The annual construction and demolition waste (CDW) generated from EU construction sector was 850 million tons, which represented 31% of the total waste generation and about 28% of CDW was ceramics (bricks and tiles). In this study, the feasibility of using CDW brick powder as the precursor of alkali activated mortar (AAM) and extruded polystyrene (XPS) as the lightweight aggregates to form lightweight brick powder AAM (LW-BP-AAM) for non-structural applications was investigated. The thermal conductivity of LP-BPAAM was 0.112 W/m·K with density of about 1,135 kg/m³ which was lower than the counterparts with similar density in literature. The acid resistance of LW-BP-AAM is comparable to conventional fly ash based AAM and superior than ordinary Portland cement. From the scanning electron microscopy with energy dispersive X-ray spectroscopy, there was no severe damage on the surface of LW-BP-AAM but aluminate was removed from the matrix which was further verified in Fourier transform infrared spectroscopy. The mass and strength loss of LP-BP-AAM was 1.5% and 33%, respectively. Although the compressive strength of the LP-BP-AAM was low (about 1.8 MPa), it can be improved by optimising the particle size of the XPS aggregates.

This study focused on hydrolysis of cosmetic fillers hyaluronic acid (HA) and kinetics of the HA hydrolysis using the homogenate of the red king crab hepatopancreas. Turbidimetric analysis of the reaction mixture revealed a bell-shaped time dependence of aggregation formation. It was shown that the obtained homogenate has the similar activity to the commercially available hyaluronidase. The atomic force microscopy (AFM) examination found that the HA fillers were represented by spherical-like structures. These structures were destroyed under the action of the homogenate of the red king crab hepatopancreas. NMR of the reaction mixture showed that HA degradation lasts for some days, but a maximum rate of the reaction is detected in the first hours of incubation. The preparation with hyaluronidase activity obtained from the red king crab hepatopancreas could be used as potentially safe product for treating filler complications.

Antioxidants for foodstuffs during processing or before packing protects colour, aroma and nutrient content. As regards food safety regulations, long-term efforts have been made in terms of food standards, food control systems, food legislation and regulatory approaches. These have, however, generated several questions on how to apply the law to the diverse food businesses. To answer these questions, a thorough examination of the EU legislator’s choices for food preservation and definitions are provided and discussed with factors affecting microbial growth.

The experiments were designed to know the function of ascorbic acid against salinity on germination, different biochemical and micronutrients concentrations of Solanum melongena. Ascorbic acid was applied as foliar spray on leaves and given in roots through irrigation at 100 and 200 ppm to the plants growed in non saline, 60mM and 100mM salt stress conditions. Different biochemical parameters i.e. chlorophyll, carotenoids, carbohydratrates, protein and micro nutrients concentrations of Solanum melongena were observed under different salt stress concentrations from control (non-saline), 60mM NaCl and 100mM NaCl solutions. The rates of different biochemical parameters and micro nutrients concentrations exhibited decrease in saline media in comparison with their respective control while ascorbic acid used as a foliar spray and through irrigation in roots at the concentration of 100 ppm and 200 ppm resulted promotion in non saline control as compared with salt concentrations media. It was determined that chlorophyll concentration was decreased considerably under salt stress. Amongst micro nutrients ionic composition of Na, K and Na/K ratio resulted that plants treated with different NaCl concentrations at 60mM NaCl and 100mM salt concentrations showed increase in Na and K ions and ascorbic acid were used as a foliar spray and in roots showed decrease in Na and K ions. Overall from the outcomes of the study it was observed that salinity stress significantly decrease vegetative and reproductive parameters that could be improved with the using of ascorbic acid. Best concentration found were 200 ppm ascorbic acid contributed towards an increase in growth irrespective of non-saline and saline conditions. Based on these findings, ascorbic acid treatment helps in alleviating the negative effects of salinity.

Iron (Fe) and zinc (Zn) deficiency in cereal grains has deleterious effects on the health of millions of people, especially in developing countries. As wheat, as a staple crop, is consumed in large quantities, its micronutrient content is important. Crops in Africa are often grown under low nitrogen (N) and low phosphorous (P) conditions. The aim of this study was to determine the effect of low N and low P stress on Fe and Zn and phytic acid concentration, in two commercial spring wheat cultivars with excellent baking quality. The two cultivars did not differ significantly for the measured characteristics. Across all treatments the average values for Fe varied between 19.60-28.61 mg kg^-1, Zn between 17.68-33.79 mg kg^-1 and phytic acid between 5.03-6.92 mg g^-1. Low P stress lead to the highest values of Fe and Zn, and the lowest value for phytic acid. Phytic acid:Fe and phytic acid:Zn ratios were also highly significantly reduced under low P stress conditions. Low N conditions caused significantly increased Zn levels. Despite this, the phytic acid:Fe and phytic acid:Zn ratios were relatively high under all conditions, indicating a low bioavailability of both Fe and Zn in these wheat cultivars.

In this study, the corrosion performances of ammonium copper quat (ACQ) and boric acid (BA) wood preservatives were investigated, with micronized copper quat (MCQ) and nano boron (NB) used as reference materials. In the study, Scots pine (Pinus sylvestris L.) wood samples were impregnated according to the full-cell process method with ACQ at 2.4% concentration, BA at 4% and MCQ and NB at 1%. The ACQ- and BA-impregnated samples were then impregnated for a second time using five different water-repellent materials: tall oil, linseed oil, sodium silicate, methyl hydrogen silicone and N'-N- (1, 8-Naphthalyl) hydroxylamine. Polyethylene glycol (PEG) 600 and aluminum sulfate were introduced as single impregnations in the form of homogeneous mixtures with the ACQ and BA. The corrosion properties of the impregnated and control samples, including metal weight loss (MWL) and corrosion depth, were examined. As a result, the MWL values of the ACQ-impregnated samples showed an increase compared to the control group. The MWL values of the MCQ-impregnated samples were lower than those of the samples impregnated with ACQ, whilst the MWL values of the BA-impregnated samples were higher than those of the samples impregnated with NB.

Hyperuricemia is a risk factor for gout. It has been well observed that a large proportion of hyperuricemia individuals have never had a gout attack(s), while some patients with gout can have a normuricemia. This raises a puzzle of the real role of serum uric acid (SUA) in the occurrence of gout attacks. As the molecule of uric acid has its dual effects in vivo with antioxidant property as well as being an inflammatory promoter, it has been placed in a delicate position in balancing metabolisms. Gout seems to be a multifactorial metabolic disease and its pathogenesis should not rely solely on hyperuricemia or MSU crystal. This critical review aims to unfold the mechanisms of the SUA role participating in gout development. It also discusses some key elements which are prerequisite for the formation of gout in association with the current therapeutic regime. The compilation should be helpful in precisely fighting for a cure of gout clinically and pharmaceutically.

Lead Acid Batteries (LABs) are used for starting, lighting, and igniting, as well as in air conditioning systems and to supply power to electric engines in transport vehicles (TVs). However, the application of LABs for TVs has faced a number of market challenges, mounted by the upcoming high energy density and long lifespan batteries, such as lithium ion. LABs, on the other hand, are inexpensive. The key research question is, how can the lifespan of LABs used in automotive industries be increased, while still ensuring a low cost solution? Thus, integrating LABs with the supercapacitor (known as an electric double layer capacitor—EDLC) is likely to outperform the competing alternative batteries for TVs. This paper proposes a multiple stage approach to hybrid lead acid batteries and a supercapacitor system for TVs that is capable of maintaining the battery state-of-charge (SOC) at statistically high limits, ranging between 90% and 95%. This SOC target will likely ensure that the lifespan of the hybrid battery system can be elongated (extended) more than its competitors. In this study, the multiple stage approach of concatenated converters has been designed in order to satisfy all energy storage requirements for different characteristics of LABs and the supercapacitor. The designed hybrid system has been simulated using Matrix Laboratory (MATLAB/Simulink (version R2016a, MathWorks, Natick, MA, USA)). The simulated results show that high transient currents from the direct current (DC) bus of LABs, caused by the regenerative braking or deceleration of the TVs, reduce the battery lifespan and induce mechanical stress. The supercapacitor reduces the stress on the LAB by absorbing high transient currents. This, in turn, keeps the LABs’ SOC between 90% and 96% and the voltage at 12 V. As indicated by the simulated results, the hybrid battery SOC is maintained at 90–96% and the terminal voltage is approximately 12 V.

Cadmium (Cd) is a heavy metal that suppresses plant growth; however, application of endophytic bacteria can increase resistance of plants against Cd, as well as improve plant growth. Two bacterial endophytic strains were isolated from Solanum nigrum and were identified as Serratia sp. AI001 and Enterobacter sp. AI002 by 16S DNA sequencing. Strains AI001 and AI002, tolerated up to 25 mg/mL Cd in broth culture and showed phosphate solubilization potential in Pikovskaya agar medium. AI001 and AI002 produced indole-3-acetic acid, which was confirmed by gas spectrometry-mass chromatography. Brassica plants stressed with 0, 5, 15, and 25 mg/L Cd showed significant decrease in plant growth, chlorophyll content and biomass, and significant increase in Cd dose-dependent electrolyte leakage. Inoculation of strain AI001 or AI002 significantly enhanced the plant growth attributes of shoot length, root length, chlorophyll content, and biomass as compared to those in uninoculated plants. Reduced glutathione contents in plants stressed with different concentrations of Cd also increased with inoculation of AI001 and AI002. The reason of Cd resistance enhancement in plants by inocula could be due to their greater plant growth promoting activities as well as their antioxidative response.

The pharmacokinetics of salicylic acid (SA) in sheep was evaluated following intravenous (IV) and oral administration of sodium salicylate (sodium salt of salicylic acid) at different doses. Six healthy sheep were administered sodium salicylate (SS) IV at doses of 10, 50, 100 and 200 mg/kg body weight and another six sheep were drenched with 100 and 200 mg/kg of SS orally. Both studies were randomised crossover trials. A one-week washout period between each treatment was allowed in both studies. Blood samples were collected at 0, 15, 30 minutes and 1, 2, 4 and 6 hours after IV and oral SS administrations. Plasma SA concentrations were determined using high performance liquid chromatography with diode array detection method. Pharmacokinetic variables were calculated in a non-compartmental model. The elimination half-life (T_{1/2 el}) of SA after IV administration of 200 mg/kg SS was 1.16 ± 0.32 hours. Mean bioavailability of SA was 64%, and mean T_{1/2 el} was 1.90 ± 0.35 hours, after 200 mg/kg of oral SS. The minimum plasma SA concentration (16.8 µg/mL) required to produce analgesia in humans was achieved after IV administration of 100 and 200 mg/kg SS in sheep for about 0.17 hour in this study. Experiments on pharmacokinetic-pharmacodynamics modelling are required to determine the actual effective plasma concentration range of SA in sheep.

There are numerous approaches to model an influence of manufacturing parameters on the dissolution and disintegration of solid dosage forms. A modern approach for modelling and simulating complex and heterogeneous systems such as pharmaceutical tablets focuses on computationally-intensive finite-element or discreet element methods. Industrial challenges such as Process Analytical Technology (PAT) and Quality by Design are stimulating computer-based technologies to design, control and improve the quality of pharmaceutical compacts and their performance. In this study the disintegration and dissolution model based on the numerical solutions of the Noyes-Whitney equation and cellular automata supported disintegration model are proposed and evaluated. The results from in vitro release studies of the mefenamic acid formulations were compared to the calculated release patterns from the tablet structures obtained from microtomography experiments and the purely algorithmically created virtual tablets.

Study of fungal antibiotics in their competitive interactions with arthropods may lead to development novel biorational insecticides. Extracts of Alternaria tenuissima MFP253011 obtained by various methods showed a wide range of biological activity, including entomotoxic properties. Analysis of their composition and bioactivity allowed to reveal several known mycotoxins and unidentified compounds that may be involved in entomotoxic activity of the extracts. Among them, tenuazonic acid (TeA), which was the major component of the A. tenuissima extracts, was found the most likely to have larvicidal activity against Galleria mellonella. In the intrahaemocoel injection bioassay, TeA was toxic to G. mellonella and of Zophobas morio with LT50 6 and 2 days, respectively, at the level of 50 µg/larva. Administered orally, TeA inhibited growth of G. mellonella larvae and caused mortality of Acheta domesticus imagines (LT50 7 days) at a concentration of 250 µg/g of feed. TeA showed weak contact-intestinal activity against the two phytophages, Tetranychus urticae and Schizaphis graminum, causing the 12 and 40% of mortality at a concentration of 1 mg/mL. TeA was cytotoxic to Sf9 cell line (IC50 25 µg/mL). Thus, model insect G. mellonella and cell line Sf9 could be used for a further toxicological characterization of TeA.

Background: Acute intermittent porphyria (AIP) is caused by haploinsufficiency of porphobilin-ogen deaminase (PBGD) enzymatic activity. Acute attacks occur in response to fasting and altera-tions in glucose metabolism, insulin resistance and mitochondrial turnover may be involved in AIP pathophysiology. Therefore, we investigated the metabolic pathways in PBGD-silenced hepatocytes and assessed the efficacy of an insulin-mimic, the α-lipoic acid (α-LA) as a potential therapeutic strategy. Methods: HepG2 cells were transfected with a siRNA targeting PBGD (siPBGD). Cells were cul-tured with low glucose concentration to mimic fasting and exposed to α-LA alone or with glu-cose. Results: At baseline, siPBGD cells showed lower expression of genes involved in glycolysis and mitochondrial dynamics along with reduced total ATP levels. Fasting further unbalanced gly-colysis by inducing ATP shortage in siPBGD cells and activated DRP1, which mediates mito-chondrial separation. Consistently, siPBGD cells in fasted state showed the lowest protein levels of Complex IV which belong to the oxidative phosphorylation (OXPHOS) machinery. α-LA up-regulated glycolysis and prompted ATP synthesis and triglyceride secretion, thus possibly providing energy fuels to siPBGD cells by improving glucose utilization. Finally, siPBGD exposed to α-LA plus glucose raised mitochondrial dynamics, OXPHOS activity and energy production. Conclusions: α-LA-based therapy may ameliorate glucose metabolism and mitochondrial dys-functions in siPBGD hepatocytes. Keywords: AIP, PBGD, glucose metabolism, mitobiogenesis, α-lipoic acid

Background & Aims: This RCT aimed to investigate the safety and efficacy of MF4637, a medical food comprising highly concentrated, highly purified, long chain (LC) omega-3 fatty acids, (460 mg eicosapentaenoic acid (EPA) and 380 mg docosahexaenoic acid (DHA)) in correcting the omega-3 fatty acid nutritional deficiency present in non-alcoholic fatty liver disease (NAFLD). The potential for MF4637 to reduce liver fat was evaluated in a subset of patients. Methods: 176 subjects with NAFLD were randomised to receive 3 g/d of LC-omega-3 fatty acids (n=87) or placebo (olive oil; n=89) for 24 weeks, in addition to following standard-of-care dietary guidelines for these patients. Thus, interventions were given on top of the dietary advice. The omega-3 index, omega-6:omega-3 fatty acid ratio (primary outcome) and quantitative measurements of red blood cell (RBC) EPA and DHA (secondary outcome) were determined at baseline and study completion. Magnetic resonance imaging-proton density fat fraction (MRI-PDFF) assessment of change in liver fat fraction was conducted in a subset of patients. Results: Of the 176 randomised subjects, 167 were analysed for the primary and secondary outcomes (n=81 in the MF4637 group; n=86 in the placebo group). Supplementation with MF4637 for 24 weeks significantly increased the omega-3 index and absolute values of RBC EPA and DHA, and decreased the omega-6:omega-3 fatty acid ratio in NAFLD patients compared to placebo (p<0.0001). There was a statistically significant reduction in liver fat content within both groups with no difference between them. An inverse relationship between change in absolute RBC EPA+DHA and change in liver fat, AST and ALT levels was seen suggesting that a greater increase in omega-3 content was associated with a reduction for both liver fat content and improvement in liver enzyme levels. Additionally, a significant liver fat-lowering effect of MF4637 compared to placebo was demonstrated in a subset of patients with baseline fatty liver index (FLI) score ≥ 40. There were no serious adverse events related to study interventions. Conclusions: The study results demonstrate that the medical food MF4637, was able to correct the nutritional deficiency of omega-3 in NAFLD patients above and beyond that obtained with nutritional counselling. This demonstrates that MF4637 is beneficial in raising the low omega-3 index observed in these patients. A reduction in hepatic steatosis was demonstrated with both intervention groups although no distinction between groups was seen. Further analyses demonstrate the potential to identify omega-3 sensitive patients using an easily available clinical tool for steatosis prediction.

