Dietary Galactooligosaccharides Supplementation as a Gut Microbiota-Regulating Approach to Lower Early Life Arsenic Exposure.

Prebiotics may stimulate beneficial gut microorganisms. However, it remains unclear whether they can lower the oral bioavailability of early life arsenic (As) exposure via regulating gut microbiota and altering As biotransformation along the gastrointestinal (GI) tract. In this study, weanling mice were exposed to arsenate (iAsV) via diet (7.5 µg As g-1) amended with fructooligosaccharides (FOS), galactooligosaccharides (GOS), and inulin individually at 1% and 5% (w/w). Compared to As exposure control mice, As concentrations in mouse blood, liver, and kidneys and As urinary excretion factor (UEF) were reduced by 43.7%-74.1% when treated with 5% GOS. The decrease corresponded to a significant proliferation of Akkermansia and Psychrobacter, reduced percentage of inorganic arsenite (iAsIII) and iAsV by 47.4% and 65.4%, and increased proportion of DMAV in intestinal contents by 101% in the guts of mice treated with 5% GOS compared to the As control group. In contrast, FOS and inulin either at l% or 5% did not reduce As concentration in mouse blood, liver, and kidneys or As UEF. These results suggest that GOS supplementation may be a gut microbiota-regulating approach to lower early life As exposure via stimulating the growth of Akkermansia and Psychrobacter and enhancing As methylation in the GI tract.

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.

Mechanistic Insights into Effects of Different Dietary Polyphenol Supplements on Arsenic Bioavailability, Biotransformation, and Toxicity Based on a Mouse Model.

Arsenic (As) exposure has been related to many diseases, including cancers. Given the antioxidant and anti-inflammatory properties, the dietary supplementation of polyphenols may alleviate As toxicity. Based on a mouse bioassay, this study investigated the effects of chlorogenic acid (CA), quercetin (QC), tannic acid (TA), resveratrol (Res), and epigallocatechin gallate (EGCG) on As bioavailability, biotransformation, and toxicity. Intake of CA, QC, and EGCG significantly (p < 0.05) increased total As concentrations in liver (0.48-0.58 vs 0.27 mg kg-1) and kidneys (0.72-0.93 vs 0.59 mg kg-1) compared to control mice. Upregulated intestinal expression of phosphate transporters with QC and EGCG and proliferation of Lactobacillus in the gut of mice treated with CA and QC were observed, facilitating iAsV absorption via phosphate transporters and intestinal As solubility via organic acid metabolites. Although As bioavailability was elevated, serum levels of alpha fetoprotein and carcinoembryonic antigen of mice treated with all five polyphenols were reduced by 13.1-16.1% and 9.83-17.5%, suggesting reduced cancer risk. This was mainly due to higher DMAV (52.1-67.6% vs 31.4%) and lower iAsV contribution (4.95-10.7% vs 27.9%) in liver of mice treated with polyphenols. This study helps us develop dietary strategies to lower As toxicity.

Arsenic Ingested Early in Life Is More Readily Absorbed: Mechanistic Insights from Gut Microbiota, Gut Metabolites, and Intestinal Morphology and Functions.

Early-life arsenic (As) exposure is a particular health concern. However, it is unknown if As ingested early in life is more readily absorbed from the gastrointestinal (GI) tract, i.e., higher in oral bioavailability. Here, weanling (3-week) and adult (6-week-old) female mice were exposed to arsenate in the diet (10 µg g-1) over a 3-week period with As oral bioavailability estimated using As urinary excretion as the bioavailability endpoint. The As urinary excretion factor was 1.54-fold higher in weanling mice compared to adult mice (82.2 ± 7.29 versus 53.1 ± 3.73%), while weanling mice also showed 2.28-, 1.50-, 1.48-, and 1.89-fold higher As concentration in small intestine tissue, blood, liver, and kidneys, demonstrating significantly higher As oral bioavailability of early-life exposure. Compared to adult mice, weanling mice significantly differed in gut microbiota, but the difference did not lead to remarkable differences in As biotransformation in the GI tract or tissue and in overall gut metabolite composition. Although the expression of several metabolites (e.g., atrolactic acid, hydroxyphenyllactic acid, and xanthine) was up-regulated in weanling mice, they had limited ability to elevate As solubility in the intestinal tract. Compared to adult mice, the intestinal barrier function and intestinal expression of phosphate transporters responsible for arsenate absorption were similar in weanling mice. However, the small intestine of weanling mice was characterized by more defined intestinal villi with greater length and smaller width, providing a greater surface area for As to be absorbed across the GI barrier. The results highlight that early-life As exposure can be more readily absorbed, advancing the understanding of its health risk.

