Molecular Editing of Pyrroles to Benzenes/Naphthalenes by N2O Deletion.

Molecular editing promises to facilitate the rapid diversification of complex molecular architectures by rapidly and conveniently altering core frameworks. This approach has the potential to accelerate both drug discovery and total synthesis. In this study, we present a novel protocol for the molecular editing of pyrroles. Initially, N-Boc pyrroles and alkynes are converted into N-bridged compounds through a Diels-Alder reaction. These compounds then undergo deprotection of the Boc group, nitrosylation, and cheletropic N2O extrusion to yield benzene or naphthalene products. By using benzyne as a substrate, this method can be conceptually viewed as a fusion of skeletal editing of the pyrrole ring and site-selective peripheral editing of the benzene ring. Furthermore, this proof-of-concept protocol has demonstrated its potential to transform the (hetero)arene motif from commercially available drugs, offering the possibility of generating new biologically active compounds.

Development of a polyurethane-coated thin film solid phase microextraction device for multi-residue monitoring of pesticides in fruit and tea beverages.

A novel solid-phase microextraction device coated with an efficient and cheap thin film of polyurethane was developed for trace determination of 13 widely used pesticides in fruit and tea beverages. A round-shaped polyurethane film covering the bottom of a glass vial was fabricated as the sorbent to exhibit a superior capacity for preconcentrating target compounds and reducing matrix interferences. After optimization of the key parameters including the film type, extraction time, solution pH, ionic strength, desorption solvent, and conditions, this device allowed an efficient adsorption-desorption cycle for the pesticides accomplished in one vial. Coupled with gas chromatography-electron capture detection, the polyurethane-coated thin film microextraction method was successfully established and applied for the analysis of real fruit and tea drinks, showing low limits of detection (0.001-0.015 µg/L), wide linear ranges (1.0-500.0 µg/L, r2  > 0.9931), good relative recoveries (77.2%-106.3%) and negligible matrix effects (86.1%-107.5%) for the target pesticides. The proposed approach revealed strong potential of extending its application by flexibly modifying the type or size of the coating film. This study provides insights into the enrichment of contaminants from complex samples using inexpensive and reusable microextraction devices that can limit the environmental and health impact of the sample preparation protocol.

Alkylgold(III) Complexes Undergo Unprecedented Photo-Induced ß-Hydride Elimination and Reduction for Targeted Cancer Therapy.

Spatiotemporally controllable activation of prodrugs within tumors is highly desirable for cancer therapy to minimize toxic side effects. Herein we report that stable alkylgold(III) complexes can undergo unprecedented photo-induced ß-hydride elimination, releasing alkyl ligands and forming gold(III)-hydride intermediates that could be quickly converted into bioactive [AuIII -S] adducts; meanwhile, the remaining alkylgold(III) complexes can photo-catalytically reduce [AuIII -S] into more bioactive AuI species. Such photo-reactivities make it possible to functionalize gold complexes on the auxiliary alkyl ligands without attenuating the metal-biomacromolecule interactions. As a result, the gold(III) complexes containing glucose-functionalized alkyl ligands displayed efficient and tumor-selective uptake; notably, after one- or two-photon activation, the complexes exhibited high thioredoxin reductase (TrxR) inhibition, potent cytotoxicity, and strong antiangiogenesis and antitumor activities in vivo.

Thermal switches between delayed fluorescence and persistent phosphorescence based on a keto-BODIPY electron acceptor.

A new type of twisted donor-acceptor molecular material 3a and 3b containing carbazole as an electron donor and keto-BODIPY bearing keto-isoindolinyl and pyridyl subunits as an acceptor has been prepared and characterized. Chemical modifications at the meso-position of keto-BODIPY with a nitrogen atom and a cyano group enhance the electron withdrawing ability and cause the emission color change from blue to yellow and red. Steady-state absorption and emission spectra of the two compounds show a strong intramolecular charge transfer (ICT) character. Time-resolved emission spectra and transient decay curves of 3a and 3b show efficient delayed fluorescence with a lifetime of 12.64 µs for 3a and 16.59 µs for 3b at room temperature, whereas persistent phosphorescence with a lifetime of 576.65 ms for 3a and 273.76 ms for 3b was obviously detected at 77 K. These photophysical behaviors have been fully revealed via X-ray diffraction analysis and theoretical calculations, and thus attributed to the hybridized local and charge-transfer (HLCT) states and increased spin-orbital coupling (SOC) strength by mixed n → π* and π → π* transitions involving heteroatom lone pairs and the π-conjugated skeleton, respectively.