Ring necked-pheasant (Phasianus colchicus) is bird of order Galliformes. Ring necked-pheasant is also known as gallinaceous bird and game bird. It looks like chicken bird. It is national bird of South Dakota. It is mostly found in wild areas but in Pakistan it exists as Domestic bird. It has high proteins and low fat in its meat. The present study was conducted to check the effect of ascorbic acid on sperm Motility, sperm cytoplasmic membrane integrity, sperm livability and acrosome integrity of Ring-necked pheasant at different concentrations of ascorbic acid (0mM, 1mM, 2mM, 3mM and 4mM) were used. Semen was collected by abdominal massage technique. Motility of sperm was greater than 70%.Then it was processed further. The cryopreservation of semen was checked at various stages like Post Dilution, Post Cooling, Post Equilibration and Post Thawing. Semen was cooled from post-dilution stage (37⁰ C) to post-cooling (20⁰C).Then it further cooled gradually to get post-equilibration stage (4⁰ C) within 24 hours. After that 10% glycerol was added to the sample. Then it was transferred to liquid nitrogen (LN₂) cylinder for 24 hours. After thawing stage sample was removed from LN₂ cylinders and placed in water bath for 4 hours to achieve post-thawing. Then performed sperm quality assays at each stage of cryopreservation. Sperm motility was assessed by Neubauer Chamber Hemocytometer. Plasma Membrane Integrity was checked by using Hypo Osmotic Swelling Test with the help to 2% Eosin. Sperm livability was assessed by Lake’s glutamate solution and sperm Acrosome Integrity was checked by dual staining technique by using Formal citrate solution and Giemsa stain. The better results were seen at 3mM treatment of ascorbic acid. Sperm motility percentage was significantly different (P < 0.05) on 3mM treatment on all the stages of cryopreservation rather than other treatments. Plasma membrane integrity assay also showed good results at same concentration (P < 0.05) on all the stages of cryopreservation rather than other treatments. At the sperm livability stage 3mM treatment showed significantly difference (P < 0.05) on all the stages of cryopreservation rather than other treatments. The sperm acrosome integrity showed highest percentage on 3mM treatment (P < 0.05) on all stages of cryopreservation rather than other treatments. Effect of ascorbic acid on all the quality parameters (sperm motility, plasma membrane integrity, livability and acrosome integrity) was showed significant difference (P < 0.05) at 3mM treatment of ascorbic acid as compare to control as well as remaining treatments. It was seen that by increasing the concentration of ascorbic acid from 3mM concentration to onward it shows negative results on its cryopreservation. Now this cryopreserved semen can be transfer from one place to another place to obtain good varieties as well as better genetic characteristics of this species.

Dental pulp tissue engineering (TE) quests to regenerate dentin/pulp complex by combining a suitable supporting matrix, stem cells, and biochemical stimuli. Such procedures foresee a matrix that can be easily introduced into the root canal system (RCS) and tightly adhere to dentin walls to assure the dentin surface's proper colonization with progenitor cells capable of restoring the dentin/pulp complex. Herein was investigated an injectable self-setting hyaluronic acid-based (HA) hydrogel system, formed by aldehyde-modified (a-HA) with hydrazide-modified (ADH), enriched with platelet lysate (PL), for endodontic regeneration. The hydrogels' working (wT) and setting (sT) times, the adhesion to the dentine walls, the hydrogel's microstructure, and the delivery of human Dental Pulp Cells (DPCs) were studied in vitro. Hydrogels incorporating PL showed a suitable wT and sT and a porous microstructure. The tensile tests showed that the breaking point occurs after 4.13 mm deformation. While in the indentation test after 1.3 mm deformation. Both breaking points occur in the hydrogel extension. The HA/PL hydrogels exhibited supportive properties and promoted cell migration toward dentin surfaces in vitro. Overall, these results support using PL-laden HA injectable hydrogels (HA/PL) as a biomaterial for DPCs encapsulation, thereby displaying great clinical potential towards endodontic regenerative therapies.

Bile acids (BA) are classically known as an agent important in lipid absorption and cholesterol metabolism. Nowadays, BAs have been found to be involved in various cellular signaling pathways such as protein kinase cascades, cyclic AMP (cAMP) synthesis and calcium mobilization. In addition, they have also been shown to regulate glucose and energy homeostasis. Bile acids are ligands for several nuclear hormone receptors, including FXR. Recently, muscarinic receptor and TGR5, G-protein-coupled receptor (GPCR), have been suggested to play a role in bile acid activity which is independent of nuclear hormone receptors. Moreover, BAs have also been studied in other GPCR associated pathways, namely sphingosine-1-posphate and glucagon receptor. Hydrophobic bile acids have been proven to affect heart rate and its contraction. Elevated bile acids are associated with arrhythmias in adults and fetal heart. Altered ratios of primary and secondary bile acid are reported in chronic heart failure patients. Meanwhile in patients with liver cirrhosis, cardiac dysfunction has been strongly linked to the increase of serum bile acid concentrations. In contrast, the most hydrophilic BA known as ursodeoxycholic acid has been found beneficial in improving peripheral blood flow in chronic heart failure patients and protecting heart against reperfusion injury.

Choline is metabolized by the gut microbiota into trimethylamine (TMA), the precursor of pro-atherosclerotic molecule trimethylamine N-oxide (TMAO). Reduction of TMA formation has been shown to provide to cardioprotective effects, and some phytochemicals may produce such reduction. This study aimed to develop an optimized, high-throughput anaerobic fermentation methodology to study inhibition of choline microbial metabolism into TMA by phenolic compounds with healthy human fecal starter. Optimal fermentation conditions were: 20 % fecal slurry (1:10 in PBS), 100 M choline, and 12 h fermentation. Also, 10 mM of 3,3-dimethyl-1-butanol (DMB) was defined as a positive TMA production inhibitor, achieving a ~50 % reduction in TMA production. Gallic acid and chlorogenic acid reported higher TMA inhibitory potential (maximum of 80 -90 % in. TMA production inhibition), with IC50 around 5 mM. Nor DMB neither gallic acid and chlorogenic acid reduced TMA production through cytotoxic effects, indicating mechanisms such as altered TMA lyase activity or expression.

This study investigated the relationship of acrosome reactions and fatty acid composition on fertility in boar sperm. The acrosome reaction of sperm was induced via methyl-beta-cyclodextrin (MBCD), and acrosome reaction, plasma membrane integrity, and fertility were analyzed. The fatty acid composition of the excess acrosome reacted sperm was determined via gas chromatography. The results showed that the acrosome reaction in sperm was induced over 85% of the time by 60 mM MBCD treatment, and the plasma membrane integrity was significantly decreased and was dependent on the MBCD level. The acrosome reacted sperm resulted in significantly higher saturated fatty acids (SFAs) and lower unsaturated fatty acids (PUFAs) than the non-acrosome reaction group. Moreover, the acrosome reacted sperm from 60 mM MBCD significantly decreased in vitro fertility and blastocyst formation relative to non-acrosome reacted sperm, and the acrosome reaction was positively correlated with SFAs and negatively correlated with PUFAs. Of these fatty acids, C22:5n-6 (docosapentaenoic acid [DPA]) and C22:6n-3 (docosahexaenoic acid [DHA]) were directly negatively correlated with the acrosome reaction (r = -0.982 and -0.947, respectively). In conclusion, the excessive acrosome reactions may occur by reducing the PUFAs, which may then dramatically decrease sperm fertility in pigs.

Depletion of ore deposits, increasing demand for raw materials, the need to process low-grade, complex and finely disseminated ores and the reprocessing of tailings are challenges, especially for froth flotation separation technologies. Even though capable of handling relatively fine grain sizes the flotation separation of very fine and ultrafine particles faces many problems still. Further, the flotation of low-contrast semi-soluble salt-type minerals with very similar surface properties, many complex interactions between minerals, reagents and dissolved species often result in poor selectivity. This study investigates the flotation beneficiation of ultrafine magnesite rich in dolomite from de-sliming, currently reported to the tailings. The paper especially focuses on the impact of the depressant sodium hexametaphosphate (SHMP) on: (i) the froth properties using dynamic froth analysis (DFA), (ii) the separation between magnesite and dolomite/calcite and (iii) its effect on the entrainment. Furthermore, the application of 1-hydroxyethylene-1,1-diphosphonic acid (HEDP) is a more environmentally friendly and low-cost alternative to SHMP is presented and discussed. The paper contributes to understanding on the complexity of depressant responses in froth flotation.

Insufficient mixing in large-scale bioreactors, provokes gradient zones of substrate, dissolved oxygen, pH and other parameters. E. coli responds to a high glucose, low oxygen feeding zone with the accumulation of mixed acid fermentation products, especially formate, but also with the synthesis of non-canonical amino acids, such as norvaline, norleucine and -methyl-norleucine. These amino acids can be mis-incorporated into recombinant products, which causes a problem for pharmaceutical production whose solution is not trivial. While these effects can also be observed in scale down bioreactor systems, these are challenging to operate. Especially the high-throughput screening of clone libraries is not easy, as fed-batch cultivations would need to be controlled via repeated glucose pulses with simultaneous oxygen limitation, as has been demonstrated in well controlled robotic systems. Here we show that not only glucose pulses in combination with oxygen limitation can provoke the synthesis of these non-canonical branched-chain amino acids, but also that pyruvate pulses produce the same effect. Therefore we combined the enzyme based glucose delivery method Enbase® in a PALL24 mini-bioreactor system and combined repeated pyruvate pulses with simultaneous reduction of the aeration rate. These cultivation conditions, produced an increase in the non-canonical branched chain amino acids norvaline and norleucine in both the intracellular soluble protein and inclusion body fractions with mini-proinsulin as an example product, and this effect was verified in a 15 L stirred tank bioreactor. To our opinion this cultivation strategy is easy to apply for the screening of strain libraries under standard laboratory conditions if no complex robotic and well controlled parallel cultivation devices are available.

In the present study, we isolated and screened thirty strains of GABA-producing lactic acid bacteria (LAB) from Indonesian traditional fermented foods. Two strains were able to convert monosodium glutamate (MSG) to GABA after 24 h of cultivation at 37oC based on thin layer chromatography (TLC) screening. 16S rDNA sequencing and proteomic identification using MALDI-TOF MS identified these two strains as Lactobacillus plantarum designated as L. plantarum FNCC 260 and L. plantarum FNCC 343. The highest yield of GABA production obtained from the fermentation of L. plantarum FNCC 260 was 809.2 mg/l of culture medium after 60 h of cultivation. Supplementation of 0.6 mM pyridoxal 5’-phosphate (PLP) and 0.1 mM pyridoxine led to the increase in GABA production to 945.3 mg/l and 969.5 mg/l, respectively. The highest GABA production of 1226.5 mg/l of culture medium was obtained with 100 mM initial concentration of MSG added in the cultivation medium. The open reading frame (ORF) of 1410 bp of the gadB gene from L. plantarum FNCC 260 encodes 469 amino acids with a calculated molecular mass of 53.57 kDa. The production of GABA via enzymatic conversion of monosodium glutamate (MSG) using purified recombinant glutamate decarboxylase (GAD) from L. plantarum FNCC 260 expressed in Escherichia coli was found to be more efficient (5-fold higher within 6 h) than the production obtained from fermentation. L. plantarum FNCC 260 could be of interest for the synthesis of GABA.

The objective of this study was to identify key transcription factors involved in lipid metabolism and immune response related to the differentially expressed genes (DEG) from the liver samples of 35 pig model for metabolic diseases fed diets containing either 1.5 or 3.0% soybean oil (SOY1.5 or SOY3.0). A total of 281 DEG between SOY1.5 and SOY3.0 diets (log2fold-change ≥ 1 or ≤ −1; FDR-corrected p-value &lt; 0.1) were identified, in which 129 were down-regulated and 152 were up-regulated in SOY1.5 group. The functional annotation analysis detected transcription factors linked to lipid homeostasis and immune response, such as RXRA, EGFR, and SREBP2 precursor. These findings demonstrated that key transcription factors related to lipid metabolism could be modulated by dietary inclusion of soybean oil. It could contribute to nutrigenomics research field that aims to elucidate dietary interventions in animal and human health, as well as to drive the food technology and science.

Dendrobium okinawense is an endangered epiphytic orchid, and there has been no scientific report so far on its propagation. Protocorm is mass of cell, and protocorm-like bodies (PLBs) look alike protocorm produced by vegetative explants in vitro. Regeneration of PLBs is the most efficient technique for the orchids micro-propagation. We used different light emitting diodes (LEDs) for the efficient PLB organogenesis of D. okinawense. PLBs regenartion under green and red LED surpassed respectively 81.1% and 71.6% in numbers, and respectively 80.8% and 57.8% in fresh weight over white fluorescent light. We manipulated the culture media by different concentrations of PCIB and HMI. PLBs organogenesis promoted by low concentration, it increased respectively 35.9% and 19.3% over control by 0.01 mg/L PCIB and 0.01 ml/L HMI in numbers. Green LED and PCIB independently produced mostly similar numbers of new PLBs. Interestingly, culture media with 0.01 mg/L of PCIB further increased 8.5% of the numbers of PLBs under green LED, whereas the culture media with 0.01 mg/L HMI reduced the number of PLBs under green LED. PLBs culture under green LED with very low concentrations of PCIB manipulated culture media can significantly increase their organogenesis of D. okinawense.

In the human organism various carotenoids are present of which, some are retinoid precursors. The bioactive derivatives of these retinoids are the retinoic acids, which can potently activate nuclear hormone receptors like the retinoic acid receptor and the retinoid X receptor. In our study using an HPLC analytical approach we aimed to assess how plasma carotenoid and retinoid concentrations along with the ratio of their isomers are altered in atopic dermatitis (AD) patients (n=20) compared to healthy volunteers (HV, n=20). We found that plasma levels of the carotenoids lutein (HV 198 ± 68 ng/ml, AD 158 ± 57 ng/ml), zeaxanthin (HV 350 ± 142 ng/ml, AD 236 ± 85) as well as the retinoids retinol (HV 216 ± 89 ng/ml, AD 167 ± 76 ng/ml) and all-trans-retinoic acid (HV 1.1 ± 0.6 ng/ml, AD 0.7 ± 0.5 ng/ml) were significantly lower in AD-patients, while lycopene, α-carotene and β-carotene levels were comparable. In addition the ratios of 13-cis vs. all-trans lycopene as well as 13-cis vs. all-trans retinoic acid were increased in the plasma of AD-patients indicating an AD-specific 13C-isomerisation. A positive correlation with SCORRAD was calculated with 13-cis vs. all-trans lycopene ratio, while a negative correlation was observed with zeaxanthin plasma levels. Based on our results we conclude that in the plasma of AD-patients various carotenoids and retinoids are at lower levels, while the ratio of lycopene isomers was also altered. The higher rate of lycopene and retinoic acid isomerisation products might be a consequence of AD or might result in an altered activation of nuclear hormone receptor signaling pathways and thus maybe partly be responsible for the AD-phenotype and additionally may represent a good plasma marker for AD.

