Recruitment or activation of mast cells in the liver aggravates the accumulation of fibrosis in carbon tetrachloride-induced liver injury.

Liver diseases caused by viral infections, alcoholism, drugs, or chemical poisons are a significant health problem: Liver diseases are a leading contributor to mortality, with approximately 2 million deaths per year worldwide. Liver fibrosis, as a common liver disease characterized by excessive collagen deposition, is associated with high morbidity and mortality, and there is no effective treatment. Numerous studies have shown that the accumulation of mast cells (MCs) in the liver is closely associated with liver injury caused by a variety of factors. This study investigated the relationship between MCs and carbon tetrachloride (CCl4)-induced liver fibrosis in rats and the effects of the MC stabilizers sodium cromoglycate (SGC) and ketotifen (KET) on CCl4-induced liver fibrosis. The results showed that MCs were recruited or activated during CCl4-induced liver fibrosis. Coadministration of SCG or KET alleviated the liver fibrosis by decreasing SCF/c-kit expression, inhibiting the TGF-ß1/Smad2/3 pathway, depressing the HIF-1a/VEGF pathway, activating Nrf2/HO-1 pathway, and increasing the hepatic levels of GSH, GSH-Px, and GR, thereby reducing hepatic oxidative stress. Collectively, recruitment or activation of MCs is linked to liver fibrosis and the stabilization of MCs may provide a new approach to the prevention of liver fibrosis.

Resveratrol attenuates intestinal epithelial barrier dysfunction via Nrf2/HO-1 pathway in dextran sulfate sodium-induced Caco-2 cells.

INTRODUCTION: The intestinal tract serves as an innate barrier, safeguarding the internal milieu from microorganisms and toxins. Various intestinal inflammatory diseases have a strong association with intestinal barrier dysfunction. The primary functional cells within the intestinal tract, intestinal epithelial cells (IECs) and their tight junctions (TJs), are crucial in preserving the integrity of this mechanical barrier. Resveratrol (Res), a plant-derived phenolic compound, exhibits a range of health-promoting benefits attributed to its anti-inflammatory properties. This study aims to examine Res's efficacy in bolstering IECs barrier function. METHODS: Dextran sulfate sodium (DSS) was employed to induce barrier dysfunction in IECs. Inflammatory cytokines in supernatants (interleukin [IL]-6, IL-1ß, tumor necrotic factor [TNF]-α, and IL-10) were quantified via enzyme-linked immunosorbent assay (ELISA). Then we assessed monolayer integrity using transepithelial electrical resistance (TEER). TJ protein expression (zonula occludens [ZO]-1 and Occludin) in IECs was evaluated through immunofluorescence and Western blot analysis. Network pharmacology helped identify the biological processes, signaling pathways, and key targets involved in Res's mitigation of DSS-induced IECs barrier dysfunction. The efficacy of the primary target was further corroborated using Western blot. RESULTS: Res was shown to increase cell viability and IL-10 expression while reducing TNF-α, IL-6, and IL-1ß levels, thus mitigating the inflammatory response. It enhanced TEER values and upregulated TJ protein expression (ZO-1 and Occludin). Network pharmacology revealed that Res potentially targets the NFE2L2 (nuclear factor erythroid-2-related factor 2, Nrf2), a vital antioxidant factor. Significantly, Res augmented Nrf2 and heme oxygenase 1 (HO-1) protein levels, counteracting oxidative stress in the IECs barrier dysfunction model. CONCLUSION: Overall, our findings suggested that Res ameliorated DSS-induced IECs barrier dysfunction by activating Nrf2/HO-1 pathway, showcasing significant therapeutic potential in the early stages of colitis.

A Review of Potato Salt Tolerance.

Potato is the world's fourth largest food crop. Due to limited arable land and an ever-increasing demand for food from a growing population, it is critical to increase crop yields on existing acreage. Soil salinization is an increasing problem that dramatically impacts crop yields and restricts the growing area of potato. One possible solution to this problem is the development of salt-tolerant transgenic potato cultivars. In this work, we review the current potato planting distribution and the ways in which it overlaps with salinized land, in addition to covering the development and utilization of potato salt-tolerant cultivars. We also provide an overview of the current progress toward identifying potato salt tolerance genes and how they may be deployed to overcome the current challenges facing potato growers.

