Characterization of Schiff Base Modified MCM-41 Molecular Sieve for Adsorption of Lead Ions from Aqueous Solution / 分析化学

A new Schiff base modified MCM-41 molecular sieve(N-MCM-41)was synthesized via post-grafting method with 2-pyridine formaldehyde for efficient removal of lead ions(Pb2+)from aqueous solution.X-ray diffraction(XRD),scanning electron microscopy(SEM),transmission electron microscopy(TEM),Fourier transform-infrared(FT-IR)spectroscopy,thermogravimetric analysis(TGA),and X-ray photoelectron spectroscopy(XPS)were employed to characterize the structure,morphology,surface functional groups and chemical states of N-MCM-41.Moreover,the adsorption behavior of Pb2+by N-MCM-41 was systematically studied.Batch adsorption studies revealed that N-MCM-41 showed the maximal adsorption capacity of 101.3 mg/g at 45℃and pH=5.5 under the initial Pb2+ concentration of 80 mg/L after 180 min adsorption.The adsorption process conformed to the Langmuir isotherm model and the pseudo-second-order kinetics model.The adsorption of Pb2+by N-MCM-41 was a spontaneous and endothermic process.Adsorption mechanism analyses suggested that functional groups on N-MCM-41 had strong coordination ability with Pb2+to improve the adsorption capacity.The synthesized N-MCM-41 adsorbent exhibited excellent reusability in five regeneration cycles.Overall,this study showed that the N-MCM-41 had good application prospect to remove Pb2+ from aqueous solution.

Mito-TEMPO inhibits the activation of BV2 microglia induced by lead exposure by reducing mitochondrial damage / 神经解剖学杂志

Objective:To explore the mechanism of Mito-TEMPO inhibiting the activation of BV2 microglia induced by lead(Pb)exposure.Methods:Mouse microglia BV2 were cultured in vitro.The effects of different concentrations of lead exposure on the viability of BV2 cells were determined by MTT colorimetric method,and a model of lead expo-sure was developed and intervened with Mito-TEMPO antioxidant.Immunofluorescence staining was used to detect the expression of M1 activation marker CD86 protein.Enzyme-linked immunosorbent assay was used to detect the expression of pro-inflammatory factors interleukin-1 β(IL-1β),tumor necrosis factor α(TNF-α),interleukin-6(IL-6).Mito-chondrial superoxide indicator(MitoSOX)staining was used to detect the level of mitochondrial oxidative stress.JC-1 staining was used to detect mitochondrial membrane potential.The respiratory ability of mitochondria was detected by cell energy metabolism analysis system(O2k).Results:Compared with the control group,the expression of CD86 protein,the levels of pro-inflammatory cytokines IL-1β,TNF-α and IL-6 in BV2 cells increased significantly,the level of oxidative stress in mitochondria increased significantly,and the mitochondrial membrane potential and respiratory ability decreased significantly in lead exposed group.Mito-TEMPO treatment significantly reduced the oxidative stress and functional damage of mitochondria in BV2 cells,and significantly inhibited the M1 activation level of BV2 cells.Conclusion:The results show that Mito-TEMPO treatment can reverse the M1 activation of BV2 cells induced by lead exposure,and the specific mechanism may be related to the reduction of mitochondrial oxidative stress and dysfunction by Mito-TEMPO.

Reconstruction of "Public" Ethic in Health Care under the Strategy of Healthy China / 中国医学伦理学

The Healthy China Strategy launched by China is not only a practical policy, but also an ethical revolution in the field of health. Under the Healthy China Strategy, the health field and its sub-field health care are defined as areas with "public" ethics as the fundamental ethical principles. Reconstructing the health care with "public" ethics should get rid of the health care oriented market lead and technical lead, and return to its "public" nature. In terms of concrete realization, the state and the government need to be the power backing of the "public" ethics of the health and medical care, the reconstructing must be leaded by Chinese Communist Party, and the fundamental realization of the "public" ethics of the health and medical care should take the institutions as the fundamental approach.