The indole-3-pyruvic acid pathway is the major route for auxin biosynthesis in higher plants. Tryptophan aminotransferases (TAA1/TAR) and members of the YUCCA family of flavin-containing monooxygenases catalyze the conversion of L-tryptophan via indole-3-pyruvic acid into indole-3-acetic acid (IAA). It has been described that locally produced jasmonic acid (JA) in response to mechanical wounding, triggers de novo-formation of IAA through the induction of two YUCCA genes, YUC8 and YUC9. Here, we report the direct involvement of a small number of basic helix-loop-helix transcription factors of the MYC family in this process. We show that the JA-mediated regulation of YUC8 and YUC9 gene expression depends on the abundance of MYC2, MYC3, and MYC4. In support of this observation, seedlings of myc knockout mutants displayed a strongly reduced response to JA-mediated IAA formation. In addition, transactivation assays provided experimental evidence for the binding of the MYC transcription factors to a particular tandem G-box motif abundant in the promoter regions of YUC8 and YUC9, but not in those of the other YUCCA genes. Moreover, we clearly demonstrate that YUC8ox and YUC9ox overexpressing plants show less damage after spider mite infestation, thereby underlining a role of auxin in plant responses toward biotic stress cues.

For the diagnosis of disease, the ability to quantitatively detect trace amounts of the causal proteins from bacteria/viruses as biomarkers in patient specimens is highly desirable. Here we introduce a simple, rapid, and colorimetric assay as a de novo, ultrasensitive detection method. This ultrasensitive assay consists of sandwich enzyme-linked immunosorbent assay (ELISA) and thionicotinamide-adenine dinucleotide (thio-NAD) cycling, forming an ultrasensitive ELISA, in which the signal substrate (i.e., thio-NADH) accumulates in a triangular manner, and the accumulated thio-NADH is measured at its maximum absorption wavelength of 400 nm. We have successfully achieved a limit of detection of ca. 10–18 moles/assay for a target protein. As an example of infectious disease detection, HIV-1 p24 could be measured at 0.0065 IU/assay (i.e., 10⁻¹⁸ moles/assay), and as a marker for a lifestyle-related disease, adiponectin could be detected at 2.3 × 10⁻¹⁹ moles/assay. In particular, despite the long-held belief that the trace amounts of adiponectin in urine can only be detected using a radioisotope, our ultrasensitive ELISA was able to detect urinary adiponectin. This method is highly versatile, because simply changing the antibody enables the detection of various proteins. This assay system requires only the measurement of absorbance, thus it requires equipment that is easily obtained by medical facilities, which facilitates diagnosis in hospitals and clinics. Moreover, we describe an expansion of our ultrasensitive ELISA to a non-amplification nucleic acid detection method for nucleic acids using hybridization. These de novo methods will enable simple, rapid, and accurate diagnosis.

Chlorotoxin (CTX) is a 36–amino acid peptide with 8 Cys residues that forms four Cys-Cys bonds. It has high affinity for the glioma-specific chloride channel and matrix metalloprotease-2. Structural and binding properties of CTX analogs with various Cys residue substitutions with L-a-aminobutyric acid (Abu) have been previously reported. Using 4.2 ìs molecular dynamics, we compared the conformational and essential space sampling of CTX and analogs [Abu/Ser^2,19]CTX, [Abu/Ser^5,28]CTX, [Abu/Ser^16,33]CTX, [Abu/Ser^20,35]CTX, and [Abu/Ser^{2,5,16,19,20,28,33,35}]CTX. The native and substituted peptides maintained a high degree of a-helix propensity from residues 8 through 21, with the exception of [Ser^5,28]CTX and [Abu^16,33]CTX. In agreement with previous circular dichroism spectropolarimetry results, the C-terminal b-sheet content varied less from residues 25 through 29 and 32 through 36 and was well conserved in all analogs, except: [Abu^16,33]CTX, [Ser^20,35]CTX, [Abu^{2,5,16,19,20,28,33,35}]CTX, and [Ser^{2,5,16,19,20,28,33,35}]CTX. The Cys¹⁶-Cys³³ and Cys²⁰-Cys³⁵ Cys-Cys bonds appear to be required to maintain the ab-motif of CTX. Their selective substitution with Ser^16,33 however, may mitigate the destabilizing effect of Cys¹⁶-Cys³³ substitution by the formation of an inter residue H-bond from OgH of Ser¹⁶ to OgH of Ser³³ bridged by a water molecule. All peptides shared considerable sampled conformational space, which explains the retained receptor binding of the nonnative analogs.

Folic acid, one of the 13 essential vitamins, plays an important role in cardiovascular development. Mutations in folic acid synthesis gene 5,10-methylenetetrahydrofolate reductase (MTHFR) is significantly associated with the occurrence of congenital heart disease. However, the mechanisms underlying the regulation of cardiac development by mthfr gene are poorly understood. Here, we exposed zebrafish embryos to excessive folate or folate metabolism inhibitors. And we established a knock-out mutant of mthfr gene in zebrafish by using CRISPR/Cas9. The zebrafish embryos of insufficient or excessive folic acid, and mthfr-/- mutant all gave rise to early pericardial edema and cardiac defect at 3 days after fertilization(dpf). Furthermore, the folic acid treated embryos showed abnormal movement at 5dpf. The expression levels of cardiac marker genes hand2, gata4 and nppa changed in the abnormality of folate metabolism embryos and mthfr-/- mutant, and there is evidence that they are related to the change of methylation level caused by the change of folate metabolism. In conclusion, our study provides a novel model for the in-depth study of MTHFR gene and folate metabolism. And our results reveal that folic acid has a dose-dependent biphasic effect on early cardiac development.

High-level quantum-chemical computations (G4MP2) are carried out in the study of complexes featuring tetrel bonding between the carbon atom in the carbenoid CB11H11 - obtained by hydride removal in the C-H bond of the known closo-monocarbadodecaborate anion CB11H12() and acting as Lewis acid (LA) - and Lewis bases (LB) of different type; the electron donor groups in the tetrel bond feature carbon, nitrogen, oxygen, fluorine, silicon, phosphorus, sulphur and chlorine atomic centers in neutral molecules as well as anions H(-), OH(-) and F(-). The empty radial 2pr vacant orbital on the carbon center in CB11H11 , which corresponds to the LUMO, acts as a Lewis acid or electron attractor, as shown by the molecular electrostatic potential (MEP) and electron localization funcion (ELF). The thermochemistry and topological analysis of the complexes {CB11H11:LB} are comprehensively analyzed, and classified according to sharing or closed-shell interactions. ELF analysis shows that the tetrel C···X bond ranges from very polarised bonds, as in H11B11C:F() to very weak interactions as in H11B11C···FH and H11B11C···O=C=O.

PHLNs (polymeric lipid hybrid nanoparticles) are core–shell nanoparticle structures made up of polymer cores and lipid shells that have properties similar to both polymeric nanoparticles and liposomes. Methotrexate (MTX) loaded PLHNPs containing tween 80, phosphatidylcholine, poly D, L-lactic-co-glycolic acid (PLGA) & glyceryl tripalmitate prepared using solvent injection & homogenization method for glioblastoma treatment option. The MTX loaded PLHNPs optimized by Box–Behnken design to minimize particle size, higher entrapment efficacy, and maximize MTX concentration in the brain at 4h. The particle size, entrapment efficacy, concentration of drug in brain at 4h, zeta potential and AUC(Brain)/AUC(Plasma) ratio were in the range of 173.51-233.37nm, 70.56-86.34%, 6.38-12.38 μg/mL, 25.78-36.31mV & 1.02-5.32. in-vitro drug release studies, cellular internalization of optimized formulation against U-87 MG shows good anticancer effects.

The aim of this study was to investigate succinic acid production from lactose concentrate, a by-product of cheese-making, using Actinobacillus succinogenes and Basfia succiniciproducens. Although the capability of these strains to metabolize different sugars is already known, their application in the conversion of lactose bears high potential for optimization. With regard to B. succiniciproducens this approach is completely novel. In particular the influence of the mediums sugar concentration and its supplementation with yeast extract to prevent a lack of proteins and vitamins were examined. Lactose based media containing sugar concentrations between 20 and 65 g L-1 and 5 g L-1 yeast extract were fermented, whereby both strains showed comparable performances. The best results in succinic acid yield and acid concentration, 0.57 g g-1 initial sugar and 23 g L1, were achieved at an initial sugar concentration of 43 g L-1. The necessity of yeast extract was demonstrated using the sugar optimized medium without supplementation. As a result, yield and concentration of succinic acid dropped to 0.34 g g-1 and 13 g L-1, the sugar consumption decreased from more than 99 to less than 55 %. Therefore the supplementation amount of 5 g L-1 yeast extract can be regarded as well-balanced.

Bacterial indole-3-acetic acid (IAA), an effector molecule in microbial physiology, plays an important role in plant growth-promotion. Here, we comprehensively analyzed about 7282 prokaryotic genomes representing diverse bacterial phyla, combined with root-associated metagenomic data to unravel the distribution of tryptophan-dependent IAA synthesis pathways and to quantify the IAA synthesis-related genes in the plant root environments. We found that 82.2% of the analyzed bacterial genomes were potentially capable of synthesizing IAA from tryptophan (Trp) or intermediates. Interestingly, several phylogenetically diverse bacteria showed a preferential tendency to utilize different pathways and tryptamine and indole-3-pyruvate pathways are most prevalent in bacteria. About 45.3% of the studied genomes displayed multiple coexisting pathways, constituting complex IAA synthesis systems. Furthermore, root-associated metagenomic analyses revealed that rhizobacteria mainly synthesize IAA via IAM and tryptamine (TMP) pathways and might possess stronger IAA synthesis abilities than bacteria colonizing other environments. The obtained results refurbished our understanding of bacterial IAA synthesis pathways and provided a faster and less labor-intensive alternative to physiological screening based on genome collections. The better understanding of IAA synthesis among bacterial communities could maximize the utilization of bacterial IAA to augment the crop growth and physiological function.

Background and objectives: This study were designed to determine uric acid concentration and renal histopathology of M. calabura L. stem bark extract in diabetic rats and to compare the natural product of M. calabura L. stem bark extract with allopurinol. Materials and Methods: A completely randomized design was used for the experiment which consisted of 6 treatment groups, each consisting of 4 rats, as follows: 1) NR, normal rat; 2) KN, diabetic rat (negative control); 3) KP, diabetic rats given allopurinol 10 mg/kg body weight; 4) EM150, diabetic rats given the test extract 150 mg/kg body weight/day; 5) EM300, diabetic rats given the test extract 300 mg/kg body weight/day; and 6) EM450, diabetic rats given the test extract 450 mg/kg body weight/ day. Results: The results showed that M. calabura L. stem bark extract decrease (p<0.05) uric acid levels in diabetic rats and no specific damage to renal proximal tubular cells was seen. Conclusions: It was concluded that M. calabura L. stem bark extract has a potential as an antihyperuricemic in diabetic rats. The recommended does was 300 mg/kg body weight to provide a significant effect on reducing the uric acid level in diabetic rats. Our findings support the use of this plant as a treatment for gout and other inflammatory diseases.

Disturbed metabolism of vitamins B1 or B6, which are essential for neurotransmitters homeostasis, may cause epilepsy. Our study aims at revealing therapeutic potential of vitamins B1 and B6 in epilepsy by estimating effects of their combined administration on a seizure and its consequences in rats subjected to pentylenetetrazole (PTZ). The PTZ dose dependence of a seizure and its parameters according to Racine’s scale along with delayed physiological and biochemical consequences next day after the seizure are assessed regarding sexual dimorphism in epilepsy. PTZ sensitivity is stronger in the female than male rats. Next day after a seizure, gender differences in behavior and brain biochemistry arise. The induced gender differences in anxiety, exploratory and locomotor activity correspond to disappearance of gender differences in the brain GABA, aspartate, alanine and serine, with appearance of those in glutamate, glutamine and tyrosine. PTZ decreases the brain malate dehydrogenase activity, glutamine and urea in the males, and phenylalanine in the females. Administration of vitamins B1 and B6 24 h before PTZ delays a seizure in female rats only. This desensitization is not observed at short intervals (0.5-2 h) between the vitamins and PTZ administration. With the increasing interval, the pyridoxal kinase (PLK) activity in the female brain decreases, suggesting that the PLK downregulation by vitamins contributes to the desensitization. Delayed effects of vitamins and/or PTZ are mostly gender-specific and interacting. Our findings on the gender differences in sensitivity to epileptogenic factors, action of vitamins B1/B6 and associated biochemical events have medical implications.

The development of platinum group metal-free (PGM-free) electrocatalysts derived from cheap and environmentally friendly biomasses for oxygen reduction reaction (ORR) is a topic of relevant interest, particularly from the point of view of sustainability. Fe-nitrogen-doped carbon materials (Fe-N-C) have attracted particular interest as alternative to Pt-based materials, due to the high activity and selectivity of Fe-Nx active sites, the high availability and good tolerance to poisoning. Recently, many studies focused on developing synthetic strategies, which could transform N-containing biomasses into N-doped carbons. In this paper chitosan was employed as a suitable N-containing biomass for preparing Fe-N-C catalyst in virtue of its high N content (7.1%) and unique chemical structure. Moreover, the major application of chitosan is based on its ability to strongly coordinate metal ions, a precondition for the formation of Fe-Nx active sites. The synthesis of Fe-N-C consists in a double step thermochemical conversion of a dried chitosan hydrogel. In acidic aqueous solution, the preparation of physical cross-linked hydrogel allows to obtain sophisticated organization, which assure an optimal mesoporosity before and after the pyrolysis. After the second thermal treatment at 900 °C, a highly graphitized material was obtained, which has been fully characterized in term of textural, morphological and chemical properties. RRDE technique was used for understanding the activity and the selectivity of the material versus the ORR in 0.5 M H2SO4 electrolyte. Special attention was put in the determination of the active site density according to nitrite electrochemical reduction measurements. It was clearly established that the catalytic activity expressed as half wave potential linearly scales with the number of Fe-Nx sites. It was also established that the addition of the iron precursor after the first pyrolysis step leads to an increased activity because of both an increased number of active sites and of a hierarchical structure, which improves the access to active sites. At the same time, the increased graphitization degree, and a reduced density of pyrrolic nitrogen groups are helpful to increase the selectivity toward the 4e- ORR pathway.

1-[5-(4-methylphenyl)-1,3,4-oxadiazol-2-yl]methanamine compound has been successfully synthesized by reacting p-Toluic hydrazide and glycine via polyphosphoric acid condensation route. The course of the reaction was found to be high yielding and the title compound was spectroscopically characterized by FT-IR, DSC, 13C/1H-NMR and Mass spectrometric techniques.

The world is now undergoing through a global emergency due to COVID-19 which needs immediate remedies in order to strengthen the healthcare facility to save the nations. Looking towards to the remedies, research on different aspects including the genomic and proteomic level characterizations of the SARS-CoV2 are necessarily important. In this present study, the spatial representation/composition of twenty amino acids across the primary protein sequences of SARS-CoV2 have been looked into through different parameters viz. Shannon entropy, Hurst exponent in order to fetch the autocorrelation and amount of information over the spatial representations. Also frequency distribution of each of the amino acids over the protein sequences have been chalked out.