Gut Microbiota Control the Bioavailability and Metabolism of Organoarsenicals of Seaweeds in Mice after Oral Ingestion.

Edible seaweed consumption is an essential route of human exposure to complex organoarsenicals, including arsenosugars and arsenosugar phospholipids. However, the effects of gut microbiota on the metabolism and bioavailability of arsenosugars in vivo are unknown. Herein, two nori and two kelp samples with phosphate arsenosugar and sulfonate arsenosugar, respectively, as the predominant arsenic species, were administered to normal mice and gut microbiota-disrupted mice treated with the broad-spectrum antibiotic cefoperazone for 4 weeks. Following exposure, the community structures of the gut microbiota, total arsenic concentrations, and arsenic species in excreta and tissues were analyzed. Total arsenic excreted in feces and urine did not differ significantly between normal and antibiotic-treated mice fed with kelp samples. However, the total urinary arsenic of normal mice fed with nori samples was significantly higher (p < 0.05) (urinary arsenic excretion factor, 34-38 vs 5-7%), and the fecal total arsenic was significantly lower than in antibiotic-treated mice. Arsenic speciation analysis revealed that most phosphate arsenosugars in nori were converted to arsenobetaine (53.5-74.5%) when passing through the gastrointestinal tract, whereas a large portion of sulfonate arsenosugar in kelp was resistant to speciation changes and was excreted in feces intact (64.1-64.5%). Normal mice exhibited greater oral bioavailability of phosphate arsenosugar from nori than sulfonate arsenosugar from kelp (34-38 vs 6-9%). Our work provides insights into organoarsenical metabolism and their bioavailability in the mammalian gut.

Effects of provisioning on the activity budget and foraging strategies of black-and-white snub-nosed monkeys (Rhinopithecus bieti) in the Baima Snow Mountain Nature Reserve, Yunnan, China.

Provisioning can significantly affect the ranging patterns, foraging strategies, and time budget of wild primates. In this study, we document for the first time, the effects of provisioning on the activity budget and foraging effort in an Asian colobine. Over 3-years, we used an instantaneous scanning method at 10-min intervals to collect data on the activity budget of a semiprovisioned breeding band (SPB) of black-and-white snub-nosed monkeys (Rhinopithecus bieti) (42-70 individuals) at Xiangguqing (Tacheng), Yunnan, China. We then compared the effects of provisioning in our study band with published data on a sympatric wild nonprovisioned breeding band (NPB) of R. bieti (ca. 360 monkeys) at the same field site. The SPB spent 25.6% of their daytime feeding, 17.1% traveling, 46.9% resting, and 10.3% socializing. In comparison, the NPB devoted more time to feeding (34.9%) and socializing (14.1%), less time to resting (31.3%), and was characterized by a greater foraging effort (1.74 versus 0.96, foraging effort = (feeding + traveling)/resting; see Methods). There was no difference between bands in the proportion of their activity budget devoted to traveling (15.7% vs. 17.1%). In addition, the SPB exhibited a more consistent activity budget and foraging effort across all seasons of the year compared to the NPB. These findings suggest that the distribution, availability, and productivity of naturally occurring feeding sites is a major determinant of the behavioral strategies and activity budget of R. bieti. Finally, a comparison of our results with data on six nonprovisioned R. bieti bands indicates that caution must be raised in meta-analyses or intraspecific comparisons of primate behavioral ecology that contain data generated from both provisioned and nonprovisioned groups.

