Although 5-methylcytosine (m
C) is a widespread modification in RNAs, its regulation and biological role in pathological conditions (such as cancer) remain unknown. Here, we provide the ...single-nucleotide resolution landscape of messenger RNA m
C modifications in human urothelial carcinoma of the bladder (UCB). We identify numerous oncogene RNAs with hypermethylated m
C sites causally linked to their upregulation in UCBs and further demonstrate YBX1 as an m
C 'reader' recognizing m
C-modified mRNAs through the indole ring of W65 in its cold-shock domain. YBX1 maintains the stability of its target mRNA by recruiting ELAVL1. Moreover, NSUN2 and YBX1 are demonstrated to drive UCB pathogenesis by targeting the m
C methylation site in the HDGF 3' untranslated region. Clinically, a high coexpression of NUSN2, YBX1 and HDGF predicts the poorest survival. Our findings reveal an unprecedented mechanism of RNA m
C-regulated oncogene activation, providing a potential therapeutic strategy for UCB.
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
The filled broken rock mass in a geothermal reservoir under high-pressure work fluid and overburden stress is of great significance to the efficient operation of the geothermal system. The pore ...structure and hydraulic properties of the broken rock mass were quantitatively investigated by the nuclear magnetic resonance (NMR) technology and the non-Darcy models. The broken rock mass at the lower compressive stress levels shows stronger compressibility, and the broken gangue with more small particles shows stronger stress sensitivity. The seepage pores in broken rock can be characterized by the fractal theory, and the fractal dimension ranges from 2.749 to 2.861, which is positively correlated with compressive stress. The increase in Dp can be attributed to the shrinkage of macropores affected by the increasing compressive stress. The flow in broken rock mass under high pressure gradient shows significant nonlinearity verified by the Forchheimer equation and the Barree-Conway equation. We proposed a logistic regression model to characterize the effects of compressive stress and GSD on the permeability and the characteristic parameter of nonlinear flow in broken rock mass, which provides a potential method for evaluating the performance of the geothermal system based on the pore structure of the reservoir rock mass.
Engineered nanoparticles (ENPs) have been widely applied in industry, commodities, biology and medicine recently. The potential for many related threats to human health has been highlighted. ENPs ...with their sizes no larger than 100 nm are able to enter the human body and accumulate in organs such as brain, liver, lung, testes, etc, and cause toxic effects. Many references have studied ENP effects on the cells of different organs with related cell apoptosis noted. Understanding such pathways towards ENP induced apoptosis may aid in the design of effective cancer targeting ENP drugs. Such ENPs can either have a direct effect towards cancer cell apoptosis or can be used as drug delivery agents. Characteristics of ENPs, such as sizes, shape, forms, charges and surface modifications are all seen to play a role in determining their toxicity in target cells. Specific modifications of such characteristics can be applied to reduce ENP bioactivity and thus alleviate unwanted cytotoxicity, without affecting the intended function. This provides an opportunity to design ENPs with minimum toxicity to non-targeted cells.
•Water-conducting channels are prone to forming in the fault, causing water inflow.•Evolution of hydraulic properties under the radial grain migration was studied.•Low GSD and high WP can enhance the ...grain migration effect.•Three permeability predicted models were verified by the testing results.•Strategies for the prevention and control of water inflow were proposed.
When fault fracture zones are encountered in the mining tunnel excavation, the water-conducting pathway is easily formed by the granular structure of the broken surrounding rock, probably resulting in water inflow hazards. Therefore, the configuration and hydrological characteristics of existing faults are key factors for the safe mining tunnel construction. In this paper, one-dimensional (1D) radial seepage experiments were carried out under variable grain size distribution (GSD) and water pressure (WP). Hydraulic properties were investigated, including porosity and permeability under the 1D radial grain migration. Experimental results show that the permeability and porosity increase with time, and the occurrence process of water inflow can divide into four stages, including the rapid increase, decelerated increase, slow climbing, and stable period. After the seepage experiment, the porosity of the sample increases gradually from the top to the bottom and reaches the maximum at the lowermost part (outlet), indicating that the spatial distribution of the porosity exhibits the non-uniform property. Through comparisons of grain migration under different conditions, it is concluded that, with the decrease of GSD and the increase of WP, more severe fine grain migration can be occurred, leading to great changes in hydraulic properties. In addition, three prediction models were verified by the testing results, and Carman-Kozoeny model shows the highest accuracy. In the same predictive model, if a sample has a smaller grain migration capacity, then there is a higher prediction accuracy of the sample. By means of Carman-Kozoeny model, it is predicted that there is a higher final permeability in the position closer to the water outlet. Based on the research results, a series of strategies were proposed to prevent and control water inflow in fault rocks.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Kinesins are essential for the proper function of many types of polar cells, including epithelial cells, neurons, and sperm. Spermatogenesis is closely associated with many different kinesins. These ...kinesins participate in several fundamental processes, including mitotic and meiotic division, essential organelle transport, and the biogenesis of peculiar structures for the formation of mature sperm. Kinesin-13, kinesin-8, and the chromokinesin families cooperate to ensure normal sister chromatid congression and segregation. The kinesin-8 family motor KIF18A, kinesin-12 motors PAKRP/kinesin12A and PAKRP1L/kinesin12B, and other kinesin-like motors are essential in the process of homologous chromosome pairing and in the separation to create haploid gametes. During spermiogenesis, the responsibility of a handful of kinesin members lies in the maturation of spermatids into mature, motile, and intact spermatozoa. Such roles are completed upon the release of viable and functional sperm into the lumen of seminiferous tubules. In this process, KIFC1, KIF5C, KRP3A, and KRP3B may be involved in acrosome biogenesis; KIFC1, KIFC5, CHO2, KIF17b, and KIF3A probably contribute to nuclear shaping; KIF17b, KIF3A, and KLC3 are implicated in the tail formation process; and KIF20 and KRP3 likely participate in sperm translocation. KIF17b also exhibited postmeiosis transcriptional activities that are critical for the dramatic alterations observed in nuclear and cytoplasmic structures. This review summarizes the roles of kinesins during mitosis, meiosis, and spermiogenesis, and proposes several important issues for further investigation.
