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Multiple roles of reactive oxygen species (ROS) and their consequences for health and disease are emerging throughout biological sciences. This development has led researchers unfamiliar with the complexities of ROS and their reactions to employ commercial kits and probes to measure ROS and oxidative damage inappropriately, treating ROS (a generic abbreviation) as if it were a discrete molecular entity. Unfortunately, the application and interpretation of these measurements are fraught with challenges and limitations. This can lead to misleading claims entering the literature and impeding progress, despite a well-established body of knowledge on how best to assess individual ROS, their reactions, role as signalling molecules and the oxidative damage that they can cause. In this consensus statement we illuminate problems that can arise with many commonly used approaches for measurement of ROS and oxidative damage, and propose guidelines for best practice. We hope that these strategies will be useful to those who find their research requiring assessment of ROS, oxidative damage and redox signalling in cells and in vivo.

In order to explore a scientific and effective fault complexity evaluation method, through analyzing the basic characteristic indicators of the fault, based on the fractal theory, selecting the fractal dimension value of the fault, the fault density value, the number of fault interchange points and the fault intensity index as the evaluation indicators, we use the idea of game theory to construct a combined weighting method of order relation analysis method and entropy weight method, and evaluate the complexity of faults in the north No.10 mining area of Jiangzhuang Coal Mine. The results are as follows: the simple and medium tectonic areas of the fault are mainly located in the west, south and north of the study area, and are distributed in a ring shape; the lower complex structural areas are mainly located in the south and north of the study area, distributed in strips and blocks; the complex structural areas are mainly located in the middle of the study area, and some are scattered in the south and north; the extremely complex structural areas are mainly distributed in the central part of the study area in large blocks.

Based on the data of drilling, geophysical exploration and roadway fault exposure of No.3 upper 107 working face in first mining area of Sanhekou Coal Mine, the water bearing capacity of Sanhekou fault and Qianzhai fault in natural state is analyzed, and the fault sealing methods such as lithology juxtaposition map, SGR method and fault plane normal pressure method are used to evaluate the fault water conductivity in natural conditions from lateral and vertical aspects. The numerical simulation of fault seepage characteristics and activation law under the condition of mining in working face is carried out. The results show that both Sanhekou fault and Qianzhai fault are water free faults under natural conditions. When the working face is excavated 30 m away from Sanhekou fault and 26 m away from Qianzhai fault, the pore water pressure in the two fault layers increases slowly, and only the upper end of the fault is damaged within a small range, and the overall water blocking performance of the fault does not change.

In order to accurately predict the development height of water-conducting fracture zone in the roof of fully mechanized caving coal of No.3 coal seam in Tengzhou Mining Area, based on the measured data of water-conducting fracture zone height and main control factors of 18 working faces in Tengzhou Mining Area, we use SPSS software to carry out correlation analysis on six factors such as mining thickness, mining depth, coal seam dip angle, strike length, dip length and roof thickness, and build the water-conducting fractured zone height of multivariate linear regression forecast model. Finally, four working faces in Tengxian Coalfield are taken as examples to calculate the height of water-conducting fracture zone and compare the error analysis by using the regulations for coal mining under buildings, water bodies and railways, standard formula and regression model. In addition, Tengdong Coal Mine also used UDEC numerical simulation analysis for auxiliary verification. The results show that the model’s predicted values in this paper are closer to the measured values(the error is controlled within 8%), and the accuracy is higher than that of the empirical formula.

During the Holocene, the upper and middle reaches of the Yellow River valley in China were pivotal areas for agricultural development. Quantitatively reconstructing the spatiotemporal changes in prehistoric human land use is essential for understanding, from a long-term perspective, the interactions among evolutions of climate, agriculture, and human activities. Based on 327 archaeological sites and the PLUM (prehistoric land use model), we quantitatively reconstructed human land use changes from 6 to 3 ka BP (thousands of years before the present) in the Tao River valley, the second-largest tributary in the upper reach of the Yellow River valley. The results indicated that regional land use areas increased from 571 km2 to 1468 km2, with spatial expansion from the lower reach to the upper–middle reach of the Tao River valley. A comparison of the five areas distributed across the upper and middle reaches of the Yellow River valley revealed two different trends of increasing land use from 8 to 3 ka BP within these areas. The first group (the Wei River and Yiluo River valleys) exhibited rapid and substantial growth before 5 ka BP, while the second group (the Huangshui River and Tao River valleys, and the Yunlin district) showed a much slower and less significant increase before 5 ka BP, but a more obvious increase thereafter. The asynchronous increases in these areas indicate an expansion of land use from the southeastern part of the upper and middle reaches of the Yellow River Valley to across the entire region between 8 and 3 ka BP, which was primarily driven by agricultural development and cultural communication. [ABSTRACT FROM AUTHOR]

