Design, Synthesis, and Antifungal Activity of Acrylamide Derivatives Containing Trifluoromethylpyridine and Piperazine.

In this study, a series of acrylamide derivatives containing trifluoromethylpyridine or piperazine fragments were rationally designed and synthesized. Subsequently, the in vitro antifungal activities of all of the synthesized compounds were evaluated. The findings revealed that compounds 6b, 6c, and 7e exhibited >80% antifungal activity against Phomopsis sp. (Ps) at the concentration of 50 µg/mL. Furthermore, the EC50 values for compounds 6b, 6c, and 7e against Ps were determined to be 4.49, 6.47, and 8.68 µg/mL, respectively, which were better than the positive control with azoxystrobin (24.83 µg/mL). At the concentration of 200 µg/mL, the protective activity of compound 6b against Ps reached 65%, which was comparable to that of azoxystrobin (60.9%). Comprehensive mechanistic studies, including morphological studies with fluorescence microscopy (FM), cytoplasmic leakage, and enzyme activity assays, indicated that compound 6b disrupts cell membrane integrity and induces the accumulation of defense enzyme activity, thereby inhibiting mycelial growth. Therefore, compound 6b serves as a valuable candidate for the development of novel fungicides for plant protection.

Design of a delivery vehicle chitosan-based self-assembling: controlled release, high hydrophobicity, and safe treatment of plant fungal diseases.

BACKGROUND: Traditional pesticides are poorly water-soluble and suffer from low bioavailability. N-succinyl chitosan (NSCS) is a water-soluble chitosan derivative, has been recently used to encapsulate hydrophobic drugs to improve their bioavailability. However, it remains challenging to synthesize pesticides of a wide variety of water-soluble drugs and to scale up the production in a continuous manner. RESULTS: A synthetic method for preparing water-soluble nanopesticides with a polymer carrier was applied. The bioactive molecule BTL-11 was loaded into hollow NSCS to promote drug delivery, improve solubility and anti-fungal activity. The synthesized nanopesticides had well controlled sizes of 606 nm and the encapsulation rate was 80%. The release kinetics, drug toxicity and drug activity were further evaluated. The inhibitory activity of nanopesticides against Rhizoctonia solani (R. solani) was tested in vivo and in vitro. In vivo against R. solani trials revealed that BTL-11 has excellent control efficiency for cultivated rice leaf and sheath was 79.6 and 76.5%, respectively. By contrast, for BTL-11@NSCS NPs, the anti-fungal ability was strongly released and afforded significant control efficiencies of 85.9 and 81.1%. Those effects were significantly better than that of the agricultural fungicide azoxystrobin (51.5 and 66.5%). The proposed mechanism was validated by successfully predicting the synthesis outcomes. CONCLUSIONS: This study demonstrates that NSCS is a promising biocompatible carrier, which can enhance the efficacy of pesticides, synergistically improve plant disease resistance, protect crop growth, and can be used for the delivery of more insoluble pesticides.

Myricetin derivatives containing the benzoxazinone moiety discovered as potential anti-tobacco mosaic virus agents.

A series of myricetin derivatives containing benzoxazinone were designed and synthesized. The structures of all compounds were characterized by NMR and HRMS. The structure of Y4 had been confirmed by single-crystal X-ray diffraction analysis. The test results of EC50 values of tobacco mosaic virus (TMV) suggested that Y8 had the best curative and protective effects, with EC50 values of 236.8, 206.0 µg/mL, respectively, which were higher than that of ningnanmycin (372.4, 360.6 µg/mL). Microscale thermophoresis (MST) experiments demonstrated that Y8 possessed a strong binding affinity for tobacco mosaic virus coat protein (TMV-CP), with a dissociation constant (Kd) value of 0.045 µM, which was superior to the ningnanmycin (0.700 µM). The findings of molecular docking studies revealed that Y8 interacted with multiple amino acid residues of TMV-CP through the formation of non-covalent bonds, which had an effect on the self-assembly of TMV particles. The malondialdehyde (MDA) and superoxide dismutase assay (SOD) content assays also fully verified that Y8 could stimulate the plant immune system and enhance disease resistance by reducing MDA content and increasing SOD content. In summary, myricetin derivatives containing benzoxazinone could be considered to further research and development as novel antiviral agents.

