Lead Toxicity in Children: Health Effects, Policies and Recommendations

Lead is a dangerous element that exists naturally in the Earth's crust. Any kind of lead causes a detrimental response in the human body. It is discharged into the environment during the manufacturing of batteries, foundries, ammunition, lead paint, water pipes, and other manufactured goods. It can enter the body through a variety of pathways, including those in the air, water, soil, food, and dust. Concern is raised since there is no amount of lead that is safe for the human body. The problem persists despite several prevention measures that the state and the federal governments have put in place. This review assesses the effects of lead exposure on children as well as suggested solutions to the issue.

Network-based Toxicogenomics Approach to Unraveling the Influence of Lead and Cadmium Mixture on the Development and Progression of Hypertension

Heavy metals, generally characterized by high densities and atomic weights, are ubiquitous in the environment and are a public health concern due to the several health issues they pose to humans. Of all heavy metals, lead and cadmium among others are known to be capable of inducing multiple health effects even at a low rate of exposure. Hypertension (HYP), a major cause of death and a risk factor for other cardiovascular diseases, is known to be caused by both lead and cadmium. While the mechanism underlying the development of HYP induced by independent exposure to lead and cadmium has been well studied, the mechanism underlying the induction and progression of HYP upon lead and cadmium co-exposure remains mildly explored. Hence, this study aimed to elucidate the mechanism using a toxicogenomic approach. The set of genes affected by both heavy metals was identified using the comparative toxicogenomics database (CTD) while HYP targets were retrieved from the Gene Cards database. The shared genes between the heavy metals and the disease were identified and subjected to further analysis. The results of our analysis revealed the signaling pathways that are dysregulated by lead and cadmium co-exposure while oxidative stress, inflammation, and endothelial dysfunction were revealed as processes pertinent to the induction and progression of HYP by lead and cadmium co-exposure. Biomarkers that could be used for prognosis evaluation were also identified. Ultimately, this study supports and advances the growing body of finding on the roles played by lead and cadmium co-exposure in inducing HYP.

Chemical elements in sediments and in bivalve mollusks from estuarine regions in the south of Bahia State, northeast Brazil / Elementos químicos em sedimentos e em moluscos bivalves de regiões estuarinas do sul do Estado da Bahia, Nordeste do Brasil

Abstract Estuaries receive daily inputs of chemical elements which can impact the quality of water and sediment, as well as the health of biota. In addition to the sediment, bivalve mollusks have been used in the chemical monitoring of these systems. This study investigated the presence and contents of As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb and Zn in superficial sediment and in bivalves (Crassostrea gasar, C. rhizophorae and Mytella guyanensis) from estuaries in the south / extreme south of Bahia State, northeast Brazil. The samples were evaluated with inductively coupled plasma optical emission spectrometry (ICP-OES, Varian 710). Except for Cd, all other elements were found in the samples, being that Co was exclusive in the sediment. The estuaries equivalent to sampling stations #1 - Valença, #2 - Taperoá, #3 - Ilhéus and #4 - Belmonte showed levels of metals compatibles with those established by the Brazilian legislation, however, the #5 - Santa Cruz Cabrália, in addition to the presence of As, presented a high level of Pb and Cu in C. gasar, which was attributed to the impacts of nautical activities in that locality.

Resumo Estuários recebem entradas diárias de elementos químicos, que podem impactar a qualidade de água e do sedimento, assim como a saúde da biota. Além do sedimento, moluscos bivalves têm sido utilizados no monitoramento químico desses sistemas. Neste estudo investigou-se a presença e os teores de As, Ba, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb e Zn no sedimento superficial e em bivalves (Crassostrea gasar, C. rhizophorae e Mytella guyanensis) de estuários do sul / extremo sul do estado da Bahia, Nordeste do Brasil. As amostras foram avaliadas por espectrometria de emissão óptica de plasma indutivamente acoplado (ICP-OES, Varian 710). Exceto Cd, todos os demais elementos foram encontrados nas amostras, sendo que Co foi exclusivo no sedimento. Os estuários equivalentes às estações amostrais #1 - Valença, #2 - Taperoá, #3 - Ilhéus e #4 - Belmonte mostraram níveis de metais compatíveis com os estabelecidos pela legislação brasileira, porém, a #5 - Santa Cruz Cabrália, além da presença de As, apresentou alto nível de Pb e de Cu em C. gasar, o que foi atribuído aos impactos por atividades náuticas nesse local.

