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The terahertz structured beams played a significant role in imaging. We utilized the transmitter with 0.1 THz to generate the quasi-Pearcey beam. The beam is produced by combining the self-designed parabola-slit modulated plate and Fourier lens, showing stripe-shaped pattern and self-focusing property. Based on that, introducing it into the testing of ptychography, we discovered there are decent effects in field reconstruction of the probe and sample with this beam by comparisons both in the simulations and the experiments. The beam has good spatial coherence through the analysis of the spatial frequency spectrums. It suggests that the beam with such features can take advantage of rapid reconstruction in full-field imaging.
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A terahertz (THz) fan-beam computed tomography (CT) system using a 0.3â THz continuous-wave sheet beam is proposed. The diffraction-free sheet beam expands in a fan shape in only one direction and provides propagation-invariant focal lines and extended the depth-of-field. The fan-beam CT based on this beam is the second-generation THz CT. It breaks the conventional 4-f symmetric structure of THz CT using the parallel beam. The fan-beam THz CT allows for use with a linear array detector, which reduces the time required to collect data. To demonstrate its feasibility for three-dimensional (3D) imaging, the 3D structure of a metal rod packed in a carton is reconstructed with the support of the system. The results show that the object's internal structure can be obtained by this new THz CT system while retaining the geometrically magnified features of the cross-sectional structure. The results of our research provide a template for the second-generation THz CT system, which provides an additional method for nondestructive testing.
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As one of the oldest infectious diseases in the world, tuberculosis (TB) is the second most deadly infectious disease after COVID-19. Tuberculosis is caused by Mycobacterium tuberculosis (Mtb), which can attack various organs of the human body. Up to now, drug-resistant TB continues to be a public health threat. Pyrazinamide (PZA) is regarded as a sterilizing drug in the treatment of TB due to its distinct ability to target Mtb persisters. Previously we demonstrated that a D67N mutation in Mycobacterium tuberculosis polynucleotide phosphorylase (MtbPNPase, Rv2783c) confers resistance to PZA and Rv2783c is a potential target for PZA, but the mechanism leading to PZA resistance remains unclear. To gain further insight into the MtbPNPase, we determined the cryo-EM structures of apo Rv2783c, its mutant form and its complex with RNA. Our studies revealed the Rv2783c structure at atomic resolution and identified its enzymatic functional groups essential for its phosphorylase activities. We also investigated the molecular mechanisms underlying the resistance to PZA conferred by the mutation. Our research findings provide structural and functional insights enabling the development of new anti-tuberculosis drugs.
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Mycobacterium tuberculosis , Tuberculosis , Humanos , Mycobacterium tuberculosis/genética , Polirribonucleótido Nucleotidiltransferasa/genética , Microscopía por Crioelectrón , Amidohidrolasas , Pruebas de Sensibilidad Microbiana , Antituberculosos/farmacología , Pirazinamida/química , Pirazinamida/uso terapéutico , Tuberculosis/tratamiento farmacológico , Tuberculosis/microbiología , Mutación , ARNRESUMEN
BACKGROUND: Definitive concurrent chemoradiotherapy (dCCRT) is the gold standard for the treatment of locally advanced esophageal squamous cell carcinoma (ESCC). However, the potential benefits of consolidation chemotherapy after dCCRT in patients with esophageal cancer remain debatable. Prospective randomized controlled trials comparing the outcomes of dCCRT with or without consolidation chemotherapy in patients with ESCC are lacking. In this study, we aim to generate evidence regarding consolidation chemotherapy efficacy in patients with locally advanced, inoperable ESCC. METHODS: This is a multicenter, prospective, open-label, phase-III randomized controlled trial comparing non-inferiority of dCCRT alone to consolidation chemotherapy following dCCRT. In total, 600 patients will be enrolled and randomly assigned in a 1:1 ratio to receive either consolidation chemotherapy after dCCRT (Arm A) or dCCRT alone (Arm B). Overall survival will be the primary endpoint, whereas progression-free survival, locoregional progression-free survival, distant metastasis-free survival, and treatment-related toxicity will be the secondary endpoints. DISCUSSION: This study aid in further understanding the effects of consolidation chemotherapy after dCCRT in patients with locally advanced, inoperable ESCC. TRIAL REGISTRATION: ChiCTR1800017646.