Biopolymer Hydrogel-Based Salt-Resistant Evaporator for Solar-Energy-Driven Desalination and Water Purification.

Interfacial solar steam generation (ISSG) has recently received much attention as a low-carbon-footprint and high-energy-efficient strategy for seawater desalination and wastewater treatment. However, achieving the goals of a high evaporation rate, ecofriendliness, and high tolerance to salt ions in brine remains a bottleneck. Herein, a novel hydrogel-based evaporator for effective solar desalination was synthesized on the basis of sodium alginate (SA) and carboxymethyl chitosan (CMCS) incorporating a carbon nanotube (CNT)-wrapped melamine sponge (MS) through a simple dipping-drying-cross-linking process. The hydrogel-based evaporator reaches a high evaporation rate of 2.18 kg m-2 h-1 in 3.5 wt % brine under 1 sun irradiation. Furthermore, it demonstrated excellent salt ion rejection in high-concentration salt water. Simultaneously, it exhibits excellent purification functionality toward heavy metals and organic dyes. This study provides a simple and efficient strategy for seawater desalination and wastewater treatment.

Myricanol attenuates sepsis-induced inflammatory responses by nuclear factor erythroid 2-related factor 2 signaling and nuclear factor kappa B/mitogen-activated protein kinase pathway via upregulating Sirtuin 1.

Sepsis, a life-threatening condition characterized by dysregulated immune responses, remains a significant clinical challenge. Myricanol, a natural compound, plays a variety of roles in regulating lipid metabolism, anti-cancer, anti-neurodegeneration, and it could act as an Sirtuin 1 (SIRT1) activator. This study aimed to explore the therapeutic potential and underlying mechanism of myricanol in the lipopolysaccharide (LPS)-induced sepsis model. In vivo studies revealed that myricanol administration significantly improved the survival rate of LPS-treated mice, effectively mitigating LPS-induced inflammatory responses in lung tissue. Furthermore, in vitro studies demonstrated that myricanol treatment inhibited the expression of pro-inflammatory cytokines, attenuated signal pathway activation, and reduced oxidative stress in macrophages. In addition, we demonstrated that myricanol selectively enhances SIRT1 activation in LPS-stimulated macrophages, and all of the protective effect of myricanol were reversed through SIRT1 silencing. Remarkably, the beneficial effects of myricanol against LPS-induced sepsis were abolished in SIRT1 myeloid-specific knockout mice, underpinning the critical role of SIRT1 in mediating myricanol's therapeutic efficacy. In summary, this study provides significant evidence that myricanol acts as a potent SIRT1 activator, targeting inflammatory signal pathways and oxidative stress to suppress excessive inflammatory responses. Our findings highlight the potential of myricanol as a novel therapeutic agent for the treatment of LPS-induced sepsis.

Pimpinellin ameliorates macrophage inflammation by promoting RNF146-mediated PARP1 ubiquitination.

Macrophage inflammation plays a central role during the development and progression of sepsis, while the regulation of macrophages by parthanatos has been recently identified as a novel strategy for anti-inflammatory therapies. This study was designed to investigate the therapeutic potential and mechanism of pimpinellin against LPS-induced sepsis. PARP1 and PAR activation were detected by western blot or immunohistochemistry. Cell death was assessed by flow cytometry and western blot. Cell metabolism was measured with a Seahorse XFe24 extracellular flux analyzer. C57, PARP1 knockout, and PARP1 conditional knock-in mice were used in a model of sepsis caused by LPS to assess the effect of pimpinellin. Here, we found that pimpinellin can specifically inhibit LPS-induced macrophage PARP1 and PAR activation. In vitro studies showed that pimpinellin could inhibit the expression of inflammatory cytokines and signal pathway activation in macrophages by inhibiting overexpression of PARP1. In addition, pimpinellin increased the survival rate of LPS-treated mice, thereby preventing LPS-induced sepsis. Further research confirmed that LPS-induced sepsis in PARP1 overexpressing mice was attenuated by pimpinellin, and PARP1 knockdown abolished the protective effect of pimpinellin against LPS-induced sepsis. Further study found that pimpinellin can promote ubiquitin-mediated degradation of PARP1 through RNF146. This is the first study to demonstrate that pimpinellin inhibits excessive inflammatory responses by promoting the ubiquitin-mediated degradation of PARP1.