The deformation-induced transformation characteristics and texture evolution of α′-martensite during cold rolling together with the tensile properties of two specially prepared initial ...microstructures (bimodal elongated γ grains and fine equiaxed γ grains) were investigated in high manganese TRIP steels. The results showed that the thermally induced martensite was restrained effectively by refining grains or introducing crystal defects like dislocations, which provided a nearly full austenite phase for the subsequent TRIP process. Compared with the solution-treated sample containing coarse equiaxed γ grains, the fine-grained sample revealed a better plasticity and a higher strength due to grain refinement and progressive TRIP process. The bimodal elongated-grained sample exhibited the highest strength and sufficient plasticity because the dislocation strengthening exceeded the fine-grain strengthening and martensitic transformation was delayed. The transformation textures of two kinds of samples differed in that the fine-grained sample demonstrated typical {113} α from the Copper-type γ texture and {332} α from the Brass-type γ texture, whereas {001} α texture occurred in the bimodal elongated-grained sample in addition to the above two components. In the early stage of TRIP, there was an obvious orientation dependence, and the {100}- and Copper-oriented γ grains preferentially transformed to martensite rather than γ grains with Brass orientation.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Water inrush is one of the most dangerous disasters in coal mining. Due to the large-scale mining and complicated hydrogeological conditions, thousands of deaths and huge economic losses have been ...caused by water inrush disasters in China. There are two main factors determining the occurrence of water inrush: water source and water-conducting pathway. Research on the formation mechanism of the water-conducting pathway is the main direction to prevent and control the water inrush, and the seepage mechanism of rock mass during the formation of the water-conducting pathway is the key for the research on the water inrush mechanism. This paper provides a state-of-the-art review of seepage mechanisms during water inrush from three aspects, i.e., mechanisms of stress-seepage coupling, flow regime transformation and rock erosion. Through numerical methods and experimental analysis, the evolution law of stress and seepage fields in the process of water inrush is fully studied; the fluid movement characteristics under different flow regimes are clearly summarized; the law of particle initiation and migration in the process of water inrush is explored, and the effect of rock erosion on hydraulic and mechanical properties of the rock media is also studied. Finally, some limitations of current research are analyzed, and the suggestions for future research on water inrush are proposed in this review.
Groundwater inrush has an impartible relationship with geological structures such as karst collapse pillars (KCPs), which are widely distributed in North China. In order to study the mechanism of ...groundwater inrush from coal seam floor, the variable mass dynamics and nonlinear dynamics were introduced. A mechanical model–plug model is established to describe the behavior of water seepage flow in coal-seam-floor containing KCP. The study shows that: (1) If the mass of the KCP keeps steady, the water seepage velocity in the KCP and the surrounding rocks will reach a constant value soon; (2) if the mass of the KCP and the surrounding rocks increases by grouting, etc, the seepage velocity in the KCP and the surrounding rocks will reach its minimum value gradually, and (3) if the mass of the KCP and the surrounding rocks decreases by scouring, the flow velocity in the KCP and the surrounding rocks shows a monotone increase, the water flow may change into pipe flow, especially when a large number of the mass of the KCP and the surrounding rocks enters into goaf road, which may lead to instable flow and cause groundwater inrush.
•Use variable mass dynamics and nonlinear dynamics to explain groundwater inrush•Plug model is established to describe the behavior of water seepage flow.•If KCP keeps steady, water seepage velocity reaches a constant value.•Water seepage velocity reaches minimum gradually with the increase of KCP.•A large mass of KCP loss can cause groundwater inrush.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
To understand combined effects of water saturation and loading rate on the fracture behavior of rock materials, dynamic notched semi-circular bending (NSCB) tests were conducted on dry and saturated ...sandstone specimens under a wide range of loading rates using a modified split Hopkinson pressure bar (SHPB) setup. Test results revealed that, the dynamic fracture initiation, propagation toughness and crack propagation velocity of saturated specimen were apparently lower than that of dry ones at the same loading rate. The above parameters increased with the increase of loading rate. Compared with the dry specimen, the saturated specimen owned a higher rate dependency of the dynamic fracture initiation, propagation toughness and a lower rate dependency of crack propagation velocity. Moreover, dual effects of water on the fracture behavior under different loading rates were discussed. It is believed that the different rate dependencies of fracture behaviors between dry and saturated specimens was governed by the combined weakening and enhancing effects of water. A micro-mechanical model was further developed to explain the experimental results based on the duality of water and linear elastic fracture mechanics (LEFM).
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
PDF
