Chronic Exposure to Drinking Water As, Pb, and Cd at Provisional Guideline Values Reduces Weight Gain in Male Mice via Gut Microflora Alterations and Intestinal Inflammation.

Few studies have investigated the long-term effect of exposure to arsenic (As), lead (Pb), and cadmium (Cd) via drinking water at the provisional guideline values on gut microflora. In this study, male and female mice were exposed to water As, Pb, or Cd at 10, 10, or 5 µg L-1 for 6 months. At the end of the exposure, the net weight gain of male mice exposed to As and Pb (9.91 ± 1.35 and 11.2 ± 1.50 g) was significantly (p < 0.05) lower compared to unexposed control mice (14.1 ± 3.24 g), while this was not observed for female mice. Relative abundance of Akkermansia, a protective gut bacterium against intestinal inflammation, was reduced from 29.7% to 3.20%, 4.83%, and 17.0% after As, Pb, and Cd exposure in male mice, which likely caused chronic intestinal inflammation, as suggested by 2.81- to 9.60-fold higher mRNA levels of pro-inflammatory factors in ileal enterocytes of male mice. These results indicate that long-term exposure to drinking water As, Pb, and Cd at concentrations equivalent to the China provisional guideline values can cause loss of protective bacteria and lead to chronic intestinal inflammation, thereby affecting body weight gain in male mice.

An interlaboratory evaluation of the variability in arsenic and lead relative bioavailability when assessed using a mouse bioassay.

Animal bioassays have been developed to estimate oral relative bioavailability (RBA) of metals in soil, dust, or food for accurate health risk assessment. However, the comparability in RBA estimates from different labs remains largely unclear. Using 12 soil and soil-like standard reference materials (SRMs), this study investigated variability in lead (Pb) and arsenic (As) RBA estimates employing a mouse bioassay in 3 labs at Nanjing University, University of Jinan, and Shandong Normal University. Two performances of the bioassay at Nanjing University in 2019 and 2020 showed reproducible Pb and As RBA estimates, but increasing the number of mouse replicates in 2020 produced more precise RBA measurements. Although there were inter-lab variations in diet consumption rate and metal accumulation in mouse liver and kidneys following SRM ingestion due to differences in diet composition, bioassays at 3 labs in 2019 yielded overall similar Pb and As RBA estimates for the 12 SRMs with strong linear correlations between each 2 of the 3 labs for Pb (R2 = 0.95-0.98 and slope = 0.85-1.02) and As RBA outcomes (R2 = 0.46-0.86 and slope = 0.56-0.79). The consistency in RBA estimates was attributed to the relative nature of the final bioavailability outcome, which might overcome the inter-lab variation in diet consumption and metal uptake in mice. These results increased the confidence of use of mouse bioassays in bioavailability studies.

Precision and accuracy of commercial assays for vancomycin therapeutic drug monitoring: evaluation based on external quality assessment scheme.

BACKGROUND: Vancomycin remains a mainstay of the treatment of Gram-positive bacterial infections. It is crucial to accurately determine vancomycin serum concentration for adequate dose adjustment. OBJECTIVES: To evaluate the precision and accuracy of commercial assay techniques for vancomycin concentration and to assess the comparability of vancomycin detection methods in Chinese laboratories. METHODS: Human serum samples spiked with known concentrations of vancomycin were provided to laboratories participating in the external quality assessment scheme (EQAS). Assay methods included chemiluminescence, enzyme immunoassay (EIA) and so on. The dispersion of the measurements was analysed and the robust coefficient of variation (rCV), relative percentage difference (RPD) and satisfactory rate for method groups were calculated. Moreover, performance of the Chinese laboratories was assessed. RESULTS: A total of 657 results from 75 laboratories were collected, including 84 samples from 10 Chinese laboratories. The median rCV, median RPD and satisfactory rates classified by methods ranged from 1.85% to 15.87%, -14.75% to 13.34% and 94.59% to 100.00%, respectively. Significant differences were seen in precision, between kinetic interaction of microparticles in solution (KIMS) and other methods, and in accuracy, between enzyme-multiplied immunoassay technique (EMIT), fluorescence polarization immunoassay (FPIA) and other techniques. Vancomycin detection in China mainly depended on the chemiluminescence and EMIT methods, which tended to result in lower measurements. CONCLUSIONS: Although almost all assays in this study achieved an acceptable performance for vancomycin serum concentration monitoring, obvious inconsistencies between methods were still observed. Chinese laboratories were more likely to underestimate vancomycin concentrations. Thus, recognizing inconsistencies between methods and regular participation in vancomycin EQAS are essential.