Genome-wide identification and analysis of TMT-based proteomes in longissimus dorsi tissue from Kazakh cattle and Xinjiang brown cattle.

With the gradual completion of the human genome project, proteomes have gained extremely important value in the fields of human disease and biological process research. In our previous research, we performed transcriptomic analyses of longissimus dorsi tissue from Kazakh cattle and Xinjiang brown cattle and conducted in-depth studies on the muscles of both species through epigenetics. However, it is unclear whether differentially expressed proteins in Kazakh cattle and Xinjiang brown cattle regulate muscle production and development. In this study, a proteomic analysis was performed on Xinjiang brown cattle and Kazakh cattle by using TMT markers, HPLC classification, LC/MS and bioinformatics analysis. A total of 13,078 peptides were identified, including 11,258 unique peptides. We identified a total of 1874 proteins, among which 1565 were quantifiable. Compared to Kazakh cattle, Xinjiang brown cattle exhibited 75 upregulated proteins and 44 downregulated proteins. These differentially expressed proteins were enriched for the functions of adrenergic signaling in cardiomyocytes, fatty acid degradation and glutathione metabolism. In our research, we found differentially expressed proteins in longissimus dorsi tissue between Kazakh cattle and Xinjiang brown cattle. We predict that these proteins regulate muscle production and development through select enriched signaling pathways. This study provides novel insights into the roles of proteomes in cattle genetics and breeding.

Comparative analysis of arthroscopic-assisted Tight-rope technique and clavicular hook plate fixation in the treatment of Neer type IIB distal clavicle fractures.

BACKGROUND: The aim of the present study was to compare the clinical efficacy of arthroscopic-assisted fixation using the Tight-rope system and clavicular hook plate fixation in the treatment of Neer IIB distal clavicle fractures. METHODS: We enrolled 48 consecutive patients with Neer IIB distal clavicle fractures who were treated at our institution from February 2016 and August 2020. These patients were divided into 2 groups based on the fixation method (16 cases with Tight-rope system and 32 cases with clavicular hook plate), and demographics and clinical characteristics of patients in different groups were compared. RESULTS: All 48 patients had functional outcome scores of the affected shoulder available at a mean of 23.8 ± 5.1 months, and there was a statistically significant improvement in the constant score, American shoulder and elbow surgeons (ASES) score, visual analogue scale (VAS) score at the end of follow-up (p < 0.001 respectively). However, the smaller length of skin incision, less estimated blood loss and shorter hospital stay were detected in the Tight-rope technique group patients than those of clavicular hook plate group patients (p < 0.001, respectively). Furthermore, the constant score, ASES score and VAS score were significantly improved in the Tight-rope technique group patients than those of clavicular hook plate group patients (p < 0.05, respectively). CONCLUSIONS: Both Tight-rope technique and clavicular hook plate fixation can provide satisfactory clinical and radiological results in the treatment of distal clavicular Neer IIB fracture. However, arthroscopic-assisted fixation using the Tight-rope technique showed better results in terms of length of hospital stay, surgical trauma, clinical scores, and diagnose and treat concomitant glenohumeral pathologies. LEVELS OF EVIDENCE: III, Case-control study Retrospective comparative study.

Cordycepin augments the chemosensitivity of osteosarcoma to cisplatin by activating AMPK and suppressing the AKT signaling pathway.

