Effect of Nicotinamide Against Candida albicans

Nicotinamide (NAM) has a long history in clinical applications and can be safely used for treating various diseases. In recent years, NAM was found to exhibit antimicrobial activities, inhibiting the growth of Plasmodium falciparum, Mycobacterium tuberculosis, and human immunodeficiency virus (HIV). Here we investigated the activity of NAM against Candida albicans, one of the most prevalent human fungal pathogens. Our results showed that NAM exhibited significant antifungal activity against C. albicans, including fluconazole-resistant isolates. NAM could also effectively suppress biofilm formation. In addition, NAM exhibited antifungal activity against non-Candida albicans species and Cryptococcus neoformans. Combination of NAM and fluconazole showed an even strong antifungal activity. The antifungal activity of NAM was further confirmed in a mouse model of disseminated candidiasis. Confocal laser scanning microscopy revealed that NAM increased cell wall β-glucans exposure and chitin content while decreased mannan level. Furthermore, by screening the C. albicans homozygous deletion mutant library, the C. albicans mutant lacking GIN4, which encodes a septin regulatory protein kinase and is essential for the maintenance of cell wall integrity, was identified to be high sensitive to NAM. These findings suggested that NAM might exhibit antifungal activities through affecting cell wall organization

Research on Fractional-Order Global Fast Terminal Sliding Mode Control of MDF Continuous Hot-Pressing Position Servo System Based on Adaptive RBF Neural Network

In this paper, a novel fractional-order global fast terminal sliding mode control (FGFTSMC) strategy based on an adaptive radial basis function (RBF) neural network is proposed to improve the performance of a medium density fiberboard (MDF) continuous hot-pressing position servo system with parameter perturbation and external load disturbance. Primarily, the mathematical model of the MDF continuous hot-pressing position servo system is constructed based on the dynamic equation of the hydraulic system. Then, a FGFTSMC is designed to speed up the convergence rate of the system, in which an adaptive law is used to estimate the upper bound of the unknown parameters to overcome the existing parameter perturbation of the system. In addition, an RBF neural network is introduced to approximate the external load disturbance of the system. The stability of MDF continuous hot-pressing position servo system based on the control scheme developed in this paper is proven using the Lyapunov theory. Finally, the simulation results show that the presented control scheme can effectively ensure the tracking accuracy of the system and enhance the robustness of the system

Research on Fractional-Order Global Fast Terminal Sliding Mode Control of MDF Continuous Hot-Pressing Position Servo System Based on Adaptive RBF Neural Network

In this paper, a novel fractional-order global fast terminal sliding mode control (FGFTSMC) strategy based on an adaptive radial basis function (RBF) neural network is proposed to improve the performance of a medium density fiberboard (MDF) continuous hot-pressing position servo system with parameter perturbation and external load disturbance. Primarily, the mathematical model of the MDF continuous hot-pressing position servo system is constructed based on the dynamic equation of the hydraulic system. Then, a FGFTSMC is designed to speed up the convergence rate of the system, in which an adaptive law is used to estimate the upper bound of the unknown parameters to overcome the existing parameter perturbation of the system. In addition, an RBF neural network is introduced to approximate the external load disturbance of the system. The stability of MDF continuous hot-pressing position servo system based on the control scheme developed in this paper is proven using the Lyapunov theory. Finally, the simulation results show that the presented control scheme can effectively ensure the tracking accuracy of the system and enhance the robustness of the system

Bioaugmentation with a propionate-degrading methanogenic culture to improve methane production from chicken manure

Volatile fatty acid (VFA) accumulation caused by high ammonia concentrations is often encountered during the anaerobic digestion (AD) of ammonia-rich substrates. In this study, propionate-degrading methanogenic cultures were introduced to augment the semi-continuous AD of chicken manure under high ammonia levels. Introduction of a methanogenic culture enhanced the methane yield in the bioaugmented digester by 17-26% when the organic loading rate (OLR) was 2-4 g L(-1)d(-1) compared to that in the control. When the OLR was further increased from 4.0 L(-1)d(-1) to 5.0 g L(-1)d(-1), and bioaugmentation ceased, methane yield improved by 15-18% under a high total ammonia nitrogen level of 5.0-8.4 g NH4+-N/L. Moreover, bioaugmentation reconstructed the methanogenic community in the digester, promoting the dominance of hydrogenotrophic Methanobacterium and slightly increasing the abundance of aceticlastic Methanothrix and the syntrophic propionate-oxidizing bacteria Syntrophobacter, which were the key contributors to the improved AD under high ammonia concentrations

Mitochondrial dysfunction and calcium dyshomeostasis in the pectoralis major muscle of broiler chickens with wooden breast myopathy

