Faecal microbial transfer and complex carbohydrates mediate protection against COPD.

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is a major cause of global illness and death, most commonly caused by cigarette smoke. The mechanisms of pathogenesis remain poorly understood, limiting the development of effective therapies. The gastrointestinal microbiome has been implicated in chronic lung diseases via the gut-lung axis, but its role is unclear. DESIGN: Using an in vivo mouse model of cigarette smoke (CS)-induced COPD and faecal microbial transfer (FMT), we characterised the faecal microbiota using metagenomics, proteomics and metabolomics. Findings were correlated with airway and systemic inflammation, lung and gut histopathology and lung function. Complex carbohydrates were assessed in mice using a high resistant starch diet, and in 16 patients with COPD using a randomised, double-blind, placebo-controlled pilot study of inulin supplementation. RESULTS: FMT alleviated hallmark features of COPD (inflammation, alveolar destruction, impaired lung function), gastrointestinal pathology and systemic immune changes. Protective effects were additive to smoking cessation, and transfer of CS-associated microbiota after antibiotic-induced microbiome depletion was sufficient to increase lung inflammation while suppressing colonic immunity in the absence of CS exposure. Disease features correlated with the relative abundance of Muribaculaceae, Desulfovibrionaceae and Lachnospiraceae family members. Proteomics and metabolomics identified downregulation of glucose and starch metabolism in CS-associated microbiota, and supplementation of mice or human patients with complex carbohydrates improved disease outcomes. CONCLUSION: The gut microbiome contributes to COPD pathogenesis and can be targeted therapeutically.

Structure-Controllable and Mass-Produced Glycopolymersomes as a Template of the Carbohydrate@Ag Nanobiohybrid with Inherent Antibacteria and Biofilm Eradication.

Glycopolymer-supported silver nanoparticles (AgNPs) have demonstrated a promising alternative to antibiotics for the treatment of multidrug-resistant bacteria-infected diseases. In this contribution, we report a class of biohybrid glycopolymersome-supported AgNPs, which are capable of effectively killing multidrug-resistant bacteria and disrupting related biofilms. First of all, glycopolymersomes with controllable structures were massively fabricated through reversible addition-fragmentation chain transfer (RAFT) polymerization-induced self-assembly (PISA) in an aqueous solution driven by complementary hydrogen bonding interaction between the pyridine and amide groups of N-(2-methylpyridine)-acrylamide (MPA) monomers. Subsequently, Ag+ captured by glycopolymersomes through the coordination between pyridine-N and Ag+ was reduced into AgNPs stabilized by glycopolymersomes upon addition of the NaBH4 reducing agent, leading to the formation of the glycopolymersome@AgNPs biohybrid. As a result, they showed a wide-spectrum and enhanced removal of multidrug-resistant bacteria and biofilms compared to naked AgNPs due to the easier adhesion onto the bacterial surface and diffusion into biofilms through the specific protein-carbohydrate recognition. Moreover, the in vivo results revealed that the obtained biohybrid glycopolymersomes not only demonstrated an effective treatment for inhibiting the cariogenic bacteria but also were able to repair the demineralization of caries via accumulating Ca2+ through the recognition between carbohydrates and Ca2+. Furthermore, glycopolymersomes@AgNPs showed quite low in vitro hemolysis and cytotoxicity and almost negligible acute toxicity in vivo. Overall, this type of biohybrid glycopolymersome@AgNPs nanomaterial provides a new avenue for enhanced antibacterial and antibiofilm activities and the effective treatment of oral microbial-infected diseases.

Central effects of mouth rinses on endurance and strength performance.

