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Biofilm-mediated osteomyelitis presents significant therapeutic challenges. Given the limitations of existing osteomyelitis treatment approaches, there is a distinct need to develop a localized drug delivery system that is biocompatible, biodegradable, and capable of controlled antibiotic release. Multivesicular liposomes (MVLs), characterized by their non-concentric vesicular structure, distinct composition, and enhanced stability, serve as the system for a robust sustained-release drug delivery platform. In this study, various hydrogel formulations composed of poloxamer 407 and other hydrogels, incorporating vancomycin hydrochloride (VAN HL)-loaded MVLs (VAN HL-MVLs), were prepared and evaluated. The optimized VAN HL-MVL sol-gel system, consisting of poloxamer 407 and hyaluronic acid, successfully maintained drug release for up to 3 weeks and exhibited shear-thinning behavior at 37°C. While complete drug release from MVLs alone took place in 312 h, the hydrogel formulation extended this release to 504 h. The released drug effectively inhibited the Staphylococcus aureus biofilms growth within 24 h and methicillin-resistant S. aureus biofilms within 72 h. It also eradicated preformed biofilms of S. aureus and methicillin-resistant S. aureus in 96 and 120 h, respectively. This injectable in situ gel system incorporating VAN HL-MVLs holds potential as an alternative to undergoing multiple surgeries for osteomyelitis treatment and warrants further studies. [ABSTRACT FROM AUTHOR]

Understanding the attributes of critical data and implementing suitable security measures help organisations bolster their data-protection strategies and diminish the potential impacts of ransomware incidents. Unauthorised extraction and acquisition of data are the principal objectives of most cyber invasions. We underscore the severity of this issue using a recent attack by the Clop ransomware group, which exploited the MOVEit Transfer vulnerability and bypassed network-detection mechanisms to exfiltrate data via a Command and Control server. As a countermeasure, we propose a method called Buffer-Based Signature Verification (BBSV). This approach involves embedding 32-byte tags into files prior to their storage in the cloud, thus offering enhanced data protection. The BBSV method can be integrated into software like MOVEit Secure Managed File Transfer, thereby thwarting attempts by ransomware to exfiltrate data. Empirically tested using a BBSV prototype, our approach was able to successfully halt the encryption process for 80 ransomware instances from 70 ransomware families. BBSV not only stops the encryption but also prevents data exfiltration when data are moved or written from the original location by adversaries. We further develop a hypothetical exploit scenario in which an adversary manages to bypass the BBSV, illicitly transmits data to a Command and Control server, and then removes files from the original location. We construct an extended state space, in which each state represents a tuple that integrates user authentication and system components at the filesystem level. [ABSTRACT FROM AUTHOR]

Since 1980 after introducing the concept of live cell encapsulation by Lim et al., this technology has received enormous attention. Several studies have been conducted to improve this technique; different polymers, either natural or synthetic, have been used as microcapsules' making materials and different substances as coating layers. Literature review leads us to the conclusion that alginate (Alg) multilayer microcapsules and, in particular, alginate-poly l-lysine (PLL)-alginate (APA) are the most used structures for live cell encapsulation. Although, disadvantages of PLL (e.g., weak mechanical strength and low biocompatibility) made researchers work on other cationic polymers to find an alternative. This review aims to discuss more popularly suggested cationic polymers such as poly l-ornithine (PLO), chitosan, etc. As alternatives for PLL and, more importantly, we want to take a closer look to see which one of these systems are closer to clinical applications. [ABSTRACT FROM AUTHOR]

Staphylococcal Enterotoxin B (SEB) is a bacterial antigen that is responsible for food poisoning in humans. Cholera toxin is the most important virulence factor in Vibrio cholera. The gene sequence of ctxB and seb were obtained from GenBank and Site-specific mutagenesis (L45R, Y89A, and Y94A, respectively) was performed in the seb gene sequence, Three-dimensional protein structure, modeling, secondary and tertiary structure, immunogenicity, and allergenic sites were predicted using online bioinformatics software. In addition to gene codons to increase the expression of the rSEB-CTXB protein in the E.coli BL21 DE3 host, different parameters affecting expression were also optimized. The thermodynamic analysis of mRNA structure was performed to investigate the stability at the transcriptional stage. The physicochemical parameters and the predicted protein structure and quality of the structures were predicted. Linear and conformational epitopes were also considered. The antigen tendencies and estimated sensitivity were performed using Algpred software. The chimeric protein is topologically close to native proteins and all domains had surface accessibility and showed the highest antigenicity index. The Codon Adaptation Index of chimer increased from 0.7 to 0.89. The protein structure showed that the predicted structure had good quality. The evaluation of silicon chimeric proteins showed that the model is suitable for the stability and solubility of mRNA. Constitutive and linear epitopes were observed in all three chimeric protein domains. This study showed that these results could have implications for the production of chimeric immunogen antigen against the toxicity of Staphylococcus aureus and Vibrio cholerae in animal models. The ctxB and Seb genes were examined for rare codons, and the genes were optimized, followed by bioinformatics. Protein expression was assessed by PAGE-SDS and Western blotting. The expression of recombinant protein from the synthetic gene led to the production of a protein with a size 51 kD. Conclusion: According to the results of bioinformatics studies and recombinant protein expression, it can be used as an immunogen for safety studies against Vibrio cholerae producing Cholera toxin and Staphylococcus aureus producing enterotoxin SEB. [ABSTRACT FROM AUTHOR]

Purpose: Poly l-lysine (PLL) has been introduced as a strengthening covering layer for alginate microcapsules which are the most convenient way for cell encapsulation. Some disadvantages of PLL such as high price and low biocompatibility have prompted scientists to find better alternatives. Linear poly ethylene imine (LPEI), thanks to its highly similar structure to PLL, could be considered as a proper cost-effective alternative. In this study LPEI and PLL were compared as covering layers of cell-loaded alginate-LPEI-alginate (cALA) and alginate-PLL-alginate (cAPA) microcapsules. Methods: In addition to the physico-mechanical properties, the encapsulation efficiency, cell survival post encapsulation, cell viability, and cellular metabolic activity within the microcapsules were evaluated using trypan blue, live/dead cell staining, and MTT test, respectively. Results: Physico-mechanical evaluation of the microcapsules revealed that the cell microencapsulation process did not affect their shape, size, and mechanical stability. Although the encapsulation efficiency for cALA and cAPA was not different (P > 0.05), cell survival post encapsulation was higher in cALA than in cAPA (P < 0.05) which could be the reason for the higher cell viability and also cellular metabolic activity within these microcapsules in comparison to cAPA. Conclusion: Here, based on these results, ALA could be introduced as a preferable alternative to APA for cell encapsulation. [ABSTRACT FROM AUTHOR]

