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Objective: An experiment was conducted to determine the effect of algae-based antioxidant containing Se yeast (EconomasE®) on the growth performance, visceral organ weight, meat quality, and oxidative stability of broiler chickens.Methods: Nine hundred sixty, day-old male broiler chickens (Cobb, 43.97±0.55 g) were divided into three dietary treatments and allocated into 12 deep litter pens in a completely randomized design giving 4 replicate cages for each treatment. Three dietary treatments were: i) control (CON, basal diet with sufficient nutrient), ii) vitamin E (VitE, basal diet supplemented with 100 IU VitE), and iii) Algae-based antioxidant containing Se yeast (EcoE, basal diet supplemented with 0.2% algae-based antioxidant containing Se yeast: EconomasE®). Maize soybean meal based basal diets were formulated to meet or exceed the nutrition requirement for broiler chickens. Chickens were fed ad-libitum experimental diets during the 42 days experiment period. On days 21 and 42, body weight and feed intake were measured to calculate the feed conversion ratio of the chickens. Intestine and visceral organs were measured together with meat quality and oxidative stability on days 14 and 42.Results: Chickens fed with EcoE showed improved (p

1.The conversion of the cyclophosphamide intermediate metabolite 4-hydroxycyclophosphamide (4-OHCP) to the final cytotoxic metabolite phosphoramide mustard (PAM) is classically assumed to occur via chemical hydrolysis of the phospho-ester bond. Whilst it has been suggested previously that this reaction could be enzyme-catalysed, there was only indirect evidence for this (i.e. formation of the by-product acrolein).2. Using an assay to detect formation of DNA-alkylating adducts which block PCR amplification (QPCR-block assay), we have demonstrated that 4-OHCP can be activated by peripheral blood mononuclear cells (PBMC). The DNA-alkylating potency of 4-OHCP in PBMC increased18-fold compared to the intrinsic reactivity of 4-OHCP for purified gDNA.3. We also found that immortalised T-cells (Jurkat) had a similar ability to activate 4-OHCP into a DNA alkylating agent, whereas there was no appreciable activation in epithelial derived (Caco-2) cells. This suggests the possibility of tissue-specific enzyme expression.4. Of the candidate enzymes tested only recombinant human cAMP-phosphodiesterase-PDE4B and snake-venom phosphodiesterase (PDE-I) could catalyse this activation into a DNA-alkylating agent.5. This enzymatic catalysis of the phospho-ester bond (P-O-C) is a hitherto unrecognised feature of this important immunomodulatory drug and should be investigated further.

We aimed to investigate the effects of dried curry leaves powder (CLP) incorporation on physicochemical, microbiological, antioxidant, and sensory properties of cream cheeses. Varying levels of CLP infusions (i.e., T1: 0% [control], T2: 0.15%, T3: 0.2%, and T4: 0.25%; w/w%) were stored for 10 days at 4°C. Antioxidant properties were evaluated using total phenolic content, 1,1‐diphenyl‐2‐picryl‐hydrazyl (DPPH) radical scavenging ability, and ferric reducing antioxidant power using in vitro assays. Total antioxidant capacity significantly (p, This study shows inclusion of dried curry leaves powder into cream cheese increased antimicrobial and antioxidative attributes with enhanced organoleptic properties, while physicochemical attributes remained unaffected.

Many optimal order multiple root techniques, which use derivatives in the algorithm, have been proposed in literature. Many researchers tried to construct an optimal family of derivative-free methods for multiple roots, but they did not get success in this direction. With this as a motivation factor, here, we present a new optimal class of derivative-free methods for obtaining multiple roots of nonlinear functions. This procedure involves Traub–Steffensen iteration in the first step and Traub–Steffensen-like iteration in the second step. Efficacy is checked on a good number of relevant numerical problems that verifies the efficient convergent nature of the new methods. Moreover, we find that the new derivative-free methods are just as competent as the other existing robust methods that use derivatives.

Field studies were conducted during the 2015 and 2016 growing seasons in south-central Texas to determine control of Palmer amaranth and annual grasses along with grain sorghum tolerance to quinclorac alone and in various combinations when applied to weeds < 5 cm (EPOST) or 10 to 16 cm tall (LPOST). When evaluated late-season quinclorac alone at 0.43 kg ae ha-1 controlled broadleaf signalgrass 72% when applied EPOST and 91% when applied LPOST. Combinations of quinclorac with either atrazine, pyrasulfotole + bromoxynil, dicamba, or dimethenamid-P controlled Palmer amaranth 88 to 100% when applied EPOST or LPOST; however, broadleaf signalgrass control with these combination was better when applied LPOST (75 to 95%) compared with EPOST (37 to 72%) applications. Texas millet control with quinclorac was poor in both years and was never greater than 54%. Quinclorac plus either atrazine, pyrasulfotole + bromoxynil, dicamba, or atrazine + dimethenamid-P caused at least 20% sorghum injury at one of three locations. No yield reductions from the untreated check were noted in either year; however, in 2016 all treatments with the exception of quinclorac alone at 0.29 kg ha-1 applied EPOST, quinclorac + pyrasulfotole + bromoxynil applied LPOST, quinclorac + atrazine + pyrasulfotole + bromoxynil applied LPOST, and quinclorac + dicamba at either application timing produced yields that were greater than the untreated check.

This study evaluated the antimicrobial effects of medium chain fatty acids (MCFAs) against Salmonella Typhimurium (ATCC 14028) when used on dry dog food kibbles. The MIC of three MCFAs, caproic (C6), caprylic (C8), and capric (C10), was determined using the broth micro- and macrodilution assay technique. Using canola oil as a fat coating, the efficacy of each MCFA was then tested on dry dog food kibbles at 37°C for up to 5 h. The MIC was found to be 0.3125, 0.3125, and 0.625% for C6, C8, and C10, respectively. When the MCFAs were tested on fat-coated dry kibbles, all three MCFAs reduced (P ≤ 0.05) Salmonella levels by >4.5 log after 5 h when the Salmonella recovery from a no-treatment control was ∼6.4 log. At each evaluation time point, the three treatments were effective in reducing (P ≤ 0.05) Salmonella loads. No countable colonies of Salmonella were detected at 4 h when the combination of C6+C8 was used on the kibbles (P ≤ 0.05), whereas with the C6+C10 combination, the Salmonella colonies were not detectable between 2 and 4 h after treatments (P ≤ 0.05). Different combinations of C8 and C10 caused Salmonella to drop to a nondetectable limit (1 CFU/g) between 1 and 5 h after treatment (P ≤ 0.05). This study suggests that the use of MCFAs during kibble coating may mitigate postprocessing Salmonella recontamination on dry dog food kibbles. HIGHLIGHTS

Background Elevated serum urate levels are associated with progression of chronic kidney disease. Whether urate-lowering treatment with allopurinol can attenuate the decline of the estimat...