Integrated metabolomics and network pharmacology revealing the mechanism of arsenic-induced hepatotoxicity in mice.

Endemic arsenic (As) poisoning is a severe biogeochemical disease that endangers human health. Epidemiological investigations and animal experiments have confirmed the damaging effects of As on the liver, but there is an urgent need to investigate the underlying mechanisms. This study adopted a metabolomic approach using UHPLC-QE/MS to identify the different metabolites and metabolic mechanisms associated with As-induced hepatotoxicity in mice. A network pharmacology approach was applied to predict the potential target of As-induced hepatotoxicity. The predicted targets of differential metabolites were subjected to a deep matching for elucidating the integration mechanisms. The results demonstrate that the levels of ALT and AST in plasma significantly increased in mice after As exposure. In addition, the liver tissue showed disorganized liver lobules, lax cytoplasm and inflammatory cell infiltration. Metabolomic analysis revealed that As exposure caused disturbance to 40 and 75 potential differential metabolites in plasma and liver, respectively. Further investigation led to discovering five vital metabolic pathways, including phenylalanine, tyrosine, and tryptophan biosynthesis and nicotinate and nicotinamide metabolism pathways. These pathways may responded to As-induced hepatotoxicity primarily through lipid metabolism, apoptosis, and deoxyribonucleic acid damage. The network pharmacology suggested that As could induce hepatotoxicity in mice by acting on targets including Hsp90aa1, Akt2, Egfr, and Tnf, which regulate PI3K Akt, HIF-1, MAPK, and TNF signaling pathways. Finally, the integrated metabolomics and network pharmacology revealed eight key targets associated with As-induced hepatoxicity, namely DNMT1, MAOB, PARP1, MAOA, EPHX2, ANPEP, XDH, and ADA. The results also suggest that nicotinic acid and nicotinamide metabolisms may be involved in As-induced hepatotoxicity. This research identified the metabolites, targets, and mechanisms of As-induced hepatotoxicity, offering meaningful insights and establishing the groundwork for developing antidotes for widespread As poisoning.

MIPs-SERS Sensor Based on Ag NPs Film for Selective Detection of Enrofloxacin in Food.

The quinolone antibiotics represented by enrofloxacin (ENRO) are harmful to the ecological environment and human health due to illegal excessive use, resulting in increasing food residues and ENRO levels in the environment. To this end, we developed a MIPs-SERS method using surface-enhanced Raman spectroscopy (SERS) and molecularly imprinted polymers (MIPs) to detect ENRO in food matrices. Firstly, a layer of silver nanoparticles (Ag NPs) with the best SERS effect was synthesized on the surface of copper rods as the enhancing material by in situ reductions, and then MIPs targeting ENRO were prepared by the native polymerization reaction, and the MIPs containing template molecules wrapped on the surface of silver nanoparticle films (Ag NPs-MIPs) were obtained. Our results showed that the Ag NPs-MIPs could specifically identify ENRO from the complex environment. The minimum detection limit for ENRO was 0.25 ng/mL, and the characteristic peak intensity of ENRO was linearly correlated to the concentration with a linear range of 0.001~0.1 µg/mL. The experimental results showed that in comparison to other detection methods, the rapid detection of ENRO in food matrices using Ag NPs-MIPs as the substrate is reliable and offers a cost-effective, time-saving, highly selective, and sensitive method for detecting ENRO residues in real food samples.

The effect of Bacillus cereus LV-1 on the crystallization and polymorphs of calcium carbonate.

