Theoretical Study on the Coordination and Separation Capacity of Macrocyclic N-Donor Extractants for Am(III)/Eu(III).

Designing ligands that can effectively separate actinide An(III)/lanthanide Ln(III) in the solvent extraction process remains one of the key issues in the treatment of accumulated spent nuclear fuel. Nitrogen donor ligands are considered as promising extractants for the separation of An(III) and Ln(III) due to their environmental friendliness. Four new macrocyclic N-donor hexadentate extractants were designed and their coordination with Am(III) and Eu(III), as well as their extraction selectivity and separation performance for Am(III) and Eu(III), were investigated by scalar relativistic density functional theory. A variety of theoretical methods have been used to evaluate the properties of the four ligands and the coordination structures, bonding properties, and thermodynamic properties of the complexes formed by the four ligands with Am(III) and Eu(III). The results of various wavefunction analysis methods including NBO analysis, quantum theory of atoms in molecules (QTAIM) analysis, and so on show that Am(III) has a stronger coordination ability with the ligands than Eu(III) due to the Am 5f orbitals more involved in bonding with the ligands than the Eu 4f orbitals, and the bonding environment of the N-donor in the ligand has a significant effect on its coordination ability of the metal ions. Thermodynamic analysis of the solvent extraction process shows that all of the four N-containing macrocyclic ligands have good extraction selectivity and separation performance for Am(III) and Eu(III). This study provides theoretical support for designing potential nitrogen-containing macrocyclic extractants with excellent separation performance.

[Molecular mechanisms of meiotic recombination suppression in plants].

Meiotic recombination not only ensures the stability of chromosome numbers during the sexual reproduction in eukaryotes, but also shuffles the maternal and paternal genetic materials to generate genetic diversity in the gametes. Therefore, meiotic recombination is an important pathway for genetic diversity, which has been considered as a major driving force for species evolution and biodiversity in nature. In most eukaryotes, meiotic recombination is strictly limited, despite the large variation of physical genome size and chromosome numbers among species, but the mechanisms suppressing meiotic recombination remain elusive. Recently, several suppressors have been identified through the forward genetics screen, and revealed the functions and regulation pathways of these suppressors. In this review, we summarize the breakthrough discovery of meiotic recombination suppressors in plants based on research in Arabidopsis, with particular focus on the gene function and its regulation network to elucidate the molecular mechanisms of meiotic recombination suppression in plants.

The comparison of biocompatibility and osteoinductivity between multi-walled and single-walled carbon nanotube/PHBV composites.

The applications of poly (3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) in tissue engineering have been widely studied. This study aimed to compare the biocompatibility and osteoinductivity of single-walled carbon nanotubes (SWCNTs)/PHBV composites with multi-walled CNTs (MWCNTs)/PHBV composites. CNTs were dispersed in PHBV by ultrasonication and composites were created using thermal injection moulding. In order to test their biocompatibility and osteoinductivity. Rat osteoblasts (rOBs) were then cultured and seeded on the composites. The composites were implanted in rat femoral bone defects. Our results showed that lower weight percentages of SWCNTs and MWCNTs (2-4%) improved both their mechanical and thermal decomposition properties. However, further reduction of rOBs cell death was observed in MWCNTs/PHBV. SWCNTs were shown to upregulate the expression of Runx-2 and Bmp-2 in early stage significantly, while MWCNTs showed a stronger long-term effect on Opn and Ocn. The in vivo result was that MWCNTs/PHBV composites induced intact rounding new bone, increased integration with new bone, and earlier completed bone remodeling when compared with SWCNTs. Immunohistochemistry also detected higher expression of RUNX-2 around MWCNTs/PHBV composites. In conclusion, there were no differences observed between SWCNTs and MWCNTs in the reinforcement of PHBV, while MWCNTs/PHBV composites showed better biocompatibility and osteoinductivity both in vitro and in vivo.

Zein nanospheres assisting inorganic and organic drug combination to overcome stent implantation-induced thrombosis and infection.

