Search

PURPOSE: Current checkpoint inhibitor immunotherapy strategies in glioblastoma are challenged by mechanisms of resistance including an immunosuppressive tumor microenvironment. T cell immunoglobulin domain and mucin domain 3 (TIM3) is a late phase checkpoint receptor traditionally associated with T cell exhaustion. We apply fluorescent imaging techniques to explore feasibility of in vivo visualization of the immune state in a glioblastoma mouse model. PROCEDURES: TIM3 monoclonal antibody was conjugated to a near-infrared fluorescent dye, IRDye-800CW (800CW). The TIM3 experimental conjugate and isotype control were assessed for specificity with immunofluorescent staining and flow cytometry in murine cell lines (GL261 glioma and RAW264.7 macrophages). C57BL/6 mice with orthotopically implanted GL261 cells were imaged in vivo over four days after intravenous TIM3-800CW injection to assess tumor specific uptake. Cell specific uptake was then assessed on histologic sections. RESULTS: The experimental TIM3-800CW, but not its isotype control, bound to RAW264.7 macrophages in vitro. Specificity to RAW264.7 macrophages and not GL261 tumor cells was quantitatively confirmed with the corresponding clone of TIM3 on flow cytometry. In vivo fluorescence imaging of the 800CW signal was localized to the intracranial tumor and significantly higher for the TIM3-800CW cohort, relative to non-targeting isotype control, immediately after tail vein injection and for up to 48 hours after injection. Resected organs of tumor bearing mice showed significantly higher uptake in the liver and spleen. TIM3-800CW was seen to co-stain with CD3 (13%), CD11b (29%), and CD206 (26%). CONCLUSIONS: We propose fluorescent imaging of immune cell imaging as a potential strategy for monitoring and localizing immunologically relevant foci in the setting of brain tumors. Alternative markers and target validation will further clarify the temporal relationship of immunosuppressive effector cells throughout glioma resistance.

Photocatalytic activation of prodrugs for killing cancer cells is an attractive alternative phototherapy to photodynamic therapy that typically relies on the supply of oxygen. Although prodrugs are...

Critical bone defects are a common yet challenging orthopedic problem. Tissue engineering is an emerging and promising strategy for bone regeneration in large-scale bone defects. The precise on-demand release of osteogenic factors is critical for controlling the osteogenic differentiation of seed cells with the support of appropriate three dimensional scaffolds. However, most of the effective osteogenic factors are biomacromolecules with release behaviors that are difficult to control. Here, the cholesterol-modified non-coding microRNA Chol-miR-26a was used to promote the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Chol-miR-26a was conjugated to an injectable poly(ethylene glycol) (PEG) hydrogel through an ultraviolet (UV)-cleavable ester bond. The injectable PEG hydrogel was formed by a copper-free click reaction between the terminal azide groups of 8-armed PEG and dibenzocyclooctyne-biofunctionalized PEG, into which UV-cleavable Chol-miR-26a was simultaneously conjugated via a Michael addition reaction. Upon UV irradiation, Gel-c-miR-26a (MLCaged) released Chol-c-miR-26a selectively and exhibited significantly improved efficacy in bone regeneration compared to the hydrogel without UV irradiation and UV-uncleavable MLControl. MLCaged significantly enhanced alkaline phosphatase activity and promoted calcium nodule deposition in vitro and repaired critical skull defects in a rat animal model, demonstrating that injectable implantation with the precise release of osteogenic factors has the potential to repair large-scale bone defects in clinical practice. Statement of significance Provide a novel and practical strategy via hydrogel for efficient delivery and precisely controlled release of miRNAs into bone defect sites. The hydrogel is formed by polyethylene glycol (PEG), which is crosslinked by ‘click’ reaction. Cholesterol-modified miR-26a loading on the hydrogel is covalently patterned onto the fibers of hydrogel through a UV light-cleavable linker, which prevents undesired release of miRNA. This hydrogel could realize the controlled release of miRNA under light regulation both in vitro and in vivo, thus realize bone regeneration.