Simultaneous Extraction and Determination of Lignans from Schisandra chinensis (Turcz.) Baill. via Diol-Based Matrix Solid-Phase Dispersion with High-Performance Liquid Chromatography.

The quality of Schisandra chinensis (Turcz.) Baill. (S. chinensis) is principally attributed to lignan compounds. In this paper, a simple and rapid strategy for simultaneous extraction and determination of 10 lignans from S. chinensis was established through matrix solid-phase dispersion (MSPD) assisted by diol-functionalized silica (Diol). The experimental parameters for MSPD extraction were screened using the response surface methodology (RSM). Diol (800 mg) was used as a dispersant and methanol (MeOH, 85%, v/v) as an eluting solvent (10 mL), resulting in a high extraction efficiency. MSPD extraction facilitated the combination of extraction and purification in a single step, which was less time-consuming than and avoided the thermal treatment involved in traditional methods. The simultaneous qualification and quantification of 10 lignans was achieved by combining MSPD and high-performance liquid chromatography (HPLC). The proposed method offered good linearity and a low limit of detection starting from 0.04 (schisandrin C) to 0.43 µg/mL (schisantherin B) for lignans, and the relative standard deviation (RSD, %) values of precision were acceptable, with a maximum value of 1.15% (schisantherin B and schisanhenol). The methodology was successfully utilized to analyze 13 batches of S. chinensis from different cultivated areas of China, which proved its accuracy and practicability in the quantitative analysis of the quality control of S. chinensis.

Parent/caregiver reported health-related functioning in Chinese children with epilepsy: A cross-sectional, parents-responded, hospital-based study.

Due to epilepsy, children have faced several difficulties and challenges. Epilepsy shows an impact on a person quality of life (QoL) which can be associated with psychological, physical, and social aspects and can have a greater impact on the QoL of the person than that do through another chronic disease(s). Health-related quality of life (HRQoL) is a multidimensional concept that includes emotional, mental, physical, behavioral, and social aspects of the well-being and functioning of the patients. The objective of the study was to assess the level of HRQoL for childhood epilepsy in Chinese children under treatment for epilepsy. Also, to identify factors that can affect QoL. A descriptive, cross-sectional, parents-responded questionnaire-based study was performed on 382, 4 to 18 years old hospitalized and outpatient units' children from various backgrounds, varying socio-economic status, and of varying intellectual capability with the most recent epilepsy. The clinical and socio-demographic parameters were collected from medical records and by an interview with parents of children. The quality of life in the children with epilepsy (QoLCE) questionnaire-91 was used to access HRQoL. The average age of children was 10.4 ±â€…3.2 years. The duration of epilepsy in children was 3.90 ±â€…2.80 years. Among the enrolled children, 153 (40%) children were girls, and 229 (60%) individuals were boys. The overall QoLCE questionnaire-91 score was 69.40 ±â€…16.40 (minimum scores: 27.80, maximum scores: 87.80). A total of 324 (84%), 41 (11%), and 17 (5%) children were from urban, suburban, and rural types, respectively. The generalized seizure (198 (52%)) is the most common type of existing seizure followed by focal seizure (152 (40%)). Male (P = .015), older children (12-14 years, P = .019), those residing in urban areas (P = .021), and those with focal seizures (P = .049) had higher QoL scores. The overall QoL of Chinese CWE is affected by sex, age, urbanization, and seizure type but not with education or economic status of the families. The study provides helpful insight for the clinicians in the management of chronic childhood epileptic conditions (Level of Evidence: II; Technical Efficacy Stage: 5).

[Simultaneous determination of five lignans from Schisandra chinensis by matrix solid-phase dispersion extraction-high performance liquid chromatography].

