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A novel approach was developed to prepare molecularly imprinted polymer (MIP) composites on filter paper and with the subsequent determination of sulfamethoxazole in food samples. Hemoglobin was firstly encapsulated in a metal-organic framework to improve its stability and catalytic performance. This mixture was modified with an initiator and immobilized in the paper to prepare the MIP using electrochemically mediated atom transfer radical polymerization. This composite exhibited excellent adsorption capacity (60.1 mg g−1) and rapid kinetics, which were better than those of previously reported MIPs. Using the optimized conditions, this MIP composite directly extracted the sulfamethoxazole from complex food samples and was placed on the surface of a screen-printed electrode to quantify sulfamethoxazole with a detection limit of 0.7 ng mL−1. Sulfamethoxazole recoveries ranged from 99.4 to 103.7% and the results were in good agreement with those obtained by a liquid chromatography – mass spectrometry (LC-MS) method (r = 0.992). This approach may also be applied for the determination of other target molecules. [ABSTRACT FROM AUTHOR]

The incidence of endometrial endometrioid carcinoma (EEC) has been gradually increasing over the past decade. Fertility-sparing therapy with progestin is a treatment option for EEC or endometrial atypical hyperplasia (AH). The present study evaluated the role of numerous prognostic factors following fertility-sparing therapy for EEC or AH. Furthermore, the present study assessed the strength of various clinicopathological indicators for the prediction of treatment efficacy. A retrospective analysis was performed of patients with EEC and AH who received fertility-sparing therapy between August 2013 and September 2021 at Peking University People's Hospital (Beijing, China). Endometrial specimens were obtained from each patient after 3 months of treatment and at the end of the fertility-sparing therapy, before treatment efficacy and prognosis were evaluated using the χ2 test. Furthermore, the protein expression levels of EEC biomarkers, such as estrogen receptor (ER), progesterone receptor (PR), paired box 2 (PAX2), PTEN and p53 were assessed using immunohistochemistry. The overall complete response (CR) rate of fertility-sparing treatment in the EEC group was 67.39% (31/46), whereas that in the AH group was 86.49% (32/37). The difference between the CR rates in the EEC and AH groups was statistically significant (P<0.05). There was no association between prognosis after treatment and ER, PAX2, PTEN or Ki-67 expression in the initially untreated AH or EEC groups. However, tissues with >50% positive PR expression were demonstrated to have a higher CR rate compared with those with ≤50% positive PR expression in both the EEC and AH groups. Furthermore, the PAX2-positive group tended to demonstrate higher CR rates compared with the PAX2-negative group in the patients with EEC. In conclusion, these data suggested that fertility-sparing therapy is effective for patients with EEC and AH who wish to remain fertile after treatment. Specifically, in the AH group, a higher proportion of patients achieved a CR whilst also achieving this more rapidly. Furthermore, PR was demonstrated to be a useful marker for the evaluation of EEC and AH. [ABSTRACT FROM AUTHOR]

β-Cyclodextrins/acrylic acid modified magnetic gelatin was prepared and then employed as the magnetic solid-phase extraction (MSPE) sorbent for extraction of moxidectin in milk samples. Due to the rigidity of hydrophobic cavity of β-cyclodextrins and carboxyl groups of acrylic acid, magnetic composites are prepared to form a complex with target molecules through various kinds of chemical reactions and then showed excellent extraction performance. This method exhibits the advantages of simplicity of implementation, short extraction time (5 min), low solvent consumption, and high extraction efficiency. A rapid, simple, and effective method for the analysis of moxidectin in milk samples was established by MSPE coupled with liquid chromatography-fluorescence detection. The limit of detection was 0.1 ng·mL−1 and the recoveries from milk samples were in the range of 93.8%–112.5%. The relative standard deviation was not higher than 6.4%. In conclusion, magnetic solid-phase extraction is a simple and robust preconcentration technique that can be coupled to other analytical methods for the quantitative determination of target molecules in complex samples. [ABSTRACT FROM AUTHOR]