Rinsing the mouth with a carbohydrate (CHO) solution has been shown to enhance exercise performance while reducing neuromuscular fatigue. This effect is thought to be mediated through the stimulation of oral receptors, which activate brain areas associated with reward, motivation, and motor control. Consequently, corticomotor responsiveness is increased, leading to sustained levels of neuromuscular activity prior to fatigue. In the context of endurance performance, the evidence regarding the central involvement of mouth rinse (MR) in performance improvement is not conclusive. Peripheral mechanisms should not be disregarded, particularly considering factors such as low exercise volume, the participant's fasting state, and the frequency of rinsing. These factors may influence central activations. On the other hand, for strength-related activities, changes in motor evoked potential (MEP) and electromyography (EMG) have been observed, indicating increased corticospinal responsiveness and neuromuscular drive during isometric and isokinetic contractions in both fresh and fatigued muscles. However, it is important to note that in many studies, MEP data were not normalised, making it difficult to exclude peripheral contributions. Voluntary activation (VA), another central measure, often exhibits a lack of changes, mainly due to its high variability, particularly in fatigued muscles. Based on the evidence, MR can attenuate neuromuscular fatigue and improve endurance and strength performance via similar underlying mechanisms. However, the evidence supporting central contribution is weak due to the lack of neurophysiological measures, inaccurate data treatment (normalisation), limited generalisation between exercise modes, methodological biases (ignoring peripheral contribution), and high measurement variability.Trial registration: PROSPERO ID: CRD42021261714.

Effect of ultra-violet light radiation on Scenedesmus vacuolatus growth kinetics, metabolic performance, and preliminary biodegradation study.

This study presents the effect of ultra-violet (UV) light radiation on the process kinetics, metabolic performance, and biodegradation capability of Scenedesmus vacuolatus. The impact of the UV radiation on S. vacuolatus morphology, chlorophyll, carotenoid, carbohydrates, proteins, lipid accumulation, growth rate, substrate affinity and substrate versatility were evaluated. Thereafter, a preliminary biodegradative potential of UV-exposed S. vacuolatus on spent coolant waste (SCW) was carried out based on dehydrogenase activity (DHA) and total petroleum hydrocarbon degradation (TPH). Pronounced structural changes were observed in S. vacuolatus exposed to UV radiation for 24 h compared to the 2, 4, 6, 12 and 48 h UV exposure. Exposure of S. vacuolatus to UV radiation improved cellular chlorophyll (chla = 1.89-fold, chlb = 2.02-fold), carotenoid (1.24-fold), carbohydrates (4.62-fold), proteins (1.44-fold) and lipid accumulations (1.40-fold). In addition, the 24 h UV exposed S. vacuolatus showed a significant increase in substrate affinity (1/Ks) (0.959), specific growth rate (µ) (0.024 h-1) and biomass accumulation (0.513 g/L) by 1.50, 2 and 1.9-fold respectively. Moreover, enhanced DHA (55%) and TPH (100%) degradation efficiency were observed in UV-exposed S. vacuolatus. These findings provided major insights into the use of UV radiation to enhance S. vacuolatus biodegradative performance towards sustainable green environment negating the use of expensive chemicals and other unfriendly environmental practices.

Isolated and combined effects of cobalt and nickel on the microalga Raphidocelis subcapitata.

Aquatic organisms are exposed to several compounds that occur in mixtures in the environment. Thus, it is important to investigate their impacts on organisms because these combined effects can be potentiated. Cobalt (Co) and nickel (Ni) are metals that occur in the environment and are used in human activities. To the best of our knowledge, there are no studies that investigated the combined effects of these metals on a freshwater Chlorophyceae. Therefore, this study analyzed the isolated and combined effects of Co and Ni in cell density, physiological and morphological parameters, reactive oxygen species (ROS), carbohydrates and photosynthetic parameters of the microalga Raphidocelis subcapitata. Data showed that Co affected the cell density from 0.25 mg Co L-1; the fluorescence of chlorophyll a (Chl a) (0.10 mg Co L-1); ROS production (0.50 mg Co L-1), total carbohydrates and efficiency of the oxygen evolving complex (OEC) at all tested concentrations; and the maximum quantum yield (ΦM) from 0.50 mg Co L-1. Ni exposure decreased ROS and cell density (0.35 mg Ni L-1); altered Chl a fluorescence and carbohydrates at all tested concentrations; and did not alter photosynthetic parameters. Regarding the Co-Ni mixtures, our data best fitted the concentration addition (CA) model and dose-ratio dependent (DR) deviation in which synergism was observed at low doses of Co and high doses of Ni and antagonism occurred at high doses of Co and low doses of Ni. The combined metals affected ROS production, carbohydrates, ΦM, OEC and morphological and physiological parameters.