BACKGROUND: Osteosarcoma is the most common primary bone tumor in children and adolescents. However, some patients with osteosarcoma develop resistance to chemotherapy, leading to a poor clinical prognosis. Hence, effective therapeutic agents that can improve the response to chemotherapy drugs to improve the prognosis of patients with osteosarcoma are urgently needed. Cordycepin has recently emerged as a promising antitumor drug candidate. This study aims to explore the effect of cordycepin in suppressing osteosarcoma in vivo and in vitro and the synergistic effect of cordycepin combined with cisplatin and to demonstrate the underlying molecular mechanism. METHODS: CCK-8 assay was performed to investigate the inhibition effect of cordycepin combined with cisplatin in osteosarcoma cell lines. The colony formation and invasion abilities were measured by colony formation assay and Transwell assay. Osteosarcoma cells apoptosis was detected by flow cytometry. Western blot analysis were used to detect the expression of cell apoptosis-related proteins and AMPK and AKT/mTOR signaling pathway-related proteins. Finally, we performed the in vivo animal model to further explore whether cordycepin and cisplatin exert synergistic antitumor effects. RESULTS: Notably, we found that treatment with cordycepin inhibited cell proliferation, invasion, and induced apoptosis in osteosarcoma cells in vitro and in vivo. Moreover, the combination of cordycepin and cisplatin led to marked inhibition of osteosarcoma cell proliferation and invasion and promoted osteosarcoma cell apoptosis in vitro and in vivo. Mechanistically, we demonstrated that cordycepin enhanced the sensitivity of osteosarcoma cells to cisplatin by activating AMPK and inhibiting the AKT/mTOR signaling pathway. CONCLUSIONS: In brief, this study provides comprehensive evidence that cordycepin inhibits osteosarcoma cell growth and invasion and induces osteosarcoma cell apoptosis by activating AMPK and inhibiting the AKT/mTOR signaling pathway and enhances the sensitivity of osteosarcoma cells to cisplatin, suggesting that cordycepin is a promising treatment for osteosarcoma.

Immune checkpoint inhibition for pancreatic ductal adenocarcinoma: limitations and prospects: a systematic review.

Pancreatic cancer is an extremely malignant tumor with the lowest 5-year survival rate among all tumors. Pancreatic ductal adenocarcinoma (PDAC), as the most common pathological subtype of pancreatic cancer, usually has poor therapeutic results. Immune checkpoint inhibitors (ICIs) can relieve failure of the tumor-killing effect of immune effector cells caused by immune checkpoints. Therefore, they have been used as a novel treatment for many solid tumors. However, PDAC is not sensitive to monotherapy with ICIs, which might be related to the inhibitory immune microenvironment of pancreatic cancer. Therefore, the way to improve the microenvironment has raised a heated discussion in recent years. Here, we elaborate on the relationship between different immune cellular components in this environment, list some current preclinical or clinical attempts to enhance the efficacy of ICIs by targeting the inhibitory tumor microenvironment of PDAC or in combination with other therapies. Such information offers a better understanding of the sophisticated tumor-microenvironment interactions, also providing insights on therapeutic guidance of PDAC targeting. Video Abstract.

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.

Re-evaluating the necessity of routine laboratory tests after high tibial osteotomy surgery.

BACKGROUND: To assess the utility of routine postoperative laboratory tests for patients undergoing high tibial osteotomy (HTO) surgery. METHODS: The associations between clinical risk factors and postoperative clinical treatment were analyzed. Additionally, a logistic regression analysis was performed to detect independent risk factors for patients requiring postoperative clinical treatment. RESULTS: A total of 482 patients with symptomatic isolated medial compartment osteoarthritis from January 2015 to May 2020 were included in the present study and underwent examination by the full set of postoperative laboratory tests within 3 days after HTO surgery. However, only a small proportion of the patients with anemia (3.9 %), hypoalbuminemia (4.1 %), and abnormal serum potassium levels (3.5 %) required clinical intervention after surgery. Binary logistic regression analysis showed that the body mass index (BMI), preoperative hemoglobin level, estimated blood loss and operative duration were independent risk factors for postoperative blood transfusion in patients who underwent HTO surgery, and factors associated with albumin supplementation were female sex and preoperative albumin level. In addition, these results indicated that preoperative potassium was potential risk factor for patients who required potassium supplementation postoperatively. CONCLUSIONS: Based on the analysis, we conclude that routinely ordering postoperative laboratory tests after HTO surgery is unnecessary. However, for patients with identified risk factors, routine postoperative laboratory tests are still needed.