Xylooligosaccharides from corn cobs alleviate loperamide-induced constipation in mice via modulation of gut microbiota and SCFA metabolism.

This study aimed to optimize the structure and efficacy of xylooligosaccharides (XOSs) from corn cobs in constipated mice. Structural analysis revealed that XOSs from corn cobs were composed of ß-Xyl-(1 →4)-[ß-Xyl-(1→4)]n-α/ß-Xyl (n = 0-5) without any other substituents. XOS administration significantly reduced the defecation time, increased the gastrointestinal transit rate, restored the gastrointestinal neurotransmitter imbalance, protected against oxidative stress, and reversed constipation-induced colonic inflammation. Fecal metabolite and microbiota analysis showed that XOS supplementation significantly increased short chain fatty acid (SCFA) levels and improved the gut microbial environment. These findings highlighted the potential of XOSs from corn cobs as an active ingredient for functional foods or as a therapeutic agent in constipation therapy.

Synthesis, physicochemical and emulsifying properties of OSA-modified tamarind seed polysaccharides with different degrees of substitution.

Octenyl succinic anhydride modified tamarind seed polysaccharides (OTSPs) with various degrees of substitution were first synthesized and characterized in this work. The structural, solid-state, solution and emulsifying properties of the OTSPs and the effect of the degree of substitution (DS) were investigated. The structural characterization confirmed the successful grafting of the OSA moiety into TSP and the chain extension of the OTSPs. The hydrophobicity of the modified polysaccharide molecules increased, the absolute value of the zeta potential increased, and the thermal stability decreased, which were positively or negatively correlated with the changes in DS. In contrast, the hydrolysis of polysaccharides in alkaline aqueous solution led to a decrease in molar mass and the rigidity of the molecules, which were not significantly related to DS. Particle size analysis showed that OTSPs tended to aggregate into relatively small agglomerates, which was confirmed by the results of morphological analysis. Most importantly, the instability indices of emulsions stabilized by TSP, arabic gum and OSA-starch were 0.521, 0.715, and 0.804, respectively, while for OTSPs this parameter was between 0.04 and 0.19 under the same conditions, indicating better physical stability of the OTSP-stabilized emulsions, especially for OTSP-30. Overall, OTSP has great potential as an emulsifier for oil-in-water emulsions, especially for emulsification and stabilization in food processing.

Self-assembly of tamarind seed polysaccharide via enzymatic depolymerization and degalactosylation enhanced ice recrystallization inhibition activity.

Polysaccharides are becoming potential candidates for developing food-grade cryoprotectants due to their extensive accessibility and health-promoting effects. However, unremarkable ice recrystallization inhibition (IRI) activity and high viscosity limit their practical applications in some systems. Our previous study found a galactoxyloglucan polysaccharide from tamarind seed (TSP) showing moderate IRI activity. Herein, the enhancement of the IRI performance of TSP via enzymatic depolymerization and degalactosylation-induced self-assembly was reported. TSP was depolymerized and subsequently removed ∼40 % Gal, which induced the formation of supramolecular rod-like fiber self-assembles and exhibited a severalfold enhancement of IRI. Ice shaping assay did not show obvious faceting of ice crystals, indicating that both depolymerized and self-assembled TSP showed very weak binding to ice. Molecular dynamics simulation confirmed the absence of molecular complementarity with ice. Further, it highlighted that degalactosylation did not cause significant changes in local hydration properties of TSP from the view of a single oligomer. The inconsistency between molecular simulation and macroscopic IRI effect proposed that the formation of unique supramolecular self-assemblies may be a key requirement for enhancing IRI activity. The findings of this study provided a new opportunity to enhance the applied potential of natural polysaccharides in food cryoprotection.