This article discusses a study that used nontargeted metabolomics and machine learning to identify potential biomarkers for cardiovascular diseases (CVD), specifically coronary heart disease (CHD) and myocardial infarction (MI). The study analyzed serum samples from a Chinese cohort of patients with CHD, MI, and controls, and identified differential metabolites that could distinguish between the groups. The researchers also conducted pathway enrichment analysis to explore the metabolic pathways involved in CHD and MI progression. They developed a model based on three metabolites (arginine, hypoxanthine, and acetylcarnitine) that could discriminate between CHD and MI with high accuracy. The study suggests that metabolomics and machine learning have the potential to improve the diagnosis of CHD and MI. [Extracted from the article]

The fault water damage accounts for most of the coal mine floor water inrush accidents in China, and the pillar design of fault waterproof coal(rock) is the main means to prevent fault water damage, which is related to the safety and efficient production of coal mine. The reasonable width of fault waterproof coal (rock) column can not only prevent the underground water from pouring into the mine through the fault, but also serve the reasonable and safe mining of coal resources. The design of fault waterproof coal (rock) column width involves many factors and is one of the focuses of many scholars and engineers. A variety of research methods have been applied at present, including theoretical calculation, multiple regression analysis, BP and RBF, similarity simulation, numerical simulation for the coal (rock) column design under different fault conditions have been specifically studied. On this basis, the research status of fault coal (rock) pillar is summarized, the existing problems are pointed out, and the future research technology and methods are prospected.

Acetaldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme detoxifying acetaldehyde and endogenous lipid aldehydes; previous studies suggest a protective role of ALDH2 against cardiovascular disease (CVD). Around 40% of East Asians carrying the single nucleotide polymorphism (SNP) ALDH2 rs671 have an increased incidence of CVD. However, the role of ALDH2 in CVD beyond alcohol consumption remains poorly defined. Here we report that ALDH2/LDLR double knockout (DKO) mice have decreased atherosclerosis compared with LDLR-KO mice, whereas ALDH2/APOE-DKO mice have increased atherosclerosis, suggesting an unexpected interaction of ALDH2 with LDLR. Further studies demonstrate that in the absence of LDLR, AMPK phosphorylates ALDH2 at threonine 356 and enables its nuclear translocation. Nuclear ALDH2 interacts with HDAC3 and represses transcription of a lysosomal proton pump protein ATP6V0E2, critical for maintaining lysosomal function, autophagy, and degradation of oxidized low-density lipid protein. Interestingly, an interaction of cytosolic LDLR C-terminus with AMPK blocks ALDH2 phosphorylation and subsequent nuclear translocation, whereas ALDH2 rs671 mutant in human macrophages attenuates this interaction, which releases ALDH2 to the nucleus to suppress ATP6V0E2 expression, resulting in increased foam cells due to impaired lysosomal function. Our studies reveal a novel role of ALDH2 and LDLR in atherosclerosis and provide a molecular mechanism by which ALDH2 rs671 SNP increases CVD., IntroductionAtherosclerosis is the major cause of cardiovascular disease (CVD), and macrophages play a central role in progression of atherosclerosis (1, 2). In the early stage of atherosclerosis, macrophages take up [...]