ABSTRACT: The incidence of wooden breast (WB) meat of commercial broiler chicken has been increasing in recent years. Histological examination found that the occurrence of WB myopathy was accompanied by the pectoralis major (PM) muscle damage. So far, the potential mechanisms are not fully understood. This study aimed to explore the underlying mechanism of the damage of WB-affected PM muscle caused by changes in mitochondrial function, mitochondrial redox status and Ca2+ homeostasis. A total of 80 market-age Arbor Acres male broiler chickens were sampled and categorized into control (CON) and WB groups based on the evaluation of myopathic lesions. PM muscle samples were collected (n = 8 in each group) for histopathological evaluation and biochemical analyses. Ultrastructural examination and histopathological changes suggested the occurrence of PM muscle damage in broiler chickens with WB myopathy. The WB group showed an increased level of reactive oxygen species and enhanced antioxidant capacities in mitochondria of PM muscle. These changes were related to impaired mitochondria morphology and mitochondrial dysfunction. In addition, abnormal expressions of Ca2+ channels led to substantial Ca2+ loss in SR and cytoplasmic Ca2+ overload, as well as Ca2+ accumulation in mitochondria, resulting in Ca2+ dyshomeostasis in PM muscle of broiler chickens with WB myopathy. Combined, these findings indicate that WB myopathy is related to mitochondrial dysfunction, mitochondrial redox status imbalance and Ca2+ dyshomeostasis, leading to WB-affected PM muscle damage

Interaction Between Root Exudates of the Poisonous Plant Stellera chamaejasme L. and Arbuscular Mycorrhizal Fungi on the Growth of Leymus Chinensis (Trin.) Tzvel

The growth of a large number of poisonous plants is an indicator of grassland degradation. Releasing allelochemicals through root exudates is one of the strategies with which poisonous plants affect neighboring plants in nature. Arbuscular mycorrhizal fungi (AMF) can form a mutualistic symbiosis with most of the higher plants. However, the manner of interaction between root exudates of poisonous plants and AMF on neighboring herbage in grasslands remains poorly understood. Stellera chamaejasme L., a common poisonous plant with approved allelopathy, is widely distributed with the dominant grass of Leymus chinensis in the degradeds of Northern China. In this study, we investigated the addition of S. chamaejasme root exudates (SRE), the inoculation of AMF, and their interaction on the growth and tissue nitrogen contents of L. chinensis, the characteristics of rhizosphere AMF, and soil physicochemical properties. Results showed that SRE had significant effects on ramet number, aboveground biomass, and total nitrogen of L. chinensis in a concentration dependent manner. Additionally, SRE had a significant negative effect on the rate of mycorrhiza infection and spore density of the AMF. Meanwhile, the addition of SRE significantly affected soil pH, electrical conductivity, available nitrogen (AN), available phosphorus (AP), total nitrogen (TN), and total carbon (TC) contents; while neither inoculation of AMF itself nor the interaction of AMF with SRE significantly affected the growth of L. chinensis. The interaction between AMF and SRE dramatically changed the pH, AP, and TC of rhizosphere soil. Therefore, we suggested SRE of S. chamaejasme affected the growth of L. chinensis by altering soil pH and nutrient availability. AMF could change the effect of SRE on soil nutrients and have the potential to regulate the allelopathic effects of S. chamaejasme and the interspecific interaction between the two plant species. We have provided new evidence for the allelopathic mechanism of S. chamaejasme and the regulation effects of AMF on the interspecific relationship between poisonous plants and neighboring plants. Our findings reveal the complex interplay between the root exudates of poisonous plants and rhizosphere AMF in regulating population growth and dynamics of neighboring plants in degraded grassland ecosystems

Discovery of Synergistic Drug Combinations for Colorectal Cancer Driven by Tumor Barcode Derived from Metabolomics “Big Data”

The accumulation of cancer metabolomics data in the past decade provides exceptional opportunities for deeper investigations into cancer metabolism. However, integrating a large amount of heterogeneous metabolomics data to draw a full picture of the metabolic reprogramming and to discover oncometabolites of certain cancers remains challenging. In this study, a tumor barcode constructed based upon existing metabolomics “big data” using the Bayesian vote-counting method is proposed to identify oncometabolites in colorectal cancer (CRC). Specifically, a panel of oncometabolites of CRC was generated from 39 clinical studies with 3202 blood samples (1332 CRC vs. 1870 controls) and 990 tissue samples (495 CRC vs. 495 controls). Next, an oncometabolite-protein network was constructed by combining the tumor barcode and its involved proteins/enzymes. The effect of anti-cancer drugs or drug combinations was then mapped into this network by the random walk with restart process. Utilizing this network, potential Irinotecan (CPT-11)-sensitizing agents for CRC treatment were discovered by random forest and Xgboost. Finally, a compound named MK-2206 was highlighted and its synergy with CPT-11 was validated on two CRC cell lines. To summarize, we demonstrate in the present study that the metabolomics “big data”-based tumor barcodes and the subsequent network analyses are potentially useful for drug combination discovery or drug repositioning

The effect of lignin molecular weight on the formation and properties of carbon quantum dots