Effects of lead exposure on development of heart and spine in zebrafish embryos / 环境与职业医学

Background Lead is widely distributed. Lead exposure interferes with early life development in zebrafish, but the mechanisms by which lead exposure affects skeletal development and cardiac development are not clear as yet. Objective To investigate the molecular mechanisms of bone development and cardiac development toxicity induced by lead acetate exposure. Methods Zebrafish embryos were exposed to different concentrations of lead acetate (0, 6, 12, 24, and 48 μmol·L−1) for 3 h post-fertilization (3 hpf) until 5 d post-fertilization (5 dpf). The malformation phenotypes of 5 dpf were counted, and the mRNA expressions of spinal development-related genes (bmp2b, bmp4, bmp9, runx2a, runx2b) and heart development-related genes (nkx2.5, myh6, myh7) were detected by quantitative PCR (qPCR). Expressions of genes of development-related regulatory pathways including Wnt/β-catenin pathway (wnt5a, wnt8a, wnt10a, β-catenin) and TGF-β pathway (tgf-β1, tgf-β2) as well as key molecule eph of Eph-Ephrin signaling were analyzed. Results At 5 dpf, the zebrafish in the lead acetate treated groups showed deformed phenotypes including spinal curvature and pericardial sac edema compared to the control group. In the lead acetate groups at 24 and 48 μmol·L−1, the spinal curvature deformity rates reached 26.47% and 71.52% (P<0.01) respectively. The qPCR results revealed that the expression levels of spinal development-related genes bmp2b, bmp4, bmp9, runx2a, and runx2b were downregulated in the 48 μmol·L−1 exposure group compared to the control group by 82.8%, 58.0%, 88.7%, 85.5%, and 69.2%, respectively (P<0.05 or P<0.01); the expression levels of heart development-related genes myh6, myh7, and nkx2.5 were down-regulated by 63.7%, 58.9%, and 55.2%, respectively (P<0.01); the expression levels of wnt8a and β-catenin in the Wnt/β-catenin pathway were down-regulated by 71.5% and 47.3% (P < 0.05 or P < 0.01), respectively; the expression level of tgf- β1 in the TGF-β pathway was down-regulated by 67.5% (P<0.01); the expression level of eph was down-regulated by 86.9% (P<0.01). Conclusion Lead acetate exerts developmental toxic effects on zebrafish heart and bone by down-regulating the expressions of genes related to spinal development and heart development, as well as inhibiting development-related Wnt/β-catenin and TGF-β pathways and Eph-Ephrin signaling, causing malformed phenotypes such as spinal curvature and pericardial sac edema.

Investigation on blood lead level of workers in a lead-acid battery factory in Wuhan / 公共卫生与预防医学