In past decades, alginate-based multilayer microcapsules have been given important attention in various pharmaceutical investigations. Alginate-poly l lysine-alginate (APA) is studied the most. Due to the similarity between the structure of polyethyleneimine (PEI) and poly-L-lysine (PLL) and also lower price of PEI than PLL, this study was conducted to compare the efficacy of linear (LPEI) and branch (BPEI) forms of PEI with PLL as covering layers in fabrication of microcapsules. The microcapsules were fabricated using electrostatic bead generator and their shape/size, surface roughness, mechanical strength, and interlayer interactions were also investigated using optical microscopy, AFM, explosion test and FTIR, respectively. Furthermore, cytotoxicity was evaluated by comparing the two anionic final covering layers alginate (Alg) and sodium cellulose sulphate (NCS) using MTT test. BPEI was excluded from the rest of the study due to its less capacity to strengthen the microcapsules and also the aggregation of the resultant alginate-BPEI-alginate microcapsules, while LPEI showed properties similar to PLL. MTT test also showed that NCS has no superiority over Alg as final covering layer. Therefore, it is concluded that, LPEI could be considered as a more cost effective alternative to PLL and a promising subject for future studies. [ABSTRACT FROM AUTHOR]

Objectives: It has been shown that nifedipine cream 0.5% is effective in the treatment of anal fissure and in reducing facial wrinkles. However, no commercially manufactured formulation of this product is available in some countries and prescriptions for the medication need to be extemporaneously compounded by retail pharmacies. So, the aim of this study was to evaluate the quality of the compounded nifedipine cream 0.5%. Methods: Twenty‐one compounding pharmacies within Tehran area were randomly included in this study. A physician wrote the prescriptions for compounded nifedipine in dexpanthenol cream (0.5%) for fictitious patients, with two refills allowed per prescription. The extemporaneous products were analysed for potency and microbial limit using validated methods. Key findings: There was a significant variability both within and between pharmacies with respect to the potency of the compounded products. By contrast, no microbial contamination was detected in these products. Of 63 prescriptions, nifedipine concentration of 21 products (33.33%) was within ±20% of the prescribed dose. Thirty‐ nine (61.90%) were sub‐potent, which ranged in potency from 24.33–77.57%. One pharmacy provided products with essentially no nifedipine. Conclusion: Compounded nifedipine obtained from pharmacies in this study did not raise safety concerns when assessed for microbial contamination. However, compounded products may be misbranded, which may negatively impact the management of anal fissure and facial wrinkles. [ABSTRACT FROM AUTHOR]

Many herbs and spices have been recommended traditionally as galactagogues and several commercial formulations prepared using herbs. Due to the presence of various compounds such as polyphenols, flavonoids, isoflavones, and terpenes, bitter and stringent taste is elicited that make the consumption of these herbal preparations unpleasant. Moreover, these compounds are unstable when exposed to environmental conditions. In this regard, different approaches are used for taste masking such as microencapsulation. In the present study, microcapsules containing herbal galactagogue extract were developed through emulsification/ external gelation and Box-Behnken design was used to investigate the effects of independent variables (sodium alginate: 1-1.5%, calcium chloride: 0.2-1% and extract concentrations: 1-5%) on encapsulation efficiency (EE%). Following evaluation of the model, the optimum condition of encapsulation process was selected as 1.49% sodium alginate, 0.84 CaCl2, and 1.58% extract with EE% of 77.97%. Microcapsules had an acceptable spherical morphology and the results of Fourier transform-infrared spectroscopy (FTIR) revealed the presence of the extract within the microcapsules. The mean diameters of the uncoated and chitosan-coated microcapsules were 52 and 123 µm and encapsulation yield was 50.21 and 69.7%, respectively. The polydispersity index of 0.45 and 0.48 were an indicative of polydisperse nature of the microcapsules. The loss of flavonoids in microcapsules stored at two different temperatures was insignificant. The in-vitro release in simulated gastric fluid (SGF; pH 1.2) and simulated intestinal fluid (SIF; pH 7.4) were 48.1% and 80.11%, respectively during 24 h. The prepared extract-loaded microcapsules have potential to be used in matrices with neutral pH. [ABSTRACT FROM AUTHOR]

In this study a simple and reliable stability-indicating RP-HPLC method was developed and validated for analysis of Dexpanthenol in an artificial tear formulation. The chromatographic separation was performed on a HPLC C18 column (25.0 cm × 4.6 mm, 5 mm) using a mixture of 0.037 M monobasic potassium phosphate in water (adjusted with 0.1% (v/v) phosphoric acid to a pH of 3.2) and methanol (90:10). The flow rate was set at 1.5 mL/min and Dexpanthenol concentration was determined at λmax = 205 nm. The HPLC analysis method was validated in terms of linearity, precision, accuracy, specificity, and sensitivity according to International Conference on Harmonization (ICH) guidelines. The results indicated that the retention time was 8 min and no interferences were observed from the formulation excipients and stress degradation products. Linear regression analysis of data for the calibration plot showed a linear relationship between peak area and concentration over the range of 10 - 100 μg/mL; the regression coefficient was 0.996 and the linear regression equation was y = 20.011 x + 146.83. This HPLC method was precise and accurate in the range of 10 – 100 μg/mL. Also, the dexpanthenol concentration in artificial tear formulation was determined by this HPLC method, which was in accordance with the label claimed. This validated HPLC method could be used for routine analysis, quality control and the stability of analysis of eye gel containing dexpanthenol formulations. [ABSTRACT FROM AUTHOR]

Over the last few years, among controlled-release delivery systems, multivesicular liposomes (MVLs) have attracted attention due to their unique benefits as a loco-regional drug delivery system. Considering the clinical limitations of the current treatment strategies for osteomyelitis, MVLs can be a suitable carrier for the local delivery of effective antibiotics. This study aimed to prepare vancomycin hydrochloride (VAN HL) loaded MVLs using the active loading method which to the best of our knowledge has not been previously reported. Empty MVLS were prepared by the double emulsion (w/o/w) method and VAN HL was loaded into the prepared liposomes by the ammonium gradient method. After full characterization, the release profile of VAN HL from MVLs was assessed at two different pH values (5.5 and 7.4), and compared with the release profile of the free drug and also passively loaded MVLs. In vitro antimicrobial activities were evaluated using the disc diffusion method. Our results demonstrated that the encapsulation efficiency was higher than 90% in the optimum actively loaded MVL. The free VAN HL was released within 6-8 h, while the passively loaded MVLs and the optimum actively loaded MVL formulation released the drug in 6 days and up to 19 days, respectively. The released drug showed effective antibacterial activity against osteomyelitis-causing pathogens. In conclusion, the prepared formulation offered the advantages of sustained-release properties, appropriate particle size as well as being composed of biocompatible materials, and thus could be a promising candidate for the loco-regional delivery of VAN HL and the management of osteomyelitis. [ABSTRACT FROM AUTHOR]