OsSYP121 Accumulates at Fungal Penetration Sites and Mediates Host Resistance to Rice Blast.

Magnaporthe oryzae is a fungal pathogen that causes rice (Oryza sativa) blast. SNAREs (soluble N-ethylmaleimide-sensitive factor attachment protein receptors) are key components in vesicle trafficking in eukaryotic cells and are known to contribute to fungal pathogen resistance. Syntaxin of Plants121 (SYP121), a Qa-SNARE, has been reported to function in nonhost resistance in Arabidopsis (Arabidopsis thaliana). However, the functions of SYP121 in host resistance to rice blast are largely unknown. Here, we report that the rice SYP121 protein, OsSYP121, accumulates at fungal penetration sites and mediates host resistance to rice blast. OsSYP121 is plasma membrane localized and its expression was obviously induced by the rice blast in both the blast-resistant rice landrace Heikezijing and the blast-susceptible landrace Suyunuo (Su). Overexpression of OsSYP121 in Su resulted in enhanced resistance to blast. Knockdown of OsSYP121 expression in Su resulted in a more susceptible phenotype. However, knockdown of OsSYP121 expression in the resistant landrace Heikezijing resulted in susceptibility to the blast fungus. The POsSYP121 ::GFP-OsSYP121 accumulated at rice blast penetration sites in transgenic rice, as observed by confocal microscopy. Yeast two-hybrid results showed that OsSYP121 can interact with OsSNAP32 (Synaptosome-associated protein of 32 kD) and Vesicle-associated membrane protein714/724. The interaction between OsSYP121 and OsSNAP32 may contribute to host resistance to rice blast. Our study reveals that OsSYP121 plays an important role in rice blast resistance as it is a key component in vesicle trafficking.

Arsenic Concentrations, Speciation, and Localization in 141 Cultivated Market Mushrooms: Implications for Arsenic Exposure to Humans.

Mushrooms accumulate arsenic (As), yet As concentrations, speciation, and localization in cultivated mushrooms across a large geographic distribution are unknown. We characterized 141 samples of nine species from markets in nine capital cities in China, with samples of Lentinula edodes, Pleurotus ostreatus, and Agaricus bisporus being analyzed for As speciation and localization. Total As concentrations ranged from 0.01 to 8.31 mg kg-1 dw, with A. bisporus (0.27-2.79 mg kg-1) containing the most As followed by P. ostreatus and L. edodes (0.04-8.31 and 0.12-2.58 mg kg-1). However, As in A. bisporus was mostly organic including nontoxic arsenobetaine, while P. ostreatus and L. edodes contained mainly inorganic As (iAs). On the basis of in situ imaging using LA-ICP-MS, As in L. edodes was localized to the surface coat of the cap, while As in P. ostreatus was localized to the junction of the pileus and stipe. When As speciation and daily mushroom consumption (1.37 g d-1 dw) are considered, daily mushroom consumption may result in elevated iAs exposure, with increased bladder and lung cancer rates up to 387 cases per 100000. Our study showed that market mushrooms could be a health risk to the general public so its production should be monitored.

Oral Bioavailability of As, Pb, and Cd in Contaminated Soils, Dust, and Foods based on Animal Bioassays: A Review.

