•First hydrogeological model established for URL site of HLW disposal in China.•The effect of the hydraulic influence zones of faults is incorporated in the numerical model.•Different variations in ...the horizontal and vertical directions of hydraulic conductivity are considered.•A total of 120 stochastic parameterized models are presented.•Hydraulic conductivity < 10−9 m/s at high-level radioactive waste disposal depth.
Deep geological disposal is internationally accepted as a feasible and safe approach for high-level radioactive waste (HLW) disposal. To evaluate hydrogeological conditions in support of safety assessments for HLW disposal at the Xinchang preselected site in China, stochastic inverse models of site-scale groundwater flow were developed in this study to generate highly parameterized hydraulic conductivity fields for the fractured medium by adopting pilot point and null-space Monte Carlo methods. The hydraulic influence zones of the faults were carefully considered to have homogenous parameter values across the zones. A total of 120 multiple random realizations were generated to characterize the 3D spatial variations in hydraulic conductivity by conditioning to 1218 fixed pilot points. The simulated hydraulic heads of the realizations were in good agreement with observational data. The hydraulic conductivity fields close to the boreholes could be characterized in detail and had relatively low uncertainties. Furthermore, the hydraulic conductivity (K) values around underground research laboratory (URL) at the HLW disposal zone depth were less than 10−9 m/s. The K values obtained for most of the influence zones of these faults at this depth were consistent with hydraulic test data and ranged from 10−10 to 10−9 m/s, thereby indicating that the surrounding rock has low permeability and is suitable for HLW disposal. These findings offer new insights into hydrogeological conditions by providing key information on the permeability characteristics that need further focus on HLW disposal.
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•Uranyl oxyhydroxide (UOH) films were deposited on silicon substrate.•Hydrolysis of UO22+ by addition of solid Mg(OH)2 led to metaschoepite.•Metaschoepite surfaces formed at 50 °C/3h ...were self-affine fractal (Df = 2.5).•Mn+ incorporation (wt. %) into metaschoepite: La > Nd > Ce > Eu > Pb ≫ Sr.•Metaschoepite and Na-uranate hydrate were formed in Cl − SO4 − Na groundwater.
Incorporation of fission products in spent nuclear fuel is of interest in the frame of safe storage of high-level nuclear waste in a deep geological repository. Uranyl oxyhydroxide films were grown on silicon wafer to represent the corrosion product formed on the surfaces of the fuel. Films were obtained by hydrolysis of uranyl ions (9 mM) in mild conditions (≤60 °C) using either Mg(OH)2, raw brucite, La(OH)3, or NH4OH to control the solution pH to ≈ 5.0. To identify the mineral phases we used the grazing-incidence X-ray technique. Atomic force microscopy data indicated that the surfaces of metaschoepite films prepared using either Mg(OH)2 or brucite at 50 °C for 3 h were self-affine fractal (Df = 2.5). The concentration (wt.%) of reactant ions detected in a metaschoepite film after reaction at 70 °C for three days as determined by X-ray fluorescence was: La (8.90) > Nd (5.6) > Ce (3.2) > Eu (2.5) > Pb (0.7) > Sr (0.14). Metaschoepite and sodium uranate hydrate were identified in a film formed in Cl-SO4-Na type groundwater from the Beishan area (China), the preselected area of a radioactive waste disposal repository.
Citrus is an important type of fruit, with antioxidant bioactivity. However, the variations in the antioxidant ability of different tissues in citrus and its metabolic and molecular basis remain ...unclear. Here, we assessed the antioxidant capacities of 12 tissues from
'Ponkan', finding that young leaves and root exhibited the strongest antioxidant capacity. Secondary metabolites accumulated differentially in parts of the citrus plant, of which flavonoids were enriched in stem, leaf, and flavedo; phenolic acids were enriched in the albedo, while coumarins were enriched in the root, potentially explaining the higher antioxidant capacities of these tissues. The spatially specific accumulation of metabolites was related to the expression levels of biosynthesis-related genes such as
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),
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), and
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), among others, in the phenylpropane pathway. Weighted gene co-expression network analysis (WGCNA) identified modules associated with flavonoids and coumarin content, among which we identified an OMT involved in coumarin
-methylation, and related transcription factors were predicted. Our study identifies key genes and metabolites influencing the antioxidant capacity of citrus, which could contribute to the enhanced understanding and utilization of bioactive citrus components.
