Thyroid nodules and goiter remain common conditions affecting healthy child development, attributable to diagnostic advances and environmental-genetic interactions. However, pediatric etiology research remains limited. A total of 997 children aged 8 to 10 years were recruited from iodine-adequate areas across 13 districts in Tianjin, China. Venous blood was collected for genotyping three single nucleotide polymorphisms (thyroid stimulating hormone receptor (TSHR) rs2268458, thyroid transcription factor 1 (TTF1) rs2076735 and phosphodiesterase 8B (PDE8B) rs4704397) using Sequenom MassARRAY. Data on up to 30 potential external factors were also collected. The detection rates of thyroid nodules and goiter were 23.57% and 8.83%, respectively. Gender, higher body surface area (BSA) (Q4: >1.30 m[2]), and living in a multistory building increased thyroid nodules risk (P < 0.05). Older children had higher goiter risk (P = 0.001), whereas higher BSA (Q3: 1.18-1.30 m[2]; Q4: >1.30 m[2]) and mothers with stable jobs reduced goiter risk (P < 0.05). In genotype-stratified analyses, TSHR, TTF1, and PDE8B polymorphisms appeared to moderate associations between multiple external factors (gender, BSA, urinary iodine, stress, anxiety) and thyroid nodules or goiter (P < 0.05), although no significant gene-environment interactions were detected in the overall models. Notably, among children with specific genotypes, certain factors that were not statistically significant in the full multivariable model, including urinary iodine with thyroid nodules and stress and anxiety with goiter, showed substantially strengthened associations. Multiple external factors are associated with thyroid nodules and goiter in children. Polymorphisms in TSHR rs2268458, TTF1 rs2076735, and PDE8B rs4704397 may modulate the effects of various external factors on childhood thyroid nodules and goiter.

Arsenic (As) is an environmental neurotoxicant that induces oxidative stress and cognitive impairment. There are limited therapeutic options to treat As-induced neurotoxicity. This study investigated the potential for repurposing metformin (Met) and memantine (Mem) use alone, and in combination to mitigate As-induced neurotoxicity in male Wistar rats. Fifty rats were randomly divided into five groups of ten each: Group I (control) received normal feed and water, group II- Sodium arsenite (20 mg/kg), group III- Sodium arsenite (20 mg/kg) + Met (75 mg/kg), group IV- Sodium arsenite (20 mg/kg) + Mem (10 mg/kg), and group V- Sodium arsenite (20 mg/kg) + Met (75 mg/kg) + Mem 10 mg/kg), all administered p.o. for 28 days. At the end of drugs treatment, several behavioral, biochemical, and histological evaluations were performed. Results showed that all drug-treated groups demonstrated enhanced spatial and recognition memory as evidenced by increased spontaneous alternation in the Y-maze task and decreased escape latencies in the Morris Water Maze test. In both behaviors, the combination group showed the best results, followed closely by the Mem alone group. All treatment groups, especially the combination, showed the best results by restoring the activity of glutathione peroxidase, catalase, and superoxide dismutase in the cortex and hippocampus. Histological examination to study cellular preservation demonstrated that Mem alone treated group showed better results. Network pharmacology identified 66 intersecting targets; molecular docking indicated that Mem and Met had the strongest affinity for MMP9 and BDNF, respectively. All hub genes showed better binding affinities with Mem as compared to Met. In conclusion, our study demonstrated that Met and Mem improved learning and memory, reduced oxidative stress, and restored cellular density. Further validation to repurpose Met and Mem for their use against As-induced neurotoxicity can be done so that they can be used in human beings in the future.

