Arsenic species were quantified to further explore the biotransformation of arsenic and better explain the potential health risks. In this research, the levels of six arsenic species (AsB, AsC, MMA, DMA, As3+, and As5+) were determined in 160 squid samples by HPLC-ICP-MS. AsB was the most predominant speciation in squid tissues. The arsenic species, including AsB, AsC, and MMA, were found in all samples, followed by DMA (49.38

6-Benzylaminopurine (6-BAP) is an important ingredient in production of "toxic bean sprouts". In order to assess health risk from 6-BAP residue in bean sprouts on a large sample size and wide sample range among large survey population, 6-BAP was detected in 149 out of 1 494 bean sprouts samples collected in 2016-2020 in Shandong Province of China. High performance liquid chromatography-tandem mass spectrometry was used for analysis. Those 10.0 % samples contained 6-BAP residue above the maximum residue limit (MRL) and the average level was 0.007 mg kg-1. Hazard quotient (HQ) of 6-BAP was 0.0 % for the general population and 0.2 % for consumers. The daily exposure of 6-BAP was accounted for 0.0 % of the the acceptable daily intake (ADI) and the estimated daily intake (EDI) of all subjects surveyed was below ADI. From the perspective of public health, the occurrence of 6-BAP residue in bean sprouts could not pose a serious health risk problem. Strict regulations on the management of 6-BAP residue in bean sprouts and human health risk assessment should be recommended.

The extensive utilization of pesticides results in their frequent detection in aquatic environments, often as complex mixtures, posing risks to aquatic organisms. The hook snout carp (Opsariichthys bidens) serves as a valuable bioindicator for evaluating the impacts of environmental pollutants in aquatic ecosystems. However, few studies examined the toxic effects of pesticides on O.bidens, let alone the characterization of the combined effects resulting from their mixtures. This study aims to elucidate the toxic effects of beta-cypermethrin and pyraclostrobin on O.bidens, individually and in combination, focusing on biochemical, transcriptional, and molecular responses. By organizing and analyzing the toxicogenomic databases, both pesticides were identified as a contributor to processes such as apoptosis, oxidative stress, and inflammatory responses. The acute toxicity test revealed comparable acute toxicity of beta-cypermethrin and pyraclostrobin on O.bidens, with LC50 being 0.019 and 0.027 mg/L, respectively, whereas the LC50 decreased to 0.0057 and 0.0079 mg/L under the combined exposure, indicating potential synergistic effects. The activities of enzymes involved in oxidative stress and detoxification were significantly altered after exposure, with superoxide dismutase (SOD) and catalase (CAT) increasing, while malondialdehyde (MDA) levels decreased. The activity of CYP450s was significantly changed. Likewise, the expression levels of genes (mn-sod, p53, esr, il-8) associated with oxidative stress, apoptosis, endocrine and immune systems were significantly increased. Combined exposure to the pesticides significantly exacerbated the aforementioned biological processes in O.bidens. Furthermore, both pesticides can modify protein activity by binding to the surface of SOD molecules and altering protein conformation, contributing to the elevated enzyme activity. Through the investigation of the synergistic toxic effects of pesticides and molecular mechanisms in O.bidens, our findings highlight the importance of assessing the combined effects of pesticide mixtures in aquatic environments.

In this study 13 heavy metals were analysed in representative livestock meat, poultry meat, livestock offal and poultry offal samples (20 per category) from marketplaces and retail stores in 16 cities in Shandong province, China. The investigated heavy metals were Cu, Cr, V, Ni, As, Se, Sn, Cd, Pb, Sb, Mn, Ba and Hg. Results revealed mean levels of total heavy metals in meat and offal of 1.56 mg/kg and 39.8 mg/kg, respectively. Cu, Cr, Mn, Ni, Se, Ba and Pb were found in all samples (100%), followed by Hg (95.0%), V (91.3%), Sn (73.8%), Cd (51.3%), As (21.3%) and Sb (11.3%). Hazard Quotient (HQ) and Hazard Index (HI) values showed that high meat intake can cause potential health risks. Thus, continuous monitoring of health risks and trends of heavy metals in meat products is needed, both for food safety and consumer’s health.