Structure-based development of potent and selective type-II kinase inhibitors of RIPK1

Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) functions as a key regulator in inflammation and cell death and is involved in mediating a variety of inflammatory or degenerative diseases. A number of allosteric RIPK1 inhibitors (RIPK1i) have been developed, and some of them have already advanced into clinical evaluation. Recently, selective RIPK1i that interact with both the allosteric pocket and the ATP-binding site of RIPK1 have started to emerge. Here, we report the rational development of a new series of type-II RIPK1i based on the rediscovery of a reported but mechanistically atypical RIPK3i. We also describe the structure-guided lead optimization of a potent, selective, and orally bioavailable RIPK1i, 62, which exhibits extraordinary efficacies in mouse models of acute or chronic inflammatory diseases. Collectively, 62 provides a useful tool for evaluating RIPK1 in animal disease models and a promising lead for further drug development.

Inhibitory effect of lead on GABA A receptor-mediated currents and GABAergic synaptic transmission in rat cortical neurons / 中国药理学与毒理学杂志

OBJECTIVE To investigate the inhibitory effect and mechanism of lead(Pb2+)on γ-amino-butyric acid(GABA)A receptor-mediated currents(IGABA)and GABAergic synaptic transmission in rat cortical neurons.METHODS ①The cortical neurons from 0 d Sprague Dawley(SD)rats were cultured for experiments.The cultured cells(7-14 d)were recorded using the patch-clamp technique to analyze the effects of Pb2+ at different concentrations(1,5,10,50 and 100 μmol·L-1)on IGABA induced by GABA 100 μmol·L-1.② The effects of Pb2+ 50 μmol·L-1 on IGABA induced by GABA at different concentrations(1,10,50,100,500 and 100 μmol·L-1)were detected.③Brain slices(350 μm)were prepared from SD rats(15-19 d).The spontaneous inhibitory post-synaptic currents(sIPSCs),miniature inhibitory post-synaptic currents(mIPSCs)and current injection-induced action potential(AP)were recorded to detect the effects of Pb2+ 10 μmol·L-1 on the amplitude and frequency of sIPSCs and mIPSCs,and the frequency of AP.RESULTS ①Pb2+ inhibited IGABA in a concentration-dependent manner,and IC50 was(68±20)μmol·L-1.②Pb2+ also suppressed the maximum current induced by GABA(P<0.01),with a significant increase of the GABA′s EC50 from(20±6)μmol·L-1 to(87±39)μmol·L-1,indicating that Pb2+ might inhibit IGABA in a non-competitive mechanism.③Pb2+ 10 μmol·L-1 inhibited the frequency(P<0.01)rather than the ampli-tude of sIPSCs reversibly,but had no effect on eigher the frequency or amplitude of mIPSCs.In addi-tion,Pb2+ decreased the frequency of evoked AP by current injection(P<0.01)and reduced the overall excitability of rat cortical neurons.CONCLUSION Pb2+ can significantly inhibit IGABA in primary cultured neurons.In the brain slice experiment,Pb2+ may affect sIPSCs frequency by inhibiting the AP of cortical neurons,suggesting that there are different intrinsic mechanisms through which Pb2+ inhibits both IGABA in primary cultured neurons and the frequency of sIPSCs in brain slice neurons,which points to the complexity of the mechanism of Pb2+ poisoning.

Application of a comprehensive index method for occupational health risk assessment in lead-acid battery enterprises / 中国职业医学

ObjectiveTo explore the application effect of using the comprehensive index method for occupational health risk assessment in the lead-acid battery enterprises. Methods Convenient sampling method was used to select two lead-acid battery enterprises A and B in Jiangsu Province, with eight key positions including ball grinding, plate casting, pasting, plate coating, plate grinding, plate slicing and brushing, welding and acid charging as the research subjects. Worksite survey of occupational health was conducted in these two lead enterprises, and the levels of lead smoke, lead dust and sulfuric acid in the key positions were detected. The health risk of occupational hazards in the eight key positions was evaluated by a comprehensive index method. Results The time-weighted average concentration (CTWA) of lead smoke in plate casting and welding positions of enterprise A, the CTWA of lead dust in plate grinding and plate slicing and brushing positions of enterprise A, the CTWA of lead dust in plate grinding position of enterprise B, the CTWA of lead smoke in welding position of enterprise B were exceeded national occupational exposure limits. The risk assessment results of the plate casting, welding, plate grinding and plate slicing and brushing positions were moderate risk, while other positions were low risk in enterprise A. The risk assessment results of the plate grinding and welding positions were moderate risk, while other positions were low risk in enterprise B. Conclusion The results of risk assessment by the comprehensive index method were consistent with the results of occupational hazard factors detection. The comprehensive index method could well evaluate the occupational health risks of lead-acid battery enterprises.