Osteoinductivity is a crucial factor to determine the success and efficiency of posterolateral spinal fusion (PLF) by employing calcium phosphate (Ca-P) bioceramics. In this study, three kinds of Ca-P ceramics with microscale to nanoscale gain size (BCP-control, BCP-micro and BCP-nano) were prepared and their physicochemical properties were characterized. BCP-nano had the spherical shape and nanoscale gain size, BCP-micro had the spherical shape and microscale gain size, and BCP-control (BAM®) had the irregular shape and microscale gain size. The obtained BCP-nano with specific nanotopography could well regulate in vitro protein adsorption and osteogenic differentiation of MC3T3 cells. In vivo rabbit PLF procedures further confirmed that nanotopography of BCP-nano might be responsible for the stronger bone regenerative ability comparing with BCP-micro and BCP-control. Collectedly, due to nanocrystal similarity with natural bone apatite, BCP-nano has excellent efficacy in guiding bone regeneration of PLF, and holds great potentials to become an alternative to standard bone grafts for future clinical applications., Graphical abstract Image 1, Highlights • The nanocrystal of porous BCP ceramic spheres is similar to natural bone apatite. • BCP nanoceramics is conducive to protein adsorption and osteogenic differentiation of MC3T3 cells. • Osteoindutivity of BCP ceramics is a crucial factor to determine the sucess and efficiency of PLF. • BCP ceramic spheres with nanotopography hold great potential in clinical PLF applications.

The known ruthenium complex [Ru(tpy)(bpy)(Hmte)](PF6)2 ([1](PF6)2, where tpy = 2,2’:6’,2″-terpyridine, bpy = 2,2’-bipyridine, Hmte = 2-(methylthio)ethanol) is photosubstitutionally active but non-toxic to cancer cells even upon light irradiation. In this work, the two analogs complexes [Ru(tpy)(NN)(Hmte)](PF6)2, where NN = 3,3'-biisoquinoline (i-biq, [2](PF6)2) and di(isoquinolin-3-yl)amine (i-Hdiqa, [3](PF6)2), were synthesized and their photochemistry and phototoxicity evaluated to assess their suitability as photoactivated chemotherapy (PACT) agents. The increase of the aromatic surface of [2](PF6)2 and [3](PF6)2, compared to [1](PF6)2, leads to higher lipophilicity and higher cellular uptake for the former complexes. Such improved uptake is directly correlated to the cytotoxicity of these compounds in the dark: while [2](PF6)2 and [3](PF6)2 showed low EC50 values in human cancer cells, [1](PF6)2 is not cytotoxic due to poor cellular uptake. While stable in the dark, all complexes substituted the protecting thioether ligand upon light irradiation (520 nm), with the highest photosubstitution quantum yield found for [3](PF6)2 (Φ[3] = 0.070). Compounds [2](PF6)2 and [3](PF6)2 were found both more cytotoxic after light activation than in the dark, with a photo index of 4. Considering the very low singlet oxygen quantum yields of these compounds, and the lack of cytotoxicity of the photoreleased Hmte thioether ligand, it can be concluded that the toxicity observed after light activation is due to the photoreleased aqua complexes [Ru(tpy)(NN)(OH2)]2+, and thus that [2](PF6)2 and [3](PF6)2 are promising PACT candidates. Graphic abstract

A simple and efficient system for the hydration and α-deuteration of nitriles to form amides, α-deuterated nitriles, and α-deuterated amides catalyzed by a single pincer complex of the earth-abundant manganese capable of metal-ligand cooperation is reported. The reaction is selective and tolerates a wide range of functional groups, giving the corresponding amides in moderate to good yields. Changing the solvent from tert-butanol to toluene and using D2O results in formation of α-deuterated nitriles in high selectivity. Moreover, α-deuterated amides can be obtained in one step directly from nitriles and D2O in THF. Preliminary mechanistic studies suggest the transformations contributing toward activation of the nitriles via a metal-ligand cooperative pathway, generating the manganese ketimido and enamido pincer complexes as the key intermediates for further transformations.