Salicylic acid (SA) is a hormone that mediates systemic acquired resistance in plants. We demonstrated that SA can interfere with group behavior and virulence of the soft-rot plant pathogen Pectobacterium spp. through quorum sensing (QS) inhibition. QS is a population density-dependent communication system that relies on the signal molecule acyl-homoserine lactone (AHL) to synchronize infection. P. parmentieri mutants, lacking the QS AHL synthase (expI-) or the response regulator (expR-), were used to determine how SA inhibits QS. ExpI was expressed in DH5α, the QS negative strain of Escherichia coli, revealing direct interference of SA with AHL synthesis. Docking simulations showed SA is a potential ExpI ligand. This hypothesis was further confirmed by direct binding of SA to purified ExpI, shown by isothermal titration calorimetry and microscale thermophoresis. Computational alanine scanning was employed to design a mutant ExpI with predicted weaker binding affinity to SA. The mutant was constructed and displayed lower affinity to the ligand in the binding assay, and its physiological inhibition by SA was reduced. Taken together, these data support a likely mode of action and a role for SA as potent inhibitor of AHL synthase and QS.

Background Fluid overload in patients undergoing hemodialysis contributes to cardiovascular morbidity and mortality. There is a global trend to lower dialysate sodium with the goal of reducing fluid overload. Methods To investigate whether lower dialysate sodium during hemodialysis reduces left ventricular mass, we conducted a randomized trial in which patients received either low-sodium dialysate (135 mM) or conventional dialysate (140 mM) for 12 months. We included participants who were aged >18 years old, had a predialysis serum sodium ≥135 mM, and were receiving hemodialysis at home or a self-care satellite facility. Exclusion criteria included hemodialysis frequency >3.5 times per week and use of sodium profiling or hemodiafiltration. The main outcome was left ventricular mass index by cardiac magnetic resonance imaging. Results The 99 participants had a median age of 51 years old; 67 were men, 31 had diabetes mellitus, and 59 had left ventricular hypertrophy. Over 12 months of follow-up, relative to control, a dialysate sodium concentration of 135 mmol/L did not change the left ventricular mass index, despite significant reductions at 6 and 12 months in interdialytic weight gain, in extracellular fluid volume, and in plasma B-type natriuretic peptide concentration (ratio of intervention to control). The intervention increased intradialytic hypotension (odds ratio [OR], 7.5; 95% confidence interval [95% CI], 1.1 to 49.8 at 6 months and OR, 3.6; 95% CI, 0.5 to 28.8 at 12 months). Five participants in the intervention arm could not complete the trial because of hypotension. We found no effect on health-related quality of life measures, perceived thirst or xerostomia, or dietary sodium intake. Conclusions Dialysate sodium of 135 mmol/L did not reduce left ventricular mass relative to control, despite improving fluid status. Clinical trial registry name and registration number The Australian New Zealand Clinical Trials Registry, ACTRN12611000975998.

A novel, eco-friendly aminated chitosan Schiff’s base (ACSSB@ZnO) was developed and utilized to remove MO from aqueous environment. The impact of different significant parameters, for example, pH (3–11), adsorbent dose (0.1–0.6 g), contact time (0–120 min), and temperature (303–323 K) have been explored by batch process. Kinetic data was illustrated by pseudo-second-order model and the isotherms fitted well with Langmuir isotherm model. The highest sorption capacity of ACSSB@ZnO was observed to be 111.11 mg/g at 323 K. Positive enthalpy and entropy values demonstrated that the MO adsorption procedure was an endothermic. Negative Gibbs free energy values implied the spontaneous nature of the adsorption system. Moreover, reusability experiments were studied and it can be regenerated by using NaOH as effluent.

Emamectin benzoate (4´-deoxy-4´-epimethylaminoavermectin B1) is a macrocyclic lactone developed for the control of insect pests in edible plant crops. The current study was taken to assess the possible ameliorative effect of piracetam (P) on emamectin benzoate (EMB) induced alterations in energy metabolism in liver, kidney, testis, heart, cerebral cortex, cerebellum and muscle of rats. Rats of normal control group (N) received water and normal diet ad libitum and (EMB as well as EMB+P) group received 5 mg/kg bw emamectin benzoate via drinking water for 4 weeks. After four weeks of EMB treatment, rats of (EMB+P) received piracetam (500 mg/kg bw, iv) for 15 days. The results demonstrate that emamectin benzoate caused a significant increase in lactate dehydrogenase activity and the level of lactate indicating organ damage in treated animals. Piracetam, the so-called ‘nootropic’ drug is mainly used to treat cognitive impairment in aging, brain injuries, as well as dementia. In the present study piracetam treatment caused a significant inhibition of lactate dehydrogenase activity in liver, kidney, testis, heart, cerebral cortex, cerebellum and muscle of rats. The amelioration of toxic effects by piracetam treatment in EMB treated rats indicate that this drug has the potential to mitigate emamectin benzoate induced toxicity in mammalian systems.

Current cell-based bone tissue regeneration strategies cannot cover large bone defects. K-carrageenan is a highly hydrophilic and biocompatible seaweed-derived sulfated polysaccharide, that has been proposed as a promising candidate for tissue engineering applications. Whether κ-carrageenan can be used to enhance bone regeneration is still unclear. In this study, we aimed to investigate whether κ-carrageenan has osteogenic potential by testing its effect on pre-osteoblast proliferation and osteogenic differentiation in vitro. Treatment with κ-carrageenan (0.5 and 2 mg/mL) increased both MC3T3-E1 pre-osteoblast adhesion and spreading at 1 h. K-carrageenan (0.125–2 mg/mL) dose-dependently increased pre-osteoblast proliferation and metabolic activity, with a maximum effect at 2 mg/mL at day three. K-carrageenan (0.5 and 2 mg/mL) increased osteogenic differentiation, as shown by enhanced alkaline phosphatase activity (1.8-fold increase at 2 mg/mL) at day four, and matrix mineralization (6.2-fold increase at 2 mg/mL) at day 21. K-carrageenan enhanced osteogenic gene expression (Opn, Dmp1, and Mepe) at day 14 and 21. In conclusion, κ-carrageenan promoted MC3T3-E1 pre-osteoblast adhesion and spreading, metabolic activity, proliferation, and osteogenic differentiation, suggesting that κ-carrageenan is a potential osteogenic inductive factor for clinical application to enhance bone regeneration.

Neutral lipids (NLs) are an abundant class of cellular lipids. They are characterized by the total lack of charged chemical groups in their structure, and, as a consequence, they play a major role in intracellular lipid storage. NLs that carry a glycerol backbone, such as triacylglycerols (TGs) and diacylglycerols (DGs), are also involved in the biosynthetic pathway of cellular phospholipids, and they have recently been the subject of numerous structural investigations by means of atomistic molecular dynamics (MD) simulations. However, conflicting results on the physicochemical behavior of NLs were observed depending on the nature of the atomistic force field used. Here, we show that current phospholipid-derived CHARMM36 parameters for DGs and TGs cannot reproduce adequately interfacial properties of these NLs, due to excessive hydrophilicity at the glycerol-ester region. By following a CHARMM36-consistent parameterization strategy, we develop new parameters for both TGs and DGs that are compatible with both cutoffbased and Particle Mesh Ewald (PME) schemes for the treatment of Lennard Jones interactions. We show that our new parameters can reproduce interfacial properties of NLs and their behavior in more complex lipid assemblies. We discuss the implications of our findings in the context of intracellular lipid storage and NLs cellular activity.