Ti6Al4V samples obtained by selective laser melting were subjected to acid treatment, chemical oxidation in hydrogen peroxide solution and subsequent thermochemical treatment. The effect of temperature and time of acid etching of Ti6Al4V samples on surface roughness, morphology, topography and chemical and phase composition after the thermochemical treatment was studied. The surfaces were characterized using scanning electron microscopy, energy dispersive X-ray spectroscopy, X-ray diffraction and contact profilometry. Pore and protrusion sizes were measured. Acid etching modified the elemental composition and surface roughness of the alloy. Temperature had a greater influence on the morphology, topography and surface roughness of samples than time. Increases in roughness values were observed when applying successive chemical oxidation and thermochemical treatment compared to the values observed on surfaces with acid etching. After the thermochemical treatment, the samples with acid etching at a temperature of 80 °C showed a multiscale topography. In addition, a network-shaped structure was obtained on all surfaces, both on their protrusions and pores previously formed during the acid etching.

We used atomistic molecular dynamics (MD) simulations to study polyelectrolyte brushes based on anionic α-L-glutamic acid and α-L-aspartic acid grafted on cellulose in the presence of divalent CaCl2 salt at different concentrations. The motivation is the search of the ways to control properties such as sorption capacity and the structural response of the brush to multivalent salts. For this detailed understanding of the role of side chain length, chemical structure and their interplay is required. It was found that in the case of glutamic acid oligomers, the longer side chains facilitate attractive interactions with the cellulose surface, which forces the grafted chains to lie down on the surface. The additional methylene group in the side chain enables side chain rotation enhancing this effect. On the other hand, the shorter and more restricted side chains of aspartic acid oligomers prevent attractive interactions to a large degree and push the grafted chains away from the surface. The difference in side chain length also leads to differences in other properties of the brush in divalent salt solutions. At a low grafting density, the longer side chains of glutamic acid allow the adsorbed cations to be spatially distributed inside the brush resulting in a charge inversion. With an increase in grafting density, the difference in the total charge of the aspartic and glutamine brushes disappears, but new structural features appear. The longer sides allow for ion bridging between the grafted chains and the cellulose surface without a significant change in main chain conformation. This leads to the brush structure being less sensitive to changes in salt concentration.

1) Background: Recently, illegal abuse of γ-hydroxybutyric acid (GHB) has increased in drug-facilitated crimes, but determination of GHB exposure and intoxication is difficult due to rapid metabolism of GHB. Its biochemical mechanism has not been completely investigated. And metabolomic study by polyamine profile and pattern analyses was not performed in rat urinefollowing intraperitoneal injection with GHB. 2) Methods: Polyamine profiling analysis by gas chromatography-mass spectrometry combined with star pattern recognition analysis was performed in this study. Multivariate statistical analysis was used to evaluate discrimination between control and GHB administration groups. 3) Results: Six polyamines were determined in control, single and multiple GHB administration groups. Star pattern showed distorted hexagonal shapes with characteristic and readily distinguishable patterns for each group. N¹-Acetylspermine (p < 0.001), putrescine (p <0.006), N¹-acetylspermidine (p <0.009), and spermine (p < 0.027) were significantly increased in single administration group but were significantly lower in the multiple administration group than in the control group. N¹-Acetylspermine was the main polyamine for discrimination between control, single and multiple administration groups. Spermine showed similar levels in single and multiple administration groups. 4) Conclusions: The polyamine metabolic pattern was monitored in GHB administration groups. N¹-Acetylspermine and spermine were evaluated as potential biomarkers of GHB exposure and addiction.

The food additive sorbic acid is considered as an effective preservative for certain cereal products, and propionic acid is commonly added in bakery wares, e.g. bread and fine bakery wares. The aim of this study is to develop and validate a new nuclear magnetic resonance spectroscopy (¹H NMR) method for routine screening and quantification of sorbic and propionic acids in bread and several bakery products for quality control purposes. Results showed that none of the screened samples contained higher concentrations than regulatory maximum limits. However, for some samples, labelling of preservatives was lacking or they were used in food categories, for which the use is not approved. It can be concluded that the developed NMR method can be used for routine screening of bakery products.

To evaluate the behaviour of the relevant microbial populations during stretched cheese production, the quantitative microbiological analysis was performed during the critical steps of the preparation. The obtained data distributions proved statistically significant increases in all indicators, on average by 4.55 ± 0.64 log CFU/g of presumptive lactococci counts, 4.06 ±0.61 of lactobacilli, 1.53 ± 0.57 log CFU/g of coliforms, 2.42 ± 0.67 log CFU/g of Escherichia coli, 1.53 ± 0.75 log CFU/g of yeasts and moulds, and 0.99 ± 0.27 log CFU/g of presumptive Staphylococcus aureus, from the early stage of milk coagulation until curd ripening (0–24 h). The following steaming/stretching process caused reductions in viable counts with the most significant inactivation effect on coliform bacteria, including E. coli (-4.0 ± 1.0 log CFU/g). Total viable counts and yeasts and moulds showed 2 and almost 3 log reduction (-2.2 ± 1.1 log CFU/g and -2.6 ± 0.9 log CFU/g), respectively. The lowest decreases in presumptive S. aureus counts were estimated at the level of -1.50 ± 0.64 log CFU/g. The counts of yeasts and moulds showed the best indicatory function during the entire storage period of vacuum-packaged cheeses at 6 °C.

The early diagnosis of mastitis represents an essential factor for a prompt detection of the animal for further actions. In fact, if not culled, infected cows must be segregated from the milking herd and milked last, or milked with separate milking units. Besides microbiological analysis, the somatic cell count (SCC) commonly used as predictor of intramammary infection, frequently lead to a misclassification of milk samples. To overcome these limitations, more specific biomarkers are continuously evaluated. Total amino acid content increases significantly in mastitic milk compared to normal one. Bovine mastitis can arise as a result of infection of the mammary gland by Staphylococcus aureus. Multiplication of this bacterium within the mammary gland is required for infection to persist. S. aureus requires branched-chain amino acids (BCAAs: isoleucine, leucine, valine) for protein synthesis, branched-chain fatty acids synthesis and environmental adaptation by responding to their availability via transcriptional regulators. The importance of BCAAs for S. aureus physiology necessitates that it either synthesize them or scavenge them from the environment. Increase of BCAAs in composite milk has been postulated to be linked to mammary infection by S. aureus. In the present work, we demonstrated, by a direct ion-pairing reversed-phase method based on the use of the evaporative light-scattering detector (IP-RP-HPLC-ELSD), applied to 65 composite cow milk samples, a correlation between the concentration of isoleucine and leucine and S. aureus load.

This work aims to investigate systematically the influence of process temperature and biomass-to-water ration on the chemical composition of aqueous and gaseous phases and mass production of chemical by hydrothermal processing of Açaí (Euterpe Oleraceae, Mart.) seeds. The hydrothermal carbonization carried out at 175, 200, 225, and 250 °C, 2 °C/min, biomass-to-water ratio of 1:10, and at 250 °C, 2 °C/min, and biomass-to-water ratios of 1:10, 1:15, and 1:20, in technical scale. The chemical composition of aqueous phase determined by GC and HPLC and the volumetric composition of gaseous phase by using an infrared gas analyzer. For constant biomass-to-water ratio of 1:10, the yields of solid, liquid, and gaseous phases varied between 53.39 and 37.01% (wt.), 46.61 and 59.19% (wt.), and 0.00 and 3.80% (wt.), respectively. The yield of solids shows a smooth exponential decay with temperature, while that of liquid and gaseous phases a smooth growth. By variation of biomass-to-water ratios, the yields of solid, liquid, and gaseous reaction products varied between 53.39 and 32.09% (wt.), 46.61 and 67.28% (wt.), and 0.00 and 0.634% (wt.), respectively. The yield of solids decreases exponentially with increasing water-to-biomass ratio and that of liquid phase increases in a sigmoid fashion. For constant biomass-to-water ratio, the concentrations of Furfural and HMF decrease drastically with temperature, reaching a minimum at 250 °C, while that of phenols increases. In addition, the concentrations of CH3COOH and total carboxylic acids increase, reaching a maximum at 250 °C. For constant process temperature, the concentrations of aromatics vary smoothly with the temperature. The concentrations of furfural, HMF, and cathecol decrease with temperature, while that of phenols increases. The concentrations of CH3COOH and total carboxylic acids decrease exponentially with temperature. Finally, for the experiments with varying water-to-biomass ratios, the productions of chemicals (furfural, HMF, phenols, cathecol, and acetic acid) in the aqueous phase is highly dependent on the biomass-to-water ratio.

This study was aimed to investigate the effect of xylan depolymerizing enzyme namely endo-xylanase (Xyn) combined with debranching enzymes namely arabinofuranosidase (Afd) and feruloyl esterase (FE) on digestion, growth performance and intestinal volatile fatty acid profile of piglets. The in vitro experiments were firstly conducted to examine the enzymological properties of Xyn, Afd and FE, the synergy among these enzymes, together with the effect of combination of these enzymes on digestion of piglet diet. The in vivo experiment was then implemented by allocating 270 35-d-old postweaning piglets into 3 treatment groups: control group, Xyn group and (Xyn+Afd+FE) group. Each group had 6 replicates (15 piglets/replicate). The results revealed a satisfying thermostability and pH stability of Xyn, Afd and FE. Combination of Xyn, Afd and FE had a superiority (P < 0.05) over Xyn alone and its combination with Afd or FE in promoting degradation of different bran fibers rich in arabinoxylan (Abx). Treatment with combination of Xyn, Afd and FE had advantages over Xyn alone to induce increasing trends (P < 0.10) of in vitro digestibility of dietary nutrients (dry matter, crude protein, crude ash and gross energy) and piglet growth performance (average daily gain, final body weight and feed efficiency), concurrent with a reduction (P < 0.05) of diarrhea rate and increases (P < 0.05) in cecal acetic acid, butyric acid and total volatile fatty acids concentrations as well as pH value of piglets. Collectively, combination of Xyn, Afd and FE was efficient in benefiting degradation of Abx in brans, as well as improving digestion, growth performance and intestinal volatile fatty acid profile of piglets.

Mitochondrial dysfunctions, e.g. abnormal handling of mitochondrial DNA in TFAM mutants or in altered mitophagy, activate innate immunity. Recent reports also showed that deletion of mitochondrial matrix peptidase ClpP in mice transcriptionally upregulates inflammatory factors. Here, we studied ClpP-null mouse brain at two ages and embryonal fibroblasts, to identify which signaling pathways are responsible, employing mass spectrometry, immunoblots, and reverse transcriptase polymerase chain reaction. Anomalies in the mitochondrial unfolded protein responses pathway were prominent for the co-chaperone DNAJA3, and for its known interactor STAT1. Their mitochondrial dysregulation affected also their extra-mitochondrial abundance, as possible innate immune modulators. Increased expression was observed not only for the transcription factors Stat1/2, but also for two interferon-stimulated genes (Ifi44, Gbp3). Inflammatory responses were strongest for RLR pattern recognition receptors (Ddx58, Ifih1, Oasl2, Trim25) and several cytosolic nucleic acid sensors (Ifit1, Ifit3, Oas1b, Ifi204, Mnda). They can be explained by the accumulation of mitoribosomes and mitochondrial nucleoids in ClpP-null cells, which may act as damage-associated molecular patterns. The consistent dysregulation of these factors from early age might influence also human Perrault syndrome, where ClpP loss-of-function leads to early infertility and deafness, with subsequent widespread neurodegeneration.

Titanium micro-scale topography results in excellent osteoconductivity and bone-implant integration. However, the biological effects of sub-micron topography are unknown. We compared osteoblastic phenotypes and in vivo bone and implant integration abilities between titanium surfaces with micro- (1–5 µm) and sub-micro-scale (0.1–0.5 µm) topographies and machined titanium. Average roughness was 12.5 ± 0.65 nm, 123 ± 6.15 nm, and 24 ± 1.2 nm for machined, micro-rough, and sub-micro-rough surfaces, respectively. The micro-rough surface showed the fewest cells attaching during the initial stage and the lowest proliferation. Calcium deposition and expression of osteoblastic genes were highest on the sub-micro-rough surface and lowest on the machined surface. Bone-to-implant integration was strongest for the micro-rough surface, consistent with it having the greatest ability to retain cells in vitro. Thus, the biological effects of titanium surfaces are not necessarily proportional to the degree of roughness in osteoblastic cultures or in vivo. Sub-micro-rough titanium ameliorates the disadvantage of micro-rough titanium by restoring cell attachment and proliferation and enhances the rate of osteoblastic differentiation over that of micro-rough titanium; however, bone integration and the ability to retain cells are compromised due to its lower interfacial mechanical locking compared to that of micro-rough titanium.

The interrelationship between periodontal disease, obesity-related hyperlipidemia and mechanical forces as well as their modulating effects on the epigenetic profile of periodontal ligament (PdL) cells are assumed to be remarkably complex. The PdL serves as connective tissue between teeth and alveolar bone for pathogen defense and inflammatory response to mechanical stimuli occurring during tooth movement. Altered inflammatory signaling could promote root resorption and tooth loss. Hyperinflammatory COX2/PGE2 signaling was reported for human PdL fibroblasts (HPdLF) concomitantly stressed with P. gingivalis lipopolysaccharides and compressive force after exposure to palmitic acid (PA). The aim of this study was to investigate to what extent this is modulated by global and gene-specific changes in histone modifications. Quantitative expression of epigenetic key players and global H3Kac as well as H3K27me3 levels were evaluated in dual stressed HPdLF exposed to PA revealing a decreased force-related reduction in repressive H3K27me3. UNC1999-induced H3K27me3 inhibition reversed the hyperinflammatory response of dual-stressed PA-cultures characterized by COX2 expression, PGE2 secretion and THP1 adhesion. Reduced expression of the anti-inflammatory cytokine IL10 and increased association of H3K27me3 at its promoter-associated sites were reversed by inhibitor treatment. Thus, the data highlight an important epigenetic interplay between different stimuli to which the PdL is exposed.

The objective of this study was to evaluate the efficacy of one-step nucleic acid amplification (OSNA) for the detection of sentinel lymph node (SLN) metastasis compared to standard pathological ultrastaging in patients with early-stage endometrial cancer (EC). A total of 526 SLNs from 191 patients with EC were included in the study. 379 SLNs (147 patients) were evaluated by both methods, OSNA and standard pathological ultrastaging. The central 1-mm portion of each lymph node was subjected to semi-serial sectioning at 200-μm intervals and examined by hematoxylin-eosin and immunohistochemistry with CK19; the remaining tissue was analysed by OSNA for CK19 mRNA. The OSNA assay detected metastases in 19.7% of patients (14.9% micrometastasis and 4.8% macrometastasis), whereas pathological ultrastaging detected metastasis in 8.8% of patients (3.4% micrometastasis and 5.4% macrometastasis). Using the established cut-off value for detecting SLN metastasis by OSNA in EC (250 copies/μl), the sensitivity of the OSNA assay was 92%; specificity was 82%; diagnostic accuracy was 83%, and the negative predictive value was 99%. Discordant results between both methods were recorded in 20 patients (13.6%). OSNA resulted in an upstaging in 12 patients (8.2%). OSNA could aid in the identification of patients requiring adjuvant treatment at the time of diagnosis.

The research progress of nano-hydroxyapatite and its composite biomaterials, which are widely used, is summarized. The preparation techniques and applications of nano-hydroxyapatite and its composites in tissue engineering scaffolds, sustained and controlled release drug carriers, targeting drug delivery and environmental functional materials show that nano-hydroxyapatite and its composites will have good prospects in the field of biomedicine. The nano-hydroxyapatite composite biomaterial is a first phase or multi-phase material added to the nano-hydroxyapatite to obtain a favorable histological reaction, satisfactory strength and rigidity, and to synthesize a scaffold material for tissue regeneration. As a scaffold for guiding bone tissue regeneration, nano-hydroxyapatite composite material can also be used as a targeted drug release system for drug delivery system. It has good biocompatibility and degradability and has become a research hotspot in bone tissue engineering. The complex is expected to be applied to medical diagnostic fields such as tumor cell detection and nano biological probes.