Objective To investigate the occupational lead exposure and blood lead levels of workers in a lead-acid battery factory in Wuhan in 2020 and analyze the influencing factors of blood lead, and to provide reference for the blood lead intervention of the workers in the lead-acid battery factory. Methods The blood lead test results of 320 occupational lead-exposed workers in the factory were investigated and the influencing factors were analyzed. Results Among the 320 blood lead samples collected, 4 people had blood lead≥400 μg/L, accounting for 1.25%, and 89 people had blood lead≥200 μg/L, accounting for 27.81%. Among them, there were 235 males with a median blood lead of 155.10 μg/L, and 85 females with a median blood lead of 82.40 μg/L. The Wilcoxon rank sum test results of two independent samples showed that the overall blood lead level of male employees was higher than that of female employees, and the difference was statistically significant (P 50 years old. Using the Bonferroni method to adjust the significance level for pairwise comparison, it was found that there were significant differences in the blood lead concentrations between the group under 40 years old, the group of 40 - 50 years old, and the group of over 50 years old ( P < 0.016 after adjustment). The employees were classified into different workshops, including 38 samples from the administrative workshop , 40 samples from the charging workshop, and 242 samples from the assembly workshop. Using the Bonferroni method to adjust the significance level for pairwise comparison, it was found that the blood lead concentrations in the administrative workshop, the charging workshop, and the assembly workshop were statistically different ( P <0.016 after adjustment). Conclusion The age, gender, and type of work of the employees in the battery factory all have a certain impact on the blood lead level. It is necessary to continuously improve the management of the labor hygiene operation system and strengthen the self-protection level of the workers, and regularly carry out occupational hygiene inspection and health monitoring.

Validity of point-of-care device for diagnosing anemia in workers exposed to lead

Detecting anemia in occupational health settings is critical in a high-risk population for anemia like the lead-exposed. Whether the point-of-care devices are sensitive to detect anemia in individuals with high levels of lead exposure is unknown. We compared hemoglobin (Hb) levels from HemoCue® Hb 301 System and standard analyzer, Mindrey-BC 5300, in individuals (n=58) exposed to lead (mean levels = 44.9 ?g/dL) for a chronic period (mean duration of exposure = 105 months). We observed high sensitivity (0.95), specificity(0.95) in detecting anemia by hemocue, and high agreement between the methods. The significant difference in Hb values between the methods (0.171g/dL, p=0.018) was clinically minimal. We conclude that hemocue is a good method for rapidly detecting anemia and estimating Hb levels among the lead-exposed in resource-limited settings.

aVR: la derivada olvidada / aVR: the forgotten lead

Resumen La derivada aVR es frecuentemente olvidada al interpretar un electrocardiograma. Esto se explica en gran medida debido a que no aporta información específica sobre el ventrículo izquierdo. Sin embargo, tiene gran utilidad en términos tanto de diagnóstico como de pronóstico en múltiples condiciones clínicas, como el síndrome coronario agudo, la pericarditis, la disección aórtica, la intoxicación por antidepresivos tricíclicos, las arritmias y múltiples trastornos de la conducción cardiaca. El objetivo de este artículo es resaltar la importancia clínica de esta derivada y así incentivar su evaluación sistemática en la práctica clínica.

Abstract aVR lead is a frequently forgotten derivative when interpreting an electrocardiogram. This may be largely explained by the fact that it does not provide specific information on the left ventricle. However, it is very useful in terms of both, diagnosis and prognosis, of different clinical entities such as acute coronary syndrome, pericarditis, aortic dissection, tricyclic antidepressants intoxication, arrhythmias and multiple cardiac conduction disorders. The main purpose of this article is to highlight the clinical importance of aVR lead and thus encourage its use in clinical practice.

Electrocardiographic Manifestations in COVID-19 Patients — An Observational Study from a Tertiary Care Centre in North Eastern India

