LncRNA MALAT1-miR-339-5p-NIS axis is involved in the increased level of thyroid stimulating hormone (TSH) induced by combined exposure of high iodine and hyperlipidemia.

Hypothyroidism and subclinical hypothyroidism were both characterized by elevated levels of thyroid stimulating hormone (TSH), previous studies had found that high iodine or hyperlipidemia alone was associated with TSH level. However, their combined effects on TSH have not been elucidated. In this study, combination of high iodine and hyperlipidemia was established through the combined exposure of high water iodine and high fat diet in Wistar rats. The results showed that combined exposure of high iodine and high fat can induce higher TSH level. The mRNA and protein levels of sodium iodide transporters (NIS) and type 1 deiodinase (D1) in thyroid tissues, which were crucial genes in the synthesis of thyroid hormones, decreased remarkably in combined exposure group. Mechanistically, down-regulated lncRNA MALAT1 may regulate the expression of NIS by increasing miR-339-5p, and regulating D1 by increasing miR-224-5p. Then, the above findings were explored in subjects exposed to high water iodine and hyperlipidemia. The results indicated that in population combined with high iodine and hyperlipidemia, TSH level increased to higher level and lncRNA MALAT1-miR-339-5p-NIS axis was obviously activated. Collectively, this study found that combined exposure of high iodine and hyperlipidemia induced a higher level of TSH, and lncRNA MALAT1-miR-339-5p-NIS axis may play important role.

PKC-θ is an important driver of fluoride-induced immune imbalance of regulatory T cells/effector T cells.

Fluoride is unnecessary in the human body. Long-term fluoride exposure may lead to immune system abnormalities. However, the mechanism remains unclear. This study aim to explore the mechanism of fluoride interference in the immune system and also identify the key indicators of fluoride-induced immune damage. Questionnaires were used to collect basic information. Multiple linear analyses and other statistical methods were used in order to process the data. Flow cytometry was used to detect relevant immunomarkers and analyze immune damage. Simultaneously, Wistar rats and cell models exposed to fluoride were established to detect the effects of fluoride on immune homeostasis. The results showed that sex, residence time, smoking, and Corona Virus Disease 2019 (COVID-19) infection may indirectly influence fluoride-induced immune damage. In residents of fluoride-exposed areas, there was a significant decrease in CD3+ T lymphocytes and CD4+ and CD8+ cells and a downward trend in the CD4+/CD8+ cell ratio. CD4+CD8+/CD4+, regulatory T cells (Tregs), and Tregs/effector T cells (Teffs) ratios showed opposite changes. Fluoride inhibits T cell activation by inhibiting the expression and phosphorylation of Protein Kinase C-θ (PKC-θ), hinders the internalization of T cell receptors, and affects NF-kB and c-Jun protein expression, leading to homeostatic Treg/Teff imbalance in vivo and in vitro experiments. This study represents the first evidence suggesting that PKC-θ may be the key to immune imbalance in the body under fluoride exposure. It is possible that Tregs/Teffs cell ratio provide a reference point for the diagnosis and treatment of fluoride-induced immune damage.

Association Between Iodine Status and Prevalence of Hypothyroidism, Autoimmune Thyroiditis, and Thyroid Nodule: a Cross-Sectional Study in Shandong Province, China.

In this study, the aim was to investigate the correlation between varying levels of urinary iodine concentration (UIC) in adults and the occurrence of thyroid diseases, with the additional objective of determining the optimal iodine status level for adults. A cross-sectional study was conducted on adults from six areas with different drinking water iodine concentrations (WIC) without eating iodized salt in Heze and Jining counties, Shandong Province, China. A total of 1336 adults were included in this study, and drinking water samples, blood samples, urine samples, thyroid ultrasound, and a questionnaire were collected. UIC, free triiodothyronine (FT3), free thyroid hormone (FT4), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb) and thyroglobulin antibody (TgAb) were detected. There were no significant differences in the detection rates of hypothyroidism and thyroid autoimmunity (TAI) among the different median UIC groups (UIC < 100 µg/L, 100-199 µg/L, 200-299 µg/L, ≥ 300 µg/L). However, the detection rates of hypothyroidism were higher in the UIC < 100 µg/L group (16.67%) and the UIC ≥ 300 µg/L group (16.51%) compared to the other groups. The detection rate of TAI increased as UIC levels increased. The detection rate of thyroid nodule (TN) in the UIC < 100 µg/L group was significantly higher than that in the UIC 200-299 µg/L UIC group (χ2 = 10.814, P = 0.001). After adjusting confounding factors, it was found that low UIC (< 100 µg/L) was a risk factor for TN (OR 1.83, 95% CI [1.04-3.22]). Meanwhile, there no statistical difference between UIC 200 and 299 µg/L and UIC 100 and199 µg/L for OR of hypothyroidism, TAI, and TN. This study identified associations between different UIC levels and the prevalence of thyroid disorders, with low UIC (< 100 µg/L) posing a risk for TN, and the detection rate of TN and hypothyroidism was the lowest in UIC (200-299 µg/L) group. Therefore, the acceptable UIC range of 'adequate' iodine intake among adults can be widened from 100-199 µg/L to 100-299 µg/L.