It is generally believed that the formation of lignin-based carbon quantum dots (L-CQDs) includes lignin depolymerization and repolymerization. However, the detailed mechanism has not been well understood. In this study, the effect of lignin molecular weight on the properties of L-CQDs is studied to elucidate the formation mechanism of L-CQDs. Firstly, alkaline lignin is sequentially fractionated into five lignin samples with a molecular weight range of 7100–2000 using a continuous organic solvent precipitation method. Then, the five lignin fractions are used to prepare five L-CQDs numbered from 1 to 5, corresponding to the lignin fractions from high to low, respectively. L-CQDs-3 that was prepared from the lignin fraction with an intermediate molecular weight of 5042 g mol−1 has a 1.86-fold increase in fluorescence intensity compared to the L-CQDs-0 prepared from pristine alkaline lignin. It is found that this lignin fraction with a molecular weight of 5042 g mol−1 can depolymerize into a large number of vanillin and benzaldehyde (2,4-dihydroxy-6-methyl) units. These low molecular weight units can easily form highly conjugated carbon core structures, thus improving the fluorescence performance of L-CQDs-3. In addition, the present study confirms the excellent imaging ability of L-CQDs-3 in the L02, HepG2 and Escherichia coli cells. This study not only supplements the existing L-CQD formation mechanism, but also provides a simple method for the preparation of L-CQDs with high fluorescence performance

The Active Components of Fuzheng Huayu Formula and Their Potential Mechanism of Action in Inhibiting the Hepatic Stellate Cells Viability – A Network Pharmacology and Transcriptomics Approach

Purpose: This study aimed to identify the active components of Fuzheng Huayu (FZHY) formula and the mechanism by which they inhibit the viability of hepatic stellate cells (HSCs) by a combination of network pharmacology and transcriptomics.Methods: The active components of FZHY formula were screened out by text mining. Similarity match and molecular docking were used to predict the target proteins of these compounds. We then searched the STRING database to analyze the key enriched processes, pathways and related diseases of these target proteins. The relevant networks were constructed by Cytoscape. A network analysis method was established by integrating data from above network pharmacology with known transcriptomics analysis of quiescent HSCs-activated HSCs to identify the most possible targets of the active components in FZHY formula. A cell-based assay (LX-2 and T6 cells) and surface plasmon resonance (SPR) analysis were used to validate the most possible active component-target protein interactions (CTPIs).Results: 40 active ingredients in FZHY formula and their 79 potential target proteins were identified by network pharmacology approach. Further network analysis reduced the 79 potential target proteins to 31, which were considered more likely to be the target proteins of the active components in FZHY formula. In addition, further enrichment analysis of 31 target proteins indicated that the HIF-1, PI3K-Akt, FoxO, and chemokine signaling pathways may be the primary pathways regulated by FZHY formula in inhibiting the HSCs viability for the treatment of liver fibrosis. Of the 31 target proteins, peroxisome proliferator activator receptor gamma (PPARG) was selected for validation by experiments at the cellular and molecular level. The results demonstrated that schisandrin B, salvianolic acid A and kaempferol could directly bind to PPARG, decreasing the viability of HSCs (T6 cells and LX-2 cells) and exerting anti-fibrosis effects.Conclusion: The active ingredients of FZHY formula were successfully identified and the mechanisms by which they inhibit HSC viability determined, using network pharmacology and transcriptomics. This work is expected to benefit the clinical application of this formula

Development and Application of an UHPLC-MS/MS Method for Comparative Pharmacokinetic Study of Eight Major Bioactive Components from Yin Chen Hao Tang in Normal and Acute Liver Injured Rats

Yin Chen Hao Tang (YCHT) is one of the most famous hepatoprotective herbal formulas in China, but its pharmacokinetic investigation in model rats has been rarely conducted. In this study, the hepatic injury model was caused by intraperitoneal injections of carbon tetrachloride (CCl4), and YCHT was orally administered to the model and normal rats. An ultrahigh performance liquid chromatography–tandem mass spectrometry (UHPLC–MS/MS) method was established to analyze the plasma pharmacokinetics of eight major bioactive ingredients from YCHT in both the normal and liver injured rats. The calibration curves presented good linearity (r > 0.9981) in the concentration range. The relative standard deviation (RSD%) of inter- and intraday precision was within 9.55%, and the accuracy (RE%) ranged from -10.72% to 2.46%. The extraction recovery, matrix effect, and stability were demonstrated to be within acceptable ranges. The lower limit of detection (LLOD) and lower limit of quantitation (LLOQ) were around 0.1 ng/mL and 0.5 ng/mL, respectively, which were much lower than those in other related researches. Results reveal that there are significant differences in the pharmacokinetics of scoparone, geniposide, rhein, aloe-emodin, physcion, and chrysophanol in hepatic injured rats as compared to those in control except for scopoletin and emodin. Our experimental results provide a meaningful reference for the clinical dosage of YCHT in treating liver disorders, and the improvement of LLOD and LLOQ can also broaden the range of our method’s application, which is very suitable for quantitating these eight compounds with low levels