Glucocorticoids (GCs) have drawn great concern due to widespread contamination in the environment and application in treating COVID-19. Most studies on GC removal mainly focused on aquatic environment, while GC behaviors in soil were less mentioned. In this study, degradation of three selected GCs in soil has been investigated using citric acid (CA)-modified Fenton-like processes (H2O2/Fe(III)/CA and CaO2/Fe(III)/CA treatments). The results showed that GCs in soil can be removed by modified Fenton-like processes (removal efficiency gt; 70% for 24 h). CaO2/Fe(III)/CA was more efficient than H2O2/Fe(III)/CA at low oxidant dosage ( 4 h). Besides the chemical assessment with GC removal, effects of Fenton-like processes were also evaluated by biological assessments with bacteria and plants. CaO2/Fe(III)/CA was less harmful to the richness and diversity of microorganisms in soil compared to H2O2/Fe(III)/CA. Weaker phytotoxic effects were observed on GC-contaminated soil treated by CaO2/Fe(III)/CA than H2O2/Fe(III)/CA. This study, therefore, recommends CaO2-based treatments to remediate GC-contaminated soils.

De-oiled grease trap waste (GTW) has been proven appropriate for anaerobic digestion treatment. Continuous hyperthermophilic at 70 ℃, thermophilic and mesophilic digestion were operated in parallel to investigate the distinctive responses to the de-oiled GTW. Mesophilic digestion achieved higher tolerance loading than the others. Biogas production was detected in the recovery period for the inhibited hyperthermophilic digester, and the recovery time lasted approximately 10 days longer than the thermophilic one. The long chain fatty acid (LCFA) concentrations at the starting points of recovery were determined to be 5.6 mmol L−1 and 6.2 mmol L−1 for the hyperthermophilic and thermophilic digestion, respectively. Under the similar lipid loading, food waste with composite fractions was observed favorable for biogas production in the hyperthermophilic digester. Residual lipid concentration remained higher for the hyperthermophilic digestion, about twice more than the others. Furthermore, composite substrate alleviated the inhibition from LCFAs, for the dominant was converted to the ones with shorter chain length.

Biogas is considered a sustainable source of energy which is largely untapped owing to its inherent weaknesses such as low thermal performance and potentially harmful emissions. Its thermal performance and emission characteristics can be enhanced through the technique of enriching with higher grade fuel. In this research study, biogas enriched with hydrogen was tested for its emission characteristics. A synthetic biogas identified as BG60 (60% CH4 and 40% CO2) enriched with 20% hydrogen (80%BG60-20%H2) was used for the test. Experiments were carried out for combustion of the enriched gas for a wide range of Reynolds numbers and equivalence ratios. The results indicate that the enriched fuel emits less CO and NOx than commonly used domestic fuel LPG. It also has a better thermal and emission performance than BG60. The low pollutant emissions compared with LPG, use of renewable feedstock for biogas production, and competitive cost may make the blended 80%BG60-20%H2 an attractive sustainable alternative domestic fuel choice for environmentally conscious urban dwellers of modern cities.

Biogas is a renewable energy source widely produced by breakdowns of organic matters in natural environment and industry. However, it is not yet an ideal replacement of fossil fuels because its high CO2 content would deteriorate its thermal performance. To upgrade biogas for possible domestic application, hydrogen enrichment is proposed by adding high-grade hydrogen (H2) to biogas in order to improve its flammability and heating value, and reduce pollutant emission. However, most previous studies on blended Biogas/H2 focus on analysing the effects of H2 fraction and nozzle-to-plate distance on the heat flux profile and flame temperature. No comprehensive study has ever demonstrated the influence of the Reynolds number and equivalence ratio under a wide operating range. In this study, a test rig was built to investigate the effects of the Reynolds number and equivalence ratio on heat flux and thermal efficiency of blended biogas/H2 impinging flame. The blended biogas/H2 consisted of 80% biogas and 20% H2 addition in volume. Biogas was artificially made by 60% CH4 and 40% CO2 (BG60). The Reynolds number ranges from 300 to 1500 and equivalence ratio ranges from 1 to 3. A comparative study was also conducted between pure biogas (BG60) and biogas with 20% H2 enrichment.