Arsenic aggravates the progression of diabetic nephropathy through miRNA-mRNA-autophagy axis.

Environmental factors play an important role in the progression of diabetic nephropathy (DN), and previous study has shown that arsenic exposure can promote kidney damage in DN rats, however there is no relevant mechanism study so far. In this study, an arsenic-exposed (10 mg/L and 25 mg/L) DN mouse model was established through drinking water for 14 weeks. The results showed that 25 mg/L arsenic exposure increased the renal fibrosis in DN mice significantly, and urinary mAlb level increased with the increasing of arsenic exposure level. Transcriptome sequencing showed that autophagy-related pathways were significantly activated under the exposure dose of 25 mg/L, and levels of Beclin1 and p-ATG16L1/ATG16L1 were significantly higher in the 25 mg/L arsenic group compared to the control group. Silico analysis predicted the microRNAs those could regulate the hub genes of Mapk1, Rhoa and Cdc42, and dual-luciferase gene reporter assay was used to verify the targeted binding between these mRNAs and microRNAs. Our results suggested that high arsenic exposure could aggravate the progression of DN by altering autophagy, the miRNA-mRNA axles of let-7a-1-3p, let-7b-3p, let-7f-1-3p, miR-98-3p/Cdc42, Mapk1, Rhoa, could be considered promising targets to explore the mechanisms and therapeutic measures of DN after exposure to high levels of arsenic.

Drinking brick tea containing high fluoride increases the prevalence of osteoarthritis in Tibetan, China.

The prevalence of osteoarthritis (OA) in Tibetans is higher than that in Han, while Tibetans have a habit of drinking brick tea with high fluoride. A cross-sectional study was conducted to explore the association between fluoride exposure in drinking brick tea and OA. All subjects were divided into four groups by the quartiles (Q) of tea fluoride (TF) and urine fluoride (UF). ROC was plotted and OR were obtained using logistic regression model. The prevalence of OA in the Q3 and Q4 group of TF were 2.2 and 2.7 times higher than in the Q1 group, and the prevalence of OA in the Q2, Q3 and Q4 group of UF were 3.2, 3.5, and 4.1 times higher than in the Q1 group. ROC analysis showed the cutoff values were 4.523 mg/day (TF) and 1.666 mg/L (UF). In conclusion, excessive fluoride in drinking brick tea could be a risk factor for developing OA.

Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway.

OBJECTIVE: Keshan disease (KD) is a myocardial mitochondrial disease closely related to insufficient selenium (Se) and protein intake. PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body. This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury. METHODS: A low Se and low protein animal model was established. One hundred Wistar rats were randomly divided into 5 groups (control group, low Se group, low protein group, low Se + low protein group, and corn from KD area group). The JC-1 method was used to detect the mitochondrial membrane potential (MMP). ELISA was used to detect serum creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and mitochondrial-glutamicoxalacetic transaminase (M-GOT) levels. RT-PCR and Western blot analysis were used to detect the expression of PINK1, Parkin, sequestome 1 (P62), and microtubule-associated proteins1A/1B light chain 3B (MAP1LC3B). RESULTS: The MMP was significantly decreased and the activity of CK-MB, cTnI, and M-GOT significantly increased in each experimental group (low Se group, low protein group, low Se + low protein group and corn from KD area group) compared with the control group (P<0.05 for all). The mRNA and protein expression levels of PINK1, Parkin and MAP1LC3B were profoundly increased, and those of P62 markedly decreased in the experimental groups compared with the control group (P<0.05 for all). CONCLUSION: Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

Effects of sodium arsenite exposure on behavior, ultrastructure and gene expression of brain in adult zebrafish (Danio rerio).

