Comparative Study on Flow Characteristics in Deep Marine and Marine-Continental Transitional Shale in the Southeastern Sichuan Basin, China.

Permeability is a significant characteristic of porous media and a crucial parameter for shale gas development. This study focuses on deep marine and marine-continental transitional shale in the southeastern Sichuan area using the gas pulse decay testing method to systematically analyze the gas permeability, stress sensitivity, and gas transport mechanisms of shale under different pressure conditions and directions. The results show that the porosity and gas permeability of the deep marine shale are greater compared to those of the marine-continental transitional shale. The elevated fluid pressure in the deep marine shale offers superior conditions for the preservation of nanopores, while the high quartz content provides advantageous conditions for fluid transport in nanopore channels. The permeability and stress sensitivity of the deep marine shale are greater than those of the marine-continental transitional shale, and the stress sensitivity is greater in the perpendicular bedding direction than in the parallel bedding direction, possibly related to the mineral composition of shale and the compaction it has undergone. The flow mechanism of the deep marine shale is transition flow and Knudsen flow, while that of the marine-continental transitional shale is transition flow. The deep marine shale possesses smaller nanopore sizes and a higher quantity of micropores, which create advantageous conditions for gas transport within nanopores. During the process of extracting shale gas, the extraction of gas causes a decrease in pore pressure and an increase in effective stress, resulting in a reduction in permeability. However, when the pore pressure reaches a specific value, the enhanced slippage effect leads to an increase in permeability, which is advantageous for gas extraction. In the later stage of shale gas well production, intermittent production plans can be developed considering the strength of the slippage effect, leading to a significant improvement in production efficiency.

Inhibition of Pi4kb activity causes malformation of vestibular apparatus in zebrafish by downregulating hey1.

Phosphatidylinositol 4 kinase-ß (PI4KB) plays critical roles in human genetic diseases. In zebrafish, Pi4kb is strongly expressed in hair cells (HCs), which are necessary for detecting sound vibrations, head movements, and water motion. However, the role of PI4KB in HC or semicircular canal development is unclear. Herein, we report that pi4kb morphants exhibit insensitivity to sound stimulation and abnormal morphological vestibular organs, including cilium loss in HCs of the cristae and semicircular canal malformation. As bone morphogenetic protein (BMP) signaling is associated with HC and semicircular canal development, we analyzed the expression of BMP-related genes; the phosphorylated Smad1/5/9 (p-Smad1/5/9) expression was markedly reduced in otic HCs. RNA-sequencing data indicated that the transcriptional levels of BMP membrane receptor 2 (bmpr2a and bmpr2b) and hes-related family of bHLH transcription factors with YRPW motif 1 (hey1), a direct downstream target gene of p-Smad, were significantly reduced in the pi4kb morphants, as verified using quantitative reverse transcription-polymerase chain reaction and in situ hybridization. Co-injection of hey1 mRNA and pi4kb morpholino notably recovered vestibular apparatus development, including the number and length of cilia in HCs of the cristae and semicircular canal formation. Collectively, these results suggest that Pi4kb is involved in vestibular apparatus development in zebrafish by regulating BMP membrane receptor 2 and p-Smad1/5/9 levels, thereby affecting the transcriptional activation of the target gene hey1. This study sheds light on the interaction between Pi4kb and the BMP-Hey1 signaling axis, which is critical for HC and semicircular canal formation.

Paraoxon attenuates vascular smooth muscle contraction through inhibiting Ca2+ influx in the rabbit thoracic aorta.

We investigated the effect of paraoxon on vascular contractility using organ baths in thoracic aortic rings of rabbits and examined the effect of paraoxon on calcium homeostasis using a whole-cell patch-clamp technique in isolated aortic smooth muscle cells of rabbits. The findings show that administration of paraoxon (30 microM) attenuated thoracic aorta contraction induced by phenylephrine (1 microM) and/or a high K+ environment (80 mM) in both the presence and absence of thoracic aortic endothelium. This inhibitory effect of paraoxon on vasoconstrictor-induced contraction was abolished in the absence of extracellular Ca2+, or in the presence of the Ca2+ channel inhibitor, verapamil. But atropine had little effect on the inhibitory effect of paraoxon on phenylephrine-induced contraction. Paraoxon also attenuated vascular smooth muscle contraction induced by the cumulative addition of CaCl2 and attenuated an increase of intracellular Ca2+ concentration induced by K+ in vascular smooth muscle cells. Moreover, paraoxon (30 microM) inhibited significantly L-type calcium current in isolated aortic smooth muscle cells of rabbits. In conclusion, our results demonstrate that paraoxon attenuates vasoconstrictor-induced contraction through inhibiting Ca2+ influx in the rabbits thoracic aorta.

Involvement of Na+/H+ exchanger 1 in advanced glycation end products-induced proliferation of vascular smooth muscle cell.

In this present study, we examined the role of Na(+)/H(+) exchanger 1 (NHE1) in the cultured rat vascular smooth muscle cell (VSMC) proliferation induced by advanced glycation end products (AGEs). AGEs significantly increased the [(3)H] thymidine incorporation of VSMC. Cariporide, an NHE1 inhibitor, dose-dependently attenuated the AGEs-induced increase in cell DNA synthesis. Thus the effect of AGEs on NHE1 activity was next examined. The cariporide-dependent intracellular pH (pH(i)) was significantly increased after 24h exposure to AGEs (10mug/ml). The direct AGEs-induced NHE1 activation was measured by the Na(+)-dependent intracellular pH recovery from intracellular acidosis. AGEs can increase the NHE1 activity in a time- and concentration-dependent manner. Inhibition of either the receptor for AGEs (RAGE) by anti-RAGE or mitogen-activated protein kinases (MAPK) by PD98059 reversed the effect of AGEs on NHE1 activity. Reverse transcription (RT)-PCR analysis revealed that AGEs dose-dependently increased NHE1 mRNA at 24h. These findings demonstrate NHE1 is required for in AGEs-induced proliferation of VSMC, and AGEs increase NHE1 activity via the MAPK pathway.

Inhibition of NA(+)/H(+) Exchanger 1 Attenuates Renal Dysfunction Induced by Advanced Glycation End Products in Rats.

It has been recognized that sodium hydrogen exchanger 1 (NHE1) is involved in the development of diabetic nephropathy. The role of NHE1 in kidney dysfunction induced by advanced glycation end products (AGEs) remains unknown. Renal damage was induced by AGEs via tail vein injections in rats. Function and morphology of kidney were determined. Compared to vehicle- or BSA-treated rats, AGEs caused abnormalities of kidney structures and functions in rats, accompanied with higher MDA level and lower GSH content. Gene expressions of NHE1 gene and TGF-ß1 in the renal cortex and urine were also increased in AGEs-injected rats. Importantly, all these detrimental effects induced by AGEs were reversed by inhibition of NHE1 or suppression of oxidative stress. These pieces of data demonstrated that AGEs may activate NHE1 to induce renal damage, which is related to TGF-ß1.