The kidney-shaped, red-colord fruit from the plant, Schisandra chinensis (Turcz.) Baill, which belongs to the Schisandraceae family, is among the most popular remedies used in traditional Chinese medicine. The English name of the plant is "Chinese magnolia vine". It has been used in Asia since ancient times to treat a variety of ailments, including chronic cough and dyspnea, frequent urination, diarrhea, and diabetes. This is because of the wide range of bioactive constituents, such as lignans, essential oils, triterpenoids, organic acids, polysaccharides, and sterols. In some cases, these constituents affects the pharmacological efficacy of the plant. Lignans with a dibenzocyclooctadiene-type skeleton are considered to be the major constituents and main bioactive ingredients of Schisandra chinensis. However, because of the complex composition of Schisandra chinensis, the extraction yields of lignans are low. Thus, it is particularly important to study pretreatment methods used during sample preparation for the quality control of traditional Chinese medicine. Matrix solid-phase dispersion extraction (MSPD) is a comprehensive process involving destruction, extraction, fractionation, and purification. The MSPD method is simple, it requires only a small number of samples and solvents, it does not require any special experimental equipments or instruments, and it can be used to prepare liquid, viscous, semi-solid, solid samples. In this study, a method combining matrix solid-phase dispersion extraction with high performance liquid chromatography (MSPD-HPLC) was established for the simultaneous determination of five lignans (schisandrol A, schisandrol B, deoxyschizandrin, schizandrin B, and schizandrin C) in Schisandra chinensis. The target compounds were separated on a C18 column with a gradient elution of 0.1% (v/v) formic acid aqueous solution and acetonitrile as the mobile phases, and detection was performed at a wavelength of 250 nm. First, the effects of 12 adsorbents, including silica gel, acidic alumina, neutral alumina, alkaline alumina, Florisil, Diol, XAmide, Xion, and the inverse adsorbents, C18, C18-ME, C18-G1, and C18-HC, on the extraction yields of lignans were investigated. Second, effects of the mass of the adsorbent, the type of eluent, and volume of eluent on the extraction yields of lignans were investigated. Xion was chosen as an adsorbent for MSPD-HPLC analysis of lignans from Schisandra chinensis. Optimization of the extraction parameters showed that the MSPD method had a high lignan extraction yield with Schisandra chinensis powder (0.25 g) as a fixed value, Xion as the adsorbent (0.75 g), and methanol as the elution solvent (15 mL). Analytical methods were developed for five lignans from Schisandra chinensis and these methods showed good linearity (correlation coefficients (R2)≥ 0.9999) for each target analyte. The limits of detection and quantification ranged from 0.0089 to 0.0294 µg/mL and 0.0267 to 0.0882 µg/mL, respectively. Lignans were tested at low, medium, and high levels. The average recovery rates were 92.2% to 111.2%, and the relative standard deviations were 0.23% to 3.54%. Both intra-day and inter-day precisions were less than 3.6%. Compared with hot reflux extraction and ultrasonic extraction methods, MSPD has the advantages of combined extraction and purification, being less time-consuming, and requiring lower solvent volumes. Finally, the optimized method was successfully applied to analyze five lignans from Schisandra chinensis samples from 17 cultivation areas.

Isolation and purification of 12 flavonoid glycosides from Ginkgo biloba extract using sephadex LH-20 and preparative high-performance liquid chromatography.

An efficient and rapid preparative method for the separation and purification of flavonoid glycosides from the Ginkgo biloba extract (GBE) was developed by sephadex LH-20 and preparative high-performance liquid chromatography (HPLC). 40 g GBE of 24% flavonoids were loaded onto the sephadex LH-20 column and five fractions (1.15, 2.57, 1.32, 4.45, and 3.31 g) at flavonoid content of 72.3, 54.2, 63.5, 51.2, and 59.2% were produced. Ultimately, 12 flavonoid glycosides that are at least purities of 97.7% were obtained from 100 mg of each fraction by preparative HPLC. The fraction A, B, and D each contained two flavonoids, yielded 35, 30, 23, 20, 25, and 25 mg, respectively. The fraction C and E each contained three flavonoids, produced 20, 13, 15, 18, 15, and 20 mg, respectively. The chemical structures of the purified compounds were identified by nuclear magnetic resonance (NMR) and electrospray ionization mass spectrometry (ESI/MS).

7-Methoxyisoflavone suppresses vascular endothelial inflammation by inhibiting the expression of endothelial adhesion molecules.