Recombinant protein production in Pichia pastoris is based on alcohol oxidase promoters which are regulated by methanol. However, the use of methanol has several disadvantages, which is why current trends in bioprocess development with Pichia pastoris (P. pastoris) are focusing on methanol mixed feeding strategies. This work aimed to develop a new experimental method and compare the effect of various fractions of sorbitol in mixed feeding strategy with stepwise addition of methanol to maximize the productivity of human growth hormone. Accordingly, fed-batch culture performed with a mixed feed of sorbitol/methanol. Sorbitol at concentrations of 30, 40, 50 and 60 gram per liter was added in batch-wise mode to the medium at the beginning of induction phase and the rate of methanol addition was increased stepwise during the first 12 h of production and then kept constant. In order to understand the effects of various co-substrate feeding strategies on P. pastoris and its production of hGH, cell mass, dry cell weight, total protein, hGH expression level and hGH concentration were analyzed and the results compared with the basic feeding protocol using one-way analysis of variance (ANOVA). According to the obtained results, sorbitol at a concentration of 50 g/L could significantly increase the production yield. Under such optimal conditions cell biomass was 108 g/L (DCW), total protein was 0.807 g/L, expression level was 83.1% and rhGH concentration was 0.667 g/L following 30 h induction. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the antibacterial effects of Thymus vulgaris, Thymus caramanicus, Zataria multiflora , Ziziphora clinopodioides and Ziziphora tenuior against four foodborne and four other bacteria including Staphylococcus aureus, Shigella dysenteriae, Salmonella typhimurium, Escherichia coli, Staphylococcus epidermidis, Bacillus subtilis, MRSA and Pseudomona aeruginosa and measuring the amount of total phenolics of the plants. The extracts were prepared by maceration method. Pre-evaluation of the antimicrobial effect was utilized by cup-plate technique and then Minimum Inhibitory Concentration was determined by agar dilution method according to NCCLS. The total phenolics as a possible cause of antibacterial effect, was measured by Folin-Ciocalteucolorimetry. The results showed that T. caramanicus and Z. multiflora were the most effective ones with MIC values between 0.78-3.125 mg/mL against all of the Bactria and Z. tenuior and Z. clinopodioides had the minimum antimicrobial activity. Total phenolic contents of these five plants were different and followed the general pattern of the antimicrobial effect. The antibacterial effects and the total phenolic content of T. caramanicus and Z. multiflora were remarkable and should be investigated more in future studies. [ABSTRACT FROM AUTHOR]

Determination of streptokinase activity is usually accomplished through two assay methods: a) Clot lysis, b) Chromogenic substrate assay. In this study the biological activity of two streptokinase products, namely Streptase®, which is a native product and Heberkinasa®, which is a recombinant product, was determined against the third international reference standard using the two forementioned assay methods. The results indicated that whilst the activity of Streptase® was found to be 101 ± 4% and 97 ± 5% of the label claim with Clot lysis and Chromogenic substrate assay respectively, for Heberkinasa® the potency values obtained were 42 ± 5% and 92.5 ± 2% of the label claim respectively. To shed some light on the reason for this finding, the n-terminal sequence of the streptokinase molecules present in the two products was determined. The results showed slight differences in the amino acid sequence of the recombinant product in comparison to the native one at the amino terminus. This finding supports those of other workers who found that n-terminal sequence of the streptokinase molecule can have significant effect on the activity of this protein. [ABSTRACT FROM AUTHOR]

Thimerosal, which is approximately 50% mercury by weight is a preservative widely used in vaccines since the 1930's. It meets the requirements for a preservative as set forth by Pharmacopeia challenge test and has been shown to be effective against a broad spectrum of pathogens. In July 1999, the Public Health Service agencies and vaccine manufacturers agreed that thimerosal should be reduced or eliminated in vaccines as a precautionary measure but, due to the lack of appropriate alternative, it is still extensively used in multiple dose formulations of vaccines such as hepatitis-B in developing countries. In this study the effect of the removal of thimerosal in two formulations of hepatitis B vaccines containing either aluminum hydroxide or aluminum phosphate were evaluated in Balb/c mice. These formulations were administered interperitoneally and the titer of antibody was determined by ELISA technique after 28 days. The geometric mean of antibody titer (GMT), seroconversion and seroprotection rates, ED50 and relative potency of different formulations were determined. The ED50 of thimerosal-free formulations were reduced by more than 35% in both preparations. In addition, GMT of antibody titer, seroconversion and seroprotection indicated significantly higher immunogenicity for thimerosal free formulations for both aluminum phosphate and hydroxide adjuvants. [ABSTRACT FROM AUTHOR]

Very high heat is generated during the polymerization of poly (methyl methacrylate) (PMMA) bone cement, which is used for implant fixation in orthopedic surgery. As such, it has been suggested that irrigating the bone cement layer in the surgical site with a saline solution is a way of cooling the layer. In this study, we aimed to determine the influence of irrigation with a saline solution on the flexural strength and the microstructure of the test specimens of two PMMA bone cement brands: Simplex P and FIX 1. Specimens were assigned to three groups: (1) irrigation with normal saline solution at 25 °C (RS group), (2) irrigation with cold saline at 4 °C (CS group), and (3) no irrigation (control group). For each of the groups, the specimens were tested after various times of aging in phosphate-buffered saline solution (PBS) at 37 °C for 1 h, 24 h, and 7 days. Flexural strength was measured following ISO 5833 protocol, and the surface microstructure was determined using scanning electron microscopy (SEM). The flexural strength results showed that for each of the cement brands, the difference between the groups was not significant, except for Simplex P specimens aged for 24 h, for which flexural strength of the RS and CS group specimens was lower than in the control group. The microstructural features of the surface of the specimens were similar across groups. These findings suggest that in a cemented arthroplasty, irrigation of the bone cement for the purpose of cooling it must only be used after very careful consideration. [ABSTRACT FROM AUTHOR]