This article presents the effect of thermal aging on threshold field strength and relative permittivity of cross-linked polyethylene (XLPE) with different cross-linking agent contents. Here, low-density polyethylene (LDPE) and dicumyl peroxide (DCP) are used as basic experimental material and cross-linking agent, respectively. Eventually, experimental results indicate that thermal aging can gradually make threshold field strength and relative permittivity of XLPE with different DCP contents increase and decrease, respectively. Besides, threshold field strength of XLPE with different DCP contents increases first and then decreases as the increase of DCP content, while relative permittivity of XLPE with different DCP contents decreases first and then increases as DCP content increases at different thermal aging time, etc. These studies in this article are the basis of the research on space charge accumulation and dissipation inside XLPE materials, which are of great significance to the normal operation of XLPE cables.

Carbofuran is a carbamate pesticide, a broad-spectrum, high-efficiency, low-residue, and highly toxic insecticide, acaricide, and nematicide, widely used in agriculture. Carbofuran is most harmful to birds, and birds or insects killed by furan poisoning can be killed by secondary poisoning after being foraged by raptors, small mammals, or reptiles. In this paper, an UPLC-MS/MS method was developed for the determination of carbofuran and its metabolite, 3-hydroxycarbofuran, in duck liver. Liver tissue was first ground into a homogenate and then passed through ethyl acetate liquid-liquid extraction processing samples. Multiple reaction monitoring (MRM) mode was used for quantitative analysis, m/z 222.1 → 165.1 for carbofuran, m/z 238.1 → 180.9 for 3-hydroxycarbofuran and m/z 290.2 → 198.2 for an internal standard. The standard curves of carbofuran and 3-hydroxycarbofuran in duck liver were within a range of 2–2000 ng/g, where the linearity was good, the lower limit of quantification was 2 ng/g. The intra-day precision of carbofuran and 3-hydroxycarbofuran was

Enzyme-mimicking artificial nanomaterials often termed nanozymes have broad applications in many fields, including biosensing, pollutant degradation and cancer diagnosis. Herein, we introduce a plasmonic gold nanoparticle-modified Mn3 O4 nanozyme (Mn3 O4 -Au). Visible or near infrared light excitation into the plasmonic absorption band of the surface-bound gold nanoparticles enhances the catalytic oxidation of tetramethylbenzidine (TMB). The mechanism of light-enhanced peroxidase activity is proposed based on the Mn3 O4 conduction band mediated hot electron transfer from photoexcited gold nanoparticles to H2 O2 which undergoes further oxygen-oxygen bond cleavage to yield hydroxyl radical. The surface decoration of plasmonic gold nanoparticles endows Mn3 O4 -Au to be a light-regulated nanozyme.

Aim: The mechanistic role of inhibitor of DNA binding or differentiation (ID) family in ovarian cancer (OC) has remained unclear. Materials & methods: We used the Oncomine, GEPIA, Kaplan–Meier Plotter, cBioPortal, SurvExpress, PROGgene V2, TIMER, and FunRich to evaluate the prognostic value of IDs in patients with OC. Results: the mRNA transcripts of all IDs were markedly downregulated in OC compared with normal tissue. The prognostic value of IDs was also explored within the subtypes, pathological stages, clinical stages and TP53 mutational status. The group with low-risk IDs showed relatively good overall survival (OS) compared with the high-risk group. Conclusion: ID1/3/4 may be exploited as promising prognostic biomarkers and therapeutic targets in OC patients.

