Coordinated pyruvate kinase activity is crucial for metabolic adaptation and cell survival during mitochondrial dysfunction.

Deoxyguanosine kinase (DGUOK) deficiency causes mtDNA depletion and mitochondrial dysfunction. We reported long survival of DGUOK knockout (Dguok-/-) mice despite low (<5%) mtDNA content in liver tissue. However, the molecular mechanisms enabling the extended survival remain unknown. Using transcriptomics, proteomics and metabolomics followed by in vitro assays, we aimed to identify the molecular pathways involved in the extended survival of the Dguok-/- mice. At the early stage, the serine synthesis and folate cycle were activated but declined later. Increased activity of the mitochondrial citric acid cycle (TCA cycle) and the urea cycle and degradation of branched chain amino acids were hallmarks of the extended lifespan in DGUOK deficiency. Furthermore, the increased synthesis of TCA cycle intermediates was supported by coordination of two pyruvate kinase genes, PKLR and PKM, indicating a central coordinating role of pyruvate kinases to support the long-term survival in mitochondrial dysfunction.

Effect and interaction of TNKS genetic polymorphisms and environmental factors on telomere damage in COEs-exposure workers.

Coke oven emissions (COEs) contain many carcinogenic polycyclic aromatic hydrocarbons (PAHs). Telomere damage is an early biological marker reflecting long-term COEs-exposure. Whereas, whether the genetic variations of telomere-regulated gene TNKS have an effect on the COEs-induced telomere damage is unknown. So we detected the environmental exposure levels, relative telomere length (RTL), and TNKS genetic polymorphisms among 544 COEs-exposure workers and 238 healthy participants. We found that the RTL of the wild homozygous GG genotype in rs1055328 locus was statistically shorter compared with the CG+CC genotype for the healthy participants using covariance analysis(P = 0.008). In the Generalized linear model (GLM) analysis, TNKS rs1055328 GG could accelerate telomere shortening (P = 0.011); and the interaction between TNKS rs1055328 GG and COEs-exposure had an effect on RTL (P = 0.002). In conclusion, this study was the first to discover the role of TNKS rs1055328 locus in COEs-induced telomere damage, and proved that chromosomal damage was a combined consequence of environmental and genetic factors.

The polymorphisms in cGAS-STING pathway are associated with mitochondrial DNA copy number in coke oven workers.

OBJECTIVE: To evaluate the interaction effects of Polycyclic aromatic hydrocarbons (PAHs) exposure and variants in cGAS-STING genes on mitochondrial DNA copy number (mtDNAcn) in workers. METHODS: The mtDNAcn was determined by real-time quantitative polymerase-chain reaction in 544 PAHs-exposed workers and 238 office workers. The polymorphisms were detected by flight mass spectrometry. RESULTS: The mtDNAcn in PAHs exposure group was significantly lower than non-occupational exposure population (P < 0.00). The cGAS rs610913 CA+AA had significant interaction effects with STING rs11554776 GG+GA (P = 0.035), rs7380824 CC+CT (P = 0.026), and rs78233829 GC+CC (P = 0.034) on mtDNAcn. The generalized linear model results showed that the influencing factors of mtDNAcn include PAHs exposure (P < 0.001) and the interaction of PAHs exposure and cGAS rs 311678 AA+AG (P = 0.047). CONCLUSION: The influencing factors of mtDNAcn include PAHs exposure and the interaction of PAHs exposure and cGAS rs 311678 AA+AG.

Association of Genetic Polymorphisms of TERT with Telomere Length in Coke Oven Emissions-Exposed Workers.

We explored the association between variations in the telomere maintenance genes and change in telomere length (TL) in workers. The TL of peripheral blood leukocytes from 544 coke oven workers and 238 controls were detected using the Real-time PCR method. Variations in four genes were then detected using the PCR based restriction fragment length polymorphism. The effects of environmental and genetic factors on TL were subsequently analyzed through covariance analysis and a generalized linear model .The TL of subjects with GG genotypes were longer than those with AG genotype in the TERT rs2736098 locus amongst the controls (P = .032). The combined effect of COEs exposure and AG+AA genotypes had a significant effect on TL (P < .001). The interaction between the COEs exposure factor and the rs2736098AG+AA genotypes had a significant effect on the TL (P < .05). The TL in coke oven workers is associated with the interactions between TERT rs2736098 AG+AA and COEs exposure.