The bulk of Internet interactions is highly redundant and also security sensitive. To reduce communication bandwidth and provide a desired level of security, a data stream is first compressed to squeeze out redundant bits and then encrypted using authenticated encryption. This generic solution is very flexible and works well for any pair of (compression, encryption) algorithms. Its downside, however, is the fact that the two algorithms are designed independently. One would expect that designing a single algorithm that compresses and encrypts (called compcrypt) should produce benefits in terms of efficiency and security. The work investigates how to design a compcrypt algorithm using the ANS entropy coding. First, we examine basic properties of ANS and show that a plain ANS with a hidden encoding table can be broken by statistical attacks. Next, we study ANS behavior when its states are chosen at random. Our compcrypt algorithm is built using ANS with randomized state jumps and a sponge MonkeyDuplex encryption. Its security and efficiency are discussed. The design provides 128-bit security for both confidentiality and integrity/authentication. Our implementation experiments show that our compcrypt algorithm processes symbols with a rate up to 269 MB/s (with a slight loss of compression rate) 178 MB/s. [ABSTRACT FROM AUTHOR]

Recurrent aphthous stomatitis (RAS) is a common condition that manifests as ulcerative lesions in the oral mucosa. In this study, bilayer, mucoadhesive nanofibers loaded with pomegranate flower extract (PFE) were prepared using thiolated gelatin (TGel) and thiolated chitosan (TCS) as the active layer and drug-free polycaprolactone (PCL) as the backing layer. Gelatin (Gel) and chitosan (CS) were successfully thiolated (proven by Ellman's assay, solubility, 1H NMR, FTIR, Raman spectroscopy, and XRD) and electrospun into active nanofibrous layers with a diameter of 356.9 nm. The in vitro release assay showed extended release of PFE, reaching about 57 % drug release in 48 h, fitted to the Korsmeyer-Peppas kinetics. FTIR, Raman spectroscopy, and XRD also showed the characteristic peaks of the nanofibers and their components. The nanofibers also exhibited significant hydrophilicity (contact angle of 47–49°), mucoadhesion (432.7 Pa), antioxidant capabilities (93.3 ± 0.2 %), and antibacterial effects against Staphylococcus aureus and Pseudomonas aeruginosa. Furthermore, PFE-loaded thiolated nanofibers significantly accelerated wound healing and epithelial tissue regeneration in vivo , reducing the ulcer area from 187 ± 19 mm on the 1st day to 68 ± 6 on the 7th day. Overall, bilayer PFE-loaded nanofibers based on TCS and TGel showed promising potential for treating RAS. [Display omitted] [ABSTRACT FROM AUTHOR]

In this study, the anticonvulsant effect of the fruit essential oil of Cuminum cyminum Linn. (Umbelliferae) was studied against seizures induced by maximal electroshock (MES) or pentylenetetrazole (PTZ) in mice. Administration of the essential oil protected mice against MES- and PTZ-induced tonic seizures. Furthermore, at some anticonvulsant doses, the essential oil produced sedation and motor impairment. [ABSTRACT FROM AUTHOR]

In this work, we have synthesized twenty five new 2-(5-(5-nitrofuran-2-yl)-1,3,4-thiadiazol-2-ylimino)thiazolidin-4-one derivatives bearing an aryl or heteroaryl methylene group on position 5 of thiazolidinone and evaluated their antimicrobial activity against Gram-positive and -negative bacteria as well as three metronidazole resistant Helicobacter pylori strains. Most of the compounds were very potent towards tested Gram-positive bacteria and showed an antibacterial efficacy substantially greater than ampicillin as the reference drug. However, no effectiveness was observed for the Gram-negative microorganisms. The compounds 9, 20 and 29 exhibited strong antimicrobial activity against Helicobacter pylori strains (inhibition zone > 30 mm) in 100 μg/disc and (inhibition zone > 20 mm) in 50 μg/disc. Taking these findings together, it seems that these potent antibacterial derivatives could be considered as promising agents for developing new anti-infectious drugs against microorganisms resistant to currently available antibiotics. [ABSTRACT FROM AUTHOR]

Microemulsion-based gels (MBGs) were prepared for transdermal delivery of lidocaine and evaluated for their potential for local anesthesia. Lidocaine solubility was measured in various oils, andphase diagrams were constructed tomapthe concentration range of oil, surfactant, cosurfactant, and water for oil-in-water (o/w) microemulsion (ME) domains, employing the water titrationmethod at different surfactant/cosurfactant weight ratios. Refractive index, electrical conductivity, droplet size, zeta potential, pH, viscosity, and stability of fluid o/w MEs were evaluated. Carbomer® 940 was incorporated into the fluid drug-loaded MEs as a gelling agent. Microemulsion-based gels were characterized for spreadability, pH, viscosity, and in-vitro drug release measurements, and based on the results obtained, the best MBGs were selected and subsequently subjected to ex-vivo rat skin permeation anesthetic effect and irritation studies. Data indicated the formation of nano-sized droplets of MEs ranging from 20 - 52 nm with a polydispersity of less than 0.5. In-vitro release and ex-vivo permeation studies on MBGs showed significantly higher drug release and permeation in comparison to the marketed topical gel. Developed MBG formulations demonstrated greater potential for transdermal delivery of lidocaine and advantage over the commercially available gel product, and therefore, they may be considered as potential vehicles for the topical delivery of lidocaine. [ABSTRACT FROM AUTHOR]

Objectives. This study aimed to evaluate the efficacy of a combination of 1% nanocurcumin gel with 0.1% triamcinolone acetonide mouth rinse for oral lichen planus (OLP). Materials and Methods. This double-blind randomized clinical trial was conducted on 31 patients with erosive or ulcerative OLP. All patients received 0.1% triamcinolone mouth rinse and were then randomly divided into two groups for combination therapy with (I) %1 nanocurcumin gel or (II) placebo gel. The reticular-erosive-ulcerative (REU) score was calculated at baseline and at two and four weeks after the intervention. The changes in the mean REU score and the efficacy index were calculated to determine the level of improvement after two and four weeks. Data were analyzed using independent t-test, repeated measures ANCOVA, Mann–Whitney test, and chi-square test. P < 0.05 was considered statistically significant. Results. There were 14 patients in the nanocurcumin and 17 patients in the placebo group. A significantly higher decrease in the mean REU score was observed in the nanocurcumin compared with the placebo group (P < 0.001). The efficacy index was significantly higher in the nanocurcumin group (P < 0.001). Conclusion. Application of 1% nanocurcumin in combination with 0.1% triamcinolone acetonide can serve as an effective treatment strategy to enhance the level of improvement of lesions compared with the use of triamcinolone acetonide alone. [ABSTRACT FROM AUTHOR]