Intervention effect of HSP60 on learning and memory impairment induced by combined exposure to lead and hypertension in mice / 中国职业医学

ObjectiveTo investigate the intervention effect of heat shock protein 60 (HSP60) on learning and memory impairment induced by combined exposure to lead and hypertension in mice, and the relative mechanism of triggering receptor expressed on myeloid cells 2 (TREM2). Methods Specific pathogen-free C57BL/6J male mice were randomly divided into control group, hypertension group, lead-exposed group and lead-exposed + hypertension group, or into control group, heat shock protein 60 (HSP60) control group, lead-exposed + hypertension group and HSP60 intervention group, with 10 mice in each group. Mice of hypertension group and lead-exposed + hypertension group were intraperitoneally injected with angiotensin Ⅱ at a dose of 0.5 mg/(kg·d) for seven consecutive days to induce hypertension model. Mice of the lead-exposed group, lead-exposed + hypertension group, and HSP60 intervention group were given lead acetate drinking water with a mass concentration of 250.0 mg/L, while mice in the control group, hypertension group, and HSP60 control group were given purified water for 12 weeks. Mice of the HSP60 control group and HSP60 intervention group were intraperitoneally injected with a solution of HSP60 at a dose of 4 mg/kg body weight, every other day for a total of three times at the 12th week. The learning and memory ability of mice was detected using the Morris water maze test. The enzyme-linked immunosorbent assay was used to detect the levels of interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) in the hippocampal tissues of the mice. The relative expression of ionized calcium binding adaptor molecule-1 (IBA1) and TREM2 protein in the hippocampus of mice was detected using Western blot. Results i) The number of platform crossings of the mice in the hypertension group and the lead-exposed group was lower than that in the control group (both P<0.05). The escape latency of the mice on the third day was longer and the number of platform crossings was lower in the lead-exposed + hypertension group compared with the control group, hypertension group and lead-exposed group (all P<0.05). The levels of IL-1β, IL-6, and TNF-α in the hippocampus of the other three groups increased compared with the control group (all P<0.05). The relative expression of IBA1 protein in the hippocampus of lead-exposed group and lead-exposed + hypertension group increased (all P<0.05), while the relative protein expression of TREM2 decreased compared with the control group (all P<0.05). The levels of IL-1β, IL-6, TNF-α, and the relative protein expression of IBA1 protein in the hippocampus of the lead-exposed+hypertension group were higher (all P<0.05), and relative expression of TREM2 protein was lower (P<0.05) than those in the hypertension group. The level of TNF-α and the relative expression of IBA1 protein in the hippocampus of lead-exposed+hypertension group were higher than those in lead-exposed group (all P<0.05). ii) The escape latency of mice in the lead-exposed + hypertension group was longer than that in the control group (P<0.05), and the number of platform crossings was fewer than that in the control group (P<0.05). The escape latency of mice in the HSP60 intervention group was shortened (P<0.05), the number of platform crossings increased (P<0.05), and the levels of IL-1β, IL-6, TNF-α and relative expression of IBA1 protein decreased in the hippocampus (all P<0.05), while the relative expression of TREM2 protein increased (P<0.05) compared with the lead-exposed+hypertension group. Conclusion Combined exposure of lead and hypertension has a synergistic effect on learning and memory impairment in mice. The mechanism may be related to the inhibition of TREM2 expression by lead in the hippocampus of hypertensive mice and aggravating the neuroinflammatory response. Intervention with TREM2 receptor agonist HSP60 can alleviate learning and memory impairment in mice exposed to lead and hypertension by up-regulating TREM2 expression in the hippocampus.