Aflatoxin B-1 (AFB(1)) can induce serious liver toxicity in human. While completely avoiding AFB(1) exposure is difficult, dietary intake of natural products may be leveraged to mitigate its adverse health effects. The roots of Lepidium meyenii (Maca) is rich in beneficial polysaccharides. Here we first evaluated dietary safety of MPs and then investigated MPs mitigating effects on the liver toxicity of AFB(1). A 28-day sub-acute administration of Maca polysaccharides (MPs) demonstrated to be safe in mice at dose 0.2-1.2 g/kg.bw/day that significantly elevated mice stamina. Also, no toxicity was observed in human PC12 cells treated with MPs 25-100 mu g/mL which successfully alleviated cobalt-caused cell apoptosis by similar to 20%. In terms of anti-AFB(1) hepatoxicity function, MPs 0.4-1.6 g/kg.bw/day significantly alleviated liver tissue damage, lipid accumulation, ROS damage, NF-kappa B p65, secretion of cytokines such as IL-6 and TNF-alpha in AFB(1)-treated mice. Flow cytometry found that MPs treatment recovered the elevation of F4/80 in the primary macrophages of AFB(1)-treated mice. At molecular level, MPs treatment activated liver NRF-2/GPX/SOD anti-oxidant system. In human macrophage model, MPs restored the inflammatory AhR/STAT3 pathway and mRNA expressions of Tnf-a, Inos, Arg-1 disrupted by AFB(1). Our findings not only add to the current understanding on the toxicity mechanism of AFB(1), but also provide references to the development of dietary intervention strategy using MPs.

We examined the occurrence and levels of 19 legacy and emerging perand polyfluoroalkyl substances (PFASs) in 7 species of marine bivalve molluscs collected from four coastal cities of Shandong Province, China. Perfluorooctanoic acid (PFOA) was the most prevalent component, accounting for 68.1 % of total PFASs. The total PFASs in bivalve molluscs ranged from 0.86 to 6.55 ng/g wet weight, with the highest concentration found in Meretrix meretrix L. The concentration of total PFASs in bivalve molluscs showed the following trend: clams > scallops > oysters > mussels. Estimation on the human intake of PFASs from consumption of bivalve molluscs resulted in hazard ratios (HR) ranging from 0.12 to 6.40. Five of the seven species had HR >1, indicating high exposure risks associated with PFASs. Therefore, the occurrence of PFASs in marine biota is particularly concerning and further investigations on the sources of PFASs in Shandong are warranted.

Aflatoxin B1 (AFB1) is a major mycotoxin contaminant showing in the environment and foods. In this study, the molecular initiating events (MIEs) of AFB1-induced steatohepatitis were explored in mice and human cell model. We observed dose -dependent steatohepatitis in the AFB1-treated mice, including triglyceride accumulation, fibrotic collagen secretion, enrichment of CD11b + and F4/80+ macrophages/Kupffer cells, cell death, lymphocytes clusters and remarkable atrophy areas. The gut barrier and gut-microbiota were also severely damaged after the AFB1 treatment and pre -conditioned colitis in the experimental mice aggravated the steatohepatitis phenotypes. We found that macrophages cells can be pro -inflammatorily activated to M1 -like phenotype by AFB1 through an AHR/TLR4/p-STAT3 (Ser727)-mediated mitochondrial oxidative stress. The phenotypes can be rescued by AHR inhibitors in the mice model and human cell model. We further showed that this signaling axis is based on the cross -talk interaction between AHR and TLR4. Gene knock -up experiment found that the signaling is dependent on AFB1 ligand-binding with AHR, but not protein expressions of TLR4. The signaling elevated NLRP3 and two immune metabolic enzymes ICAM-1 and IDO that are associated with macrophage polarization. Results from intervention experiments with natural anti -oxidant and AHR inhibitor CH223191 suggest that the macrophage polarization may rely on AHR and ROS. Our study provides novel and critical references to the food safety and public health regulation of AFB1.

Pesticide residue was one of the stress factors affecting quality and safety of Chinese herbal medicines (CHMs). The present study was designed to investigate the occurrence and dietary exposure of 70 pesticide residues in 307 samples of CHMs, including 104 American ginseng, 100 Ganoderma lucidum (G. lucidum), and 103 Dendrobium officinale (D. officinale) in Shandong Province, China. The study revealed that a total of 29 pesticides were detected in the majority (92.5

Neurofibromatosis type 1 is a rare autosomal dominant genetic disorder, with up to 50% of patients clinically displaying skeletal defects. Currently, the pathogenesis of bone disorders in NF1 patients is unclear, and there are no effective preventive and treatment measures. In this study, we found that knockout of the NF1 gene reduced cAMP levels and osteogenic differentiation in an osteoblast model, and icariin activated the cAMP/PKA/CREB pathway to promote osteoblast differentiation of the NF1 gene knockout cell model by increasing intracellular cAMP levels. The PKA selective inhibitor H89 significantly impaired the stimulatory effect of icariin on osteogenesis in the NF1 cell model. In this study, an osteoblast model of NF1 was successfully constructed, and icariin was applied to the cell model for the first time. The results will help to elucidate the molecular mechanism of NF1 bone disease and provide new ideas for the clinical prevention and treatment of NF1 bone disease and drug development in the future.