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Quimioradioterapia , Quimioterapia de Consolidación , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/radioterapia , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Estudios Prospectivos , Ensayos Clínicos Controlados Aleatorios como Asunto , Estudios Multicéntricos como Asunto , Ensayos Clínicos Fase III como Asunto , Estudios de Equivalencia como AsuntoRESUMEN
Genetic and environmental factors can independently or coordinatively drive ocular axis growth. Mutations in FRIZZLED5 (FZD5) have been associated with microphthalmia, coloboma, and, more recently, high myopia. The molecular mechanism of how Fzd5 participates in ocular growth remains unknown. In this study, we compiled a list of human genes associated with ocular growth abnormalities based on public databases and a literature search. We identified a set of ocular growth-related genes from the list that was altered in the Fzd5 mutant mice by RNAseq analysis at different time points. The Fzd5 regulation of this set of genes appeared to be impacted by age and light damage. Further bioinformatical analysis indicated that these genes are extracellular matrix (ECM)-related; and meanwhile an altered Wnt signaling was detected. Altogether, the data suggest that Fzd5 may regulate ocular growth through regulating ECM remodeling, hinting at a genetic-environmental interaction in gene regulation of ocular axis control.
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Receptores Frizzled , Microftalmía , Animales , Humanos , Ratones , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Regulación de la Expresión Génica , Vía de Señalización WntRESUMEN
Three novel phragmalin-type limonoids, swieteliacates S-U (1-3), were isolated from Swietenia macrophylla leaves, alongside four previously identified limonoids (4-7). The structures, encompassing absolute configurations, were delineated through 1D and 2D NMR analyses, high-resolution mass spectrometry (HR-MS), and NMR and ECD calculations. Swieteliacate S (1) is a distinctive cryptate comprising a tricyclo[4.2.110,30.11,4]decane fragment and an additional five-membered oxygen ring. Compounds 3 and 5 exhibited inhibition rates of 26.08 ± 2.26% and 15.42 ± 3.66%, respectively, on triglyceride (TG) production in Hep G2 cells at 40 µM.
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Limoninas , Meliaceae , Limoninas/química , Limoninas/farmacología , Estructura Molecular , Espectroscopía de Resonancia Magnética , Meliaceae/químicaRESUMEN
Photochemically generated reactive oxygen species (ROS) are widespread on the earth's surface under sunlight irradiation. However, the nonphotochemical ROS generation in surface water (e.g., paddy overlying water) has been largely neglected. This work elucidated the drivers of nonphotochemical ROS generation and its spatial distribution in undisturbed paddy overlying water, by combining ROS imaging technology with in situ ROS monitoring. It was found that H2O2 concentrations formed in three paddy overlying waters could reach 0.03-16.9 µM, and the ROS profiles exhibited spatial heterogeneity. The O2 planar-optode indicated that redox interfaces were not always generated at the soil-water interface but also possibly in the water layer, depending on the soil properties. The formed redox interface facilitated a rapid turnover of reducing and oxidizing substances, creating an ideal environment for the generation of ROS. Additionally, the electron-donating capacities of water at soil-water interfaces increased by 4.5-8.4 times compared to that of the top water layers. Importantly, field investigation results confirmed that sustainable â¢OH generation through nonphotochemical pathways constituted of a significant proportion of total daily production (>50%), suggesting a comparable or even greater role than photochemical ROS generation. In summary, the nonphotochemical ROS generation process reported in this study greatly enhances the understanding of natural ROS production processes in paddy soils.