Traditional fermented buffalo milk gel; Meekiri, is a popular buffalo milk-derived product in Sri Lanka. Predominantly, it is produced using the back-slopping (adding a small amount of the previous fermentate) technique, following the life-long traditions available at the cottage level. Hence, diverse and unclassified starter cultures are likely to be established across the varying geographical regions of Meekiri production. In the present study, we aimed to elucidate the diversity of lactic acid bacteria (LAB) and their characteristics including probiotic properties from major Meekeri production areas (n = 22) in Sri Lanka. Lactic acid bacteria was isolated from locally produced Meekiri samples (n = 23) and characterized based on morphological, biochemical, physiological profiles and potential of probiotic properties. The isolates revealed five different colony and cell morphologies and were classified as heterofermenters, homofermenters and facultative heterofermenters based on CO2 production using glucose. None of the isolates showed the ability to grow either at 5 °C or 0 °C, while 71 % and 100 % survival of the isolates were observed at 15 °C and 45 °C, respectively. Amplified ribosomal DNA restriction analysis (ARDRA) primarily grouped the isolates into three distinct clusters based on their DNA banding patterns. Subsequently, 16S rRNA sequencing of isolates revealed the presence of four species namely, Limosilactobacillus fermentum (n = 18), Latilactobacillus curvatus (n = 2), Lactobacillus acidophilus (n = 2) and Lactiplantibacillus plantarum (n = 1) and in the phylogenetic analysis, it was represented by four distinctive clades. All the isolated species demonstrated promising probiotic potential with antibiotic sensitivity, antimicrobial properties, bile acid tolerance and acid tolerance. In conclusion, traditional back-slopping Meekiri in Sri Lanka contains diverse LAB, with a negligible geographical variation at species-level. Our work provides a strong foundation and insights into future applications in starter culture development for the fermentation of buffalo's milk., Meekiri, Buffalo milk, Lactic acid bacteria, 16S rRNA sequencing, Probiotic.

Osteocytes comprise > 95% of the cellular component in bone tissue and produce a wide range of cytokines and cellular signaling molecules in response to mechanical stimuli. In this review, we aimed to summarize the molecular mechanisms involved in the osteocyte-mediated translation of mechanical stimuli to cellular signaling, and discuss their role in skeletal (bone) diseases and extra-skeletal (non-bone) clinical complications. Two decades before, osteocytes were assumed as a dormant cells buried in bone matrix. In recent years, emerging evidences have shown that osteocytes are pivotal not only for bone homeostasis but also for vital organ functions such as muscle, kidney, and heart. Osteocyte mechanotransduction regulates osteoblast and osteoclast function and maintains bone homeostasis. Mechanical stimuli modulate the release of osteocyte-derived cytokines, signaling molecules, and extracellular cellular vesicles that regulate not only the surrounding bone cell function and bone homeostasis but also the distant organ function in a paracrine and endocrine fashion. Mechanical loading and unloading modulate the osteocytic release of NO, PGE2, and ATPs that regulates multiple cellular signaling such as Wnt/β-catenin, RANKL/OPG, BMPs, PTH, IGF1, VEGF, sclerostin, and others. Therefore, the in-depth study of the molecular mechanism of osteocyte mechanotransduction could unravel therapeutic targets for various bone and non-bone-related clinical complications such as osteoporosis, sarcopenia, and cancer metastasis to bone.

Cuprous oxide nanoparticles were synthesized by the reduction of copper sulphate pentahydrate salt at different concentration using sodium borohydride as a reducing agent, polyethylene glycol-6000 as a stabilizer by simple, chemical co-precipitation methods and the effect of concentration on particle size were also studied. The crystalline size and phase of Cu2O nanoparticles (NPs) were authenticated by X-ray diffraction (XRD), morphology and structure by scanning electron microscopy (SEM), transmission electron microscopy (TEM), and elemental analysis was carried out by energy-dispersive X-ray spectroscopy (EDX). The concentration-dependent antimicrobial properties of Cu2O NPs were studied for a different strain of bacteria. XRD and selected area electron diffraction studies (SAED) patterns confirmed the formation of face-centered-cubic Cu2O nanoparticles with size 4.77 nm and 8.02 nm at two different concentrations of 0.01 M and 0.1 M CuSO4, respectively. SEM and TEM images showed that the nanoparticles were uniform, in the form of clusters, and homogeneously distributed. EDX confirmed that synthesized nanoparticles were in pure form having copper and oxygen ratio 3:1 based on the atomic percentage of the chemical species. Cu2O nanoparticles showed excellent antibacterial activity against both bacterial strains Gram-positive (Staphylococcus aureus) and Gram-negative (Escherichia coli). The antibacterial activities of Cu2O NPs were found to be concentration-dependents and large bactericidal effect were seen for Gram-positive (Staphylococcus aureus) bacteria at higher concentrations of Cu2O NPs.

This study was conducted to evaluate the effects of sodium bisulfate (SBS), lactic acid (LA), phosphoric acid (PA), and combinations of organic acids with SBS on Salmonella in rendered chicken fat and in water. The MICs of the antimicrobials individually and in combination were determined. Efficacies of the antimicrobials against Salmonella were tested in both media. The MICs of SBS, LA, and PA were 0.5, 0.5, and 0.25%, respectively. At the given concentrations in the water phase, 0.5% SBS was more effective (P 4-log reductions at 2 h and complete kill at 6 h. After 24 h, each of the chemicals completely eliminated the Salmonella. However, because of low recovery in the fat phase, Salmonella was not detected after 12 h and all three chemicals effectively reduced (P 5.5 log CFU/mL after 12 h. The SBS+LA combinations were effective (P < 0.05) after 2 h. The combinations of SBS+PA resulted in ∼3.5-log reductions in Salmonella (P < 0.05) after 6 h. In the fat phase, except for the SBS+PA combination, Salmonella reduction was not different from that for the positive control. When SBS was combined with organic acids, Salmonella inhibition was achieved at a lower SBS concentration, indicating a possibly synergistic effect of these chemicals. These results suggest that inclusion of SBS or LA at 0.5% individually or a combination of SBS with organic acids could reduce Salmonella in rendered chicken fat contaminated by residual water encountered during storage and transport.