Metal contamination in soil, dust, and food matrices impacts the health of millions of people worldwide. During the past decades, various animal bioassays have been developed to determine the relative bioavailability (RBA) of As, Pb, and Cd in contaminated soils, dust, and foods, which vary in operational approaches. This review discusses the strengths and weaknesses of different animal models (swine and mice), dosing schemes (single gavage dose, repeated gavage dose, daily repeated feeding, and free access to diet), and end points (blood, urine, and tissue) in metal-RBA measurement; compares metal-RBA obtained using mouse and swine bioassays, different dosing schemes, and different end points; and summarizes key findings on As-, Pb-, and Cd-RBA values in contaminated soils, dust, and foods. Future directions related to metal-RBA research are highlighted, including (1) comparison of metal-RBA determinations between different bioassays and different laboratories to ensure robust bioavailability data, (2) enhancing the metal-RBA database for contaminated dust and foods, (3) identification of physiological and physicochemical mechanisms responsible for variability in metal-RBA values, (4) formulation of strategies to decrease metal-RBA values in contaminated soils, dust, and foods, and (5) assessing the impacts of cocontaminants on metal-RBA measurement.

Antagonistic Interactions between Arsenic, Lead, and Cadmium in the Mouse Gastrointestinal Tract and Their Influences on Metal Relative Bioavailability in Contaminated Soils.

Soils are often co-contaminated with As, Pb, and Cd. To what extent ingested metal(loid)s interact with each other in the gastrointestinal tract and influence their RBA (relative bioavailability) is largely unknown. Three soils predominantly contaminated with As (MS, mining/smelting impacted), Pb (WR, wire rope production impacted), and Cd (EP, enamel pottery production impacted) were administered to mice individually or in binary and tertiary combinations with sodium arsenate, Cd chloride, and/or Pb acetate. In binary combinations, ∼10-fold higher Pb addition decreased As-RBA in MS (26.0 ± 6.28% to 17.1 ± 1.08%), while ∼10-fold higher As addition decreased Pb-RBA in WR (61.3 ± 2.41% to 28.8 ± 5.45%). This was possibly due to the formation of insoluble Pb arsenate in mouse intestinal tract, as indicated by the formation of precipitates when As and Pb co-occurred in water or simulated human gastrointestinal fluids. Due to competition for shared absorption transporters, ∼10- and 100-fold higher Pb addition decreased Cd-RBA in EP (95.8 ± 12.9% to 67.8 ± 12.8% and 62.8 ± 8.24%). Tertiary combinations showed that interactions between two metal(loid)s were affected by the presence of the third metal(loid). Our study suggests that As oxyanion could interact with Pb or Cd ions in the mouse gastrointestinal tract, and the interactions vary depending on concentration and solution characteristics.

Quantitative analysis of the relationship between the myocardial bridge and the FAI of pericoronal fat on computed tomography.

We performed this cohort study to investigate whether the myocardial bridge (MB) affects the fat attenuation index (FAI) and to determine the optimal cardiac phase to measure the volume and the FAI of pericoronary adipose tissue (PCAT). The data of 300 patients who were diagnosed with MB of the left anterior descending (LAD) coronary artery were retrospectively analyzed. All of patients were divided into the MB group and the MB with atherosclerosis group. In addition, 104 patients with negative CCTA results were enrolled as the control group. There was no significant difference between FAI values measured in systole and diastole (P > 0.05). There was no significant difference in FAI among the MB group, the MB with atherosclerosis group, and the control group (P > 0.05). In MB with atherosclerosis group, LAD stenosis degree (< 50%) (OR = 0.186, 95% CI 0.036-0.960; P = 0.045) and MB located in the distal part of LAD opening (OR = 0.880, 95% CI 0.789-0.980; P = 0.020) were protective factors of FAI value. A distance (from the LAD opening to the proximal point of the MB) of 29.85 mm had the highest predictive value for abnormal FAI [area under the curve (AUC), 0.798], with a sensitivity of 81.1% and a specificity of 74.6%.

Quantitative computed tomography angiography evaluation of the coronary fractional flow reserve in patients with left anterior descending artery myocardial bridging.