A novel thiol-saccharide mucolytic for the treatment of muco-obstructive lung diseases.

BACKGROUND: Mucin disulfide cross-links mediate pathologic mucus formation in muco-obstructive lung diseases. MUC-031, a novel thiol-modified carbohydrate compound, cleaves disulfides to cause mucolysis. The aim of this study was to determine the mucolytic and therapeutic effects of MUC-031 in sputum from patients with cystic fibrosis (CF) and mice with muco-obstructive lung disease (ßENaC-Tg mice). METHODS: We compared the mucolytic efficacy of MUC-031 and existing mucolytics (N-acetylcysteine (NAC) and recombinant human deoxyribonuclease I (rhDNase)) using rheology to measure the elastic modulus (G') of CF sputum, and we tested effects of MUC-031 on airway mucus plugging, inflammation and survival in ßENaC-Tg mice to determine its mucolytic efficacy in vivo. RESULTS: In CF sputum, compared to the effects of rhDNase and NAC, MUC-031 caused a larger decrease in sputum G', was faster in decreasing sputum G' by 50% and caused mucolysis of a larger proportion of sputum samples within 15 min of drug addition. Compared to vehicle control, three treatments with MUC-031 in 1 day in adult ßENaC-Tg mice decreased airway mucus content (16.8±3.2 versus 7.5±1.2 nL·mm-2, p<0.01) and bronchoalveolar lavage cells (73 833±6930 versus 47 679±7736 cells·mL-1, p<0.05). Twice-daily treatment with MUC-031 for 2 weeks also caused decreases in these outcomes in adult and neonatal ßENaC-Tg mice and reduced mortality from 37% in vehicle-treated ßENaC-Tg neonates to 21% in those treated with MUC-031 (p<0.05). CONCLUSION: MUC-031 is a potent and fast-acting mucolytic that decreases airway mucus plugging, lessens airway inflammation and improves survival in ßENaC-Tg mice. These data provide rationale for human trials of MUC-031 in muco-obstructive lung diseases.

Apoplastic sugar may be lost from grape berries and retrieved in pedicels.

In ripening grape (Vitis sp.) berries, the combination of rapid sugar import, apoplastic phloem unloading, and water discharge via the xylem creates a potential risk for apoplastic sugar to be lost from the berries. We investigated the likelihood of such sugar loss and a possible sugar retrieval mechanism in the pedicels of different Vitis genotypes. Infusion of D-glucose-1-13C or L-glucose-1-13C to the stylar end of attached berries demonstrated that both sugars can be leached from the berries, but only the nontransport sugar L-glucose moved beyond the pedicels. No 13C enrichment was found in peduncles and leaves. Genes encoding 10 sugar transporters were expressed in the pedicels throughout grape ripening. Using an immunofluorescence technique, we localized the sucrose transporter SUC27 to pedicel xylem parenchyma cells. These results indicate that pedicels possess the molecular machinery for sugar retrieval from the apoplast. Plasmodesmata were observed between vascular parenchyma cells in pedicels, and movement of the symplastically mobile dye carboxyfluorescein demonstrated that the symplastic connection is physiologically functional. Taken together, the chemical, molecular, and anatomical evidence gathered here supports the idea that some apoplastic sugar can be leached from grape berries and is effectively retrieved in a two-step process in the pedicels. First, sugar transporters may actively retrieve leached sugar from the xylem. Second, retrieved sugar may move symplastically to the pedicel parenchyma for local use or storage, or to the phloem for recycling back to the berry.