Reinvestigation of the Psychological Mechanisms of Construction Experience on Hazard Recognition Performance.

OBJECTIVE: The study aimed to reinvestigate psychological mechanisms of the influence of construction workers' experience on hazard recognition performance, with signal detection theory (SDT) and electroencephalogram (EEG) readings. BACKGROUND: Existing evidence regarding the effect of experience on hazard recognition performance in the construction industry remains inconsistent. Behavior-wise, identification of dominant hazard recognition factors (sensitivity or response bias, or both) would help determine appropriate training strategies to improve hazard recognition. In terms of neuro-responses, induced gamma-band activity was expected to reflect the cognitive functions mediating the psychological effects of experience. METHOD: Seventy-seven construction workers participated in a predesigned hazard recognition task, in which participants judged whether a hazard was present from a series of construction scenario pictures. We computed and compared the sensitivity and response bias of SDT and time-frequency representations of recorded EEG signals of the two experience-level groups. RESULTS: Novice workers had higher hazard recognition rates. Behavior-wise, novices were more sensitive than more experienced workers. Compared with experienced workers, novices showed stronger gamma-band difference power (hazardous minus safe) in the left frontal and right posterior parietal areas during the hazard recognition process. CONCLUSION: Novices performed better at hazard recognition, indicating their sensitivity to the hazards without a clear difference in response bias. Based on the EEG data, novices' sensitivity may be attributed to more efficient working memory and attentional control. APPLICATION: There is a need for continuous refreshment of hazard recognition skills for experienced workers for safety interventions.

The association between polymorphisms in miRNA and the cholinesterase activity of workers in an omethoate-exposed environment.

To explore the association between polymorphisms in microRNAs (miRNAs) and the cholinesterase (ChE) activity in omethoate-exposed workers, we recruited 180 omethoate-exposed workers and 115 controls to measure their ChE activity using acetylcholine and dithio-bis-(nitrobenzoic acid) and genotype susceptible SNPs in their miRNA by time-of-flight mass spectrometry. ChE activity in the exposure group was lower than that in the control group (P < 0.001). The analysis of covariance result showed that ChE activity was lower in the (- -/- T) genotype in miR-30a rs111456995 (1.97 ± 0.47) than in the TT genotype (2.23 ± 0.59) of the exposure group (P = 0.004). Multivariate linear regression was performed to find influencing factors on ChE activity, and variables kept in the model included omethoate exposure (b = -1.094, P < 0.001), gender (b = -0.381, P < 0.001), miR-30a rs111456995 (- -/- T)(b = -0.248, P < 0.001), and drinking (b = 0.258, P =0.019). The results suggest that individuals carrying a (- -/- T) genotype in miR-30a rs111456995 were more susceptible to damage in their cholinesterase induced by omethoate exposure.

Severe mtDNA depletion and dependency on catabolic lipid metabolism in DGUOK knockout mice.

Deoxyguanosine kinase (DGUOK) provides guanosine and adenosine nucleotides for mitochondrial DNA (mtDNA) replication, and its deficiency in humans leads to hepatocerebral mtDNA depletion syndrome or to isolated hepatic disease. There are poor treatment options for DGUOK deficiency and the aim of this study was to generate a model for further studies of the disease that could reveal novel treatment strategies. We report a Dguok-deficient mouse strain that, similar to humans, is most severely affected in the liver. The Dguok complete knockout mice (Dguok-/-) were born normal, but began to lose weight at week 6. A change of fur color from black to blueish grey started at week 16 and was complete at week 20. The movements and behavior were indistinguishable compared to wild-type (wt) mice. A decrease of mtDNA copy number occurred in multiple tissues, with the liver being the most severely affected. The mtDNA-encoded protein cytochrome c oxidase was much lower in Dguok-/- liver tissue than in the wt, whereas the expression of the nuclear-encoded succinate dehydrogenase complex subunit A was unaffected. Histopathology showed severe alterations and immunohistochemistry showed signs of both oxidative stress and regeneration in Dguok-/- liver. The subcutaneous fat layer was undetectable in Dguok-/-, which, in addition to gene expression analysis, indicated an altered lipid metabolism. We conclude that Dguok has a major role for the synthesis of deoxyribonucleotides for mtDNA replication particularly in the liver, similar to the human disorder. Our data also show a catabolic lipid metabolism in liver tissue of Dguok-/-.

Genetic variants in telomerase-associated protein 1 are associated with telomere damage in PAH-exposed workers.