Laminates or sequential build-up (SBU) laminate comprised of dielectric materials, metal traces, and metal vias not only serve as the mechanical support for the silicon integrated circuits (ICs), but also electrically connect ICs to ball grid array (BGA); by way of an embedded power delivery structure. Electrical current required to power the ICs is carried through spatially distributed metal traces and vias. The non-uniformity in the power distribution may induce hotspots due to parasitic Ohmic heating; especially in regions with high current density. Electrical packaging engineers need effective tools to identify, quantify, and mitigate hot spots in the laminate. Thermoelectrical multiphysical simulation provides a robust platform integrating the electrical, and thermal analyses for the study of joule heating in a complex design. Conventional simulations simplify detailed laminate wiring layout as a single planar with effective orthogonal material properties. Such simplification provides a solution to the inherent simulation challenges encountered with a complex design (i.e. tiny characteristic lengths, high aspect ratios, excessive computational time and resources). However, simplification comes with a price. Information required to optimize the detail trace and via wiring physical design is unavailable in a solution incorporating an effective laminate; laminate joule heating as well as non-uniform trace wiring are left out. The laminate temperature profile is averaged based on effective material properties. Without accurate joule heating evaluation, the hotspots cannot be identified or quantified. Overheating inside the laminate compromises signal speed and integrity, raises reliability concerns, and may even trigger catastrophic damage of dielectric material breakdown. This work introduces an iterative approach integrating the detailed laminate electrical computer aided design (ECAD) and package design to simulate the joule heating with minimum simplification. The iterative loop enables constant update of temperature (thru thermal simulation platform) and power distribution (thru electrical simulation platform) in each trace layer and via. An accurate temperature dependent Joule Heating assessment is achieved upon convergence. The solution captures the dependence on temperature of the material properties and of the Joule heating itself. The package level structure including an IC with a power map is incorporated to simulate in-situ package operating condition. After thorough investigation and analyses of laminate joule heating phenomena under different conditions, a predictive curve for maximum temperature rise percentage has been proposed to guide laminate wiring layout physical design and optimization. A ratio exceeding 4–5% joule heating to IC power is recommended as the check point for simulation to assess laminate overheating issues with detailed trace layout information.

Organoleptic properties of skimmed milk fermented gels are progressively demanding to produce optimal quality yogurts. Chr-Hansen trademark registered cultures were used to produce low-protein (3.4%) gels to assess the ability to redesign the sensorial and textural properties with the choice of starter culture. Resulting gels were assessed for sensorial, textural, rheological, and microstructural properties and compared with a commercial control (4.5% protein). Mouth thickness, syneresis, firmness, elasticity, and consistency values were lower for polysaccharides-producing cultures. Such cultures contributed to the higher creaminess and tended to give higher ropiness. Observed differences among microstructures of the gel were minute. Microstructural and rheological data corresponded and reflected the instrumental and sensory interpretations. Strong correlations were observed between sensory and instrumental data. Nonprobiotics cultures resulted in promising overall gel properties compared with probiotic cultures according to the principal component analysis. Yet probiotic cultures resulted in lower syneresis than nonprobiotic cultures. Thus, the choice of bacterial culture modifies the sensorial and textural properties of fermented gel with strong correlations, as a result of altered gel network formation with the production of polysaccharides. Inferior textural and sensorial quality aspects, particularly at low protein levels, have negative impact on consumer demand of low protein yogurts. Thus, we attempted to gain required gel textural and sensorial properties with a choice of starter culture with a low protein level. Resulting gel properties at lowered protein content with different starter cultures are not fully known. The present study compares the effect of probiotic and nonprobiotic starter cultures on gel properties, as gel texture and sensory properties are of great interest and thus not willing to be compromised. In addition, we examined the overall texture profile of studied cultures and correlate with sensory properties. Therefore, reducing protein level in milk and achieving required gel properties with the choice of appropriate starter culture is of great commercial interest as a cost-cutting strategy to produce low-cost optimum quality yogurt.

Objective: The primary objective of the project was to formulate and evaluate hard capsule containing the solution of ibuprofen. It also included enhancement of solubility of ibuprofen in hydrophilic solvents to obtain a unit dose capsule acceptable for human consumption. Methods: Solution of ibuprofen was developed by the salt formation of partial drug using potassium hydroxide in PEG 600 and water. The solution was encapsulated in hard capsules with band sealing. The final formulation was evaluated for uniformity of weight, disintegration, drug content and stability. The dissolution profile was compared with that of available marketed tablets and softgels. Results: The capsules were evaluated and found compliant as per specifications mentioned in general monograph of capsules in IP 2014. The uniformity of weight of the batch of capsules was found to be 734.8 mg (±0.58). The disintegration time of these capsules was observed to be 4.45 min. The drug content was found to be 100.03% and the product is stable over three months of test period under room temperature as well as accelerated conditions. The dissolution profile showed that softgels take longer time to release the drug whereas marketed tablets showed a dissolution profile comparable with that of formulated capsules. Conclusion: The developed capsule is a unit dose of liquid containing solubilized ibuprofen delivering the drug directly into the gastrointestinal tract (GIT). These are newer solid oral dosage forms with higher patient compliance and ease in manufacturing. They require lesser steps and manufacturing area when compared to the manufacturing of compressed tablets.

An elevated level of pro-inflammatory cytokines in inflammatory conditions causes bone loss and disrupts vital organ function. Osteocytes comprise > 95% of the cellular component in bone tissue, produce a range of cytokines and signaling molecules, and influence bone and other organ function. In this review, we hypothesized that an elevated level of pro-inflammatory cytokines in inflammatory conditions affects osteocyte survival and function thereby possibly amplifying inflammation, and causing bone loss and non-bone clinical complications. Several studies have reported that the elevated level of pro-inflammatory cytokines in inflammatory conditions alters osteocyte mechanosensitivity, causes osteocyte apoptosis, and modulates osteocyte-derived production of various inflammatory cytokines and signaling molecules. Cytokines and signaling molecules released from osteocytes affect surrounding bone cells and distant organ function in a paracrine and endocrine fashion. Inflammatory diseases including diabetes, chronic kidney disease, rheumatoid arthritis, and periodontitis affect osteocyte survival and function, and upregulate osteocyte-derived expression of sclerostin, RANKL, TNFα, FGF23, DKK1, and other signaling molecules.

Ultrasonic processing of fermented milk products has created much interest in current research on dairy products. This has been employed in cultured milk products to enhance the emulsification of milk fat and to intensify the fermentation process. Benefits including remarkable product stability, reduced processing time and enhanced quality are being recorded. Ultrasound (US) altered the colour and flavour profile of milk; however, the effect of US-induced fermentation on the synthesis of flavour compounds in milk has not been reported in the literature. This review paper presents a comprehensive scenario on the impact of power US on the fermentation profile and quality of ultrasonically processed dairy products. A theoretical background on US and details of its effect on the metabolic performance of lactic acid bacteria are presented. Finally, it describes how the quality attributes of fermented milk gels are modified due to the intensification of the fermentation process with US.

The occurrence of recalls involving pathogenic Escherichia coli-contaminated wheat flours show the need for incorporating antimicrobial interventions in wheat milling. The objectives of this study were to assess the efficacy of sodium bisulfate (SBS) tempering in reducing E. coli O121 (ATCC 2219) and O26 (ATCC 2196) wheat load and to evaluate the impact of effective (≥3.0 log reductions) SBS treatments on wheat flour quality. Wheat grains were inoculated with E. coli (~6 log CFU/g) and tempered (17% moisture, 24 h) using the following SBS concentrations (%wheat basis): 0, 0.5, 0.75, 1.0, 1.25, and 1.5% SBS. Reductions in E. coli O121 and O26 wheat load at different time intervals (0.5, 2, 6, 12, 18, and 24 h) during tempering were evaluated. The addition of SBS during tempering resulted in E. coli (O121 and O26) log reductions of 2.0 (0.5% SBS) to &gt, 4.0 logs (1.5% SBS) (p ≤ 0.05). SBS tempering (1.25 and 1.5% SBS) produced acidic wheat flours (pH = 4.51–4.60) but had comparable wheat flour properties in terms of composition, dough, and bread-making properties relative to the control (0% SBS). SBS tempering reduced the E. coli O121 and O26 load of wheat after tempering with minimal effects on wheat flour quality.

