UNASSIGNED: Zinc (Zn), an essential trace element, has an adverse influence on the prognosis of several cancers. However, the association between the preoperative serum Zn level and outcomes in patients with advanced esophageal cancer in the current neoadjuvant treatment era remains unclear.
UNASSIGNED: This study involved 185 patients with esophageal cancer who underwent R0 surgery after neoadjuvant chemotherapy from August 2017 to February 2021. We retrospectively investigated the relationship between the preoperative serum Zn level and the patients\' outcomes.
UNASSIGNED: The patients were divided into a low Zn group (<64 μg/dL) and a high Zn group (≤64 μg/dL) according to the mean preoperative serum Zn level. Low Zn had significantly worse overall survival (OS) (2-year OS rate: 76.2% vs. 83.3% in low vs. high Zn; p = 0.044). A low Zn in pathological non-responders (Grade ≤ 1a) was significantly associated with a shorter 2-year recurrence-free survival (RFS) rate (39.6% vs. 64.1% in low vs. high Zn; p = 0.032). The multivariate analysis identified low BMI and Zn level among preoperative nutritional status indices as an independent risk factor for worse RFS in non-responders. Compared with responders, pathological non-responders comprised significantly more males and a performance status of ≥1, and there was no difference in Zn level according to pathological response.
UNASSIGNED: A preoperative low Zn level had a negative impact on early recurrence in esophageal cancer patients who underwent neoadjuvant chemotherapy. This suggests the need to administer Zn supplementation to patients with esophageal cancer who have preoperative Zn deficiency.

Essential trace elements (ETEs) play essential roles in vital functions, but their effects on epigenetic aging remain poorly understood.
This study aimed to investigate the associations of ETEs with four epigenetic aging indicators and assess the potential mediating role of inflammation.
We recruited 93 individuals from hospitals between October 2018 and August 2019. Plasma levels of cobalt, copper, iron, manganese, molybdenum, selenium, and zinc were measured by ICP-MS, and leukocyte DNA methylation levels were measured using Illumina MethylationEPIC beadchip. Linear regression was used to estimate the association between seven plasma ETEs and epigenetic aging indicators. Weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to evaluate the effect of ETEs mixtures. Inflammatory status was assessed using four systemic inflammation indices (neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), monocyte-to-lymphocyte ratio (MLR), and systemic immune-inflammation index (SII)) and three cytokines (IL-4, IL-6, and IL-13). Mediation analysis was performed to explore the role of inflammation in the above associations.
Plasma Se levels were significantly negatively associated with DunedinPACE, whereas Cu levels were significantly positively associated with it. Both WQS regression and BKMR models suggested that Se and Cu dominate the effect of the ETEs mixture. MLR and interleukin 6 were significantly and positively associated with DunedinPACE. Further mediation analysis indicated that inflammation partially mediated the association between ETEs and DunedinPACE.
Plasma Se and Cu levels are closely associated to epigenetic aging, and inflammation might be a potential mechanism underlying this relationship. These findings contribute to the prevention of health hazards associated with population aging.