Research progress on cognitive dysfunction induced by occupational noise and combined exposure to heavy metals / 中国职业医学

Exposure to occupational noise and heavy metals are common occupational hazards in workplaces. Occupational noise exposure not only leads to noise-induced hearing loss but also cognitive dysfunction. Exposure to common heavy metals such as lead, manganese, and cadmium during work is closely related to cognitive dysfunction in workers. Combined exposure to noise and heavy metals is common in workplaces. However, current research on the combined effects of exposure to occupational noise with lead or manganese on workers' cognitive function is not comprehensive or systematic. The method for cognitive dysfunction identification varies, leading to a lack of comparability. And the causality between occupational exposure and cognitive dysfunction in workers has not been clarified. Therefore, studying the cognitive dysfunction due to combined exposure to noise and common heavy metals is of great significance for workers' occupational health. In the future, it is necessary to unify the method for cognitive dysfunction identification and conduct systematic and comprehensive research on the effects, mechanisms, and combined effects of exposure to occupational noise with lead, manganese, cadmium, and other heavy metals on workers' cognitive dysfunction, to ensure the occupational health rights and interests of workers.

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.

Integridad Del ADN Espermático Y La Toxicidad Reproductiva Del Nitrato De Plomo En Ratones Machos Adultos

Introducción: La toxicidad del plomo se ha relacionado a diferentes patologías en humanos y varias evidencias sugieren una fuerte relación con el daño observado sobre la función reproductiva en humanos y roedores. Método: Se proporcionó a ratones una dosis única de nitrato de plomo (NP) (50mg/kg/pc), los cuales fueron eutanizados siete días postinyección con el objetivo de evaluar los espermatozoides que han salido de los túbulos seminíferos y están en tránsito por el epidídimo; además, se evaluó la fragmentación del ADN espermático mediante el ensayo tunel. Resultados: La disminución del peso corporal en ratones, tratados con NP (p 0,05); de igual manera, los valores fisiológicos como conteo y movilidad espermática no disminuyeron con el tratamiento (p > 0.05). El tránsito y maduración de los espermatozoides en el epidídimo no sería afectado por el NP, y al no observar aumento en la fragmentación del ADN espermático en el grupo tratado (p > 0,05), la protaminación espermática estaría cumpliendo su rol protector sobre el material genético murino, por lo que no hubo daños genotóxicos por el NP. Conclusión: La administración intraperitoneal de 50mg/kg/pc de NP, por siete días, no causa toxicidad sistémica ni efecto en la espermatogénesis en ratón.

Introduction: Lead toxicity has been linked to different diseases in humans and several evidences suggest a strong relationship with the observed damage on reproductive function in humans and rodents. Methods: Mice were given a single dose of lead nitrate (NP) (50mg/kg/bw), which were euthanized seven days post-injection with the aim of evaluating sperm to come out from the seminiferous tubules and are in transit through the epididymis. Also, the Tunel test was done to evaluate the sperm DNA fragmentation. Results: The decrease in body weight in mice treated with ln (p 0.05), in the same way physiological values such as sperm concentration and motility didn´t decrease with the treatment (p > 0.05). Transit and sperm maturation in the epididymis would not be affected by the ln, and because we did not observe increased sperm DNA fragmentation in the treated group (p > 0.05), sperm protamination would be fulfilling its protective role on murine genetic material avoiding genotoxic damage by ln. Conclusion: The intraperitoneal administration of 50mg/kg/pc of ln for seven days does not cause systemic toxicity or effect on spermatogenesis in mice.