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Especies Reactivas de Oxígeno , Suelo , Agua , Especies Reactivas de Oxígeno/metabolismo , Suelo/química , Oxidación-Reducción , Peróxido de HidrógenoRESUMEN
17α-Hydroxyprogesterone (17α-OHP) quantification in dried blood spots (DBS) is essential for newborn screening for congenital adrenal hyperplasia (CAH), which is challenging due to its low physiological concentration. The high false-positive rates of immunoassays necessitate the development of more accurate methods. Liquid chromatography tandem mass spectrometry (LC-MS/MS) offers increased specificity and sensitivity, yet standardized procedures for 17α-OHP measurement are required for clinical application. A candidate reference measurement procedure (cRMP) using isotope dilution LC-MS/MS was developed for 17α-OHP quantification in DBS. By utilizing stable isotope-labeled D8-17α-OHP as an internal standard, the cRMP was optimized, covering sample preparation, calibration, and LC-MS/MS analysis. The method performance was validated across several parameters, including precision, accuracy, specificity, detection limits, and matrix effects. Clinical applicability was further assessed through the establishment of reference intervals for healthy newborns. The developed cRMP exhibited a linear range of 1.00 to 80.00 ng/mL for 17α-OHP, with detection and quantification limits of 0.14 ng/mL and 0.52 ng/mL, respectively. Inter- and intraday precision demonstrated coefficients of variation within 1.27 to 5.69%. The recovery rates and matrix effects were well within acceptable limits, ensuring method reliability. Clinical application showed distinct reference intervals for healthy newborns that were unaffected by sex but influenced by weight and gestational age. This method significantly enhances CAH diagnostic accuracy in newborns, providing a valuable tool for clinical laboratories and improving newborn screening program standardization and traceability.
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17-alfa-Hidroxiprogesterona , Pruebas con Sangre Seca , Espectrometría de Masas en Tándem , Humanos , Espectrometría de Masas en Tándem/métodos , Pruebas con Sangre Seca/métodos , 17-alfa-Hidroxiprogesterona/sangre , Recién Nacido , Cromatografía Liquida/métodos , Límite de Detección , Estándares de Referencia , Hiperplasia Suprarrenal Congénita/sangre , Hiperplasia Suprarrenal Congénita/diagnóstico , Tamizaje Neonatal/métodos , Reproducibilidad de los Resultados , Técnicas de Dilución del Indicador , Femenino , Valores de ReferenciaRESUMEN
Male Japanese quails (Coturnix japonica) have been found to exhibit a three-phase metabolic change when subjected to prolonged fasting, during which basal thermogenesis is significantly reduced. A study had shown that there is a significant difference in the body temperature between male and female Japanese quails. However, whether female Japanese quails also show the same characteristic three-phase metabolic change during prolonged fasting and the underlying thermogenesis mechanisms associated with such changes are still unclear. In this study, female Japanese quails were subjected to prolonged starvation, and the body mass, basal metabolic rate (BMR), body temperature, mass of tissues and organs, body fat content, the state-4 respiration (S4R) and cytochrome c oxidase (CCO) activity in the muscle and liver of these birds were measured to determine the status of metabolic changes triggered by the starvation. In addition, the levels of glucose, triglyceride (TG) and uric acid, and thyroid hormones (T3 and T4) in the serum and the mRNA levels of myostatin (MSTN) and avian uncoupling protein (av-UCP) in the muscle were also measured. The results revealed the existence of a three-phase stage similar to that found in male Japanese quails undergoing prolonged starvation. Fasting resulted in significantly lower body mass, BMR, body temperature, tissues masses and most organs masses, as well as S4R and CCO activity in the muscle and liver. The mRNA level of av-UCP decreased during fasting, while that of MSTN increased but only during Phase I and II and decreased significantly during Phase III. Fasting also significantly lowered the T3 level and the ratio of T3/T4 in the serum. These results indicated that female Japanese quails showed an adaptive response in basal thermogenesis at multiple hierarchical levels, from organismal to biochemical, enzyme and cellular level, gene and endocrine levels and this integrated adjustment could be a part of the adaptation used by female quails to survive long-term fasting.