The study of CaCO3 polymorphism is of great significance for understanding the mechanism of carbonate mineralization induced by bacteria and the genesis of carbonate rock throughout geological history. To investigate the effect of bacteria and shear force on CaCO3 precipitation and polymorphs, biomineralization experiments with Bacillus cereus strain LV-1 were conducted under the standing and shaking conditions. The results show that LV-1 induced the formation of calcite and vaterite under the standing and shaking conditions, respectively. However, the results of mineralization in the media and the CaCl2 solution under both kinetic conditions suggest the shear force does not affect the polymorphs of calcium carbonate in abiotic systems. Further, mineralization experiments with bacterial cells and extracellular polymeric substances (EPS) were performed under the standing conditions. The results reveal that bacterial cells, bound EPS (BEPS), and soluble EPS (SEPS) are favorable to the formation of spherical, imperfect rhombohedral, and perfect rhombohedral minerals, respectively. The increase in the pH value and saturation index (SI) caused by LV-1 metabolism under the shear force played key roles in controlling vaterite precipitation, whereas bacterial cells and EPS do not play roles in promoting vaterite formation. Furthermore, we suggest that vaterite formed if pH > 8.5 and SIACC > 0.8, while calcite formed if pH was between 8.0-9.0 and SIACC < 0.8. Bacterial cells and BEPS are the main factors affecting CaCO3 morphologies in the mineralization process of LV-1. This may provide a deeper insight into the regulation mechanism of the polymorphs and morphologies during bacterially induced carbonate mineralization.

Rapid and Sensitive Detection of Pentachloronitrobenzene by Surface-Enhanced Raman Spectroscopy Combined with Molecularly Imprinted Polymers.

Molecularly imprinted polymers (MIPs) specifically targeting pentachloronitrobenzene (PCNB) and containing silver nanoparticles have been prepared by free radical polymerization reaction using methyl methacrylate (MMA) as a functional monomer, PCNB as a template molecule, 1,4-butanedioldimethacrylate as a cross linker, lauroyl peroxide (LPO) as an initiator, and the silver nanoparticles with the best surface-enhanced Raman scattering (SERS) effect as SERS enhancement materials. Our results indicated that MIPs specifically recognize PCNB from complex matrices. The intensity of the PCNB characteristic peak was proportional to the concentration, with a linear range of 0.005 to 0.15 µg/mL and a limit of detection of 5.0 ng/mL. The recovery rates and relative standard deviation for the detection of PCNB spiked in the rice samples were from 94.4% to 103.3% and from 4.6% to 7.4%, respectively. The experimental results are consistent with those by the GC-MS method, indicating that the rapid detection of PCNB in food matrices by SERS-MIPs is reliable. In view of the insolubility of PCNB in water, oil-soluble silver nanoparticles were synthesized which can be expanded to detect oil-soluble toxic substances. For the first time, the proposed method provides a point-of-care and cost-effective tool for rapidly detecting PCNB in food matrices with high sensitivity and selectivity by employing SERS-MIPs method.

Polycyclic aromatic hydrocarbons at subcritical levels as novel indicators of microbial adaptation in a pre-industrial river delta.

Marine sediment is considered a vast sink for organic pollutants including polycyclic aromatic hydrocarbons (PAHs). However, little is known about the relationship between subcritical PAH allocation and benthic microbial patterns. Thus, we carried out a field investigation at the abandoned Yellow River Delta (AYRD) to deepen the understanding of PAHs' horizontal distribution and ecological roles on the continental shelf. The PAH level in the AYRD is relatively low and distance-independent, indicating it resulted from long-term, chronic, anthropogenic input. The combined application of diagnostic molecular ratios reported inconsistent PAH sources, which might be due to the low PAH concentrations and the complexity of contributing sources. Positive Matrix Factorization provided a more robust source classification and identified three main PAH sources-coal combustion and vehicle emissions, petrogenic process, and fossil fuels. The benthic microbiome did not show a significant response to PAHs in terms of microbial assemblage or alpha-diversity. However, Operational Taxonomic Units in some specific phyla, like Thaumarchaeota, Proteobacteria, Acidobacteria, and Chytridiomycota, correlated with the PAH source indicators, supporting the notion that PAH source indicators can act as a novel environmental indicator for microbial adaption. What's more, Microbial Ecological Networks show more connection at sites identified as biomass combustion by both Fluoranthene/(Fluoranthene + Pyrene) and Indeno(1,2,3-cd)pyrene/(Indeno(1,2,3-cd)pyrene + Benzo(ghi)perylene) compared to the ones identified as biomass combustion by Fluoranthene/(Fluoranthene + Pyrene) and petroleum combustion by Indeno(1,2,3-cd)pyrene/(Indeno(1,2,3-cd)pyrene + Benzo(ghi)perylene). Herein, we demonstrate that the PAHs' source indicator can serve as a novel indicator of the interactions between microorganisms, and thus, should be applied to the sustainable management effort in the offshore area.

Hepatotoxicity of cantharidin is associated with the altered bile acid metabolism.

