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Per-and polyfluoroalkyl substances (PFASs) have garnered significant attention owing to their prevalence and adverse effects on humans. The direct dietary intake of perfluoroalkyl acids (PFAAs) and PFAAs precursors (pre-PFAAs) biotransformation are considered major contributors to human exposure to PFASs. However, little information is available on analytical methods for the simultaneous detection of PFAAs and pre-PFAAs. In the present study, a single-step sample-treatment-based supramolecular solvents-dispersed liquid-liquid microextraction (SUPRASs-DLLME) technique was established for the analysis of 16 PFAAs and 7 pre-PFAAs in aquatic food. SUPRASs were synthesized using 1-heptanol (3 mL) and tetrahydrofuran (4 mL), which were self-assembled in water. The parameters for microextraction, such as extraction method and enrichment capacity, were optimized. Under the optimum conditions, the limit of detection (LOD) and limit of quantification (LOQ) were 0.03-0.15 ng·g-1 and 0.1-0.5 ng·g-1, respectively. Good linearities (R2 > 0.996) were obtained for all the target compounds, and the recoveries ranged 81.1-120 % with relative standard deviations (RSDs) lower than 20 %. This method was applied to the analysis of 16 PFAAs and 7 pre-PFAAs in aquatic food samples (crabs, prawns, and fish). This study provides a new idea for analyzing other pollutants in biological samples.
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Immunotherapy represents a widely employed modality in clinical oncology, leveraging the activation of the human immune system to target and eradicate cancer cells and tumor tissues via endogenous immune mechanisms. However, its efficacy remains constrained by inadequate immune responses within "cold" tumor microenvironment (TME). In this study, a multifunctional nanoscale pyroptosis inducer with cascade enzymatic activity (IMZF), comprising superoxide dismutase (SOD), catalase (CAT), peroxidase (POD), and glutathione oxidase (GSHOx), is dissociated within the acidic and glutathione-rich TME. The vigorous enzymatic activity not only generates oxygen (O2) to alleviate hypoxia and promote M2 to M1 macrophage polarization but also yields reactive oxygen species (ROS) and depletes glutathione (GSH) within the TME. Functioning as an immunogenic cell death (ICD) activator and pyroptosis inducer, IMZF synergistically triggers dendritic cell maturation and inflammatory lymphocyte infiltration via ICD-associated pyroptosis, thereby reversing immune suppression within the TMEs. Consequently, it exerts inhibitory effects on both primary and distal tumors. This cascade enzymatic platform-based pyroptosis inducer offers an intelligent strategy for effectively overcoming immune suppression within "cold" tumors, thereby providing a promising avenue for advanced immunotherapeutic interventions.
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This study established novel and high-throughput strategies for the simultaneous analysis of 30 fluorinated emerging pollutants in different matrices from the shrimp aquaculture system in eastern China using UHPLC-MS/MS. The parameters of SPE for analysis of water samples and of QuEChERS methods for sediment and shrimp samples were optimized to allow the simultaneous detection and quantitation of 17 per- and polyfluoroalkyl substances (PFASs) and 13 fluoroquinolones (FQs). Under the optimal conditions, the limits of detection of 30 pollutants for water, sediment, and shrimp samples were 0.01-0.30 ng/L, 0.01-0.22 µg/kg, and 0.01-0.23 µg/kg, respectively, while the limits of quantification were 0.04-1.00 ng/L, 0.03-0.73 µg/kg, and 0.03-0.76 µg/kg, with satisfactory recoveries and intra-day precision. The developed methods were successfully applied to the analysis of multiple samples collected from aquaculture ponds in eastern China. PFASs were detected in all samples with concentration ranges of 0.18-0.77 µg/L in water, 0.13-1.41 µg/kg (dry weight) in sediment, and 0.09-0.96 µg/kg (wet weight) in shrimp, respectively. Only two FQs, ciprofloxacin and enrofloxacin, were found in the sediment and shrimp. In general, this study provides valuable insights into the prevalence of fluorinated emerging contaminants, assisting in the monitoring and control of emerging contaminants in aquatic foods.