This thorough study analyses the amounts of 43 minerals and trace elements in non-traditional wheat grains, flakes, and undigested flake portions using ICP-MS and establishes declines in their respective contents after the flake production. It also identifies appropriate dietary intakes, in vitro digestibility values, retention factors, and metal pollution indexes. The element contents in wheat flakes are lower than in wheat grains after the hydrothermal treatment process, and their declines are: Na (48-72%), Ce (47-72%), Sr (43-55%), Tl (33-43%), Ti (32-41%), U (31-44%), Ho (29-69%), Cr (26-64%), Zr (26-58%), Ag (25-52%), and Ca (25-46%). The flakes significantly contributed to the recommended dietary intake or adequate intake of particular elements for men of all categories as follows: Mn (143%) > Mo > Cu > Mg ≥ Cr > Fe (16%); for women: Mn (up to 183%) > Mo > Cu > Cr ≥ Mg > Fe (7-16%); for pregnant women aged 19-30: Mn (165%) > Mo > Cu > Mg > Cr (25%); and finally, for lactating women: Mn (127%) > Mo > Cu > Mg > Cr (17%). The contributions to the provisional tolerable weekly or monthly intakes of all toxic elements were established as being within the official limits. The daily intakes for non-essential elements were also calculated. The retention factors were calculated to assess the element concentrations in the undigested part using the digestibility values (87.4-90.5%). The highest retention factors were obtained for V (63-92%), Y (57-96%), Ce (43-76%), Pb (34-58%), Tl (32-70%), Ta (31-66%), and Ge (30-49%). K, Mg, P, Zn, Ba, Bi, Ga, Sb, Cu, Ni, and As appear to be released easily from flake matrices during digestion. The metal pollution index has been confirmed as being lower for non-traditional wheat flakes when compared with grains. Importantly, 15-25% of the metal pollution index assessed for native flakes remains in the undigested flake portion after in vitro digestion.

A solid phase chemical fractionation (SPCF) of the Mn in hot infusions prepared from commercial samples of roasted (RM) and green mate (GM) using a chelating resin Chelex 100 (NH4+ form) was performed to assess the relative lability of this essential trace element (ETE). In addition, total Mn contents in the RM and GM samples and their infusions were determined by flame atomic absorption spectrometry. Total polyphenol (TP) contents and the presence of soluble melanoidins (SM) were correlated with the Mn solubility in the RM and GM infusions. From the SPCF study, it was possible to observe that the soluble Mn forms in the mate infusions were essentially associated with relatively noninert chemical species (98.4-99.7%), suggesting that they may be potentially bioavailable. In addition, the soluble Mn contents in the GM infusions were 20.5% higher than those found in the RM. Mn solubility in the (RM) infusions was highly and directly correlated (r = 0.99) with the soluble TP, while in the GM infusions, it was high and inversely correlated with soluble TP (r =  -0.87). On the other hand, Mn solubility in the RM and GM infusions was weakly correlated with the SM. It should be stressed that GM infusions can contribute with 57 and 44% more than the RM infusions to the recommended adequate intake of Mn established for females and males, respectively. Moreover, this work is the first to evaluate and compare the relative lability of Mn and its solubility in the RM and GM infusions.

Early embryonic arrest (EEA) leads to repeated cessation of fresh cycles among infertile women undergoing in vitro fertilization (IVF). Whether the levels of some essential trace elements [copper (Cu), zinc (Zn), selenium (Se) and cobalt (Co)] in the bodies of women are related to the risk of EEA warrants study.
Our study aimed to investigate the associations of peripheral blood levels of Cu, Zn, Se, and Co and their mixtures with the risk of EEA.
A total of 74 EEA cases (123 IVF cycles) and 157 controls (180 IVF cycles) from the reproductive center of the First Affiliated Hospital of Anhui Medical University in Hefei, China, between June 2017 and March 2020 were included in our study. Demographic and clinical data were collected from electronic medical records. Cu, Zn, Se, and Co levels were measured in blood samples collected on the day of oocyte retrieval when infertile women entered clinical treatment for the first time using an inductively coupled plasma mass spectrometer (ICP-MS). Generalized estimating equation (GEE) models were used to evaluate the associations of four essential trace element concentrations individually with the risk of EEA, and Bayesian kernel machine regression (BKMR) was used to explore the associations between four essential trace element mixtures and the risk of EEA.
Se concentrations of infertile women were significantly lower in the case group compared with the control group. Co levels were significantly higher in the case group compared with the control group. The differences in Cu and Zn concentrations between the two groups were not significant. Based on single-metal models, Co was positively associated with the risk of EEA before and after adjustment for all confounders (odd ratio (OR) = 1.72, 95% confidence interval (CI): 1.18-2.52; OR = 2.27, 95% CI: 1.37-3.77, respectively), and Se was negatively associated with the risk of EEA before adjustment for all confounders (OR = 0.18, 95% CI: 0.07-0.51). BKMR analyses showed that Se was significantly and negatively associated with the risk of EEA when all the other three metals (Cu, Zn, and Co) were fixed at the 25th, 50th, or 75th percentiles, whereas Zn displayed a significant and positive association with the risk of EEA when all the other three metals (Cu, Se and Co) were fixed at the 25th, 50th, or 75th percentiles. Co did not show any effect on the risk of EEA when all the other metals (Cu, Zn, and Se) were fixed at the 25th, 50th, or 75th percentiles. In addition, an increasing trend of the joint effect of four essential trace elements on the risk of EEA was found, although it was not statistically significant.
The levels of essential trace elements (Cu, Zn, Se, and Co) might correlate with the risk of EEA to some extent. The present study might provide a real-world perspective on the relationship between essential trace elements and the risk of EEA when considering them as a single element or as mixtures.