The capsular polysaccharide (CPS) is a major virulence factor of the pathogenic Acinetobacter baumannii and a promising target for vaccine development. However, the synthesis of the 1,2- cis -2-amino-2-deoxyglycoside core of CPS remains challenging to date. Here we develop a highly α-selective ZnI 2 -mediated 1,2- cis 2-azido-2-deoxy chemical glycosylation strategy using 2-azido-2-deoxy glucosyl donors equipped with various 4,6- O -tethered groups. Among them the tetraisopropyldisiloxane (TIPDS)-protected 2-azido-2-deoxy-d-glucosyl donor afforded predominantly α-glycoside (α : β = >20 : 1) in maximum yield. This novel approach applies to a wide acceptor substrate scope, including various aliphatic alcohols, sugar alcohols, and natural products. We demonstrated the versatility and effectiveness of this strategy by the synthesis of A. baumannii K48 capsular pentasaccharide repeating fragments, employing the developed reaction as the key step for constructing the 1,2- cis 2-azido-2-deoxy glycosidic linkage. The reaction mechanism was explored with combined experimental variable-temperature NMR (VT-NMR) studies and mass spectroscopy (MS) analysis, and theoretical density functional theory calculations, which suggested the formation of covalent α-C1 GlcN -iodide intermediate in equilibrium with separated oxocarbenium-counter ion pair, followed by an S N 1-like α-nucleophilic attack most likely from separated ion pairs by the ZnI 2 -activated acceptor complex under the influence of the 2-azido gauche effect., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Synchronous endometrial and ovarian endometrioid carcinoma, which simultaneously involves the endometrium and ovary, is a relatively rare entity among gynecological cancers. Precise diagnosis and risk stratification are crucial for disease management. We present a unique case of a 40-year-old woman diagnosed with synchronous endometrial and ovarian endometrioid carcinoma carrying a monoallelic pathogenic MUTYH germline variant. Despite the histological morphology of the right ovarian tumor exhibiting some differences compared to the uterine tumor, we identified three identical somatic mutations shared between the uterine tumor and right ovarian tumor, along with four additional mutations exclusive to the uterine tumor, through the utilization of massively parallel sequencing of a 196-gene panel. These findings enabled us to elucidate the clonal relatedness and potential clonal evolution of the tumor across the two anatomical sites. Furthermore, in accordance with the 2023 FIGO staging system, the patient was diagnosed with Stage IIIB2 uterine cancer, and consequently, adjuvant radiation and chemotherapy were administered after surgery. She is being followed periodically and is normal 15 months after surgery. To the best of our knowledge, this study presents the first case of a patient with synchronous endometrial and ovarian endometrioid carcinoma harboring a monoallelic pathogenic MUTYH germline variant., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 by the International Society of Gynecological Pathologists.)

Compared with stereoselective glycosylation methods mainly addressed on the preparation of pyranose glycosides, the furanosylation has been more limited, especially for the 1,2- cis arabinofuranosylation. Herein, we report a novel stereoselective 1,2- cis -arabinofuranosylation strategy using a conformationally restricted 3,5- O -xylylene-protected arabinofuranosyl donor on activation with B(C 6 F 5 ) 3 for desired targets in moderate to excellent yields and β-stereoselectivity. The effectiveness of the 1,2- cis -arabinofuranosylation strategy was demonstrated successfully with various acceptors, including carbohydrate alcohols., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

Objective: Early gastric cardia adenocarcinoma (EGCA) is a highly heterogeneous cancer, and the understanding of its classification and malignant progression is limited. This study explored the cellular and molecular heterogeneity in EGCA using single-cell RNA sequencing (scRNA-seq)., Design: scRNA-seq was conducted on 95 551 cells from endoscopic biopsies of low-grade intraepithelial neoplasia, well/moderately/poorly differentiated EGCA and their paired adjacent nonmalignant biopsy samples. Large-scale clinical samples and functional experiments were employed., Results: Integrative analysis of epithelial cells revealed that chief cells, parietal cells and enteroendocrine cells were rarely detected in the malignant epithelial subpopulation, whereas gland and pit mucous cells and AQP5 + stem cells were predominant during malignant progression. Pseudotime and functional enrichment analyses showed that the WNT and NF-κB signalling pathways were activated during the transition. Cluster analysis of heterogeneous malignant cells revealed that NNMT-mediated nicotinamide metabolism was enriched in gastric mucin phenotype cell population, which was associated with tumour initiation and inflammation-induced angiogenesis. Furthermore, the expression level of NNMT was gradually increased during the malignant progression and associated with poor prognosis in cardia adenocarcinoma. Mechanistically, NNMT catalysed the conversion of nicotinamide to 1-methyl nicotinamide via depleting S-adenosyl methionine, which led to a reduction in H3K27 trimethylation (H3K27me3) and then activated the WNT signalling pathway to maintain the stemness of AQP5 + stem cells during EGCA malignant progression., Conclusion: Our study extends the understanding of the heterogeneity of EGCA and identifies a functional NNMT + /AQP5 + population that may drive malignant progression in EGCA and could be used for early diagnosis and therapy., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Conventional glycosylation with galactosyl donors having C-2 benzyl (Bn) ether-type functionality often leads to anomeric mixtures, due to the anomeric and steric effects that stabilize the 1,2- cis -α- and 1,2- trans -β-glycosides, respectively. Herein we report a versatile ZnI 2 -directed β-galactosylation approach employing a 4,6- O -tethered and 2- O -Bn galactosyl donor for the stereoselective and efficient synthesis of β- O -galactosides. With a broad substrate scope, the reaction tolerates a wide range of functional groups and complex molecular architectures, providing stereocontrolled β-galactosides in moderate to excellent yields. The practicality of this transformation is demonstrated through the synthesis of a tetrasaccharide arabinogalactan fragment with high stereoselectivity.