The complication of stent implantation is the biggest obstacle to the success of its clinical application. In this study, we developed a combination way of 3D printing and the coating technique for preparation of functional polyurethane stents against stent implantation-induced thrombosis and postoperative infection. SEM, XPS, static water contact angle, and XRD demonstrated that the functional polyurethane stent had a 37 µm-thickness membrane composed of zein nanospheres (250-350 nm). Meanwhile, ZnO nanoparticles were encapsulated in zein nanospheres while heparin was adsorbed on the surface, causing 97.1 ± 6.4 % release of heparin in 120 min (first-order kinetic model) and 62.7 ± 5.6 % release of Zn2+ in 9 days (Korsmeyer-Peppas model). The mechanical analysis revealed that the functional polyurethane stents had about 8.61 MPa and 2.5 MPa tensile strength and bending strength, respectively. The in vitro biological analysis showed that the functional polyurethane stents had good EA.hy926 cells compatibility (97.9 ± 3.8 %), anti-coagulation response (comparable plasma protein, platelet adhesion and suppressed clotting) and sustained antibacterial activities by comparison with the bare polyurethane stent. The preliminary evaluation by rabbit ex vivo carotid artery intervention experiment demonstrated that the functional polyurethane stents could maintain blood circulation under the continuous stresses of blood flow. Meanwhile, the detailed data from the simulated implant infection experiment in vivo showed the functional polyurethane stents could effectively reduce microbial infection by 3-6 times lower and improve fibrosis and macrophage infiltration.

Oral Administration of the Antimicrobial Peptide Mastoparan X Alleviates Enterohemorrhagic Escherichia coli-Induced Intestinal Inflammation and Regulates the Gut Microbiota.

The gut microbiota plays an important role in intestinal immune system development and in driving inflammation. Antibiotic administration for therapeutic purposes causes an imbalance in the gut microbiota. Antimicrobial peptides can regulate the gut microbiota and maintain intestinal homeostasis. The aim of this study was to investigate the anti-inflammatory effects and regulation of the gut microbiota by the orally administered antimicrobial peptide mastoparan X (MPX). In this study, Escherichia coli was used to induce intestinal inflammation, and the results showed that MPX+ E. coli alleviated weight loss and intestinal pathological changes in necropsy specimens of E. coli-infected mice. MPX+ E. coli reduced the serum levels of the inflammation-related proteins interleukin-2, interleukin-6, tumour necrosis factor-α, myeloperoxidase, and lactate dehydrogenase on days 7 and 28. Furthermore, MPX+ E. coli increased the length of villi and reduced the infiltration of inflammatory cells into the jejunum and colon post infection. Scanning electron microscopy and transmission electron microscopy results showed that MPX could improve the morphology of jejunum villi and microvilli and increase tight junction protein levels. 16S rRNA sequencing analysis of caecal content samples showed that the species diversity and richness were lower in the E. coli-infected group. At the genus level, MPX+ E. coli significantly reduced the abundance of Bacteroidales and Alistipes and enhanced the relative abundance of Muribaculaceae. Alpha-diversity analyses (Shannon index) showed that MPX significantly increased the microbial diversity of mice. Overall, this study is the first to investigate the effects of oral administration of MPX on intestinal inflammation and the gut microbiota, providing a new perspective regarding the prevention of enteritis and maintenance of intestinal homeostasis.

Effectiveness and safety of traditional Chinese herbs in children with cough variant asthma: a systematic review and Meta-analysi.

OBJECTIVE: To systematically investigate the clinical effectiveness and safety of traditional Chinese herbs (TCHs) as an alternative to conventional medicine (CM) in children with cough variant asthma(CVA). METHODS: Randomized controlled trial (RCT) studies that were published from their inceptions to March 31, 2020, were identified from the electronic databases of China National Knowledge Infrastructure, Wangfang, PubMed, and Cochrane Central Library. The primary outcome of the review was the total effective rate (TER), and the secondary outcomes were immunoglobulin E (IgE), peak expiratory flow (PEF), adverse drug reactions, and relapse rates of interventions. RESULTS: For the Meta-analysis, 13 studies involving 992 children with CVA were included. In terms of TER and IgE, the experimental interventions of TCH, when compared with the control interventions of CM, on pediatric CVA were found to be significantly effective (P < 0.0001), whereas for spirometry, PEF was not significantly improved in the TCH group (P = 0.48). The incident rates of adverse drug reaction and relapse were found to be significantly lower in the TCH group than those in the CM group (P = 0.02 and P < 0.0001, respectively). CONCLUSION: Compared with CM therapy, the effects of TCH therapy on pediatric CVA were significantly beneficial in terms of TER and IgE, but not for PEF, and the methodological quality of included studies was poor. Therefore, the results should be interpreted with caution. More randomized controlled trials with rigorous experimental methodologies are required for objectivity in the future.