Simultaneous determination of neonicotinoid insecticides and metabolites in rice by dispersive solid-liquid microextraction based on an in situ acid-base effervescent reaction and solidification of a floating organic droplet.

A sensitive and rapid method named dispersive solid-liquid microextraction combining in situ acid-base reaction-based effervescence and solidification of a floating organic droplet was developed for the simultaneous determination of eight neonicotinoid insecticides and two metabolites in rice by ultra-performance liquid chromatography-tandem mass spectrometry. The samples were extracted with sodium citrate monobasic-modified acetonitrile by vortexing and purified by primary secondary amine, and then a mixture of 1-undecanol and sodium carbonate aqueous solution was rapidly injected. An acid-base reaction and carbon dioxide bubbles were generated in situ, which promoted the dispersion of 1-undecanol droplets and subsequent transfer of the analytes from the acidified acetonitrile extract to 1-undecanol. The 1-undecanol phase was easily retrieved by centrifugation and solidification in an ice bath. This novel dispersive solid-liquid microextraction fully utilized the advantages of the effervescent reaction and floating droplet solidification, which was carried out in a tube and did not require stepwise analysis for a solid matrix. Under the optimized conditions, the average recoveries of the analytes ranged from 77.8 to 97.1% with relative standard deviations less than 7.3. The limits of detection varied between 0.01 and 0.1 µg kg-1, and enrichment factors were 42-55. The proposed method provides a quantitative, sensitive, and convenient analytical tool applicable for routine monitoring of neonicotinoids in rice. Graphical abstract ᅟ.

Self-acidity induced effervescence and manual shaking-assisted microextraction of neonicotinoid insecticides in orange juice.

A novel dispersive liquid-liquid microextraction that combines self-induced acid-base effervescent reaction and manual shaking, coupled with ultra high performance liquid chromatography with tandem mass spectrometry was developed for simultaneous determination of ten neonicotinoid insecticides and metabolites in orange juice. An innovative aspect of this method was the utilization of the acidity of the juice for a self-reaction between acidic components contained in the juice sample and added sodium carbonate which generated carbon dioxide bubbles in situ, accelerating the analytes transfer to the extractant of 1-undecanol. The total acid content of juice sample was measured to produce the maximum amount of bubbles with minimum usage of carbonate. Manual shaking was subsequently adopted and was proven to enhance the extraction efficiency. The factors affecting the performance, including the type and the amount of the carbon dioxide source and extractant, and ionic strength were optimized. Compared with conventional methods, this approach exhibited low limits of detection (0.001-0.1 µg/L), good recoveries (86.2-103.6%), high enrichment factors (25-50), and negligible matrix effects (-12.3-13.7%). The proposed method was demonstrated to provide a rapid, practical, and environmentally friendly procedure due to no acid reagent, toxic solvent, or external energy requirement, giving rise to potential application on other high acid-content matrices.

A polyurethane-based thin film for solid phase microextraction of pyrethroid insecticides.