Telomeres are functional complexes at the ends of linear chromosomes, and telomerase aids in their maintenance and replication. Additionally, accumulating evidence suggests that telomerase-associated protein 1 (TEP1) is a component of the telomerase ribonucleoprotein complex and is responsible for catalyzing the addition of new synthetic telomere sequences to chromosome ends. In our previous study, we found that genetic variants of the TERT gene participated in the regulation of telomere length. Exposure to particulate matter, environmental pollutants, oxidative stress, and pesticides is associated with shortening of telomere length. However, it is unknown whether genetic variants in the TEP1 gene may affect telomere length (TL) in polycyclic aromatic hydrocarbon (PAH)-exposed workers. Therefore, we measured the peripheral leukocyte TL and genotyped the polymorphism loci in the TEP1 gene among 544 PAH-exposed workers and 238 healthy controls. Covariance analysis showed that the individuals carrying TEP1 rs1760903 CC and TEP1 rs1760904 TT had longer TL in the control group (P < 0.05). In the generalized linear model, we found that rs1760903 CC was a protective factor against TL shortening, and PAH exposure could promote telomere shortening (P < 0.05). Thus, this study reinforces the roles of environmental factors and genetic variations in telomere damage, and provides a theoretical foundation for the early detection of susceptible populations and the establishment of occupational standards.

Activation of Mitochondrial 2-Oxoglutarate Dehydrogenase by Cocarboxylase in Human Lung Adenocarcinoma Cells A549 Is p53/p21-Dependent and Impairs Cellular Redox State, Mimicking the Cisplatin Action.

Genetic up-regulation of mitochondrial 2-oxoglutarate dehydrogenase is known to increase reactive oxygen species, being detrimental for cancer cells. Thiamine diphosphate (ThDP, cocarboxylase) is an essential activator of the enzyme and inhibits p53-DNA binding in cancer cells. We hypothesize that the pleiotropic regulator ThDP may be of importance for anticancer therapies. The hypothesis is tested in the present work on lung adenocarcinoma cells A549 possessing the p53-p21 pathway as fully functional or perturbed by p21 knockdown. Molecular mechanisms of ThDP action on cellular viability and their interplay with the cisplatin and p53-p21 pathways are characterized. Despite the well-known antioxidant properties of thiamine, A549 cells exhibit decreases in their reducing power and glutathione level after incubation with 5 mM ThDP, not observed in non-cancer epithelial cells Vero. Moreover, thiamine deficiency elevates glutathione in A549 cells. Viability of the thiamine deficient A549 cells is increased at a low (0.05 mM) ThDP. However, the increase is attenuated by 5 mM ThDP, p21 knockdown, specific inhibitor of the 2-oxoglutarate dehydrogenase complex (OGDHC), or cisplatin. Cellular levels of the catalytically competent ThDP·OGDHC holoenzyme are dysregulated by p21 knockdown and correlate negatively with the A549 viability. The inverse relationship between cellular glutathione and holo-OGDHC is corroborated by their comparison in the A549 and Vero cells. The similarity, non-additivity, and p21 dependence of the dual actions of ThDP and cisplatin on A549 cells manifest a common OGDHC-mediated mechanism of the viability decrease. High ThDP saturation of OGDHC compromises the redox state of A549 cells under the control of p53-p21 axes.

Effect of TRF1 rs3863242 polymorphism on telomere length in omethoate-exposed workers.

Telomere length was found to be associated with omethoate exposure and polymorphisms in certain genes among occupational workers. However, whether the polymorphisms in telomere-binding protein genes influence telomere length remains unclear. To explore the correlation between telomere length and polymorphisms in telomere-binding protein genes, telomere length in peripheral blood leukocytes was determined by real-time quantitative polymerase chain reaction in 180 omethoate-exposed workers and 115 healthy controls. Polymorphisms in 10 pairs of alleles were detected using flight mass spectrometry or polymerase chain reaction-restriction fragment length polymorphism technique. The results showed that individuals with GG genotype in TRF1 rs3863242 had longer telomere lengths than those with AG + AA genotype in the control group (p = 0.005). The multiple regression analysis suggested that both omethoate exposure (b = 0.526, p < 0.001) and TRF1 rs3863242 GG (b = 0.220, p = 0.002) were related to a longer telomere length. In conclusion, GG genotype in TRF1 rs3863242 is linked to prolongation of telomere length, and individuals with GG genotype are recommended to strengthen health protection in a Chinese occupational omethoate-exposed population.