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Coturnix , Codorniz , Femenino , Masculino , Animales , Coturnix/metabolismo , Codorniz/metabolismo , Ayuno/metabolismo , Termogénesis , ARN Mensajero/genéticaRESUMEN
BACKGROUND: Bamboo leaf flavonoids (BLF) are the main bioactive ingredients in bamboo leaves. They have antioxidant, anti-inflammatory, antibacterial, and other effects. In this study, the effects of dietary BLF on growth performance, immune response, antioxidant capacity, and intestinal microbiota of broilers were investigated. A total of 288 broilers were divided into three groups with eight replicates and 12 birds in each replicate. Broilers were fed a basic diet or the basic diet supplemented with 1000 or 2000 mg kg-1 BLF for 56 days. RESULTS: The results showed that supplementation of BLF increased body weight (BW) and average daily weight gain (ADG), and reduced average daily feed intake (ADFI) (P < 0.05). The serum immunoglobulin A (IgA), immunoglobulin M (IgM), and interleukin 10 (IL-10) content of broilers in the BLF1000 group was increased and the interleukin 1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) content was decreased (P < 0.05). The levels of IgM and IL-10 in jejunum mucosa were found to be enhanced by BLF (P < 0.05). The BLF1000 group exhibited a significant reduction in the concentration of TNF-α (P < 0.05). Serum and jejunum mucosa total antioxidant capacity (T-AOC) levels in the BLF1000 group were increased (P < 0.05). The serum catalase (CAT) and glutathione peroxidase (GSH-Px) effects of the BLF1000 group and serum CAT effects of BLF2000 group were increased (P < 0.05). The CON group demonstrated a lower relative abundance of Christensenellaceae_R-7_group and Oscillibacter than the BLF group (P < 0.05). CONCLUSION: Dietary BLF inclusion enhanced the growth performance, immune, and antioxidant functions, improved the intestinal morphology, and ameliorated the intestinal microflora structure in broiler. Adding 1000 mg kg-1 BLF to the broiler diet can be considered as an effective growth promoter. © 2024 Society of Chemical Industry.
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Alimentación Animal , Antioxidantes , Ciego , Pollos , Flavonoides , Microbioma Gastrointestinal , Intestinos , Hojas de la Planta , Animales , Pollos/crecimiento & desarrollo , Pollos/inmunología , Pollos/microbiología , Pollos/metabolismo , Antioxidantes/metabolismo , Antioxidantes/farmacología , Antioxidantes/administración & dosificación , Microbioma Gastrointestinal/efectos de los fármacos , Hojas de la Planta/química , Flavonoides/administración & dosificación , Flavonoides/farmacología , Ciego/microbiología , Ciego/metabolismo , Ciego/efectos de los fármacos , Alimentación Animal/análisis , Intestinos/efectos de los fármacos , Intestinos/microbiología , Intestinos/inmunología , Suplementos Dietéticos/análisis , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Masculino , Bacterias/clasificación , Bacterias/efectos de los fármacos , Bacterias/aislamiento & purificación , Bacterias/genética , Inmunoglobulina M/sangre , Inmunoglobulina A/sangre , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/sangre , Bambusa/química , Interleucina-10/sangre , Interleucina-10/metabolismo , Sasa/químicaRESUMEN
Polyploid giant cancer cells (PGCCs) play a fundamental role in tumor initiation, dormancy, drug resistance, and metastasis, although the detailed biology of PGCCs remains poorly understood. The lack of literature on establishing a reproducible in vitro system for generating PGCCs is the leading technological obstacle to studying the biology of PGCCs. Here we provide a detailed protocol for generating stable PGCCs from Hey cancer cells and studying the PGCCs' embryonic stemness. This protocol includes (1) generating PGCCs of high purity in 2D culture by exposing Hey cells to paclitaxel, monitoring the cell cycle and amitotic budding of daughter cells from PGCCs, and collecting and studying the daughter cells; (2) inducing PGCCs to form spheroids expressing embryonic stemness markers and observing the spheroids' cleavage and blastocyst-like structure; and (3) inducing redifferentiation of PGCCs into different lineages of differentiated cells.