This work introduces polyurethane (PU) as an efficient and economic sorbent for thin film solid phase microextraction of pyrethroid insecticides, specifically of bifenthrin, fenpropathrin, lambda-cyhalothrin, permethrin, cypermethrin, flucythrinate, fenvalerate and deltamethrin. The PU film is immersed into chrysanthemum tea under ultrasonication for the adsorption of the analytes, and the analytes are desorbed by a mixture of hexane and ethyl acetate and then quantified by gas chromatography with electron capture detection. The film type, adsorption temperature, extraction time, sample condition, and desorption procedure were optimized. The adsorption capacity and robustness of the PU film is found to be excellent for analysis of pyrethroids in chrysanthemum tea. The limits of detection and method limits of detection range from 0.05-0.5 µg L-1 and 0.0003-0.003 µg L-1, respectively. The relative recoveries from spiked samples are between 84.5 and 104.1%, and enrichment factors up to 188. The method was validated through blind split analyses of chrysanthemum tea infusion and ready-to-drink samples with liquid-liquid extraction. Good agreement between the two approaches shows the method to have an accuracy that is similar to that of the conventional technique. Compared with other reported approaches, the PU-based method exhibites a higher sensitivity, easier operation, lower costs and less matrix effects. Graphical abstract Schematic representation of the use of a polyurethane film as an efficient and economic sorbent for the microextraction of 8 pyrethroids by gas chromatography. This method exhibites excellent performance of accuracy, sensitivity, and robustness, demonstrating its potential of application in the analysis of complex matrix.

Effervescence-assisted dispersive liquid-liquid microextraction using a solid effervescent agent as a novel dispersion technique for the analysis of fungicides in apple juice.

A novel effervescence-assisted dispersive liquid-liquid microextraction method has been developed for the determination of four fungicides in apple juice samples. In this method, a solid effervescent agent is added into samples to assist the dispersion of extraction solvent. The effervescent agent is environmentally friendly and only produces an increase in the ionic strength and a negligible variation in the pH value of the aqueous sample, which does not interfere with the extraction of the analytes. The parameters affecting the extraction efficiency were investigated including the composition of effervescent agent, effervescent agent amount, formulation of effervescent agent, adding mode of effervescent agent, type and volume of extraction solvent, and pH. Under optimized conditions, the method showed a good linearity within the range of 0.05-2 mg/L for pyrimethanil, fludioxonil, and cyprodinil, and 0.1-4 mg/L for kresoxim-methyl, with the correlation coefficients >0.998. The limits of detection for the method ranged between 0.005 and 0.01 mg/L. The recoveries of the target fungicides in apple juice samples were in the range of 72.4-110.8% with the relative standard deviations ranging from 1.2 to 6.8%.

Determination of strobilurin fungicides in cotton seed by combination of acetonitrile extraction and dispersive liquid-liquid microextraction coupled with gas chromatography.

The simultaneous determination of four strobilurin fungicides (picoxystrobin, kresoxim-methyl, trifloxystrobin, and azoxystrobin) in cotton seed by combining acetonitrile extraction and dispersive liquid-liquid microextraction was developed prior to GC with electron capture detection. Several factors, including the type and volume of the extraction and dispersive solvents, extraction condition and time, and salt addition, were optimized. The analytes were extracted with acetonitrile from cotton seed and the clean-up was carried out by primary secondary amine. Afterwards, 60 µL of n-hexane/toluene (1:1, v/v) with a lower density than water was mixed with 1 mL of the acetonitrile extract, then the mixture was injected into 7 mL of distilled water. A 0.1 mL pipette was used to collect a few microliters of n-hexane/toluene from the top of the aqueous solution. The enrichment factors of the analytes ranged from 36 to 67. The LODs were in the range of 0.1 × 10(-3) -2 × 10(-3) mg/kg. The relative recoveries varied from 87.7 to 95.2% with RSDs of 4.1-8.5% for the four fungicides. The good performance of the method, compared with the conventional pretreatments, has demonstrated it is suitable for determining low concentrations of strobilurin fungicide residues in cotton seed.

Common chaperone activity in the G-domain of trGTPase protects L11-L12 interaction on the ribosome.

Translational GTPases (trGTPases) regulate all phases of protein synthesis. An early event in the interaction of a trGTPase with the ribosome is the contact of the G-domain with the C-terminal domain (CTD) of ribosomal protein L12 (L12-CTD) and subsequently interacts with the N-terminal domain of L11 (L11-NTD). However, the structural and functional relationships between L12-CTD and L11-NTD remain unclear. Here, we performed mutagenesis, biochemical and structural studies to identify the interactions between L11-NTD and L12-CTD. Mutagenesis of conserved residues in the interaction site revealed their role in the docking of trGTPases. During docking, loop62 of L11-NTD protrudes into a cleft in L12-CTD, leading to an open conformation of this domain and exposure of hydrophobic core. This unfavorable situation for L12-CTD stability is resolved by a chaperone-like activity of the contacting G-domain. Our results suggest that all trGTPases-regardless of their different specific functions-use a common mechanism for stabilizing the L11-NTD•L12-CTD interactions.