Introduction : The Coronavirus disease 2019 (COVID-19) primarily involves respiratory system but may also affect the Cardiovascular System leading to abnormal ECGs. Its early recognition is crucial as it may be associated with increased mortality. Hence we aimed to find out various Electrocardiographic (ECG) manifestations of COVID19 patients admitted in a Tertiary Care Hospital and its relation to disease severity. Methods : We performed a hospital-based retrospective observational study between April, 2021 to November 2021 and analyzed the ECG changes at admission by three Cardiologists according to standard definitions and diagnostic criteria. Results : Out of 579 patients, ECG of 473 was available for analysis. ECG was normal in 227 (48%) and abnormal in 246 (52%) patients. Most common abnormal ECG finding in COVID19 patients was Sinus Tachycardia(19.5%) and less common findings were Sinus Bradycardia (5.3%), Incomplete Right Bundle Branch Block (RBBB) (3.2%), atrial fibrillation (2.5%), complete RBBB (2.3%), atrial premature complexes (2.3%), S1Q1T3 pattern (2.1%), first degree AV block (1.5%), ST-T wave changes (1.3%), Atrial flutter (1.1%). In mechanically ventilated patients, incidence of acute Right Ventricular Pressure Overload (RVPO) related ECG findings were more frequent. Conclusion : There is a wide spectrum of ECG manifestations in COVID-19 patients which varies depending upon the severity of COVID as well as prior Cardiovascular status, associated comorbidities and need for ventilatory support. Knowledge of ECG changes might help in risk stratification and triaging of COVID-19 patients.

Protección de embarazadas en radiología oral / Protection of pregnant women in oral radiology

Las radiografías dentales son necesarias para diagnosticar y hacer seguimiento de múltiples enfermedades orales. Sin embargo, debido a los conocidos efectos estocásticos de los rayos X dentales es imprescindible garantizar protección a los pacientes. Especial atención merecen las mujeres embarazadas por cuanto el feto es altamente vulnerable a la radiación, sobre todo enlas primeras semanas. Algunas recomendaciones de protección radiológica en esta población son: El uso de radiografías ha sido justificado; realizar el estudio 10 días después del inicio de la menstruación; informar del procedimiento a la embarazada a fin de evitar el miedo; optimizar el procedimiento (haz colimado, alto kVp, control manual de disparo, calibración regular etc.) y usar delantal plomado solo si las condiciones de optimización son insuficientes

Dental x-rays are necessary to diagnose and monitor multiple oral diseases. However, due to the well-known stochastic effects of dental X-rays, it is essential to guarantee patient protection. Pregnant women deserve special attention because the fetus is highly vulnerable to radiation, especially in the first weeks. Some recommendations for radiological protection in this population are the use of radiographs has been justified; conduct the study 10 days after the onset of menstruation; inform the pregnant woman about the procedure to avoid fear; optimize the procedure (collimated beam, high kVp, manual trip control, regular calibration etc.) and use a lead apron only if the optimization conditions are insufficient.

Exposición ambiental a plomo y biomarcadores de estrés oxidativo en niños sanos de La Plata, Argentina / Environmental exposure to lead and oxidative stress biomarkers among healthy children in La Plata, Argentina

Introducción. La exposición ambiental a plomo (Pb) aún constituye un problema de salud pública, particularmente para los niños. El estrés oxidativo podría representar un mecanismo primario asociado a su toxicidad. El objetivo del presente estudio fue determinar los niveles de Pb en sangre (Pb-S) en niños de 1 a 6 años de La Plata y alrededores con exposición ambiental, y su relación con biomarcadores de estrés oxidativo. Población y métodos. Estudio analítico de corte transversal. Se evaluaron niños clínicamente sanos de 1 a 6 años. Se determinaron los niveles de Pb-S, las actividades de enzimas antioxidantes y el grado de peroxidación lipídica. Se utilizó el paquete estadístico R versión 3.5.1. Resultados. Participaron 131 niños, mediana de edad 2,33 años. La media geométrica de los niveles de Pb-S fue 1,90 µg/dL; el 32 % presentó plombemias cuantificables y el 3 %, niveles ≥5 µg/dL (referencia internacional). Al comparar los biomarcadores de estrés oxidativo según los niveles de Pb-S, solo se observó diferencia significativa entre las medianas de las sustancias reactivas al ácido tiobarbitúrico (TBARS): 12,0 versus 10,0 nmol MDA/mL plasma; p = 0,02. Asimismo, la correlación entre las plombemias y las TBARS fue positiva (r = 0,24; p = 0,012). Conclusiones. La mayoría de los niños mostraron niveles de Pb-S menores a los límites recomendados por agencias internacionales, que si bien, no producen alteraciones en la actividad de enzimas antioxidantes, sí inducen peroxidación lipídica. Estos resultados reflejan la utilidad de este biomarcador como una herramienta diagnóstica temprana para evaluar los efectos subtóxicos del Pb.