Ulcerative colitis is intricately linked to intestinal oxidative stress and dysbiosis of the gut microbiota. Lonicera japonica Thunb. (LJ) is a traditional edible and medical flower in China, and ...chlorogenic acid (CGA) is one of its characteristic components. However, it remains unclear whether gut microbiota plays a role in the therapeutic effects of LJ and GCA on colitis. Here, we first observed that oral administration of LJ and CGA for 3 weeks dramatically promoted the growth of Lactobacillus and fecal short‐chain fatty acids (SCFAs) production in healthy mice. Subsequently, the alleviating effects of LJ and CGA on colitis were explored with a dextran sulfate sodium‐induced colitis mice model. The intervention of LJ and CGA notably alleviated inflammation, intestinal barrier impairment, and oxidative stress in colitis and led to a significant elevation in Lactobacillus and fecal SCFAs. Eventually, the key role of gut microbiota and their metabolites on the therapeutic effects was validated by performing fecal microbiota transplantation and sterile fecal suspensions transplantation from LJ and CGA‐treated healthy mice to colitis mice. Our findings demonstrated that consumption of LJ and CGA could benefit the host both in healthy condition and colitis. The beneficial effects were attributed to the improvement of the endogenous antioxidant system and promotion of the probiotic Lactobacillus and SCFAs production. Our study highlighted the great potential of LJ and CGA to be consumed as functional foods and provided novel mechanisms by which they alleviated colitis.
Lonicera japonica Thunb. (LJ) extract and chlorogenic acid (CGA) significantly alleviated inflammation, intestinal barrier injury, and oxidative stress in dextran sulfate sodium (DSS)‐induced murine colitis. The intervention of LJ extract and CGA promoted the growth of Lactobacillus and short‐chain fatty acids production both in healthy and colitis mice. Fecal microbiota transplantation of LJ and CGA‐mediated gut microbiota alleviated DSS‐induced colitis in mice.
The gut microbiota—the community of microorganisms in the gut—has been implicated in many physical and mental disorders in addition to intestinal diseases. Diets are the most studied and promising ...factors for altering it. Indeed, certain dietary interventions that increase fiber intake rapidly change levels of certain nutrients that can modify the composition of the microbiota, promoting richness and diversity. Recent intriguing evidence from several human clinical trials suggested that the composition and diversity of patients’ gut microbiotas at baseline can influence their responses to cancer immunotherapy. If the factors that influence the gut microbiota were fully understood, it is conceivable that manipulating them could boost therapeutic responses in cancer patients. In this review, we investigate the possibility of using fruits, vegetables, or whole grains to enhance response to cancer therapies in humans, as current evidence suggests that these dietary components can manipulate and enhance diversity of the gut microbiota. Accordingly, dietary interventions with locally available fruits, vegetables, and whole grains might be an affordable and safe approach to enhancing the diversity of the gut microbiota before immunotherapy, in turn improving patients’ responses to their treatments.
Graphical Abstract
Chinese bayberry has been used to treat diarrhea in China for more than 2,000 years, but the mechanism is not clear. Due to the extensive use of antibiotics, antibiotic-associated diarrhea (AAD) is ...becoming more and more common in clinic, but there is no effective drug for the treatment. The present study aimed to explore the therapeutic effect of Chinese bayberry on AAD for the first time, and explained the underlying mechanism from different aspects. The BALB/c mice model was established by intragastric administration of lincomycin (3 g/kg). Successfully modeled mice were treated with purified water, dried bayberry powder suspension (100 mg/kg), C3G suspension (40 mg/kg) and montmorillonite powder suspension (40 mg/kg), respectively. The changes of body weight, diarrhea index, diarrhea status score were recorded and calculated regularly. 16S rRNA gene sequencing, intestinal immunofluorescence and inflammatory factor detection were further performed. The treatment with dried bayberry powder suspension and C3G suspension could rapidly reduce the diarrhea score and diarrhea index, increase food intake and restore body weight gain. The gut microbiota richness and diversity were significantly increased after dried bayberry powder suspension and C3G suspension treatments, typically decreased bacterial genera
Enterococcus
and
Clostridium senus stricto 1
. In addition, intake of Chinese bayberry powder and C3G significantly decreased the level of p65 phosphorylation, and up-regulated the expression of intestinal tight junction protein claudin-1 and ZO-1. Chinese bayberry fruit had the effect of alleviating AAD, and C3G was supposed to play the predominant role. The mechanism was indicated to be related with restoring the homeostasis of gut microbiota, inhibiting the level of harmful bacteria and increasing the abundance of beneficial bacteria, down-regulating TNF-α, IL-6, and IL-12 factors to reduce inflammation, restoring intestinal tight junction proteins and reducing intestinal permeability.
