Search

Excessive accumulation of extracellular matrix (ECM) components within the liver leads to a pathological condition known as liver fibrosis. Alcohol abuse, non-alcoholic fatty liver disease (NAFLD), autoimmune issues, and viral hepatitis cause chronic liver injury. Exploring potential therapeutic targets and understanding the molecular mechanisms involved in liver fibrosis are essential for the development of effective interventions. The goal of this comprehensive review is to explain how the PI3K/AKT signaling pathway contributes to the reduction of liver fibrosis. The potential of this pathway as a therapeutic target is investigated through a summary of results from in vivo and in vitro studies. Studies focusing on PI3K/AKT activation have shown a significant decrease in fibrosis markers and a significant improvement in liver function. The review emphasizes how this pathway may prevent ECM synthesis and hepatic stellate cell (HSC) activation, ultimately reducing the fibrotic response. The specific mechanisms and downstream effectors of the PI3K/AKT pathway in liver fibrosis constitute a rapidly developing field of study. In conclusion, the PI3K/AKT signaling pathway plays a significant role in attenuating liver fibrosis. Its complex role in regulating HSC activation and ECM production, demonstrated both in vitro and in vivo, underscores its potential as a effective therapeutic approach for managing liver fibrosis and slowing disease progression. A comprehensive review of this field provides valuable insights into its future developments and implications for clinical applications.

The terpolymerization of ethylene with hexene and styrene derivatives was achieved with a rare earth metal catalyst (C5Me4SiMe3)Sc(CH2C6H4NMe2-o)2 to prepare functional polyethylene. The catalyst system exhibited high activity in the terpolymerization of ethylene with hexene and amine-substituted styrene, affording terpolymers a moderate molecular weight and a unimodal molecular weight distribution. In addition, the comonomer content of the terpolymers can be controlled by changing the feeding ratio of monomers. The aliphatic region of the 13C NMR spectra reveals that the structural units of the comonomers are separately incorporated into the polyethylene backbone. Terpolymers containing styrene derivatives exhibit enhanced tensile strength and significantly improve hydrophilic properties. [ABSTRACT FROM AUTHOR]

Abstract Aim To explore the effects of hypothermia and hypoxia on rat skeletal muscle and lipid metabolism. Method Forty male rats were randomly divided into blank group, low-temperature group, hypoxia group, and hypothermia combined with hypoxia group. The body weight of the rats was monitored. The changes of Irisin were detected by ELISA, and LDL, HDL, TC, and TG levels in serum were detected by blood biochemistry. Western blot was used to detect the changes of lipid metabolism-related proteins. CCK8 was used to verify the effect of AMPK/PGC1α on the proliferation of rat skeletal muscle cells. Result In the case of cold stimulation and hypoxia, the weight of the rats decreased significantly, and the levels of LDL, HDL, TC, and TG in the serum were abnormal. The activity of fatty acid metabolism factors Irisin, UCP-1, and FABP4 is down-regulated by hypothermia and hypoxia. The activity of fat metabolism-related enzymes, ATGL, HSL, and MGL increased under hypothermia and low oxygen conditions. Hypothermia and hypoxia affected the morphology of skeletal muscle, and AMPK/PGC-1α can regulate the proliferation of skeletal muscle cells. Conclusion Hypothermia and hypoxia can reduce the body weight of rats, and affect the structure of skeletal muscle to promote lipid metabolism through AMPK/PGC-1α signaling pathway.

Pulmonary hypertension (PH) is an intractable, severe, and progressive cardiopulmonary disease. Recent findings suggest that human umbilical cord mesenchymal stromal cells (HUCMSCs) and HUCMSC-derived exosomes (HUCMSC-Exos) possess potential therapeutic value for PH. However, whether they have beneficial effects on hypoxic pulmonary hypertension (HPH) is unclear. Exos are released into the extracellular environment by the fusion of intracellular multivesicular bodies with the cell membrane, and they play an important role in cellular communication. Exos ameliorate immune inflammation levels, alter macrophage phenotypes, regulate mitochondrial metabolic function, and inhibit pulmonary vascular remodeling, thereby improving PH. Macrophages are important sources of cytokines and other transmitters and can promote the release of cytokines, vasoactive molecules, and reactive oxygen species, all of which are associated with pulmonary vascular remodeling. Therefore, the aim of this study was to investigate whether HUCMSC-Exos could improve the lung inflammatory microenvironment and inhibit pulmonary vascular remodeling by targeting macrophages and identifying the underlying mechanisms. The results showed that HUCMSC-Exos promoted M2 macrophage polarization, decreased pro-inflammatory factors, increased IL-10 levels, and inhibited IL-33/ST2 axis expression, thereby inhibiting hypoxia-induced proliferation of pulmonary artery smooth muscle cells and ameliorating HPH. [ABSTRACT FROM AUTHOR]