Antidepressant-like activity of T. kotschyanus has been recently reported by scientists but insufficient attention has been so far devoted to T. kotschyanus, and there is a lack of information on the other neurobehavioral effects and side effects of this species. In the current study, the anticonvulsant, anxiolytic, and sedative-hypnotic, effects of Thymus kotschyanus extract on male NMRI mice were evaluated using pentylenetetrazole, maximal electroshock, elevated plus maze, and pentobarbital-induced sleeping tests. Since phenolic compounds and flavonoids have main roles in pharmacological effects of most plant extracts, the phenolic and flavonoid contents of the extract were measured with Folin-Ciocalteu and AlCl3 reagents. Acute toxicity, passive avoidance, and open field tests were carried out to assess the toxicity of the extract. To find out the possible mechanism of action, flumazenil as the specific GABAA receptor antagonist was used. Anticonvulsant and hypnotic effects of the extract were observed at 400 and 600 mg/kg. The extract at the dose of 200 mg/kg revealed significant anxiolytic effects, but it did not show any adverse effects on learning and memory at all the tested doses. Results of this study indicate that Thymus kotschyanus extract has anticonvulsant, anxiolytic, and hypnotic effects, which are likely related to the ability of some phenolic compounds to activate α1-containing GABAA receptors but more experiments still need to be carried out in order to find the exact mechanism, active component, and the toxicity of the Thymus kotschyanus extract. [ABSTRACT FROM AUTHOR]

Prolonged and impaired wound healing is a serious complication, and there is an emerging demand for strategies to overcome this problem. In this study, we developed electrospun bilayer nanofibers consisting of a chitosan/PVA active layer loaded with pomegranate flower extract (PFE) and a PCL inactive back layer. Structural, morphological, and physicochemical properties of nanofibers were characterized and wound healing effects of PFE-loaded nanofibers were assessed by in vitro and in vivo experiments, including antibacterial tests, wound closure measurements, and histological and immunohistochemical (IHC) analyses. Nanofibers with optimum formulation showed good hydrophilicity, a mean diameter of 404 nm, and an average roughness of 217 nm. TGA and FTIR studies exhibited typical absorption characteristics of PFE, PCL, and PVA and the compatibility of PFE with the components of bilayer nanofibers. The cumulative amount of PFE released from the monolayer and bilayer fibers after 6 h was measured to be 100% and 64%, respectively, indicating the more sustained release of PFE from bilayer scaffolds. Based on mechanical studies, a more ductile behavior was observed for bilayer fibers than monolayer fibers. The antibacterial assay for PFE-loaded nanofibers exhibited an inhibition zone with a diameter of 19.0 ± 0.5 mm and 15.8 ± 0.3 mm for S. aureus and P. aeruginosa , respectively. PFE-loaded nanofiber exposure contributed to faster wound closure (88% in 14 days) and a significant rise in the expression of α-SMA, CD31, collagen I, and vimentin, indicating a higher tissue regeneration rate for PFE - loaded nanofibers over other treatment groups. In conclusion, bilayer nanofibers containing PFE have a promising potential for wound healing acceleration. [Display omitted] • Pomegranate flower extract-loaded chitosan/PVA/PCL nanofibers were fabricated. • Bilayer nanofibers proposed a ductile behavior and a sustained drug release. • Nanofibers showed antibacterial effects against S. aureus and P. aeruginosa. • In vivo exposure led to improved wound closure and increased tissue regeneration. • Pomegranate flower extract-loaded nanofibers can accelerate wound healing process. [ABSTRACT FROM AUTHOR]

Source coding has a rich and long history. However, a recent explosion of multimedia Internet applications (such as teleconferencing and video streaming, for instance) renews interest in fast compression that also squeezes out as much redundancy as possible. In 2009 Jarek Duda invented his asymmetric numeral system (ANS). Apart from having a beautiful mathematical structure, it is very efficient and offers compression with a very low coding redundancy. ANS works well for any symbol source statistics, and it has become a preferred compression algorithm in the IT industry. However, designing an ANS instance requires a random selection of its symbol spread function. Consequently, each ANS instance offers compression with a slightly different compression ratio. The paper investigates the compression optimality of ANS. It shows that ANS is optimal for any symbol sources whose probability distribution is described by natural powers of 1/2. We use Markov chains to calculate ANS state probabilities. This allows us to precisely determine the ANS compression rate. We present two algorithms for finding ANS instances with a high compression ratio. The first explores state probability approximations in order to choose ANS instances with better compression ratios. The second algorithm is a probabilistic one. It finds ANS instances whose compression ratios can be made as close to the best ratio as required. This is done at the expense of the number θ of internal random "coin" tosses. The algorithm complexity is O (θ L 3) , where L is the number of ANS states. The complexity can be reduced to O (θ L log 2 L) if we use a fast matrix inversion. If the algorithm is implemented on a quantum computer, its complexity becomes O (θ (log 2 L) 3) . [ABSTRACT FROM AUTHOR]

The purpose of this study was to prepare and characterize a hybrid system of moxifloxacin loaded niosomes incorporated into chitosan gel as a potential carrier for topical antimicrobial delivery. The prepared system was characterized regarding entrapment efficiency, particle size, zeta potential, in vitro drug release kinetics, morphology, FTIR analysis, bioadhesive strength and rheological behavior. The effect of different formulation parameters (surfactant type, surfactant to drug ratio, cholesterol percentage and loading methodology) on moxifloxacin entrapment and drug release was evaluated. The antibacterial effectiveness of various formulations was also assessed by measuring the minimal inhibitory concentrations, minimal bactericidal concentrations and agar diffusion assay using Pseudomonas aeruginosa and Staphylococcus aureus as model pathogens. The optimized niosomal formulation showed 73% drug entrapment, 47% drug release in 8 h and was ∼290 nm in particle diameter and negatively charged ( ζ ∼ −23 mV). The gel-embedded niosomes exhibited pseudo-plastic flow behavior and more sustained drug release profile compared to niosomes. The niosomal formulation of moxifloxacin was the most efficient system against P. aeruginosa , while gel based formulations were superior against S. aureus . Taken together, moxifloxacin-in-niosomes-in-gels hold great promise for topical microbial infections. [ABSTRACT FROM AUTHOR]