Metal Exposure in Arica, Chile: Examining Toxic Elements / Análisis de exposición a metales en Arica, Chile: niveles de elementos tóxicos

BACKGROUND: Bioaccumulation of toxic metals in the population is associated with adverse health effects. Although some elements are essential for humans, high levels of exposure can be dangerous. OBJECTIVE: To describe the levels of Inorganic Arsenic (AsIn), Cadmium (Cd), Chromium (Cr), and Mercury (Hg) in urine, and Lead (Pb) in blood in the population of Arica, Chile. METHODOLOGY: Descriptive study. Beneficiaries of the Health Surveillance Program of Law 20.590 in sites of higher risk of exposure in the commune of Arica were considered eligible. The results of biological samples to measure their concentrations of AsIn, Cd, Cr, Hg in urine, and Pb in blood between August 2016 and May 2021 are described. RESULTS: 9520 samples from a population with a mean age of 40.5 years were studied. 4.21% of the adult population and 6.57% of the children had AsIn values above 35 μg/L, while at least 95 % of the total samples had levels below 33 μg/L. At least 90 % of the samples had Cd levels below 1.1 μg/L, and 8.44 % had Cd levels above 2 μg/L, higher in males (11.67%). There were no values above the reference in children. 99.77% and 99.33% had Cr and Pb values below the reference limit, respectively (using the lowest reference range established by Chile Ministry of Health (MINSAL) < 5 μg/L). Children did not present risk values for Cr, and 0.16% presented Pb concentrations between 5-10 μg/dL. All samples presented Hg concentrations below risk levels (< 10 μg/L). CONCLUSIONS: The results of this study suggest that a small percentage of the samples analyzed in the beneficiary population of Arica register metal concentration levels above national reference levels established by MINSAL, mainly AsIn, Cd, and Pb. It is essential to continue biomonitoring to reduce and prevent exposure to these metals, which can have harmful effects on human health.

ANTECEDENTES: La bioacumulación de metales en la población está asociada a efectos adversos y pueden ser peligrosos. OBJETIVO: Describir los niveles de Arsénico Inorgánico (AsIn), Cadmio (Cd), Cromo (Cr), Mercurio (Hg) y Plomo (Pb) en la población de Arica, Chile. MATERIALES Y MÉTODOS: Estudio descriptivo. Se incluyeron todas las personas beneficiarias del Programa de Vigilancia de Salud de la Ley 20.590 en sitios de riesgo de mayor exposición en la comuna de Arica entre agosto 2016 y mayo 2021. RESULTADOS: Se estudiaron 9.520 muestras provenientes de una población con una edad media de 40.5 años. 4.21% de la población adulta y el 6.57% de los niños presentaron valores de AsIn superiores a 35 μg/L y al menos el 95% de las muestras totales tenía niveles inferiores a 33 μg/L. Más del 90 % de las muestras tuvieron niveles de Cd menores a 1.1 μg/L y un 8.44% registró niveles de Cd superiores 2 μg/L. El 99.77% y 99.33% exhibieron valores normales de Cr y Pb, respectivamente. Todas las muestras presentaron concentraciones de Hg por debajo de los niveles de riesgo (< 10 μg/L). CONCLUSIONES: Los resultados sugieren que un porcentaje pequeño de la población de Arica registra niveles de concentración de metales por sobre niveles de referencia nacional establecidos por el Ministerio de Salud de Chile, principalmente de AsIn, Cd y Pb. Es importante continuar con la vigilancia para reducir y prevenir la exposición a estos metales, que pueden generar efectos nocivos en la salud humana.

Effects of lead exposure on blood pressure in 665 lead workers / 公共卫生与预防医学

Objective To investigate the effect of lead exposure on blood pressure of lead workers. Methods A total of 665 lead workers from some lead-acid battery enterprises in Wuhan were selected as the lead exposure group, and 708 ordinary workers without lead exposure were selected as the control group. The blood pressure in the workers of both groups was measured. The blood lead concentrations were measured in the lead-exposed group. The independent samples t-test was used to compare the blood pressure between the two groups. Linear regression model was used to analyze the relationship between the blood lead concentration and the blood pressure in the lead-exposed group. Logistic regression analysis was used to analyze the relationship between the risk of hypertension and blood lead concentration in lead-exposed group. Results The mean values of systolic blood pressure, diastolic blood pressure and pulse in the lead exposure group were significantly higher than those in the control group, and the difference was statistically significant (P0.05). Linear regression analysis revealed that blood lead concentrations were significantly correlated with both systolic and diastolic blood pressure in the lead exposure group. For each increase of 1μg/L of blood lead concentration in the lead exposure group, the systolic blood pressure of lead workers increased by 0.011 mmHg, and the diastolic blood pressure increased by 0.007 mmHg. Logistic regression analysis found that men in the lead-exposed group had a higher risk of hypertension than women. The older the age and the higher the blood lead concentration, the higher the risk of development of hypertension. Conclusion There is a positive correlation between the blood lead concentration and the systolic and diastolic blood pressure in lead workers. The older the lead worker, the higher the risk of developing high blood pressure. The higher the lead concentration in lead workers, the higher the risk of developing high blood pressure.