Oxidative Dehydrogenation of Hydrazobenzenes toward Azo Compounds Catalyzed by tert-Butyl Nitrite in EtOH.

We describe a tert-butyl nitrite-catalyzed oxidative dehydrogenation of hydrazobenzenes for producing azobenzenes. This method proceeds at ambient temperature and under an atmospheric environment by employing eco-friendly EtOH as the medium, representing a mild, general route to the synthesis of various symmetrical and nonsymmetrical azobenzenes in excellent yields with broad functional group tolerance.

Facile Fabrication of Superhydrophobic Copper- Foam and Electrospinning Polystyrene Fiber for Combinational Oil⁻Water Separation.

Membrane-based metal substrates with special surface wettability have been applied widely for oil/water separation. In this work, a series of copper foams with superhydrophobicity and superoleophilicity were chemically etched using 10 mg mL-1 FeCl3/HCl solution with consequent ultrasonication, followed by the subsequent modification of four sulfhydryl compounds. A water contact angle of 158° and a sliding angle lower than 5° were achieved for the copper foam modified using 10 mM n-octadecanethiol solution in ethanol. In addition, the interaction mechanism was initially investigated, indicating the coordination between copper atoms with vacant orbital and sulfur atoms with lone pair electrons. In addition, the polymeric fibers were electrospun through the dissolution of polystyrene in a good solvent of chlorobenzene, and a nonsolvent of dimethyl sulfoxide. Oil absorption and collection over the water surface were carried out by the miniature boat made out of copper foam, a string bag of as-spun PS fibers with high oil absorption capacity, or the porous boat embedded with the as-spun fibers, respectively. The findings might provide a simple and practical combinational method for the solution of oil spill.

Neuropharmacological profile of novel and selective 5-HT6 receptor agonists: WAY-181187 and WAY-208466.

One of the most recently identified serotonin (5-hydroxytryptamine (5-HT)) receptor subtypes is the 5-HT6 receptor. Although in-depth localization studies reveal an exclusive distribution of 5-HT6 mRNA in the central nervous system, the precise biological role of this receptor still remains unknown. In the present series of experiments, we report the pharmacological and neurochemical characterization of two novel and selective 5-HT6 receptor agonists. WAY-181187 and WAY-208466 possess high affinity binding (2.2 and 4.8 nM, respectively) at the human 5-HT6 receptor and profile as full receptor agonists (WAY-181187: EC50=6.6 nM, Emax=93%; WAY-208466: EC50=7.3 nM; Emax=100%). In the rat frontal cortex, acute administration of WAY-181187 (3-30 mg/kg, subcutaneous (s.c.)) significantly increased extracellular GABA concentrations without altering the levels of glutamate or norepinephrine. Additionally, WAY-181187 (30 mg/kg, s.c.) produced modest yet significant decreases in cortical dopamine and 5-HT levels. Subsequent studies showed that the neurochemical effects of WAY-181187 in the frontal cortex could be blocked by pretreatment with the 5-HT6 antagonist, SB-271046 (10 mg/kg, s.c.), implicating 5-HT6 receptor mechanisms in mediating these responses. Moreover, the effects of WAY-181187 on catecholamines were attenuated by an intracortical infusion of the GABA A receptor antagonist, bicuculline (10 microM), confirming a local relationship between 5-HT6 receptors and GABAergic systems in the frontal cortex. In the dorsal hippocampus, striatum, and amygdala, WAY-181187 (10-30 mg/kg, s.c.) elicited robust elevations in extracellular levels of GABA without producing similar effects on concentrations of norepinephrine, serotonin, dopamine, or glutamate. In contrast to these brain regions, WAY-181187 had no effect on the extracellular levels of GABA in the nucleus accumbens or thalamus. Additional studies showed that WAY-208466 (10 mg/kg, s.c.) preferentially elevated cortical GABA levels following both acute and chronic (14 day) administration, indicating that neurochemical tolerance does not develop following repeated 5-HT6 receptor stimulation. In hippocampal slice preparations (in vitro), 5-HT(6) receptor agonism attenuated stimulated glutamate levels elicited by sodium azide and high KCl treatment. Furthermore, in the rat schedule-induced polydipsia model of obsessive compulsive disorder (OCD), acute administration of WAY-181187 (56-178 mg/kg, po) decreased adjunctive drinking behavior in a dose-dependent manner. In summary, WAY-181187 and WAY-208466 are novel, selective, and potent 5-HT6 receptor agonists displaying a unique neurochemical signature in vivo. Moreover, these data highlight a previously undescribed role for 5-HT6 receptors to modulate basal GABA and stimulated glutamate transmission, as well as reveal a potential therapeutic role for this receptor in the treatment of some types of anxiety-related disorders (eg OCD).