Effect of 1-year daily protein supplementation and physical exercise on muscle protein synthesis rate and muscle metabolome in healthy older Danes: a randomized controlled trial.

BACKGROUND: The skeletal muscle mass decreases with age and the responsiveness of aging muscles' protein synthesis rate (MPS) to protein intake seems to deteriorate. OBJECTIVE: This study investigated the impact of 12 months of protein supplementation with or without physical exercise training on the basal and postprandial MPS and the skeletal muscle metabolome of healthy older Danes (> 65 years, 29 females/37 males). METHODS: Subjects were randomized to follow one of five intervention groups: (1) carbohydrate, (2) collagen protein, (3) whey protein, (4) home-based light resistance training with whey protein, and (5) center-based heavy-load resistance training with whey protein. Before and after the intervention, a tracer infusion trial was conducted to measure basal and postprandial MPS in response to intake of a cocktail consisting of 20 g whey hydrolysate + 10 g glucose. In addition, the skeletal muscle metabolome was measured using gas chromatography-mass spectrometry (GC-MS) at basal state and 4 h after the intake of the cocktail. RESULTS: One year of daily protein or carbohydrate supplementation did not alter the basal and protein-stimulated postprandial muscle protein synthesis rate or the muscle metabolome of healthy older Danes. Basal MPS (%/h) at baseline for all subjects were 0.0034 ± 0,011 (mean ± SD). In contrast to previous studies, no difference was observed in basal MPS between males and females (p = 0.75). With the developed untargeted GC-MS methodology, it was possible to detect and tentatively annotate > 70 metabolites from the human skeletal muscle samples. CONCLUSION: One year of protein supplementation in comparison to an isocaloric-control supplement seems to affect neither the MPS at basal or postprandial state nor the skeletal muscle metabolome. CLINICAL TRIAL REGISTRY: Number: NCT02115698, clinicaltrials.gov/ct2/show/NCT02115698.

Macronutrients effects on satiety and food intake in older and younger adults: A randomised controlled trial.

Older adults are advised to increase their protein intake to maintain their muscle mass. However, protein is considered the most satiating macronutrient and this recommendation may cause a decrease in total energy intake. To date, satiety studies comparing all three macronutrients have been undertaken in young adults, and it is unclear if the same response is seen in older adults. The objective of this study was to compare the effect of preloads high in protein, fat, and carbohydrate but equal in energy (∼300 kcal) and volume (250 ml) on energy intake, perceived appetite, and gastric emptying in younger and older adults. Twenty older and 20 younger adults completed a single-blinded randomised crossover trial involving three study visits. Participants consumed a standard breakfast, followed by a preload milkshake high in either carbohydrate, fat, or protein. Three hours after the preload, participants were offered an ad libitum meal to assess food intake. Visual analogue scales were used to measure perceived appetite and gastric emptying was measured via the 13C-octanoic acid breath test. There was no significant effect of preload type or age on energy intake either at the ad libitum meal, self-recorded food intake for the rest of the test day or subjective appetite ratings. There was a significant effect of preload type on gastric emptying latency phase and ascension time, and an effect of age on gastric emptying latency and lag phase such that older adults had faster emptying. In conclusion, energy intake, and perceived appetite were not affected by macronutrient content of the preloads in both younger and older adults, but gastric emptying times differed.

First Synthesis of DBU-Conjugated Cationic Carbohydrate Derivatives and Investigation of Their Antibacterial and Antifungal Activity.