Arsenic, a common metal-like substance, has been demonstrated to pose potential health hazards and induce behavioral changes in humans and rodents. However, the chronic neurotoxic effects of arsenic on aquatic animals are still not fully understood. This study aimed to investigate the effects of arsenic exposure on adult zebrafish by subjecting 3-month-old zebrafish to three different sodium arsenite water concentrations: 0 µg/L (control group), 50 µg/L, and 500 µg/L, over a period of 30 days. To assess the risk associated with arsenic exposure in the aquatic environment, behavior analysis, transmission electron microscopy techniques, and quantitative real-time PCR were employed. The behavior of adult zebrafish was evaluated using six distinct tests: the mirror biting test, shoaling test, novel tank test, social preference test, social recognition test, and T maze. Following the behavioral tests, the brains of zebrafish were dissected and collected for ultrastructural examination and gene expression analysis. The results revealed that sodium arsenite exposure led to a significant reduction in aggression, cohesion, social ability, social cognition ability, learning, and memory capacity of zebrafish. Furthermore, ultrastructure and genes regulating behavior in the zebrafish brain were adversely affected by sodium arsenite exposure.

A Cohort Study on the Effects of Maternal High Serum Iodine Status During Pregnancy on Infants in Terms of Iodine Status and Intellectual, Motor, and Physical Development.

The objective of the present study was to explore the effects of maternal iodine excess during pregnancy on infants' neurodevelopment and physical development. A total of 143 mother-child pairs were enrolled in this cohort study. Maternal blood samples were collected during the obstetric examination. A mother-child questionnaire survey was conducted, and infants' blood samples were collected during the newborn physical examination. Infants' single-spot urine samples were collected, and intellectual, motor, and physical development were assessed at 2 months of age. The median (IQR) maternal serum iodine concentrations (SICs) in the first, second, and third trimesters of pregnancy were 91.2 (74.4, 102.2) µg/L, 81.2 (70.6, 94.8) µg/L, and 82.0 (68.9, 100.3) µg/L, respectively. In the first trimester of pregnancy, infants' psychomotor developmental index (PDI), body mass index (BMI) and weight-for-length Z score (WLZ) were higher with maternal suitable SIC (40 ~ 92 µg/L) than with maternal excess SIC (P < 0.05). Infants' PDI, BMI, weight-for-age Z score (WAZ) and WLZ were negatively correlated with maternal SIC (P < 0.05). Maternal excess SIC had a slightly negative effect on infants' MDI (OR = 1.304, P = 0.035, 95% CI = 1.019 ~ 1.668), PDI (OR = 1.124, P = 0.001, 95% CI = 1.052 ~ 1.200) and BMI (OR = 0.790, P = 0.005, 95% CI = 0.669 ~ 0.933). In the third trimester, infants' length-for-age Z score (LAZ) was higher with maternal high SIC (> 92 µg/L) (P = 0.015), and maternal SIC was positively correlated with infants' urine iodine concentration (UIC) (P = 0.026). Maternal iodine excess in the first trimester had a slightly negative effect on infants' intellectual, motor, and physical development. In the third trimester, maternal iodine excess only may have a positive impact on infants' height. Additionally, maternal iodine status was closely related to infants' iodine status.

The Role of Thyroid Hormone Synthesis Gene-Related miRNAs Profiling in Structural and Functional Changes of The Thyroid Gland Induced by Excess Iodine.