The phenylpropanoid pathway is a major secondary metabolite pathway that helps plants overcome biotic and abiotic stress and produces various by-products that promote human health. Its byproduct, chloroquinic acid (CQA), is a soluble phenolic compound present in many angiosperms. Hy-droxycinnamate-CoA shikimate/quinate transferase(BAHDs superfamily enzyme) is a significant en-zyme that plays a role in accumulating CQA biosynthesis. This study analyzed transcriptome-wide identification of the phenylpropanoid to chloroquinic acid biosynthesis candidate genes in A. spathulifolius flowers and leaves. Transcriptomic analyses of the flowers and leaves showed a differential expression of the PPP and CQA biosynthesis regulated unigenes. An analysis of PPP captive unigenes revealed the following: the major duplication of the key enzyme, PAL, 120 unigenes in leaves and 76 in flowers; the gene encoding C3’H, 169 unigenes in leaves and 140 unigenes in flowers; duplicated unigenes of 4CL, 41 in leaves and 27 in flowers. In addition, C4H unigenes had 12 unigenes in the leaves of A. spathulifolius and four in the flowers. The characterization of the BAHDs superfamily members identified 82 in leaves and 72 in flowers. Among them, phylogenetic analysis showed that five unigenes encoded HQT and three en-coded HCT in A. spathulifolius. The three HQT are common to both leaves and flowers, whereas the two HQT were specialized for leaves. The pattern of HQT synthesis was upregulated in flowers, whereas HCT was expressed strongly in the leaves of A. spathulifolius. Overall, 4CL, C4H, and HQT are expressed strongly in flowers, and caffeic acid and HCT show more expression in leaves. Therefore, CQA biosynthesis occurs in the flowers of A. spathulifolius rather than leaves.

This study aimed to identify new drug molecules against Leishmania parasites, leishmaniasis's causal agent, using Pistacia atlantica leaves as source. The evaluation of the anti-leishmania potential against the promastigote form of Leishmania. infantum and Leishmania. major was performed. A new in silico study was accomplished using molecular docking, with Autodock vina program, to find the binding affinity of two important phytochemical compounds from this plant (Masticadienonic acid, 3-Methoxycarpachromene) towards the trypanothione reductase as target drugs, responsible for defence mechanism against oxidative stress and virulence of this parasites. Results: Several concentrations showed a significant decrease in cell viability (P<0.0001), with IC50 values of 0.3 mg/ mL for L. infantum and 0.12 mg/ mL L. major; The molecular docking confirms the significant relationship between Leishmania survival and the inhibition of this crucial enzyme. There were promising and new positive results on binding modes of selected ligands and the trypanothione reductase for the first time. Through this work, we propose 3-Methoxycarpachromene and Masticadienonic acid as anti Trypanosomatidae species drug.

Residential dust is recognized as a major source of environmental contaminants, including polycyclic aromatic hydrocarbons (PAHs) and phthalic acid esters (PAEs). To characterize the thoracic dust fraction (PM10), a sampling campaign was carried out with an in-situ resuspension chamber in three rooms (kitchen, living room and bedroom) of four Spanish houses. Two samples per room were collected with, at least, a one-week interval. The PM₁₀ samples were analyzed for their carbonaceous content by a thermo-optical technique and, after solvent extraction, for 20 PAHs, 8 phthalate plasticizers (PAEs) and one non-phthalate plasticizer (DEHA) by gas chromatography-mass spectrometry. In general, higher dust loads were observed for parquet flooring compared with tile. The highest dust loads were obtained for rugs. Total carbon accounted for 9.3 to 51%wt of the PM₁₀ mass. Plasticizer mass fractions varied from 5 µg g-1 to 17 mg g^-1 PM₁₀, whereas lower contributions were registered for PAHs (0.98–116 µg g^-1). The plasticizer and PAH daily intakes for children and adults via dust ingestion were estimated to be 3–4 orders of magnitude higher than those via inhalation and dermal contact. Potential carcinogenic and negligible non-carcinogenic risks arising from exposure to PAHs were found.

Four naturally occurring zeolites AZLB-Ca and AZLB-Na (Bowie, Arizona), NM-Ca (Winston, New Mexico), and NV-Na (Ash Meadows, Nevada) were studied to evaluate structural modifications after treatment with HCl acid. AZLB-Ca and AZLB-Na are chabazite-like species and become amorphous when boiled in concentrated HCl acid as confirmed by powder X-ray diffraction. In contrast, NM-Ca and NV-Na which are clinoptilolite-like species withstood boiling in concentrated HCl acid. This treatment removes calcium, magnesium, sodium, potassium, aluminum, and iron atoms or ions from the framework while leaving the silicon framework intact as confirmed via X-ray fluorescence and diffraction. SEM images on calcined and HCl treated NV-Na were obtained. BET surface area analysis confirmed an increase in surface area for the two zeolites after treatment, NM-Ca (20.0(1) to 111(4) m2/g) and NV-Na (19.0(4) to 158(7) m2/g). 29Si and 27Al MAS NMR were performed on the natural and treated NV-Na zeolite and the data for the natural NV-Na zeolite suggested a Si:Al ratio of 4.33 similar to that determined by X-Ray fluorescence of 4.55. Removal of lead ions from solution decreased from the native (NM-Ca, 0.27(14), NV-Na, 1.50(17) meq/g) compared to the modified zeolites (30 min HCl treated NM-Ca 0.06(9) and NV-Na, 0.41(23) meq/g) and also decreased upon K+ ion pretreatment in the HCl modified zeolites.

BODIPY dyes have recently raised attention as potential photosensitizers. In this work, commercial and novel photosensitizers (PSs) based on BODIPY chromophores (haloBODIPYs and orthogonal dimers strategically designed with intense bands in the blue, green or red region of the Visible spectra and high singlet oxygen production) were covalently linked to mesoporous silica nanoparticles (MSNs) further functionalized with PEG and folic acid (FA). MSNs of approximately 50 nm in size with different functional groups were synthesized to allow multiple alternatives of PS-PEG-FA decoration of their external surface. Different combinations varying the type of PS (commercial Rose Bengal, Thionine and Chlorine e6 or custom-made BODIPY-based), the linkage design and the length of PEG are detailed. All the nanosystems were physicochemically characterized (morphology, diameter, size distribution and PS loaded amount) and photophysically studied (absorption capacity, fluorescence efficiency, and singlet oxygen production) in suspension. For the most promising PS-PEG-FA silica nanoplatforms, the biocompatibility in dark conditions and the phototoxicity under suitable irradiation wavelengths (blue, green, or red) at regulated light doses (10-15 J/cm2) were compared with PSs free in solution in HeLa cells in vitro.

The Ijen volcano has Pleistocene age (294.00 ± 0.03 Ma), and this stratovolcano was very acidic crater water with a pH of 0-1. The acidic crater water seeps into the Banyupait river flow. Asembagus is a research area located on the northern slope of the Ijen volcano, and the Banyupait River drains this. The acidic river water flows from the Ijen Crater Lake, so the pH of the water river was very acidic. This study used several different analytic methodologies with some previous researchers, namely using the method of geological mapping, pH measurement, spectrophotometry, IRMS (Isotope Ratio Mass Spectrometer), and the technique of Induced Coupled Mass Spectrometry (ICP-MS). Besides, the petrographic analysis is used to determine the composition of rock minerals due to rocks interacting with acidic water. Banyupait River water in the Asembagus area has a pH of river water around 3-7.3, SO4 (220-683 ppm), and the type of water is meteoric water. Also, concentrations of Ca, K, Mg in the west Banyupait river irrigation water flow showed higher levels when compared to the eastern Banyupait River water flow. Likewise, REE elements from the Asembagus region showed lower concentrations compared to Ijen Crater water. This change in the level of chemical elements is caused by the acidity of the Banyupait River being diluted or mixed with water from other water. However, the spring was not affected by acidic water. The process of acidic water interaction with rocks can also be observed from rocks traversed by the Banyupait River flow. Chalcedony and hematite replace the primary minerals of basaltic rocks. This research is expected to improve the quality of water needed by the Asembagus community so that people can live healthily.

Nanoparticles of graphene and carbon nanotubes are attractive materials for improvement of mechanical and barrier properties and functionality of biodegradable polymers for food packaging applications. However, the increase of the manufacture and consumption increases the probability of exposure of human and environment to such nanomaterials, this rising questions about the risks of nanomaterials since they can be toxic. For a risk assessment, it is crucial to know whether airborne nanoparticles of graphene and carbon nanotubes can be released from nanocomposites into the environment at their end-life, or they remain embedded in the matrix. In this work the release of graphene and carbon nanotubes from the poly(lactic) acid nanocomposite films were studied for the scenarios of: (i) biodegradation of matrix polymer at the disposal of wastes; and (ii) combustion and fire of nanocomposite wastes. Thermogravimetric analysis in air atmosphere, TEM, AFM and SEM were used to verify the release of nanoparticles from nanocomposite films. The three factors model was applied for the quantitative and qualitative risk assessment to the release of graphene and carbon nanotubes from nanocomposite wastes for these scenarios. Safety concern is discussed in respect to the existing regulations for nanowastes stream.

Deuterostomes make a sudden appearance in the fossil record during the Early Cambrian. Two deuterostome groups, the chordates and the vetulicolians, are of particular interest for understanding the evolutionary dynamics of the Cambrian evolutionary event. Lagerstätten in China and elsewhere have dramatically improved our understanding of the range of variation in these ancient animals. Cephalochordate and vertebrate body plans are well established at least by Cambrian Series 2. Taken together, roughly a dozen chordate genera and fifteen vetulicolian genera document an explosive radiation of deuterostomes at the base of the Cambrian. A new vetulicolian (••• nov. gen. nov. sp.) with a polygonal anterior section and a narrow, unsegmented posterior region (‘tail’) bearing possible myotomes provides new insight into the affinities of the various body plans that emerged during the Early Cambrian. It seems clear that the advent of deuterostomes near the Cambrian boundary involved both a reversal of gut polarity and a two-sided retinoic acid gradient, with a gradient discontinuity at the midpoint of the organism that is reflected in the sharp division of vetulicolians into anterior and posterior sections.

Long-chain omega-3 fatty acid status during pregnancy may influence newborn anthropometry and duration of gestation. Evidence from high-quality trials from LMICs is limited. We conducted a double-blind, randomized, placebo-controlled trial among 957 pregnant women (singleton gestation, 14-20 weeks’ gestation at enrollment) in India to test the effectiveness of 400 mg/d algal docosahexaenoic acid (DHA) compared to placebo provided from enrollment through delivery. Among 3379 women who were screened, 1171 were found eligible; 957 enrolled and were randomized. The intervention was two microencapsulated algal DHA (200 X 2= 400 mg/d) or two microencapsulated soy and corn oil placebo tablets to be consumed daily from enrollment (20 weeks) through delivery. The primary outcome was newborn anthropometry (birth weight, length, head circumference). Secondary outcomes were gestational age and 1 and 5 min Appearance, Pulse, Grimace, Activity, and Respiration (APGAR) score. The groups (DHA; n=478 and placebo; n=479) were well balanced at baseline. There were 902 live births. Compliance with the intervention was similar across groups (DHA: 88.5%; placebo: 87.1%). There were no significant differences between DHA and placebo group for birth weight (2750.6 ± 421.5 vs. 2768.2 ± 436.6 g, p=0.54), length (47.3 ± 2.0 vs. 47.5 ±2.0 cm, p=0.13) or head circumference (33.7 ± 1.4 vs 33.8 ± 1.4 cm, p=0.15). The mean gestational age at delivery was similar between groups (DHA: 38.8 ± 1.7 placebo: 38.8 ± 1.7 wk, p= 0.54) as were APGAR scores at 1 and 5 min. Supplementing mothers through pregnancy with 400mg/d DHA did not impact the offspring birthweight, length or head circumference.

Gambogic acid, a common traditional Chinese medicine and widely distributed throughout South China, Vietnam, Cambodia, and Thailand. It is prenylated xanthone which is the significant bioactive compound of gamboge. Gambogic acid is known as a strong apoptotic inducer in cancer cells. It has been found as strong anticancer agent against various types of cancer cells lines such as breast cancer, pancreatic, and cervical cancer. It induces apoptosis, down regulates the anti-apoptotic proteins (survivin and BCL2,) and down regulates the activities of P-glycoprotein in drug sensitive human breast MCF-7 and drug-resistant MCF-7/ADR cells. Similarly, it also exerts alteration in P13K, AKT, p21, MMP-2 &-9, and phosphorylated-AKT expressions. The current review highlights the anticancer and chemo-preventive perspectives of gambogic acid and its mechanistic role against human and animal cancers.

Plukenetia volubilis is an underutilized oilseed crop native to the Amazon basin, where it has been utilised by humans since Incan times. The large seeds contain approx. 45–50 % lipid, of which approx. 35.2–50.8 % is α-linolenic acid (C18:3 n-3, ω-3) and approx. 33.4–41.0 % is linoleic acid (C18:2 n-6, ω-6), the two essential fatty acids required by humans. The seeds also contain 22–30 % protein and have antioxidant properties. Due to its excellent nutritional composition and good agronomic properties, it has attracted increasing attention in recent years, and cultivation is expanding. When considering current global challenges, a reformation of our food systems is imperative in order to ensure food security, mitigation of climate change, and alleviation of malnutrition. For this purpose, underutilized crops may be essential tools, which can provide agricultural hardiness and reduced need for external inputs, climate resilience, diet diversification, and improved income opportunities for smallholders. Plukenetia volubilis is a promising up and coming crop in this regard and has considerable potential for further domestication; it has an exceptional oil composition, good sensory acceptability, is well suited for cultivation, and has numerous potential applications in, e.g. gastronomy, medicine, and cosmetics.

Salinity is a serious environmental hazard which limits world agricultural production by adversely affects plant physiology and biochemistry. Hence increase tolerance against salt stress is very important. In this study, we explored the function of β-aminobutyric acid (BABA) in enhancing salt stress tolerance in rapeseed (Brassica napus L.). After pretreatment with BABA, seedlings were exposed to NaCl (100 mM and 150 mM) for 2 days. Salt stress increased Na content and decreased K content in shoot and root. It disrupted the antioxidant defense system by producing reactive oxygen species (ROS; H2O2 and O2•−), methylglyoxal (MG) content and causing oxidative stress. It also reduced the growth and photosynthetic pigments of seedlings but increased proline (Pro) content. However, BABA pretreatment in salt-stressed seedlings increased ascorbate (AsA) and glutathione (GSH) contents; GSH/GSSG ratio; and the activities of ascorbate peroxidase (APX), monodehydroascorbate reductase (MDHAR), dehydroascorbate reductase (DHAR), glutathione reductase (GR), glutathione peroxidase (GPX), superoxide dismutase (SOD), catalase (CAT), glyoxalase I (Gly I), and glyoxalase II (Gly II) as well as growth and photosynthetic pigments of plants. In addition, compared to salt stress alone BABA increased Pro content, reduced the H2O2, MDA and MG contents and decreased Na content in root and increased K content in shoot and root of rapeseed seedlings.

This work reports of the use of a bench scale chemostat (CSTR) in continuous mode and of a pilot scale membrane bioreactor (MBR) in fed-batch mode to intensively produce acetic and butyric acids using Cl. butyricum grown on synthetic media. These studies were then used to perform a cost estimation study of the MBR system to assess the potential economic impact of this proposed methodology. The MBR system was found highly productive reaching 37.88 g L-1 h-1 of acetic and 14.44 g L-1 h-1 of volumetric cell productivity, favoring acetic acid production to butyric at a ratio 3:1. The cost of preparation and production of carboxylic acids using this system was found as 0.0062 £PS/kg respectively and an up to 99% carbon recovery.