Introduction. Environmental exposure to lead is still a major public health problem, especially in children. Oxidative stress may be a primary mechanism associated with toxicity. Theobjective of this study was to measure blood lead levels (BLLs) in children aged 1 to 6 years expos to lead in La Plata and suburban areas and their relation to oxidative stress biomarkers. Population and methods. Cross-sectional,analytical study. Clinically healthy children aged1 to 6 years were analyzed. BLLs, antioxidant enzyme activity, and extent of lipid peroxidation were measured. The statistical softwarepackage R, version 3.5.1, was used. Results. A total of 131 children participated; their median age was 2.33 years. The geometric mean of BLLs was 1.90 µg/dL; 32% showed a measurable BLL and 3%, BLLs ≥ 5 µg/dL (international reference). The comparison ofoxidative stress biomarkers based on BLshowed a significant difference in median thiobarbituric acid reactive substances (TBARS):12.0 versus 10.0 nmol MDA/mL of plasma;p = 0.02. In addition, the correlation between BLLs and TBARS was positive (r = 0.24; p = 0.012 Conclusions. Most children had a BLL below the limit recommended by international agencies; although such BLLs do not affantioxidant enzyme activity, they can induce lipid peroxidation. These results demonstrate theusefulness of this biomarker as an early diagnosistool to assess subtoxic lead effects.

Trace Element Levels and Socio-Demography of Pre-Teen Nigerians with Homozygous Sickle Cell Disorder

Objectives: Homozygous sickle cell disorder (SCD) children are known to have abnormal anthropometric parameters which mostly have been linked with altered zinc status. Alteration in trace element status which occurs from interaction between essential and non-essential elements has not been well studied in SCD. Therefore, the aim of the study is to relate concentrations of Zn, Cd, and Pb with anthropometric parameters. Moreover, it will be established if correlation (interaction) exists between zinc and these two non-essential elements. Methods: Twenty-seven SCD patients and 25 age and sex-matched children with hemoglobin genotype HbAA served as test and control groups respectively. Anthropometric parameters and information on demography, dietary zinc status and socio-economic status were obtained. The plasma and red cells obtained from 5 mL of blood were used to determine zinc and heavy metal (Pb, Cd) levels respectively by atomic absorption spectrophotometry. Data were analyzed using Student`s t-test, Chi- square test, and Pearson抯 correlation coefficient. P< 0.05 was considered significant. Results: There were significant differences in the mean values of mid-upper-arm circumference, weight and BMI. On the other hand, there were no significant differences in mean values of head circumference, height and the trace elements in test and control groups. No association between trace elements and BMI as well as between dietary zinc content and socio-economic status was observed. Conclusion: the result of the study suggests there is no correlation between the toxic metals and zinc, and it seems that toxic metals play no role in abnormal BMI that is a common feature of SCD.