Uranium is a naturally occurring trace element with established radiological and chemical toxicity, yet its blood burden in patients with cancer remains poorly characterized. This exploratory cross-sectional study used radon[-222] as a tracer to derive model-based uranium estimates in patients with gastrointestinal (GI) cancer and healthy controls from southern Iraq, a region with documented elevated environmental radioactivity. Blood samples were collected from 78 patients with histologically confirmed GI cancer (39 females and 39 males) and 58 healthy controls (29 females and 29 males) at the National Oncology and Hematology Hospital, Najaf. CR-39 poly(allyl diglycol carbonate) solid-state nuclear track detectors were sealed with blood samples for 90 days. Track densities were quantified using TASLIMAGE automated analysis, and radon concentrations were calculated using an experimentally established calibration factor (0.048 tracks cm[-2] Bq[-1] m[3] d). Model-based uranium estimates were derived assuming secular equilibrium between uranium-238 and radon[-222]. Daily alpha-particle flux, annual effective dose, and excess lifetime cancer risk were calculated according to ICRP Publications 103 and 119. Group differences were evaluated using Levene-corrected independent-samples t-tests, and effect sizes were quantified using Cohen's d. Mean estimated blood uranium concentrations were higher in male patients than male controls (15.48 ± 5.16 vs. 10.17 ± 3.39 parts per billion (ppb)) and in female patients than female controls. Correspondingly, mean blood radon concentrations were higher in patients (males: 3.99 ± 1.50 vs. 2.62 ± 0.80 Bq m[-3]; females: 3.21 ± 1.07 vs. 2.31 ± 0.77 Bq m[-3]). Excess lifetime cancer risk remained well below the ICRP reference level in all groups (1.10 × 10[-7] for male patients and 8.82 × 10[-8] for female patients). Although between-group differences were not statistically significant (males: p = 0.275; females: p = 0.187), the observed effect sizes were large (Cohen's d = 1.10 for male radon), suggesting that the study may have been underpowered to detect statistically significant differences. These findings indicate consistently higher model-based uranium estimates in patients with GI cancer than in healthy controls. However, because uranium concentrations were estimated indirectly using a model-based approach and the study employed a cross-sectional design, no causal relationship between uranium exposure and GI cancer can be inferred. Further studies with larger cohorts and direct uranium measurements using ICP-MS are warranted.

In recent decades, selenium nanoparticles have attracted increasing attention as therapeutic agents for the treatment of various types of cancer. However, at certain physicochemical parameters and dosages, they can have a toxic effect or exacerbate pathological processes caused by the toxin. The aim of this study was to investigate the effect of low doses of spherical selenium nanoparticles of two sizes (50 and 100 nm), produced by laser ablation, on the mitigation of pathological processes caused by long-term injections of thioacetamide. The practical significance of this study is to understand the therapeutic value of taking dietary supplements based on selenium nanoparticles for the prevention of various liver pathologies, particularly hepatocellular carcinoma. To this end, we selected the well-known toxin thioacetamide as an HCC inducer. We administered it intraperitoneally to animals, followed by injections of 50-100 nm selenium nanoparticles. In this study, we used ultra-low concentrations of selenium nanoparticles (1 ng/g per day) with the aim of using these nanoparticles for the prevention of fibrosis, cirrhosis, and liver cancer. The results obtained in this study demonstrate a size-dependent divergence in the biological behavior of the nanoparticles: 50 nm nanoparticles failed to inhibit tumor growth and, on the contrary, exacerbated pathological processes in the liver, kidneys, and lungs across several parameters, while 100 nm selenium nanoparticles, conversely, demonstrated a powerful therapeutic effect. This paradox is confirmed at all levels: organ, tissue, and cellular. The molecular mechanisms regulating these processes using 50 and 100 nm selenium nanoparticles are also presented.

Nalidixic acid (Nal) is a quinolone antibiotic with activity against Gram-negative bacteria and is used to treat urinary tract infections caused by microorganisms belonging to the genera Escherichia, Proteus, Shigella, Enterobacter, and Klebsiella. The complexation of this molecule with zinc and auxiliary ligands such as phenanthroline (Phen) and 2,2'-bipyridine (Bipy) could modify its pharmacological and pharmacokinetic properties. This work presents the synthesis and characterization of the ZnNal complex ([Zn(Nal)2(H2O)2]·2MeOH). Its molecular structure in the solid state was determined by X-ray diffraction. The complex crystallizes in the monoclinic space group P21/n with Z = 2 molecules per unit cell. In the solid state, the nalidixic acid (Nal) molecule appears as its anionic form (Nal[-]), deprotonated in the carboxyl group. The complex is centrosymmetric, with the Zn(II) ion at the center of a slightly elongated octahedral geometry, equatorially coordinated to a bidentate nalidixate anion and axially to a water molecule. The study includes the evaluation of antimicrobial activity of the binary complex and its derivatives with phenanthroline (ZnNalPhen) and bipyridine (ZnNalBipy) against both ATCC strains and clinical isolates. Additionally, compound safety was assessed using the Artemia salina model. ZnNal preserves the antimicrobial potency of the free ligand while exhibiting attenuated toxicity in this model, suggesting a more favorable biocompatibility profile for potential therapeutic applications. Notably, ZnNalPhen was the only complex active against Candida strains, highlighting that coordination with 1,10-phenanthroline expanded the antimicrobial spectrum of the parent ligand Nal to include antifungal activity. Furthermore, both ternary complexes showed an improved safety profile compared to Nal alone. Besides, zinc(II) complexes can be efficiently transported by albumin, which is a key factor in their potential therapeutic application.