Cantharidin (CTD) is an effective antitumor agent. However, it exhibits significant hepatotoxicity, the mechanism of which remains unclear. In this study, biochemical and histopathological analyses complemented with ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS)-based targeted metabolomic analysis of bile acids (BAs) were employed to investigate CTD-induced hepatotoxicity in rats. Sixteen male and female Sprague-Dawley rats were randomly divided into two groups: control and CTD (1.0 mg/kg) groups. Serum and liver samples were collected after 28 days of intervention. Biochemical, histopathological, and BA metabolomic analyses were performed for all samples. Further, the key biomarkers of CTD-induced hepatotoxicity were identified via multivariate and metabolic pathway analyses. In addition, metabolite-gene-enzyme network and Kyoto Encyclopedia of Genes and Genomes pathway analyses were used to identify the signaling pathways related to CTD-induced hepatotoxicity. The results revealed significantly increased levels of biochemical indices (alanine aminotransferase, aspartate aminotransferase, and total bile acid). Histopathological analysis revealed that the hepatocytes were damaged. Further, 20 endogenous BAs were quantitated via UHPLC-MS/MS, and multivariate and metabolic pathway analyses of BAs revealed that hyocholic acid, cholic acid, and chenodeoxycholic acid were the key biomarkers of CTD-induced hepatotoxicity. Meanwhile, primary and secondary BA biosynthesis and taurine and hypotaurine metabolism were found to be associated with the mechanism by which CTD induced hepatotoxicity in rats. This study provides useful insights for research on the mechanism of CTD-induced hepatotoxicity.

Asymmetrical cortical vessel sign predicts prognosis after acute ischemic stroke.

INTRODUCTION: To assess whether the asymmetrical cortical vessel sign (ACVS) on susceptibility-weighted imaging (SWI) could predict 90-day poor outcomes in anterior circulation acute ischemic stroke (AIS) patients treated with recombinant tissue plasminogen activator (r-tPA). METHODS: Clinical data of consecutive patients with anterior circulation AIS treated with r-tPA were retrospectively analyzed. Clinical variables included age, sex, vascular risk factors, NIHSS score, onset to treatment time, and initial hematologic and neuroimaging findings. Follow-up was performed 90 days after onset. Poor outcome was defined as a modified Rankin scale (mRS) ≥3 at 90 days. RESULTS: A total of 145 patients were included, 35 (24.1%) patients presented with ACVS (≥Grade 1) on SWI. Fifty-three (36.6%) patients had a poor outcome at 90 days. ACVS (≥Grade 1) occurred in 21 (39.6%) patients with poor outcome compared with 14 (15.2%) patients with favorable outcome (p = .001). Univariate analysis indicated that age, NIHSS score on admission, previous stroke, hemorrhagic transformation, severe intracranial large artery stenosis or occlusion (SILASO), and ACVS were associated with 90-day poor outcome (p < .05). Since SILASO and ACVS were highly correlated and ACVS had different grades, we used three logistic regression models. Results from the three models showed that ACVS was associated with 90-day poor outcome. CONCLUSIONS: In r-tPA-treated patients with anterior circulation AIS, ACVS might be a helpful neuroimaging predictor for poor outcome at 90 days.

Uptake, biotransformation and physiological response of TBBPA in mangrove plants after hydroponics exposure.

To better understand the uptake, biotransformation and physiological response to tetrabromobisphenol A (TBBPA) in mangrove plants, a short term 14-day hydroponic assay with two mangrove species, Avicennia marina (A. marina) and Kandelia obovata (K. obovata), was conducted. Results showed that two mangrove species could uptake, translocate and accumulate TBBPA from solution. The hydroxylation and debromination metabolites of TBBPA, including OH-TBBPA, TriBBPA, MonoBBPA, and BPA, were found in both mangroves for the first time. The high-level TBBPA suppressed the growth and increased malondialdehyde (MDA) content of K. obovata, did not pose any negative affect on A. marina. The activities of superoxide dismutase (SOD), peroxidase (POD) and catalase (CAT) of K. obovata significantly increased in the 7th day, whereas, SOD and POD activities at high-levels of TBBPA became comparable to the control in the 14th day. Contrastingly, the antioxidant enzymes activities of A. marina were positively stimulated by TBBPA during the 14-day of observation, indicating that A. marina was more tolerant of TBBPA.