PURPOSE: To quantitatively investigate the effect of myocardial bridge (MB) in the left anterior descending artery (LAD) on the fractional flow reserve (FFR). MATERIALS AND METHODS: Three-hundred patients with LAD MB who had undergone coronary artery CT angiography (CCTA) were retrospectively enroled, and 104 normal patients were enroled as the control. The CCTA-derived fractional flow reserve (FFRCT) was measured at the LAD 10 mm proximal (FFR1) and 20-40 mm distal (FFR3) to the MB and at the MB location (FFR2). RESULTS: FFR2 and FFR3 of the MB (with BM only) and MBLA (with both MB and atherosclerosis) groups were significantly (p < 0.01) lower than those of the control. The FFR3 distal to the MB was significantly lower (p < 0.01) than that of the control. The FFRCT of the whole LAD in the MBLA group was significantly (p < 0.05) lower than that of the MB and control group (p < 0.05). MB length (OR 1.061) and MB muscle index (odds ratio or OR 1.007) were two risk factors for abnormal FFRCT, and MB length was a significant independent risk factor for abnormal FFRCT (OR = 1.077). LAD stenosis degree was a risk factor for abnormal FFRCT values (OR 3.301, 95% confidence interval [CI] 1.441-7.562, p = 0.005) and was also a significant independent risk factor (OR = 3.369, 95% CI: 1.392-8.152; p = 0.007) for abnormal FFRCT. CONCLUSION: MB significantly affects the FFRCT of distal coronary artery. For patients with MB without atherosclerosis, the MB length is a risk factor significantly affecting FFRCT, and for patients with MB accompanied by atherosclerosis, LAD stenotic severity is an independent risk factor for FFRCT.

Left atrial appendage filling defects restricted to the early phase of cardiac computed tomography is significantly associated with ischemic stroke.

PURPOSE: To investigate the relationship between filling defects in the left atrial appendage restricted to the early phase of cardiac computed tomography (CCT), and ischemic stroke in patients with atrial fibrillation (AF). MATERIALS AND METHODS: A total of 152 patients with non-valvular AF were retrospectively enrolled and divided into two groups according to the stroke history, as confirmed by brain computed tomography (CT) or magnetic resonance imaging (MRI), as the non-stroke group (n = 89) and stroke group (n = 63), respectively. The numbers of patients with filling defects in the early phase of CCT images without thrombi were recorded. Morphological parameters of the LAA were measured for all participants. All patients with early-phase filling defects (n = 44) were assigned to two groups according to ischemic stroke history: the filling defects with stroke group (n = 28) and the filling defects without stroke group (n = 16). The clinical characteristics and LAA morphological parameters were compared. RESULTS: Univariate analysis showed that compared with the non-stroke group，LAA volume index and age were higher in the stroke group, and the ratio of early phase filling defect in LAA, hypertension and diabetes were also higher, in the meanwhile the LVEF and BMI were lower (P < 0.05).After adjusting confounding factors by the multivariate logistic regression analysis, filling defect was significantly related with stroke [odds ratio (OR): 4.339, 95% confidence interval (CI): 1.951-9.653, P = 0.000]. LAA morphological parameters were not significantly different between the filling defects with stroke group and the group without stroke. CONCLUSION: AF patients with LAA non-thrombotic filling defects in the early-phase of CCT had an increased risk of ischemic stroke compared to those without filling defects. This finding may help to optimize stroke risk stratification in patients with AF.

Microplastics affect arsenic bioavailability by altering gut microbiota and metabolites in a mouse model.