Endothelial cells (ECs) are vital regulators of inflammatory processes, there is the potential for inhibition of EC inflammation to be a therapeutic target in chronic inflammatory diseases. This study aimed to investigate the effect of 7-methoxyisoflavone (7-Mif) on endothelial inflammation. Our results showed that 7-Mif have no cytotoxicity on HUVECs. Pretreatment with 5 µM, 10 µM and 50 µM 7-Mif significantly reduced IL-1ß-induced ICAM-1 (28.1% ± 4.1%, 25.9 ± 2.5% and 32.0% ± 3.2%, respectively) and VCAM-1 (48.0% ± 5.6%, 40.1 ± 3.1% and 39.6% ± 3.1%, respectively) mRNA expression. And pretreatment with 10 µM and 50 µM 7-Mif significantly reduced IL-1ß-induced ICAM-1 (45.1% ± 4.4% and 33.6 ± 4.4%, respectively) and VCAM-1 (53.0% ± 3.7% and 53.7 ± 5.1%, respectively) protein levels. Furthermore, pretreatment with 50 µM 7-Mif inhibited monocyte-endothelial cell adhesion (50.2% ± 4.2%). Mechanistically, our results showed that 7-Mif reversed IL-1ß-induced NF-κB activation and p65 translocation to the nucleus, therefore inhibiting endothelial cell inflammation. In addition, we confirmed that 7-Mif 10 mg/kg and 20 mg/kg reduced LPS-induced ICAM-1 (47.3% ± 1.3% and 39.0% ± 3.2%, respectively) and VCAM-1 (56.5 ± 2.8% and 47.8 ± 4.3%, respectively) expression and attenuated inflammatory injury in mice. In conclusion, we showed the inhibitory effect of 7-Mif on endothelial inflammation by suppressing the expression of endothelial adhesion molecules and monocyte adhesion. Our data illustrated that 7-Mif could positively regulate the process of endothelial inflammation.

Dual-Layer Multichannel Hydrogel Evaporator with High Salt Resistance and a Hemispherical Structure toward Water Desalination and Purification.

Interfacial solar steam generation technology has been considered as one of the most promising methods for seawater desalination. However, in practical applications, salt precipitation on the evaporation surface reduces the evaporation rate and impairs long-term stability. Herein, a dual-layer hydrogel-based evaporator that contains a microchannel-structured water-supplying layer and a nanoporous light-absorbing layer was synthesized via sol-gel transition and "hot-ice" template methods. Contributed by the designed structure-induced accelerated salt ion exchange, the hemispherical dual-layer hydrogel evaporator showed excellent salt formation resistance property, as well as a high evaporation rate reaching 2.03 kg m-2 h-1 even under high brine concentration conditions. Furthermore, the hydrogel-based evaporator also demonstrated excellent ion rejection, high/low pH tolerance, and excellent purification properties toward heavy metals and organic dyes. It is believed that this type of dual-layer multichannel evaporator is promising to be used in seawater desalination, water pollution treatment, and other environmental remediation-related applications.

The Efficacy and Safety of Bivalirudin Versus Heparin in the Anticoagulation Therapy of Extracorporeal Membrane Oxygenation: A Systematic Review and Meta-Analysis.

Background: Bivalirudin is a direct thrombin inhibitor (DTI) that can be an alternative to unfractionated heparin (UFH). The efficacy and safety of bivalirudin in anticoagulation therapy in extracorporeal membrane oxygenation (ECMO) remain unknown. Methods: This study followed the preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. A systematic literature search was performed in PubMed, EMBASE, and The Cochrane Library databases to identify all relevant original studies estimating bivalirudin's efficacy and safety versus UFH as anticoagulation therapy in ECMO. The time limit for searching is from the search beginning to June 2021. Two researchers independently screened the literature, extracted data and evaluated the risk of bias of the included studies. The meta-analysis (CRD42020214713) was performed via the RevMan version 5.3.5 Software and STATA version 15.1 Software. Results: Ten articles with 847 patients were included for the quantitative analysis. Bivalirudin can significantly reduce the incidence of major bleeding in children (I 2 = 48%, p = 0.01, odd ratio (OR) = 0.17, 95% confidence interval (CI): 0.04-0.66), patient thrombosis (I 2 = 0%, p = 0.02, OR = 0.58, 95% CI: 0.37-0.93), in-circuit thrombosis/interventions (I 2 = 0%, p = 0.0005, OR = 0.40, 95% CI: 0.24-0.68), and in-hospital mortality (I 2 = 0%, p = 0.007, OR = 0.64, 95% CI: 0.46-0.88). Also, comparable clinical outcomes were observed in the incidence of major bleeding in adults (I 2 = 48%, p = 0.65, OR = 0.87, 95% CI: 0.46-1.62), 30-day mortality (I 2 = 0%, p = 0.61, OR = 0.83, 95% CI: 0.41-1.68), and ECMO duration in adults (I 2 = 41%, p = 0.75, mean difference (MD) = -3.19, 95% CI: -23.01-16.63) and children (I 2 = 76%, p = 0.65, MD = 40.33, 95% CI:-135.45-216.12). Conclusions: Compared with UFH, bivalirudin can be a safe and feasible alternative anticoagulant option to UFH as anticoagulation therapy in ECMO, especially for heparin resistance (HR) and heparin-induced thrombocytopenia (HIT) cases.

