Chromatin accessibility and transcriptional landscape in PK-15 cells during early exposure to Aflatoxin B1.

Aflatoxin B1 (AFB1) not only causes significant losses in livestock production but also poses a serious threat to human health. It is the most carcinogenic among known chemicals. Pigs are more susceptible to AFB1 and experience a higher incidence. However, the molecular mechanism of the toxic effect of AFB1 remains unclear. In this study, we used assay for transposase-accessible chromatin using sequencing (ATAC-seq) and RNA-seq to uncover chromatin accessibility and gene expression dynamics in PK-15 cells during early exposure to AFB1. We observed that the toxic effects of AFB1 involve signaling pathways such as p53, PI3K-AKT, Hippo, MAPK, TLRs, apoptosis, autophagy, and cancer pathways. Basic leucine zipper (bZIP) transcription factors (TFs), including AP-1, Fos, JunB, and Fra2, play a crucial role in regulating the biological processes involved in AFB1 challenge. Several new TFs, such as BORIS, HNF1b, Atf1, and KNRNPH2, represent potential targets for the toxic mechanism of AFB1. In addition, it is crucial to focus on the concentration of intracellular zinc ions. These findings will contribute to a better understanding of the mechanisms underlying AFB1-induced nephrotoxicity and offer new molecular targets.

Investigation of critical factors influencing the underestimation of hearing loss predicted by the ISO 1999 predicting model.

OBJECTIVE: To analyze factors influencing the underestimation of noise-induced permanent threshold shift (NIPTS) among manufacturing workers, providing baseline data for revising noise exposure standard. DESIGN: A cross-sectional study was designed with 2702 noise-exposed workers from 35 enterprises from 10 industries. Personal noise exposure level(LAeq,8h) and noise kurtosis level were determined by a noise dosimeter. Questionnaires and hearing loss tests were performed for each subject. The predicted NIPTS was calculated using the ISO 1999:2013 model for each participant, and the actual measured NIPTS was corrected for age and sex. The factors influencing the underestimation of NIPTS were investigated. RESULTS: The predicted NIPTS at each test frequency (0.5, 1, 2, 3, 4, or 6kHz) and mean NIPTS at 2, 3, 4, and 6kHz (NIPTS2346) using the ISO 1999:2013 model were significantly lower than their corresponding measured NIPTS, respectively (P < 0.001). The ISO model significantly underestimated the NIPTS2346 by 12.36 dB HL. The multiple linear regression analysis showed that noise exposure level, exposure duration, age, and kurtosis could affect the degree of underestimation of NIPTS2346. The generalized additive model (GAM) with (penalized) spline components showed nonlinear relationships between critical factors (age, exposure duration, noise level, and kurtosis) and the underestimated NIPTS2346.The underestimated NIPTS2346 decreased with an increase in exposure duration (especially over ten years). There was no apparent trend in the underestimated NIPTS2346 with age. The underestimated NIPTS2346 decreased with the increased noise level [especially > 90 dB(A)]. The underestimated NIPTS2346 increased with an increase in noise kurtosis after adjusting for the noise exposure level and exposure duration and ultimately exhibiting a linear regression relationship. CONCLUSIONS: The ISO 1999 predicting model significantly underestimated the noise-induced hearing loss among manufacturing workers. The degree of underestimation became more significant at the noise exposure condition of fewer than ten years, less than 90 dB(A), and higher kurtosis levels. It is necessary to apply kurtosis to adjust the underestimation of hearing loss and consider the applying condition of noise energy metrics when using the ISO predicting model.

An Improvement to a Multi-Client Searchable Encryption Scheme for Boolean Queries.

The migration of e-health systems to the cloud computing brings huge benefits, as same as some security risks. Searchable Encryption(SE) is a cryptography encryption scheme that can protect the confidentiality of data and utilize the encrypted data at the same time. The SE scheme proposed by Cash et al. in Crypto2013 and its follow-up work in CCS2013 are most practical SE Scheme that support Boolean queries at present. In their scheme, the data user has to generate the search tokens by the counter number one by one and interact with server repeatedly, until he meets the correct one, or goes through plenty of tokens to illustrate that there is no search result. In this paper, we make an improvement to their scheme. We allow server to send back some information and help the user to generate exact search token in the search phase. In our scheme, there are only two round interaction between server and user, and the search token has [Formula: see text] elements, where n is the keywords number in query expression, and [Formula: see text] is the minimum documents number that contains one of keyword in query expression, and the computation cost of server is [Formula: see text] modular exponentiation operation.

Development and application of UPLC-Q-Orbitrap HRMS methods for the determination of eight metabolites of p-chloronitrobenzene in human urine.