Novel pharmacological activity of loperamide and CP-339,818 on human HCN channels characterized with an automated electrophysiology assay.

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels underlie the pacemaker currents in neurons (I(h)) and cardiac (I(f)) cells. As such, the identification and characterization of novel blockers of HCN channels is important to enable the dissection of their function in vivo. Using a new IonWorks HT electrophysiology assay with human HCN1 and HCN4 expressed stably in cell lines, four HCN channel blockers are characterized. Two blockers known for their activity at opioid/Ca(2+) channels and K(+) channels, loperamide and CP-339,818 (respectively), are described to block HCN1 more potently than HCN4. The known HCN blocker ZD7288 was also found to be more selective for HCN1 over HCN4, while the HCN blocker DK-AH269 was equipotent on HCN4 and HCN1. Partial replacement of the intracellular Cl(-) with gluconate reduced the potency on both channels, but to varying degrees. For both HCN1 and HCN4, ZD7288 was most sensitive in lower Cl(-) solutions, while the potency of loperamide was not affected by the differing solutions. The block of HCN1 for all compounds was voltage-dependent, being relieved at more negative potentials. The voltage-dependent, Cl(-) dependent, HCN1 preferring compounds described here elaborate on the current known pharmacology of HCN channels and may help provide novel tools and chemical starting points for the investigation of HCN channel function in natively expressing systems.

[In-site total N content prediction of soil with Vis/NIR spectroscopy].

The Vis/NIR spectroscopy as an efficient tool to predict within-filed soil properties is significantly valuable when establishing agricultural field trials and in precision farming. The object of the study was to investigate the feasibility and possibility of using transformed in-site spectra by relative transformation method (RTM) to prediction soil properties. One hundred and three samples of paddy and fluvo-aquic soil in central china were collected. The in-site moisture (R(w)) and dried (R(d)) Vis/NIR spectra were measured by ASD field handHeld analyzer. The spectral characteristics of two kind soils were analyzed comparatively. The Rw spectra were transformed by RTM into R(n), which were of similar information content and charatistics with R(d). The first derivatives of three spectra revealed that the method could reduce the water disturb on and noise in R(w) Vis/NIR spectrum. The PLS regession model was applied to predict total nitrogen (TN) respectively using R(w), R(d) and R(n) as predictor. The models with Rw predicted TN respectively of paddy, fluvo-aquic and all samples with poor adjusted r2 (< 0.5), while R(d) with good adjusted r2 0.70, 0.88 and 0.71 and R(n) 0.53, 0.62 and 0.64. The result showed that the RTM was efficient to enhance analysis and prediction of soil properties using Vis/NIR spectrum measured on the spot. The combination of PLS and RTM could help implemention of real-time analyzing soil properties using Vis/NIR spectrum.