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Given the high toxicity of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) derivatives, such as 6PPD quinone (6PPDQ) to salmon, as well as their ubiquitous presence in the environment, the contaminant of aquatic food products has drawn significant attention. However, analytical methods for p-Phenylenediamines (PPDs) and their transformation products (TPs) in aquatic products remain underdeveloped. In particular, the degradation of some compounds and strong matrix effects complicate detection. In this study, we present a stable, rapid, and sensitive method combining salt-out assisted extraction, antioxidant protection, and multi-plug filtration clean-up (m-PFC) to detect two PPDs and five TPs in aquatic products. Crucially, the appropriate selection of antioxidants prevented the degradation of the easily oxidized target compounds. Further, the m-PFC method significantly enhanced the purification efficiency, achieving satisfactory recoveries (62.1-115 %), and method detection limits (MDLs) ranging from 0.00300 to 0.400 µg/kg. Subsequently, the method was applied to monitor PPDs and their TPs in aquatic products systematically, revealing the presence of 6PPD and N-isopropyl-N'-phenyl-1,4-phenylenediamine (IPPD) in white shrimp from aquafarms, whereas none of the seven target analytes were detected in fish and crab samples. These findings contribute to the detection of PPDs, their TPs and other unstable chemicals in aquatic products, thereby providing insights into their concentrations in these products.
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We investigated the effects of different nanoplastic (NP, size = 100 nm) concentrations on red crayfish (Cherax quadricarinatus) and examined toxicity mechanisms. We established four concentration groups (control (CK): 0 µg/L; Low: 100 µg/L; Medium: 500 µg/L; and High: 1000 µg/L) and analyzed toxicity effects in C. quadricarinatus hepatopancreas using histopathological, transcriptomic, metabolomic, and fluorescence methods. NP exposure caused histological lesions and oxidative stress in hepatopancreas, and also significantly decreased glutathione (GSH) (P < 0.05) but significantly increased malondialdehyde content (MDA) (P < 0.05) in NP-treated groups. By analyzing different metabolic indicators, total cholesterol (T-CHO) content significantly increased (P < 0.05) and triglyceride (TG) content significantly decreased in Medium and High (P < 0.05). Transcriptomic analyses revealed that NPs influenced apoptosis, drug metabolism-cytochrome P450, and P53 signaling pathways. Metabolomic analyses indicated some metabolic processes were affected by NPs, including bile secretion, primary bile acid biosynthesis, and cholesterol metabolism. Caspase 3, 8, and 9 distribution levels in hepatopancreatic tissues were also determined by immunofluorescence; positive caspase staining increased with increased NP concentrations. Additionally, by examining relative Bcl-2, Bax, Apaf-1, and p53 mRNA expression levels, Bcl-2 expression was significantly decreased with increasing NP concentrations; and the expression of Bcl-2 was increasing significantly with the NPs concentration increasing. Bax expression in Low, Medium, and High groups was also significantly higher when compared with the CK group (P < 0.05); with High group levels significantly higher than in Low and Medium groups (P < 0.05). P53 expression was significantly increased in Low, Medium, and High groups (P < 0.05). Thus, NPs induced apoptosis in C. quadricarinatus hepatopancreatic cells, concomitant with increasing NP concentrations. Therefore, we identified mechanisms underpinning NP toxicity in C. quadricarinatus and provide a theoretical basis for exploring NP toxicity in aquatic organisms.
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Astacoidea , Contaminantes Químicos del Agua , Animales , Astacoidea/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Hepatopáncreas/efectos de los fármacos , Hepatopáncreas/metabolismo , Estrés Oxidativo , Apoptosis/efectos de los fármacos , Transcriptoma , Nanopartículas/toxicidad , Metabolómica , MultiómicaRESUMEN
Bioelectronic therapies modulating the vagus nerve are promising for cardiovascular, inflammatory, and mental disorders. Clinical applications are however limited by side-effects such as breathing obstruction and headache caused by non-specific stimulation. To design selective and functional stimulation, we engineered VaStim, a realistic and efficient in-silico model. We developed a protocol to personalize VaStim in-vivo using simple muscle responses, successfully reproducing experimental observations, by combining models with trials conducted on five pigs. Through optimized algorithms, VaStim simulated the complete fiber population in minutes, including often omitted unmyelinated fibers which constitute 80% of the nerve. The model suggested that all Aα-fibers across the nerve affect laryngeal muscle, while heart rate changes were caused by B-efferents in specific fascicles. It predicted that tripolar paradigms could reduce laryngeal activity by 70% compared to typically used protocols. VaStim may serve as a model for developing neuromodulation therapies by maximizing efficacy and specificity, reducing animal experimentation.