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Neoplasias Ováricas , Poliploidía , Humanos , Neoplasias Ováricas/patología , Neoplasias Ováricas/metabolismo , Femenino , Línea Celular Tumoral , Diferenciación Celular , Células Gigantes , Técnicas de Cultivo de Célula/métodos , Células Madre Neoplásicas/metabolismo , Células Madre Neoplásicas/patología , Células Madre Neoplásicas/efectos de los fármacos , Esferoides Celulares , Paclitaxel/farmacología , Ciclo Celular/efectos de los fármacosRESUMEN
Cyclic volatile methylsiloxanes (cVMS) have been widely found in various types of environmental media and attracted increasing attention as new pollutants. However, there is still a great challenge in the accurate quantification of trace cVMS, due to their volatility, and the high background originating from GC/MS accessories and surroundings. In this work, the main sources of the high background were investigated in detail for octamethylcyclotetrasiloxane (D4), decmethylcyclopentasiloxane (D5) and dodecmethylcyclohexosiloxane (D6). Several effective measures were employed to minimize these backgrounds, including the delayed injection method to minimize the interference from the injection septum. Then, a GC-MS method was developed for the accurate determination of D4, D5 and D6, with a linear range of 2 - 200 µg/L. The coefficient of determination was 0.9982-0.9986, the limit of detection (LOD) was 0.40-0.52 µg/L, and the quantitative range was 1.88-190 µg/L. Good reproducibility and recovery were obtained, indicating the reliability of the established analytical method.
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Cromatografía de Gases y Espectrometría de Masas , Límite de Detección , Siloxanos , Siloxanos/análisis , Siloxanos/química , Cromatografía de Gases y Espectrometría de Masas/métodos , Reproducibilidad de los Resultados , Volatilización , Compuestos Orgánicos Volátiles/análisisRESUMEN
Microplastics (MPs), especially polystyrene microplastics (PS-MPs), have emerged a new worldwide pollutant, prompting significant public concern regarding their detection in environmental media. Analysis of PS-MPs in soil remains as a challenging task for analysts due to the highly intricate matrices. This work presents a practical approach for detecting PS-MPs in soil, which involves dilute HCl-assisted extraction and gel permeation chromatography- ultraviolet detection (GPC-UV) analysis. The presence of MPs in soil was confirmed through the use of a scanning electron microscope in conjunction with energy dispersive spectroscopy investigation. PS-MPs was isolated from soil, by agitating it with a diluted HCl solution, filtering the resulting liquid, and dissolving the residue on the filter with THF. The extractant was subsequently determined by GPC-UV. The introduction of a small amount of HCl into the extraction system was found to greatly expedite the settling of soil in water and enhance the efficacy of extracting PS-MPs in about 30 min. The linear range of PS-MPs was from 1.0 to 100 µg/mL with R2 > 0.999. Good reproducibility was obtained with the intra-day relative standard deviation (RSD, n = 3) of 1.36 % and the inter-day RSD (n = 3) of 4.78 %. The concentration of PS-MPs in soil samples were N.D. - 2.33 µg/g, and the good recoveries were 76.7-100.3 %. The corresponding AFGEEprer score was calculated to be 0.59, indicating the concept of green analytical chemistry for the pretreatment method. These results indicated that this method has a powerful potential for the accurate and rapid determination of PS-MPs in soil.