Anti-bacterial mechanism of baicalin-tobramycin combination on carbapenem-resistant Pseudomonas aeruginosa.

BACKGROUND: Pseudomonas aeruginosa (P. aeruginosa) is an important cause of nosocomial infections, and contributes to high morbidity and mortality, especially in intensive care units. P. aeruginosa is considered a 'critical' category bacterial pathogen by the World Health Organization to encourage an urgent need for research and development of new antibiotics against its infections. AIM: To investigate the effectiveness of baicalin combined with tobramycin therapy as a potential treatment method for carbapenem-resistant P. aeruginosa (CRPA) infections. METHODS: Polymerase chain reaction (PCR) and RT-PCR were used to detect the expression levels of drug-resistant genes (including VIM, IMP and OprD2) and biofilm-related genes (including algD, pslA and lasR) in CRPA that confer resistance to tobramycin, baicalin and tobramycin combined with baicalin (0, 1/8, 1/4, 1/2 and 1MIC). RESULTS: There was a correlation between biofilm formation and the expression of biofilm-related genes. In addition, VIM, IMP, OprD2, algD, pslA and lasR that confer biofilm production under different concentrations in CRPA were significantly correlated. The synergistic effect of baicalin combined with tobramycin was a significant down-regulation of VIM, IMP, algD, pslA and lasR. CONCLUSION: Baicalin combined with tobramycin therapy can be an effective treatment method for patients with CRPA infection.

Synthesis, antifungal activity and mechanism of action of novel chalcone derivatives containing 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole.

A series of chalcone derivatives containing 1,2,4-triazolo-[3,4-b]-1,3,4-thiadiazole was designed and synthesized. Structures of all compounds were characterized by 1H NMR, 13C NMR, 19F NMR, and HRMS. The biological activities of the compounds were determined with the mycelial growth rate method, and further studies showed that some compounds had good antifungal activities at the concentration of 100 µg/mL. The EC50 value of compound L31 was 15.9 µg/mL against Phomopsis sp., which were better than that of azoxystrobin (EC50 value was 69.4 µg/mL). In addition, the mechanism of action of compound L31 shown that compound can affect mycelial growth by disrupting membrane integrity against Phomopsis sp., and that the higher the concentration of the compound is, the greater the disruption of membrane integrity is.

Design, Synthesis and Antifungal Activity of Novel 1,4-Pentadiene-3-one Containing Quinazolinone.

Twenty 1,4-pentadiene-3-one derivatives containing quinazolinone (W1-W20) were designed and synthesized. The bioactivity test results showed that some compounds had antifungal activities in vitro. W12 showed excellent bioactivity against Sclerotinia sclerotiorum (S. sclerotiorum) and Phomopsis sp., with EC50 values of 0.70 and 3.84 µg/mL, which are higher than those of the control drug azoxystrobin at 8.15 and 17.25 µg/mL. In vivo activity tests were carried out on oilseed rape and kiwifruit. The protective effect of W12 on oilseed rape infected with S. sclerotiorum (91.7 and 87.3%) was better than that of azoxystrobin (90.2 and 79.8%) at 100 and 50 µg/mL, respectively, and the protective effect on kiwifruit infected with Phomopsis sp. (96.2%) was better than that of azoxystrobin (94.6%) at 200 µg/mL. Scanning electron microscopy results showed the hyphae of S. sclerotiorum treated with compound W12 abnormally collapsed and shriveled, inhibiting the growth of mycelium and, thus, laying the inhibiting effect on S. sclerotiorum. The results of the mechanism research showed that the action of W12 changed the mycelial morphology of S. sclerotiorum, affected the permeability of cells, increased the leakage of cytoplasm and allowed the cell membrane to break down. This study shows that 1,4-pentadiene-3-one derivatives containing quinazolinone have good effects on plant fungi and the potential for becoming new fungicides.