Anaerobic digestion is promising for waste activated sludge (WAS) degradation. However, conventional processes were generally stuck with limited hydrolysis and poor pathogen destruction. Hyperthermophilic digestion at 70 °C has drawn attention in overcoming those issues at a relatively low energy requirement and operating difficulties. In order to illuminate its operation characteristics, a single-stage hyperthermophilic digester was controlled at 70 °C and operated continuously to degrade WAS. 88.7 mL/g VSadded of methane yield could be achieved in the hyperthermophilic system, fourfold higher than that in the mesophilic system. Kinetic analysis revealed that hyperthermophilic digestion was advantageous in converting the non-degradable fraction. Consequently, hydrolysis under the hyperthermophilic condition was able to be significantly improved. Above 10 d was necessary for the hyperthermophilic system to gain such a high methane production. In the case of stability, the organic loading of higher than 10.2 g VS/L/d resulted in increasing limitation from methanogenesis and accumulation of propionic, butyric and valeric acids. In addition to the dominant acetoclastic genus Methanothrix for methane production in the hyperthermophilic system, two hydrogenotrophic methanogens Methanospirillum and Methanothermobacter reached 18.84% and 8.31%, respectively. The genus Coprothermobacter, affiliated with the phylum Firmicutes, made more contribution to protein hydrolysis in the hyperthermophilic digester.

Context Dacomitinib and poziotinib, irreversible ErbB family blockers, are often used for treatment of non-small cell lung cancer (NSCLC) in the clinic. Objective This study investigates the effect of dacomitinib on the pharmacokinetics of poziotinib in rats. Materials and methods Twelve Sprague–Dawley rats were randomly divided into two groups: the test group (20 mg/kg dacomitinib for 14 consecutive days) and the control group (equal amounts of vehicle). Each group was given an oral dose of 10 mg/kg poziotinib 30 min after administration of dacomitinib or vehicle at the end of the 14 day administration. The concentration of poziotinib in plasma was quantified by UPLC-MS/MS. Both in vitro effects of dacomitinib on poziotinib and the mechanism of the observed inhibition were studied in rat liver microsomes and human liver microsomes. Results When orally administered, dacomitinib increased the AUC, Tmax and decreased CL of poziotinib (p

Many synthetic nanomaterials known as nanozymes can catalyze biologically relevant molecular transformations just as natural enzyme does. “Photonanozyme” utilizes light as a spatial and temporal co...

International audience; Glycolic acid is a useful and important α-hydroxy acid that has broad applications. Herein, we report the homogeneous ruthenium catalyzed reforming of aqueous ethylene glycol to generate glycolic acid as well as pure hydrogen gas, without concomitant CO2 emission. This approach provides a clean and sustainable direction to glycolic acid and hydrogen, based on inexpensive, readily available and renewable ethylene glycol using 0.5 mol% of catalyst. In-depth mechanistic experimental and computational studies highlight key aspects of the PNNH-ligand framework involved in this transformation.

Albumin-based nanomedicines are important nanoplatforms for cancer drug delivery. The drugs are either physically encapsulated or covalently conjugated to albumin or albumin-based nanosystems. Physical encapsulation is advantageous due to requiring no chemical modification of drug molecules, but many drugs, for instance, camptothecin (CPT) and curcumin (CCM), though very hydrophobic, can't be loaded in or form nanoformulations with albumin. Herein, we demonstrate prodrugs readily binding to proteins via iminoboronates and forming nanoparticles for cancer drug delivery. CPT and CCM were functionalized with 2-acetylphenylboronic acid (2-APBA) to produce prodrugs CPT-SS-APBA and CCM- APBA. The prodrugs bound to bovine serum albumin (BSA) via formation of iminoboronates and the produced BSA/prodrug readily self-assembled into well-defined nanoparticles with high loading efficiency, improved colloidal stability, and much-improved pharmacokinetics. The nanoparticles effectively released drugs in the intracellular acidic environment or the cytosol rich in glutathione (GSH). In vivo, the nanoparticles showed enhanced anticancer efficacy compared with clinically used irinotecan or sorafenib in subcutaneous 4 T1 or HepG2 tumor models. This work demonstrates a versatile protein-binding prodrug platform applicable to protein-based drug formulations and even antibody-drug conjugates.

