Hepatoprotective mechanism of Silybum marianum on nonalcoholic fatty liver disease based on network pharmacology and experimental verification

The study aimed to identify the key active components in Silybum marianum (S. marianum) and determine how they protect against nonalcoholic fatty liver disease (NAFLD). TCMSP, DisGeNET, UniProt databases, and Venny 2.1 software were used to identify 11 primary active components, 92 candidate gene targets, and 30 core hepatoprotective gene targets in this investigation, respectively. The PPI network was built using a string database and Cytoscape 3.7.2. The KEGG pathway and GO biological process enrichment, biological annotation, as well as the identified hepatoprotective core gene targets were analyzed using the Metascape database. The effect of silymarin on NAFLD was determined using H&E on pathological alterations in liver tissues. The levels of liver function were assessed using biochemical tests. Western blot experiments were used to observe the proteins that were expressed in the associated signaling pathways on the hepatoprotective effect, which the previous network pharmacology predicted. According to the KEGG enrichment study, there are 35 hepatoprotective signaling pathways. GO enrichment analysis revealed that 61 biological processes related to the hepatoprotective effect of S. marianum were identified, which mainly involved in response to regulation of biological process and immune system process. Silymarin was the major ingredient derived from S. marianum, which exhibited the hepatoprotective effect by reducing the levels of ALT, AST, TC, TG, HDL-C, LDL-C, decreasing protein expressions of IL-6, MAPK1, Caspase 3, p53, VEGFA, increasing protein expression of AKT1. The present study provided new sights and a possible explanation for the molecular mechanisms of S. marianum against NAFLD

The effects of intro-oral parathyroid hormone on the healing of tooth extraction socket: an experimental study on hyperglycemic rats

Objective: To investigate the effects of intro-oral injection of parathyroid hormone (PTH) on tooth extraction wound healing in hyperglycemic rats. Methodology: 60 male Sprague-Dawley rats were randomly divided into the normal group (n=30) and DM group (n=30). Type 1 diabetes mellitus (DM) was induced by streptozotocin. After extracting the left first molar of all rats, each group was further divided into 3 subgroups (n=10 per subgroup), receiving the administration of intermittent PTH, continuous PTH and saline (control), respectively. The intermittent-PTH group received intra-oral injection of PTH three times per week for two weeks. A thermosensitive controlled-release hydrogel was synthesized for continuous-PTH administration. The serum chemistry was determined to evaluate the systemic condition. All animals were sacrificed after 14 days. Micro-computed tomography (Micro-CT) and histological analyses were used to evaluate the healing of extraction sockets. Results: The level of serum glucose in the DM groups was significantly higher than that in the non-DM groups (p<0.05); the level of serum calcium was similar in all groups (p>0.05). Micro-CT analysis showed that the DM group had a significantly lower alveolar bone trabecular number (Tb.N) and higher trabecular separation (Tb.Sp) than the normal group (p<0.05). The histological analyses showed that no significant difference in the amount of new bone (hard tissue) formation was found between the PTH and non-PTH groups (p>0.05). Conclusions: Bone formation in the extraction socket of the type 1 diabetic rats was reduced. PTH did not improve the healing of hard and soft tissues. The different PTH administration regimes (continuous vs. intermittent) had similar effect on tissue healing. These results demonstrated that the metabolic characteristics of the hyperglycemic rats produced a condition that was unable to respond to PTH treatment

BALF metagenomic next-generation sequencing analysis in hematological malignancy patients with suspected pulmonary infection: clinical significance of negative results

PurposeMetagenomic next-generation sequencing (mNGS) of bronchoalveolar lavage fluid (BALF) is gradually being used in hematological malignancy (HM) patients with suspected pulmonary infections. However, negative results are common and the clinical value and interpretation of such results in this patient population require further analysis.MethodsRetrospective analysis of 112 HM patients with suspected pulmonary infection who underwent BALF mNGS and conventional microbiological tests. The final diagnosis, imaging findings, laboratory results and treatment regimen of 29 mNGS-negative patients were mainly analyzed.ResultsA total of 83 mNGS positive and 29 negative patients (15 true-negatives and 14 false-negatives) were included in the study. Compared to false-negative patients, true-negative patients showed more thickening of interlobular septa on imaging (p < 0.05); fewer true-negative patients had acute respiratory symptoms such as coughing or sputum production (p < 0.05) clinically; On the aspect of etiology, drug-related interstitial pneumonia (6/15, 40%) was the most common type of lung lesion in true-negative patients; on the aspect of pathogenesis, false-negative patients mainly missed atypical pathogens such as fungi and tuberculosis (8/14, 57.1%). Regarding treatment, delayed anti-infection treatment occurred after pathogen missing in mNGS false-negative patients, with the longest median time delay observed for anti-tuberculosis therapy (13 days), followed by antifungal therapy (7 days), and antibacterial therapy (1.5 days); the delay in anti-tuberculosis therapy was significantly longer than that in antibacterial therapy (p < 0.05).ConclusionFor HMs patients with imaging showing thickening of interlobular septa and no obvious acute respiratory symptoms, lung lesions are more likely caused by drug treatment or the underlying disease, so caution should be exercised when performing BALF mNGS. If BALF mNGS is negative but infection is still suspected, atypical pathogenic infections should be considered