Structure-function relationship between galactomannans and their effects on freeze-thaw stability, retrogradation, and texture of corn starch gels during cold storage.

In this study, structural characteristics of Fenugreek (FG), Guar (GG), Locust bean (LBG), and Tara gums (TG) and their influence on physicochemical properties of corn starch (CS) gels were investigated. Results showed that FG presented a rigid rod structure, and GG, LBG, and TG showed an extended structure. The Mannose/Galactose (Man/Gal) ratio of FG, GG, LBG, and TG was 1.37, 1.96, 2.99, and 3.46, respectively. The molecular weight (Mw) of FG, GG, LBG, and TG was 0.89 × 106, 2.71 × 106, 3.61 × 106, and 2.77 × 106 Da, respectively. The structure-function relationship indicated that galactomannans with a high Man/Gal ratio and extended structure presented a higher apparent viscosity, formed gel more easily, and could limit retrogradation and improve freeze-thaw stability and textural profile of CS gels. Consequently, the results could be beneficial for the application of galactomannans in starch-based foods to improve their sensory characteristics and storage quality.

AuNPs and graphdiyne nanocomposite as robust electrocatalyst for methyl parathion detection in real samples.

The present work describes a simple and rapid synthesis method of gold nanoparticles and graphdiyne (AuNPs@GDY) nanocomposites including porous structure. Moreover, the synthesized AuNPs@GDY material was decorated on the glassy carbon electrode (GCE) with a drop coating method to construct a non-enzymatic electrochemical pesticides sensor. The micro-morphology and elemental composition of the materials were characterized by transmission electron microscopy (TEM) and energy dispersive spectroscopy (EDS). The electrocatalysis and conductivity of the material were studied with cyclic voltammetry (CV) and impedance method, respectively. The properties of the sensor were investigated by CV and differential pulse voltammetry (DPV). The results showed that AuNPs@GDY exhibited excellent electrocatalytic ability for methyl parathion in a wide linear range (from 0.25 ng/mL to 24.43 µg/mL) and low limit of detection value (6.2 pg/mL). Furthermore, the DPV method used in this paper was accurate and sensitive, and could be used for routine quality control of methyl parathion in kiwi fruit and tomato samples.

Changes in serum angiogenic factors among patients with acute pain and subacute pain.

Screening serum biomarkers for acute and subacute pain is important for precise pain management. This study aimed to examine serum levels of angiogenic factors in patients with acute and subacute pain as potential biomarkers. Serum samples were collected from 12 healthy controls, 20 patients with postherpetic neuralgia (PHN), 4 with low back pain (LBP), and 1 with trigeminal neuralgia (TN). Pain intensity in these patients was evaluated using the visual analog scale (VAS). The serum concentrations of 11 angiogenic biomarkers were examined by Milliplex Map Human Angiogenesis Magnetic Bead Panel 2. The pain assessment from VAS showed that all patients showed moderate and severe pain. Among 11 angiogenic factors, osteopontin (OPN), thrombospondin-2 (TSP-2), soluble platelet endothelial cell adhesion molecule-1 (sPECAM-1), soluble urokinase-type plasminogen activator receptor (suPAR), and soluble epidermal growth factor receptors (sErbB2) were up-regulated and soluble interleukin-6 receptor α (sIL-6Rα) were down-regulated in patients with pain compared to the healthy participants (all P-values were < 0.005). Moreover, a linear regression model showed that the serum OPN concentration was correlated with pain intensity in patients with PHN (P = 0.03). There was no significant difference between the serum concentration of soluble epidermal growth factor receptors, sErbB3, soluble AXL, tenascin, and soluble neuropilin-1 in patients with acute and subacute pain and that of healthy controls. The results of this study provided new valuable insights into our understanding of angiogenic factors that may contribute to as mechanistic biomarkers of pain, and reveal the pathophysiological mechanism of pain. Clinical Trial Registration: www.chictr.org.cn, identifier ChiCTR2200061775.