Objective: Drug resistance is the main hindrance to improve the prognosis of patients with gastric cancer. Amino, acid metabolic reprograming is essential to satisfy the different requirements of cancer cells during drug resistance,, of which serine deprivation could promote resistance to cisplatin in gastric cancer. As the key enzyme in the de novo, biosynthesis of serine, phosphoglycerate dehydrogenase (PHGDH) inhibition could also induce cisplatin resistance in, gastric cancer. This study aims to reveal the potential mechanisms of drug resistance induced by PHGDH inhibition via, exploring the global mRNA expression profiles., Materials and Methods: In this experimental study, the viability and the apoptotic rate of gastric cancer cells, were evaluated by using Cell Counting Kit-8 (CCK-8) analysis and flow cytometric determination, respectively. The, identification of differentially expressed genes (DEGs) was tested by mRNA-sequencing (mRNA-Seq) analysis. The, confirmation of sequencing results was verified using real-time quantitative reverse transcription polymerase chain, reaction (RT-qPCR)., Results: The inhibition of PHGDH significantly increased the viability and decreased the apoptotic rate induced by cisplatin, in gastric cancer cells. mRNA-Seq analysis revealed that the combined treatment of NCT503 reduced the number of DEGs, induced by cisplatin. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment, Analysis (GSEA) showed that unfolded protein response, ECM receptor interaction and cell cycle signaling pathways were, modulated by NCT503 treatment. Hub genes were identified by using protein-protein interaction network modeling, of which E1A binding protein p300 (EP300) and heat shock protein family A (Hsp70) member 8 (HSPA8) act as the vital genes in cisplatin resistance induced by the inhibition of PHGDH., Conclusion: These findings suggested that the inhibition of PHGDH promoted cisplatin resistance in gastric cancer, through various intercellular mechanisms. And appropriate serine supplementation or the modulation of EP300 and, HSPA8 may be of great help in overcoming cisplatin resistance in gastric cancer.

Objective: Tumor drug resistance is a vital obstacle to chemotherapy in lung cancer. Methionine adenosyltransferase 2A has been considered as a potential target for lung cancer treatment because targeting it can disrupt the tumorigenicity of lung tumor-initiating cells. In this study, we primarily observed the role of methionine metabolism in cisplatin-resistant lung cancer cells and the functional mechanism of MAT2A related to cisplatin resistance., Materials and Methods: In this experimental study, we assessed the half maximal inhibitory concentration (IC 50 ) of cisplatin in different cell lines and cell viability via Cell Counting Kit-8. Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the expression of relative proteins and genes. Crystal violet staining was used to investigate cell proliferation. Additionally, we explored the transcriptional changes in lung cancer cells via RNA-seq., Results: We found H460/DDP and PC-9 cells were more resistant to cisplatin than H460, and MAT2A was overexpressed in cisplatin-resistant cells. Interestingly, methionine deficiency enhanced the inhibitory effect of cisplatin on cell activity and the pro-apoptotic effect. Targeting MAT2A not only restrained cell viability and proliferation, but also contributed to sensitivity of H460/DDP to cisplatin. Furthermore, 4283 up-regulated and 5841 down-regulated genes were detected in H460/DDP compared with H460, and 71 signal pathways were significantly enriched. After treating H460/DDP cells with PF9366, 326 genes were up-regulated, 1093 genes were down-regulated, and 13 signaling pathways were significantly enriched. In TNF signaling pathway, CAS7 and CAS8 were decreased in H460/DDP cells, which increased by PF9366 treatment. Finally, the global histone methylation (H3K4me3, H3K9me2, H3K27me3, H3K36me3) was reduced under methionine deficiency conditions, while H3K9me2 and H3K36me3 were decreased specially via PF9366., Conclusion: Methionine deficiency or MAT2A inhibition may modulate genes expression associated with apoptosis, DNA repair and TNF signaling pathways by regulating histone methylation, thus promoting the sensitivity of lung cancer cells to cisplatin., Competing Interests: There is no conflict of interest in this study., (Copyright© by Royan Institute. All rights reserved.)