ANGIOGRAPHIC CORRELATION OF ST ELEVATION IN LEAD AVR DURNG TMT IN PATIENTS WITH LMCA DISEASE

BACKGROUND:Treadmill testing is the most widely used method for evaluating patients with coronary artery disease. Predicting the left main coronary artery disease (LMCA) before invasive procedure is important in risk assessment because of its grave clinical outcome. Lead aVR can be very useful in identifying LMCAobstruction. It is also valuable lead not only in diagnosis but also predicting the prognosis. AIM: To examine whether STelevation in aVR during TMTcorrelates with LMCAdisease in coronary Angiogram METHOD: In this study 100 patients with positive TMT were included. The study group consisted of 60 patients with ST elevation of > 1mm in aVR. 40 patients also have TMT positive but with < 1mm of ST elevation in aVR is the control group. All patients underwent coronary angiography. RESULTS: Coronary Angiography in the study group revealed significant LMCA disease in 36 (63%) patients whereas no LMCA disease in control group 12 (20%) patients had ostioproximal LAD leisions in study group 4 (10%) patients in the control group. Triple vessel disease in 10 (17%) patients in study group 6 (15%) patients in control group. Since the p value was significant, ST Elevation in aVR during TMT strongly predicts the presence of LMCADisease. CONCLUSION: STsegment elevation in aVR > 1mm during Treadmill testing is a strong predictor of LMCAdisease

Protective effect of Rheum ribes extract against lead-induced hepatotoxicity in male rats

Abstract The effects of Rheum ribes on lead acetate levels and hepatic biochemical factors due to lead acetate toxicity were investigated. Forty male Wistar rats were designated into four groups: Control; lead acetate (receiving in drinking water at 0.6 g/L, daily); hydroalcoholic extract groups (200 and 400 mg/kg doses, gavage, once daily). Treatments were conducted for 10 days. On the 11th day, blood samples were collected to measure lead acetate levels and biochemical factors. Liver tissue samples were examined for histopathological changes. Lead serum levels were increased in lead acetate-treated rats (p<0.001). Lead acetate treatment was associated with a significant increase in liver tissue damage (p<0.001), while R. ribes extract prevented liver tissue damage (p<0.05). The levels of alanine aminotransferase and aspartate aminotransferase were significantly lower in the groups lead acetate + extract (two doses) than in the lead acetate group (p<0.001 and P<0.01, respectively), but alkaline phosphatase level, prothrombin time, partial thromboplastin time and international normalized ratio were not different between the lead acetate + extract groups and the lead acetate group. The results showed the inhibitory role of R. ribes on lead-induced hepato-toxicity. The results make Rhubarb a good candidate to protect against the deleterious effect of chronic lead intoxication after complementary studies.

Effects of arsenic, selenium, lead and chromium in urine on blood pressure in people from arsenic exposure areas of Togtoh County, Inner Mongolia Autonomous Region / 中华地方病学杂志

Objective:To learn about the incidence of hypertension in residents of arsenic exposure areas of Togtoh County, Inner Mongolia Autonomous Region, and to analyze the influencing factors of hypertension.Methods:In Inner Mongolia Autonomous Region, Ciweigou of Togtoh County, a drinking water-type endemic arsenic poisoning area, and Lanjiayao of Horinger County, a non-arsenic poisoning area with similar living habits and economic conditions, permanent residents who had lived for ≥10 years were selected as the survey subjects. Totally 116 residents of Ciweigou (exposure group) and 68 residents of Lanjiayao (control group) were included in the survey. Blood pressure was measured and the contents of arsenic, selenium, lead and chromium in urine were detected, multivariate logistic regression was used to analyze the influencing factors of hypertension.Results:The detection rates of hypertension in exposure group and control group were 53.45% (62/116) and 70.59% (48/68), respectively, and the difference between the two groups was statistically significant (χ 2 = 5.33, P = 0.022). The contents of arsenic, selenium and chromium in urine of exposure group were higher than those of control group, and the content of lead in urine was lower than that of control group, and the differences were statistically significant ( Z = 13.04, 6.34, 11.28, - 9.91, P < 0.001). The results of multivariate logistic regression analysis showed that female, age ≥60 years old and high urinary arsenic content were the influencing factors of hypertension [odds ratio ( OR) = 2.074, 2.004, 0.424, 95% confidence interval ( CI): 1.113 - 3.866, 1.035 - 3.879, 0.219 - 0.820] in arsenic exposure areas. Conclusion:Female, age ≥60 years old and high urinary arsenic content are the influencing factors of hypertension in arsenic exposure areas of Togtoh County, Inner Mongolia Autonomous Region.