目的 观察长期低剂量邻苯二甲酸二(2-乙基己基)酯[di(2-ethylhexyl)phthalate,DEHP]暴露及高脂喂养对小鼠脑组织氨基酸类神经递质和神经元的影响.方法 选择体质量16～18 g SPF级雌性C57BL/6J小鼠,适应性喂养1周,随机分为对照组(Con组)、DEHP组(DEHP组)、高脂组(HFD组)、DEHP暴露联合HFD喂养组(HFD+DEHP组).DEHP组和HFD+DEHP组小鼠经口给予50μg/kg DEHP,Con组、HFD组小鼠给予等体积溶剂,Con组、DEHP小鼠喂饲普通维持饲料,HFD组、HFD+DEHP组小鼠喂饲高脂饲料.第24周末,每组随机取8只小鼠脱臼处死,取脑组织制备匀浆,并采用高效液相色谱法检测脑组织氨基酸类神经递质水平;每组剩余4只小鼠经体内灌注固定,制备大脑冰冻切片,采用尼氏染色观察神经元的变化.结果 HFD+DEHP组大脑皮层GABA高于Con组、DEHP组,HFD组、HFD+DEHP组Glu/GABA低于Con组(P＜0.05);各组其他指标比较差异无统计学意义(P＞0.05).各组中脑中氨基酸类神经递质水平比较差异无统计学意义(P＞0.05).DEHP组、HFD组、HFD+DEHP组小脑Gly均高于Con组,HFD+DEHP组GABA高于Con组、DEHP组、HFD组(P＜0.05);各组其他指标比较差异无统计学意义(P＞0.05).与Con组相比,DEHP组、HFD组及HFD+DEHP组小鼠大脑神经元中尼氏体颜色变淡、着色颗粒稀疏,以HFD+DEHP组最为明显.结论 DEHP长期暴露和高脂饮食可破坏小鼠脑内氨基酸类神经递质的内稳态,导致神经元损伤.

Human exposure to aflatoxins (AFs) and zearalenone (ZEA) has not been sufficiently investigated. Here, we analyzed the exposure level and health risks posed by AFs (B1, B2, G1, G2) and ZEA through cooking oil consumption in Shandong, China. The individual daily consumption of cooking oil was calculated through 2745 questionnaires during 2017–2019. The average contamination levels of mycotoxins were estimated by examining 60 cooking oil samples. For the peanut oil, AFs ranged from <0.2 to 274 μg/kg, with a positive rate of 66.6

BackgroundHuman gut microbiota play a crucial role in the immune response of the host to respiratory viral infection. However, evidence regarding the association between the gut microbiome, host immune responses, and disease severity in coronavirus disease 2019 (COVID-19) remains insufficient.MethodsTo better comprehend the interactions between the host and gut microbiota in COVID-19, we conducted 16S rRNA sequencing and characterized the gut microbiome compositions in stool samples from 40 COVID-19 patients and 33 non-pneumonia controls. We assessed several hematological parameters to determine the immune status.ResultsWe found that the gut microbial composition was significantly changed in COVID-19 patients, which was characterized by increased opportunistic pathogens and decreased commensal bacteria. The frequency of prevalent opportunistic pathogens Enterococcus and Lactobacillus increased, especially in severe patients; yet the abundance of butyrate-producing bacteria, Faecalibacterium, Roseburia, and Anaerostipes, decreased significantly, and Faecalibacterium prausnitzii might help discriminate severe patients from moderate patients and non-pneumonia people. Furthermore, we then obtained a correlation map between the clinical characteristics of COVID-19 and severity-related gut microbiota. We observed a notable correlation between the abundance of Enterococcus faecium and abnormal neutrophil or lymphocyte percentage in all COVID-19 patients. Faecalibacterium was positively correlated with lymphocyte counts, while negatively correlated with neutrophil percentage.ConclusionThese results suggested that the gut microbiome could have a potential function in regulating host immune responses and impacting the severity or consequences of diseases.