A method combining QuEChERS with liquid chromatography-tandem mass spectrometry (LC-MS/MS) was developed for the determination of higenamine in Chinese herbal medicine, condiments, and topical medicine. The sample was subjected to extraction using a formic acid-ethanol mixture, followed by purification of the QuEChERS sorbents; then, the extraction solution was introduced into the LC-MS/MS system for detection in multiple reaction monitoring (MRM) mode. Under the optimal conditions, the detection limit of the developed method was 0.03 ng/g, and the linear range was 0.10-100 ng/g with a relative standard deviation (RSD) of 4.33% (0.5 ng/g, n =7). The method was then applied to the determination of higenamine in 13 kinds of Chinese herbal medicine, four kinds of condiments, and a topical medicine. Higenamine was detected in dried lotus leaf, dried lotus seed, Chinese yam, Yuzhu, Yam, Sichuan pepper, Cassia, and the topical medicine at 9667.6, 1183.8, 21.5, 8.2, 8.5, 148.6, 21.3, and 173.3 μg/kg, respectively. The recoveries of higenamine in Sichuan pepper and cassia was 92.6%-109.8%. In conclusion, the method is fast, simple, reliable, and suitable for use in batch operation.

A high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was established for the determination of ten alkaloids in cosmetics. Extraction conditions, purification methods and instrumental parameters were optimized. The samples were ultrasonically extracted with 80% (v/v) methanol aqueous solution. The extracts were separated and filtered after centrifugation. The analytes were separated on a Waters BEH C 18 column, and detected in the selected reaction monitoring mode. Ten alkaloids were quantified by the external standard method. The ten alkaloids showed good linearity with correlation coefficients ( R 2 ) greater than 0.9900. The limits of detection (LODs) and the limits of quantification (LOQs) of the ten alkaloids were in range of 5.0-12.5 μg/kg and 12.5-50.0 μg/kg, respectively. The average spiked recoveries in the cosmetics ranged from 70.91% to 116.75%, and the relative standard deviations (RSDs) ranged from 0.49% to 9.98%. The method can be used for the rapid screening and quantitative analysis of ten alkaloids in cosmetics.

An accurate quantitative determination and confirmative method for bisphenol diglycidyl ether residues, bisphenol A diglycidyl ether (BADGE), bisphenol F diglycidyl ether (BFDGE), bisphenol A (2,3-dihydroxypropyl) glycidyl ether (BADGE H2O), bisphenol A bis (2,3-dihydroxypropyl) ether (BADGE x 2H2O), bisphenol A (3-chloro-2-hydroxy propyl) (2,3-dihydroxypropyl) ether (BADGE x H2O x HCl), bisphenol A (3-chloro-2-hydroxypropyl) glycidyl ether (BADGE x HCl), bisphenol A bis(3-chloro-2-hydroxypropyl) ether (BADGE x 2HCl), bisphenol F bis (2, 3-dihydroxypropyl) ether (BFDGE x 2H2O), bisphenol F bis (3-chloro-2-hydroxypropyl) ether (BFDGE x 2HCl) in canned foodstuffs by high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) has been established. The sample was extracted with tert-butylmethyl ether and the extract was cleaned-up and concentrated on a Waters Oasis HLB column. The target compounds were analyzed by HPLC-MS/MS on a C18 column by the gradient elution with methanol and 5 mmol/L ammonium acetate containing 0.1% formic acid in a multiple reaction monitoring (MRM) scan mode. External matrix standard solutions were used for the quantitative determination and the calibration curves showed good linearity in the concentration range of 10.0 -2 000.0 microg/L for the nine target compounds. The limits of quantification of the nine compounds were 10.0 microg/kg (S/N > or = 10). The average recoveries of the nine compounds ranged from 79.6% to 100.9% at the spiked levels of 10.0, 100.0, 1 000.0 microg/kg with the relative standard deviations (RSDs) of 6.3%-12.1%. The method is sensitive, accurate, and suitable for the rapid determination of bisphenol diglycidyl ether residues in canned foodstuffs.