Development and validation of an alternative to conventional pretreatment methods for residue analysis of butachlor in water, soil, and rice.

A rapid and effective alternative analytical method for residues of butachlor in water, soil, and rice was established. The operating variables affecting performance of this method, including different extraction conditions and cleanup adsorbents, were evaluated. The determination of butachlor residues in soil, straw, rice hull, and husked rice was performed using GC/MS after extraction with n-hexane and cleanup with graphite carbon black. The average recoveries ranged from 81.5 to 102.7%, with RSDs of 0.6-7.7% for all of the matrixes investigated. The limits of quantitation were 0.05 mg/kg in water and rice plant, and 0.01 mg/kg in soil, straw, rice hull, and husked rice. A comparison among this proposed method, the conventional liquid-liquid extraction, the Quick, Easy, Cheap, Effective, Rugged, and Safe method, and Soxhlet extraction indicated that this method was more suitable for analyzing butachlor in rice samples. The further validation of the proposed method was carried out by Soxhlet extraction for the determination of butachlor residues in the husked rice samples, and the residue results showed there was no obvious difference obtained from these two methods. Samples from a rice field were found to contain butachlor residues below the maximum residue limits set by China (0.5 mg/kg) and Japan (0.1 mg/kg). The proposed method has a strong potential for application in routine screening and processing of large numbers of samples. This study developed a more effective alternative to the conventional analytical methods for analyzing butachlor residues in various matrixes.

Efficient and practical in-jar silicone rubber based passive sampling for simultaneous monitoring of emerging fungicides in water and soils.

The occurrence and ecological impacts of emerging fungicides in the environment has gained increasing attention. This study applied an in-jar passive sampling device based on silicone rubber (SR) film to measuring the freely dissolved concentration (Cfree) of 6 current-use fungicides as a critical index of bioavailability in water and soils. The kinetics parameters including SR-water, soil-water, and organic carbon-water partition coefficients and sampling rates of the target fungicides were first attained and characterized well with their physicochemical properties. The in situ and ex situ field deployment in Hefei City provided the assessment of contaminated levels for these fungicides in rivers and soils. The Cfree of triadimefon and azoxystrobin was estimated at 0.54 ± 0.07-17.4 ± 2.5 ng L-1 in Nanfei River and Chao Lake, while triadimefon was only found in Dongpu Reservoir water with Cfree below 0.66 ± 0.04 ng L-1. The results exhibited that the equilibrium duration of 7 d was suitable for water application but a longer interval of 14 d was recommended for soil sampling. This work demonstrated the advantages of the proposed strategy in terms of fast monitoring within 2 weeks and high sensitivity down to detection limits in 0.5-5 ng L-1. The in-jar passive sampling device can be extrapolated to the evaluation for a wide coverage of organic pollutants in water and soils.

Skeletal Editing of Benzene Motif: Photopromoted Transannulation for Synthesis of DNA-Encoded Seven-Membered Rings.

In this report, we present a photopromoted, metal-free transannulation of phenyl azides for the synthesis of DNA-encoded seven-membered rings. The transformation is efficiently achieved through a skeletal editing strategy targeting the benzene motif coupled with a Reversible Adsorption to Solid Support (RASS) strategy. A variety of valuable DNA-encoded seven-membered ring compounds, including DNA-encoded 3H-azepines, azepinones, and unnatural amino acids, are now accessible. Crucially, this DNA-compatible protocol can also be applied for the introduction of complex molecules, as exemplified by Lorcaserin and Betahistine. The selective conversion of readily available phenyl rings into high-value seven-membered rings offers a promising avenue for the construction of diversified and drug-like DNA-encoded library.