Raw cow milk serves as a critical nutritional resource yet may simultaneously act as a vehicle for toxic element exposure, particularly in regions where livestock management practices increase contamination risk. This study investigated the concentrations of six potentially toxic elements (PTEs), namely nickel (Ni), zinc (Zn), cadmium (Cd), copper (Cu), iron (Fe), and lead (Pb), in raw cow milk collected from 40 sites across Ranya district, Kurdistan Region of Iraq. Samples were analyzed using energy dispersive X-ray fluorescence (EDXRF) spectrometry, and human health risks were assessed through estimated daily intake (EDI), target hazard quotient (THQ), hazard index (HI), and carcinogenic risk (CR) metrics across three age groups: adults, children, and infants. Detected metal concentrations followed a descending order of Zn > Fe > Ni > Cu > Pb > Cd. Several metals, including Fe, Cu, and Pb, exceeded permissible thresholds. Health risk evaluation revealed that while mean THQ and HI values for adults and children remained within acceptable boundaries, infants exhibited mean HI values surpassing the safety threshold of 1.0, indicating a genuine cumulative non-carcinogenic risk. Carcinogenic risk assessment identified Ni as the predominant concern, with CR values exceeding acceptable limits across all age groups, most markedly in infants. The elevated contamination levels observed are attributable largely to the practice of grazing livestock on unmanaged pastures and allowing consumption of water from natural, untreated sources. These findings underscore the necessity of continuous PTE surveillance in raw dairy products and the implementation of targeted public health interventions to safeguard vulnerable populations, particularly infants, within the study region.

The trace element boron is a bioactive and potentially essential element for humans with a broad range of physiological effects. While dietary sources of boron are well known, significant knowledge gaps remain regarding boron intake in special dietary patterns. We estimated dietary boron intake and quantified urinary boron excretion in long-term lacto-ovo-vegetarians, vegans and omnivores in Germany. Dietary intake was estimated using weighed food diaries linked to existing databases. Boron excretion was measured using 24-hour urine samples. Differences between diet groups were compared using non-parametric tests (Kruskal-Wallis H test). The sample included 89 participants, including 28 lacto-ovo-vegetarians and 29 vegans. Vegans had the highest median boron intake (1913.38 (interquartile range: 1467.11-2615.14) µg/d), followed by lacto-ovo-vegetarians (1654.36 (1249.75-2366.01) µg/d) and omnivores (1515.35 (944.33-2067.52) µg/d). Interindividual boron intake varied largely, and ranged from 657.09 to 5835.74 µg/d. No participant exceeded the European Food Safety Authority tolerable upper intake level for boron (10 mg/day). Creatinine-corrected urinary boron excretion was highest in vegans (1559.20 (1150.62-2057.23) µg/g creatinine), followed by lacto-ovo-vegetarians (1235.40 (877.96-1814.61) µg/g creatinine) and omnivores (919.34 (639.18-1380.97) µg/g creatinine). Strong correlations between boron intakes and 24-hour urinary excretion were found in vegans (r = 0.79) and omnivores (r = 0.74) with p-values < 0.001 for both. The correlation in lacto-ovo-vegetarians was less pronounced (r = 0.43). A higher urinary boron excretion was associated with a higher excretion of potassium in all dietary patterns and specifically phosphorus in vegans (r = 0.57, p < 0.001). Our data suggest that boron intake varies across different dietary patterns. We provide first insights in boron status in German lacto-ovo-vegetarians and vegans.