Risk assessment of dietary lead exposure in Shanghai residents over 15 years old / 上海预防医学

ObjectiveTo investigate the risk of dietary lead exposure in residents aged 15 years and above in Shanghai. MethodsBased on the dietary consumption survey of residents aged 15 years and above in spring 2012 and the monitoring data of food lead contamination in Shanghai from 2020 to 2021， the dietary exposure level was assessed using the point assessment method and compared with the provisional weekly tolerable intake （PTWI） to assess the exposure risk. ResultsThe overall detection rate of lead in 9 commonly consumed food categories by residents in Shanghai was 56.82%， with a total excess rate of 0.23%. The average weekly dietary lead exposure （by body weight） of residents was 2.979 4 μg·kg⁻¹. The top three dietary lead contributing factors were vegetables （30.69%）， cereals （28.88%）， and aquatic products （11.12%）. The average weekly dietary lead exposure （by body weight） of residents in urban， suburban， and rural areas were 3.282 5， 2.979 5 and 2.478 0 μg·kg⁻¹， respectively. The food with the highest contribution rate of dietary lead exposure in these regions was vegetables， with contribution rates of 33.65%， 29.69%， and 25.22%， respectively. The average weekly dietary lead exposure （by body weight） of male and female residents was 3.077 7 and 2.881 5 μg·kg⁻¹， respectively， with vegetables being the main source of dietary lead， contributing 30.03% and 31.39%， respectively. The average weekly dietary lead exposure （by body weight） of residents aged 15‒， 45‒， and ≥60 years old was 3.084 2，3.009 9 and 2.874 4 μg·kg⁻¹， respectively. The food with the highest contribution rate of dietary lead exposure in these groups was vegetables， contributing 27.12%， 32.10%， and 32.26%， respectively. ConclusionThe dietary lead exposure of Shanghai residents aged 15 years and above is at an acceptable level， and the vegetables， cereals， and aquatic products with high contribution rates need to be supervised more closely.

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.

Research progress of the screening and generation of lead compounds based on artificial intelligence model / 中国药科大学学报

@#Excellent lead compounds have a profound influence on drug development and can improve the success rate of product launch. It is expensive and time-consuming to discover lead compounds by traditional methods, yet artificial intelligence (AI) can discover good lead compounds efficiently.This article systematically summarizes the research progress of obtaining lead compounds through the screening and generation models of AI, classifies different models according to the type of information input, focuses on drug repurposing by screening model and multi-objective drug design by generation model, and discusses the development prospect of AI in the research field of lead compounds, aiming to provide new research ideas for the application of AI in lead compounds.

Research progress of feature-based deep learning for predicting compound-protein interaction / 中国药科大学学报

@#The prediction of compound-protein interaction (CPI) is a critical technological tool for discovering lead compounds and drug repurposing during the process of drug development.In recent years, deep learning has been widely used in CPI research, which has accelerated the development of CPI prediction in drug discovery.This review focuses on feature-based CPI prediction models.First, we described the datasets, as well as typical feature representation methods commonly used for compounds and proteins in CPI prediction.Based on the critical problems in modeling, we discussed models for CPI prediction from two perspectives: multimodal features and attention mechanisms.Then, the performance of 12 selected models was evaluated on 3 benchmark datasets for both classification and regression tasks.Finally, the review summarizes the existing challenges in this field and prospects for future directions.We believe that this investigation will provide some reference and insight for further research on CPI prediction.