Epigenetic-Based Biomarkers in the Malignant Transformation of BEAS-2B Cells Induced by Coal Tar Pitch Extract.

Background and objectives: The carcinogenicity of coal tar pitch (CTP) to occupational workers has been confirmed by the International Agency for Research on Cancer, especially for lung cancer. Herein, we explored the dynamic changes of epigenetic modifications in the malignant transformation process of CTP-induced BEAS-2B cells and also provided clues for screening early biomarkers of CTP-associated occupational lung cancer. Methods: BEAS-2B cells treated with 3.0 µg/mL CTP extract (CTPE) were cultured to the 30th passage to set up a malignant transformation model, which was confirmed by platelet clone formation assay and xenograft assay. DNA methylation levels were determined by ultraviolet-high performance liquid chromatography. mRNA levels in cells and protein levels in supernatants were respectively detected by Real-Time PCR and enzyme-linked immunosorbent assay. Results: The number of clones and the ability of tumor formation in nude mice of CTPE-exposed BEAS-2B cells at 30th passage were significantly increased compared to vehicle control. Moreover, genomic DNA methylation level was down-regulated. The mRNA levels of DNMT1, DNMT3a and HDAC1 as well as the expression of DNMT1 protein were up-regulated since the 10th passage. From the 20th passage, the transcriptional levels of DNMT3b, let-7a and the expression of DNMT3a, DNMT3b, and HDAC1 proteins were detected to be higher than vehicle control, while the level of miR-21 increased only at the 30th passage. Conclusion: Data in this study indicated that the changes of epigenetic molecules including DNMT1, DNMT3a, DNMT3b, HDAC1, and let-7a occurred at the early stages of BEAS-2B cell malignant transformation after CTPE exposure, which provided critical information for screening early biomarkers of CTP-associated occupational lung cancer.

Association of genetic polymorphisms of miR-145 gene with telomere length in omethoate-exposed workers.

Omethoate, an organophosphorous pesticide, causes a variety of health effects, especially the damage of chromosome DNA. The aim of the study was to assess the correlation between polymorphisms of encoding miRNA genes and telomere length in omethoate-exposure workers. 180 workers with more than 8 years omethoate-exposure and 115 healthy controls were recruited in the study. Genotyping for the selected single nucleotide polymorphisms loci were performed using the flight mass spectrometry. Real-time fluorescent quantitative polymerase chain reaction(PCR) method was applied to determine the relative telomere length(RTL) in human peripheral blood leukocytes DNA. After adjusting the covariate of affecting RTL, covariance analysis showed that the female was significantly longer than that of the male in control group(P < 0.046). For the miR-145 rs353291 locus, this study showed that RTL of mutation homozygous AG+GG individuals was longer than that of wild homozygous AA in the exposure group (P = 0.039). In the control group, RTL with wild homozygous TT genotype in miR-30a rs2222722 polymorphism locus was longer than that of the mutation homozygous CC genotype (P = 0.038). After multiple linear regression analysis, the independent variables of entering into the model were omethoate-exposure (b = 0.562, P < 0.001), miR-145 rs353291 (AG+GG) (b = 0.205, P = 0.010). The prolongation of relative telomere length in omethoate exposed workers was associated with AG+GG genotypes in rs353291 polymorphism of encoding miR-145 gene.

Benchmark dose assessment for coke oven emissions-induced telomere length effects in occupationally exposed workers in China.

Telomeres are DNA-protein structures that protect chromosome ends from degradation and fusion, which are shortened by oxidative stress, for example air pollution including benzene, toluene, Coke Oven Emissions (COEs), and so on. As a biomarker of health and disease, telomere length is associated with cardiovascular, diabetes and cancers. The aim of this study was to estimate the effects of COEs exposure on telomere length and the benchmark dose (BMD) of COEs. A total of 542 coke oven workers and 235 healthy controls without exposure to toxicants were recruited. Quantitative PCR was used to determine the telomere length in human peripheral blood leukocytes DNA. Propensity scoring was used to match coke oven workers to healthy controls. Linear regression models and trend tests were used to the relationship between COEs exposure and telomere length. Telomere length in COEs exposed group 0.764 (0.536, 1.092) was significantly shorter than that in the control group 1.064(0.762, 1.438), (P < 0.001). There were significantly dose-response relationships between COEs exposure and telomere damage with telomere length as a biomarker. A BMDL value lower than the present occupational exposure limits (OELs) of COEs exposure was evaluated using the BMD approach in coke oven workers. Our results suggested that shorter telomere length is related to occupational exposure to COEs and the level of COEs exposure lower than the current national OELs in China and many other countries could induce telomere damage.