Concentrations of 22 essential and non-essential trace elements (Be, Al, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, As, Se, Mo, Ag, Cd, Sb, Ba, Tl, Pb, Th, U, and Hg) were measured in the organs of a mother-fetus pair (at the last trimester of pregnancy) of spotted seals from the Sea of ​Japan. The concentrations of eleven elements are reported for the first time. Eight organs of the pair were examined: lungs, heart, liver, kidneys, intestines, spleen, muscles, and bones. All trace elements detected in the organs of the mother were found also in the organs of the fetus at various concentrations. Placenta is not an effective barrier to prevent non-essential elements from getting into the fetus, but can control entry of some of them, e.g., aluminum, cadmium, and mercury. In most organs of the fetus, the concentrations of toxic trace elements (beryllium, antimony, thorium, and uranium) were noticeably higher than in the same organs of the mother, which indicates that during pregnancy female removes excess of non-essential trace elements by transferring them to the fetal body through the placental barrier.

Deficient or excessive quantities of essential trace elements (ETEs)1 in the fetal environment can compromise developmental processes. We investigated whether concentrations of zinc (Zn), manganese (Mn), selenium (Se), cobalt (Co), molybdenum (Mo), and nickel (Ni) in umbilical cord tissue are associated with risk for neural tube defects (NTDs). Umbilical cord tissues from 166 cases of NTD cases and 166 matched controls were collected and element concentrations were measured using inductively coupled plasma-mass spectrometry. Associations between ETE concentrations and the risk for NTDs were estimated using multivariate logistic regression while adjusting for potential confounders. Bayesian kernel machine regression (BKMR) was used to examine the joint effects of these ETEs. We found that median concentrations of Ni were higher but those of Mo and Co were lower in the NTD group than in the control group. Co was the only element that was associated with NTD risk after adjusting for confounders (OR 0.31, 95 % CI 0.12-0.79 for the second and OR 0.37, 95 % CI 0.15-0.91 for the top tertile relative to the lowest tertile). The association between Co and NTD risk was confirmed with the BKMR model. In addition, a joint effect of the six ETE mixture on NTD risk was observed: the risk decreased with the levels of the mixture from 25th percentile through 75th percentile. In conclusion, higher levels of Co were associated with lower risk for NTDs, and NTD risk decreased with the levels of the six ETEs as a co-exposure mixture, suggesting a protective effect.