Halide perovskite materials have attracted great interest for applications in low-cost, solution-processed solar cells and other optoelectronics applications. The role of moisture in perovskite device degradation and crystal formation processes remains poorly understood. Here, we use a data-driven approach to discover the influence of trace amounts of water on perovskite crystal formation by analyzing a comprehensive dataset of 8470 inverse-temperature crystallization lead iodide perovskite synthesis reactions, performed over 20 months using a robotic system. We identified discrepancies between the empirical crystal formation rates in batches of experiments conducted under different ambient relative humidity conditions for each organoammonium cation. We prioritized these using a statistical model and then used the robotic system to conduct 1296 controlled interventional experiments, in which small amounts of water were deliberately introduced to the reactions. The addition of trace amounts of water promotes crystal formation for 4-methoxyphenylammonium lead iodide and iso-propylammonium lead iodide and inhibits crystal formation for dimethylammonium lead iodide and acetamidinium lead iodide. We also performed thin-film syntheses of these four materials and determined the grain size distributions using scanning electron microscopy. The addition of water results in smaller grain sizes for dimethylammonium and larger grain sizes for iso-propylammonium, consistent with earlier or delayed nucleation, respectively. The agreement between the inverse temperature crystallization and thin film results indicates that this is a feature of the organoammonium-water interaction that persists despite differences in the synthesis method.

Synthetic membranes are currently employed for multiple separation applications in various industries. They may have been prepared from organic or inorganic materials. Present research majorly focuses on polymeric (i.e., organic) membranes because they show better flexibility, pore formation mechanism, and thermal and chemical stability, and demand less area for installation. Dendritic, carbon nanotube, graphene and graphene oxide, metal and metal oxide, zwitter-ionic, and zeolite-based membranes are among the most promised water treatment membranes. This paper critically reviews the ongoing developments to utilize nanocomposite membranes to purify water. Various membranes have been reported to study their resistance and fouling properties. A special focus is given towards multiple ways in which these nanocomposite membranes can be employed. Therefore, this review provides a platform to develop the awareness of current research and motivate its readers to make further progress for utilizing nanocomposite membranes in water purification.

Uncontrolled drug-seeking and -taking behaviors are generally driven by maladaptive corticostriatal synaptic plasticity. The orbital frontal cortex (OFC) and its projections to the dorsomedial striatum (DMS) have been extensively implicated in drug-seeking and relapse behaviors. The influence of the synaptic plasticity of OFC projections to the DMS (OFC→DMS) on drug-seeking and -taking behaviors has not been fully characterized. To investigate this, we trained rats to self-administer 20% alcohol and then delivered an in vivo optogenetic protocol designed to induce long-term potentiation (LTP) selectively at OFC→DMS synapses. We selected LTP induction because we found that voluntary alcohol self-administration suppressed OFC→DMS transmission and LTP may normalize this transmission, consequently reducing alcohol-seeking behavior. Importantly, ex vivo slice electrophysiology studies confirmed that this in vivo optical stimulation protocol resulted in a significant increase in excitatory OFC→DMS transmission strength on day two after stimulation, suggesting that LTP was induced in vivo. Rat alcohol-seeking and -taking behaviors were significantly reduced on days 1-3, but not on days 7-11, after LTP induction. Striatal synaptic plasticity is modulated by several critical neurotransmitter receptors, including dopamine D1 receptors (D1Rs) and adenosine A2A receptors (A2ARs). We found that delivery of in vivo optical stimulation in the presence of a D1R antagonist abolished the LTP-associated decrease in alcohol-seeking behavior, whereas delivery in the presence of an A2AR antagonist may facilitate this LTP-induced behavioral change. These results demonstrate that alcohol-seeking behavior was negatively regulated by the potentiation of excitatory OFC→DMS neurotransmission. Our findings provide direct evidence that the OFC exerts "top-down" control of alcohol-seeking behavior via the DMS.

Pectinases are a group of enzymes with broad application, including in plant fiber processing, pectic wastewater treatment, paper pulping, fruit juice extraction, and clarification. With an increasing industrial demand for these enzymes, it is useful to isolate organisms that produce large amounts of pectinase and possess wide ranges of stability factors like temperature and pH. In this study, 17 out of 29 bacteria (58.62%) from forest soil samples were pectinolytic. However, only four bacteria (S-5, S-10, S-14, and S-17) showed high pectin hydrolysis zones (ranging from 0.2 cm to 1.7 cm). These four bacteria were identified based on colony morphology, microscopic characterization, biochemical characteristics, and 16S rDNA sequencing. They were designated as Streptomyces sp. (S-5, S-14), Cellulomonas sp. (S-10), and Bacillus sp. (S-17). Interestingly, bacteria showed cellulase and xylanase activity in addition to pectinase. The quantitative assay for pectinase activity of the four isolates provided proof that they are pectinase producers and can be considered potential candidates for industrial uses. The crude enzyme extracts of these bacteria are applicable in oil and juice extraction from sesame seeds and apples, respectively.

Introduction The Endosialin/CD248/TEM1 protein is expressed in adipose tissue and its expression increases with obesity. Recently, genetic deletion of CD248 has been shown to protect mice against atherosclerosis on a high fat diet. Objectives We investigated the effect of high fat diet feeding on visceral fat pads and circulating lipid profiles in CD248 knockout mice compared to controls. Methods From 10 weeks old, CD248−/− and +/+ mice were fed either chow (normal) diet or a high fat diet for 13 weeks. After 13 weeks the metabolic profiles and relative quantities of circulating lipid species were assessed using ultra high performance liquid chromatography-quadrupole time-of flight mass spectrometry (UHPLC–MS) with high resolution accurate mass (HRAM) capability. Results We demonstrate a specific reduction in the size of the perirenal fat pad in CD248−/− mice compared to CD248+/+, despite similar food intake. More strikingly, we identify significant, diet-dependent differences in the serum metabolic phenotypes of CD248 null compared to age and sex-matched wildtype control mice. Generalised protection from HFD-induced lipid accumulation was observed in CD248 null mice compared to wildtype, with particular reduction noted in the lysophosphatidylcholines, phosphatidylcholines, cholesterol and carnitine. Conclusions Overall these results show a clear and protective metabolic consequence of CD248 deletion in mice, implicating CD248 in lipid metabolism or trafficking and opening new avenues for further investigation using anti-CD248 targeting agents.

Hydrogen is a promising alternative to fossil fuels because of its environment-friendly characteristics. It has been used widely in varied sectors such as chemical production, electronic devices, food industries, desulfurization of crude oil, and steel industries. Due to its increasing use and demand, it is essential to develop a cheaper and energy-efficient source of hydrogen production. This review synthesizes and discusses various aspects of hydrogen production methods and processes, the challenges, and economic perspective for sustainable production of biohydrogen. Compared to electrolysis, thermochemical and electrochemical processes, the biohydrogen production is environment friendly and energy efficient. Various factors such as feedstock, pH, temperature, partial pressure of hydrogen, and hydraulic retention time are responsible for the biological process and yield of biological hydrogen production. This review suggests that lignocellulosic biomass is commonly available, cheaper and eco-friendly source of hydrogen production.