Inhibition of glutamate oxaloacetate transaminase 1 in cancer cell lines results in altered metabolism with increased dependency of glucose.

BACKGROUND: Glutamate oxaloacetate transaminase 1 (GOT1) regulates cellular metabolism through coordinating the utilization of carbohydrates and amino acids to meet nutrient requirements. KRAS mutated cancer cells were recently shown to rely on GOT1 to support long-term cell proliferation. The aim of the present study was to address the role of GOT1 in the metabolic adaption of cancer cells. METHODS: GOT1-null and knockdown cell lines were established through CRISPR/Cas9 and shRNA techniques. The growth properties, colony formation ability, autophagy and selected gene expression profiles were analysed. Glucose deprivation decreased the viability of the GOT1-null cells and rescue experiments were conducted with selected intermediates. The redox NADH/NAD+ homeostasis as well as lactate secretion were determined. GOT1 expression levels and correlation with survival rates were analysed in selected tumor databases. RESULTS: Inhibition of GOT1 sensitized the cancer cells to glucose deprivation, which was partially counteracted by oxaloacetate and phosphoenol pyruvate, metabolic intermediates downstream of GOT1. Moreover, GOT1-null cells accumulated NADH and displayed a decreased ratio of NADH/NAD+ with nutrient depletion. The relevance of GOT1 as a potential target in cancer therapy was supported by a lung adenocarcinoma RNA-seq data set as well as the GEO:GSE database of metastatic melanoma where GOT1 expression was increased. High levels of GOT1 were further linked to poor survival as analysed by the GEPIA web tool, in thyroid and breast carcinoma and in lung adenocarcinoma. CONCLUSIONS: Our study suggests an important role of GOT1 to coordinate the glycolytic and the oxidative phosphorylation pathways in KRAS mutated cancer cells. GOT1 is crucial to provide oxaloacetate at low glucose levels, likely to maintain the redox homeostasis. Our data suggest GOT1 as a possible target in cancer therapy.

Immunization with recombinant schistosome adenylate kinase 1 partially protects mice against Schistosoma japonicum infection.

Highly effective and safe prophylactic vaccines are urgently needed to sustainably control schistosomiasis, one of the most serious endemic zoonoses in China. In this study, we characterized adenylate kinase 1 from Schistosoma japonicum (SjAK1), a phosphotransferase that regulates cellular energy and metabolism, and evaluated its potential as a recombinant vaccine. Based on real-time quantitative PCR, western blot, and immunolocalization, SjAK1 is active throughout the life of the worm, although its expression is higher in 21-day-old schistosomula, adult worms, and eggs deposited in the host liver. Further, the enzyme accumulates in the eggshell, intestinal epithelium, integument of adult worms and in the vitellaria tissue in female worms. A 594-bp full-length complementary DNA (cDNA) encoding SjAK1 was synthesized from total RNA of 3-day-old schistosomes, and immunization with recombinant SjAK1 reduced worm burden by 50%, decreased the density of eggs deposited in the host liver by 40%, and reduced the area of granulomas in the host liver by 56%. ELISA results showed that recombinant SjAK1 also stimulated Th1 cytokines such as IL-2 and IFN-γ, but not IL-5 and IL-4. Collectively, a recombinant form of the enzyme SjAK1 elicits partial protective immunity against Schistosoma japonicum infection and the induction of Th1 cytokines. Thus, the enzyme has potential as a component of a multivalent vaccine against schistosomiasis.

Long term expression of Drosophila melanogaster nucleoside kinase in thymidine kinase 2-deficient mice with no lethal effects caused by nucleotide pool imbalances.

