Blocking exosomal secretion aggravated 1,4-benzoquinone-induced cytotoxicity.

Benzene exposure inhibits the hematopoietic system and leads to the occurrence of various types of leukemia. However, the mechanism underlying the hematotoxicity of benzene is still largely unclear. Emerging evidence has shown that exosomes are involved in toxic mechanisms of benzene. To understand the effect of 1,4-benzoquinone (PBQ; an active metabolite of benzene in bone marrow) on the exosomal release characteristics and role of exosomal secretion in PBQ-induced cytotoxicity. Exosomes were isolated from PBQ-treated HL-60 cells, purified by ultracentrifugation, and verified by transmission electron microscopy, nanoparticle tracking analysis and the presence of specific biomarkers. Our results showed that PBQ increased exosomal secretion in a dose-dependent manner, reaching a peak in 3 h at 10 µM PBQ treatment and then slowly decreasing in HL-60 cells. The exosomes contained miRNAs, which have been reported to be associated with benzene exposure or benzene poisoning. In particular, mir-34a-3p and mir-34A-5p were enriched in exosomes derived from PBQ-treated cells. In addition, the inhibition of exosomal release by GW4869 (an inhibitor of exosomal release) exacerbated PBQ-induced cytotoxicity, including increased intracellular reactive oxygen species levels, decreased mitochondrial membrane potential, and increased the apoptosis rate. Our findings illustrated that exosomes secretion plays an important role in antagonizing PBQ-induced cytotoxicity and maintaining cell homeostasis.

Management of public and private expenditures-CO2 emissions nexus in China: do economic asymmetries matter?

Environmental sustainability is becoming a crucial objective in this modern era. To attain this objective, it is important to reduce CO2 emissions for ensuring sustainable development. This study examined the nonlinear impact of government and household expenditures on CO2 emissions in China during 1984-2019. The modified nonlinear ARDL method is used for estimates. Asymmetric empirical outcomes show that a positive and negative change in government expenditure has reduced CO2 emissions in the short and long run in China. However, the positive and negative effects of government expenditure are higher in long run than short run. Furthermore, the asymmetric model gives much more significant results than the traditional symmetric model. Similarly, a positive change in household expenditure has a positive influence on CO2 emissions in the short and long run, while a negative change in household expenditure has a negative impact on CO2 emissions in the long run. The findings of the study recommended that there is a need to promote green spending in the economy that encourages environmental sustainability.

Estimating Nitrogen Use Efficiency, Profitability, and Greenhouse Gas Emission Using Different Methods of Fertilization.

Fertilization is a way to better use nitrogen fertilizers and increase productivity, but in another way, fertilization is also a source of anthropogenic greenhouse gas emissions. The study was carried out to measure the profitability ratio, technical efficiency, and CO2 from the top dressing (TD) and deep placement (DP) fertilization. The study was based on primary data, which were collected from different respondents and areas through a well-designed questionnaire. The study finds that DP fertilization is more profitable, least costly, and more efficient than TD fertilization. The finding observed that the yield of the TD growers is 727.82 kg/ha more than that of TD respondents. The efficiency score shows that to reach the 90% efficiency level, the farmers of TD need to use DP fertilization. The farmers of TD and DP can still increase their efficiency up to 12% and 9% by using the same inputs. The findings also clarify that manufacturing of synthetic nitrogen (N), direct use of N, Yield, and Area-Scaled greenhouse gas (GHG) emissions from the use of synthetic N through TD fertilization are greater than that of the DP group. The farming community needs to be aware of greenhouse gas emissions and how they can be reduced. It is also suggested that farmers need to shift toward DP fertilization to increase yield, profit, efficiency, food security, and reduce GHG emissions.

An asymmetric analysis of the impacts of energy use on carbon dioxide emissions in the G7 countries.

The foremost theme of the paper is to explore the asymmetric/symmetric impact of energy consumption on the carbon dioxide emission of G7 countries (Germany, Canada, USA, Italy, France, Italy, UK, and Japan). The nonlinear autoregressive distributed lag is used to measure asymmetric/symmetric cointegration by using annual data of G7 countries from 1965 to 2019. The augmented Dickey-Fuller and structural break unit root test is employed to measure the stationarity in variables while the Brock, Dechert, and Scheinkman test is used for measuring nonlinearity and the Wald test is used to figure out short- and long-run asymmetries/symmetries, respectively. The estimated findings of the nonlinear autoregressive distribution lag model show a significant effect of energy use on the ecological footprint. The asymmetric causality test provides evidence of unidirectional, bidirectional, and asymmetrical/symmetrical causality among the variables of G7 nations. The finding of the study suggested policy for the government of Canada and France to use coal instead of oil and gas while the USA, Germany, Italy, UK, and Japan are required to consume gas as compared to oil and coal. Similarly, the study also suggests using modern technology, renewable energy, and preventive measurement for ensuring environmental betterment.