Association between exposure to lead, cadmium, and arsenic and blood pressure in workers from a smelter / 环境与职业医学

Background Occupational exposure to lead, cadmium, or arsenic is a potential risk factor for blood pressure elevation. Current studies mainly focus on the relationship between a single metal and blood pressure. However, mixed metal exposure often exists in the actual working environment, and the interactive effects of polymetallic interactions on blood pressure and the dose-effect relationship remain unclear yet. Objective To explore the influence proportion of occupational exposure to lead, cadmium, or arsenic on blood pressure and their interactive effects. Methods From January to December 2021, workers from a smelter in southern China were selected. Demographic characteristics, height, weight, and blood pressure of workers were collected through questionnaire and physical examination. At the same time, their urine samples were collected and the levels of urinary lead, urinary cadmium, and urinary arsenic were detected by inductively coupled plasma mass spectrometry, and corrected by urinary creatinine (Cr). Linear regression and logistic regression were used to analyze the relationship between urinary lead, cadmium, and arsenic and blood pressure. Weighted quantile sum (WQS) regression was applied to evaluate the dose-effect relationship between urinary lead, cadmium, and arsenic exposures and blood pressure and the effect weight of each metal on blood pressure. Generalized linear regression and additive/multiplicative scaling were used to identify interactive effects of the three metals on blood pressure. Results A total of 1075 workers were included in this study, with a mean age of (44.68±5.11) years and mean working seniority of (24.66±5.23) years. There were 891 males (88.9%) and 184 were females (17.1%); 24.7% workers were drinkers and 45.7% workers were smokers; 302 workers (28.1%) reported hypertension and 37 of them were taking antihypertensive drugs. The P50 (P25, P75) levels of urinary lead, urinary cadmium, and urinary arsenic were 6.11 (3.71, 11.08), 3.88 (2.68, 5.44), and 26.04 (19.99, 35.11) μg·g−1, respectively. After adjusting for gender, age, working seniority, body mass index, smoking, drinking, and the usage of antihypertensive drugs, systolic and diastolic blood pressure increased by 0.772 and 0.418 mmHg respectively for 10% increase in lead, cadmium, and arsenic mixed exposure. Urinary cadmium, among the three single exposures, had the greatest effect on systolic and diastolic blood pressure, weight (w)=0.523 and 0.551 respectively. The interaction of urinary lead and urinary cadmium was positively correlated with the occurrence of hypertension, multiplicative interaction OR (ORint)=1.88 (95%CI: 1.09, 3.63), attributable proportion due to interaction (AP)=1.19 (95%CI: 0.40, 8.18). Conclusion This study shows that mixed exposure to lead, cadmium, and arsenic has a positive relationship with blood pressure, in which cadmium plays a major role. Co-exposure to lead and cadmium has a positive interactive effect on hypertension development and systolic blood pressure elevation.

Association between combined exposure of heavy metals and biomarkers of early renal damage in occupational population / 中国职业医学

Objective: To investigate the effect of combined exposure to four heavy metals (lead, cadmium, arsenic, mercury) on early kidney injury in occupational population. Methods: A total of 384 workers exposed to combined heavy metals in a non-ferrous metal smelting plant in Guangdong Province were selected as the research subjects using judgment sampling method. The levels of blood lead, urinary cadmium and urinary arsenic were detacted by inductively coupled plasma mass spectrometry, while urinary mercury levels were measured using cold atomic absorption spectroscopy (acidic tin chloride reduction method). The levels of biomarkers such as urinary β2-microglobulin (β2-MG), kidney injury molecule-1 (Kim-1) and neutrophil gelatinase-associated lipocalin (NGAL) were detected by enzyme-linked immunosorbent assay. Spearman correlation analysis, linear regression, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) models were used to analyze the association between the exposure to the four heavy metals and early kidney injury biomarkers. Results: The median of blood lead, urinary cadmium, urinary arsenic and urinary mercury were 0.47 μmol/L and 4.450, 27.790 and 0.520 μg/gCr, respectively. The median of urinary β2-MG, Kim-1 and NGAL were 62.960, 1.130 and 18.150 μg/gCr, respectively. Spearman correlation analysis showed that urinary levels of β2-MG, Kim-1, and NGAL were weakly correlated with blood lead and urinary mercury levels (all P<0.01), but not correlated with urinary cadmium and urinary arsenic (all P>0.05). The results of multiple linear regression analysis showed that urinary mercury was positively correlated with urinary β2-MG, Kim-1 and NGAL (all P<0.01), urinary arsenic was positively correlated with urinary β2-MG level (P<0.01), and blood lead was negatively correlated with urinary β2-MG and Kim-1 (all P<0.05). The WQS regression analysis showed that the combined effect of the four heavy metals was positively correlated with urinary β2-MG, Kim-1 and NGAL (all P<0.01), with mercury having the highest impact and lead the lowest. BKMR model analysis showed the increasing trend in urinary β2-MG, Kim-1 and NGAL with the increasing levels of the combined exposure to the four heavy metals. Urinary β2-MG, Kim-1 and NGAL decreased when urinary mercury level increased from the 25th percentile to the 75th percentile and the other metals were correspondingly fixed at a certain level. When the blood exposure levels of other metals remained at the corresponding median levels, urinary β2-MG, Kim-1 and NGAL levels were positively correlated with urinary arsenic level, but no significant linear dose-response relationship was observed with the other three heavy metals. Conclusion: sLead, arsenic, and mercury are independently associated with early kidney injury biomarkers in occupational population from non-ferrous metal smelting. The four heavy metals had positive combined effects on urinary β2-MG, Kim-1 and NGAL, with mercury having the greatest impact.