In the present study, we propose a novel field-scale analytical tool for rapid screening of microbiological quality in raw milk using aqueous extracts of plant materials, i.e. flowers (e.g. Hibiscus rosa-sinensis L. and Clitoria ternatea), taproots (e.g. Beta vulgaris) and pricklypears (e.g. Opuntia dillenii). For each plant extract, the colour changes in raw milk were evaluated between 4.5 and 6.5 pH against the resazurin dye as a control. The plant anthocyanin content in each extract was analyzed by the differential pH method using a spectrophotometer. The Hibiscus rosa-sinensis flower extract was opted to further test since it had a pH-sensitive colour change (6.5; maroon to 6.2; light-pink) compared to other plant extracts, which did not indicate a noticeable colour variation with pH. Anthocyanin content of the Hibiscus extract was 0.59 g/mL. The novel method showed high linearity (R2 = 0.95), 100% accuracy and greater repeatability with an intermediate level of precision. The limit of quantification and detection was 0.46 and 0.15 g/mL, respectively. In conclusion, we demonstrated the potential in using water extract of Hibiscus rosa-sinensis L. flowers as an alternative to the resazurin dye reduction method for rapid and accurate microbiological quality control for raw milk procurement in remote areas.

Background: Bone grafts are in high demand due to the increase in the cases of bone defects mainly caused by trauma, old age, and disease-related bone damages. Tissue-engineered calcium phosphate (CaP) biomaterials match the major inorganic contents of bone, thereby could be the potential bone graft substitute. However, CaP-bone grafts lack the osteoinductivity that is vital for effective bone regeneration. In this study, we aimed to test the bone defect healing potential of biomimetically fabricated low dose BMP2-doped CaP (BMP2.BioCaP) grafts in a large animal model.Methods: Low dose BMP2 was doped internally (BMP2-int.BioCaP) or on the surface of CaP (BMP2-sur.BioCaP) grafts during the fabrication process. Our previous study showed the robust bone regenerative potential of BMP2-int.BioCaP and BMP2-sur.BioCaP grafts in the rat ectopic model. In this study, we investigated the bone defect healing potential of BMP2.BioCaP grafts in sheep humerus/femoral defects, as well as compared with that of autologous bone graft and clinically used deproteinized bovine bone (DBB) xenograft.Results: Different ways of BMP2 doping did not affect the surface morphology and degradation properties of the graft materials. Micro-CT and histology results showed robustly higher bone defect-healing potential of the BMP2.BioCaP grafts compared to clinically used DBB grafts. The bone defect healing potential of BMP2.BioCaP grafts was as effective as that of the autologous bone graft. Although, BMP2-int.BioCaP doped half the amount of BMP2 compared to BMP2-sur.BioCaP, its' bone defect healing potential was even robust. The BMP2.BioCaP grafts showed less immunogenicity compared to BioCaP or DBB grafts. The volume density of blood vessel-like and bone marrow-like structures in both BMP2.BioCaP graft groups were in a similar extent to the autologous group. Meticulous observation of higher magnification histological images showed active bone regeneration and remodeling during bone defect healing in BMP2.BioCaP graft groups.Conclusion: The robust bone regenerative potential of BMP2.BioCaP grafts in the ectopic model and in-situ bone defects in small and large animals warrant the pre-clinical studies on large animal critical-sized segmental bone defects.

Giardiasis, caused by the intestinal parasite Giardia lamblia, is a severe diarrheal disease, endemic in poverty-stricken regions of the world, and also a common infection in developed countries. The available therapeutic options are associated with adverse effects, and G. lamblia resistance to the standard-of-care drugs is spreading. Fumagillin, an antimicrosporidiosis drug, is a therapeutic agent with potential for the treatment of giardiasis. However, it exhibits considerable, albeit reversible, toxicity when used to treat immunocompromised microsporidiosis patients. Fumagillin is also a highly unstable compound. To address these liabilities, we designed and synthesized stable fumagillol derivatives with lower levels of permeation across polarized epithelial Caco-2 cells and better potency against G. lamblia trophozoites than fumagillin. Metronidazole-resistant G. lamblia strains were also susceptible to the new fumagillol derivatives. In addition, these compounds were more potent against the amebiasis-causing parasite Entamoeba histolytica than fumagillin. Two compounds exhibited better thermal and acid stability than fumagillin, which should prolong the drug shelf life and reduce compound degradation in the stomach. Studies with a mouse model of giardiasis with the most stable compound, 4-(((((3R,4S,5S,6R)-5-methoxy-4-((2R,3R)-2-methyl-3-(3-methylbut-2-en-1-yl)oxiran-2-yl)-1-oxaspiro[2.5]octan-6-yl)oxy)carbonyl)amino)benzoic acid (compound 9), revealed that it had better efficacy (effective dose [ED]) than fumagillin at both the fully curative dose (the 100% ED) of 6.6 mg/kg of body weight and a 50% ED of 0.064 mg/kg. Plasma pharmacokinetics revealed the slow absorption of compound 9 through the gut, consistent with the in vitro characterization in Caco-2 cells. An acute-dose study yielded a maximum tolerated dose (MTD) of 1,500 mg/kg, 227-fold higher than the fully curative dose. Thus, along with improved stability, compound 9 also exhibited an excellent therapeutic window.

Fibrin gel-based scaffolds have promising potential for microtia reconstruction. Autologous chondrocytes and chondrocyte cell sheets are frequently used seed cell sources for cartilage tissue engineering. However, the aesthetic outcome of chondrocyte-based microtia reconstruction is still not satisfactory. In this study, we aimed to fabricate the chondrocytes/chondrocyte-microtissues laden fibrin gel auricular scaffold for microtia reconstruction. We designed a unique auricular mold that could fabricate a fibrin gel scaffold resembling human auricle anatomy. Primary chondrocytes were harvested from rabbit auricular cartilage, and chondrocyte cell sheets were developed. Chondrocyte-microtissues were prepared from the cell sheets. The mixture of chondrocytes/chondrocyte-microtissues was laden in fibrin gel during the auricular scaffold fabrication. The protrusions and recessed structure in the auricular scaffold surface were still clearly distinguishable. After a one-week in vitro culture, the 3 D structure and auricular anatomy of the scaffold were retained. And followed by eight-week subcutaneous implantation, cartilaginous tissue was regenerated in the artificial auricular structure as indicated by the results of H&E, Toluidine blue, Safranin O, and type II collagen (immunohistochemistry) staining. Protrusions and depressions of the auricular scaffold were slightly deformed, but the overall auricular anatomy was maintained after 8-week in vivo implantation. Extracellular matrix components content were similar in artificial auricular cartilage and rabbit native auricular cartilage. In conclusion, the mixture of chondrocytes/chondrocyte-microtissues laden fibrin gel auricular scaffold showed a promising potential for cartilaginous tissue regeneration, suggesting this as an effective approach for autologous chondrocyte-based microtia reconstruction.