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Recognizing the pervasive presence of alumina minerals and low-molecular-weight organic acids (LMWOAs) in the environment, this study addressed the gap in the interaction mechanisms within the ternary system involving these two components and Fe(II). Specifically, the impacts of LMWOAs on hydroxyl radicals (â¢OH) production and iron species transformation during Fe(II) oxidation on γ-Al2O3 mineral surface were examined. Results demonstrated that adding 0.5 mM oxalate (OA) or citrate (CA) to the γ-Al2O3/Fe(II) system (28.1 µM) significantly enhanced â¢OH production by 1.9-fold (51.9 µM) and 1.3-fold (36.2 µM), respectively, whereas succinate (SA) exhibited limited effect (30.7 µM). Raising OA concentration to 5 mM further promoted â¢OH yield to 125.0 µM after 24 h. Deeper analysis revealed that CA facilitated the dissolution of adsorbed Fe(II) and its subsequent oxygenation by O2 through both one- and two-electron transfer mechanisms, whereas OA enhanced the adsorption of dissolved Fe(II) and more efficient two-electron transfer for H2O2 production. Additionally, LMWOAs presence favored the formation of iron minerals with poor crystallinity like ferrihydrite and lepidocrocite rather than well-crystallized forms such as goethite. The distinct impacts of various LMWOAs on Fe(II) oxidation and â¢OH generation underscore their unique roles in the redox processes at mineral surface, consequently modulating the environmental fate of prototypical pollutants like phenol.
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Óxido de Aluminio , Radical Hidroxilo , Oxidación-Reducción , Radical Hidroxilo/química , Óxido de Aluminio/química , Minerales/química , Hierro/química , Adsorción , Ácido Cítrico/químicaRESUMEN
Introduction: This trial was conducted to compare the effect of diets supplemented with plant essential oil (PEO) and coated plant essential oil (CEO) on growth performance, immunity, antioxidant activity, and fecal microbiota of weaned piglets. Methods: A total of 360 21-day-old weaned piglets were randomly allocated into three groups, namely, CON, PEO, and CEO (basal diets supplemented with 0, 500 mg/kg PEO, and 500 mg/kg CEO, respectively) for a 4-week feeding trial. Results and discussion: The results showed that dietary supplementation with CEO improved the average final weight and average daily gain, decreased the diarrhea rate, increased antioxidant enzyme activities, enhanced immunoglobulin concentrations, and decreased concentrations of pro-inflammatory cytokines in the serum of weaned piglets (p < 0.05). In addition, CEO addition increased the fecal concentrations of propionic acid and isovaleric acid of piglets (p < 0.05). Spearman correlation analysis showed that fecal microorganisms at the genus level were closely correlated with the volatile fatty acid concentrations. The present study indicated that PEO and CEO could improve growth performance, enhance immunity, and increase antioxidant capacity by modulating the microbial flora in weaned piglets. Moreover, CEO addition seemed to offer more positive results than of PEO addition.
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Aims: This cohort study aimed to explore the effect of a one-day online continuing medical education (CME) on the improvement of physicians' knowledge and clinical practice on functional dyspepsia (FD). Methods: Physicians were invited to participate in this CME via medical education applications. FD training videos made in advance were sent to participants via a weblink. Before and after training, participants were required to finish the FD knowledge test and provide case information of FD patients. McNemar test, Wilcoxon rank-sum test, Freidman test, Chi-square test, quantile regression, and generalized estimating equations (GEE) were used to perform statistical analysis. Results: There were 397 of 430 (92.33%) physicians finished this CME program. The total score of the FD knowledge test after training was significantly higher compared with before training [488.3 (468.3-510.0) vs. 391.7 (341.7-450.0), p < 0.001]. Particularly, physicians from primary hospitals show more increase in total scores than physicians from secondary and tertiary hospitals. According to the GEE model, receiving this online training was an independent predictor of physicians' choice of upper gastrointestinal endoscopy in patients with FD [OR 1.73, 95%CI (1.09-2.73), p = 0.020], especially in PDS. Also, it was an independent predictor of physicians' choice of acid-suppressive drugs in patients with FD [OR 1.30, 95%CI (1.03-1.63), p = 0.026], especially in EPS and PDS overlapping EPS. Conclusion: This one-day online CME program effectively and conveniently improved physicians' knowledge and clinical practice, providing new ideas for future CME and facilitating precise clinical management of FD patients with different subtypes especially in primary hospitals.