Accurate, reliable, and sensitive methods for the determination of eight metabolites of p-chloronitrobenzene (p-CNB) were developed based on ultra-performance liquid chromatography - quadrupole - orbitrap high resolution mass spectrometry (UPLC-Q-Orbitrap HRMS). The free and conjugated forms of metabolites were determined before and after urine samples were hydrolyzed with acid. Subsequently, three solid phase extraction steps were used for concentration and purification. The calibration curves of the eight metabolites exhibited good linearity with an R2 of >0.999, and the precision was good as well, with the coefficient of variations of intra-day and inter-day being lower than 7.0 % and 8.5 %, respectively. Analytical accuracy for all metabolites varied within ranges of 76.0-102.9 %, and the limit of detection and limit of quantification of all the metabolites varied within ranges of 0.2-7.7 µg/L and 0.6-25.6 µg/L in human urine, respectively. In addition, the application potential of the proposed methods were evaluated by applying them to the determination of metabolites in the urine of workers exposed to p-CNB, and these results showed that these methods were accurate, reliable, and sensitive, which makes them an excellent choice for detecting the metabolites of p-CNB in the urine of exposed workers.

Functional Mutations in the microRNA-155 Promoter Modulate its Transcription Efficiency and Expression.

Limited research has been conducted on porcine miR-155 promoters, and previous study from our group have identified two haplotypes (TT and CC) in different pig breeds, each associated with five fully linked mutation sites within or near the miR-155 gene (Li et al. Dev Comp Immunol 39(1):110-116, 2013). In this study, the promoter region of porcine miR-155 was screened, and two important transcription factors, Foxp3 and RelA, were identified. The binding ability of Foxp3 protein was found to be affected by the first mutation site (A/C) using EMSA analysis. In vitro experiments revealed that the expression level of miR-155 was significantly higher in the C haplotype compared to the T haplotype. Additionally, northern blotting assays indicated that both the first mutation site (A/C) and the fourth mutation site (G/T) had a significant impact on miR-155 expression levels. These findings provide further insights into the transcriptional regulation of porcine miR-155 and identify crucial mutation sites that influence miR-155 expression. This knowledge can serve as a basis for identifying potential molecular markers associated with disease resistance in swine.

Levels, sources, variations, and human health risk assessment of 90Sr and 137Cs in water and food around Sanmen Nuclear Power Plant (China) from 2011 to 2020.

Objectives: Radioactivity monitoring around nuclear facilities is crucial to provide important baseline data for effective detection of radioactive leakage to the environment. We aim to establish a baseline study for monitoring radioactive levels of 90Sr and 137Cs around Sammen Nuclear Power Plant (SNPP) and to assess their associated health impact on surrounding residents. Methods: In this study, we collected water and food samples around the SNPP from 2011 to 2020 and determined for 90Sr and 137Cs activity concentrations. We statistically analyzed the temporal trends of 90Sr and 137Cs and evaluated their radiation exposure to the local residents. Results: During this period, the activity concentrations of 90Sr and 137Cs varied within 1.2-9.9 mBq/L and 0.10-7.6 mBq/L in water, and 0.037-1.3 Bq/kg and 0.011-0.45 Bq/kg in food, respectively, with no significant seasonal variation trend. Conclusions: All reported activity concentrations of 90Sr and 137Cs were significantly lower than the recommended value of WHO and Chinese national standards. There is no indication of notable radioactive release into the study area due to the operation of SNPP during 2018-2020. The annual effective doses (AEDs) from the ingestion of 90Sr and 137Cs in water and food were well below the international permissible limits, indicating the radiation exposure around SNPP during 2011-2020 was kept at a safe level.

Research progress in toxicological effects and mechanism of aflatoxin B1 toxin.

Fungal contamination of animal feed can severely affect the health of farm animals, and result in considerable economic losses. Certain filamentous fungi or molds produce toxic secondary metabolites known as mycotoxins, of which aflatoxins (AFTs) are considered the most critical dietary risk factor for both humans and animals. AFTs are ubiquitous in the environment, soil, and food crops, and aflatoxin B1(AFB1) has been identified by the World Health Organization (WHO) as one of the most potent natural group 1A carcinogen. We reviewed the literature on the toxic effects of AFB1 in humans and animals along with its toxicokinetic properties. The damage induced by AFB1 in cells and tissues is mainly achieved through cell cycle arrest and inhibition of cell proliferation, and the induction of apoptosis, oxidative stress, endoplasmic reticulum (ER) stress and autophagy. In addition, numerous coding genes and non-coding RNAs have been identified that regulate AFB1 toxicity. This review is a summary of the current research on the complexity of AFB1 toxicity, and provides insights into the molecular mechanisms as well as the phenotypic characteristics.

Evaluation of strategies for the occupational health risk assessment of chemical toxicants in the workplace based on a quantitative analysis model.

