Alcoholic liver disease caused by chronic excessive drinking has become one of the most common types of liver disease. Alcohol-induced inflammatory immune responses play a central role in the ...development of alcohol-associated steatohepatitis. The content and expression of ATP and P2X4 in the livers of alcoholic steatohepatitis mice are significantly increased. The content of ATP increased by 20 percent and the expression of P2X4 receptor protein was 1.3 times higher than that in the livers of normal mice. Treatment with 5-BDBD, a P2X4 receptor-specific inhibitor, significantly reduced alcohol-induced liver inflammation and lipid deposition. In RAW264.7 cell experiments, 5-BDBD inhibited the expression of P2X4 and alleviated alcohol-induced inflammation, while the CD39-specific inhibitor POM-1 reduced extracellular ATP degradation and promoted the expression of P2X4, thereby exacerbating inflammation. After treatment with 5-BDBD, P2X4 receptor protein expression decreased by 0.2 times and after treatment with POM-1, P2X4 receptor protein expression increased by 0.1 times compared to the alcohol-stimulated group. In addition, inhibition of P2X4 expression in RAW264.7 cells reduced calcium influx in RAW264.7 cells. P2X4 may induce the activation of NLRP3 inflammasomes by mediating calcium influx, thus exacerbating the inflammatory response, and inhibition of P2X4 expression can effectively block this process. Conclusion: These results suggest that the ATP-P2X4 signaling pathway promotes the inflammatory response in alcoholic steatohepatitis and that CD39 may play a protective role in regulating P2X4 expression by hydrolyzing ATP. In conclusion, the CD39 and ATP-P2X4 signaling pathways may be potential therapeutic targets for alcoholic steatohepatitis.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Apigenin, identified as 4′, 5, 7-trihydroxyflavone, is a natural flavonoid compound that has many interesting pharmacological activities and nutraceutical potential including anti-inflammatory and ...antioxidant functions. Chronic, low-grade inflammation and oxidative stress are involved in both the initiation and progression of hypertension and hypertension-induced cardiac hypertrophy. However, whether or not apigenin improves hypertension and cardiac hypertrophy through modulating NADPH oxidase-dependent reactive oxygen species (ROS) generation and inflammation in hypothalamic paraventricular nucleus (PVN) has not been reported. This study aimed to investigate the effects of apigenin on hypertension in spontaneously hypertensive rats (SHRs) and its possible central mechanism of action. SHRs and Wistar-Kyoto (WKY) rats were randomly assigned and treated with bilateral PVN infusion of apigenin or vehicle (artificial cerebrospinal fluid) via osmotic minipumps (20 μg/h) for 4 weeks. The results showed that after PVN infusion of apigenin, the mean arterial pressure (MAP), heart rate, plasma norepinephrine (NE), Beta 1 receptor in kidneys, level of phosphorylation of PKA in the ventricular tissue and cardiac hypertrophy, perivascular fibrosis, heart level of oxidative stress, PVN levels of oxidative stress, interleukin 1β (IL-1β), interleukin 6 (IL-6), iNOS, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), NOX2 and NOX4 were attenuated and PVN levels of interleukin 10 (IL-10), superoxide dismutase 1 (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67) were increased. These results revealed that apigenin improves hypertension and cardiac hypertrophy in SHRs which are associated with the down-regulation of NADPH oxidase-dependent ROS generation and inflammation in the PVN.