The aim of this study is to compare the regulatory abilities of citrus flavonoids on the oscillating expression of circadian genes. Seven varieties of citrus fruits and twenty-five citrus flavonoids ...were selected and evaluated. Per2 luciferase bioluminescence report system and serum shock were used to induce circadian gene expression in mouse microglia BV-2 cells. In vivo experiments were carried out using C57BL6/J mice to evaluate the regulation of flavonoids on the oscillatory expression of liver biorhythm genes. Lipopolysaccharide was used to interfere the gene oscillating expression. QRT-PCR was performed to detect the expression of circadian rhythm-related genes, including Clock, Bmal1, Per1, Per2, Per3, Cry1, Cry2, Rev-erbα, Rev-erbβ, Rorα, Dbp, and Npas2. The results show that the polymethoxyflavones (PMFs) exerted stronger circadian gene regulatory capability, while the flavonoids containing glycosides showed no biological activity. Also, all tested flavonoids decreased LPS-induced nitric oxide release, but only polymethoxyflavones inhibited circadian rhythm disorder. PMFs inhibited Nlrp3 inflammasome-related genes and proteins, including Nlrp3, IL-1β, ASC, and Caspase1, while other flavonoids only affected IL-1β and Caspase1 expression. This mechanism was preliminarily verified using the Nlrp3 inhibitor INF39.
Limonin is an important bioactive substance in citrus fruits, especially in seeds, which has great potential in cancer prevention and treatment. In order to explore the anticancer activity based on ...interaction between limonin and NQO1, Human promyelocytic leukemia cells (HL‐60) were studied in vitro. We found that limonin could inhibit proliferation and promote apoptosis of HL‐60 cells, and the effect was positively correlated with its dosage. Western blot results showed that limonin could activate the endogenous apoptosis pathway mediated by mitochondria via up‐regulating pro‐apoptotic proteins (Bax, cytochrome c, Caspase3, and Caspase9) and down‐regulating anti‐apoptotic proteins (Bcl‐2), thus inhibiting the proliferation of HL‐60 cells and promoting apoptosis, which further proved the anticancer activity of limonin from the molecular mechanism. At the same time, limonin down‐regulated the expression of NQO1, indicating that limonin may indirectly act on the apoptosis pathway by regulating the expression activity of antioxidant enzymes in vivo, thus exerting its inhibitory effect on tumor cells, which provides an idea for the molecular mechanism that natural products can indirectly exert their anticancer effect by regulating the activity of antioxidant enzymes.
Limonin, a citrus nutrient factor, was used as the subject material, which showed a proliferation inhibitory effect on HL‐60 cells. Mechanism exploration found that this effect was caused by activating the apoptosis pathway through inhibiting NQO1 expression.
Berries are fairly favored by consumers. Phenolic compounds are the major phytochemicals in berries, among which anthocyanins are one of the most studied. Phenolic compounds are reported to have ...prebiotic-like effects. In the present study, we identified the anthocyanin profiles, evaluated and compared the antioxidant capacities and gut microbiota modulatory effects of nine common berries, namely blackberry, black goji berry, blueberry, mulberry, red Chinese bayberry, raspberry, red goji berry, strawberry and white Chinese bayberry. Anthocyanin profiles were identified by UPLC-Triple-TOF/MS. In vitro antioxidant capacity was evaluated by four chemical assays (DPPH, ABTS, FRAP and ORAC). In vivo antioxidant capacity and gut microbiota modulatory effects evaluation was carried out by treating healthy mice with different berry extracts for two weeks. The results show that most berries could improve internal antioxidant status, reflected by elevated serum or colonic T-AOC, GSH, T-SOD, CAT, and GSH-PX levels, as well as decreased MDA content. All berries significantly altered the gut microbiota composition. The modulatory effects of the berries were much the same, namely by the enrichment of beneficial SCFAs-producing bacteria and the inhibition of potentially harmful bacteria. Our study shed light on the gut microbiota modulatory effect of different berries and may offer consumers useful consumption guidance.
The determination of the redox potential (Eh) of underground water in repository site is extremely important for long-term safety evaluation. The present study has developed a novel methodology for ...Eh estimation of the underground water of Beishan borehole 28 (BS28), which consists of the on site logging, the modelling with the characteristics of sampled water and rock cores and the verification study dedicated to evaluate the reliability of the Eh measurement. An Eh range between − 56 and 118 mV is suggested for BS28 underground water at 365–690 m deep after a thorough analysis of both modelling data and measurements.
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