advanced drug delivery system.