At recent years, the impairment caused by iodine excess are paid more attention. However, there is still largely unknown about the exact mechanism induced by excessive iodine. MiRNAs have been found to act as biomarkers for a variety of diseases, whereas fewer studies focused on miRNAs related to a cluster of genes regulating thyroid hormone synthesis, such as NIS, Pendrin, TPO, MCT8, TSHR, TSHα, and TSHß-related miRNAs in structural and functional changes of the thyroid gland induced by subchronic and chronic high iodine exposure. In the present study, one hundred and twenty 4-week-old female Wistar rats were randomly divided into control group (I50µg/L KIO3); HI 1 (I6000µg/L KIO3); HI 2 (I10000µg/L KIO3); and HI 3 (I50000µg/L KIO3), the exposure period was 3 months and 6 months, respectively. The iodine contents in the urine and blood, thyroid function, and pathological changes were determined. In addition, levels of thyroid hormone synthesis genes and the associated miRNAs profiling were detected. The results showed that subclinical hypothyroidism occurred in the high iodine groups with subchronic high iodine exposure, while 6-month exposure led to hypothyroidism in the I10000µg/L and I50000µg/L groups. Subchronic and chronic high iodine exposure caused mRNA and protein levels of NIS, TPO, and TSHR decreased significantly, and Pendrin expression increased significantly. In addition, MCT8 mRNA and protein levels are only remarkably decreased under the subchronic exposure. PCR results showed that levels of miR-200b-3p, miR-185-5p, miR-24-3p, miR-200a-3p, and miR-25-3p increased significantly exposed to high iodine for 3 months, while miR-675-5p, miR-883-5p, and miR-300-3p levels increased significantly under the exposure to high iodine for 6 months. In addition, miR-1839-3p level was markedly decreased exposed to high iodine for 3 and 6 months. Taken together, the miRNA profiling of genes regulating thyroid hormone synthesis remarkably altered from subclinical hypothyroidism to hypothyroidism induced by excess iodine exposure, and some miRNAs may play an important role in subclinical hypothyroidism or hypothyroidism through regulating NIS, Pendrin, TPO, MCT8, and TSHR providing promising targets to alleviate the impairment on the structure and function of thyroid gland.

Effects of Inorganic Arsenic on Type 2 Diabetes Mellitus In Vivo: the Roles and Mechanisms of miRNAs.

Accumulating studies have shown that chronic exposure to iAs correlates with an increased incidence of diabetes. In recent years, miRNA dysfunction has emerged both as a response to iAs exposure and independently as candidate drivers of metabolic phenotypes such as T2DM. However, few miRNAs have been profiled during the progression of diabetes after iAs exposure in vivo. In the present study, high iAs (10 mg/L NaAsO2) exposure mice models of C57BKS/Leprdb (db/db) and C57BLKS/J (WT) were established through the drinking water, the exposure duration was 14 weeks. The results showed that high iAs exposure induced no significant changes in FBG levels in either db/db or WT mice. FBI levels, C-peptide content, and HOMA-IR levels were significantly increased, and glycogen levels in the livers were significantly lower in arsenic-exposed db/db mice. HOMA-ß% was decreased significantly in WT mice exposed to high iAs. In addition, more different metabolites were found in the arsenic-exposed group than the control group in db/db mice, mainly involved in the lipid metabolism pathway. Highly expressed glucose, insulin, and lipid metabolism-related miRNAs were selected, including miR-29a-3p, miR-143-3p, miR-181a-3p, miR-122-3p, miR-22-3p, and miR-16-3p. And a series of target genes were chosen for analysis, such as ptp1b, irs1, irs2, sirt1, g6pase, pepck and glut4. The results showed that, the axles of miR-181a-3p-irs2, miR-181a-3p-sirt1, miR-22-3p-sirt1, and miR-122-3p-ptp1b in db/db mice, and miR-22-3p-sirt1, miR-16-3p-glut4 in WT mice could be considered promising targets to explore the mechanisms and therapeutic aspects of T2DM after exposure to high iAs.

Association between different water iodine exposures and thyroid cancer: A retrospective study of high water iodine areas in China from 2009 to 2020.

In recent years, the incidence of thyroid cancer has been on a significant rise worldwide, and a number of environmental factors have been suspected to be risk factors for thyroid cancer, especially the relationship between iodine intake and thyroid cancer has attracted attention. In this study, we want to assess the relationship between different water iodine exposures and thyroid cancer incidence before and after water alteration in areas with high water iodine in China. Thyroid cancer patients (2009-2020) were enrolled at two hospitals, both in Heze City, Shandong Province, an area with high water iodine levels. According to the criteria of the study, 5826 cases out of 8785 cases were selected for inclusion in the study. Before and after water alteration, the incidence of thyroid cancer was highest in areas with water iodine concentrations of 200-300 µg/L in high iodine areas. In areas where water iodine decreased to adequate iodine levels, there was a strong negative correlation between the decreased level of water iodine and the incidence of thyroid cancer. In addition, in cases with pathology reports, we found that the greater the decrease in water iodine values, the markedly smaller the maximum diameter of the thyroid cancer lesions. Taken together, these findings suggest that we should continue to monitor the incidence of thyroid cancer in areas with high water iodine and continue to optimize population iodine intake to reduce the incidence of thyroid cancer.