Thyroid hormone levels in healthy adults with non-occupational exposure to cadmium， lead and perfluoroalkyl substances / 上海预防医学

ObjectiveTo assess the effects of non-occupational mixed exposure to cadmium， lead and perfluoroalkyl substances （PFASs） on thyroid hormones （TH） in healthy adult residents in Shanghai. MethodsIn November 2018， adults in Shanghai Suburban Adult Cohort and Biobank study， who visited a community health service center for examination with no history of occupational exposure， thyroid diseases or chronic diseases， were recruited. A social-demographic information questionnaire survey was conducted and urine and blood samples were collected. Inductively coupled plasma mass spectrometry （ICP-MS） was used to measure their urinary cadmium （UCd）， blood cadmium （BCd） and blood lead （BPb） concentrations. Ultra-high performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry （UPLC-Q/TOF MS） was used to measure 11 kinds of PFASs. Total and free triiodothyronine （TT3， FT3）， total and free thyroxine （TT4， FT4） and thyroid simulating hormones were measured by chemiluminescence enzyme-linked immunoassay. 436 participants were finally included and LASSO regression， multivariate regression and weighted quantile sum regression were used to evaluate the associations of these environmental pollutants with thyroid hormones. ResultsAmong the participants， 185 were male （42.5%） and the median age was 60 （P25‒P75： 50‒66）. The detection rates of urinary cadmium， blood cadmium and blood lead were all more than 95% and the detection rates of 7 PFASs （PFOS， PFOA， PFHxS， PFUnDA， PFNA， PFD， and PFBS） were more than 90%. The median exposure level of PFOA was the highest （49.6 µg‧L-1） among PFASs， followed by PFHxS （22.8 µg‧L-1） and PFOS （15.4 µg‧L-1）， and the median exposure levels of urinary cadmium， blood cadmium and blood lead were 0.7 μg‧g-1（Corrected for creatinine of urine）， 0.8 µg‧L-1， and 15.4 µg‧L-1， respectively. The results showed that UCd was negatively associated with TSH and BCd was positively associated with TT3， while PFASs mainly affected FT4， TT4， and TT3， with gender differences. In males， 7 PFASs had a significant negative mixture effect on TT3 and TT4， while the direction of effect of PFASs in females differed， with PFOS and PFUnDA having a significant positive correlation with FT4 and TT4 while PFDA having a significant negative correlation with FT4 and TT4. ConclusionIn a healthy population with no occupational exposure， co-exposure to cadmium， lead and PFASs affects different thyroid hormone indicators， and such effect could be gender-related， indicating that the effect of mixed exposure to metal and emerging compounds on thyroid functions warrants further attention.

Validation of compound C19 as a glutaminase C inhibitor / 药学学报

The mitochondrial enzyme glutaminase C (GAC) is highly expressed in a variety of cancer cells, resulting in increased glutamine metabolism and cancer development. Therefore, GAC has become a potential target for anti-tumor drug development. However, current GAC inhibitors shared similar structural characteristics, few new scaffolds were reported. By conducting a prokaryotic Escherichia coli expression system, human GAC protein of high-purity was obtained through lysozyme digestion combined with ultrasound dissociation, and cobalt magnetic beads purification, Moreover, we performed studies to validate interaction between small molecules and GAC protein through thermal shift assay, drug affinity responsive target stability assay, protein crosslinking and GAC enzyme activity detection. Meanwhile, a comprehensive small molecule-protein interaction confirmation and systematic pharmacodynamic study in vitro were carried out on compound C19, which was a reported GAC inhibitor screened from the Enamine database. Results showed that C19 directly bind to GAC protein, disturbed GAC tetramers formation, and inhibited its enzyme catalytic activity. By interfering GAC function, C19 dose-dependently suppressed GAC-mediated glutamine metabolism, reduced glutamate in cancer cells, and thus alleviated A549 and NCI-H1299 non-small cell lung cancer cell growth. Together, C19 was identified as a lead compound, providing a new strategy for the structural design of drugs targeting GAC.