Systems pharmacology-based drug discovery and active mechanism of natural products for coronavirus pneumonia (COVID-19): An example using flavonoids.

BACKGROUND: Recently, the value of natural products has been extensively considered because these resources can potentially be applied to prevent and treat coronavirus pneumonia 2019 (COVID-19). However, the discovery of nature drugs is problematic because of their complex composition and active mechanisms. METHODS: This comprehensive study was performed on flavonoids, which are compounds with anti-inflammatory and antiviral effects, to show drug discovery and active mechanism from natural products in the treatment of COVID-19 via a systems pharmacological model. First, a chemical library of 255 potential flavonoids was constructed. Second, the pharmacodynamic basis and mechanism of action between flavonoids and COVID-19 were explored by constructing a compound-target and target-disease network, targets protein-protein interaction (PPI), MCODE analysis, gene ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. RESULTS: In total, 105 active flavonoid components were identified, of which 6 were major candidate compounds (quercetin, epigallocatechin-3-gallate (EGCG), luteolin, fisetin, wogonin, and licochalcone A). 152 associated targets were yielded based on network construction, and 7 family proteins (PTGS, GSK3ß, ABC, NOS, EGFR, and IL) were included as central hub targets. Moreover, 528 GO items and 178 KEGG pathways were selected through enrichment of target functions. Lastly, molecular docking demonstrated good stability of the combination of selected flavonoids with 3CL Pro and ACEⅡ. CONCLUSION: Natural flavonoids could enable resistance against COVID-19 by regulating inflammatory, antiviral, and immune responses, and repairing tissue injury. This study has scientific significance for the selective utilization of natural products, medicinal value enhancement of flavonoids, and drug screening for the treatment of COVID-19 induced by SARS-COV-2.

Theoretical design and preparation research of molecularly imprinted polymers for steviol glycosides.

In this paper, a novel molecularly imprinted polymer (MIP) for specific adsorption of steviol glycosides was designed, and the imprinting mechanism of self-assembly system between template and monomers was clearly explored. Firstly, steviol (STE) was chosen as dummy template, and the density functional theory (DFT) at B3LYP/6-31 + G (d, p) level was used to select monomers, imprinting molar ratios, solvents, and cross-linking agents. The selectivity to five steviol glycosides was also calculated. Importantly, reduced density gradient (RDG) theory combined with atom in molecules (AIM) and infrared spectrum (IR) was applied to investigate the bonding situation and the nature of noncovalent interaction in self-assembly system. The theoretical designed results showed that the template which interacts with acrylic acid (AA) has the minimum binding energy, and the complex with the molar ratio of 1 : 4 has the most stable structure. Toluene (TL) and ethylene glycol dimethacrylate (EGDMA) were chosen as the optimal solvent and cross-linking agent, respectively. Five hydrogen bonds formed in the self-assembly system are the key forces at the adsorption sites of MIPs through the RDG and AIM analyses. The MIPs were synthesized by theoretical predictions, and the results showed that the maximum adsorption capacity towards dulcoside A is 26.17 mg/g. This work provided a theoretical direction and experimental validation for deeper researches of the MIPs for steviol glycosides. In addition, the method of RDG theory coupled with AIM and IR also could be used to analyze other imprinting formation mechanisms systematically.

Study on Mechanism of Ginkgo biloba L. Leaves for the Treatment of Neurodegenerative Diseases Based on Network Pharmacology.