Unveiling the LncRNA-miRNA-mRNA Regulatory Network in Arsenic-Induced Nerve Injury in Rats through High-Throughput Sequencing.

Arsenic is a natural toxin which is widely distributed in the environment, incurring diverse toxicities and health problems. Previous studies have shown that long non-coding RNAs (LncRNAs) are also reported to contribute to As-induced adverse effects. LncRNAs are involved in the development of nerve injury, generally acting as sponges for microRNAs (miRNAs). This study aimed to investigate the competitive endogenous RNA (ceRNA) regulatory networks associated with arsenic-induced nerve damage. A total of 40 male Wistar rats were exposed to different doses of arsenic for 12 weeks, and samples were collected for pathological observation and high-throughput sequencing. The ceRNA network was constructed using Cytoscape, and key genes were identified through the PPI network and CytoHubba methods. A real-time quantitative PCR assay was performed to validate gene expression levels. The results showed that subchronic exposure to arsenic in drinking water resulted in pathological and ultrastructural damage to the hippocampal tissue, including changes in neuron morphology, mitochondria, and synapses. Exposure to arsenic results in the dysregulation of LncRNA and mRNA expression in the hippocampal tissues of rats. These molecules participated in multiple ceRNA axes and formed a network of ceRNAs associated with nerve injury. This study also verified key molecules within the ceRNA network and provided preliminary evidence implicating the ENRNOT-00000022622-miR-206-3p-Bdnf axis in the mechanism of neural damage induced by arsenic in rats. These findings provide novel insights into the underlying mechanism of nervous system damage induced by arsenic exposure.

Subchronic Arsenic Exposure Induces Behavioral Impairments and Hippocampal Damage in Rats.

This study investigated the effects of subchronic arsenic exposure on behavior, neurological function, and hippocampal damage in rats. Thirty-two male Wistar rats were divided into four groups and exposed to different concentrations of arsenic in their drinking water for 12 weeks, while weekly water intake and body weight were recorded. Various neurobehavioral tests were conducted, evaluating overall activity levels, exploratory behavior, short-term memory, spatial learning and memory, anxiety-like behavior, and depressive-like states. Arsenic levels in urine, serum, and brain tissue were measured, and histopathological analysis assessed hippocampal damage using hematoxylin and eosin staining. The results demonstrated that arsenic exposure did not significantly affect overall activity or exploratory behavior. However, it impaired short-term memory and spatial learning and memory functions. Arsenic-exposed rats exhibited increased anxiety-like behavior and a depressive-like state. Arsenic levels increased dose-dependently in urine, serum, and brain tissue. The histopathological examinations revealed significant hippocampal damage, including neuronal shrinkage, cell proliferation, irregular structure, disordered arrangement, and vacuolation. These findings emphasize the importance of understanding the impact of arsenic exposure on behavior and brain health, highlighting its potential neurological consequences.

MiR-96-5p Suppresses Progression of Arsenite-Induced Human Keratinocyte Proliferation and Malignant Transformation by Targeting Denticleless E3 Ubiquitin Protein Ligase Homolog.