Milk fat production is important in the New Zealand (NZ) dairy industry. Elsewhere, an amino acid substitution (K232A) in the enzyme diacylglycerol acyl-CoA acyltransferase (DGAT1) has been reported to explain variation in some milk traits, including variation in milk fatty acid (FA) profile. In this study, associations between K232A, and milk traits including milk FA composition, were studied in wholly pasture-fed NZ Holstein-Friesian × Jersey (HF×J) cross-bred dairy cows. With a high frequency of K variant (61.9%), the KK cows produced more milk fat than the AA cows (5.41 ± 0.04 % vs 4.42 ± 0.05 %). The milk volume, fat concentration and protein concentration of AK cows were between the genotypes, AA and KK. More C16:0, CLA and C18:3 cis-9, 12, 15 FA were found in the milk of Kiwi-cross cows feed in outdoor pasture grazing system., and the influence of DGAT1 K232A, on these FAs from mid- and late lactation stages were significant. The AA cows produced (P < 0.001) more CLA and C18:3 cis-9, 12, 15, but less C16:0 (1.137 ± 0.047, 0.855 ± 0.015 and 35.170 ± 0.355) than the KK cows (0.934 ± 0.025, 0.778 ± 0.009 and 38.010 ± 0.250).

Targeted therapies with antiangiogenic drugs (e.g., sunitinib) and immune checkpoint inhibitors (e.g., anti-PD-1 antibodies) are the standard of care for patients with metastatic renal cell carcinoma. Although these treatments improve patient survival, they are rarely curative. We previously hypothesized that advanced cancers might be treated without drugs by using artificial diets in which the levels of specific amino acids (AAs) are manipulated. In this work, after showing that AA manipulation induces selective anticancer activity in renal cell carcinoma cells in vitro, we evaluated the anticancer activity of 17 artificial diets in a challenging animal model of renal cell carcinoma. The model was stablished by injecting murine renal cell carcinoma (Renca) cells into the peritoneum of immunocompetent BALB/cAnNRj mice. Mice survival was markedly improved when their normal diet was replaced with our artificial diets. Mice fed a diet lacking six AAs (diet T2) lived longer than mice treated with sunitinib or anti-PD-1 immunotherapy; several animals lived very long or were cured. Controlling the levels of several AAs (e.g., cysteine, methionine and leucine) and lipids was important for the anticancer activity of the diets. Additional studies are needed to further evaluate the therapeutic potential of this simple and inexpensive anticancer strategy.

The evolutionary success of land plants largely relies on their ability to cope with constant environmental fluctuations, which negatively impact their reproductive fitness and trigger adaptational responses to biotic and abiotic stresses. In this challenging scenario, comprehensive research efforts so far aimed at depicting the roles of well-known phytohormones, mainly auxins, along with brassinosteroids, jasmonates, and abscisic acid, although the signaling networks coordinating the crosstalk among them remains vaguely understood. Accordingly, this review focuses on the Arabidopsis Amidase Signature (AS) superfamily members, highlighting the hitherto relatively underappreciated functions of AMIDASE1 (AMI1) and FATTY ACID AMIDE HYDROLASE (FAAH), as crucial coordinators of the growth-defense response trade-off by modulating auxin and ABA homeostasis.

Pentadecanoic acid (C15:0) and heptadecanoic acid (C17:0) have been described as dietary biomarkers of dairy-fat consumption with varying degrees of reliability between studies. It remains unclear how the total amount of dietary fat; one of the main confounding factors in these biomarker investigations, affects C15:0 and C17:0 circulating compositions independently to their relative intake. Additionally, it is unknown how changes in the dietary total-fat affects other fatty acids in circulation. Through two dietary studies with different total-fat levels but maintaining individual fatty acid compositions we were able to see how the dietary total-fat affects the fatty acids in circulation. We saw that there was a significant, proportionate, and robust decrease in the endogenous C15:0 levels with an increase in dietary total-fat. However, there was an increase in the circulating C17:0 compositions as the total-fat increased. To conclude, the dietary total-fat content and fat-type have a very complex influence on the relative compositions of circulating fatty acids, which are independent to the actual dietary fatty acid composition. Knowing how to manipulate circulating C15:0 and C17:0 composition is far-reaching in nutritional/pathological research as they highlight a dietary route to attenuate the development of metabolic disease (both by reducing risk and improving prognosis).

Background Natural Saccharomyces cerevisiae yeast strains exhibit very large genotypic and phe-notypic diversity. Breeding programs taking advantage of this characteristic, are widely used for yeast selection in the wine industry, especially in the recent years when winemakers need to adapt their production to climate change. The aim of this work was to evaluate a Marker Assisted Se-lection (MAS) program to improve malic acid consumption capacity of Saccharomyces cerevisiae in grape juice. Methods Optimal individuals of two unrelated F1-hybrids were crossed to get a new genetic background carrying many “malic consumer” loci. Then, eleven QTLs already identified were used for implementing the MAS breeding program. Results By this way, extreme individuals able to consume more than 70% of malic acid in grape juice were selected. These individuals were tested in different enological matrixes and compared to their original parental strains. They greatly reduced the malic acid content at the end of alcoholic fermentations, they appeared to be robust to the environment and accelerate the ongoing of malo-lactic fermentations by Oenococcus oeni. Conclusions This study illustrates how MAS can be efficiently used for selecting industrial Saccharomyces cerevisiae strains with outlier properties for winemaking.

Mining-induced water contamination remains a significant concern in many regions of the world due to the high concentrations of toxic ions often associated with it. In this study, cellulose-supported ferrihydrite composites (CNF-Fe) were prepared by seeding of ferrihydrite nanoparticles on cellulose nanofibres (CNFs) and employed for the removal of As(III), As(V) and Cr(VI) from contaminated water. The adsorbent was characterized by electron microscopy, gas adsorption, point of zero charge (pH_PZC), X-ray diffractometry (XRD), as well as infrared and Raman spectroscopy. Compared to parent CNFs, CNF-Fe adsorbents had lower crystallinity and a higher surface area: 218.76 m² g^-1. Further, with a pH_PZC of 6.3, CNF-Fe was positively charged at low pH and suitable for adsorption of anions at acidic conditions characteristic of acid mine drainage. In single-ions solutions, the removal efficiency of CNF-Fe was in the order Cr(VI)>As(V)>As(III) (i.e. 0.15, 0.12 and 0.11 mg g^-1 respectively). Adsorption kinetics followed the pseudo second-order model and isotherms were best fitted by the Freundlich, Dubinin-Radushkevich, and Temkin models. However, when CNF-Fe was applied to AMD-contaminated water (pH 2.7), Cr(VI) uptake decreased to ~39% which was likely due to competition from sulphate and selenium ions. Nevertheless, the adsorbent displayed regeneration capabilities with ~98% As and ~45% Cr desorbed after 24 hours of treatment. Together, these results suggest that cellulose supported ferrihydrite composites can be applied in treatment of mine drainage-contaminated water in conjunction with pre-treatments that limit SO₄^2- and selenium concentrations.

To understand the physiological basis of tolerance to combined stresses to low phosphorus (P) and drought in mungbean (Vigna radiata (L.) R. Wilczek), a core set of 100 accessions were evaluated in hydroponics at sufficient (250 μM) and low (3 μM) P, and exposed to drought (dehydration) stress. The principal component analysis and ranking of accessions based on relative values revealed that IC280489, EC397142, IC76415, IC333090, IC507340 and IC121316 performed superior while IC119005, IC73401, IC488526 and IC325853 performed poorly in all treatments. Selected accessions were evaluated in soil under control (sufficient P, irrigated), low P (without P, irrigated), drought (sufficient P, withholding irrigation) and combined stress (low P, withholding irrigation). Under combined stress, a significant reduction in gas exchange traits (photosynthesis, stomatal conductance, transpiration, instantaneous water use efficiency), P uptake in seed and shoot was observed under combined stress as compared to individual stresses. Among accessions, IC488526 was most sensitive while IC333090 and IC507340 exhibited tolerance to individual or combined stress. The water balance and low P adaptation traits like membrane stability index, relative water content, specific leaf weight, organic acid exudation, biomass, grain yield and P uptake can be used as physiological markers to evaluate for agronomic performance. Accessions with considerable resilience to low P and drought stress can be either used as ‘donors’ in Vigna breeding program or cultivated in areas with limited P and water availability or both.

A series of chiral complexes of the form Ir(NHC)2(aa)(H)(X) (NHC = N-heterocyclic carbene, aa = chelated amino acid, X = halide) was synthesized by oxidative addition of -amino acids to iridium(I) bis-NHC compounds and screened for asymmetric transfer hydrogenation of ketones. Following optimization of the reaction conditions, NHC, and amino acid ligands, high enantioselectivity was achieved when employing the Ir(IMe)2(l-Pro)(H)(I) catalyst (IMe = 1,3-dimethylimidazol-2-ylidene), which asymmetrically reduces a range of acetophenone derivatives in up to 95% enantiomeric excess.

(1) Background:A BMI &gt; 25 is the most decisive, albeit modifiable,risk factors for knee osteoarthritis (OA). This study aimed at assessing the efficacy of intra-articular injections of hybrid hyaluronic acid (HA) complexes (Synovial® H-L)for the treatment of kneeOA in overweight patientsin terms ofdisease severity, cardiocirculatory capacity, and quality of life. (2) Materials: In this single-site, open-label, prospective trial, 37 patients with symptomatic knee OA were assessed at baseline and 3 months after ultrasound-guided intra-articular injection of hybrid HA complexes (Synovial® H-L). (3) Results: Primary variables displaying a statistically significant improvement after treatment were pain (NRS), disease severity (WOMAC), and cardiopulmonary capacity a(6-Minute Walk Test). Among secondary variables, quality of life (SF-12) improved significantly, as did analgesic intake for pain control. No statistically significant difference was observed in body fat and muscle mass percentage measured by bioelectrical impedance analysis. (4) Conclusions:Intra-articular hybrid HA injections are significantly effective in improving OA-related disease severity, cardiopulmonary function, and analgesic intake. This supports the role of hybrid HA viscosupplementation as a non-pharmacological treatment to relieve pain, reduce disability and improve quality of life, and limit the risk of polypharmacy in overweight patients with knee OA.

We investigated effects of molecular hydrogen (H2) supplementation on acid-base status, pulmonary gas exchange responses, and local muscle oxygenation during incremental exercise. Eighteen healthy, trained subjects in a randomized, double-blind, crossover design received H2-rich calcium powder (HCP) (1500 mg/day, containing 2.544 µg/day of H2) or H2-depleted placebo (1500 mg/day) for 3 consecutive days. They performed cycling incremental exercise starting at 20-watts work rate, increasing by 20 watts/2 min until exhaustion. Breath-by-breath pulmonary ventilation (VE) and CO2 output (VCO2) were measured and muscle deoxygenation (deoxy[Hb + Mb]) was determined via time-resolved-NIRS in the vastus lateralis (VL) and rectus femoris (RF). Blood gases' pH, lactate, and HCO3− concentrations were measured at rest and 120-, 200-, and 240-watt work rates. At rest, the HCP group had significantly lower VE, VCO2, and higher HCO3−, PCO2 versus placebo. During exercise, a significant pH decrease and greater HCO3− continued until 240-watts work rate in HCP. The VE was significantly lower in HCP versus placebo, but HCP did not affect the gas exchange status of VCO2 or oxygen uptake (VO2). HCP increased absolute values of deoxy[Hb + Mb] at the RF but not VL. Thus, HCP-induced hypoventilation would lead to lower pH and secondarily impaired balance between O2 delivery and utilization in the local RF during exercise, suggesting that HCP supplementation, which increases the at-rest antioxidant potential, affects the lower ventilation and pH status during incremental exercise. HPC induced a significantly lower O2 delivery/utilization ratio in the RF but not the VL, which may be because these regions possess inherently different vascular/metabolic control properties, perhaps related to fiber-type composition.

Cationised hemp cellulose was prepared by etherification with two quaternary ammonium salts: 3-chloro-2-hydroxypropyl trimethyl ammonium chloride (CHPTAC) and glycidyltrimethylammonium chloride (GTMAC) and examined for (i) the efficiency of Cr(VI) removal under acid mine-drainage (AMD) conditions, and (ii) antibacterial activity. Adsorbents were characterised by electron microscopy, Fourier transform infrared (FTIR), CP-MAS ¹³C nuclear magnetic resonance (NMR) spectroscopy, elemental composition and surface charge. FTIR and solid state ¹³C NMR confirmed the introduction of quaternary ammonium moieties on cellulose. ¹³C NMR also showed that cationisation decreased the degree of crystallisation and lateral dimensions of cellulose fibrils. Nevertheless, 47 % - 72% of Cr(VI) ions were removed from solutions at pH 4, by 0.1 g of CHPTAC and GTMAC-cationised cellulose, respectively. Adsorption kinetics followed the pseudo-second order model and isotherms were best described by the Freundlich and Dubinin-Radushkevich models. When GTMAC-modified cellulose was applied to AMD contaminated water (pH 2.7), however, Cr(VI) uptake removal decreased to 22% likely due to competition from Al and Fe ions. Nevertheless, cationised materials displayed considerable antibacterial effects, reducing the viability of Escherichia coli by up to 45 % after just 3 hours of exposure. Together, these results suggest that cationised cellulose can be applied in the treatment of Cr(VI)-contaminated mine water particularly if pre-treatments to reduce Fe and Al concentrations are applied.

A new pathway leading to the n-10 fatty acid series has been recently evidenced, starting from sapienic acid - a monounsaturated fatty acid (MUFA) resulting from the transformation of palmitic acid by delta-6 desaturase. Sapienic acid attracts attention as novel marker of cancer cell plasticity. Here, we analyzed fatty acids including the n-10 fatty acid contents, and compared for the first time cell membranes and the corresponding extracellular vesicles (EV) of two human prostatic adenocarcinoma cell lines of different aggressiveness (PC3 and LNCaP). The n-10 components were 9-13% of the total fatty acids in both cancer cell lines and EVs, with total MUFA levels significantly higher in EVs of the most aggressive cell type (PC3). High sapienic/palmitoleic ratios indicated the preference for delta-6 vs. delta-9 desaturase enzymatic activity in these cell lines. The expressions analysis of enzymes involved in desaturation and elongation by qRT-PCR showed a higher desaturase activity in PC3 and a higher elongase activity toward polyunsaturated fatty acids than toward saturated fatty acids, compared to LNCaP cells. Our results improve the present knowledge in cancer fatty acid metabolism and lipid phenotypes, highlighting EV lipidomics to monitor positional fatty acid isomer profiles and MUFA levels in cancer.

The design of multifunctional microcarriers has attracted significant attention because they combine various functions within a single system. In this study, we developed a set of multi-layered hydrogel microcarriers, which were first loaded with chemotherapeutic curcumin (CUR), then using the layer-by-layer (LbL) technique, coated through a polyelectrolyte shell consisting of chitosan (CHIT) or poly(allylamine hydrochloride) (PAH). As an outer layer with antimicrobial function, newly synthesised alkylene quaternary ammonium salt functionalised polyelectrolytes (A-QAS-PEs) were applied. For this purpose, poly(acrylic acid) (PAA) was decorated with dif-ferent hydrophobic side chains (n-hexane and n-dodecane side entities) and different degrees of substitution (m) of quaternary ammonium groups (abbreviated as PAA-C(O)O-(CH2)n-N+(CH3)3(m); n=6,12; m=8-14%). The grafting approach of PAA with the al-kylene quaternary ammonium salt moiety was performed under mild reaction conditions using Steglich esterification followed by quaternisation. The structure of antimicrobial decorated PAA was confirmed by 1H NMR and FTIR, and the mean diameter of all multifunctional microparticles was characterised by SEM. The viscoelastic properties of the functional layers were studied using QCM-D. The release of CUR from the microcarriers was described using a hybrid model, i.e., a combination of first-order kinetics and the Korsmeyer-Peppas model. The antimicrobial activity of functionalised PAA and multilayered CUR-loaded hydrogel microcarriers with quaternary am-monium function was assessed against Staphylococcus aureus and Serratia marcescens by the agar diffusion assay method. Only a limited inhibition zone of PAA was observed, but in the case of both antimicrobial decorated PAA and the corresponding multilayered nanocarriers, the inhibi-tory activity increase was achieved against both strains of bacteria.