Microplastics exposure is a new human health crisis. Although progress in understanding health effects of microplastic exposure has been made, microplastic impacts on absorption of co-exposure toxic pollutants such as arsenic (As), i.e., oral bioavailability, remain unclear. Microplastic ingestion may interfere As biotransformation, gut microbiota, and/or gut metabolites, thereby affecting As oral bioavailability. Here, mice were exposed to arsenate (6 µg As g-1) alone and in combination with polyethylene particles of 30 and 200 µm (PE-30 and PE-200 having surface area of 2.17 × 103 and 3.23 × 102 cm2 g-1) in diet (2, 20, and 200 µg PE g-1) to determine the influence of microplastic co-ingestion on arsenic (As) oral bioavailability. By determining the percentage of cumulative As consumption recovered in urine of mice, As oral bioavailability increased significantly (P < 0.05) from 72.0 ± 5.41% to 89.7 ± 6.33% with PE-30 at 200 µg PE g-1 rather than with PE-200 at 2, 20, and 200 µg PE g-1 (58.5 ± 19.0%, 72.3 ± 6.28%, and 69.2 ± 17.8%). Both PE-30 and PE-200 exerted limited effects on pre- and post-absorption As biotransformation in intestinal content, intestine tissue, feces, and urine. They affected gut microbiota dose-dependently, with lower exposure concentrations having more pronounced effects. Consistent with the PE-30-specific As oral bioavailability increase, PE exposure significantly up-regulated gut metabolite expression, and PE-30 exerted greater effects than PE-200, suggesting that gut metabolite changes may contribute to As oral bioavailability increase. This was supported by 1.58-4.07-fold higher As solubility in the presence of up-regulated metabolites (e.g., amino acid derivatives, organic acids, and pyrimidines and purines) in the intestinal tract assessed by an in vitro assay. Our results suggested that microplastic exposure especially smaller particles may exacerbate the oral bioavailability of As, providing a new angle to understand health effects of microplastics.

Cadmium oral bioavailability is affected by calcium and phytate contents in food: Evidence from leafy vegetables in mice.

To test high cadmium (Cd) concentration may not be high in health risk when considering Cd bioavailability, we assessed variation of Cd relative bioavailability (RBA, relative to CdCl2) using a mouse assay for 14 vegetables of water spinach, amaranth, and pakchoi. Cadmium concentration varied from 0.13 ± 0.01-0.37 ± 0.00 µg g-1 fw. Cadmium-RBA also varied significantly from 22.9 ± 2.12-77.2 ± 4.46%, however, the variation was overall opposite to that of Cd concentration, as indicated by a strong negative correlation between Cd-RBA and Cd concentration (R2 = 0.43). Based on both Cd concentration and bioavailability, the identified high-Cd pakchoi variety resulted in significantly lower Cd intake than the high-Cd varieties of water spinach and amaranth (4.74 ± 0.05 vs. 10.1 ± 0.54 and 8.03 ± 0.04 µg kg-1 bw week-1) due to significantly lower Cd-RBA (22.9 ± 2.12 vs. 77.2 ± 4.46 and 51.3 ± 2.93%). The lower Cd-RBA in pakchoi was due to its significantly higher Ca and lower phytate concentrations, which facilitated the role of Ca in inhibiting intestinal Cd absorption. This was ascertained by observation of decreased Cd-RBA (90.5 ± 12.0% to 63.5 ± 5.53%) for a water spinach when elevating its Ca concentration by 30% with foliar Ca application. Our results suggest that to assess food Cd risk, both total Cd and Cd bioavailability should be considered.

[Anti-tumor activity of components isolated from purple sweet potato polysaccharides].

OBJECTIVE: To isolate and purify components from polysaccharides of purple sweet potato (PPSP) and to test their anti-tumor activity. METHODS: DEAE-Cellulose and CM-Cellulose exchange chromatography were applied to separate components of PPSP. The anti-tumor activities of each component were measured by MTT assay on Hela and HepG(2) cells and their monosaccharide composition were analyzed by TLC chromatography, followed by infrared spectroscopy studies. RESULTS: Through weak anion exchange chromatography and gradient elution by sodium chloride solution, four components were separated and named as PPSP, PPSPII, PPSPIII and PPSPIV, respectively. MTT tests showed that PPSP II and PPSPIII inhibited Hela and HepG2 tumor cells in a certain extent. The structural analysis revealed that PPSPI was mainly composed of glucose and galactose, PPSP II was composed of glucose and had a typical absorption peak of ß-D-glucose chitosan pyranose, PPSP III was a glycoprotein showing a protein absorption peak. CONCLUSION: Four components were separated from PPSP successfully, among which PPSP II and PPSP III shows anti-tumor activities on Hela and HepG(2) cells in vitro.