Phylogeny and biogeography of Fagus (Fagaceae) based on 28 nuclear single/low-copy loci

Fagus L. is a key component in temperate deciduous broadleaf forests of the Northern Hemisphere. However, its biogeographic history has not been examined under the framework of a fully resolved and reasonably time-calibrated phylogeny. In this study, we sequenced 28 nuclear single/low-copy loci (18 555 bp in total) of 11 Fagus species/segregates and seven outgroups. Phylogenetic trees were reconstructed using both concatenation-based (maximum parsimony, maximum likelihood, and Bayesian inference) and coalescent-based methods (StarBEAST2, ASTRAL). The monophyly of two subgenera (Fagus and Engleriana) and most sections was well supported, except for sect. Lucida, which was paraphyletic with respect to sect. Longipetiolata. We also found a major phylogenetic conflict among North American, East Asian, and West Eurasian lineages of subgen. Fagus. Three segregates that have isolated distribution (F. mexicana, F. multinervis, and F. orientalis) were independent evolutionary units. Biogeographic analysis with fossils suggested that Fagus could have originated in the North Pacific region in late early Eocene. Major diversifications coincided with a climate aberration at the Eocene/Oligocene boundary and the global cooling since mid-Miocene. The late Miocene accelerated global cooling and the Pleistocene glaciations would have driven beeches into East Asia, North America, and West Eurasia. Meanwhile, range reduction and extinction in high latitudes, central Asia, and western North America converged to form the beech modern distribution pattern. This study provides a first attempt to disentangle the biogeographic history of beeches in the context of a nearly resolved and time-calibrated phylogeny, which could shed new insights into the formation of the temperate biome in the Northern Hemisphere.This work was supported by the National Natural Science Foundation of China (Grant Nos. 31770236, 30760016, and 31560064) and the Strategic Priority Research Program of Chinese Academy of Sciences (XDB31000000).1 Introduction 2 Material and Methods 2.1 Taxon sampling 2.2 Screening of nuclear single/low-copy orthologous locus 2.3 DNA extraction, PCR protocol, and sequencing 2.4 Phylogenetic analyses and molecular dating 2.5 Ancestral area reconstruction 3 Results 3.1 Concatenated tree 3.2 Species tree and molecular dating 3.3 Ancestral area reconstruction 4 Discussion 4.1 Nearly resolved and well supported phylogeny of Fagus 4.2 Species delimitation of three segregates within Fagus 4.3 Biogeographic history of beech species Acknowledgement

Hyper-Crosslinked Porous Organic Nanomaterials: Structure-Oriented Design and Catalytic Applications

Hyper-crosslinked porous organic nanomaterials, especially the hyper-crosslinked polymers (HCPs), are a unique class of materials that combine the benefits of high surface area, porous structure, and good chemical and thermal stability all rolled into one. A wide range of synthetic methods offer an enormous variety of HCPs with different pore structures and morphologies, which has allowed HCPs to be developed for gas adsorption and separations, chemical adsorption and encapsulation, and heterogeneous catalysis. Here, we present a systematic review of recent approaches to pore size modulation and morphological tailoring of HCPs and their applications to catalysis. We mainly compare the effects of pore size modulation and morphological tailoring on catalytic applications, aiming to pave the way for researchers to develop HCPs with an optimal performance for modern applications

Effect of different stunning methods on antioxidant status, myofibrillar protein oxidation, and gelation properties of large yellow croaker during postmortem

Post-mortem muscle biochemical processes play a crucial role on fish fillets quality and they are strictly linked to stunning methods. The improper stunning methods before slaughter could cause the fish to deteriorate more quickly during cold storage. This study aimed to investigate the effect of stunning methods (hit on the head, T1; gill cut, T2; immersion in ice/water slurry, T3; CO2 narcosis, T4; 40% CO2 + 30 % N2 + 30% O2, T5) on myofibrillar proteins (MPs) of large yellow croaker. The results indicated that T2 and T3 samples were significantly damaged compared with other samples, which reflected that the activities of total superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were significantly damaged during cold storage in T2 and T3 samples. And the gill cut and immersion in ice/water slurry resulted in the generation of protein carbonyl, the decrease of Ca2+-ATPase, free ammonia and protein solubility, and the production of dityrosine during storage. In addition, MPs gel of T2 and T3 samples showed the decrease of water hold capacity (WHC) and whiteness, structure destruction, and water migration. The T4 samples had the least damage of MPs and gel structure during cold storage

Effects of Tricaine Methanesulphonate (MS-222) on Physiological Stress and Fresh Quality of Sea Bass (<i>Lateolabrax maculatus</i>) under Simulated High-Density and Long-Distance Transport Stress