Mitochondrial DNA depletion caused by thymidine kinase 2 (TK2) deficiency can be compensated by a nucleoside kinase from Drosophila melanogaster (Dm-dNK) in mice. We show that transgene expression of Dm-dNK in Tk2 knock-out (Tk2(-/-)) mice extended the life span of Tk2(-/-) mice from 3 weeks to at least 20 months. The Dm-dNK(+/-)Tk2(-/-) mice maintained normal mitochondrial DNA levels throughout the observation time. A significant difference in total body weight due to the reduction of subcutaneous and visceral fat in the Dm-dNK(+/-)Tk2(-/-) mice was the only visible difference compared with control mice. This indicates an effect on fat metabolism mediated through residual Tk2 deficiency because Dm-dNK expression was low in both liver and fat tissues. Dm-dNK expression led to increased dNTP pools and an increase in the catabolism of purine and pyrimidine nucleotides but these alterations did not apparently affect the mice during the 20 months of observation. In conclusion, Dm-dNK expression in the cell nucleus expanded the total dNTP pools to levels required for efficient mitochondrial DNA synthesis, thereby compensated the Tk2 deficiency, during a normal life span of the mice. The Dm-dNK(+/-) mouse serves as a model for nucleoside gene or enzyme substitutions, nucleotide imbalances, and dNTP alterations in different tissues.

Transgene expression of Drosophila melanogaster nucleoside kinase reverses mitochondrial thymidine kinase 2 deficiency.

A strategy to reverse the symptoms of thymidine kinase 2 (TK2) deficiency in a mouse model was investigated. The nucleoside kinase from Drosophila melanogaster (Dm-dNK) was expressed in TK2-deficient mice that have been shown to present with a severe phenotype caused by mitochondrial DNA depletion. The Dm-dNK(+/-) transgenic mice were shown to be able to rescue the TK2-deficient mice. The Dm-dNK(+/-)TK2(-/-) mice were normal as judged by growth and behavior during the observation time of 6 months. The Dm-dNK-expressing mice showed a substantial increase in thymidine-phosphorylating activity in investigated tissues. The Dm-dNK expression also resulted in highly elevated dTTP pools. The dTTP pool alterations did not cause specific mitochondrial DNA mutations or deletions when 6-month-old mice were analyzed. The mitochondrial DNA was also detected at normal levels. In conclusion, the Dm-dNK(+/-)TK2(-/-) mouse model illustrates how dTMP synthesized in the cell nucleus can compensate for loss of intramitochondrial dTMP synthesis in differentiated tissue. The data presented open new possibilities to treat the severe symptoms of TK2 deficiency.

Long term survival and abnormal liver fat accumulation in mice with specific thymidine kinase 2 deficiency in liver tissue.

Deficiency in thymidine kinase 2 (TK2) causes mitochondrial DNA depletion. Liver mitochondria are severely affected in Tk2 complete knockout models and have been suggested to play a role in the pathogenesis of the Tk2 knockout phenotype, characterized by loss of hypodermal fat tissue, growth retardation and reduced life span. Here we report a liver specific Tk2 knockout (KO) model to further study mechanisms contributing to the phenotypic changes associated with Tk2 deficiency. Interestingly, the liver specific Tk2 KO mice had a normal life span despite a much lower mtDNA level in liver tissue. Mitochondrial DNA encoded peptide COXI did not differ between the Tk2 KO and control mice. However, the relative liver weight was significantly increased in the male Tk2 KO mouse model. Histology analysis indicated an increased lipid accumulation. We conclude that other enzyme activities can partly compensate Tk2 deficiency to maintain mtDNA at a low but stable level throughout the life span of the liver specific Tk2 KO mice. The lower level of mtDNA was sufficient for survival but led to an abnormal lipid accumulation in liver tissue.

Exploring construction workers' brain connectivity during hazard recognition: a cognitive psychology perspective.

Monitoring brain activity is a novel development for hazard recognition in the construction industry. However, very few empirical studies have investigated the causal connections within the brain. This study aimed to explore the brain connectivity of construction workers during hazard recognition. Electroencephalogram data were collected from construction workers to perform image-based hazard recognition tasks. The Granger causality-based adaptive directed transfer function was used to simulate directed and time-variant information flow across the observed brain activity from the perspective of cognitive psychology. The results suggested a top-down modulation of behavioral goals originating from the dorsal attention network during hazard relocation. The sensory cortex predominantly serves as the information outlet center and interacts extensively with the frontal and visual cortices, reflecting a top-down attention reorientation mechanism for processing threatening stimuli. Our findings of brain effective connectivity supplement new evidence underpinning parallel distributed processing theory for workplace hazard recognition.

Corrigendum: MicroRNAs: Potential mediators between particulate matter 2.5 and Th17/Treg immune disorder in primary membranous nephropathy.

[This corrects the article DOI: 10.3389/fphar.2022.968256.].