Oxidized phospholipids (OxPLs) are present on apolipoprotein (a) [apo(a)] and lipoprotein (a) [Lp(a)] but the determinants influencing their binding are not known. The presence of OxPLs on apo(a)/Lp(a) was evaluated in plasma from healthy humans, apes, monkeys, apo(a)/Lp(a) transgenic mice, lysine binding site (LBS) mutant apo(a)/Lp(a) mice with Asp(55/57)→Ala(55/57) substitution of kringle (K)IV10)], and a variety of recombinant apo(a) [r-apo(a)] constructs. Using antibody E06, which binds the phosphocholine (PC) headgroup of OxPLs, Western and ELISA formats revealed that OxPLs were only present in apo(a) with an intact KIV10 LBS. Lipid extracts of purified human Lp(a) contained both E06- and nonE06-detectable OxPLs by tandem liquid chromatography-mass spectrometry (LC-MS/MS). Trypsin digestion of 17K r-apo(a) showed PC-containing OxPLs covalently bound to apo(a) fragments by LC-MS/MS that could be saponified by ammonium hydroxide. Interestingly, PC-containing OxPLs were also present in 17K r-apo(a) with Asp(57)→Ala(57) substitution in KIV10 that lacked E06 immunoreactivity. In conclusion, E06- and nonE06-detectable OxPLs are present in the lipid phase of Lp(a) and covalently bound to apo(a). E06 immunoreactivity, reflecting pro-inflammatory OxPLs accessible to the immune system, is strongly influenced by KIV10 LBS and is unique to human apo(a), which may explain Lp(a)'s pro-atherogenic potential.

Oxidation of low-density lipoprotein (LDL) is one of the major causative mechanisms in the development of atherosclerosis. In previous studies, we showed that minimally oxidized LDL (mmLDL) induced inflammatory responses in macrophages, macropinocytosis and intracellular lipid accumulation and that oxidized cholesterol esters (OxCEs) were biologically active components of mmLDL. Here we identified a specific OxCE molecule responsible for the biological activity of mmLDL and characterized signaling pathways in macrophages in response to this OxCE. Using liquid chromatography - tandem mass spectrometry and biological assays, we identified an oxidized cholesteryl arachidonate with bicyclic endoperoxide and hydroperoxide groups (BEP-CE) as a specific OxCE that activates macrophages in a TLR4/MD-2-dependent manner. BEP-CE induced TLR4/MD-2 binding and TLR4 dimerization, phosphorylation of SYK, ERK1/2, JNK and c-Jun, cell spreading and uptake of dextran and native LDL by macrophages. The enhanced macropinocytosis resulted in intracellular lipid accumulation and macrophage foam cell formation. Bone marrow-derived macrophages isolated from TLR4 and SYK knockout mice did not respond to BEP-CE. The presence of BEP-CE was demonstrated in human plasma and in the human plaque material captured in distal protection devices during percutaneous intervention. Our results suggest that BEP-CE is an endogenous ligand that activates the TLR4/SYK signaling pathway. Because BEP-CE is present in human plasma and human atherosclerotic lesions, BEP-CE-induced and TLR4/SYK-mediated macrophage responses may contribute to chronic inflammation in human atherosclerosis.

Cytochrome (cyt) c can uncouple from the respiratory chain following mitochondrial stress and catalyze lipid peroxidation. Accumulating evidence shows that this phenomenon impairs mitochondrial respiratory function and also initiates the apoptotic cascade. Therefore, under certain conditions a pharmacological approach that can inhibit cyt c catalyzed lipid peroxidation may be beneficial. We recently showed that acetaminophen (ApAP) at normal pharmacologic concentrations can prevent hemoprotein-catalyzed lipid peroxidation in vitro and in vivo by reducing ferryl heme to its ferric state. We report here, for the first time, that ApAP inhibits cytochrome c-catalyzed oxidation of unsaturated free fatty acids and also the mitochondrial phospholipid, cardiolipin. Using isolated mitochondria, we also showed that ApAP inhibits cardiolipin oxidation induced by the pro-apoptotic protein, tBid. We found that the IC(50) of the inhibition of cardiolipin oxidation by ApAP is similar in both intact isolated mitochondria and cardiolipin liposomes, suggesting that ApAP penetrates well into the mitochondria. Together with our previous results, the findings presented herein suggest that ApAP is a pleiotropic inhibitor of peroxidase catalyzed lipid peroxidation. Our study also provides a potentially novel pharmacological approach for inhibiting the cascade of events that can result from redox cycling of cyt c.