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ETHNOPHARMACOLOGY RELEVANCE: Traditional herbal medicines have been considered as a novel and effective way to treat many diseases. Lizhong decoction (LZD), a classical prescription composed of Zingiber officinale Rosc., Panax ginseng C. A. Mey., Atractylodes macrocephala Koidz., and Glycyrrhiza uralensis Fisch., has been used to treat gastrointestinal disorders in clinical practices for thousands of years. However, the mechanism of LZD in alleviating ulcerative colitis (UC) is still unclear. AIM OF THE STUDY: The purpose of this study was to clarify the potential molecular mechanism of LZD in improving UC. MATERIALS AND METHODS: The amelioration of LZD on dextran sodium sulfate (DSS)-induced UC mice was evaluated by body weight, colon length, pathology of colon tissues, pro-inflammatory cytokines, and intestinal tight junction (TJ) proteins. Moreover, the gene expression profiles of UC patients were extracted to investigate potential pathological mechanisms of UC. The influence of LZD on ferroptosis was analyzed by iron load, malondialdehyde (MDA), and the expression of ferroptosis-associated proteins. Meanwhile, the inhibition of LZD on oxidative stress (OS) was assessed by the superoxide dismutase (SOD) activity, as well as the expression levels of glutathione (GSH) and glutathione disulfide (GSSG). Furthermore, the influence of LZD on ferroptosis was assessed by inhibiting nuclear factor (erythroid-derived-2)-like 2 (Nrf2). RESULTS: LZD showed significant therapeutic effects in UC mice, including reduction of intestinal injury and inflammation. Moreover, LZD treatment notably upregulated the expression of TJ proteins. Further investigation indicated that LZD significantly inhibited the ferroptosis of enterocytes by decreasing iron load and MDA, and increasing the expression levels of solute carrier family 7 member 11 (SLC7A11) and glutathione peroxidase 4 (GPX4) in colon tissues. Furthermore, the decreased activity of SOD, reduced level of GSH, and increased content of GSSG in UC mice were notably reversed by LZD. Consistent with in vivo results, LZD could markedly inhibit ferroptosis and OS in RSL3-induced Caco-2 cells. Mechanistically, LZD alleviated ferroptosis by suppressing OS through the activation of Nrf2 signaling. CONCLUSIONS: Collectively, LZD remarkably improved intestinal pathological injury in UC mice, and its potential mechanism was the suppression of ferroptosis in enterocytes by the Nrf2/SLC7A11/GPX4 pathway.
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Colitis Ulcerosa , Colitis , Ferroptosis , Humanos , Animales , Ratones , Colitis Ulcerosa/inducido químicamente , Colitis Ulcerosa/tratamiento farmacológico , Enterocitos , Fosfolípido Hidroperóxido Glutatión Peroxidasa , Factor 2 Relacionado con NF-E2 , Disulfuro de Glutatión , Células CACO-2 , Glutatión , Hierro , Superóxido Dismutasa , Sulfato de Dextran/toxicidad , Ratones Endogámicos C57BL , Sistema de Transporte de Aminoácidos y+RESUMEN
Chiral pesticides exhibit enantioselective differences in processes such as biological absorption, metabolism, and toxic effects. Organisms have different physiological characteristics at different developmental stages. Therefore, conducting enantiomeric toxicity studies at different developmental stages of organisms can help deepen the understanding of the ecological effects of chiral pesticides. This study focused on trans-tetramethrin (Tet) and investigated the enantioselectivity in bioconcentration, developmental toxicity, estrogenic effects, and immunotoxicity of Tet's racemate ((±)-Tet) and its two enantiomers ((+)-Tet and (-)-Tet) in three developmental stages of zebrafish: embryos, yolk sac larvae, and juveniles. The results showed that Tet exhibited different enantioselectivity in lethal, bioconcentration, and teratogenic effects on zebrafish at different developmental stages. The LC50 value was (+)-Tet > (±)-Tet > (-)-Tet, with embryos being the most sensitive, followed by juveniles and yolk sac larvae. The enantioselective bioconcentration was (±)-Tet > (+)-Tet > (-)-Tet, and the bioconcentration effect was greater in embryos than that in yolk sac larvae and juveniles. Developmental toxicity indicated that (+)-Tet and (±)-Tet had higher teratogenic effects on yolk sac larvae than on embryos. Tet exhibited different enantioselective effects on the expression of zebrafish estrogen-related genes and innate immune-related genes at different developmental stages. These results will contribute to a more comprehensive assessment of the aquatic toxicity and environmental risks of chiral pesticides.