The expression of adhesion molecules in Z310 cells induced by combined exposure to black carbon and lead / 中国职业医学

Objective: To investigate the effects of combined exposure to black carbon and lead on the expression of cell adhesion molecules and their regulating microRNAs (miRNAs) in the rat choroid plexus epithelial Z310 cells. Methods: i) Z310 cells were randomly divided into control group, black carbon exposure group, lead exposure group and combined exposure group. The lead exposure group and black carbon exposure group were treated with 10 μmol/L lead acetate and 10 mg/L black carbon, respectively, and the combined exposure group was treated with both in the above doses. After 12.0 hours, the expressions of intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and mucosal vascular addressin cell adhesion molecule-1 (MAdCAM-1) in Z310 cells was detected by Western blotting. The expression of miR-326, miR-328-3p and miR-542-3p which regulated ICAM-1 was detected by real-time fluorescent quantitative polymerase chain reaction. ii) Z310 cells or Z310 cells transfected with miRNA-326 mimic were randomly divided into control group, miRNA-326 transfection control group, combined exposure group and miRNA-326 transfection combined exposure group. Cells in the two control groups were not treated. The two combined exposure groups were treated with 10 mg/L black carbon and 10 μmol/L lead acetate for 12.0 hours. The expression of ICAM-1 was detected by Western blotting. Results: i) The relative expression of ICAM-1, VCAM-1 and MAdCAM-1 in the cells of black carbon exposure group and ICAM-1 in the lead exposure group was higher than those in the control group (all P<0.05). The relative expression of ICAM-1 and MAdCAM-1 in the combined exposure group was higher than those in the other three groups (all P<0.05). The relative expression of VCAM-1 in cells of combined exposure group was higher than those in the control group and lead exposed group (all P<0.05). The relative expression of miR-326 in cells of the lead exposure group and black carbon exposure group was lower than those in the control group (all P<0.05). The relative expression of miR-326 in the combined exposure group was lower than that in the other three groups (all P<0.05). There was no significant difference between miR-328-3p and miR-542-3p in the four groups (all P>0.05). ii) The relative expression of ICAM-1 in cells of the miR-326 transfection control group cells was lower than that in the control group (P<0.05), while in the cells in the combined exposure and miRNA-326 transfection combined exposure group, it was higher than that in the control and miRNA-326 transfection control groups (all P<0.05), and lower in the miRNA-326 transfection combined exposure group than in the combined exposure group (P<0.05). Conclusion: Black carbon or lead exposure can upregulate the expression of ICAM-1, VCAM-1 and MAdCAM-1 in Z310 cells. Black carbon and lead combined exposure lead to a synergistic effect on upregulation of ICAM-1 and MAdCAM-1 expression, particularly ICAM-1. The combined exposure of black carbon and lead may upregulate the expression of ICAM-1 by downregulating the expression of miR-326.