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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
Radical-involved multicomponent difunctionalization of 1,3-dienes has recently emerged as a promising strategy for rapid synthesis of valuable allylic compounds in one-pot operation. However, the ...expansion of radical scope and enantiocontrol remain two major challenges. Herein, we describe an unprecedented photoinduced copper-catalyzed highly enantioselective three-component radical 1,2-azidooxygenation of 1,3-dienes with readily available azidobenziodazolone reagent and carboxylic acids. This mild protocol exhibits a broad substrate scope, high functional group tolerance, and exceptional control over chemo-, regio- and enantioselectivity, providing practical access to diverse valuable azidated chiral allylic esters. Mechanistic studies imply that the chiral copper complex is implicated as a bifunctional catalyst in both the photoredox catalyzed azidyl radical generation and enantioselective radical C-O cross-coupling.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
The observation of very-high-energy (VHE; > 10 GeV)
γ
-ray emission from
γ
-ray bursts (GRBs), especially in the prompt phase, will provide critical information for understanding many ...aspects of their nature including the physical environment, the relativistic bulk motion, the mechanisms of particle acceleration of GRBs, and for studying Lorentz invariance violation, etc. For the afterglow phase, the highest-energy photons detected to date by the imaging atmospheric Cherenkov telescopes extend to the TeV regime. However, for the prompt phase, years of efforts in searching for the VHE emission has yielded no statistically significant detections. A wide field of view and large effective area above tens of GeV are essential for detecting the VHE emissions from GRBs in the prompt phase. The High Altitude Detection of Astronomical Radiation (HADAR) experiment has such merits. In this paper, we report the estimates of its expected annual GRB detection rate, which are obtained by combining the performance of the HADAR instrument with the theoretical calculations based on a phenomenological model to generate the pseudo-GRB population. The expected detectable gamma-ray signal from GRBs above the background is then obtained to give the detection rate. In the spectral model, an extra component is assigned to every GRB event in addition to the Band function. The results indicate that if the energy of the cutoff due to internal absorption is higher than 50 GeV, the detection rate for GRBs for the HADAR experiment is approximately two or three GRBs per year, which varies slightly depending upon the characteristics of the extra component.
Background
Laparoscopic splenectomy and azygoportal disconnection (LSD) is widely used for the treatment of esophagogastric variceal haemorrhage and hypersplenism owing to cirrhotic portal ...hypertension. However, whether LSD improves liver synthesis function and cirrhosis remains unclear. The aim of this study is to investigate the effect of LSD on liver synthesis function and cirrhosis based on a prospective 2-year follow-up study.
Methods
A total of 118 patients with cirrhotic portal hypertension who underwent LSD were included in this study. We analysed clinical data including routine blood parameters, liver function, liver-synthesised proteins (antithrombin III, protein S, and protein C), liver fibrotic markers (type IV collagen (IV-C), procollagen type III (PC-III), laminin, and hyaluronidase), portal vein diameter, and portal blood flow velocity.
Results
Postoperative portal vein diameter and portal blood flow velocity all showed gradual declines during the 2-year follow-up; compared with preoperative values, these were all significantly decreased from postoperative week (POW) 1 (all
P
< 0.001). Postoperative Child–Pugh scores and total bilirubin, albumin, international normalised ratio, antithrombin III, protein S, protein C, IV-C, PC-III, laminin, and hyaluronidase levels also all showed gradual improvements during the 2-year follow-up; compared with preoperative levels, these were all significantly improved from postoperative month (POM) 6, POW 1, POM 3, POM 3, POM 3, POM 6, POM 18, POW 1, POM 3, POM 24, and POM 18, respectively (all
P
< 0.05).
Conclusion
LSD not only decreases portal hypertension and improves liver function, it also enhances liver synthesis function and reduces liver fibrosis.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
is an extraordinary medicinal plant, and its stem bark is a famous traditional Chinese medicine in China, containing a number of phytochemicals with biological and pharmacological functions. Studies ...have shown that the medicinal ingredients in
from various regions are different, as soil types might be important factors affecting the growth and quality of
. In this study, the effects of acidic purple soil, alkaline purple soil, yellow soil and red soil on the growth, nutrient element accumulation and partitioning in
seedlings were studied. Our results showed that the biomass of leaves and stems in acidic purple soil was significantly higher than in other soils, and the root biomass was significantly lower than that in yellow soil. C, N, P and Ca contents cultured in acidic purple soil were the highest compared to other soils, and K and Mg content were the highest in yellow soil and red soil, respectively. The distribution of carbon between different organs can reflect environmental stress. N has become a limiting factor for the growth and development of
seedlings. C:N and C:P ratios in the leaves were significantly lower than those in the stem and roots. Among four soil types, the highest N:P ratio was 1.65 in
seedlings. These results suggest that four soil types may significantly affect the accumulation and distribution of biomass and nutrient elements in
seedlings. The characteristic patterns in different organs have different responses. Acidic purple soil is more suitable for the growth of
. These findings will help to understand the distribution characteristics and requirements of nutrient elements in
seedlings, and further provide a theoretical basis and reference for site selection and cultivation strategy.