Rare earth elements (REEs) can cause neoplasms, reduce bone density, affect children's intelligence, etc., and diet is an important way for the human body to absorb REEs. With the increasing use of REEs, the impact on human health is becoming more and more important. So, we used a probabilistic assessment method with Monte Carlo simulation to evaluate the dietary intake of REEs by residents of a large light rare earth mining area in Shandong Province. 16 REEs in 447 samples (including wheat, maize, dry beans, vegetables, fruits and eggs) were detected. The mean value of total REEs for all samples was 286.96 μg/kg, and of light rare earth elements (LREEs) was 270.18 μg/kg. Among of LREEs, Ce, La, Nd and Pr were dominant. The REEs content of different food categories showed that wheat, leafy vegetables and allium vegetables had higher content of REEs, melons vegetables, root vegetables, fruits and eggs had the lowest content. The mean dietary intake of rare earth oxides for the whole population was 4.20 μg/kg bw/d, wheat and vegetables (leafy vegetables, allium vegetables and root vegetables) were the main sources of REEs. Dietary intake estimates of REEs by age and gender did not exceed the acceptable daily intake which means implying no impact on human health.

Polychlorinated biphenyls (PCBs) are persistent organic pollutants, and the widespread use of PCBs has had adverse effects on human and animal health. This study experiment explored the effects of 2,3',4,4',5-pentachlorobiphenyl (PCB118) on the mammalian reproductive system. PCB118 was administered to pregnant mice from 7.5 to 12.5 days of gestation; F-1 mice were obtained and the reproductive system of F-1 male mice was examined. PCB118 damaged the reproductive system in male F-1 mice, as evidenced by negative effects on the testicular organ coefficient (testes weight/bodyweight), a decrease in the diameter of seminiferous tubules and a significant reduction in the anogenital distance in 35-day-old F-1 mice. In addition, methylation levels of genomic DNA were reduced, with reductions in the expression of the DNA methyltransferases DNMT1, DNMT3A and DNMT3B, as well as that of the epigenetic regulatory factor ubiquitin like with PHD and ring finger domains 1 (Uhrf1). Together, the results of this study provide compelling evidence that exposure of pregnant mice to PCB118 during primordial germ cell migration in the fetus affects the reproductive system of the offspring and decreases global methylation levels in the testis.

OBJECTIVE:To investigate the expression of S100β protein and mRNA of Schwann cells(SC) in sciatic nerves of 2, 5-hexanedione(HD) intoxicated rats.METHODS:Nine-week old SPF male Wistar rats were administered at daily dosing of 100 and 300 mg/kg by intraperitoneal injection for continuous 8 weeks(five times every week). Age-matched control rats received an equivalent volume of normal saline. Ten rats in each group were sacrificed and sciatic nerves were excised for S100β determination, with excised sciatic nerves from another three rats for morphological observation through electron microscope. At the end of the exposure, the other 8-week treated animals were allowed to naturally recover for 8 weeks and sciatic nerves were excised at the end of the test. S100β protein contents were determined by immunohistochemistry method, and mRNA expression was observed by real-time quantitative polymerase chain reaction(PCR).RESULTS:HD intoxication with 300 mg/kg was associated with severe neurological deficits of paralysis in hindlimbs, accompanied with evident movement gait abnormalities for 100 mg/kg dosage. The morphological abnormalities in myelin sheath of sciatic nerves were observed through electron microscope after HD-exposure. The S100β contents in 100 mg/kg and 300 mg/kg groups remained relatively unaffected with 92% and 79% of the control respectively after HD-intoxication, and a increase to 149%(P&lt;0. 05) and 119% after a recovery of 8 weeks was accompanied with. As to S100β mRNA, HD-intoxication was associated with decreased expression to 0. 65(P&lt;0. 05) and 0. 56 times(P&lt;0. 05) of the control, and 1. 46 and 0. 87 times for 8-week recovery individually.CONCLUSION:The S100β protein and mRNA levels were influenced by HD exposure, and the result suggested that S100β might be involved in HD-induced peripheral axonopathy.