In Vitro Anti-Toxoplasma gondii Activity Evaluation of a New Series of Quinazolin-4(3H)-one Derivatives.

Toxoplasmosis post serious threaten to human health, leading to severely eye and brain disease, especially for immunocompromised patients and pregnant women. The multiple side effects and long dosing period of current main treatment regiments calls for high effective and low toxicity anti-toxoplasmosis drugs. Herein, we report our efforts to synthesize a series of 2-(piperazin-1-yl)quinazolin-4(3H)-one derivatives and investigate their activity against Toxoplasma gondii tachyzoites in vitro based on cell phenotype screening. Among the 26 compounds, 8w and 8x with diaryl ether moiety at the side chain of piperazine exhibited good efficacy to inhibit T. gondii, with IC50 values of 4 µM and 3 µM, respectively. Structure-activity relationship (SAR) studies implies that hydrophobic aryl at the side chain would be preferred for improvement of activity. Molecular docking study reveals these two compounds appeared high affinity to TgCDPK1 by interaction with the hydrophobic pocket of ATP-binding cleft.

Investigating Lead Species and Bioavailability in Contaminated Soils: Coupling DGT Technique with Artificial Gastrointestinal Extraction and in Vivo Bioassay.

Although strong in vivo-in vitro correlations (IVIVCs) between relative bioavailability (RBA) and bioaccessibility of soil Pb were well reported, knowledge on the fractions of bioaccessible Pb in simulated gastrointestinal (GI) fluids that are available for absorption into the systemic circulation is limited. Here, Pb-RBA in 14 Pb-contaminated soils were assessed using an in vivo mouse bioassay and compared to Pb bioaccessibility by the gastrointestinal phase of the UBM (Unified Bioaccessibility research group of Europe (BARGE) Method) in vitro assay with and without 0.45 µm filtration of GI fluid. Results showed good IVIVC between Pb-RBA and Pb bioaccessibility without filtration ( r 2 = 0.62), while Pb bioaccessibility with filtration provided a poor correlation with Pb-RBA ( r 2 = 0.16). This suggested that besides dissolved Pb ions, Pb-complexes formed in the UBM gastrointestinal fluid might also contribute to bioavailable Pb. To ascertain this, DGT (diffusive gradients in thin-films) devices which can measure both Pb2+ ions and labile inorganic and organic Pb-complexes were introduced to the UBM fluids to measure Pb DGT-bioaccessibility, which showed strong correlation to Pb-RBA ( r 2 = 0.71). With increasing diffusive gel thickness which could enhance release of Pb ions from Pb-complexes, Pb DGT-bioaccessibility increased by 3.4-5.7 times, while inclusion of dialysis membrane within DGT devices significantly decreased Pb DGT-bioaccessibility by inhibiting diffusion of Pb complexes to binding gel. These results confirmed the contribution of Pb-complexes to Pb bioavailability, providing new insights to Pb bioavailability.

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.

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.

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.

Metals in paints on chopsticks: Solubilization in simulated saliva, gastric, and food solutions and implication for human health.

