Liver fibrosis and hepatic stellate cells: Etiology, pathological hallmarks and therapeutic targets

Liver fibrosis is a reversible wound-healing process aimed at maintaining organ integrity, and presents as the critical pre-stage of liver cirrhosis, which will eventually progress to hepatocellular carcinoma in the absence of liver transplantation. Fibrosis generally results from chronic hepatic injury caused by various factors, mainly viral infection, schistosomiasis, and alcoholism; however, the exact pathological mechanisms are still unknown. Although numerous drugs have been shown to have antifibrotic activity in vitro and in animal models, none of these drugs have been shown to be efficacious in the clinic. Importantly, hepatic stellate cells(HSCs) play a key role in the initiation, progression, and regression of liver fibrosis by secreting fibrogenic factors that encourage portal fibrocytes, fibroblasts, and bone marrow-derived myofibroblasts to produce collagen and thereby propagate fibrosis. These cells are subject to intricate cross-talk with adjacent cells, resulting in scarring and subsequent liver damage. Thus, an understanding of the molecular mechanisms of liver fibrosis and their relationships with HSCs is essential for the discovery of new therapeutic targets. This comprehensive review outlines the role of HSCs in liver fibrosis and details novel strategies to suppress HSC activity, thereby providing new insights into potential treatments for liver fibrosis.

Curvature-enhanced multipartite coherence in the multiverse

Here,we study the quantum coherence of N-partite Greenberger-Horne-Zeilinger(GHZ)and W states in the multiverse consisting of N causally disconnected de Sitter spaces.Interestingly,N-partite coherence increases monotonically with curvature,whereas the curvature effect destroys quantum entanglement and discord,indicating that the curvature effect is beneficial to quantum coherence and harmful to quantum correlations in the multiverse.We find that with an increase in n expanding de Sitter spaces,the N-partite coherence of the GHZ state increases monotonically for any curvature,whereas the quantum coherence of the W state decreases or increases monotonically depending on the curvature.We find a distribution relationship,which indicates that the correlated coherence of the N-partite W state is equal to the sum of all bipartite correlated coherence in the multiverse.Multipartite coherence exhibits unique properties in the multiverse,suggesting that it may provide some evidence for the existence of the multiverse.

Effect of annealing time on microstructure and mechanical properties of cryorolled AISI 310S stainless steel

AISI 310S stable austenitic stainless steel was subjected to 90%cryorolling and then annealed at 800 ℃ for 2-60 min.The effect of annealing time on the microstructure and mechanical properties was studied by optical microscopy,scanning electron microscopy,transmission electron microscopy,microhardness and tensile test.The results show that the grain size of AISI 310S stainless steel is refined to the nanometer level after 90%cryorolling,and the grain size is approximately 20 nm.With the increase in annealing time,the degree of grain recrystallization occurs more fully and completely,as the grain begins to grow and then tends to stabilize.The strength and hardness of the annealed specimens decrease with increasing annealing time,while elongation tends to increase.When the annealing time is 10 min,the yield strength increases by about 2 times compared to that of the original austenite(unrolled),and the elongation is also above 20%,which is the best preparation process for ultra-fine grain austenitic stainless steel under this experimental condition.As the annealing time treatment increases,the fracture morphology changes from mixed quasi-cleavage and ductile fracture(after cryorolling)to ductile fracture(after annealing).

Effects of solid-solution temperature on microstructure and mechanical properties of a novel 2000MPa grade ultra-high-strength steel

A novel 2000 MPa grade ultra-high-strength steel AIR0509 with high fracture toughness and low cost has recently been developed. The effects of solid-solution temperature on the microstructure and mechanical properties of this steel were inves-tigated. The increase in solid-solution temperature first increased and then decreased the values of ultimate strength (UTS) and Charpy U-notch (CUN) energy. The increase in the UTS and CUN values was caused by the dissolution of the primary carbides M6C and MC, while the decrease in both strength and toughness was due to the increase in the prior austenite grain size. Samples that were solid-solution treated at 1000℃ exhibited an optimal combination of strength and toughness with a UTS of 2020MPa, yield strength of 1780MPa, and CUN energy of 68J, as well as a correlative fracture toughness KIC value of about 105MPam1/2.

Phase Stability,Elastic,Thermo-physical and Electronic Properties of Hexa-(Mo,Cr,W)_2C from First-principles Calculations

Phase stability,elastic properties,thermo-physical properties,as well as electronic properties of hexa-（Mo,Cr,W）2C carbides were investigated by first-principles calculations.The results indicated that the Mo8C4,Mo7Cr1C4,Mo7W1C4,Mo6W2C4,and Mo6W1Cr1C4 are stable and the stability follows the sequence：Mo6W1Cr1C4〉Mo7W1C4〉Mo7Cr1C4〉 Mo6W2C4〉 Mo8C4.Mo6W1Cr1C4 shows the highest stability,deformation resistance and hardness.G/B（shear modulus/bulk modulus）and Poisson′s ratio of the stable hexa-（Mo,Cr,W）2C are all larger than 1.75 and 0.26,respectively,which indicates that they are all brittle.The anisotropies are mainly due to the different Vogit shear modulus/Reuss shear modulus;the mechanical anisotropy of Mo7Cr1C4 is the largest,and that of Mo8C4 is the smallest.Moreover,the obtained Debye temperatureΘDand heat capacity Cpindicate that Mo6W2C4 possesses the best thermal conductivity（ΘD=497.72K）,while Mo7Cr1C4 and Mo6W2C4possess the largest heat capacity when the temperature is in the range of 0-10 Kand larger than 10 K,respectively.From the electronic property analysis,the doped Cr and W atoms can not only participate in orbitals hybridization themselves but also enhance the orbitals hybridization between Mo and C atoms,which can reinforce the interatomic interactions.