Subcritical water extraction of low methoxyl pectin from pomelo (Citrus grandis (L.) Osbeck) peels.

Low methoxyl (LM) pectin was extracted from pomelo peels using subcritical water in a dynamic mode. The effects of pressure and temperature were analyzed through a face-centred central composite design. Extraction yield and the rate of extraction were found to be predominantly influenced by temperature. Optimization of the subcritical water extraction (SWE) yielded an optimized operating condition of 120°C and 30bar with a predicted pectin yield of 18.8%. The corresponding experimental yield was 19.6%, which is in close agreement with the predicted data. The pectin obtained from the optimized condition was further analyzed for its physicochemical properties. The kinetics of the SWE was also evaluated whereby the one-site kinetic desorption model was found to be in good agreement with experimental data (R2>0.94).

Purine Nucleotide Availability Regulates mTORC1 Activity through the Rheb GTPase.

Pharmacologic agents that interfere with nucleotide metabolism constitute an important class of anticancer agents. Recent studies have demonstrated that mTOR complex 1 (mTORC1) inhibitors suppress de novo biosynthesis of pyrimidine and purine nucleotides. Here, we demonstrate that mTORC1 itself is suppressed by drugs that reduce intracellular purine nucleotide pools. Cellular treatment with AG2037, an inhibitor of the purine biosynthetic enzyme GARFT, profoundly inhibits mTORC1 activity via a reduction in the level of GTP-bound Rheb, an obligate upstream activator of mTORC1, because of a reduction in intracellular guanine nucleotides. AG2037 treatment provokes both mTORC1 inhibition and robust tumor growth suppression in mice bearing non-small-cell lung cancer (NSCLC) xenografts. These results indicate that alterations in purine nucleotide availability affect mTORC1 activity and suggest that inhibition of mTORC1 contributes to the therapeutic effects of purine biosynthesis inhibitors.

Characterization of Gpr101 expression and G-protein coupling selectivity.

This report describes the identification and characterization of the murine orphan GPCR, Gpr101. Both human and murine genes were localized to chromosome X. Similar to its human ortholog, murine Gpr101 mRNA was detected predominantly in the brain within discrete nuclei. A knowledge-restricted hidden Markov model-based algorithm, capable of accurately predicting G-protein coupling selectivity, indicated that both human and murine GPR101 were likely coupled to Gs. This prediction was supported by the elevation of cyclic AMP levels and the activation of a cyclic AMP response element-luciferase reporter gene in HEK293 cells over-expressing human GPR101. Consistent with this, over-expression of human GPR101 in a yeast-based system yielded an elevated, agonist-independent reporter gene response in the presence of a yeast chimeric Galphas protein. These results indicate that GPR101 participates in a potentially wide range of activities in the CNS via modulation of cAMP levels.

[Chemical constituents of Knoxia valerianoides].

AIM: To study the chemical constituents of Knoxia valerianoides Thorel et Pitard. METHODS: Chromatographic methods were used for the isolation and purification. Structures were elucidated on the basis of chemical analysis and spectroscopic data. RESULTS: Three anthraguinones were isolated from K. valerianoides and identified as 1, 3, 5-trihydroxy-2-methyl-6-methoxyl-anthraguinone (kaoxiadin, I), 1, 3, 6-trihydroxy-5-ethoxylmethyl-anthraguinone (II) and 1, 3-dihydroxy-2-methylanthraguinone (rubiadin, III). CONCLUSION: Compound II is a new anthraguinone constituent.

Sequential ultrasound-microwave assisted acid extraction (UMAE) of pectin from pomelo peels.