The emergence of drug-resistant bacteria and fungi represents a serious health problem worldwide. It has long been known that cationic compounds can inhibit the growth of bacteria and fungi by disrupting the cell membrane. The advantage of using such cationic compounds is that the microorganisms would not become resistant to cationic agents, since this type of adaptation would mean significantly altering the structure of their cell walls. We designed novel, DBU (1,8-diazabicyclo[5.4.0]undec-7-ene)-derived amidinium salts of carbohydrates, which may be suitable for disturbing the cell walls of bacteria and fungi due to their quaternary ammonium moiety. A series of saccharide-DBU conjugates were prepared from 6-iodo derivatives of d-glucose, d-mannose, d-altrose and d-allose by nucleophilic substitution reactions. We optimized the synthesis of a d-glucose derivative, and studied the protecting group free synthesis of the glucose-DBU conjugates. The effect of the obtained quaternary amidinium salts against Escherichia coli and Staphylococcus aureus bacterial strains and Candida albicans yeast was investigated, and the impact of the used protecting groups and the sugar configuration on the antimicrobial activity was analyzed. Some of the novel sugar quaternary ammonium compounds with lipophilic aromatic groups (benzyl and 2-napthylmethyl) showed particularly good antifungal and antibacterial activity.

Galectin-9 in Gastroenterological Cancer.

Immunochemotherapy has become popular in recent years. The detailed mechanisms of cancer immunity are being elucidated, and new developments are expected in the future. Apoptosis allows tissues to maintain their form, quantity, and function by eliminating excess or abnormal cells. When apoptosis is inhibited, the balance between cell division and death is disrupted and tissue homeostasis is impaired. This leads to dysfunction and the accumulation of genetically abnormal cells, which can contribute to carcinogenesis. Lectins are neither enzymes nor antibodies but proteins that bind sugar chains. Among soluble endogenous lectins, galectins interact with cell surface sugar chains outside the cell to regulate signal transduction and cell growth. On the other hand, intracellular lectins are present at the plasma membrane and regulate signal transduction by regulating receptor-ligand interactions. Galectin-9 expressed on the surface of thymocytes induces apoptosis of T lymphocytes and plays an essential role in immune self-tolerance by negative selection in the thymus. Furthermore, the administration of extracellular galectin-9 induces apoptosis of human cancer and immunodeficient cells. However, the detailed pharmacokinetics of galectin-9 in vivo have not been elucidated. In addition, the cell surface receptors involved in galectin-9-induced apoptosis of cancer cells have not been identified, and the intracellular pathways involved in apoptosis have not been fully investigated. We have previously reported that galectin-9 induces apoptosis in various gastrointestinal cancers and suppresses tumor growth. However, the mechanism of galectin-9 and apoptosis induction in gastrointestinal cancers and the detailed mechanisms involved in tumor growth inhibition remain unknown. In this article, we review the effects of galectin-9 on gastrointestinal cancers and its mechanisms.

A Comparison of the Antibacterial Efficacy of Carbohydrate Lipid-like (Thio)Ether, Sulfone, and Ester Derivatives against Paenibacillus larvae.

Paenibacillus larvae is the causative agent of American foulbrood (AFB), the most serious bacterial disease affecting developing honeybee larvae and pupas. In this study, a library of 24 (thio)glycosides, glycosyl sulfones, 6-O-esters, and ethers derived from d-mannose, d-glucose, and d-galactose having C10 or C12 alkyl chain were evaluated for their antibacterial efficacy against two P. larvae strains. The efficacy of the tested compounds determined as minimal inhibitory concentrations (MICs) varied greatly. Generally, dodecyl derivatives were found to be more potent than their decylated analogs. Thioglycosides were more efficient than glycosides and sulfones. The activity of the 6-O-ether derivatives was higher than that of their ester counterparts. Seven derivatives with dodecyl chain linked (thio)glycosidically or etherically at C-6 showed high efficacy against both P. larvae strains (MICs ranged from 12.5 µM to 50 µM). Their efficacies were similar or much higher than those of selected reference compounds known to be active against P. larvae-lauric acid, monolaurin, and honeybee larval food components, 10-hydroxy-2-decenoic acid, and sebacic acid (MICs ranged from 25 µM to 6400 µM). The high efficacies of these seven derivatives suggest that they could increase the anti-P. larvae activity of larval food and improve the resistance of larvae to AFB disease through their application to honeybee colonies.

Carbohydrate-Small Molecule Hybrids as Lead Compounds Targeting IL-6 Signaling.