Objectives: The commonly used methods for the occupational health risk assessment (OHRA) of chemical toxicants cannot fully meet the needs of practical work. This study evaluated OHRA strategies for chemical toxicants in the workplace by establishing a quantitative analysis model. Methods: Five typical industries in China that implement OHRA using the six common models (the Environmental Protection Agency, Australian, Romanian, Singaporean, International Council on Mining and Metals, and the Control of Substances Hazardous to Health models) were selected as the research objects. We established a quantitative analysis model to compare the six models and applied it to compare the results obtained using each model and preliminarily analyze the advantages, limitations, and application scope of each method. Results: The risk ratio (RR) values of the six methods decreased in the following order: RREPA > RRCOSHH > RRICMM > RRAustralia > RRSingaporean > RRRomanian (P < 0.05). Among the six models, the Singaporean model had the strongest RR correlation with the other models (P < 0.01). The sequence of RRs obtained from the Singaporean, ICMM, Australian, and Romanian models in the five industries was consistent with the sequence of the three inherent risk levels in those industries. Only the Romanian model could distinguish between the RRs of all five industries. The EPA and Singaporean models could effectively distinguish the differences in inherent risk for four hazard factors (manganese and inorganic compounds, benzene, xylene, and ethyl acetate), with the assessment accuracy being relatively higher for the EPA model. Conclusions: Among the six models, the EPA model had the relatively highest accuracy in assessing chemical toxicants, followed by the Singaporean model. The EPA and Romanian models were strongest in differentiating the differences in toxicity risk. More studies on OHRA methodology are needed.

Quantitative differences between common occupational health risk assessment models.

OBJECTIVES: Methodological studies on occupational health risk assessment (OHRA) models are rarely reported. This study aimed to explore the quantitative differences between common OHRA models. METHODS: The risk ratios (RRs) in five typical industries (leather, wooden furniture manufacturing, printing and dyeing, printing, and garment manufacturing) were investigated using six OHRA models, namely the models from the US Environmental Protection Agency (EPA), Singapore, the Control of Substances Hazardous to Health (COSHH), Australia, Romania, and International Council on Mining and Metals (ICMM). The consistency, correlation, and reliability were evaluated for quantitative differences between the models. RESULTS: The order of the RRs obtained from the EPA, Singaporean, and COSHH models in the five industries was consistent with the order of the inherent risk levels in those industries. The EPA and Singaporean models could effectively distinguish the inherent risk levels of risk factors like xylene and ethyl acetate. The order of RR between the six models was: RR EPA  > RR COSHH  > RR Singaporean  > RR Australian  > RR Romanian and RR ICMM (P < .05). The EPA model had the weakest correlations with other models. The Singaporean model had positive correlations in RRs with the other models (P＜0.01). CONCLUSIONS: The EPA and Singaporean models exhibited good reliability since they could distinguish the inherent risk of the industry or risk factor and tended to get higher risk levels. The EPA model was independent and the Singaporean model had a good correlation with other models. More studies on OHRA methodology are needed.

The immunomodulatory peptide bursopentin (BP5) enhances proliferation and induces sIgM expression in DT40 cells.

BACKGROUND: In the recent past, many studies have been focused on extracts of BF and multiple biologically active factors and their effects on humoral immune system in chickens and birds. However, the mechanism of those immunomodulatory peptides on the B lineage cells proliferation and antibody production in chicken is fairly unknown. DT40 cell line, an avian leucosis virus-induced chicken pre-B cell line, expresses immunoglobulin M (IgM) isotype B cell reporter in the plasma membrane. There are many evidences suggesting that DT40 cells are best characterized as a bursal stem cell line. Because of the unique characteristics of DT40 cell line, it has been widely used to observe biological processes of pre-B lymphocyte cell within living cells. METHODS: The chicken B cell line DT40 was cultured in Roswell Park Memorial Institute (RPMI) 1640 medium and cytotoxicity was studied. Also, effect of BP5 on cell proliferation and cell cycle distribution of DT40 cells was studied. Also, the effect of BP5 on sIgM mRNA expression was studied by using real-time PCR. OBJECTIVES: To investigat the effects of Bursopentin (Cys-Lys-Arg-Val-Tyr, BP5) on a chicken promyelocyte cell line DT40, assays of cell proliferation, cell cycle distribution, detection of surface immunoglobulin G (sIgM) mRNA expression and gene microarray analysis were performed. RESULTS: The results showed that BP5 displayed concentration-dependent effects on the proliferation, cell cycle, and sIgM mRNA expression in DT40 cells. And the analysis of expression profiles identified a signature set of 3022 genes (1254 up regulated genes, 1762 down regulated genes), which clearly discriminated the BP5-treated DT40 cells from control with high certainty (P≤0.02). The results of microarray analysis were confirmed by quantitative reverse transcription-polymerase chain reaction for 12 of the differentially expressed genes. CONCLUSION: Theses findings showed the immuno-activity effect of BP5 on B lymphocyte and indicated that BP5 treatment regulated eight signaling pathways, in which Toll-like signaling pathway was the most significant enrichment pathway.