[Removal Behavior of Protein-like Dissolved Organic Matter During Different Water Treatment Processes in Full-Scale Drinking Water Treatment Plants].

Protein-like dissolved organic matter (pDOM), which is ubiquitous in natural waters, is a critical precursor of nitrogenous disinfection byproducts. Recently, the control and elimination of pDOM have been a growing concern during drinking water treatment processes. In this study, a high-performance size exclusion chromatography system coupled with photo-diode array, fluorescence detector, and online organic carbon detector (HPSEC-PDA/FLD/OCD) was used to determine the removal behaviors of different-sized pDOM from two full-scale drinking water treatment plants (DWTPs). Coagulation and activated carbon adsorption were selected for bench-scale experiments to further assess the removal behavior of pDOM during conventional water treatment processes. The results showed that different-sized pDOM fractions exhibited different removal characteristics. Pre-oxidation can effectively remove some tyrosine-like and tryptophan-like components with high MW, and as the oxidization effect was enhanced, more high MW fractions decomposed into low MW ones. Conversely, some aliphatic pDOM fractions in high MW (e.g., aliphatic proteins) were not subject to pre-oxidation removal. The coagulation-sedimentation unit was efficient in removing high MW fractions, specifically tryptophan-like fractions. Additionally, some pDOM components may be released during coagulation. pDOM with low MW and high hydrophobicity were easily removed during activated carbon filtration. However, long-term operation of the activated carbon filter may breed microorganisms, resulting in the partial release of pDOM fractions. Moreover, UV disinfection processes promoted the degradation of low MW pDOM components. Due to the complex water quality and uncontrollable microbial activities, the aforementioned water treatment units did not exhibit a synergistic effect on pDOM removal. In comparison with humic-like substances, pDOM was susceptible to water quality changes, and its removal was limited in the surveyed DWTPs. Therefore, DWTPs must strengthen pDOM monitoring in influent and effluent and adjust the operating parameters of different treatment units in a timely manner. Moreover, the combination of advanced water treatment processes, such as ozone-biological activated carbon process and nanofiltration, should also be considered to strictly control pDOM component removal.

[Effect of CDK1 Interferes with the Regulation of PLK1, Aurora B and TRF1 on the Proliferation of Leukemia Cells].

OBJECTIVE: To investigate the effect of CDK1 interference regulation of PLK1, Aurora B and TRF1 on the proliferation of leukemia cells. METHODS: The human myelogenous leukemia cell line HL-60 was selected as the research object, and the effect of TRF1 expression and its changes on cell proliferation and cycle was investigated by regulating intracellular CDK1 expression. The objects were divided into 5 groups, including control group, shRNA-NC group, CDK1-shRNA group, pcDNA group and pcDNA-CDK1 group. RT-PCR was used to detect the CDK1 expression of cells in each group; colony formation was used to detect the proliferation of the cells. Western blot was used to detect the expression of CDK1, PLK1, Aurora B, TRF1, and cyclin p53, p27, cyclinA. RESULTS: The phosphorylation level of PLK1, Aurora B and the expression of TRF1 in the CDK1-shRNA group were significantly down-regulated as compared with those in the control group (P<0.05). Compared with the control group, the cells in CDK1-shRNA group showed lower clone formation rate, the increasing of cycle-associated proteins p53 and p27 and the decreasing of cyclinA expression (P<0.05). It was shown that interfered CDK1 expression could inhibit the proliferation of HL-60 cells and prolong the time that they enter mitosis, thereby extending the cell cycle. Compared with the control group, the overexpressed CDK1 in the pcDNA-CDK1 group made the phosphorylation level of PLK1, Aurora B, and TRF1 expression increase significantly (P<0.05), also the colony formation rate (P<0.05). The cycle-related proteins p53 and p27 was down-regulated, while cyclinA expression was up-regulate significantly (P<0.05). The results indicted that overexpressed CDK1 could stimulate adverse reactions, thereby promoting the proliferation of HL-60 cells and shortening the cell cycle. CONCLUSION: Knocking out CDK1 can inhibit the phosphorylation of PLK1 and Aurora B and negatively regulate TRF1, thereby inhibiting the proliferation of leukemia cells.