In the past 25 years, a number of efforts have been made toward the development of small molecule interleukin-6 (IL-6) signaling inhibitors, but none have been approved to date. Monosaccharides are a diverse class of bioactive compounds, but thus far have been unexplored as a scaffold for small molecule IL-6-signaling inhibitor design. Therefore, in this present communication, we combined a structure-based drug design approach with carbohydrate building blocks to design and synthesize novel IL-6-signaling inhibitors targeting glycoprotein 130 (gp130). Of this series of compounds, LS-TG-2P and LS-TF-3P were the top lead compounds, displaying IC50 values of 6.9 and 16 µM against SUM159 cell lines, respectively, while still retaining preferential activity against the IL-6-signaling pathway. The carbohydrate moiety was found to improve activity, as N-unsubstituted triazole analogues of these compounds were found to be less active in vitro compared to the leads themselves. Thus, LS-TG-2P and LS-TF-3P are promising scaffolds for further development and study as IL-6-signaling inhibitors.

Exercise training attenuates pulmonary inflammation and mitochondrial dysfunction in a mouse model of high-fat high-carbohydrate-induced NAFLD.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) can lead to pulmonary dysfunction that is associated with pulmonary inflammation. Moreover, little is known regarding the therapeutic role of exercise training on pulmonary pathophysiology in NAFLD. The present study aimed to investigate the effect of exercise training on high-fat high-carbohydrate (HFHC)-induced pulmonary dysfunction in C57BL/6 mice. METHODS: Male C57BL/6 mice (N = 40) were fed a standard Chow (n = 20) or an HFHC (n = 20) diet for 15 weeks. After 8 weeks of dietary treatment, they were further assigned to 4 subgroups for the remaining 7 weeks: Chow (n = 10), Chow plus exercise (Chow+EX, n = 10), HFHC (n = 10), or HFHC plus exercise (HFHC+EX, n = 10). Both Chow+EX and HFHC+EX mice were subjected to treadmill running. RESULTS: Chronic exposure to the HFHC diet resulted in obesity with hepatic steatosis, impaired glucose tolerance, and elevated liver enzymes. The HFHC significantly increased fibrotic area (p < 0.001), increased the mRNA expression of TNF-α (4.1-fold, p < 0.001), IL-1ß (5.0-fold, p < 0.001), col1a1 (8.1-fold, p < 0.001), and Timp1 (6.0-fold, p < 0.001) in the lung tissue. In addition, the HFHC significantly altered mitochondrial function (p < 0.05) along with decreased Mfn1 protein levels (1.8-fold, p < 0.01) and increased Fis1 protein levels (1.9-fold, p < 0.001). However, aerobic exercise training significantly attenuated these pathophysiologies in the lungs in terms of ameliorating inflammatory and fibrogenic effects by enhancing mitochondrial function in lung tissue (p < 0.001). CONCLUSIONS: The current findings suggest that exercise training has a beneficial effect against pulmonary abnormalities in HFHC-induced NAFLD through improved mitochondrial function.

Targeting the Central Pocket of the Pseudomonas aeruginosa Lectin LecA.

Pseudomonas aeruginosa is an opportunistic ESKAPE pathogen that produces two lectins, LecA and LecB, as part of its large arsenal of virulence factors. Both carbohydrate-binding proteins are central to the initial and later persistent infection processes, i. e. bacterial adhesion and biofilm formation. The biofilm matrix is a major resistance determinant and protects the bacteria against external threats such as the host immune system or antibiotic treatment. Therefore, the development of drugs against the P. aeruginosa biofilm is of particular interest to restore efficacy of antimicrobials. Carbohydrate-based inhibitors for LecA and LecB were previously shown to efficiently reduce biofilm formations. Here, we report a new approach for inhibiting LecA with synthetic molecules bridging the established carbohydrate-binding site and a central cavity located between two LecA protomers of the lectin tetramer. Inspired by in silico design, we synthesized various galactosidic LecA inhibitors with aromatic moieties targeting this central pocket. These compounds reached low micromolar affinities, validated in different biophysical assays. Finally, X-ray diffraction analysis revealed the interactions of this compound class with LecA. This new mode of action paves the way to a novel route towards inhibition of P. aeruginosa biofilms.