Various detailed characteristics of a new enhanced neurotrophic factor secreting rat derived bone marrow mesenchymal stem cells and its preliminary application in rat models of ischemic stroke.

Because MSC-NTF has a higher ability to secrete neurotrophic factors, it may have a greater potential than ordinary MSC in clinical applications. At present, research on MSC-NTF mainly focuses on clinical aspects, but its basic research is relatively few. In particular, the research on the comprehensive and detailed characteristics of MSC-NTF is missing. And its in vivo research in animals is also rare. Since the transplantation of human-derived MSC-NTF into rats is cross-species, its survival in the rat and the therapeutic effect may be seriously affected due to severe immune rejection. This will inevitably affect the research on the basic characteristics and the therapeutic mechanisms of MSC-NTF in vivo. Therefore, we chose the rat-derived MSCs to be induced as the MSC-NTF which had a stronger neurotrophic factor secretion function. This will also be helpful to perform the research of the basic therapeutic mechanisms of MSC-NTF in vivo. In addition, we have established some important characteristics that can be used to distinguish between MSC-NTF and MSCs: different multi-factor secretion ability and secretion characteristics, immunogenicity, three-line differentiation ability, stemness, etc. In addition to paying attention to their safety differences, this study also explored the differences in their in vivo survivability. Finally, we applied this newly induced rat-derived MSC-NTF in a rat model of ischemic stroke, and obtained beneficial therapeutic effects.

A low-carbon high inulin diet improves intestinal mucosal barrier function and immunity against infectious diseases in goats.

Introduction: Abrupt weaning is a major stressful event, contributing to intestinal abnormalities and immune system dysfunction in weaned kids. Inulin is a prebiotic fiber with many positive functions, including promoting intestinal fermentation and enhancing host immunity in monogastric animals. However, the effects of a high-inulin, energy-rich diet on ruminal fermentation characteristics, methane emission, growth performance, and immune systems of weaned kids have not been investigated. Methods: A fully automated in vitro fermentation system was used to investigate ruminal fermentation characteristics and methane emission of a mixed substrate of inulin and fat powder (1.31: 1) in comparison with maize grain-based starter concentrate. During a 1-week adaptation and 4-week trial phase, 18 weaned kids (8.97 ± 0.19 kg) were randomly assigned to two groups, one with a conventional diet (83% maize grain; CON) and the other with a low-carbon, high-inulin diet (41.5% maize grain, 14.4% fat powder, 18.9% inulin; INU). Results: In the in vitro rumen fermentation experiment, the total gas production was not different (p > 0.05); however, a lower (p < 0.05) methane production was observed for INU as compared to CON. The average daily gain and the ratio of feed intake and growth performance of kids fed with INU were higher (p < 0.05) than those fed with CON. Serum concentrations of alanine transaminase (ALT) and lactate dehydrogenase (LDH) were lower (p < 0.05), whereas the concentration of high-density lipoprotein (HDL) and cholesterol (CHOL) were higher (p < 0.05) in kids fed with the INU diet as compared CON. Dietary inulin significantly increased (p < 0.05) the secretion of immunoglobulins (IgA, IgG, and IgM) and inflammatory cytokines (IFN-γ and IL-10) in ileum tissue. Although no differences (p > 0.05) were observed in mRNA expression of tight junction markers, the INU diet tended to increase (p = 0.09) gene expression of ribosomal protein S6 kinase beta-1 (P70S6K) in the mammalian target of rapamycin (mTOR) pathway of longissimus dorsi muscle. Conclusion: Our findings highlighted that a low-carbon high-inulin energy-rich diet could be used as a promising strategy to improve gut immunity and growth performance of weaned kids under abrupt weaning stress and reduce methane production.

Sodium Alginate Binders for Bivalency Aqueous Batteries.