A novel and mild Cu-catalyzed oxidative dual arylation of carbon-carbon double bonds in acrylamides with 3-aminoindazoles is proposed for the synthesis of cyanoarylated oxindoles. Notably, 3-aminoindazoles are employed as efficient arylating agents via the cleavage of two C-N bonds. This oxidative dual arylation of active alkenes involves a radical process and undergoes a sequence of 3-aminoindazole oxidation, two-C-N-bond cleavage, cyanoaryl radical addition, and intramolecular cyclization.

Multidrug resistance (MDR) is considered as a critical limiting factor for the successful chemotherapy, which is mainly characterized by the overexpression of ATP-binding cassette (ABC) transporter ABCB1 or ABCG2. In this study, folate-targeted polymeric micellar carrier was successfully constructed to co-delivery of doxorubicin (DOX) and SIS3 (FA/DOX/SIS3 micelles), a specific Smad3 inhibitor which sensitizes ABCB1- and ABCG2-overexpressing cancer cells to chemotherapeutic agents. The ratio of DOX to SIS3 in polymeric micelles was determined based on the anti-tumor activity against resistant breast cells. In addition, FA/DOX/SIS3 micelles exhibited a much longer circulation time in blood and were preferentially accumulated in resistant tumor tissue. Pharmacodynamic studies showed that FA/DOX/SIS3 micelles possessed superior anti-tumor activity than other DOX-based treatments. Overall, FA/DOX/SIS3 micelles are a promising formulation for the synergistic treatment of drug-resistant tumor.

Amphiphilic block copolymer prodrugs, which can self-assemble into stable core–shell micelles, have been widely used for anticancer drug delivery. However, a major challenge is to design drug-conjugating linkers stable in blood but selectively cleavable inside tumor cells for drug release. Hydrogen sulfide (H2S) is an important gaseous signaling molecule involved in tumor formation, development, and metastasis and is highly upregulated in multiple cancer types. Accordingly, we designed an H2S-sensitive azide-based linker and used it to conjugate paclitaxel (PTX) to a prodrug copolymer (PEG-PAMPTX). The amphiphilic PEG-PAMPTX self-assembled into micelles with a diameter of about 30 nm, stable under normal physiological conditions for long blood circulation. Once in tumors, the intratumoral H2S selectively reduced the azide group into an amino group, triggering self-cyclization to release PTX rapidly. As a result, the micelles showed remarkably enhanced antitumor activity compared to Taxol in a triple-negative breast cancer orthotopic model.

In recent years, tantalum pentoxide (Ta2O5) ceramic coating has attracted considerable attention in the modification of implants due to its excellent biocompatibility, high corrosion resistance, and good wear resistance. However, the poor adhesion to the substrate degrades its performance and may become a significant obstacle to its clinical application. In the paper, Ta2O5 monolayer, Ta2O5/Ti bilayer, and Ta2O5/Ta2O5-Ti/Ti multilayer coatings were prepared on the Ti-6Al-4V alloy by magnetron sputtering. The microstructure, chemical composition, residual thermal stress, adhesion strength, mechanical properties, tribological behaviors, and corrosion resistance of the coatings were investigated and compared. The results showed that these deposited coatings were composed of an amorphous nano-Ta2O5 phase, and their surfaces were smooth, dense, and homogeneous without any cracks. Ta2O5/Ta2O5-Ti/Ti coatings exhibited lower thermal residual stress than that of the Ta2O5 and Ta2O5/Ti coatings, which could be attributed to the decrease of the coefficient of thermal expansion (CTE) mismatch between the Ta2O5 film and Ti-6Al-4V substrate due to the introduction of the Ta2O5-Ti/Ti double-interlayer. Moreover, Ta2O5/Ta2O5-Ti/Ti coating was significantly superior to Ta2O5 and Ta2O5/Ti coatings in the adhesion strength, mechanical properties, and wear resistance. These Ta2O5-based coatings can provide excellent corrosion protection for Ti-6Al-4V alloy in simulated body fluids (SBF). The Ta2O5 monolayer coating samples showed the best corrosion resistance, mainly due to its thick out-layer Ta2O5 film. These experimental results provide a feasible way to improve the performances of Ta2O5 coating on Ti-6Al-4V alloy.