Paints are often used on chopsticks, however, a paucity of studies has assessed metals in the paints and the associated health risk. In this study, total Pb, Cd, Cr, Co, and Ni concentrations in paints were assessed for 72 wood and 29 stainless steel chopsticks with different colors while metal solubilization from paints in simulated saliva, 0.07 M HCl, and 1% citric acid solutions was measured for 9 samples having total Pb > 90 mg kg-1, representing exposure scenarios of mouthing, incidental paint ingestion, and metal migration in food. Results showed that Pb (0.12-500,000 mg kg-1), Cd (0.002-120,000 mg kg-1), Cr (2.2-8400 mg kg-1), Co (0.004-2600 mg kg-1), and Ni (0.10-150,000 mg kg-1) concentrations varied considerably among paint samples. Most samples showed low metal concentrations, however, high metal concentrations were observed in red and green paints on stainless steel chopsticks, while paints on wood chopsticks showed lower metal concentrations. Estimation of daily metal intakes incorporating metal solubilization data in saliva, 0.07 M HCl, and 1% citric acid solutions suggested that the health risk via saliva contact was negligible, while unacceptable health risk was observed for Pb and Cd via their solubilization in 0.07 M HCl and 1% citric acid solutions from paints with high Pb and Cd concentrations. To avoid Pb and Cd exposure, use of metal-based paints on chopsticks should be banned, particularly in countries where food is regularly consumed with chopsticks.

Mineral Dietary Supplement To Decrease Cadmium Relative Bioavailability in Rice Based on a Mouse Bioassay.

To determine the effectiveness of mineral dietary supplements to modulate cadmium (Cd) exposure, an in vivo mouse bioassay was conducted to determine Cd relative bioavailability (Cd-RBA) in Cd-contaminated rice (0.80 mg Cd kg-1) with and without Zn, Fe, or Ca supplements as nitrate or chloride salts. Without mineral supplements, Cd-RBA was 43 ± 5.3% based on average Cd accumulation in the liver plus kidneys as the end point. Among Ca(NO3)2, Zn(NO3)2, and Fe(NO3)2 supplements, 150-5000 mg kg-1 Ca was the most effective in reducing rice Cd-RBA by 31-80% to 8.5-29%, while 30-200 mg kg-1 Zn supplements was ineffective, with Cd-RBA being 33-57%. Low Fe at <40 mg kg-1 had little impact on rice Cd-RBA (39-47%), while high Fe at 80-200 mg kg-1 decreased Cd-RBA by 37% to 26-27%. The ineffectiveness of Zn supplements in reducing Cd-RBA was probably due to coinciding 8.3- and 3.1-fold increases in Zn accumulation in mouse kidneys and liver with Zn supplements, while Ca and Fe supplements led to much-smaller increases in Ca and Fe accumulation in mouse tissues (1.3-1.6 fold). In addition, compared to Ca(NO3)2 supplements, Cd-RBA values determined with CaCl2 supplements were significantly higher (25-67% versus 8.5-29%), suggesting that chloride enhanced Cd-RBA. Results of this study have important implications for developing effective dietary strategies to reduce dietary Cd exposure and the associated health risks in humans.

Applying Cadmium Relative Bioavailability to Assess Dietary Intake from Rice to Predict Cadmium Urinary Excretion in Nonsmokers.

Dietary Cd intake is often estimated without considering Cd bioavailability. Measured urinary Cd for a cohort of 119 nonsmokers with rice as a staple was compared to predicted values from rice-Cd intake with and without considering Cd relative bioavailability (RBA) in rice based on a steady state mouse kidney bioassay and toxicokinetic model. The geometric mean (GM) of urinary Cd and ß2-microglobulin was 1.08 and 234 µg g-1 creatinine. Applying Cd-RBA in foods to aggregate Cd intake (41.5 ± 12.4, 48.0 ± 9.3, 48.8 ± 21.3% for rice, wheat, and vegetables), rice was the largest contributor (71%). For 63 participants providing paired urine and rice samples, the predicted GM of urinary Cd at 4.14 µg g-1 based on total Cd in rice was 3.5 times that of measured value at 1.20 µg g-1, while incorporating Cd-RBA to assess rice-Cd intake made the two closer with GM at 1.07 µg g-1. The cohort findings were extended to a national scale, with urinary Cd for nonsmokers from rice Cd intake was mapped at province/city levels after considering rice Cd-RBA. Therefore, incorporating Cd bioavailability to assess dietary Cd intake is a valuable tool to accurately estimate human Cd exposure and associated health risk.