Photodetectors are widely used in various fields, such as industrial manufacturing and military defense. Researchers have recently sought a photodetector that combines high polarization sensitivity and a robust optical response. As an anisotropic semiconductor material, SnS holds potential for photodetection across the visible light spectrum. This study employs first-principles density functional theory (DFT) along with the non-equilibrium Green's function (NEGF) method to theoretically investigate the optoelectronic properties of the SnS monolayer in two device orientations: Armchair and Zigzag. It is found that the maximum photocurrent values between the two orientations are small at zero bias voltage, and stable photocurrent can be obtained by adding bias voltage. We examine the maximum photocurrent variation under linearly polarized light irradiation within a small bias voltage range (0.1 to 1.0 V), found for the maximum photoresponse of monolayer SnS to be large and stable at photon energy of 2.4 and 3.2 eV, and analyze the underlying mechanism of photoresponse, employing energy band and density of state diagrams. Additionally, we have calculated the extinction ratio of the SnS monolayer, confirming its strong polarization sensitivity. Finally, by subjecting the device to biaxial strain, we significantly speculate to enhance its asymmetry, leading to a substantial increase in photocurrent at zero bias. A compressive strain of - 6% notably increases the photocurrent. These findings offer valuable theoretical insights for the design of SnS monolayers as photodetectors. [ABSTRACT FROM AUTHOR]

AIM: To investigate the effect of hypoxia-preconditioned human umbilical cord mesenchymal stem cell-derived exosomes (hUCMSC-Exos) on pulmonary vascular endothelial-mesenchymal transition (EndMT) in hypoxic pulmonary hypertension (HPH). METHODS: (l) Primary hUCMSCs were isolated and cultured by tissue adhesion method, and hUCMSC-Exos were extracted by ultrafiltration and identified. (2) Twenty-four SPF male SD rats were randomly divided into normoxia (N) group, hypoxia (H) group, hypoxia+normoxic hUCMSC-Exos group and hypoxia+hypoxia-preconditioned hUCMSC-Exos group, with 6 rats in each group. The rats in H group and intervention groups were placed in a cabin that simulated the hypoxic environment at an altitude of 5 000 m, and normoxic hUCMSC-Exos, hypoxia-precon-ditioned hUCMSC-Exos or equivalent volume of PBS were injected through the tail vein on the 3rd, 5th, 7th, 10th and 14th days in hypoxia environment. After 21 d of modeling, the right ventricular systolic pressure (RVSP) and right ventricular hypertrophy index (RVHI) of the rats were detected, and the pathological changes of lung tissues were observed by HE staining. (3) After starvation for 12 h, human pulmonary arteriole endothelial cells (HPAECs) were randomly divided into normoxic control (N-Con) group, hypoxic model (H-Con) group, hypoxia+normoxic hUCMSC-Exos group and hypoxia+hypoxia-preconditioned hUCMSC-Exos group. The migration ability and tube formation ability of HPAECs were detected by Transwell assay and tube formation experiment. The expression of CD31 and α-smooth muscle actin (α-SMA) in HPAECs was detected by immunofluorescence double-staining. The protein levels of CD31, VE-cadherin, α-SMA and vimentin in pulmonary vessels and HPAECs were assessed by Western blot. RESULTS: (1) The HPH rat model was successfully established after 21 d of hypoxia, and EndMT occurred in pulmonary vessels. Compared with N group, the levels of RVSP, RVHI, percentage of vascular wall area (WA%) and percentage of vascular wall thickness (WT%) in H group were significantly increased (P<0.01), pulmonary vascular wall thickening and the protein levels of CD31 and VE-cadherin were significantly decreased (P<0. 01), while the protein levels of α-SMA and vimentin were significantly increased in pulmonary vessels (P<0.05 or P<0.01). Compared with H group, the RVSP, RVHI, WA% and WT% (P<0.01) were significantly decreased (P<0.05 or P<0.01), and pulmonary vascular remodeling was attenuated after normoxic or hypoxia-preconditioned hUCMSC-Exos intervention. After hypoxia-preconditioned hUCMSC-Exos intervention, HPH pul-monary vascular remodeling and EndMT formation were significantly inhibited. (2) After 48 h of hypoxic treatment, the migration, tubule formation and EndMT of HPAECs were induced. Compared with H-Con group, cell migration and tube formation were significantly decreased after hypoxia-preconditioned hUCMSC-Exos intervention (P<0. 01). The protein levels of CD31 and VE-cadherin were increased, while the protein levels of α-SMA and vimentin were decreased (P<0.05 or P<0.01). CONCLUSION: Hypoxia-preconditioned hUCMSC-Exos attenuate the formation of HPH pulmonary vascular remodeling by inhibiting pulmonary vascular EndMT. [ABSTRACT FROM AUTHOR]

MoTe2 has been widely studied due to its special stacking mode and rich phase structure, especially the suitable band gap which makes it have a promising application in the field of optoelectronic devices. Based on the non-equilibrium Green's function-density functional theory, the influence of different atomic vacancy defects on the photogalvanic effect of monolayer 2H-MoTe2 was studied by the first-principles calculation method. The results show that the photocurrent function of 2H-MoTe2 devices with different vacancies is consistent with the phenomenological theory. In the photon energy range from 1.0 eV to 2.8 eV, 2Te vacancy significantly improves the photocurrent of 2H-MoTe2, especially when the photon energy is 2.6 eV, the maximum photocurrent of all devices is obtained. With the energy band structure, it is found that different atomic vacancy defects lead to the shift of the valence band to the high energy level and the conduction band to the low energy level, which reduces the band gap between the four devices and conducive to the transition of electrons from the valence band to the conduction band to form photocurrent under the irradiation of linearly polarized light. It is found that the monolayer 2H-MoTe2 of 1Te vacancy and Mo vacancy has a similar energy band structure far away from the Fermi level, which leads to the same change trend of the device photocurrent when the photon energy is greater than 1.6 eV. These results can be used to guide the design of MoTe2 optoelectronic devices. [ABSTRACT FROM AUTHOR]