Tea is one of the most widely consumed beverages worldwide and can contribute to dietary exposure to both essential and potentially toxic elements. This study investigated the effects of brewing time and lemon juice addition on the concentrations and multivariate relationships among selected metals in commercial black tea infusions. Brewing time significantly affected the concentrations of Pb, Cd, Mn, and Al, whereas acidification through lemon juice addition influenced Pb, Cr, Zn, Cu, Mn, and Al. Prolonged brewing increased Mn and Al concentrations but reduced Pb and Cd levels. Lemon juice addition enhanced the concentrations of Al, Mn, Zn, and Cr while decreasing Cu concentration in the infusions. Principal component analysis demonstrated that acidification was the primary factor shaping the elemental profile of tea infusions, exerting a greater influence than brewing time. The strongest responses to both experimental factors were observed for Mn and Al, whose concentrations increased markedly under acidic conditions and with extended brewing time. Despite these changes, the contribution of Ni, Al, Zn, Cu, Pb, Cd, and Cr to dietary intake or exposure remained low across all brewing variants. In contrast, tea infusions represented a substantial source of Mn, providing approximately 30-60% of the adequate intake, depending on preparation conditions. These findings indicate that common brewing practices can significantly modify the elemental composition of black tea infusions, with acidification having a stronger effect than extraction time. Nevertheless, consumption of the investigated teas is unlikely to pose a significant health risk and may contribute beneficially to manganese intake.

Rare earth elements and yttrium (REE + Y) are increasingly mobilized in modern environments, affecting human physiological processes through multiple exposure pathways. Pathological biominerals, such as kidney stones, may provide valuable records of long-term elemental deposition. However, it remains unclear whether REE + Y directly inherit environmental signals or are reshaped by physiological and mineralogical processes. This study analyzed kidney stones from a high-incidence karst region in eastern Yunnan, China. The results indicate that regional hydrogeochemical background and the mineralogical pathways jointly control the REE + Y distribution of kidney stones. Fourier transform infrared spectroscopy combined with non-negative matrix factorization identified the dominant spectral components and their relative proportions in the stones. The total REE + Y load was mainly controlled by the dominant mineral phase, with the median in uric acid stones (36.4 ng/g) remaining significantly lower than in calcium-bearing stones (up to 218.2 ng/g). This study further found that increasing phosphate proportions were significantly correlated with weaker Yb anomalies and higher Lu concentrations, whereas total REE concentrations showed no significant change. Unsupervised and supervised model analyses demonstrated that REE + Y distribution patterns can reliably distinguish stones with different dominant mineral types. These results indicate that REE + Y are sensitive to biomineralization processes in kidney stones and may serve as potential tracers for apatite incorporation in calcium-bearing stones. Moreover, although human metabolism and biomineralization filter most environmental signals, the light REE-enriched patterns in calcium-bearing stones are broadly compatible with the karst hydrogeochemical background. Overall, this study reveals the REE + Y fingerprints support precise subtyping of kidney stones, serving as composite geochemical archives reflecting both environmental signals and pathological biomineralization.

Tibetan Plateau, which was once a severe endemic area of Kashin-Beck disease (KBD), was low with selenium in the soil geochemical background and with harsh environment, thus resulting in selenium deficiency in local foods while high environmental-derived oxidative stress and inflammatory responses in human body. Diet was the major selenium source for humans, while external environment conditions could influence selenium consumption and disturb the selenium metabolism. This study explored the influence on urinary selenium of Tibetan population from the pespevtive of selenium intake, represented by food patterns and selenium concentration, and from the perspective of selenium metabolism caused by environmental stress. From 2019 to 2022, 572 food consumption questionnaires of Tibetan residents, matched urine samples, staple food samples, and local agricultural soil and water samples were collected. Environmental stressors, including absolute oxygen concentration, temperature-humidity index and ultraviolet radiation intensity were considered. Statistical analysis and Random Forest (RF) were used to explore the association, contribution importance and interactive effect of the factors above on urinary selenium concentrations. Urinary selenium concentrations of Tibetan residents were still generally low, declined with age whereas no difference was found between genders. In terms of food consumption patterns, dietary diversity score (DDS) and non-local food intake, poultry consumption frequency in particular were positively associated with urinary selenium, exerted a pro-linear relationship. Highland barley and wheat flour selenium concentrations showed positive impact on the urinary selenium concentrations, and the magnitude of impact was more obvious when the highland barley selenium concentration exceeded 0.04 µg/g, and the wheat flour selenium concentration was lower than 0.051 µg/g. The soil and water selenium concentrations also positively influenced the urinary selenium concentrations. Environmental stressors exerted distinct influencing curves on urinary selenium concentrations, with higher ultraviolet radiation intensity (UVRI) and lower environmental comfort induced by cold and dry conditions positively regulating urinary selenium concentrations, while oxygen concentration exhibited a marginal effect only when it reached a certain threshold. Food diversity, non-local food intake, staple food selenium concentrations and local agricultural selenium concentrations were all important factors for elevating the selenium status among Tibetan residents. Environmental stressors regulated the urinary selenium concentrations differently due to the divergent action pathways on the selenium depletion and metabolism. Correspondingly, increasing the food diversity through introducing non-local food, increasing the selenium level of local food and elevating the human selenium reference standards were suggested.