Long-term exposure to arsenic has been linked to a variety of cancers, among which skin cancer is the most prevalent form. However, the mechanism underlying arsenic carcinogenesis is unclear, and there is still limited information on the role of miRNAs in arsenic-induced skin cancer. This study aims to explore the role of miR-96-5p in the arsenite-induced proliferation and malignant transformation of human HaCaT keratinocytes. The GEO database (accession numbers GSE97303, GSE97305, and GSE97306) was used to extract mRNA and miRNA expression profiles of HaCaT cells treated with or without 0.1 µmol/L sodium arsenite for 3 and 7 weeks. In this paper, according to the CCK8 assay result, HaCaT cells exposed to 0.1 µmol/L sodium arsenite for 48 h were finalized. CCK8, MTT, EdU incorporation, and colony formation assays were used to determine the viability and proliferation of HaCaT cells and transformed HaCaT (T-HaCaT) cells. The subcellular localization and relative expression levels of DTL, as well as miR-96-5p in HaCaT cells induced by arsenite, were determined via immunofluorescence, RT-qPCR, and Western blot. Dual-luciferase reporter assay was performed to identify miR-96-5p bound directly to DTL. Transfection of miR-96-5p mimics or DTL siRNA was conducted to verify the arsenite-induced viability of HaCaT cells and T-HaCaT cells. T-HaCaT cells and nude mice were used to construct arsenite-induced malignant transformation and an in vivo xenograft model to demonstrate the over-expressed effect of miR-96-5p. The results showed that DTL was the target gene of miR-96-5p. Meanwhile, we also found that 0.1 µmol/L sodium arsenite upregulated DTL by decreasing the miR-96-5p level, leading to the proliferation and malignant transformation of HaCaT cells. MiR-96-5p agomir treatment slowed the growth of transplanted HaCaT cells transformed by arsenite in a manner associated with DTL downregulation in the nude mice xenograft model. Taken together, we confirmed that miR-96-5p, as a potent regulator of DTL, suppressed arsenite-induced HaCaT cell proliferation and malignant transformation, which might provide a novel therapeutic target for the treatment of arsenic-induced skin cancer.

Time to establish an international vaccine candidate pool for potential highly infectious respiratory disease: a community's view.

In counteracting highly infectious and disruptive respiratory diseases such as COVID-19, vaccination remains the primary and safest way to prevent disease, reduce the severity of illness, and save lives. Unfortunately, vaccination is often not the first intervention deployed for a new pandemic, as it takes time to develop and test vaccines, and confirmation of safety requires a period of observation after vaccination to detect potential late-onset vaccine-associated adverse events. In the meantime, nonpharmacologic public health interventions such as mask-wearing and social distancing can provide some degree of protection. As climate change, with its environmental impacts on pathogen evolution and international mobility continue to rise, highly infectious respiratory diseases will likely emerge more frequently and their impact is expected to be substantial. How quickly a safe and efficacious vaccine can be deployed against rising infectious respiratory diseases may be the most important challenge that humanity will face in the near future. While some organizations are engaged in addressing the World Health Organization's "blueprint for priority diseases", the lack of worldwide preparedness, and the uncertainty around universal vaccine availability, remain major concerns. We therefore propose the establishment of an international candidate vaccine pool repository for potential respiratory diseases, supported by multiple stakeholders and countries that contribute facilities, technologies, and other medical and financial resources. The types and categories of candidate vaccines can be determined based on information from previous pandemics and epidemics. Each participant country or region can focus on developing one or a few vaccine types or categories, together covering most if not all possible potential infectious diseases. The safety of these vaccines can be tested using animal models. Information for effective candidates that can be potentially applied to humans will then be shared across all participants. When a new pandemic arises, these pre-selected and tested vaccines can be quickly tested in RCTs for human populations.

Distribution of iodine concentration in drinking water in China mainland and influence factors of its variation.

OBJECTIVE: To identify the current spatial distribution of iodine concentration in drinking water (dWIC) at the township-level across China and its influencing factors through visualization and spatial statistical analysis by the geographic information system. METHODS: The dWIC for each township was used to describe the distribution by ArcGIS 10.7. The spatial aggregation characteristics were analyzed by spatial auto-correlation analysis. The inverse distance weight method was used to predict the dWIC at nonsampling sites. The correlation between the dWIC and the distance from each township to the Yellow River as well as the depth of tube wells were analyzed by ordinary least squares and geographically weighted regression, respectively. RESULTS: A total of 37,541 townships were included in this study. dWIC ranged from 0 to 1113.7 µg/L, and the median was 3.3 µg/L. There were 35,606 townships < 40 µg/L (94.85 % of surveyed townships), 40 µg/L ≤ 1015 townships ≤100 µg/L (2.70 % of surveyed townships), and 920 townships > 100 µg/L (2.45 % of surveyed townships). The results were statistically significant of global autocorrelation analysis (Moran's I = 0.43, Z = 922.15, P < 0.01). Local Moran's I showed that 3128 townships (8.33 % of surveyed townships) belong to H-H cluster areas. The dWIC was partially negatively correlated with the distance from each township to the Yellow River, as well as positively correlated with the depth of tube wells in partial areas. CONCLUSIONS: The dWIC varied widely across mainland China (from 0 µg/L to 1113.7 µg/L). 94.85 % of surveyed townships were below 40 µg/L and 2.45 % of surveyed townships were exceeding 100 µg/L. Moreover, the distance from each township to the Yellow River may be one of the geneses of iodine-excess areas. Finally, this study has provided a visible reference of dWIC for the precise control strategy and focused monitoring in China.