Environmental friendly sodium alginate (SA) cannot be used as a binder in aqueous batteries due to its high solubility in water. A water-insoluble polyvinylidene difluoride (PVDF) binder has been widely applied for an aqueous battery, in which the toxic and expensive organic solvent of N-methy-2-pyrrolidone (NMP) is required during the coating process. Herein, we report that the water-soluble SA can be utilized as a binder in aqueous Zn batteries because SA could cross-link with the Zn2+ ion to form a water-insoluble and mechanically super strong binder for electrodes. Aqueous Zn||LiFePO4 cells are assembled to demonstrate the performance of the SA binder for LiFePO4 cathodes. Due to the high adhesion strength of cross-linked Zn-SA, LiFePO4 with the SA binder displays a high capacity retention of 93.7% with a high Coulombic efficiency of nearly 100% after 100 cycles at a 0.2 C rate, while the capacity of LiFePO4 with the PVDF binder quickly decays to 84.7% after 100 cycles at 0.2 C. In addition, the LiFePO4 cathode with the SA binder also has smaller redox polarization, faster ion diffusion rate, and more favorable electrochemical kinetics than that with the PVDF binder.

Plan, Do, Check, Act (PDCA) Cycle Nursing Model Reduces the Risk of Hemangioma in Hemodialysis Patients.

Background: We aimed to explore the effect of Plan, Do, Check, Act (PDCA) circulation nursing on the prevention of aneurysm after hemodialysis. Methods: A total of 139 hemodialysis patients from Oct 2018 to Jan 2020 in Nephrology Department of the First People's Hospital of Lianyungang, China were enrolled. They were randomly divided into control group and PCDA group, including 58 patients in control group and 81 patients in PCDA group. Patients' satisfaction, blood flow in arteriovenous internal fistula and the incidence of post-dialysis vascular-related complications were statistically investigated in the two groups. Results: The satisfaction of patients in PDCA group was significantly higher than that in control group (P<0.001). In addition, when there was no statistical difference in blood flow between the two groups, the probability of complications such as internal fistula obstruction, thrombosis, infection, secondary puncture and aneurysm was lower in patients in the PDCA group, none of which occurred aneurysm. Conclusion: PDCA circulation nursing can effectively improve the quality of care and medical effect of hemodialysis patients with internal arteriovenous fistula, improve patient satisfaction and reduce the incidence of complications.

Correction: Two Ln-based metal-organic frameworks based on the 5-(1H-1,2,4-triazol-1-yl)-1,3-benzenedicarboxylic acid ligand: syntheses, structures, and photocatalytic properties.

[This corrects the article DOI: 10.1039/D0RA07159E.].

Two Ln-based metal-organic frameworks based on the 5-(1H-1,2,4-triazol-1-yl)-1,3-benzenedicarboxylic acid ligand: syntheses, structures, and photocatalytic properties.

Two new metal-organic frameworks (MOFs) having the formula [Ln2(H2O)3(L)3·3H2O] n (Ln = Sm for MOF-Sm and Tb for MOF-Tb) have been synthesized solvothermally by reacting LnCl3·6H2O with 5-(1H-1,2,4-triazol-1-yl)-1,3-benzenedicarboxylic acid (H2L) and characterized. Single crystal X-ray analyses for MOF-Sm and MOF-Tb revealed that both MOFs are isostructural and display a (6,8)-connected 3D structure with a point symbol of (35·44·66)(35·46·517). The natures of weak interactions existing in both MOFs have been assessed using Hirshfeld surface analyses and fingerprint plots. The utility of MOF-Sm as a photocatalyst for the safe photodegradation of the model aromatic dye methyl violet (MV) is also checked. The photocatalysis results showed that MOF-Sm offers reasonable photocatalytic degradation of this dye. The plausible photocatalytic mechanism of MOF-Sm aided photocatalysis has been explained with the help of band gap calculations using density of states (DOS) and partial DOS plots.