PINK1/Parkin-mediated mitophagy was activated against 1,4-Benzoquinone-induced apoptosis in HL-60 cells.

Hematotoxicity of benzene is derived mainly from its active metabolite, 1,4-Benzoquinone (1,4-BQ), which induces cell apoptosis and mitochondrial damage. Damaged mitochondria are degraded through a specialized autophagy pathway, called mitophagy, which is driven by PINK1/Parkin signaling. However, whether mitophagy is involved in 1,4-BQ-induced toxicity remains unclear. This study was designed to investigate whether PINK1/Parkin-mediated mitophagy is activated in 1,4-BQ-treated HL-60 cells, and the roles mitophagy plays in 1,4-BQ-induced apoptosis. Our results demonstrated that 1,4-BQ induced autophagy in HL-60 cells, characterized by increased LC3-II/LC3-I ratio and Beclin1 expression, as well as decreased expression of p62. We confirmed the presence of mitophagosomes using electron microscopy, and found that 1,4-BQ-induced autophagy was blocked by pretreatment with the mitophagy inhibitor Cyclosporine A (CsA). In addition, we found that 1,4-BQ induced mitochondrial stress through decreased mitochondrial membrane potential (MMP) and increasedproduction of reactive oxygen species (ROS). We also confirmed that 1,4-BQ-induced mitophagy was mediated by the PINK1/Parkin pathway, illustrated by increased expression of PINK1 and Parkin mRNA and protein. Finally, we examined 1,4-BQ-induced apoptosis with or without CsA, which demonstrated that apoptosis increased after mitophagy inhibition, suggesting that mitophagy has a protective effect in this context. In conclusion, this study demonstrates that the activated PINK1/Parkin-mediated mitophagy exerts a significantly protective effect against 1,4-BQ-induced apoptosis in HL-60 cells.

[mRNA expression and methylation status of p15 promoter in mouse bone marrow cells exposed to 1,4-benzoquinone].

OBJECTIVE: To detect the expression and the CpG island methylation status of tumor suppressor gene p15 after exposure to 1,4-benzoquinone (1,4-BQ) in primary cultivated C57BL/6J mouse bone marrow cells in vitro. METHODS: The mouse bone marrow cells were isolated in vitro. The effect of 0, 0.1, 1, 5, 10, 20, and 40 µmol/L 1,4-BQ on cell viability (CKK-8) was detected. 0, 0.1, 1, 10 µmol/L 1,4-BQ were used to intoxicate the mouse bone marrow cells for 24 h; Real-time PCR was employed to analyze the mRNA expression level of p15; The bisulfite sequencing PCR (BSP) was used to look into the methylation status of CpG islands in p15 promoter region. RESULTS: 1,4-BQ exhibited dose-dependent toxicity to mouse bone marrow cells, and the LC(50) was 8.3 µmol/L (95%CI: 4.6 - 10.6 µmol/L). The mRNA expression of p15 in 10 µmol/L group was only equivalent to 43% of control group. Compared with control group, the decrease of p15 mRNA expression in1 and 10 µmol/L concentration were obvious, and the differences had statistical significance (P < 0.05 or P < 0.01). BSP sequencing results were same between the exposure groups and control group, the 56 CpG sites on CpG islands remained in the state of unmethylated. CONCLUSION: mRNA expression of p15 gene decreases after exposure to 1,4-BQ, but the CpG islands methylation status in promoter is not affected, suggesting that methylation does not participate in 1,4-BQ-mediated p15 gene expression decrease, other effect mechanisms still need to be investigated.

Improvement of Laih and Yen's multisignature scheme.

A new attack is proposed to show that a specified group of verifiers can cooperate to forge the signature for any message by secret key substitution due to the leaked secret key or by the group public key adjustment because of the renewed members. This paper presents the improvement scheme which overcomes the security weakness of Laih and Yen's scheme.