The development of highly-efficient metal organic framework (MOF) based supercapacitors has attracted much attention. In this work, hollow structure Ni/Co-MOFs have been facilely synthesized by using Co ions as structure-directing agents. Various structures of MOFs, such as hollow, yolk–shell and solid spheres, can be easily obtained through adjusting the molar ratio of Ni/Co. The introduction of an appropriate amount of Co ions can induce the formation of hollow spheres, where the hollow structure can offer rich redox reaction sites and provide fast transport pathways. Moreover, adsorption simulations and density of states calculations illustrate that the adsorbability of OH− and the electrochemical activity on the mixed-metallic MOFs are improved after introducing the Co ions, which can promote the reversible redox reaction activity of the electrode materials. The as-obtained hollow Ni/Co-MOF with the optimized amount of Co ions yields a high capacitance of 1498 F g−1 at 1 A g−1, an excellent rate capability of 67% capacitance retention at 30 A g−1 and a good cycling stability of 71% after 3000 cycles at 5 A g−1. This work may provide useful guidance for tuning the structure and electronic properties of MOFs to enhance the electrochemical performance for supercapacitors.

A nitrogen-centered radical-mediated carbon-carbon bond cleavage strategy is described to synthesize functionalized 3-acylcoumarins. The strategy is enabled by the visible-light-induced acylation/cyclization of alkynoates with various acyl oxime compounds in acetonitrile. The difunctionalization of carbon-carbon triple bonds precedes the generation of iminyl radicals, which is followed by the formation of acyl radicals. The acyl radicals then attack the carbon-carbon triple bonds, followed by 5-exo-trig cyclization and 1,2-ester migration. This strategy has wide substrate adaptability and good substituent tolerance.

Background. Anisatin is a neurotoxic sesquiterpene dilactone wildly found in plants of the family Illiciaceae. Due to morphological similarities among Illiciaceae fruits, fatal poisonings are frequent. Objective. This study is aimed at developing a rapid, simple ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method to determine anisatin’s bioavailability in mouse blood and the method’s application to pharmacokinetics. Methods. Blood samples were preprocessed by protein precipitation using acetonitrile. Salicin (internal standard, IS) and anisatin were gradient-eluted by a mobile phase of methanol and water (0.1% formic acid) in a UPLC BEH C18 column. This step involved using an electrospray ionization source of anisatin at a mass-to-charge ratio (m/z) of 327.1 → 127.0 and IS at m/z 285.1 → 122.9 in the negative ion mode with multiple reaction monitoring. Results. The calibration curve ranged from 1 to 2000 ng/ml ( r > 0.995 ), with the method’s accuracy ranging from 86.3% to 106.9%. Intraday and interday precision were lower than 14%, and the matrix effect was between 93.9% and 103.3%. The recovery rate was higher than 67.2%. Conclusions. The developed UPLC-MS/MS method was successfully used for a pharmacokinetic study of oral (1 mg/kg) and intravenous (0.5 mg/kg) administration of anisatin to mice—the absolute bioavailability of anisatin in the mouse blood was 22.6%.