The effects of mixing orders of tannic acid (TA), starch and α-amylase on the enzyme inhibition of TA were studied, including mixing TA with α-amylase before starch addition (order 1), mixing TA with pre-gelatinized starch before α-amylase addition (order 2) and co-gelatinizing TA with starch before α-amylase addition (order 3). It was found that the enzyme inhibition was always highest for order 1 because TA could bind with the enzyme active site thoroughly before digestion occurred. Both order 2 and 3 reduced α-amylase inhibition through decreasing binding of TA with the enzyme, which resulted from the non-covalent physical adsorption of TA with gelatinized starch. Interestingly, at low TA concentration, α-amylase inhibition for order 2 was higher than order 3, while at high TA concentration, the inhibition was shown with opposite trend, which arose from the difference in the adsorption property between the pre-gelatinized and co-gelatinized starch at the corresponding TA concentrations. Besides, both the crystalline structures and apparent morphology of starch were not significantly altered by TA addition for order 2 and 3. Conclusively, although a polyphenol may have an acceptable inhibitory activity in vitro, the actual effect may not reach the expected one when taking processing procedures into account.

Accelerated degradation of collagen membranes (CMs) in diabetic rats is associated with increased infiltration of macrophages and blood vessels. Since pre-implantation immersion of CMs in cross-linked high molecular weight hyaluronic acid (CLHA) delays membrane degradation, we evaluated its effect on the number of macrophages and endothelial cells (ECs) within the CM. Diabetes was induced with streptozotocin in 16 rats, while 16 healthy rats served as control. CM discs were labeled with biotin, soaked in CLHA or PBS and implanted under the scalp. Fourteen days later, CMs were embedded in paraffin and the number of macrophages and ECs within the CMs was determined using antibodies against CD68 and Transglutaminase II, respectively. Diabetes increased the number of macrophages and ECs within the CMs (∼2.5-fold and 4-fold, respectively). Immersion of CMs in CLHA statistically significantly reduced the number of macrophages (p<0.0001) in diabetic rats, but not that of ECs. In the healthy group, CLHA had no significant effect on the number of either cells. Higher residual collagen area and membrane thickness in CLHA-treated CMs in diabetic animals were significantly correlated with reduced number of macrophages but not ECs. Immersion of CM in CLHA inhibits macrophage infiltration and reduces CM degradation in diabetic animals.

The host glycosylation mechanism synthesizes the carbohydrates of glycoproteins of viral envelopes. Due to the loss of the Cytidine Monophospho-N-Acetylneuraminic Acid Hydroxylase gene by some mammalian species, including humans (negative-CMAH), Neu5Gc is no longer synthesized. Uptake of Neu5Gc by negative-CMAH species, through the intake of food products derived from positive-CMAH mammals, leads to incorporating Neu5Gc-glycans in the glycocalyx (xenosialylation). Neu5Gc, being a Mammalian-associated Carbohydrate Antigen (MCA), acts as a non-self-antigen, inducing an inflammatory reaction (Xenosialitis), and triggering the production of circulating antiNeu5Gc antibodies to attack/remove all incorporated Neu5Gc. In the state of Xenosialitis, the virus-neutralizing antibodies produced by a heavily xenosialylated patient following exposure to viral infection (including SarsCoV2) or anti SarsCoV2 vaccination cross-react against all incorporated non-self Neu5Gc-MCA glycans due to their resemblance with viral envelope antigens synthesized by the host glycosylation mechanism. In addition, the circulating anti-XeSias antibodies determine the massive removal of the circulating neutralizing FC-xeno-contaminated antibodies by the serum, living only the hyper-inflammatory agalattosylated antiviral IgG antibodies. Therefore, we hypothesize that the combination of antibody cross-reaction against non-self Neu5Gc-MCA glycans and the massive removal of the xeno-contaminated newly formed neutralizing antibodies in favor of hyper reactive antibodies, could be the cause of the massive inflammatory reaction (cytokine storm, coagulopathies, neuropathies) observed in Covid 19 patients or after anti-SarsCoV2 vaccination. This analysis is an invitation to investigate the post-infectious and/or post-vaccination adverse phenomena in the light of xenosialization as a key to understanding the severe post viral and post vaccine complications, including SARS-CoV2 infection or related vaccination.

Three kinds of hydrophobic groups grafted starches of maleic anhydride grafted starch (MAH-g-starch), lactic acid grafted starch (LA-g-starch), and methyl acrylate grafted starch (MA-g-starch) were prepared by in-situ solid phase polymerization. The results of Fourier transform infrared spectroscopy (FT-IR) and X-ray photoelectron spectroscopy (XPS) were confirmed successful grafting. The grafting ratios of MAH-g-starch, LA-g-starch and MA-g-starch were 6.50%, 12.45%, and 0.57%, respectively. Influenced by the grafting ratio, LA-g-starch had the best hydrophobic properties and the largest molecular weight, and those for MA-g-starch was the worst. The surfaces of grafted starches were covered with graft polymer, with obvious surface roughness and bond degree of MAH-g-starch and LA-g-starch. The crystalline structure of grafted starches showed some damage, with LA-g-starch exhibiting the greatest decrease in crystallinity, and less of a change for MA-g-starch. Overall, the grafting reaction improved thermoplasticity, with LA-g-starch the most improved, followed by MAH-g-starch, and then MA-g-starch.

Microcephaly has been regarded the most remarkable consequence of the Zika virus (ZIKV) epidemic in Brazil 2015. It remains to be determined whether there are factors that contribute to the degree of brain lesion associated with ZIKV infection during pregnancy. Previous studies showed that socioeconomic conditions correlate with ZIKV-associated microcephaly. Certain nutritional deficits display the potential to interfere in the mechanistic target of rapamycin (mTOR) signaling, which plays a major role in the pathophysiology of ZIKV-associated microcephaly. We hypothesize that a nutritional or environmental co-factor that interferes in mTOR signaling correlates with ZIKV-associated birth defects. To assess this hypothesis, we plan to: 1) develop a mouse model of ZIKV-associated microcephaly through intravenous injection of ZIKV and rapamycin for a straightforward interference on mTOR receptor; 2) determine in the experimental model and in cases of ZIKV-associated microcephaly the epigenetic signature (DNA methylation pattern) in neurons and muscle cells harvested by biopsy, and in hematopoietic and mesenchymal stem cells sorted from blood; 3) analyze through mass spectrometry in serum of pregnant female mice submitted to ZIKV and rapamycin injection and in serum of mothers of children with ZIKV-associated microcephaly the metabolomic pattern of cholesterol (a nutritional status marker), vitamin A and its metabolite retinoic acid, folate, and other metabolites related to these three nutritional factors; 4) check whether pregnant female mice submitted to intravenous injection of ZIKV and feed with a deficient diet of the most likely co-factor found in this study give birth to microcephalic mice with features that mimic clinical cases. In summary, our general objective is to develop an experimental model that mimics ZIKV-associated microcephaly cases and to find a co-factor involved in the microcephaly outbreak in Brazil 2015.

The development of a highly specific drug delivery system (DDS) for anti-cancer therapeutics is an area of intense research focus. Chemical engineering of a “smart” DDS to specifically target tumor cells has gained interest, designed for safer, more efficient, and effective use of chemotherapeutics for the treatment of cancer. However, the selective targeting and choosing the critical cancer surface biomarker are essential for targeted treatments to work. The folic acid receptor alpha (FRalpha) has gained popularity as a potential target in triple-negative breast cancer (TNBC). We have previously reported on a functionalized folic acid (FA)-conjugated amphiphilic alternating copolymer poly(styrene-alt-maleic anhydride) (FA-DABA-SMA) via a biodegradable linker 2,4-diaminobutyric acid (DABA) that has the essential features for efficient “smart” DDS. This biocompatible DDS self-assembles in a pH-dependent manner, providing stimuli-responsive, active targeting, extended-release of hydrophobic chemotherapeutic agents, and can effectively penetrate the inner core of 3-dimensional cancer spheroid models. The empty FA-DABA-SMA decreased spheroid volume, revealing a previously unknown mechanism of action. Upon further investigation, a size- and shape-dependent interaction FA-DABA-SMA with FR reduced the expression of p53, the product of the highly mutated TP53 gene, and additional oncogenic c-Myc and STAT3 proteins. Here, we investigated how this copolymer influences FR behavior and disrupting the receptor’s functions. Results indicate that FA-DABA-SMA increases FR expression levels in breast MDA MB-231 cancer cells and disrupting FR signaling by the reduction in HES1 and NOTCH1 protein expression levels. Also, FA-DABA-SMA induces apoptosis and further causes a change in the morphology of the MDA MB-231 cells, as well as significantly reduces their ability to migrate in a Scratch wound assay. Collectively, these findings provide a novel insight into the functionalized FA-DABA-SMA copolymer. The 350 kDa and 20 kDa copolymers actively target FRα to initialize internationalization. However, only the large size and sheet-shaped 350 kDa copolymers disrupt FRα signaling. The significance of these novel findings reveals the intracellular activity of the copolymer that is critically dependent on the size and structural shape. This report offers novel therapeutic insight into a dual mechanism of FA-DABA-SMA copolymer for its therapeutic potential for the treatment of cancer.

The present study assessed the effect of abscisic acid (ABA; 25 µM) and/or nitrogen (N; 10 mM) in minimization of salinity (NaCl; 100mM)-impact on growth, photosynthetic efficiency, Rubisco activity, nitrogen and sulfur assimilation, oxidative stress (H₂O₂), lipid peroxidation measured as thiobarbituric acid reactive substances, (TBARS), osmolyte (Proline) content, and the activity of antioxidant enzymes (superoxide dismutase, SOD glutathione reductase, GR; ascorbate peroxidase, APX) in cultivar RH0-749 of Brassica juncea L. NaCl stress caused significant elevations in H₂O₂ and TBARS, and differentially modulated proline content, the activity of antioxidant enzymes, and impaired growth and photosynthetic functions. Exogenously applied 25 µM ABA negatively affected plant growth and photosynthesis in B. juncea without NaCl. In contrast, exogenously applied 25 µM ABA and 10 mM N, alone or in combination minimized oxidative stress, and maintained a fine-tuning between proline content and the activity of antioxidant enzymes, and thereby improved plant growth and photosynthetic functions in NaCl exposed B. juncea.

Objectives To determine the effects of omega-3 polyunsaturated fatty acids (ω-3 PUFA) from animal and plant sources on glucolipid metabolism and lipoprotein subfractions in type 2 diabetic patients with dyslipidemia. Methods Participants were recruited from the diabetes clinic at the Guanlin Hospital, Yixing City in Jiangsu province, China, from March 2017 through June 2017. Ninety participants were randomly assigned to take 3g/day fish oil (FO, containing EPA and DHA), 3g/day perilla oil (PO, containing ALA), or 3g/day blend oil containing fish oil and linseed oil (BO, containing EPA, DHA and ALA) for 3 months. The levels of serum glucose, glycated hemoglobin (HbA1c), C-peptide, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), non-HDL, apolipoprotein A1 (Apo A1), apolipoprotein B (Apo B), lipoprotein a (Lp(a)), and free fatty acids were determined at baseline and after the 3 months. In addition, four fatty acids in serum and red blood cells membranes (RBCm) were analyzed using gas chromatography-mass spectrometry. The Lipoprint System was used to determine the lipoprotein subfractions. Results All 90 participants completed the final 3-month follow-up at the end of the study. After three months of intervention, blood glucose and HbA1c levels in the PO group were significantly lower than those at the baseline (p < 0.05). On the other hand, in the BO group, the HbA1c, non-HDL, Apo A1 and Lp(a) levels were significantly lower, while the C-peptide levels were significantly higher after intervention compared to the baseline (p < 0.05). In the FO group, the HbA1c and TG levels were significantly lower after the intervention compared to the baseline (p < 0.05). In addition, at the end of the study, there was significant increase in the levels of DPA and DHA in serum and RBCm of the FO group (p < 0.05), while in the BO group, there was significant increase in the levels of EPA, DPA and DHA in RBCm (p < 0.05). Finally, the FO group had the highest levels of large HDL subfractions compared to the BO and PO groups, but had the lowest levels of small HDL subfractions among the three groups. Conclusion For patients with diabetes, plant-derived ω-3 PUFAs are more effective at controlling blood glucose than animal-derived ω-3 PUFAs. However, animal-derived ω-3 PUFAs play a critical role in controlling blood lipids. Particularly, fish oil can effectively increase the beneficial large HDL subfractions and reduce the nonbeneficial small HDL subfractions. Both the animal- and plant-derived ω - 3 PUFAs have practical value in improving glucose and lipids metabolism in T2DM patients with dyslipidemia.

: Coffee is one of the most consumed beverages in the world; its production is based mainly on varieties of the Coffea arabica species. Mexico stands out for its specialty and organic coffee. In Guerrero the production is given by small indigenous community’s cooperatives that market their product as raw material. Official Mexican Standards stipulate the necessary requirements for its commercialization within the national ter-ritory. In this work, the physical, chemical, and biological characterizations of green, medium, and dark roasted beans from C. arabica varieties were carried out. Analysis of HPLC showed higher chlorogenic acid (55 mg/g) and caffeine (1.8 mg/g) contents in the green beans of the Bourbon and Oro Azteca varieties. The caffeine (3.88 mg/g) and melanoidins (97 and 29 mg/g) contents increased according to the level of roasting; a dissimilar effect was found in the chlorogenic acid content (14.5 mg/g). The adequate nutritional content and the sensory evaluation allowed the classification of dark roasted as premium coffee (84.25 points) and the roasted medium as specialty coffee (86.25 points). The roasted coffees presented antioxidant activity without cytotoxic effect. The results obtained will serve as a basis for making decisions on the improvements of the coffees analyzed.

Chitosan is a chitin-derived fiber, extracted from the shellfish shells, a by-product of fish industry, or from fungi grown in bioreactors. In oenology, it is used for the control of Brettanomyces spp., for the prevention of ferric, copper and protein casse and for clarification. The International Organisation of Vine and Wine established the exclusive utilization of fungal chitosan to avoid the eventuality of allergic reactions. This work focuses on the differences between two chitosan categories, fungal and animal chitosan, characterizing several samples in terms of chitin content and degree of deacety-lation. In addition, different acids were used to dissolve chitosans, and their effect on viscosity and on the efficacy in wine clarification were observed. Results demonstrated that, even if fungal and animal chitosans shared similar chemical properties (deacetylation degree and chitin content), they showed different viscosity depending on the acid used to dissolve them. A significant difference was discovered on their fining properties, as animal chitosans showed a faster and greater sedimentation compared to the fungal, independently from the acid used for their dissolution. This suggests that physic-chemical differences in the molecular structure occur between the two chitosan categories and that this affect significantly their technologic (oenological) properties.

Ferulic acid (FA) is known for its excellent antioxidant properties that can provide a lot of health benefits. One of its drawbacks is being unstable under UVA light that limits its potency. In this study, new peptides LW2 (QNKRFYFRKNQ) and CW2 (a cyclic form of LW2) have been designed based on bovine serum albumin site ⅡA conformation. UVA irradiation experiment was performed to investigate the protective ability of these peptides towards FA against UVA damage. The percentage of FA remaining under UV irradiation by the protection of CW2 and LW2 was 83%, 76% respectively. The results showed the importance of the cationic residues and hydrophobic residues included in the peptide sequences. Moreover, the cyclic rigid structure showed more protecting ability over that of the linear counterpart.