In light of their remarkable predictive capabilities, artificial intelligence (AI) models driven by deep learning (DL) have witnessed widespread adoption in the agriculture sector, contributing to diverse applications such as enhancing crop management and agricultural productivity. Despite their evident benefits, the integration of AI in agriculture brings forth security risks, a concern further exacerbated by the comparatively lower security awareness among agriculture stakeholders. This position paper endeavors to amplify the security consciousness among stakeholders (e.g., end-users such as farmers and governmental bodies) engaged in the implementation of AI systems within the agricultural sector. In our systematic categorization of security threats to AI systems, we delineate three primary avenues of attack: (1) Adversarial Example Attacks, (2) Poisoning Attacks, and (3) Backdoor Attacks. Adversarial example attacks manipulate inputs during the model's inference phase to induce incorrect predictions. Poisoning attacks corrupt the training data, compromising the model's availability by indiscriminately degrading its performance on legitimate inputs. Backdoor attacks, typically introduced during the training phase, undermine the model's integrity, enabling attackers to trigger specific behaviors or outputs through predetermined hidden patterns. An example of compromising AI integrity for malicious purposes is DeepLocker, highlighted by IBM researchers. A detailed examination of attacks in each category is provided, emphasizing their tangible threats to real-world agricultural applications. To illustrate the practical implications, we conduct case studies on specific agricultural applications, focusing on precise irrigation schedules and plant disease detection, utilizing authentic agricultural datasets. Comprehensive countermeasures against each attack type are presented to assist agriculture stakeholders in actively safeguarding their AI applications. Additionally, we address challenges inherent in securing agriculture AI and offer our perspectives on mitigating security threats in this context. This work aims to equip agriculture stakeholders with the knowledge and tools necessary to fortify their AI systems against evolving security challenges. The artifacts of this work are released at https://github.com/garrisongys/Casestudy. • First time pinpointing the security threats to AI-powered agricultural systems. • Identifying diverse agricultural scenarios where adversarial attacks occur. • Considers three case study for each type of three AI adversarial attacks. [ABSTRACT FROM AUTHOR]

Current study intended to prepare and evaluate phospholipid-based, mixed micelles (MMs) to improve the ocular delivery of posaconazole (POS), a broad-spectrum antifungal drug. For this, MMs based on egg phosphatidylcholine (EPC), as the main component, in combination with various bile salts (sodium cholate (NaC), sodium deoxycholate (NaDC), sodium taurocholate (NaTC)) or non-ionic surfactants (Pluronic® F-127, Pluronic® F-68, Tween 80, Labrasol® ALF, and d-a-tocopheryl polyethylene glycol 1000 succinate (TPGS)) were prepared. Particle size, polydispersity index, zeta potential and entrapment efficiency were evaluated to optimize the composition and preparation method of the MMs. Finally, morphology, stability, in vitro release pattern, and in vitro antifungal activity of the optimized formulation were investigated. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30, prepared by the thin-film hydration method, showed more appropriate features. Among the prepared MMs, vesicles composed of EPC: TPGS with a molar ratio of 70:30 showed more appropriate features, including an entrapment efficiency (EE) greater than 80%, spherical shape morphology, an average particle size of about 58 nm, desirable stability over a month, slow-release without a noticeable initial burst, and a significantly higher in vitro antifungal activity in comparison with the drug suspension. Therefore, this formulation was selected as the optimal MMs and could be considered as a promising carrier for topical ocular delivery of POS. Graphical Abstract [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD), the second most prevalent neurological disorder in the elderly, manifests with distinctive movement disorders, including bradykinesia, resting tremor, and stiffness. With a progressive course, current treatment strategies primarily target symptomatic relief. Crocin is a chemical compound isolated from the dry stigma of Crocus sativus, and has demonstrated neuroprotective properties. This study explores the impact of crocin on movement disorders and neuronal oxidative DNA damage in PD patients. Conducted as a randomized, blinded, and controlled trial, this research focused on patients aged 30 to 80 with idiopathic PD. Using the second and third parts of the movement disorder society-unified PD rating scale (MDS-UPDRS), aspects of daily life activity and movement disorders were assessed before and after an 8-week intervention. Patients in the crocin groups received capsules containing 30 mg of crocin twice daily. Additionally, the 8-hydroxy-2-deoxydiguanosine (8-OHdG) to urinary creatinine ratio (8-OHdG/uCr) was measured to evaluate neuronal oxidative DNA damage. Out of the initially evaluated 164 patients, 30 were randomly assigned to each group, with 53 subjects completing the study. Within-group analysis revealed a significant improvement in the second and third parts of MDS-UPDRS after 8 weeks of crocin intervention (P < 0.05). However, the 8-OHdG/uCr did not show significant changes. The well-tolerated daily dose of 60 mg of crocin demonstrated minimal side effects. This study establishes the efficacy of crocin in enhancing daily life activities and mitigating movement disorders, suggesting its potential as a supplementary intervention alongside conventional PD medications. • Crocin is a substance extracted from the Crocus sativus plant that has dopaminergic and serotonergic effects. • It seems that crocin with its dopaminergic effect can reduce movement disorders caused by Parkinson's disease. • Parkinson's patients receiving crocin have improved in the second and third parts of the MDS-UPDRS questionnaire. • Using 30 mg twice a day of crocin in patients with crocin is safe and has no dangerous side effects. • Crocin may be able to increase the quality of life by Reducing movement disorders and simultaneously improving depression. [ABSTRACT FROM AUTHOR]

Introduction: Augmented renal clearance (ARC) defined as creatinine clearance (Clcr) above 130 mL/min/1.73m2 may lead to suboptimal antibacterial treatment. The aim of this study was to determine a strategy for meropenem administration to achieve both pharmacodynamic-pharmacokinetic (PK-PD) target (50%fT > MIC) and better clinical outcomes in patients with VAP and ARC. Materials and methods: In this randomized clinical trial, patients with VAP and high risk for ARC were recruited. An 8-h urine collection was performed on the 1st, 3rd, and 5th days of study to measure Clcr. Included patients were divided into three groups: (1) 1 g meropenem, 3-h infusion, (2) 2 g meropenem, 3-h infusion, (3) 1 g meropenem, 6-h infusion. On the 2nd, 3rd, and 5th days of treatment, peak and trough blood samples were collected to undergo HPLC assay. MICs were assessed using microdilution method. Patients were also clinically monitored for 14 days. Results: Forty-five patients were included. Group 3 showed significanty higher rate of patients achieving fT > MIC > 50% (100% for group 3 versus 40% for group 2 and 13% for group 1; p = 0.0001). Mean fT > MIC% was significantly higher in group 3 (78.77 ± 5.87 for group 3 versus 49.6 ± 7.38 for group 2 and 43.2 ± 7.98 for group 1; p = 0.0001). Statistical analysis showed no significant differences among groups regarding clinical improvement. Conclusion: According to the findings of this trial, prolonged meropenem infusion is an appropriate strategy compared to dose elevation among ARC patients. [ABSTRACT FROM AUTHOR]