Terrestrial-derived soil protein in coastal water: metal sequestration mechanism and ecological function.

Terrestrial fungi, especially arbuscular mycorrhizal (AM) fungi, enhance heavy metal sequestration and promote ecosystem restoration. However, their ecological functions were historically overlooked in discussions regarding water quality. As an AM fungi-derived stable soil protein fraction, glomalin-related soil protein (GRSP) may provide insights into the ecological functions of AM fungi associated with water quality in coastal ecosystems. Here, we first assessed the metal-loading dynamics and ecological functions of GRSP transported into aquatic ecosystems, characterized the composition characteristics, and revealed the mechanisms underlying Cu and Cd sequestration. Combining in situ sampling and in vitro cultures, we found that the composition characteristics of GRSP were significantly affected by the element and mineral composition of sediments. In situ, GRSP-bound Cu and Cd contributed 18.91-22.03% of the total Cu and 2.27-6.37% of the total Cd. Functional group ligands and ion exchange were the principal mechanisms of Cu binding by GRSP, while Cd binding was dominated by functional group ligands. During the in vitro experiment, GRSP sequestered large amounts of Cu and Cd and formed stable complexes, while further dialysis only released 25.74 ±â€¯3.85% and 33.53 ±â€¯3.62% of GRSP-bound Cu and Cd, respectively.

Clinical characteristics and magnetic resonance imaging findings in nine patients with nonalcoholic Wernicke's encephalopathy: a retrospective study.

PURPOSE: Wernicke's encephalopathy (WE) is a severe neurological disorder caused by thiamine deficiency. The most common cause of WE is alcoholism. However, there is a significant paucity of information in the existing literature relating to nonalcoholic WE. In this study, we investigated the clinical characteristics and neuroimaging findings of nine patients with nonalcoholic WE. PATIENTS AND METHODS: We retrospectively collated clinical data from nine patients who had been diagnosed with WE in accordance with established criteria including age, gender, risk factors and clinical manifestations. We also collated initial hematological and neuroimaging findings. RESULTS: The mean age of the nine patients was 54.0±17.1 years; four of these patients (44.4%) were male. All nine patients had a history of fasting (range, 5-47 days) prior to WE. Four of the nine patients (44.4%) exhibited the classical triad, and eight (88.9%) showed alterations in mental status. Magnetic resonance imaging (MRI) scans showed that all nine patients had symmetric lesions of the medial thalamus. MRI also revealed other WE-related lesions in mammillary bodies (22.2%), the periaqueductal region (55.6%), the tectal plate of the midbrain (77.8%), cranial nerve nuclei (77.8%) and in the symmetric subcortical white matter (11.1%). CONCLUSION: Our analysis showed that fasting is a common cause of WE in nonalcoholic patients and that MRI is a useful tool for the diagnosis of WE. The most common MRI findings were symmetrical lesions of the medial thalamus lesions, followed by the tectal plate of the midbrain and cranial nerve nuclei.

Intestinal transport of scutellarein and scutellarin and first-pass metabolism by UDP-glucuronosyltransferase-mediated glucuronidation of scutellarein and hydrolysis of scutellarin.

Scutellarin (SG) is a bioactive flavonoid used to treat cardiovascular disease. Scutellarein (S) is the aglycone form of SG. This study aimed to characterize their intestinal transport and first-pass metabolism by UDP-glucuronosyltransferase-mediated glucuronidation and ß-glucuronidase-mediated hydrolysis. Results showed that S is more readily passed through Caco-2 cell monolayers by passive diffusion than SG. SG was the predominant metabolite of S, which was formed during the transportation of S across Caco-2 cell monolayers or following incubation of S with human microsomes. SG was extensively generated in human liver microsomes (HLMs), which was demonstrated by its higher catalyzing efficiency (C(lint)) in liver microsomes than in human intestinal microsomes (HIMs). Enzymatic kinetic analysis indicated that the catalyzing efficiency of UGT1A9 was the highest among the tested UGTs under the present experimental conditions, followed by UGT1A1 and UGT1A3. No significant P450-mediated hydroxylation of S was found. SG may be hydrolyzed into S in both HLMs and HIMs.