目的 初步观察2,5-己二酮(HD)染毒大鼠中毒性周围神经病变时坐骨神经中神经细胞粘附因子(CNTF)蛋白与mRNA表达变化,为HD导致的感觉运动型周围神经病变的发生、发展、控制提供理论依据.方法 9周龄(体重280～310 g)SPF级Wistar雄性大鼠,分为3组,每组23只,经腹腔注射染毒给予HD,低剂量和高剂量组剂量分别为100和300 mg/(kg·d),连续8w,每周5次;对照组给予等体积生理盐水.处死各组10只动物并分离坐骨神经,采用免疫组化方法检测CNTF蛋白表达和实时定量PCR方法观察mRNA表达,另取3只分离坐骨神经用于电镜观察.其余30只动物停止染毒、自然恢复8 w后取材.结果 染毒后高剂量组动物第4 w起后肢热痛觉阈值升高,8 w后后肢全部瘫痪;低剂量组动物步态异常.电镜观察染毒组动物坐骨神经髓鞘厚薄不均等形态异常.染毒8 w时300 mg/(kg·d)剂量组中CNTF表达量下降至对照组62.6％(P＜0.01);染毒终止、恢复8w后100 mg/(kg·d)剂量组升高至176.8％(P＜0.01),300 mg/(kg·d)剂量组恢复至98.7％(P＞0.05).染毒8 w时,300 mg/(kg·d)剂量组RNA表达水平降低为0.54倍(P＜0.05);恢复8w后100 mg/(kg·d)剂量组升高至1.94倍(P＜0.05),300 mg/(kg·d)恢复至0.95(P＞0.05).结论 HD染毒大鼠中毒性周围神经病变时坐骨神经CNTF蛋白和mRNA表达发生变化,CNTF参与了正己烷中毒性周围神经病变发生.

目的 初步观察2,5-己二酮(2,5-hexanetione,HD)染毒大鼠中毒性周围神经病变时坐骨神经和大脑皮质中神经细胞粘附因子(neural cell adhesion molecule,NCAM)蛋白的表达变化.方法 9周龄(体重280～310 g)SPF级Wistar雄性大鼠分为3组,每组23只,每日经腹腔注射染毒给予HD(低剂量组100 mg/kg,高剂量组300 mg/kg),连续8周,每周5次,对照组给予等体积生理盐水.处死各组10只动物并分离、冻存坐骨神经和大脑皮质运动代表区,采用免疫组化方法检测NCAM的蛋白表达.另取3只分离坐骨神经用于电镜观察.剩余动物停止染毒、自然恢复8周后取材.结果 染毒后高剂量组动物第4周起动物后肢热痛觉阈值升高,染毒8周后高剂量组动物后肢全部瘫痪,低剂量组动物后肢肌力下降,步态异常.电镜观察染毒组动物坐骨神经髓鞘形态异常.对于坐骨神经,染毒8周时低、高剂量组中NCAM表达量分别为对照组的144％和85％,染毒终止、恢复8周后为166％(P＜0.05)和145％.对于大脑皮质,染毒8周时与染毒终止、恢复8周时各剂量组蛋白表达与对照组差异无统计学意义(P＞0.05).结论 HD染毒大鼠中毒性周围神经病变时坐骨神经NCAM蛋白表达发生变化,NCAM参与了中毒性周围神经病变发生.

促黑素细胞皮质素原/阿黑皮素(POMC)是促肾上腺皮质激素(ACTH)、β-内啡肽和促黑激素(MSH)等活性肽的前体,这些活性肽与体内某些相关受体结合共同参与许多重要的信号通路.有研究发现POMC基因甲基化与精神活性物质、抑郁障碍及非自杀性自伤(NSSI)行为等可能有关,从而在精神心理领域中越来越受到人们的关注.本文就POMC基因甲基化与精神心理疾病之间的研究进展进行综述.

OBJECTIVETo study the teratogenic effect caused by Xanthoceras sorbifolia Bunge seed on SD rats.METHODSThe experiments were performed in the groups of 2. 0, 4. 0 and 8. 0 g/kg, purified water negative control group and cyclophosphamide positive control group. On the 6 th to 15 th day of pregnancy, the SPF SD rats were exposed to Xanthoceras sorbifolia Bunge seed. All the rats were sacrificed on the day before delivery. Examination were performed on the bones stained by alizarin red and internal organs fixed with Bouins fluid.RESULTSMaternal body weight, weight gain, uterine fetal weight, net weigh, bed number, corpus luteum number, absorbing births number, live births number, still birth number and percentage and the abnormal rate of appearance, bone, internal organs of each dose group of Xanthoceras sorbifolia, there was no statistical significant difference between Bunge seed groups and negative control group.CONCLUSIONUnder the conditions of this experiment, the Xanthoceras sorbifolia Bunge seed had no maternal toxicity to pregnant SD rats, no teratogenic and developmental toxicity to fetal rats. No Observed Adverse Effect Level of maternal toxicity and the minimum teratogenic dose of fetal rats is >8. 0 g/kg.