This study examined the associations between concentrations of cobalt (Co), iron (Fe), manganese (Mn), molybdenum (Mo), selenium (Se), and zinc (Zn) in placental tissue and risks for NTDs with a case-control design consisting of 408 fetuses or newborns with neural tube defects (NTDs) and 593 non-malformed fetuses or newborns. The concentrations of Zn and Fe were determined by inductively coupled plasma-emission spectrometer and the other four elements by inductively coupled plasma-mass spectrometer. Element concentrations were presented in ng/g or µg/g dry weight of placental tissue. The associations between the levels of each of the six ETEs and risk for NTDs were evaluated using multivariable logistic regression, and the associations between overall levels of all six ETEs and risk for NTDs were examined using Bayesian kernel machine regression (BKMR). Concentrations above the median concentration of all participants for an individual element were associated with increased risk for NTDs: Mn, 3.17-fold (95% CI 2.35-4.28); Mo, 3.73-fold (95% CI 2.74-5.07); Se, 3.28-fold (95% CI 2.44-4.42); and Zn, 2.85-fold (95% CI 2.13-3.83), and a decreased risk for Co [OR, 0.18 (95% CI 0.14-0.25)]. The risk for NTDs increased with the increase in the concentrations of Mn, Mo, Se, and Zn, but decreased for Co, in the second, third, and fourth quartiles, respectively, compared to their lowest quartile (all Pstrend < 0.01). In BKMR model, the risk for NTDs increased constantly when the overall exposure levels were higher than the median of the six ETEs as a co-exposure mixture, and the associations between Co, Mn, Se, and Zn and NTD risk remained when the remaining five elements were taken into consideration simultaneously. Taken together, when evaluated individually, higher levels of Mn, Se, and Zn in placental tissue are associated with increased risk for NTDs, while higher levels of Co are associated with decreased risk for NTDs; when examined collectively, the risk of NTDs increases continuously when exposure levels are higher than the median of the six ETE mixture.

BACKGROUND: Disturbances in the homeostasis of essential trace elements (ETEs) may interfere with embryonic organogenesis. However, the effect of ETEs on the development of orofacial clefts (OFCs) remains unclear.
OBJECTIVE: This study examined associations between concentrations of iron (Fe), zinc (Zn), selenium (Se), cuprum (Cu), cobalt (Co), and molybdenum (Mo) in maternal serum and risk for OFCs in offspring.
METHODS: A total of 130 cases of OFCs and 260 nonmalformed controls were included in this study. Concentrations of Fe, Zn, Se, Cu, Co, and Mo in maternal serum were detected by inductively coupled plasma mass spectrometry. We examined associations between levels of the six ETEs in maternal serum and risk for OFCs for each element separately using multilevel mixed-effects logistic regression and for all elements collectively using Bayesian kernel machine regression (BKMR).
RESULTS: Higher concentrations of Mo and Co in maternal serum were associated with a decreased risk for OFCs in a dose-dependent manner, with odds ratios and 95% confidence intervals of 0.37 (0.20-0.66) for the second tertile of Mo, 0.28 (0.15-0.54) for the third tertile of Mo, 0.54 (0.29-1.00) for the second tertile of Co, and 0.47 (0.25-0.87) for the third tertile of Co, with the lowest tertile as the referent. When all six ETEs were considered together, increased levels of ETEs were associated with a decreased risk for OFCs. In addition, Mo showed a protective effect against risk for OFCs when the other ETEs were fixed at their 25th, 50th, or 75th percentile, whereas the protective effect of Co turned to a null effect in the BKMR model. No association was observed between levels of Fe, Zn, Se, or Cu and risk for OFCs in either statistical model.
CONCLUSIONS: Elevated concentrations of Mo in maternal serum were associated with a reduced risk for OFCs.

Selenium is an essential micronutrient that is required for the synthesis of selenocysteine-containing selenoproteins, processing a wide range of health effects. It is known that the thyroid is one of the tissues that contain more selenium. The \"selenostasis\" maintenance seems to contribute to the prevention of immune mediated thyroid disorders. Prospective, observational studies, randomized, controlled studies evaluating selenium supplementation, and review articles that are available in Medline and PubMed have undergone scrutiny. The differences concerning methodology and results variability have been analyzed. Several authors support the idea of a potential efficacy of selenium (mainly selenomethionine) supplementation in reducing antithyroperoxidase antibody levels and improve thyroid ultrasound features. In mild Graves\' orbitopathy, selenium supplementation has been associated with a decrease of the activity, as well as with quality of life improvement. Future research is necessary to clearly understand the selenium supplementation biologic effects while considering the basal selenium levels/biomarkers, selenoprotein gene polymorphisms that may be involved, underlying comorbidities and the major clinical outcomes.