Osteocytes are the most abundant (~95%) cells in bone with the longest half-life (~25 years) in humans. In the past osteocytes have been regarded as vestigial cells in bone, since they are buried inside the tough bone matrix. However, during the last 30 years it has become clear that osteocytes are as important as bone forming osteoblasts and bone resorbing osteoclasts in maintaining bone homeostasis. The osteocyte cell body and dendritic processes reside in bone in a complex lacuno-canalicular system, which allows the direct networking of osteocytes to their neighboring osteocytes, osteoblasts, osteoclasts, bone marrow, blood vessels, and nerves. Mechanosensing of osteocytes translates the applied mechanical force on bone to cellular signaling and regulation of bone adaptation. The osteocyte lacuno-canalicular system is highly efficient in transferring external mechanical force on bone to the osteocyte cell body and dendritic processes via displacement of fluid in the lacuno-canalicular space. Osteocyte mechanotransduction regulates the formation and function of the osteoblasts and osteoclasts to maintain bone homeostasis. Osteocytes produce a variety of proteins and signaling molecules such as sclerostin, cathepsin K, Wnts, DKK1, DMP1, IGF1, and RANKL/OPG to regulate osteoblast and osteoclast activity. Various genetic abnormality-associated rare bone diseases are related to disrupted osteocyte functions, including sclerosteosis, van Buchem disease, hypophosphatemic rickets, and WNT1 and plastin3 mutation-related disorders. Meticulous studies during the last 15 years on disrupted osteocyte function in rare bone diseases guided for the development of various novel therapeutic agents to treat bone diseases. Studies on genetic, molecular, and cellular mechanisms of sclerosteosis and van Buchem disease revealed a role for sclerostin in bone homeostasis, which led to the development of the sclerostin antibody to treat osteoporosis and other bone degenerative diseases. The mechanism of many other rare bone diseases and the role of the osteocyte in the development of such conditions still needs to be investigated. In this review, we mainly discuss the knowledge obtained during the last 30 years on the role of the osteocyte in rare bone diseases. We speculate about future research directions to develop novel therapeutic drugs targeting osteocyte functions to treat both common and rare bone diseases.

Dicalcium silicate microparticle (C2S)-based biomaterials have a potential for bone and dental tissue regenerative applications. The C2S-mediated transcriptome level mechanism in mesenchymal stem cells (MSCs) during bone-defect healing has not been investigated yet. In this study, we elucidated the differential expression pattern of messenger RNAs (mRNAs) and circular RNAs (circRNAs) in C2S-treated MSCs and their involvement in the osteogenesis process. C2S robustly enhanced the osteogenic differentiation of MSCs and cranial bone defect healing. C2S-treatment modulated the differential expression of mRNAs and circRNAs in MSCs. Differentially expressed circRNAs and mRNAs were involved in competing endogenous RNA (ceRNA-interaction networks). These ceRNA-interaction networks regulated the signaling pathways associated with osteogenesis, e.g., Wnt, PI3K-Akt, MAPK, and JAK/STAT signaling. C2S-treatment upregulated the expression of circ_1983, Gas7, and Runx2 in BMSCs. RNase R and luciferase activity assay confirmed the stability and miR-6931 sponging property of circ_1983, respectively. Knockdown of circ_1983 enhanced miR-6931 expression but inhibited Gas7 and Runx2 expression and osteogenic differentiation in C2S-treated MSCs. In conclusion, for the first time, we report the role of cicr_1983-miR-6931-Gas7 ceRNA-interaction in C2S-induced osteogenic differentiation of MSCs and bone defect healing. This study opens a new research stream "the role of circRNAs-mediated ceRNA-interaction in biomaterials and stem cell-based bone tissue engineering".

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the strain of coronavirus that causes coronavirus disease 2019 (COVID-19), a respiratory illness. COVID-19 has now become a global public health crisis causing alarming numbers of morbidity and mortality. Ever since the COVID-19 pandemic started scientists, researchers, universities, companies, and institutions all around the world have been endeavoring to discover a potential treatment for COVID-19. Numerous studies and clinical trials on vaccines and drugs for the prevention and treatment of COVID-19 are underway across the world. However, the uncertainty around the efficacy and safety of various treatment regimens have become one of the biggest challenges in the battle against the SARS-CoV-2. This paper is a narrative review of articles regarding the various treatments and vaccines being tested for the SARS-CoV-2, available in the PubMed database along with Google Scholar. There are ongoing clinical trials on potential drugs such as remdesivir, favipiravir, lopinavir/ritonavir, chloroquine, and hydroxychloroquine, corticosteroids tocilizumab, azithromycin, anakinra, etc. and other therapeutic modalities like convalescent plasma therapy. Likewise, vaccines against SARS-CoV-2 are being developed and tested, including mRNA, non-replicating viral vector, DNA, protein subunit candidate vaccines, etc. Although some early-stage clinical trials and studies on these drugs and vaccines have shown positive results, definitive and conclusive results are yet to be obtained. Keywords: COVID-19; antiviral drugs; COVID-19 treatment; COVID-19 vaccine; SARS-CoV-2

After reaching a device efficiency level comparable to silicon, perovskite solar cell's next big challenge is to tackle its environmental instability issue. To solve this problem, researchers have started incorporating a buffer layer called ‘capping layer’, consisting of low dimensional (LD) perovskite, sandwiched between perovskite absorber and hole transport layer. However, there is no conclusive agreement on how to select capping layer material that best extends the stability. By using feature importance rank on the regression models, we can start to see which molecular properties on capping layer have significant impact in suppressing degradation.

The differences in the recovery of Salmonella from rendered chicken fat treated with sodium bisulfate (SBS) when inoculated with a dry versus wet inoculum were evaluated. Food-grade rendered chicken fat was inoculated with a dry inoculum and a wet inoculum containing a cocktail of Salmonella serovars (Enteritidis, Heidelberg, and Typhimurium). In addition, the effect of an antimicrobial treatment (SBS) against Salmonella in both the aqueous phase and fat phase of the chicken fat was evaluated. The untreated control samples in the aqueous phase had a consistent level of Salmonella (∼7 log) when both the dry and wet inocula were used. In the SBS-treated aqueous phase, Salmonella pathogens were not detectable after 6 h when the wet inoculum was used; when the dry inoculum was used, Salmonella pathogens were not detectable at 24 h. Salmonella pathogens were detected for up to 6 h in the SBS-treated fat phase when the dry inoculum was used compared with 2 h with the wet inoculum. The 24-h fat samples that failed to show growth on Trypticase soy agar were enriched for Salmonella isolation, followed by confirmation by PCR using primers for the invA gene. SBS-treated and control samples from the dry-inoculated rendered chicken fat and the inoculated control from the wet-inoculated rendered chicken fat tested positive for Salmonella. However, the SBS-treated sample from the wet-inoculated fat was negative for Salmonella. The use of dry SBS powder against dry Salmonella inoculum in the fat matrix caused only ∼2.8-log reduction after 24 h compared with ∼2.2-log reduction in the positive control. However, the recovery of Salmonella from untreated control fat was lower and was not different (P > 0.05) from that recovered from the SBS-treated fat. The results suggest that viable but nonculturable states of Salmonella may develop in rendered chicken fat or that injured cells may be present, which indicates that testing should include an enrichment and appropriate molecular confirmation instead of agar plating alone. HIGHLIGHTS