Hormonal disturbances that women in postmenopause face favor increased redistribution of fat into visceral compartments, leading to central obesity and related disorders. The mechanisms underlying dysregulated zinc (Zn) metabolism in individuals with obesity and related disorders remain unresolved. This study aimed to investigate the association between serum Zn levels and conventional and novel anthropometric parameters in the cohort of postmenopausal women in Montenegro. A cohort of 94 postmenopausal women (mean age 64.55 ± 8.71 years) was consecutively included. Zn determination was performed using inductively coupled plasma optical emission spectrometry. Multivariable ordinal logistic regression analysis was used to estimate associations of demographic data, obesity-related scores, and laboratory markers with Zn tertile levels. Serum Zn levels were negatively correlated with conventional [body mass index (BMI) and waist-to-height ratio (WHtR)] and novel [body adiposity index (BAI), body roundness index (BRI), and cardiometabolic index (CMI)] anthropometric parameters in postmenopausal women. Although no difference in hip circumference and height across Zn tertiles was found, the BAI, as a composite index of both parameters, showed an association with serum Zn levels. Similarly, despite no difference in waist circumference across Zn tertiles, the BRI as a composite index of waist circumference and height was correlated with Zn levels. Serum Zn concentrations were positively associated with HDL-C levels, but not with other lipid parameters. The measurement of new anthropometric parameters, in addition to traditional ones, may add a contribution to the relationship between adiposity indices and serum Zn levels in postmenopausal women.

Boron is a biologically active trace element essential to plants and is increasingly recognized as a potentially important modulator of human physiology. This critical narrative review evaluates evidence concerning mineral metabolism, endocrine-related pathways, redox balance, immune signaling, neurological function, cardiometabolic health, osteoarticular disorders, host-microbiome interactions, and boron-containing pharmaceuticals. Boron's Lewis acid properties and its ability to form reversible complexes with cis-diol-containing biomolecules provide a plausible basis for its broad biological effects, including interactions with NAD[+]- and S-adenosylmethionine-related pathways, membrane-associated glycoconjugates, and inflammatory signaling networks. Experimental and limited clinical studies suggest that boron intake at the doses evaluated may influence bone mineralization, vitamin D metabolism, selected endocrine-related biomarkers, antioxidant defense, and inflammatory homeostasis. In parallel, boron-containing compounds have emerged as valuable pharmacological scaffolds, as illustrated by boron-based agents used in oncology, dermatology, infectious disease, and boron neutron capture therapy. However, despite promising mechanistic and translational findings, evidence for boron's strict essentiality in humans remains limited, and no indispensable boron-dependent human pathway has yet been established. Recent concepts, such as conditional essentiality, suggest that boron may become biologically relevant in specific nutritional, metabolic, inflammatory, skeletal, or microbiome-related contexts. Nevertheless, small sample sizes, short intervention periods, heterogeneous formulations, and reliance on surrogate endpoints continue to constrain clinical interpretation. Future studies require speciation-resolved dosing, pharmacokinetic monitoring, adequately powered randomized designs, long-term safety assessment, and clinically meaningful outcomes. Overall, boron represents a promising but incompletely defined trace element at the intersection of nutrition, immunometabolism, host-microbiome biology, and therapeutic drug design.