Antibiotic exposure decreases soil arsenic oral bioavailability in mice by disrupting ileal microbiota and metabolic profile.

Oral bioavailability of arsenic (As) determines levels of As exposure via ingestion of As-contaminated soil, however, the role of gut microbiota in As bioavailability has not evaluated in vivo although some in vitro studies have investigated this. Here, we made a comparison in As relative bioavailability (RBA) estimates for a contaminated soil (3913 mg As kg-1) using a mouse model with and without penicillin perturbing gut microbiota and metabolites. Compared to soil exposure alone (2% w/w soil in diets), addition of penicillin (100 or 1000 mg kg-1) reduced probiotic Lactobacillus and sulfate-reducing bacteria Desulfovibrio, enriched penicillin-resistant Enterobacter and Bacteroides, and decreased amino acid concentrations in ileum. With perturbed gut microbiota and metabolic profile, penicillin and soil co-exposed mice accumulated 2.81-3.81-fold less As in kidneys, excreted 1.02-1.35-fold less As in urine, and showed lower As-RBA (25.7-29.0%) compared to mice receiving diets amended with soil alone (56 ± 9.63%). One mechanism accounted for this is the decreased concentrations of amino acids arising from the gut microbiota shift which resulted in elevated iron (Fe) and As co-precipitation, leading to reduced As solubilization in the intestine. Another mechanism was conversion of bioavailable inorganic As to less bioavailable monomethylarsonic acid (MMAV) and dimethylarsinic acid (DMAV) by the antibiotic perturbed microflora. Based on in vivo mouse model, we demonstrated the important role of gut microbiota and gut metabolites in participating soil As solubilization and speciation transformation then affecting As oral bioavailability. Results are useful to better understand the role of gut bacteria in affecting As metabolism and the health risks of As-contaminated soils.

A meta-analysis of treatment effects of imiquimod for basal cell carcinoma.

OBJECTIVE: We conducted this meta-analysis to assess the efficacy and safety of imiquimod in comparison with other treatments in patients with BCC. METHODS: A comprehensive literature search was performed in the database of PubMed, Embase, and Web of Science. Outcomes of interest included histological/composite clearance rate, success rate, complete response rate, tumor free survival, and adverse events. Pooled risk ratio (RR) with 95% confidence intervals (CIs) using a fixed-effects or random-effects model were determined for each outcome. RESULTS: A total of 13 studies involving 4256 patients were identified. Imiquimod was associated with significantly higher histological clearance rate (RR = 9.28, 95%CI: 5.56, 15.49; P < .001) and composite clearance rate (RR = 34.24, 95%CI: 21.29, 55.06; P = .001). Moreover, imiquimod also significantly increased complete response rate (RR = 3.15, 95%CI: 1.55, 6.38; P = .001) but had no effect in the success rate (RR = 0.98, 95%CI: 0.89, 1.08; P = .727) and probability of tumor-free survival (RR = 1.15, 95%CI: 0.98, 1.35; P = .088), as compared with other treatments. There were more patients in imiquimod group who developed adverse events than in other treatment group (RR = 2.00, 95%CI: 1.39, 2.88; P < .001). CONCLUSION: This study indicated the effects of imiquimod in improving the histological/composite clearance rates as compared with other treatments. However, its treatment-related adverse events also should be noticed. Our findings supported that, imiquimod could be used as the first-choice treatment for BCC.

Lead bioavailability in different fractions of mining- and smelting-contaminated soils based on a sequential extraction and mouse kidney model.