Stem cells from human exfoliated deciduous teeth (SHEDs) are ideal seed cells in bone tissue engineering. As a first-line anti-diabetic drug, metformin has recently been found to promote bone formation. The purpose of this study was to investigate the effect of metformin on osteogenic differentiation of SHEDs and its underlying mechanism. SHEDs were isolated from the dental pulp of deciduous teeth from healthy children aged from 6 to 12, and their surface antigen markers of stem cells were detected by flow cytometry. The effect of metformin (10 - 200 μM) treatment on SHEDs cell viability, proliferation, and osteogenic differentiation was analyzed. The activation of adenosine 5'-monophosphate-activated protein kinase (AMPK) was determined by western blot assay for the AMPK phosphorylated at Thr172 (p-AMPK). SHEDs were confirmed as mesenchymal stem cells (MSCs) based on the expression of characteristic surface antigens. Metformin (10-200 μM) did not affect the viability and proliferation of SHEDs, but significantly increased the expression of osteogenic genes, the activity of alkaline phosphatase, matrix mineralization, and p-AMPK level in SHEDs. Compound C, a specific inhibitor of AMPK pathway, abolished metformin-induced osteogenic differentiation of SHEDs. Moreover, metformin treatment enhanced pro-angiogenic/osteogenic growth factors BMP2 and VEGF but reduced the osteoclastogenic factor RANKL/OPG expression in SHEDs. In conclusion, metformin could induce the osteogenic differentiation of SHEDs by activating the AMPK pathway and regulates the expression of pro-angiogenic/osteogenic growth factors and osteoclastogenic factors in SHEDs. Therefore, SHEDs, combined with metformin possesses therapeutic potential for bone regeneration and bone defect repair.

Introduction: Renal cell carcinoma epitomizes a diversified group of tumors which contributes more than 15,000 deaths annually worldwide. In spite of tremendous efforts to identify prognostic factors apart from grade, histology and tumor size, they are not so obvious yet to fulfill the requirement. In this study, the prognostic role of serum matrix metalloproteinase (MMP)-2, 9, and vascular endothelial growth factor (VEGF) levels in patients with pre and postoperative renal cell carcinoma are evaluated to use as biomarker. Patients and methods: A total of 100 patients with a diagnosis of renal cell carcinoma included in the study. Additionally, hundred healthy kidney donors enrolled as control, serum MMP-2, MMP-9, and VEGF levels were analyzed in the serum of post and preoperative patients and parallel in control serum samples by ELISA method. Result: Most of the patients with RCC were found to have high concentrations of serum MMP-2, MMP-9, and VEGF. The levels of MMP-2 in the serum of preoperative patients ranged from 627 to 1117 ng/ml (833.90 ± 111.91), postoperative MMP-2 range 302–913 (553.02 ± 150.08), control range 122–384 (228.33 ± 72.52). In MMP-9 pre-operative range 619–1233 (862.32 ± 119.77), post-operative range 124–909 (552.88 ± 151.91) and control range 42–467 (245.44 ± 116.52 and in VEGF preoperative range was 0.792–2.214 (1.35 ± 0.36), postoperative range was 0.315–1.917 (0.81 ± 0.46) and in control it was 0.01–0.39 (0.10 ± 0.09). We observed that preoperative levels of all three markers, were significantly increased if compared with postoperative and control levels (P = 0.001) however, no any significant correlation found when the levels correlated with grade, stage, size, and type for MMP-2 and MMP-9, but VEGF shows some significance in comparison. Conclusion: The present data shows relevance and strong significant decrease in the level of MMP-2, MMP-9, and VEGF after surgery, so they could use as biomarkers in early disease diagnosis and also in monitoring disease recurrence. Keywords: RCC, MMP-2, MMP-9, VEGF, Biomarker

Implant surface modification that provides local sustained release of osteoinductive therapeutic agents enhances implant stability. We designed a mesoporous TiO2-layered titanium implant (MLT) by modified anodization technique that allowed local sustained release of zoledronic acid up to 21 days. Mesoporous layer has pore size 15 nm, depth ∼30 μm, volume 0.32 cm3/g, surface area 112.3 m2/g, surface roughness 20 nm and water contact angle 18.3°. Zoledronic acid-loaded MLT (MLT-Z) was biocompatible, showed anabolic effect on bone forming osteoblasts and catabolic effect on bone resorbing osteoclasts. MLT or MLT-Z implants were implanted in osteoporotic rat-tail vertebrae. Smooth implant in healthy rats were used as a positive control. Histomorphometric analysis showed that bone implant contact of smooth implant in osteoporotic rats was reduced by 4.1-fold compared to healthy rats and MLT-Z rescued the effect by 53%. Similar effect was observed in implant fixation, mechanical stability, BV/TV ratio, Tb.N, Tb.Th and OI% among the groups. Histological and μ-CT images strongly supported the above-mentioned findings. In conclusion, a novel surface-fabricated MLT-Z gives local sustained drug release, robustly enhances implant osseointegration and stability in osteoporotic condition, suggesting it as a promising implant model for patients with compromised bone quality.

Micro- and nanocrystalline cellulose were extracted from wheat stalk (WS) using different thermomechanical and chemical treatments and characterized by spectroscopic, microscopic and diffraction techniques. The virgin WS fibers were found to be structurally quite similar to the commercial microcrystalline cellulose (MCC). Similar to the commercial one, the MCC extracted from the WS possessed intense infrared (IR) peaks whereas those peaks became more broader in the nanocrystalline cellulose (NCC) of the same origin, which can be attributed to possible breakdown of inter- and intramolecular H-bonding due to strong acid treatment of the MCC. Microscopic results revealed characteristic textures of the MCC and the NCC, the MCC being irregular bundles of the primary crystals bound together with the amorphous phase. The latter was found to disintegrate upon acid hydrolysis giving rise to the rod-shaped nanocrystals having much larger surface area and thus possessing more intense hydrophilic character. The MCC was found to be more stable than the NCC which can be attributed to the presence of protective and binding coating provided by the amorphous cellulosic matter.BIBECHANA 16 (2019) 177-186

For composites based on polypropylene (PP) filled with short carbon fibres (CF), extrusion-based additive manufacturing provides a promising and cost-effective manufacturing technique that utilises the flow-induced orientation of the fibres for their targeted alignment through the control of the printing direction. This study investigates the impact of the fibre orientation on mechanical properties and thermal conductivity of 3D-printed PP composites filled with short-CF. Provided a homogeneous fibre-dispersion and a good fibre-matrix adhesion, the composites showed considerably improved mechanical properties compared to neat PP regardless of the fibre orientation. However, for the different printing orientations, a strong anisotropy in terms of flexural and impact properties and thermal conductivity was observed. For example, it was found that the thermal conductivity along the printing and, thus, the fibre direction was three times higher than perpendicular to that direction. The present work provides a key to the fabrication of parts with tailored, orientation-dependent properties.