Illegal and excessive use of veterinary antibiotics as a food additive for growth promotion in livestock can lead to allergic reactions and antibiotic resistance, which is a worldwide concern. A biochip-based semi-quantitative screening method of antimicrobial residues in milk was validated based on Commission Decision 2002/657/EC and the European guideline to validate screening methods for veterinary medicines. This multi-analytical screening method enables to determine of 3 beta-lactams (cefalexin, ampicillin, and cefuroxime) simultaneously. Analysis of 20 blank and 20 spiked milk samples showed that for all 3 antibiotic residues, the positivity threshold T was above cut-off value Fm, and no false-positive results were obtained for all 3 antibiotics. All detection capabilities (CCβ) were below Maximum Residue Level (MRL) authorized by European Commission. 47 UHT cow's milk samples collected from Tehran province, IR Iran, were screened, and compliance was found in 100% of samples. This study found that the biochip method is valid to determine antibiotic residues in milk samples at the measured validation levels. The method was fast, simple, and able to simultaneous screen three families of beta-lactams from a single milk sample with almost no sample preparation. [ABSTRACT FROM AUTHOR]

Mobilization and engraftment of Hematopoietic Stem Cells (HSCs) are challenging issues in Autologous HSC transplantation (AHSCT) so several attempts such as colony-stimulating factors (CSF) and plerixafor have been used for enhancement of HSCs mobilization and engraftment. In this randomized, double-blind and placebo-controlled study, we evaluated the melatonin's efficacy and safety, as endogenous CSF inducer, co-administered with Filgrastim in mobilizing and engraftment of HSC. AHSCT patients were randomized to receive either Melatonin or placebo plus filgrastim. Of Fifty-one patients, 26 patients received the melatonin (In mobilization phase 3 mg sublingual twice daily, then 9 mg single dose 30 min before apheresis session and then 3 mg twice daily from +1 until engraftment) and 25 patients received the placebo. The mean number of CD34 cells/kg × 106 in the melatonin group was 6.54 versus 4.22 in the placebo group (p = 0.025). The mean day to neutrophil engraftment in the melatonin group was 11.69 ± 2.093, whereas 12.68 ± 2.42 days in the placebo group (p = 0.021). In this study, the second apheresis session requirement, the use of plerixafor and hospital stay duration, were comparable between the two groups. Considering the result of the study, it could be suggested that melatonin plus Filgrastim can be effectively used in AHSCT patients to enhance the number of peripheral CD34 cells/kg × 106 and decrease the day number of neutrophil engraftment. [ABSTRACT FROM AUTHOR]

Coronavirus disease-19 (COVID-19) pandemic, caused by SARS-CoV-2, has gradually spread worldwide, becoming a major public health event. This situation requires designing a novel antiviral agent against the SARS-CoV-2; however, this is time-consuming and the use of repurposed medicines may be promising. One such medicine is favipiravir, primarily introduced as an anti-influenza agent in east world. The aim of this study was to evaluate the efficacy and safety of favipiravir in comparison with lopinavir-ritonavir in SARS-CoV-2 infection. In this randomized clinical trial, 62 patients were recruited. These patients had bilateral pulmonary infiltration with peripheral oxygen saturation lower than 93%. The median time from symptoms onset to intervention initiation was seven days. Favipiravir was not available in the Iranian pharmaceutical market, and it was decided to formulate it at the research laboratory of School of Pharmacy, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The patients received favipiravir tablet at a dose of 1600 mg orally twice a day for day one and then 600 mg orally twice a day for days 2 to 6. In the second group, the patients received lopinavir-ritonavir combination tablet at a dose of 200/50 mg twice a day for seven days. Fever, cough, and dyspnea were improved significantly in favipiravir group in comparison with lopinavir-ritonavir group on days four and five. Mortality rate and ICU stay in both groups were similar, and there was no significant difference in this regard (P = 0.463 and P = 0.286, respectively). Chest X-ray improvement also was not significantly different between the two groups. Adverse drug reactions occurred in both groups, and impaired liver enzymes were the most frequent adverse effect. In conclusion, early administration of oral favipiravir may reduce the duration of clinical signs and symptoms in patients with COVID-19 and hospitalization period. The mortality rate also should be investigated in future clinical trials. [ABSTRACT FROM AUTHOR]

Human exposure to polycyclic aromatic hydrocarbons (PAHs) is known as a carcinogen risk factor. In this study, a gas chromatography-mass spectrometry (GC-MS) technique combined with the QuEChERS extraction method was developed for concurrent analysis of 10 polycyclic aromatic hydrocarbons (PAHs) in Iranian traditional Sangak bread samples. The method was validated by determining different parameters, including; linearity, accuracy, precision, limit of detection (LOD) and limit of quantitation (LOQ). Calibration curves showed a linear relationship in the concentration range of 10-500 ng/g with a coefficient of determination (R2) ranged between 0.994 and 0.999. The obtained mean recoveries were 92-106% with the relative standard deviations (RSDs) in the range of 3-7% with an acceptable precision (RSD < 20%). The Limit of detections (LODs) for different PAHs were between 0.14-0.78 ng/g, while the limit of quantitation (LOQ) was 0.46-2.60 ng/g. Matrix effect studies showed that the analytes concluded signal suppressions or enhancements. Therefore, spiked calibration curves were used for overcoming this issue. The result of Sangak bread samples analysis using the validated method showed that 9 (19.4%) out of 47 Sangak bread samples were contaminated with phenanthrene (PHE) and anthracene (ANT) at the mean level of 10.08 ± 6.38 ng/g which were higher than the permissible limit of European Commission regulatory control value for BaP (1 µg/kg of wet weight) in processed cereal-based foods and baby foods for infants and young children. [ABSTRACT FROM AUTHOR]

The aim of this study is to investigate the novel application of a handheld near infra-red spectrophotometer coupled with classification methodologies as a screening approach in detection of adulterated lime juices. For this purpose, a miniaturized near infra-red spectrophotometer (Tellspec®) in the spectral range of 900-1700 nm was used. Three diffuse reflectance spectra of 31 pure lime juices were collected from Jahrom, Iran and 25 adulterated juices were acquired. Principal component analysis was almost able to generate two clusters. Partial least square discriminant analysis and k-nearest neighbors algorithms with different spectral preprocessing techniques were applied as predictive models. In the partial least squares discriminant analysis, the most accurate prediction was obtained with SNV transforming. The generated model was able to classify juices with an accuracy of 88% and the Matthew's correlation coefficient value of 0.75 in the external validation set. In the k-NN model, the highest accuracy and Matthew's correlation coefficient in the test set (88% and 0.76, respectively) was obtained with multiplicative signal correction followed by 2nd-order derivative and 5th nearest neighbor. The results of this preliminary study provided promising evidence of the potential of the handheld near infra-red spectrometer and machine learning methods for rapid detection of lime juice adulteration. Since a limited number of the samples were used in the current study, more lime juice samples from a wider range of variability need to be analyzed in order to increase the robustness of the generated models and to confirm the promising results achieved in this study. [ABSTRACT FROM AUTHOR]