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Simulación por Computador , Estimulación del Nervio Vago , Nervio Vago , Animales , Porcinos , Nervio Vago/fisiología , Estimulación del Nervio Vago/métodos , Frecuencia Cardíaca/fisiología , AlgoritmosRESUMEN
Multi-drug resistance (MDR) is a major cause of cancer therapy failure. Photodynamic therapy (PDT) is a promising modality that can circumvent MDR and synergize with chemotherapies, based on the generation of reactive oxygen species (ROS) by photosensitizers. However, overproduction of glutathione (GSH) by cancer cells scavenges ROS and restricts the efficacy of PDT. Additionally, side effects on normal tissues are unavoidable after PDT treatment. Here, to develop organic systems that deliver effective anticancer PDT and chemotherapy simultaneously with very little side effects, three GSH-sensitive photosensitizer-drug conjugates (CyR-SS-L) are designed and synthesized. CyR-SS-L localized in the mitochondria then is cleaved into CyR-SG and SG-L parts by reacting with and consuming high levels of intracellular GSH. Notably, CyR-SG generates high levels of ROS in tumor cells instead of normal cells and be exploited for PDT and the SG-L part is used for chemotherapy. CyR-SS-L inhibits better MDR cancer tumor inhibitory activity than indocyanine green, a photosensitizer (PS) used for PDT in clinical applications. The results appear to be the first to show that CyR-SS-L may be used as an alternative PDT agent to be more effective against MDR cancers without obvious damaging normal cells by the combination of PDT, GSH depletion, and chemotherapy.
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Resistencia a Múltiples Medicamentos , Resistencia a Antineoplásicos , Glutatión , Mitocondrias , Fotoquimioterapia , Fármacos Fotosensibilizantes , Fármacos Fotosensibilizantes/farmacología , Glutatión/metabolismo , Resistencia a Múltiples Medicamentos/efectos de los fármacos , Humanos , Resistencia a Antineoplásicos/efectos de los fármacos , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fotoquimioterapia/métodos , Animales , Ratones , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/metabolismo , Modelos Animales de Enfermedad , Antineoplásicos/farmacologíaRESUMEN
Perfluorooctane sulfonate (PFOS) is a typical persistent organic pollutant that is characterized by environmental persistence, bioaccumulation, and toxicity. In this study, we investigated the gut microbial response of the red claw crayfish Cherax quadricarinatus after 28 days of exposure to 0 ng/L, 1 ng/L, 10 µg/L, or 10 mg/L of PFOS as a stressor. We measured oxidative stress-related enzyme activities and expression of molecules related to detoxification mechanisms to evaluate the toxic effects of PFOS. We found that PFOS disturbed microbial homeostasis in the gut of C. quadricarinatus, resulting in increased abundance of the pathogen Shewanella and decreased abundance of the beneficial bacterium Lactobacillus. The latter especially disturbed amino acid transport and carbohydrate transport. We also found that the activities of glutathione S-transferase and glutathione peroxidase were positively correlated with the expression levels of cytochrome P450 genes (GST1-1, GSTP, GSTK1, HPGDS, UGT5), which are products of PFOS-induced oxidative stress and play an antioxidant role in the body. The results of this study provided valuable ecotoxicological data to better understand the biological fate and effects of PFOS in C. quadricarinatus.