This study aims to optimize sequential ultrasound-microwave assisted extraction (UMAE) on pomelo peel using citric acid. The effects of pH, sonication time, microwave power and irradiation time on the yield and the degree of esterification (DE) of pectin were investigated. Under optimized conditions of pH 1.80, 27.52min sonication followed by 6.40min microwave irradiation at 643.44W, the yield and the DE value of pectin obtained was respectively at 38.00% and 56.88%. Based upon optimized UMAE condition, the pectin from microwave-ultrasound assisted extraction (MUAE), ultrasound assisted extraction (UAE) and microwave assisted extraction (MAE) were studied. The yield of pectin adopting the UMAE was higher than all other techniques in the order of UMAE>MUAE>MAE>UAE. The pectin's galacturonic acid content obtained from combined extraction technique is higher than that obtained from sole extraction technique and the pectin gel produced from various techniques exhibited a pseudoplastic behaviour. The morphological structures of pectin extracted from MUAE and MAE closely resemble each other. The extracted pectin from UMAE with smaller and more regular surface differs greatly from that of UAE. This has substantiated the highest pectin yield of 36.33% from UMAE and further signified their compatibility and potentiality in pectin extraction.

[The chemical constituents of Knoxia valerianoides].

AIM: To study chemical constituents of Knoxia valerianoides Thorel et Pitard. METHODS: Chromatographic methods were used for the isolation and purification. Structures was elucidated on the basis of chemical analysis and spectroscopic data. RESULTS: Two anthraquinone were isolated from Knoxia valerianoides Thorel et Pitard and identified as 1,3,5-trihydroxy-2-ethoxymethyl-6-methoxyl-anthraquinone (I) and 1,3-dihydroxy-2-ethoxymethyl-anthraquinone (II). CONCLUSION: The compound I was found to be a novel anthraquinone constituent and II was isolated from Knoxia valerianoides Thorel et Pitard for the first time.

Validation of an atomic absorption rubidium ion efflux assay for KCNQ/M-channels using the ion Channel Reader 8000.

M-channels (M-current), encoded by KCNQ2/3 K(+) channel genes, have emerged as novel drug targets for a number of neurological disorders. The lack of direct high throughput assays combined with the low throughput of conventional electrophysiology (EP) has impeded rapid screening and evaluation of K(+)-channel modulators. Development of a sensitive and efficient assay for the direct measurement of M-current activity is critical for identifying novel M-channel modulators and subsequent investigation of their therapeutic potential. Using a stable CHO cell line expressing rat KCNQ2/3 K(+) channels confirmed by EP, we have developed and validated a nonradioactive rubidium (Rb(+)) efflux assay in a 96-well plate format. The Rb(+) efflux assay directly measures the activity of functional channels by atomic absorption spectroscopy using the automated Ion Channel Reader (ICR) 8000. The stimulated Rb(+) efflux from KCNQ2/3-expressing cells was blocked by the channel blockers XE991 and linopirdine with IC(50) values of 0.15 microM and 1.3 microM, respectively. Twelve compounds identified as KCNQ2/3 openers were further assessed in this assay, and their EC(50) values were compared with those obtained with EP. A higher positive correlation coefficient between these two assays (r = 0.60) was observed than that between FlexStation membrane potential and EP assays (r = 0.23). To simplify the assay and increase the throughput, we demonstrate that EC(50) values obtained by measuring Rb(+) levels in the supernatant are as robust and consistent as those obtained from the ratio of Rb(+) in supernatant/lysate. By measuring the supernatant only, the throughput of ICR8000 in an eight-point titration is estimated to be 40 compounds per day, which is suitable for a secondary confirmation assay.

[A novel phlegmariurine type alkaloid from Huperzia serrata (Thunb.) Trev].

AIM: To study the alkaloid constituents of Huperzia serrata (Thunb.) Trev.. METHODS: Chromatographic methods were used for the isolation and purification. Structure was elucidated on the basis of chemical analysis and spectroscopic data. RESULTS: An alkaloid constituent was isolated from H. serrata (Thumb.) Trev.. CONCLUSION: The compound was found to be a novel phlegmariurine type alkaloid, named 8 beta-hydroxy phlegmariurine B.

[Structural identification of huperzinine C].

AIM: To study the alkaloid constituents of Huperzia serrata (Thunb.) Trev.. METHODS: Chromatographic methods were used for the isolation and purification. Structure was elucidated on the basis of chemical analysis and spectroscopic data. RESULTS: An alkaloid constituent was isolated from H. serrata (Thunb.) Trev.. CONCLUSION: The compound was found to be a novel lycodine type alkaloid with tricyclic structure named huperzinine C.