The methylotrophic yeast Pichia pastoris is a well-established expression host, which is often used in the production of protein pharmaceuticals. This work aimed to evaluate the effect of various concentrations of ascorbic acid in mixed feeding strategy with sorbitol/methanol on productivity of recombinant human growth hormone (r-hGH). The relevant concentration of ascorbic acid (5, 10, or 20 mmol) and 50 g/L sorbitol were added in batch-wise mode to the medium at the beginning of induction phase. The rate of methanol addition was increased stepwise during the first 12 h of production and then kept constant. Total protein and r-hGH concentrations were analyzed and the results compared with sorbitol/methanol feeding using one-way analysis of variance. Moreover, an effective clarification process using activated carbon was developed to remove process contaminants like pigments and endotoxins. Finally, a three-step chromatographic process was applied to purify the product. According to the obtained results, addition of 10 mmol ascorbic acid to sorbitol/methanol co-feeding could significantly increase cell biomass (1.7 fold), total protein (1.14 fold), and r-hGH concentration (1.43 fold). One percent activated carbon could significantly decrease pigments and endotoxins without any significant changes in r-hGH assay. The result of the study concluded that ascorbic acid in combination with sorbitol could effectively enhance the productivity of r-hGH. This study also demonstrated that activated carbon clarification is a simple method for efficient removal of endotoxin and pigment in production of recombinant protein in the yeast expression system. [ABSTRACT FROM AUTHOR]

Objectives. This study aimed to assess the effect of hydroalcoholic extract of Punica granatum Linn. (P. granatum) petal on Streptococcus sanguinis, Streptococcus mutans, Streptococcus salivarius, Streptococcus sobrinus, and Enterococcus faecalis. Materials and Methods. In this in vitro study, P. granatum extract was prepared using powdered petals and water-ethanol solvent. Antibacterial effect of the extract, chlorhexidine (CHX), and ampicillin was evaluated on brain heart infusion agar (BHIA) using the cup-plate method. By assessing the diameter of the growth inhibition zone, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extract were determined for the above-mentioned bacteria. Results. Hydroalcoholic extract of P. granatum petal had inhibitory effects on the proliferation of all five bacterial strains with maximum effect on S. mutans with MIC and MBC of 3.9 mg/mL. The largest growth inhibition zone diameter belonged to S. sanguinis and the smallest to E. faecalis. Ampicillin and CHX had the greatest inhibitory effect on S. sanguinis. Conclusions. Hydroalcoholic extract of P. granatum had a significant antibacterial effect on common oral bacterial pathogens with maximum effect on S. mutans, which is the main microorganism responsible for dental plaque and caries. [ABSTRACT FROM AUTHOR]

In this study a novel High Performance Liquid Chromatography for the assay of nystatin in oral and vaginal tablets were optimized and validated using Box-Behnken experimental design. The method was performed in the isocratic mode on a RP-18 column (30 °C) using a mobile phase consisting of ammonium acetate 0.05 M buffer/ Methanol mixture (30:70) and a flow-rate of 1.0 mL/min. The specificity, linearity, precision, accuracy, LOD and LOQ of the method were validated. The method was linear over the range of 5-500 µg/mL with an acceptable correlation coefficient (r² = 0.9996). The method's limit of detection (LOD) and quantification (LOQ) were 0.01 and 0.025 µg/mL respectively. The results indicate that this validated method can be used as an alternative method for assay of nystatin. [ABSTRACT FROM AUTHOR]

Background and Objectives: Recently, use of herbal medicine and plant extracts as a substitute for commercially available chemical drugs for control of infectious diseases such as dental caries and periodontal disease has become increasingly popular. The present study was aimed to evaluate the effect of Rhus coriaria L. water extract on five common oral bacteria and bacterial biofilm formation on orthodontic wire. Materials and Methods: For primary assessment of the antibacterial properties of Rhus coriaria L. water extract, the well-plate method in BHIA (Brain Heart Infusion Agar, Merck, Germany) medium was used. Using macrodilution method, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the extract against each microorganism were determined. The effect of Rhus coriaria L. on bacterial biofilm formation on orthodontic wire was assessed using viable cell count in biofilm medium (BM) containing 3% sucrose. In the final phase, after fixation of samples in alcohol and glutaraldehyde, samples were prepared for SEM (Scanning Electron Microscopy) analysis. Results: The diameter of the zone of growth inhibition was proportionate to the tested concentrations of the extract. The lowest MIC (0.390 mg/ml) and MBC (1.5 mg/ml ) of the Rhus coriaria L. were found to be against Streptococcus sobrinus ATCC 27607. Rhus coriaria L. water extract decreased bacterial biofilm formation on orthodontic wire at MIC and 1/8 of MIC by S. sanguinis ATCC 10556, S. sobrinus ATCC 27607, S. salivarius ATCC 9222, S. mutans ATCC 35608 and E. faecalis CIP 55142 by 24.2%-43%, 68.5%-91.6%, 10.6%-79.1%, 22.2%-86.1% and 40.6%-76.4%, respectively. Conclusion: Based on the results, Rhus coriaria L. water extract had significant antibacterial properties against five common oral bacteria and was able to inhibit bacterial biofilm formation on orthodontic wire. Further investigations are recommended for widespread clinical use of this extract. [ABSTRACT FROM AUTHOR]

• Organic acids content is a critical parameter for detecting lime juice adulteration. • Iso-citric acid level is considered as a main criterion in the adulterated samples. • LC–MS/MS and HPLC-DAD help in the detection of citric-adulterated lime juices. In the present study, a novel liquid chromatography-tandem mass spectrometry (LC–MS/MS) method was developed and validated for the simultaneous determination of citric acid, iso-citric acid, and malic acid. Method validation was performed by studying accuracy, precision, linearity, limit of detection, and limit of quantification. Besides, the obtained results were compared to a validated HPLC-DAD method. The use of isotopically labeled citric acid as the internal standard allowed the accurate quantitation of organic acids without any significant matrix effects. Following quantification of main organic acids in the hand-squeezed lime juice samples, it was revealed that citric acid, iso-citric acid, and malic acid contents in the Persian lime juices ranged from 48.30 to 66.54 g/L, 0.24 to 0.61 g/L, and 1.73 to 10.49 g/L, respectively. Finally, among 30 industrial and 20 non-industrial lime juice samples collected from the market, 53 % of industrial and 60 % of non-industrial samples were detected as adulterated based on the citric acid to iso-citric acid ratio (over 300). The results of method validation demonstrated that LC–MS/MS could be used as a confirmatory method for the authenticity assessment of lime juice by regulatory bodies. [ABSTRACT FROM AUTHOR]