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Ácidos Alcanesulfónicos , Antioxidantes , Astacoidea , Fluorocarburos , Microbioma Gastrointestinal , Estrés Oxidativo , Contaminantes Químicos del Agua , Animales , Astacoidea/efectos de los fármacos , Astacoidea/fisiología , Astacoidea/microbiología , Ácidos Alcanesulfónicos/toxicidad , Fluorocarburos/toxicidad , Microbioma Gastrointestinal/efectos de los fármacos , Contaminantes Químicos del Agua/toxicidad , Antioxidantes/metabolismo , Glutatión Transferasa/metabolismoRESUMEN
Sleep deprivation (SD) is highly prevalent in the modern technological world. Emerging evidence shows that sleep deprivation is associated with oxidative stress. At the organelle level, the Golgi apparatus actively participates in the stress response. In this study, to determine whether SD and Golgi apparatus stress are correlated, we rationally designed and fabricated a novel Golgi apparatus-targeted ratiometric nanoprobe called Golgi dots for O2·- detection. This probe exhibits high sensitivity and selectivity in cells and brain slices of sleep-deprived mice. Golgi dots can be readily synthesized by coprecipitation of Golgi-F127, an amphiphilic polymer F127 modified with a Golgi apparatus targeting moiety, caffeic acid (CA), the responsive unit for O2·-, and red emissive carbon nanodots (CDs), which act as the reference signal. The fluorescence emission spectrum of the developed nanoprobe showed an intense peak at 674 nm, accompanied by a shoulder peak at 485 nm. As O2·- was gradually added, the fluorescence at 485 nm continuously increased; in contrast, the emission intensity at 674 nm assigned to the CDs remained constant, resulting in the ratiometric sensing of O2·-. The present ratiometric nanoprobe showed high selectivity for O2·- monitoring due to the specific recognition of O2·- by CA. Moreover, the Golgi dots exhibited good linearity with respect to the O2·- concentration within 5 to 40 µM, and the limit of detection (LOD) was ~ 0.13 µM. Additionally, the Golgi dots showed low cytotoxicity and an ability to target the Golgi apparatus. Inspired by these excellent properties, we then applied the Golgi dots to successfully monitor exogenous and endogenous O2·- levels within the Golgi apparatus. Importantly, with the help of Golgi dots, we determined that SD substantially elevated O2·- levels in the brain.
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Encéfalo , Ácidos Cafeicos , Polietilenos , Polipropilenos , Privación de Sueño , Animales , Ratones , Aparato de Golgi , Suplementos DietéticosRESUMEN
Objective: With the improvement of living standards, consumers are paying more and more attention to the quality of rice. Traditional rice quality detection relies on human sensory judgment, which is inaccurate and inefficient. With the continuous development of molecular imaging technology, more and more scholars at home and abroad have begun to pay attention to its application in the nondestructive testing of agricultural products. Molecular imaging technology combines the advantages of spectral technology and image technology, which can achieve rapid, nondestructive and accurate detection of rice quality. In this paper, taking rice as the research object, we carried out nondestructive detection research on rice varieties, moisture and starch content using molecular imaging technology. We proposed a rapid detection method based on molecular imaging technology for rice variety identification, moisture content and starch content. Molecular images of the rice samples from four origins were obtained using a molecular imaging system, the regions of interest of the rice were identified and, spectral data, textural features and morphological features of the rice were extracted. Spectral, textural and morphological features were selected by principal component analysis (PCA), and nine feature wavelengths were obtained and an optimal model was established with an accuracy of 91.67%, which demonstrated the feasibility of molecular imaging. By comparing the models, the BCC-LS-SVR model based on the RB function had the highest accuracy with R2 of 0.989, RMSEP of 0.767%, R2 of 0.985, and RMSEC of 0.591%. Moreover, starchy rice was detected using molecular imaging. The PCA-SVR model based on the RBF kernel function had the highest accuracy with R2 of 0.989, RMSEC of 0.445%, R2 of 0.991, and RMSEP of 0.669%. Our models demonstrated high accuracy in identifying rice varieties, as well as quantifying moisture and starch content, showcasing the feasibility of molecular imaging technology in rice quality assessment. This research offers a rapid, nondestructive, and accurate method for rice quality assessment, promising significant benefits for agricultural producers and consumers.