This study aimed to evaluate the effect of different transport densities on water deterioration, physiological response, nutrients, and fresh quality of sea bass (Lateolabrax maculatus) at 30 mg/L tricaine methanesulphonate (MS-222) before and after simulated live transport. The results indicated that the addition of MS-222 could effectively decrease mortality compared with the control (CK) sample during the simulated live transport. The concentration of dissolved oxygen was lower and the total ammonia nitrogen was higher in the high transport density samples than those of low transport density samples after 72 h in transport. The level of blood cortisol (COR), glucose (GLU), lactic acid (LD), aspartate aminotransferase (AST), alanine aminotransferase (ALT) for the sea bass were significantly higher compared with the CK sample (p < 0.05) during the simulated live transport and after 12 h of recovery. These results indicated that the sea bass presented a strong stress response in high-density transport. The glycogen, fat, and protein of the sea bass were degraded to supply the energy for the body in the process of surviving the transportation, resulting in the decreased nutrient content in the muscle, which recovered to the initial level (CK) after 12 h. The increase in flavor substance content, such as free amino acids, nucleotides, organic acids, and minerals, enhanced the special flavor of the muscle during the simulated live transport. This study demonstrates that the addition of MS-222 at 30 mg/L to the transport water is an effective method for live fish to realize low mortality and physiological response during high-density and long-distance transport

Human Activity Intensity in China under Multi-Factor Interactions: Spatiotemporal Characteristics and Influencing Factors

Human activities involving nature have various environmental impacts. The assessment of the spatial and temporal evolution of human activity intensity (HAI) and its driving forces is significant for determining the effects of human activities on regional ecological environments and regulating such activities. This research quantified the HAI of China, assessed its spatiotemporal characteristics, and analyzed its influencing factors based on the land use data and panel data of 31 provinces in mainland China. The results indicate that the HAI in China is increasing, with the average value increasing from 15.83% in 1980 to 20.04% in 2018, and the HAI was relatively serious in the Beijing–Tianjin–Hebei region, Yangtze River Delta and Pearl River Delta in this period. The spatial differences in the HAI in China show a pattern of being strong in the east and weak in the west, and the spatial center of gravity of China’s HAI has gradually moved west, changing from a central enhancement mode to a point-like “core” enhancement mode. The dominant factors affecting spatial differences in HAI are economic and industrial levels. Labor, population, and capital factors also strongly impact HAI, and energy consumption and pollution emissions have little impact. These results deepen the understanding of the underlying mechanism of the environmental impact of human activities and provide a scientific basis for land-use-related decision making and eco-environment construction

Comparison of Estimating Missing Values in IoT Time Series Data Using Different Interpolation Algorithms

When collecting the Internet of Things data using various sensors or other devices, it may be possible to miss several kinds of values of interest. In this paper, we focus on estimating the missing values in IoT time series data using three interpolation algorithms, including (1) Radial Basis Functions, (2) Moving Least Squares (MLS), and (3) Adaptive Inverse Distance Weighted. To evaluate the performance of estimating missing values, we estimate the missing values in eight selected sets of IoT time series data, and compare with those imputed by the standard kNN estimator. Our experiments indicate that in most experiments the estimation based on the Lancaster’s MLS is the best. It is also found that the number of nearest observed values for reference and the distribution of missing values could strongly affect the accuracy of imputation

Apoptotic Changes, Oxidative Stress and Immunomodulatory Effects in the Liver of Japanese Seabass (<i>Lateolabrax japonicus</i>) Induced by Ammonia-Nitrogen Stress during Keep-Live Transport

This study investigated the effects of NH3-N on antioxidant responses, histoarchitecture, and immunity of Japanese seabass (Lateolabrax japonicus) during keep-live transport. The findings suggest that NH3-N stress transport alters the transcription of P53, Caspase 9, Bcl2, Caspase 3 and Bax genes, demonstrating that NH3-N stress can trigger the apoptotic pathway of P53-Bax-Bcl2 and Caspase and induce apoptosis. NH3-N stress transport also evoked transcriptional upregulation of inflammatory cytokines (tumor necrosis factor α (TNF-α), Toll-like receptor 3 (TLR-3), nuclear factor kappa β (NF-κB), interleukin 6 (IL-6) and interleukin 1β (IL-1β)) and increased complement C3, C4, lysozyme (LZM) and immunoglobulin (IgM) levels, activating the innate immunological system during keep-live transport. In addition, NH3-N stress transport altered changes in the levels of superoxide dismutase (SOD), catalase (CAT), glutathione-related enzymes, and heat shock proteins 70 and 90 in the liver, indicating that the antioxidant system and Hsp protected the cells from NH3-N-induced oxidative stress. When excess ROS were not removed, they caused the body to respond with immunological and inflammatory responses, as well as apoptosis and tissue damage. This helps towards understanding the effect of NH3-N levels on sea bass during keep-live transport