Lead bioavailability in contaminated soils varies considerably depending on Pb speciation and sources of contamination. However, little information is available on bioavailability of Pb associated with different fractions. In this study, the Tessier sequential extraction was used to fractionate Pb in 3 contaminated soils to exchangeable (F1), carbonate-bound (F2), Fe/Mn oxides-bound (F3), organic-bound (F4), and residual fractions (F5). In addition, soil residues after F1-F2 extraction (F345), F1-F3 extraction (F45), and F1-F4 extraction (F5) were measured for Pb relative bioavailability (RBA) using a mouse kidney model. Based on the mouse model, Pb-RBA in the soils was 44-93%, which decreased to 43-89%, 28-75%, and 15-68% in the F345, F45, and F5 fractions, respectively. Based on Pb-RBA in the soil residues, Pb-RBA in different fractions was calculated based on a mass balance. The data showed that Pb-RBA was the highest (∼100%) in the exchangeable and carbonate fraction, and the lowest (15-68%) in the residual fraction. In addition, Pb in the first three fractions (F1-F3) contributed most (83-89%) to bioavailable Pb in contaminated soils. Our study shed light on oral bioavailability of Pb in contaminated soils of different fractions based on sequential extraction and provide important information for soil remediation.

As, Cd, and Pb relative bioavailability in contaminated soils: Coupling mouse bioassay with UBM assay.

The robustness of in vitro bioaccessibility assays to predict oral relative bioavailability (RBA) of multiple metals in contaminated soils requires validation using additional soil samples. In this study, 11 contaminated soils from mining/smelting areas were analyzed for As-, Cd-, and Pb-RBA using a mouse bioassay and metal bioaccessibility via the UBM gastric phase assay. Metal-RBA varied considerably among soils, with As-RBA (2.5-23%, mean 12%) being generally lower than Cd-and Pb-RBA (3.4-88 and 3.3-59%, mean 42 and 28%), due to higher proportions of As in the residual fractions. Metal-RBA generally decreased with increasing metal concentrations probably due to reduced labile metal fractions. In addition, strong negative correlations were observed between total Fe with As-, Cd-, and Pb-RBA (R2 = 0.46-0.77), suggesting the role of Fe in controlling metal-RBA in soils. Like RBA, metal bioaccessibility by the UBM assay also varied among samples. However, strong in vivo-in vitro correlations (IVIVCs) were observed between metal-RBA and bioaccessibility (R2 = 0.52-0.81). Further, there were little differences when As-, Cd-, and Pb-IVIVCs established using soils from this study and soils pooled from literature were compared, suggesting the robustness of the UBM assay to predict metal-RBA in contaminated soils.

Food influence on lead relative bioavailability in contaminated soils: Mechanisms and health implications.

To determine the effects of dietary constituents on soil Pb oral bioavailability, Pb relative bioavailability (RBA) in 3 soils contaminated by zinc smelting (ZS), wire-rope production (WR), and metal mining (MM) was measured under fasted and fed states with 9 foods. Under fasted state, Pb-RBA was 84.4 ±â€¯10.3, 82.6 ±â€¯4.70, and 32.3 ±â€¯1.10% for ZS, WR, and MM soils; however, it decreased by 1.3-3.5 fold to 23.9-58.8, 25.6-49.9, and 14.8-24.2% under fed states with foods excluding Pb-RBA with egg in WR soil (97.3 ±â€¯4.46%), and with cabbage and egg in MM soil (40.0 ±â€¯8.62 and 44.4 ±â€¯0.96%). In the presence of foods, egg and pork with significantly higher protein and fat contents leaded to the highest soil Pb-RBA (44.4-97.3%), while Pb-RBA determined with mineral-rich mouse feed was 1.6-7.9 fold lower (9.41-13.5%), suggesting high fat and protein foods tended to increase soil Pb-RBA, while high mineral diets decreased soil Pb-RBA. The increased Pb-RBA of MM soil with cabbage compared to fasted state was due to high organic content in cabbage, which could increase soil Pb solubility by inhibiting Fe and Pb co-precipitation in the intestine. For accurate assessment of health risks of contaminated soils, dietary influence on soil Pb-RBA should be considered.