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The determination of catalytically active sites is crucial for understanding the catalytic mechanism and providing guidelines for the design of more efficient catalysts. However, the complex structure of supported metal nanocatalysts (e.g., support, metal surface, and metal-support interface) still presents a big challenge. In particular, many studies have demonstrated that metal-support interfaces could also act as the primary active sites in catalytic reactions, which is well elucidated in oxide-supported metal nanocatalysts but is rarely reported in carbon-supported metal nanocatalysts. Here, we fill the above gap and demonstrate that metal-sulfur interfaces in sulfur-doped carbon-supported metal nanocatalysts are the primary active sites for several catalytic hydrogenation reactions. A series of metal nanocatalysts with similar sizes but different amounts of metal-sulfur interfaces were first constructed and characterized. Taking Ir for quinoline hydrogenation as an example, it was found that their catalytic activities were proportional to the amount of the Ir-S interface. Further experiments and density functional theory (DFT) calculations suggested that the adsorption and activation of quinoline occurred on the Ir atoms at the Ir-S interface. Similar phenomena were found in p-chloronitrobenzene hydrogenation over the Pt-S interface and benzoic acid hydrogenation over the Ru-S interface. All of these findings verify the predominant activity of metal-sulfur interfaces for catalytic hydrogenation reactions and contribute to the comprehensive understanding of metal-support interfaces in supported nanocatalysts.
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Hydroponic cultivation of fresh produce is gaining popularity worldwide, but few studies have provided a comparative assessment of hydroponic and conventional soil-based vegetables. In this study, we analyzed a series of hazardous chemicals, including 120 pesticides, 18 phthalates (PAEs), and 2 heavy metals (lead and cadmium) in four vegetable commodities (lettuces, celeries, tomatoes, and cucumbers) from hydroponic and conventional soil-based cultivation. Our study showed that at least one pesticide was present in 84% of the conventionally grown samples, whereas only 30% of the hydroponic samples contained detectable pesticide residues. Regarding the total PAE concentrations, there was no significant difference between conventional and hydroponic vegetables. The lead and cadmium residues in conventionally cultivated vegetables were significantly higher than in those produced from hydroponic cultivation. Lead is the primary heavy metal pollutant across all vegetable samples. The hazard index (HI) values of the hydroponic and conventional vegetables were 0.22 and 0.64, respectively. Since both values are below one, the exposure to these hazardous chemicals through consumption of the studied vegetables may not pose a significant health risk. The HI values also suggested that the health risks of eating hydroponic vegetables are lower than for conventional soil-based vegetables.
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Seasonal (temporal) variations can influence the δ13C, δ2H, δ18O, and δ15N values and nutrient composition of organic (ORG), green (GRE), and conventional (CON) vegetables with a short growth cycle. Stable isotope ratio mass spectrometry (IRMS) and near-infrared spectroscopy (NIRS) combined with the partial least squares-discriminant analysis (PLS-DA) method were used to investigate seasonal effects on the identification of ORG, GRE, and CON Brassica chinensis L. samples (BCs). The results showed that δ15N values had significant differences among the three cultivation methods and that δ13C, δ2H, and δ18O values were significantly higher in winter and spring and lower in summer. The NIR spectra were relatively clustered across seasons. Neither IRMS-PLS-DA nor NIRS-PLS-DA could effectively identify all BC cultivation methods due to seasonal effects, while IRMS-NIRS-PLS-DA combined with Norris smoothing and derivative pretreatment had better predictive abilities, with an 89.80% accuracy for ORG and BCs, 88.89% for ORG and GRE BCs, and 75.00% for GRE and CON BCs. The IRMS-NIRS-PLS-DA provided an effective and robust method to identify BC cultivation methods, integrating multi-seasonal differences.
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Microwaves have the advantage of penetrating vegetation and exhibit sensitivity to properties such as vegetation water content (VWC); yet, their potential utility in the fire domain is infrequently investigated. This study elucidates the different impacts of the microwave VWC index EDVI on fire radiative energy (FRE) across various biome types and the significant predictive power for high-severity fires (defined based on FRE) in mainland Southeast Asia. While EDVI exhibits lower predictive power for high severe fires compared to the commonly used fire weather indices (e.g., FWI), an enhancement is observed when these predictors are used in combination. Either by employing EDVI or fire weather indices, the predictability of fires is found to be highest over forests and lowest over croplands. Factors such as increasing human influence and fuel limitation in croplands are likely reducing the roles of VWC and weather on fires, contributing to the lower prediction skill of EDVI and fire weather. These results indicate the usefulness of microwave VWC index in fire studies. Although fire weather presents more considerable impacts on fires, the microwave VWC index seem to still provide some complementary information in fire danger assessment.