Discovery of novel KRAS‒PDEδ inhibitors with potent activity in patient-derived human pancreatic tumor xenograft models

KRAS‒PDEδ interaction is revealed as a promising target for suppressing the function of mutant KRAS. The bottleneck in clinical development of PDEδ inhibitors is the poor antitumor activity of known chemotypes. Here, we identified novel spiro-cyclic PDEδ inhibitors with potent antitumor activity both in vitro and in vivo. In particular, compound 36l (K D = 127 ± 16 nmol/L) effectively bound to PDEδ and interfered with KRAS-PDEδ interaction. It influenced the distribution of KRAS in Mia PaCa-2 cells, downregulated the phosphorylation of t-ERK and t-AKT and promoted apoptosis of the cells. The novel inhibitor 36l exhibited significant in vivo antitumor potency in pancreatic cancer patient-derived xenograft (PDX) models. It represents a promising lead compound for investigating the druggability of KRAS‒PDEδ interaction.

Environmental exposure to cadmium but not lead is associated with decreased semen quality parameters: quality regionalism of sperm properties / 亚洲男科学杂志(英文版)

Environmental factors may negatively contribute to a progressive worsening of semen quality, and differences in semen quality may result from different environmental exposures (regional differences) or lifestyle differences. Heavy metals are factors with a confirmed negative influence on male fertility. Among them, lead and cadmium are commonly found in human surroundings. Thus, we analyzed semen parameters (according to the World Health Organization 2010 recommendations) and semen lead and cadmium concentrations in 188 men from two different regions in Poland, a typical agricultural area and an industrial area, in couples that had been diagnosed with infertility. The assays were performed using flameless electrothermal atomic absorption spectrometry. In the statistical analysis, regional comparisons and then taxonomic comparisons based on three parameters (age, semen concentration, and sperm morphology) were applied. We showed that more cadmium than lead accumulated in semen, a higher cadmium concentration was observed in semen obtained from men from the agricultural region, and better semen quality and lower cadmium concentrations were found in the semen of men from the industrial, more polluted region. We thus showed an existing regionalism in the sperm quality properties. However, semen parameters such as morphology and progressive and nonprogressive motility followed the same trends, regardless of the patient's age, region, or class. We could conclude that the environment has a minor impact on sperm morphology and progressive and nonprogressive motility and that other existing factors could have an indirect influence on semen quality.

Automatic detection model of hypertrophic cardiomyopathy based on deep convolutional neural network / 生物医学工程学杂志

The diagnosis of hypertrophic cardiomyopathy (HCM) is of great significance for the early risk classification of sudden cardiac death and the screening of family genetic diseases. This research proposed a HCM automatic detection method based on convolution neural network (CNN) model, using single-lead electrocardiogram (ECG) signal as the research object. Firstly, the R-wave peak locations of single-lead ECG signal were determined, followed by the ECG signal segmentation and resample in units of heart beats, then a CNN model was built to automatically extract the deep features in the ECG signal and perform automatic classification and HCM detection. The experimental data is derived from 108 ECG records extracted from three public databases provided by PhysioNet, the database established in this research consists of 14,459 heartbeats, and each heartbeat contains 128 sampling points. The results revealed that the optimized CNN model could effectively detect HCM, the accuracy, sensitivity and specificity were 95.98%, 98.03% and 95.79% respectively. In this research, the deep learning method was introduced for the analysis of single-lead ECG of HCM patients, which could not only overcome the technical limitations of conventional detection methods based on multi-lead ECG, but also has important application value for assisting doctor in fast and convenient large-scale HCM preliminary screening.