Ligand-free high loading capacity ursolic acid self-carried nanovesicles enable hepatocyte targeting via absorbing apolipoproteins.

Ursolic acid (UA), a natural pentacyclic terpenoid carboxylic acid that can exert a potent hepatoprotective activity, has been developed into various types of nanoparticles to improve its pharmacological effects, however, the phagocytosis of nanoparticles by Kupffer cells greatly limits its efficacy. Herein, UA/Tween 80 nanovesicles (V-UA) were constructed and despite its simple composition, it fulfills multiple functions simultaneously: UA served as not only an active ingredient in the nanovesicle drug delivery system, but also acts as part of the carrier to stabilize UA/Tween 80 nanostructure; with a molar ratio of UA to Tween 80 up to 2:1, the formulation possesses a significant advantage of higher drug loading capacity; relative to liposomal UA (Lipo-UA), a conditional cellular uptake and higher accumulation of V-UA in hepatocytes provide insights into the hepatocytes targeting mechanisms of this nanovesicles. Favorable hepatocyte targeting ability also facilitates the treatment of liver diseases, which was well validated in three liver disease models.

The mechanism underlying fluoride-induced low-renin hypertension is related to an imbalance in the circulatory and local renin-angiotensin systems.

The renin-angiotensin system (RAS) is an important fluid regulation system in the body, and excessive activation of the circulatory or local RAS can increase blood pressure (BP). Excess fluoride can increase BP, although the underlying mechanism related to activation of the RAS remains unclear. Thus, the aim of this study was to elucidate the role of the RAS in fluoride-induced hypertension. Markers of the circulating and local RASs related to pathological changes to the kidneys, myocardium, and aorta were measured. Fluoride reduced serum levels of renin, angiotensin II (Ang II), and angiotensin (1-7) [Ang (1-7)], and dysregulated plasma levels of aldosterone and potassium levels. Excess fluoride can damage the kidneys, myocardium, and aorta, overactivate the renal angiotensin converting enzyme (ACE)-Ang II-angiotensin type 1 receptor axis, and inhibit activation of the ACE2-Ang (1-7)-Mas axis, leading to dysregulation of alpha epithelial sodium channels and significantly increased expression of Ang II in the myocardium and aorta. Hence, excess fluoride can cause low-renin hypertension via an imbalance between the circulatory and local RASs.

Serum thyroglobulin as a biomarker of iodine excess and thyroid disease occurrence in adults.

BACKGROUND: Thyroglobulin (Tg) is considered a sensitive indicator of iodine deficiency. However, the usefulness of Tg as a biomarker of excess iodine is uncertain. The present study aimed to determine the influence of different iodine intake on serum Tg levels, evaluate the influence of thyroid diseases on the distribution of Tg, and identify the factors that may affect Tg levels. METHODS: A cross-sectional survey with a total of 1208 adults was conducted in different water iodine areas in China. Urinary iodine concentration (UIC), water iodine concentration (WIC), serum Tg, thyroid-stimulating hormone (TSH), and thyroid antibodies were measured. The thyroid volumes and nodules were measured by B-scan ultrasound. RESULTS: Based on the WIC data, subjects were divided into three groups. Based on the median urinary iodine concentration (MUIC) data, the iodine levels were adequate, more than adequate, and excess for the WIC < 10 µg/L group, 10 µg/L ≤ WIC ≤ 100 µg/L g, and WIC > 100 µg/L groups, respectively. The median Tg was significantly higher in the excess iodine group than in the adequate iodine group and the more than adequate iodine group (14.6 µg/L vs.12.7 µg/L, P = 0.042; 14.6 µg/L vs.12.5 µg/L, P = 0.004). Multiple linear regression analysis showed that excess iodine intake, goitre, thyroid nodules, and hypothyroidism were significantly related to higher serum Tg levels. CONCLUSION: Serum Tg level can be a promising biomarker of excessive iodine intake, but other factors, especially the presence of thyroid disease, should be considered when using this parameter.