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Microondas , Tiempo (Meteorología) , Humanos , Ecosistema , Bosques , Agua , Asia SudorientalRESUMEN
Perfluoroalkyl substances (PFASs) have become a new food-safety problem. Dietary intake is a major pathway of human exposure to PFASs. Chinese mitten crab (Eriocheir sinensis) is a high-end aquaculture product popular among consumers in China. Conventional extraction methods for PFASs are cumbersome and time consuming, and result in incomplete purification; thus, this technique does not meet the requirements for PFAS detection. Herein, an analytical strategy was established for the rapid detection of 14 PFASs in Chinese mitten crab based on multi-plug filtration cleanup (m-PFC) and ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). The carbon-chain length of the 14 PFASs analyzed in this study ranged from 4 to 14, and they are perfluorobutanoic acid (PFBA), perfluoro-n-pentanoic acid (PFPeA), perfluorohexanoic acid (PFHxA), perfluoroheptanoic acid (PFHpA), perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorodecanoic acid (PFDA), perfluoroundecanoic acid (PFUnDA), perfluorododecanoic acid (PFDoDA), perfluorotetradecanoic acid (PFTeDA), perfluoro-1-butane sulfonic acid (PFBS), perfluoro-1-hexane sulfonic acid (PFHxS), perfluoro-1-octane sulfonic acid (PFOS), and perfluoro-1-decanesulfonate (PFDS). The m-PFC column was prepared using carboxy-based multiwalled carbon nanotubes, and used to reduce the interference of sample impurities. The samples were extracted with 5 mL of 0.1% formic acid aqueous solution, 15 mL of acetonitrile and extraction salt (2 g Na2SO4 and 2 g NaCl). The supernatant (10 mL) was purified using the m-PFC column, concentrated to near dryness under nitrogen, and then redissolved in 1 mL of methanol. Finally, the sample solution was filtered through a 0.22 µm polypropylene syringe filter for UPLC-MS/MS analysis. The target analytes were separated using a Shimadzu Shim-pack G1ST-C18 chromatographic column (100 mm×2.1 mm, 2 µm) using methanol (A) and 5 mmol/L ammonium acetate aqueous solution (B) as the mobile phases via gradient elution. The linear gradient program were as follows: 0-0.5 min, 10%A-35%A; 0.5-3 min, 35%A-60%A; 3-5 min, 60%A-100%A; 5-6.5 min, 100%A; 6.5-7 min, 100%A-10%A. The target analytes were analyzed using negative electrospray ionization in multiple-reaction monitoring mode, and quantitative analysis was performed using the internal standard method. In this study, we optimized the mobile-phase system as well as the extraction solvent, time, volume, and salt. The 14 PFASs exhibited good peak shapes and sensitivities when the 5 mmol/L ammonium acetate solution-methanol system was used as the mobile phase. Compared with acetonitrile or methanol alone, the extraction efficiencies of the 14 PFASs were significantly improved when 5 mL of 0.1% formic acid aqueous solution was added, followed by 15 mL of acetonitrile. The extraction efficiencies of the 14 PFASs did not differ significantly when the extraction time was within 3-15 min. The extraction salt (MgSO4, Na2SO4, NaCl, (NH4)2SO4, and Na2SO4+NaCl) significantly affected the extraction efficiencies of the 14 PFASs. The highest extraction efficiencies of the 14 PFASs, which ranged from 47.9% to 121.9%, were obtained when Na2SO4+NaCl was used as the extraction salt. Under the optimal experimental conditions, good linearities (R2=0.998-0.999) were obtained for seven PFASs (PFBS, PFHxA, PFHpA, PFHxS, PFDA, PFDoDA, PFTeDA) at 0.10-100 µg/L, and seven PFASs (PFBA, PFPeA, PFOA, PFOS, PFNA, PFUnDA, PFDS) at 0.50-100 µg/L. The average spiked recoveries for the 14 PFASs in Chinese mitten crabs at three levels ranged from 73.1% to 120%, with relative standard deviations (RSDs) in the range of 1.68%-19.5%(n=6). The limits of detection (LODs) and quantification (LOQs) of the 14 PFASs were in the range of 0.03-0.15 and 0.10-0.50 µg/kg, respectively. The developed method was applied to the analysis of crab samples collected from three farms in Shanghai, and PFASs with total concentrations of 3.52-37.77 µg/kg were detected in all samples. The detection frequencies for PFDA, PFUnDA, PFDoDA, PFTeDA, and PFOS were 100%. PFDA, PFUnDA, PFOS, and PFDoDA were the most abundant congeners, accounting for 31.2%, 30.6%, 15.0%, and 10.9%, respectively, of the 14 PFASs detected. The proposed method is simple, efficient, accurate, and suitable for the rapid analysis of 14 PFASs in Chinese mitten crabs.