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High grade epithelial ovarian carcinoma is an aggressive tumor. Treatment includes platinum therapy, however it recurs in most patients due to therapy resistance. In this project, we study the immunohistochemical (IHC) expression of five potential biomarkers/prognostic markers in high grade epithelial ovarian carcinoma: EGFR, HLA-G, CD70, c-MET, and NY-ESO1. A cohort of 274 patients is used. We compare the IHC expression with age, stage, ascites status, family history of cancer, disease free survival (DFS) and overall survival (OS). EGFR expression is significantly correlated with family history and worse OS. HLA-G is associated with worse OS. To confirm the results of EGFR and HLA-G, a second separated cohort of 248 patients is used. Positive EGFR expression again shows worse OS, while HLA-G expression has worse prognostic trend. CD70 has a worse OS trend. C-MET and NY-ESO1 do not have any clinical correlations. EGFR can potentially serve as target in future clinical immune therapy trials.
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Antígenos de Neoplasias , Biomarcadores de Tumor , Carcinoma Epitelial de Ovario , Receptores ErbB , Antígenos HLA-G , Proteínas de la Membrana , Neoplasias Ováricas , Proteínas Proto-Oncogénicas c-met , Humanos , Femenino , Biomarcadores de Tumor/metabolismo , Proteínas de la Membrana/metabolismo , Proteínas Proto-Oncogénicas c-met/metabolismo , Receptores ErbB/metabolismo , Carcinoma Epitelial de Ovario/patología , Carcinoma Epitelial de Ovario/metabolismo , Carcinoma Epitelial de Ovario/mortalidad , Persona de Mediana Edad , Neoplasias Ováricas/metabolismo , Neoplasias Ováricas/patología , Neoplasias Ováricas/mortalidad , Pronóstico , Antígenos de Neoplasias/metabolismo , Antígenos HLA-G/metabolismo , Anciano , Adulto , Clasificación del Tumor , Inmunohistoquímica , Anciano de 80 o más AñosRESUMEN
In Southern China, the co-occurrence of arsenic (As) and antimony (Sb) contamination in soils around Sb mines presents an environmental challenge. During the flooding period of mining-impacted soils, anaerobic reduction of iron (Fe) oxides enhances the mobilization and bioavailability of Sb and As, further elevating the risk of Sb and As entering the food chain. To address this problem, activated carbon (AC) and biochar (BC) were applied to remediate flooded mining-impacted soils. Our results explored that AC can significantly decrease mobilization by 9-97 % for Sb and 9-67 % for As through inhibiting Fe(III) mineral reduction and dissolution in flooded soils. In contrast, there was no significant effect of BC. This was attributed to the strong adsorption of soil dissolved organic matter (DOM) by AC compared to BC, while DOM as electron shuttle is crucial for microbial Fe(III) reduction. Consequently, the DOM sequestration by AC effectively mitigates Sb and As leaching in contaminated mining soils.