Ginkgo biloba L. leaves (GBLs), as widely used plant extract sources, significantly improve cognitive, learning and memory function in patients with dementia. However, few studies have been conducted on the specific mechanism of Neurodegenerative diseases (NDs). In this study, network pharmacology was employed to elucidate potential mechanism of GBLs in the treatment of NDs. Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) was used to obtain the chemical components in accordance with the screening principles of oral availability and drug-like property. Potential targets of GBLs were integrated with disease targets, and intersection targets were exactly the potential action targets of GBLs for treating NDs; these key targets were enriched and analyzed by the protein protein interaction (PPI) analysis and molecular docking verification. Key genes were ultimately used to find the biological pathway and explain the therapeutic mechanism by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Twenty-seven active components of GBLs may affect biological processes such as oxidative reactions and activate transcription factor activities. These components may also affect 120 metabolic pathways, such as the PI3K/AKT pathway, by regulating 147 targets, including AKT1, ALB, HSP90AA1, PTGS2, MMP9, EGFR and APP. By using the software iGEMDOCK, the main target proteins were found to bind well to the main active components of GBLs. GBLs have the characteristics of multi-component and multi-target synergistic effect on the treatment of NDs, which preliminarily predicted its possible molecular mechanism of action, and provided the basis for the follow-up study.

Ginkgolide B­induced AMPK pathway activation protects astrocytes by regulating endoplasmic reticulum stress, oxidative stress and energy metabolism induced by Aß1­42.

Ginkgolide B (GB), the diterpenoid lactone compound isolated from the extracts of Ginkgo biloba leaves, significantly improves cognitive impairment, but its potential pharmacological effect on astrocytes induced by ß­amyloid (Aß)1­42 remains to be elucidated. The present study aimed to investigate the protective effect and mechanism of GB on astrocytes with Aß1­42­induced apoptosis in Alzheimer's disease (AD). Astrocytes obtained from Sprague Dawley rats were randomly divided into control, Aß, GB and GB + compound C groups. Cell viability and apoptosis were analyzed using Cell Counting Kit­8 and flow cytometry assays, respectively. Protein and mRNA expression levels were analyzed using western blotting and reverse transcription­quantitative PCR, respectively. The levels of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH­Px), reactive oxygen species (ROS) and ATP were determined using the corresponding commercial kits. The findings revealed that GB attenuated Aß1­42­induced apoptosis and the 5' adenosine monophosphate­ activated protein kinase (AMPK) inhibitor compound C reversed the protective effects of GB. In addition, GB reversed Aß1­42­induced oxidative damage and energy metabolism disorders, including decreases in the levels of SOD, GSH­Px and ATP and increased the levels of MDA and ROS in astrocytes, while compound C reversed the anti­oxidative effect and the involvement of GB in maintaining energy metabolism in astrocytes. Finally, GB decreased the expression levels of the endoplasmic reticulum stress (ERS) proteins and the apoptotic protein CHOP and increased both mRNA and protein expression of the components of the energy metabolism­related AMPK/peroxisome proliferator­activated receptor γ coactivator 1α/peroxisome proliferator­activated receptor α and anti­oxidation­related nuclear respiratory factor 2/heme oxygenase 1/NAD(P)H dehydrogenase (quinone 1) pathways and downregulated the expression of ß­secretase 1. However, compound C could antagonize these effects. In conclusion, the findings demonstrated that GB protected against Aß1­42­induced apoptosis by inhibiting ERS, oxidative stress, energy metabolism disorders and Aß1­42 production probably by activating AMPK signaling pathways. The findings provided an innovative insight into the treatment using GB as a therapeutic in Aß1­42­related AD.

NOGEA: A Network-oriented Gene Entropy Approach for Dissecting Disease Comorbidity and Drug Repositioning.

Rapid development of high-throughput technologies has permitted the identification of an increasing number of disease-associated genes (DAGs), which are important for understanding disease initiation and developing precision therapeutics. However, DAGs often contain large amounts of redundant or false positive information, leading to difficulties in quantifying and prioritizing potential relationships between these DAGs and human diseases. In this study, a network-oriented gene entropy approach (NOGEA) is proposed for accurately inferring master genes that contribute to specific diseases by quantitatively calculating their perturbation abilities on directed disease-specific gene networks. In addition, we confirmed that the master genes identified by NOGEA have a high reliability for predicting disease-specific initiation events and progression risk. Master genes may also be used to extract the underlying information of different diseases, thus revealing mechanisms of disease comorbidity. More importantly, approved therapeutic targets are topologically localized in a small neighborhood of master genes in the interactome network, which provides a new way for predicting drug-disease associations. Through this method, 11 old drugs were newly identified and predicted to be effective for treating pancreatic cancer and then validated by in vitro experiments. Collectively, the NOGEA was useful for identifying master genes that control disease initiation and co-occurrence, thus providing a valuable strategy for drug efficacy screening and repositioning. NOGEA codes are publicly available at https://github.com/guozihuaa/NOGEA.