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Fluorocarburos , Nanotubos de Carbono , Humanos , Espectrometría de Masas en Tándem , Cromatografía Liquida , Cloruro de Sodio/análisis , Metanol , Nanotubos de Carbono/análisis , China , Fluorocarburos/análisis , Ácidos Sulfónicos/análisis , Acetonitrilos , Cromatografía Líquida de Alta Presión , Extracción en Fase SólidaRESUMEN
The occurrence and development of tumors require the metabolic reprogramming of cancer cells, namely the alteration of flux in an autonomous manner via various metabolic pathways to meet increased bioenergetic and biosynthetic demands. Tumor cells consume large quantities of nutrients and produce related metabolites via their metabolism; this leads to the remodeling of the tumor microenvironment (TME) to better support tumor growth. During TME remodeling, the immune cell metabolism and antitumor immune activity are affected. This further leads to the escape of tumor cells from immune surveillance and therefore to abnormal proliferation. This review summarizes the regulatory functions associated with the abnormal biosynthesis and activity of metabolic signaling molecules during the process of tumor metabolic reprogramming. In addition, we provide a comprehensive description of the competition between immune cells and tumor cells for nutrients in the TME, as well as the metabolites required for tumor metabolism, the metabolic signaling pathways involved, and the functionality of the immune cells. Finally, we summarize current research targeted at the development of tumor immunotherapy. We aim to provide new concepts for future investigations of the mechanisms underlying the metabolic reprogramming of tumors and explore the association of these mechanisms with tumor immunity.
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Reprogramación Metabólica , Neoplasias , Humanos , Transducción de Señal , Vigilancia Inmunológica , Inmunoterapia , Microambiente TumoralRESUMEN
The hair follicle (HF) is the fundamental unit for fleece and cashmere production in cashmere goats and is crucial in determining cashmere yield and quality. The mechanisms regulating HF development in cashmere goats during the embryonic period remain unclear. Growing evidence suggests that HF development involves complex developmental stages and critical events, and identifying the underlying factors can improve our understanding of HF development. In this study, samples were collected from embryonic day 75 (E75) to E125, the major HF developmental stages. The embryonic HFs of cashmere goats were subjected to proteomic and metabolomic analyses, which revealed dynamic changes in the key factors and signalling pathways controlling HF development at the protein and metabolic levels. Gene ontology and the Kyoto Encyclopaedia of Genes and Genomes were used to functionally annotate 1784 significantly differentially expressed proteins and 454 significantly differentially expressed metabolites enriched in different HF developmental stages. A joint analysis revealed that the oxytocin signalling pathway plays a sustained role in embryonic HF development by activating the MAPK and Ca2+ signalling pathways, and a related regulatory network map was constructed. This study provides a global perspective on the mechanism of HF development in cashmere goats and enriches our understanding of embryonic HF development.