Comparison of different sample pre-treatments for multi-residue analysis of organochlorine and pyrethroid pesticides in chrysanthemum by gas chromatography with electron capture detection.

The widespread use of insecticides in Chinese herbal medicines has created a compelling need for the development of a multiresidue analytical method to help assure herbs safety. The operating variables affecting the performance of the multiresidue analysis of 34 organochlorine and 12 pyrethroid pesticides in chrysanthemum, a widely used kind of Chinese herbal medicines, were evaluated. Three different extraction solvents including n-hexane and its mixtures with acetone and petroleum ether were compared, and n-hexane was found to be an appropriate option. A combination of gel permeation chromatography and SPE was selected as the optimum cleanup, in comparison with dispersive SPE, or the two former methods alone. The determination of the 46 pesticide residues in the spiked chrysanthemum samples was performed by GC with electron capture detection. The average recoveries ranged from 71.3 to 102.6% with RSDs of 1.4-15.7% for all of the pesticides. The LOQs were in the range of 0.0015-0.2 mg/kg, while the LODs were between 0.0005 and 0.1 mg/kg. The satisfactory accuracy, and precision, in combination with a good separation and few interferences, have demonstrated the strong potential of this technique for its application in chrysanthemum analysis.

Dissipation and residue of fenpropidin in wheat and soil under field conditions.

The residue levels and dissipation rate of fenpropidin in wheat and soil were investigated by LC-MS/MS and GC-MS, respectively. The dissipation rates of fenpropidin were described using first-order kinetics and its half-life ranged from 3.1 to 3.3 days in wheat plants and 13.4-16.5 days in soils. During harvest time, the terminal residues of fenpropidin in wheat were below the EUs maximum residue limit (MRL, 0.5 mg kg(-1)) when collected 20 days after the final application, which suggested that the use of this fungicide was safe for humans. The residues persistence varied between two geographically separated experimental sites, indicating that it might be influenced by climate, soil properties and growth dilution factor. These results would be helpful in setting MRL guidance of fenpropidin in wheat in China.

The role of splicing factor PRPF8 in breast cancer.

BACKGROUND: Alternative splicing is a mechanism to produce different proteins with diverse functions from one gene. Many splicing factors play an important role in cancer progression. PRPF8 is a core protein component of the spliceosome complex, U4/U6-U5 tri-snRNP. OBJECTIVE: However, PRPF8 involved in mRNA alternative splicing are rarely included in the prognosis. METHODS: We found that PRPF8 was expressed in all examined cancer types. Further analyses found that PRPF8 expression was significantly different between the breast cancer and paracancerous tissues. RESULTS: Survival analyses showed that PRPF8-high patients had a poor prognosis, and the expression of PRPF8 is associated with distant metastasis-free survival (DMFS) and post progression survival (PPS). Gene Set Enrichment Analysis (GSEA) has revealed that PRPF8 expression is correlated with TGF-ß, JAK-STAT, and cell cycle control pathways. Consistent with these results, upon PRPF8 silencing, the growth of MCF-7 cells was reduced, the ability of cell clone formation was weakened, and p⁢21 expression was increased. CONCLUSIONS: These results have revealed that PRPF8 is a significant factor for splicing in breast cancer progression.

Estimating the bioavailability of acetochlor to wheat using in situ pore water and passive sampling.

The intensive use of acetochlor in China leads to its extensive existence in soil which may result in contamination of crops and commodities. Therefore, it is vital to assess the bioavailability and phytotoxicity of acetochlor to crops. In this study, four measurements involved in in situ pore water extraction (CIPW), passive sampling extraction (Cfree), ex situ pore water extraction (CEPW), and organic solvent extraction (Csoil) were conducted to assess the bioavailability and phytotoxicity of acetochlor to wheat plant plants in five soils. The results showed that the acetochlor concentrations accumulated in wheat foliage and roots were in the range of 0.11-0.87 mg/kg and 0.09-2.02 mg/kg in the five tested soils, respectively, and had a significant correlation with the acetochlor values analyzed by CIPW (R2 = 0.83-0.90, p < 0.0001) or the Cfree method (R2 = 0.86-0.92, p < 0.0001). The acetochlor concentrations in the five soils measured by these two methods were also correlated with the IC50 values of acetochlor in wheat foliage and roots (R2 > 0.69, p ≤ 0.05). The results indicated that the CIPW and Cfree methods were effective in evaluating acetochlor toxicity to wheat and the acetochlor concentrations in wheat. The effects of soil physical and chemical properties including pH, organic matter content (OMC), clay content, and cation exchange capacity (CEC) on the acetochlor toxicity to wheat were analyzed, and soil OMC was found to be the dominant factor affecting the toxicity of acetochlor in the soil-wheat system.