3-Bromopyruvate decreased kidney fibrosis and fibroblast activation by suppressing aerobic glycolysis in unilateral ureteral obstruction mice model.

AIMS: Enhanced aerobic glycolysis is a motivation of fibroblast-myofibroblast transdifferentiation (FMT), leading to kidney fibrosis. 3-Bromopyruvate (3-BrPA) is a glycolysis inhibitor and has fibrosis-protected effect in liver. This study aims to explore the effects of 3-BrPA on aerobic glycolysis and kidney fibrosis in a unilateral ureteral obstruction (UUO) mice model and transforming growth factor-ß1(TGF-ß1)-stimulated normal rat kidney fibroblast (NRK49F) cell model in vitro. MAIN METHODS: In vivo UUO mouse model and in vitro TGF-ß1 stimulated cell model were built. Immunohistochemical staining, Western blots, Real-time PCR and fluorescence microscopy were employed to detect extra cellular matrix (ECM) synthesis, fibroblast activation, aerobic glycolysis switch and related signaling pathways. KEY FINDINGS: HE and Masson's Trichrome staining showed that 3-BrPA substantially suppressed kidney injury and interstitial collagen production. 3-BrPA also attenuated ECM accumulation in a dose-dependent manner, as shown by immunohistochemistry staining, RT-PCR and western blot. Furthermore, 3-BrPA inhibited FMT, as indicated by α-SMA and PCNA immunofluorescence double staining. Additionally, the results of MTT assay indicated 3-BrPA prevented TGF-ß1 induced fibroblasts proliferation in a time- and dose-dependent manner. Mechanistically, molecular docking results showed that 3-BrPA effectively decreased the aerobic glycolysis related enzymes Hexokinase-2 (HK-2), Lactate dehydrogenase A (LDHA) and Pyruvate kinase isozymes M2 (PKM-2), as well as inhibited IL-1 receptor-associated kinase 4 (IRAK4)/MYC protein levels. SIGNIFICANCE: Our study highlighted that 3-BrPA is a potential reno-protective agent in kidney fibrosis through the inhibition of fibroblasts aerobic glycolysis might via IRAK4/MYC signal pathways.

A RNA-seq approach for exploring the protective effect of ginkgolide B on glutamate-induced astrocytes injury.

ETHNOPHARMACOLOGICAL RELEVANCE: There is substantial experimental evidence to support the view that Ginkgo biloba L. (Ginkgoaceae), a traditional Chinese medicine known to treating stroke, has a protective effect on the central nervous system and significantly improves the cognitive dysfunction caused by disease, including alzheimer disease (AD), vascular dementia, and diabetic encephalopathy. Although a number of studies have reported that ginkgolide B (GB), a diterpenoid lactone compound extracted from Ginkgo biloba leaves, has neuroprotective effects, very little research has been performed to explore its potential pharmacological mechanism on astrocytes under abnormal glutamate (Glu) metabolism in the pathological environment of AD. AIM OF THE STUDY: We investigated the protective effect and mechanism of GB on Glu-induced astrocytes injury. METHODS: Astrocytes were randomly divided into the control group, Glu group, GB group, and GB + IWP-4 group.The CCK-8 assay was used to determine relative cell viability in vitro. Furthermore, RNA sequencing (RNA-seq) was performed to assess the preventive effects of GB in the Glu-induced astrocyte model and reverse transcription quantitative polymerase chain reaction (RT-qPCR) was used to validate the possible molecular mechanisms. The effects of GB on the Glu transporter and Glu-induced apoptosis of astrocytes were studied by RT-qPCR and western blot. RESULTS: GB attenuated Glu-induced apoptosis in a concentration-dependent manner, while the Wnt inhibitor IWP-4 reversed the protective effect of GB on astrocytes. The RNA-seq results revealed 4,032 differential gene expression profiles; 3,491 genes were up-regulated, and 543 genes were down-regulated in the GB group compared with the Glu group. Differentially expressed genes involved in a variety of signaling pathways, including the Hippo and Wnt pathways have been associated with the development and progression of AD. RT-qPCR was used to validate 14 key genes, and the results were consistent with the RNA-seq data. IWP-4 inhibited the regulation of GB, disturbed the apoptosis protective effect on astrocytes, and promoted Glu transporter gene and protein expression caused by Glu. CONCLUSION: Our findings demonstrate that GB may play a protective role in Glu-induced astrocyte injury by regulating the Hippo and Wnt pathways. GB was closely associated with the Wnt pathway by promoting expression of the Glu transporter and inhibiting Glu-induced injury in astrocytes.