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A sensitive and reliable method for determining 25 polybrominated diphenyl ethers (PBDEs) in Chinese mitten crabs and their ecosystems ranging from the growing environment to edible feed by gas chromatography coupled to triple quadrupole mass spectrometry with advanced electron ionization (GC-AEI-MS/MS) was developed and validated. Accelerated solvent extraction (ASE) and liquid-liquid extraction were used to extract solid and water samples, respectively. On the basis of a traditional acid-base silica column, deactivated silica was added and n-hexane elution was used to increase the effect of separation and purification. Two oven temperature programs were applied to achieve good separation of low brominated congeners and increase the sensitivity of high brominated congeners. The method provided good linearity (>0.9996). The recoveries of four matrices were in the range of 82-115% and the method quantification limits (MQLs) in crabs, feed, sediment and water ranged from 0.36-6 pg per g wet weight, 0.69-22.29 pg per g dry weight, 1.02-25.26 pg per g dry weight, and 2.43-40.14 pg L-1, respectively. The proposed method was used for ten samples from two aquatic sites and PBDEs were detected in Chinese mitten crabs, commercial feed and sediment, with the highest in crabs. This analytical technique can be used to monitor the content and the accumulation behavior of PBDEs in Chinese mitten crab ecosystems or other aquaculture systems.
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Braquiuros , Éteres Difenilos Halogenados , Ecosistema , Cromatografía de Gases y Espectrometría de Masas , Espectrometría de Masas en Tándem , AnimalesRESUMEN
OBJECTIVES: Low-intensity, focused ultrasound (FUS) is an emerging noninvasive neuromodulation approach, with improved spatial and temporal resolution and penetration depth compared to other noninvasive electrical stimulation strategies. FUS has been used to modulate circuits in the brain and the peripheral nervous system, however, its potential to modulate spinal circuits is unclear. In this study, we assessed the effect of trans-spinal FUS (tsFUS) on spinal reflexes in healthy rats. MATERIALS AND METHODS: tsFUS targeting different spinal segments was delivered for 1 minute, under anesthesia. Monosynaptic H-reflex of the sciatic nerve, polysynaptic flexor reflex of the sural nerve, and withdrawal reflex tested with a hot plate were measured before, during, and after tsFUS. RESULTS: tsFUS reversibly suppresses the H-reflex in a spinal segment-, acoustic pressure- and pulse-repetition frequency (PRF)-dependent manner. tsFUS with high PRF augments the degree of homosynaptic depression of the H-reflex observed with paired stimuli. It suppresses the windup of components of the flexor reflex associated with slower, C-afferent, but not faster, A- afferent fibers. Finally, it increases the latency of the withdrawal reflex. tsFUS does not elicit neuronal loss in the spinal cord. CONCLUSIONS: Our study provides evidence that tsFUS reversibly suppresses spinal reflexes and suggests that tsFUS could be a safe and effective strategy for spinal cord neuromodulation in disorders associated with hyperreflexia, including spasticity after spinal cord injury and painful syndromes.
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Cashmere, a keratinised product of secondary hair follicles (SHFs) in cashmere goats, holds an important place in international high-end textiles. However, research on the complex molecular and signal regulation during the development and growth of hair follicles (HFs), which is essential for the development of the cashmere industry, is limited. Moreover, increasing evidence indicates that non-coding RNAs (ncRNAs) participate in HF development. Herein, we systematically investigated a competing endogenous RNA (ceRNA) regulatory network mediated by circular RNAs (circRNAs), microRNAs (miRNAs), and messenger RNAs (mRNAs) in skin samples of cashmere goat embryos, using whole-transcriptome sequencing technology. We obtained 6468, 394, and 239 significantly differentially expressed mRNAs, circRNAs, and miRNAs, respectively. These identified RNAs were further used to construct a ceRNA regulatory network, mediated by circRNAs, for cashmere goats at a late stage of HF development. Among the molecular species identified, miR-184 and fibroblast growth factor (FGF) 10 exhibited competitive targeted interactions. In secondary HF dermal papilla cells (SHF-DPCs), miR-184 promotes proliferation, inhibits apoptosis, and alters the cell cycle via the competitive release of FGF10. This study reports that FGF10 and its interaction with ncRNAs significantly affect SHF-DPCs, providing a reference for research on the biology of HFs in cashmere goats and other mammals.