A reactive oxygen species Ca2+ signalling pathway identified from a chemical screen for modifiers of sugar-activated circadian gene expression.

Sugars are essential metabolites for energy and anabolism that can also act as signals to regulate plant physiology and development. Experimental tools to disrupt major sugar signalling pathways are limited. We performed a chemical screen for modifiers of activation of circadian gene expression by sugars to discover pharmacological tools to investigate and manipulate plant sugar signalling. Using a library of commercially available bioactive compounds, we identified 75 confident hits that modified the response of a circadian luciferase reporter to sucrose in dark-adapted Arabidopsis thaliana seedlings. We validated the transcriptional effect on a subset of the hits and measured their effects on a range of sugar-dependent phenotypes for 13 of these chemicals. Chemicals were identified that appear to influence known and unknown sugar signalling pathways. Pentamidine isethionate was identified as a modifier of a sugar-activated Ca2+ signal that acts as a calmodulin inhibitor downstream of superoxide in a metabolic signalling pathway affecting circadian rhythms, primary metabolism and plant growth. Our data provide a resource of new experimental tools to manipulate plant sugar signalling and identify novel components of these pathways.

Mapping sex differences in the effects of protein and carbohydrates on lifespan and reproduction in Drosophila melanogaster: is measuring nutrient intake essential?

Understanding how diet affects reproduction and survival is a central aim in evolutionary biology. Although this relationship is likely to differ between the sexes, we lack data relating diet to male reproductive traits. One exception to this general pattern is Drosophila melanogaster, where male dietary intake was quantified using the CApillary FEeder (CAFE) method. However, CAFE feeding reduces D. melanogaster survival and reproduction, so may distort diet-fitness outcomes. Here, we use the Geometric Framework of Nutrition to create nutrient landscapes that map sex-specific relationships between protein, carbohydrate, lifespan and reproduction in D. melanogaster. Rather than creating landscapes with consumption data, we map traits onto the nutrient composition of forty agar-based diets, generating broad coverage of nutrient space. We find that male and female lifespan was maximised on low protein, high carbohydrate blends (~ 1P:15.9C). This nutrient ratio also maximised male reproductive rates, but females required more protein to maximise daily fecundity (1P:1.22C). These results are consistent with CAFE assay outcomes. However, the approach employed here improved female fitness relative to CAFE assays, while effects of agar versus CAFE feeding on male fitness traits depended on the nutrient composition of experimental diets. We suggest that informative nutrient landscapes can be made without measuring individual nutrient intake and that in many cases, this may be preferable to using the CAFE approach. The most appropriate method will depend on the question and species being studied, but the approach adopted here has the advantage of creating nutritional landscapes when dietary intake is hard to quantify.

Synthesis and application of phosphorylated saccharides in researching carbohydrate-based drugs.

Phosphorylated saccharides are valuable targets in glycochemistry and glycobiology, which play an important role in various physiological and pathological processes. The current research on phosphorylated saccharides primarily focuses on small molecule inhibitors, glycoconjugate vaccines and novel anti-tumour targeted drug carrier materials. It can maximise the pharmacological effects and reduce the toxicity risk caused by nonspecific off-target reactions of drug molecules. However, the number and types of natural phosphorylated saccharides are limited, and the complexity and heterogeneity of their structures after extraction and separation seriously restrict their applications in pharmaceutical development. The increasing demands for the research on these molecules have extensively promoted the development of carbohydrate synthesis. Numerous innovative synthetic methodologies have been reported regarding the continuous expansion of the potential building blocks, catalysts, and phosphorylation reagents. This review summarizes the latest methods for enzymatic and chemical synthesis of phosphorylated saccharides, emphasizing their breakthroughs in yield, reactivity, regioselectivity, and application scope. Additionally, the anti-bacterial, anti-tumour, immunoregulatory and other biological activities of some phosphorylated saccharides and their applications were also reviewed. Their structure-activity relationship and mechanism of action were discussed and the key phosphorylation characteristics, sites and extents responsible for observed biological activities were emphasised. This paper will provide a reference for the application of phosphorylated saccharide in the research of carbohydrate-based drugs in the future.