A novel online preparative high-performance liquid chromatography system with the multiple trap columns-valve switch technique for the rapid and efficient isolation of main flavonoids from Epimedium koreanum Nakai.

In this work, a new online preparative high-performance liquid chromatography was developed for the fast and efficient separation of complex chemical mixtures from natural products. This system integrates two chromatographic systems into an online automatic separation system using the technique of multiple trap columns with valve switching. The sample was first separated into 18 subfractions in the online preparative high-performance liquid chromatography, and the sample eluents were then diluted and captured online on 18 trap columns by the multiple trap columns technique, respectively. Each subfraction retained on the trap column was transferred online to the separation column for the second separation. Finally, the target compounds were purified by appropriate separation conditions and multiple heart-cutting strategies. Importantly, the system was successfully used to separate 18 high-purity flavonoids from the crude extract of Epimedium koreanum Nakai online in one step. The entire separation time was approximately 20 h, and the structures were characterized by the high-performance liquid chromatography quadrupole time-of-flight tandem mass spectrometry and nuclear magnetic resonance. This online preparative high-performance liquid chromatography system represents an efficient and rapid separation system that has the potential for a wide array of applications in the separation of complex chemical components from natural products.

Continuous chromatography with multi-zone and multi-column dynamic tandem techniques for the isolation and enrichment of class compounds from natural products of Panax notoginseng.

Efficient and economical separation and enrichment of high-content class compounds from complex natural plants are of great importance. This study describes a novel continuous chromatography system (CCS) with multi-zone and multi-column dynamic tandem techniques for the efficient and economical separation and enrichment of high-content class compounds from natural products. The CCS was split into eight zones (each zone covered 2 or 3 columns connected dynamically in a series) via a multi-channel logic control valve to continuously and automatically separate and enrich class compounds from complex natural plants. CCS separation conditions were optimized by static and dynamic adsorption and desorption experiments. With the CCS system, 120.82 kg of Panax notoginseng saponins (PNS) was isolated from 1.0 t of P. notoginseng. Importantly, the total contents of five main saponins (R1, Rg1, Re, Rb1, and Rd) in PNS exceeded 90%, and the recovery rate exceeded 85%. In addition, this separation system enhanced the separation efficiency and decreased the mobile phase used. Thus, CCS with multi-zone and multi-column dynamic tandem techniques is an efficient and economical method for the large-scale preparation of high-content total saponins from P. notoginseng and will have wide application prospects, especially in the large-scale preparation of high-content class compounds from natural plants.

Feasibility Study of Tissue Transglutaminase for Self-Catalytic Cross-Linking of Self-Assembled Collagen Fibril Hydrogel and Its Promising Application in Wound Healing Promotion.

Collagen-based bio-hydrogels are undoubtedly a hot spot in the development of biological dressings for wound healing promotion. Herein, glutamine transaminase (TGase), a biological nontoxic cross-linker with high specific activity and reaction rate under mild conditions, was utilized for the self-catalytic cross-linking of the regenerated collagen (COL) fibril hydrogel fabricated through a molecular self-assembly method. The results showed that the natural triple helical conformation of COL remained completely integrated after self-catalytic cross-linking TGase, which was definitively the fundamental for maintaining its superior bioactivity. It was worth noting that TGase could promote the self-assembly process of COL building blocks into a higher order D-period cross-striated structure. Also, the reconstructed TGase cross-linked COL fibrils exhibited a higher degree of interfiber entanglements with more straight and longer fibrils. Meanwhile, the thermal stability of COL was significantly improved after introducing TGase. Besides, the cytocompatibility analysis suggested that the regenerated COL fibril hydrogel showed excellent cell growth activity and proliferation ability when the dosage of TGase is less than 40 U/g. Further, animal experiments indicated that the targeted COL fibril hydrogel could significantly promote skin wound healing, exhibiting better capacity of skin tissue for regeneration than the COL hydrogel untreated as expected. Therefore, the reconstructed TGase cross-linked COL fibril hydrogel could serve as a novel soft material for wound healing promotion.