Synthesis, Properties, and Packing Structures of Wing-Shaped N-Doped Nanographene in Various Oxidation States.

A rigid wing-shaped bicyclo[2.2.2]octadiene-fused bis-hexapyrrolohexaazacoronene (HPHAC) is synthesized, and subsequent chemical oxidation affords a stable biradical dication and an aromatic tetracation. The physicochemical properties and single-crystal structures in various oxidation states are characterized. The face-to-face π-stacked dimeric structures are observed in the neutral and dicationic states. The HPHAC flakes can act as aromatic walls in a tetracation state, producing enlarged induced magnetic shielding space through the superimposition effect.

Oral short-chain fatty acids administration regulates innate anxiety in adult microbiome-depleted mice.

Anxiety is characterized by feelings of tension and worry even in the absence of threatening stimulus. Pathological condition of anxiety elicits defensive behavior and aversive reaction ultimately impacting individuals and society. The gut microbiota has been shown to contribute to the modulation of anxiety-like behavior in rodents through the gut-brain axis. Several studies observed that germ-free (GF) and the broad spectrum of antibiotic cocktail (ABX)-treated rodents display lowered anxiety-like behavior. We speculate that gut microbial short-chain fatty acids (SCFA) modulate the innate anxiety response. Herein, we administered SCFA in the drinking water in adult mice treated with ABX to deplete the microbiota and tested their anxiety-like behavior. To further augment the innate fear response, we enhanced the aversive stimulus of the anxiety-like behavior tests. Strikingly, we found that the anxiety-like behavior in ABX mice was not altered when enhanced aversive stimulus, while control and ABX mice supplemented with SCFA displayed increased anxiety-like behavior. Vagus nerve serves as a promising signaling pathway in the gut-brain axis. We determined the role of vagus nerve by subdiaphragmatic vagotomy (SDV) in ABX mice supplemented with SCFA. We found that the restored anxiety-like behavior in ABX mice by SCFA was unaffected by SDV. These findings suggest that gut microbiota can regulate anxiety-like behavior through their fermentation products SCFA.

Multi-residue determination of plant growth regulators in apples and tomatoes by liquid chromatography/tandem mass spectrometry.

A sensitive and rapid multi-residue analytical method for plant growth regulators (PGRs) (i.e., chlormequat, mepiquat, paclobutrazol, uniconazole, ethephon and flumetralin) in apples and tomatoes was developed using high-performance liquid chromatography/tandem mass spectrometry (HPLC/MS/MS). A homogenised sample was extracted with a mixture of methanol/water (90:10, v/v) and adjusted to pH <3 with formic acid. Primary secondary amine (PSA) adsorbent was used to clean up the sample. The determination was performed using electrospray ionisation (ESI) and a triple quadrupole (QqQ) analyser. Under the optimised method, the results showed that, except for ethephon, the recoveries were 81.8-98.1% in apples and tomatoes at the spiked concentrations of 0.005 to 2 mg/kg, with relative standard deviations (RSDs) of less than 11.7%. The limits of quantification (LOQs) were lower than their maximum residue limits (MRLs). The procedure was concluded as a practical method to determine the PGR residues in fruit and vegetables and is also suitable for the simultaneous analysis of the amounts of samples for routine monitoring. The analytical method described herein demonstrates a strong potential for its application in the field of PGR multi-residue analysis to help assure food safety.