1H-imidazo[4,5-f][1,10]phenanthroline carbohydrate conjugates: Synthesis, DNA interactions and cytotoxic activity.

Here we present a novel family of carbohydrate conjugates based on the 2-aryl-imidazo[4,5-f][1,10]phenanthroline core modified with carbohydrates (carb-APIPs). The hybrid compounds were prepared by direct treatment of the unprotected carbohydrate with 2-(4-aminophenyl)-1H-imidazo[4,5-f][1,10]phenanthroline (APIP). The N-glycosylation reactions with the monosaccharides tested afforded stereoselectively the more stable N-ß-glycopyranosylamines that, in solution, underwent a dynamic equilibrium leading to anomeric mixtures with a small participation of the α isomer. DNA interaction experiments with telomeric G-quadruplex DNA included DNA FRET melting assays, circular dichroism, and equilibrium dialysis and revealed that the novel carb-APIPs bind the G-quadruplex structure with high affinity. Interestingly, the presence of the carbohydrate confers good selectivity towards the telomeric quadruplex structure, as suggested by competition DNA FRET melting assays. Besides the extended aromatic surface that allows π-stacking interactions, the carbohydrate part of the conjugate may contribute to groove binding recognition, as indicated by viscosity experiments. In addition, the novel carb-APIPs showed significant cytotoxic properties in PC3 and HeLa cells and, to a lesser extent, in MCF7 cells and normal human fibroblasts (HFF1).

Potential of selected plant extracts to control severe subacute ruminal acidosis in vitro as compared with monensin.

BACKGROUND: In recent years, researchers have become increasingly interested in developing natural feed additives that can stabilize ruminal pH and thus prevent or eliminate the risk of severe subacute rumen acidosis. Herein, 3 experiments were conducted using a semi-automated in vitro gas production technique. In the experiment (Exp.) 1, the efficacy of 9 plant extracts (1.5 mg/ml), compared to monensin (MON; 12 µg/ml), to counteract ruminal acidosis stimulated by adding glucose (0.1 g/ml) as a fermentable carbohydrate without buffer was assessed for 6 h. In Exp. 2, cinnamon extract (CIN) and MON were evaluated to combat glucose-induced acidosis with buffer use for 24 h. In Exp. 3, the effect of CIN and MON on preventing acidosis when corn or barley grains were used as substrate was examined. RESULTS: In Exp. 1, cinnamon, grape seeds, orange, pomegranate peels, propolis, and guava extracts significantly increased (P < 0.05) pH compared to control (CON). Both CIN and MON significantly increased the pH (P < 0.001) but reduced cumulated gas production (P < 0.01) compared to the other treatments. In Exp. 2, the addition of CIN extract increased (P < 0.01) pH value compared to CON at the first 6 h of incubation. However, no significant differences in pH values between CIN and CON at 24 h of incubation were observed. The addition of CIN extract and MON decreased (P < 0.001) lactic acid concentration and TVFA compared to CON at 24 h. The CIN significantly (P < 0.01) increased acetate: propionate ratio while MON reduced it. In Exp. 3, both CIN and MON significantly increased (P < 0.05) ruminal pH at 6 and 24 h and reduced lactic acid concentration at 24 h compared to CON with corn as substrate. However, CIN had no effect on pH with barley substrate at all incubation times. CONCLUSIONS: It can be concluded that CIN can be used effectively as an alternative antibiotic to MON to control ruminal acidosis when corn is used as a basal diet.