Introduction: Valproic acid (VPA) is an antiepileptic drug extensively used for treating partial and generalised seizures, acute mania and as prophylaxis for bipolar disorder. Drug-induced liver injury (DILI) persists as a significant issue related to fatal outcomes by VPA. The aim of this study was to increase our knowledge about this condition and to better identify patients affected. Methods: We conducted an observational retrospective case-control study that identified cases of DILI by VPA from the Pharmacovigilance Programme from our Laboratory Signals at La Paz University Hospital from January 2007 to December 2019. From the Therapeutic VPA Monitoring Programme, two control groups were assigned, VPA-tolerant patients and the other with patients who developed mild VPA-related hepatitis but who did not meet the DILI criteria, matched for date, age and sex. Results: A total of 60 patients were included in the study: 15 cases of DILI, 30 VPA-tolerant controls and 15 controls with mild hepatitis. Mean age for the cases was 45.7 years, 4(26.7%) were women and 5(33.34%) were children under 18 years, of them 3(20%) were fatal. Polytherapy with other antiepileptic drugs (p=0.047) and alcohol consumption (p<0.001) were associated with a greater risk of developing DILI by VPA. A diagnosis of epileptic seizure was more frequently related to DILI when compared with the VPA-tolerant controls (p<0.001). The cases developed hepatocellular hepatitis (p<0.001), while the mild hepatitis controls had a higher rate of cholestatic hepatitis (p<0.001). The laboratory lactate dehydrogenase values were statistically higher (even at baseline) in patients with DILI than in both control groups (p= 0.033 and p=0.039). Conclusions: VPA hepatotoxicity remains a considerable problem. This study offers interesting findings for characterising VPA-induced liver injury and at-risk patients.

Fatty Acid Amide Hydrolase (FAAH) is one of the enzymes responsible of endocannabinoids metabolism. The inhibition of FAAH is a useful and indirect strategy to raise endogenous cannabinoid concentrations, which would be useful for the treatment of various pathological processes in which cannabinoid concentrations are lowered. In the present work, we present an extensive 3D-QSAR/CoMSIA study on a series of 90 irreversible inhibitors of FAAH of pyrimidinyl-piperazine-carboxamide structure. The final model obtained was extensively validated (q2 = 0.734; r2test = 0.966; r2m = 0.723), and based on the information derived from the contour maps we reported a series of 10 new compounds designed as powerful FAAH inhibitors (pIC50 of the best-proposed compounds = 12.196; 12.416).

The limited information available on the structure of complexes involving transcription factors and cognate DNA response elements represents a major obstacle in the quest to understand their mechanism of action at the molecular level. We implemented a concerted structural proteomics approach, which combined hydrogen-deuterium exchange (HDX), quantitative protein-protein and protein-nucleic acid cross-linking (XL), and homology analysis, to model the structure of the complex between the full-length DNA binding domain (DBD) of FOXO4 and its DNA binding element (DBE). The results confirmed that FOXO4-DBD assumes the characteristic forkhead topology shared by these types of transcription factors, but its binding mode differs significantly from those of other members of the family. The results showed that the binding interaction stabilized regions that were rather flexible and disordered in the unbound form. Surprisingly, the conformational effects were not limited only to the interface between bound components but extended also to distal regions that may be essential to recruiting additional factors to the transcription machinery. In addition to providing valuable new insights into the binding mechanism, this project provided an excellent evaluation of the merits of structural proteomics approaches in the investigation of systems that arematerial not directly amenable to traditional high-resolution techniques.

Equipped with an early social predisposition immediately post-birth, humans typically form associations with mothers and other family members through exposure learning, canalized by a spontaneous predisposition to biological motion, face configuration, and other cues of animacy. If impaired, reduced social preferences can lead to social interaction impairments such as autism spectrum disorder (ASD) via misguided canalization. Despite being taxonomically distant, domestic chicks also follow a homologous developmental trajectory toward adaptive socialization through imprinting, which is guided via predisposed preferences that are homologous to those of humans, thereby suggesting that chicks are valid animal models of ASD. In addition to the convergent similarities in predisposition with human newborns, accumulating evidence suggests the construct validity of the chick model. Considering the recent progress in the evolutionary neurobiology of vertebrates, we reviewed the advantages and limitations of the chick model of developmental mental diseases in humans.

Lipid-based drugs are emerging as an interesting class of novel anticancer drugs with the potential to target specific cancer cell metabolic pathway linked to their proliferation and invasiveness. In particular, ω−3 polyunsaturated fatty acids (PUFA) derivatives such as epoxides and their bioisosteres have demonstrated the potential to suppress growth and promote apoptosis in triple-negative human breast cancer cells MDA-MB-231. In this study 16-(4’-chloro-3’-trifluorophenyl)carbamoylamino]hexadecanoic acid (ClFPh-CHA), an anticancer lipid derived from ω−3,17,18-epoxyeicosanoic acid, was formulated as a stable nanoemulsion with size around 150 nm and narrow droplet size distribution (PDI<0.200) through phase-inversion emulsification process followed by high pressure homogenization in view of an oral administration. The ClFPh-CHA-loaded nanoemulsions were able to significantly decrease the relative tumor volume in mice bearing an intramammary tumor xenograft at all doses tested (2.5, 10 and 40 mg/kg) after 32 days of daily oral administration. Furthermore, absolute tumor weight was decreased to 50% of untreated control at 10 and 40 mg/kg, while intraperitoneal administration could achieve a significant reduction only at the highest dose of 40 mg/kg. Results suggest that oral administration of ClFPh-CHA formulated as a nanoemulsion has a sufficient bioavailability to provide an anticancer effect in mice and that the activity is at least equal if not superior to that obtained by a conventional parenteral administration of equivalent doses of the same drug.

Zinc is mostly extracted from zinc oxide and sulfide minerals, and this process involves flotation as a key step. While it is easier to float the sulfide mineral, its consumption and depletion has led to an increased reliance on zinc oxide minerals, including smithsonite; hence the development of efficient ways of collecting smithsonite by flotation is an important objective. Herein, we describe the use of 2-(hexadecanoylamino)acetic acid (HAA), a novel surfactant, as a collector during smithsonite flotation. The mechanism and flotation performance of HAA during smithsonite flotation were investigated by total organic carbon (TOC) content studies, zeta potential measurements, FTIR spectroscopy, and XPS analyses, combined with micro-flotation experiments. The flotation results revealed that HAA is an excellent collector in pulp over a wide pH range (9–12) and at a relatively low concentration (2 × 10^‒4 mol/L), at which a recovery of close to 90% of the smithsonite mineral was obtained. TOC-content studies reveal that the good flotation recovery is ascribable to large amounts of collector molecule adsorbed on the smithsonite surface, while zeta potential measurements show that the HAA is chemically adsorbed onto the smithsonite. FTIR and XPS analyses reveal that the HAA-collector molecules adsorb onto the smithsonite surface as zinc-HAA complexes involving carboxylate moieties and Zn sites on the smithsonite surface in alkaline solution.

Almond (Prunus dulcis (Mill.) D.A.Webb) is one of the largest nut crops in the world. Recently, phenolic compounds, mostly stored in almond skin, have been associated with much of the health-promoting behavior associated with their intake. The almond skin enriched fraction obtained from cold-pressed oil residues of the endemic Moroccan Beldi ecotypes is particularly rich in chlorogenic acid. In this study, both almond skin extract (AE) and chlorogenic acid (CHL) supplements, similar to traditional positive control resveratrol, significantly increased the replicative life-span of yeast compared to the untreated group. Our results showed that AE and CHL significantly reduced the production of reactive oxygen and nitrogen species (ROS/RNS), most likely due to their ability to maintain mitochondrial function during aging, as indicated by the maintenance of normal mitochondrial membrane potential in treated groups. This may be associated with the observed activation of the anti-oxidative stress response in treated yeast, which results in activation at both gene expression and enzymatic activity levels for SOD2 and SIR2, the latter being an upstream inducer of SOD2 expression. Interestingly, the differential gene expression induction of mitochondrial SOD2 gene at the expense of the cytosolic SOD1 gene confirms the key role of mitochondrial function in this regulation. Furthermore, AE and CHL have contributed to the survival of yeast under UV-C-induced oxidative stress, by reducing the development of ROS / RNS, resulting in a significant reduction in cellular oxidative damage as evidenced by decreased membrane lipid peroxidation, protein carbonyl content and 8-oxo-guanine formation in DNA. Together, these results demonstrate the interest of AE and CHL as new regulators in the replicative life-span and control of the oxidative stress response of yeast.

Endothelial cells form a powerful interface between tissues and immune cells. In fact, one of the underappreciated roles of endothelial cells is to orchestrate immune attention to specific sites. Tumor endothelial cells have a unique ability to dampen the immune responses and thereby maintain an immunosuppressive microenvironment. Recent approaches to trigger immune responses in cancers have focused on activating nucleic acid sensors such as cGAS/STING in combination with immunotherapies. In this review, we present a case for targeting nucleic acid sensing pathways within the tumor vasculature to invigorate tumor immune responses. We introduce two specific nucleic acid sensors, the DNA sensor TREX1 and the RNA sensor RIG-I and discuss their functional roles in the vasculature. Finally, we present perspectives on how these nucleic acid sensors in the tumor endothelium can be targeted in an antiangiogenic and immune activation context. We believe understanding the role of nucleic acid sensing in the tumor vasculature can enhance our ability to design more effective therapies targeting the tumor microenvironment.

The changes in nutritional quality, bioactive compounds and antioxidant enzymes in the juice of four blood orange cultivars (‘Moro’, ‘Tarocco’, ‘Sanguinello’ and ‘Sanguine’) stored during 6 months at 2 and 5 °C plus 2 days at 20 °C for shelf life were studied. Sucrose was the sugar found at higher concentration and decreased during storage for all cultivars, as did glucose and fructose. Organic acids decreased at both temperatures and the highest content was found in ‘Sanguinello’, especially the major (citric acid) and ascorbic acid. Total phenolics content (TPC), total anthocyanins (TAC), and the individual (cyanidin 3-glucoside and cyanidin 3-(6″-malonylglucoside)) increased for all cultivars, the ‘Sanguinello’ having the higher concentrations. Antioxidant enzymes catalase (CAT), ascorbate peroxidase (APX) and superoxide dismutase (SOD) were higher also in ‘Sanguinello’ and increased during storage. Overall, these results together with the sensory analysis suggest that ‘Sanguinello’ would be the best cultivar for prolonged storage.

The effects of orally administered lactic acid bacteria metabolites on the skin were studied using an atopic dermatitis-like murine model created by feeding mice with HR-AD. The lactic acid bacteria metabolites were obtained by inoculating 35 strains of 16 species of lactic acid bacteria into soy milk and culturing them. The atopic dermatitis-like murine model was created by feeding HR-1 mice HR-AD for 40 days. The skin condition of mice that were fed HR-AD worsened compared with normal mice, i.e., reduced water content in the stratum corneum, increased transepidermal water loss (TEWL), reduced ceramide AP content in the stratum corneum, and increased epidermis thickness. When mice that had been fed the HR-AD diet was administered a raw liquid of lactic acid bacteria metabolites orally, the measured values related to water content in the stratum corneum, TEWL, ceramide AP content in the stratum corneum, and epidermis thickness improved. To find out the active components for these effects, filtrate and residue from the raw liquid of lactic acid bacteria metabolites and lipid components extracted from the raw liquid were examined at the same time. Results showed that the water-soluble components or residue after filtration did not demonstrate effects but the raw liquid and the lipid fraction did. These findings suggest that lactic acid bacteria metabolites improve skin injury in an atopic dermatitis-like murine model.

This work aims to investigate systematically the influence of process temperature, bio-mass-to-water ratio, and production scales (laboratory and pilot) on the chemical composition of aqueous and gaseous phases and mass production of chemical by hydrothermal processing of Açaí (Euterpe Oleraceae, Mart.) seeds. The hydrothermal carbonization carried out at 175, 200, 225, and 250 °C, 2 °C/min, biomass-to-water ratio of 1:10, and at 250 °C, 2 °C/min, and biomass-to-water ratios of 1:10, 1:15, and 1:20, in technical scale, as well as at 200, 225, and 250 °C, 2 °C/min, bio-mass-to-water ratio of 1:10, in laboratory scale. The elemental composition (C, H, N, S) of solid phase determined to compute the HHV. The chemical composition of aqueous phase determined by GC and HPLC and the volumetric composition of gaseous phase by using an infrared gas an-alyzer. For the experiments in pilot scale with constant biomass-to-water ratio of 1:10, the yields of solid, liquid, and gaseous phases varied between 53.39 and 37.01% (wt.), 46.61 and 59.19% (wt.), and 0.00 and 3.80% (wt.), respectively. The yield of solids shows a smooth exponential de-cay with temperature, while that of liquid and gaseous phases a smooth growth. By varying the biomass-to-water ratios, the yields of solid, liquid, and gaseous reaction products varied be-tween 53.39 and 32.09% (wt.), 46.61 and 67.28% (wt.), and 0.00 and 0.634% (wt.), respectively. The yield of solids decreases exponentially with increasing water-to-biomass ratio and that of liquid phase increases in a sigmoid fashion. For constant biomass-to-water ratio, the concentrations of Furfural and HMF decrease drastically with increasing temperature, reaching a minimum at 250 °C, while that of phenols increases. In addition, the concentrations of CH3COOH and total car-boxylic acids increase, reaching a maximum at 250 °C. For constant process temperature, the concentrations of aromatics vary smoothly with the temperature. The concentrations of furfural, HMF, and cathecol decrease with temperature, while that of phenols increases. The concentra-tions of CH3COOH and total carboxylic acids decrease exponentially with temperature. Finally, for the experiments with varying water-to-biomass ratios, the productions of chemicals (furfu-ral, HMF, phenols, cathecol, and acetic acid) in the aqueous phase is highly dependent on the biomass-to-water ratio. For the experiments in laboratory scale with constant biomass-to-water ratio of 1:10, the yields of solid ranged between 55.9 and 51.1% (wt.), showing not only a linear decay with tem-perature, but also a lower degradation grade. The chemical composition of main organic compounds (furfu-ral, HMF, phenols, cathecol, and acetic acid) dissolved in the aqueous phase in laboratory scale shows the same behavior of those in obtained in pilot scale.

The purpose of the current study was directed to investigate the effectiveness of docosahexaenoic acid (DHA) as a chemopreventive agent on experimentally induced hamster buccal pouch (HBP) carcinogenesis; Material and methods: 40 Syrian male hamsters, five weeks old, were divided into 4 groups of 10 animals in each as follows, GI: Topical application of liquid paraffin alone (thrice a week for 14 weeks), GII: Topical application of 7, 12 dimethyl benz[a]anthracene (DMBA) alone (0.5 % in liquid paraffin, thrice a week for 14 weeks), GIII: Topical application of DMBA (0.5 % in liquid paraffin, thrice a week for 14 weeks) + Oral administration of DHA (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks on alternative days of DMBA application), GIV : Oral administration of DHA alone (125 mg/kg b.w. in 1 ml distilled water by oral gavage, thrice a week for 14 weeks); Results: Gross observations and histopathological findings revealed a-GI: normal stratified squamous epithelium b- GII: well and moderately differentiated squamous cell carcinoma (SCC) c-: GIII: showed variable results ranges from hyperkeratosis, hyperkeratosis and focal hyperplasia, mild dysplasia, and well differentiated SCC with superficial invasion of tumor cells not extended to deeper areas d: GIV: normal similar to GI. Immunohistochemical results revealed that oral DHA treatment to DMBA treated hamsters restored the normal expression of bcl-2; Conclusion: DHA has the potential to be a dietary chemopreventive agent due to its capacity to improve carcinogen detoxification and to block/suppress the initiation and promotion stages of experimentally produced HBP carcinogenesis.