This study focuses on addressing the limitations associated with most chemical derivatization methods commonly used for formaldehyde detection. These methods often suffer from prolonged derivative ...times (≥30 min) and complex procedures, which hinder their ability to meet the requirements of real-time and accurate sensing. In this research, a novel formaldehyde indicator system based on hyperbranched polyamine molecule was developed, and its mechanism and principles of color change were investigated. The findings revealed that hyperbranched polyamine molecule effectively reacts with formaldehyde, leading to a reduction in electron cloud density in the amine group N and subsequently causing a decrease in pH value. This reaction enables the visualization of formaldehyde detection through changes in the indicator spectrum. Moreover, the spectral variation pattern exhibits a strong linear correlation with the formaldehyde concentration when the PAMAM concentration is optimized. The detection limit of this method was determined to be 1.8 ppm. Notably, the reaction between PAMAM and formaldehyde is almost instantaneous, the color change is insensitive to temperature, and the method demonstrates high selectivity. Overall, this research contributes to the advancement of real-time formaldehyde monitoring technology and provides insights for future developments in this field.
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•A new rapid and visual FA detection method was developed.•The reaction of hyperbranched polyamines and FA can lead to a change in pH.•The reason for the change of pH is due to decrease of Mulliken charges of N atom.•The change in pH was transformed into a regular shift in the spectrum of the solution.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Pericytes, as the mural cells surrounding the microvasculature, play a critical role in the regulation of microcirculation; however, how these cells respond to ischemic stroke remains unclear. To ...determine the temporal alterations in pericytes after ischemia/reperfusion, we used the 1-hour middle cerebral artery occlusion model, which was examined at 2, 12, and 24 hours after reperfusion. Our results showed that in the reperfused regions, the cerebral blood flow decreased and the infarct volume increased with time. Furthermore, the pericytes in the infarct regions contracted and acted on the vascular endothelial cells within 24 hours after reperfusion. These effects may result in incomplete microcirculation reperfusion and a gradual worsening trend with time in the acute phase. These findings provide strong evidence for explaining the "no-reflow" phenomenon that occurs after recanalization in clinical practice.
We performed a genome-wide scan to detect selection signatures that showed evidence of positive selection in the domestication process by re-sequencing the whole genomes of Landrace and Yorkshire ...pigs. Fifteen annotated elements with 13 associated genes were identified using the Z-transformed FST (Z(FST)) method, and 208 annotated elements with 140 associated genes were identified using the Z-transformed heterozygosity (ZHp) method. The functional analysis and the results of previous studies showed that most of the candidate genes were associated with basic metabolism, disease resistance, cellular processes, and biochemical signals, and several were related to body morphology and organs. They included PPP3CA, which plays an essential role in the transduction of intracellular Ca2+-mediated signals, and WWTR1, which plays a pivotal role in organ size control and tumor suppression. These results suggest that genes associated with body morphology were subject to selection pressure during domestication, whereas genes involved in basic metabolism and disease resistance were subject to selection during artificial breeding. Our findings provide new insights into the potential genetic variation of phenotypic diversity in different pig breeds and will help to better understand the selection effects of modern breeding in Landrace and Yorkshire pigs.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Background
Conventional open and conventional laparoscopic splenectomy and azygoportal disconnection (CLSD) result in poor quality of life because of damage to the vagal nerve. We have developed ...vagus nerve-preserving laparoscopic splenectomy and azygoportal disconnection (VLSD). This study aimed to evaluate whether VLSD is effective and safe, and to determine whether a reduction in the incidence of postoperative complications improves postoperative quality of life compared with CLSD.
Methods
We retrospectively evaluated outcomes in 72 cirrhotic patients with portal hypertensive bleeding and secondary hypersplenism who underwent CLSD (
n
= 40) or VLSD (
n
= 32) between April 2015 and December 2016. Their demographic, intraoperative, and postoperative variables were compared.
Results
No patients required conversion to laparotomy in CLSD and VLSD. There was no difference in estimated intraoperative blood loss, volume of intraoperative blood transfused, time to first flatus, time to off-bed activity, and postoperative hospital stay between the two groups. VLSD was associated with a shorter operation time (
P
= 0.020) and less postoperative complications (
P
< 0.0001), including less diarrhea (
P
< 0.0001), epigastric fullness (
P
< 0.0001), and delayed gastric emptying (
P
< 0.0001), compared with CLSD. With VLSD, there was a significant increase in body weight and plasma albumin levels at 6 months postoperatively compared with preoperative values (all
P
< 0.05). The curative effect of improving esophageal/gastric variceal bleeding was similar in the groups.
Conclusions
VLSD is effective and safe for reducing the incidence of postoperative complications, contributing to improving postoperative quality of life.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