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Background Streptococcus pneumoniae (Pneumococcus) has remained a leading cause of fatal infections such as pneumonia, meningitis, and sepsis. Moreover, this pathogen plays a major role in bacterial co-infection in patients with life-threatening respiratory virus diseases such as influenza and COVID-19. High morbidity and mortality in over one million cases, especially in very young children and the elderly, are the main motivations for pneumococcal vaccine development. Due to the limitations of the currently marketed polysaccharide-based vaccines, non-serotype-specific protein-based vaccines have received wide research interest in recent years. One step further is to identify high antigenic regions within multiple highly-conserved proteins in order to develop peptide vaccines that can affect various stages of pneumococcal infection, providing broader serotype coverage and more effective protection. In this study, immunoinformatics tools were used to design an effective multi-epitope vaccine in order to elicit neutralizing antibodies against multiple strains of pneumococcus. Results The B- and T-cell epitopes from highly protective antigens PspA (clades 1–5) and PhtD were predicted and immunodominant peptides were linked to each other with proper linkers. The domain 4 of Ply, as a potential TLR4 agonist adjuvant candidate, was attached to the end of the construct to enhance the immunogenicity of the epitope vaccine. The evaluation of the physicochemical and immunological properties showed that the final construct was stable, soluble, antigenic, and non-allergenic. Furthermore, the protein was found to be acidic and hydrophilic in nature. The protein 3D-structure was built and refined, and the Ramachandran plot, ProSA–web, ERRAT, and Verify3D validated the quality of the final model. Molecular docking analysis showed that the designed construct via Ply domain 4 had a strong interaction with TLR4. The structural stability of the docked complex was confirmed by molecular dynamics. Finally, codon optimization was performed for gene expression in E. coli, followed by in silico cloning in the pET28a(+) vector. Conclusion The computational analysis of the construct showed acceptable results, however, the suggested vaccine needs to be experimentally verified in laboratory to ensure its safety and immunogenicity.

Background The pathogenicity of pneumococcus with high morbidity, mortality, and multi-drug resistance patterns has been increasing. The limited coverage of the licensed polysaccharide-based vaccines and the replacement of the non-vaccine serotypes are the main reasons for producing a successful serotype-independent vaccine. Pneumococcal surface protein A (PspA) is an extremely important virulence factor and an interesting candidate for conserved protein-based pneumococcal vaccine classified into two prominent families containing five clades. PspA family-elicited immunity is clade-dependent, and the level of the PspA cross-reactivity is restricted to the same family. Methods To cover and overcome the clade-dependent immunity of the PspAs in this study, we designed and tested a PspA1-5c+p vaccine candidate composed of the highest immunodominant coverage of B- and T-cell epitope truncated domain of each clade focusing on two cross-reactive B and C regions of the PspAs. The antigenicity, toxicity, physicochemical properties, 3D structure prediction, stability and flexibility of the designed protein using molecular dynamic (MD) simulation, molecular docking of the construct withHLADRB1*(01:01) and human lactoferrin N-lop, and immune simulation were assessed using immunoinformatics tools. In the experimental section, after intraperitoneal immunization of the mice with Alum adjuvanted recombinant PspA1-5c+p, we evaluated the immune response, cross-reactivity, and functionality of the Anti-PspA1-5c+p antibody using ELISA, Opsonophagocytic killing activity, and serum bactericidal assay. Results For the first time, this work suggested a novel PspA-based vaccine candidate using immunoinformatics tools. The designed PspA1-5c+p protein is predicted to be highly antigenic, non-toxic, soluble, stable with low flexibility in MD simulation, and able to stimulate both humoral and cellular immune responses. The designed protein also could interact strongly with HLADRB1*(01:01) and human lactoferrin N-lop in the docking study. Our immunoinformatics predictions were validated using experimental data. Results showed that the anti-PspA1-5c+p IgG not only had a high titer with strong and same cross-reactivity coverage against all pneumococcal serotypes used but also had high and effective bioactivity for pneumococcal clearance using complement system and phagocytic cells. Conclusion Our findings elucidated the potential application of the PspA1-5c+p vaccine candidate as a serotype-independent pneumococcal vaccine with a strong cross-reactivity feature. Further in-vitro and in-vivo investigations against other PspA clades should be performed to confirm the full protection of the PspA1-5c+p vaccine candidate.

Because of increasing interest in environmentally benign supercapacitors, earth-abundant biopolymers have found their way into value-added applications. Herein, a promising nanocomposite based on an interpenetrating network of polyaniline and sulfonated lignin (lignosulfonate, LS) is presented. On the basis of an appropriate regulation of the nucleation kinetics and growth behavior via applying a series of rationally designed potential pulse patterns, a uniform PANI-LS film is achieved. On the basis of the fast rate of H+ insertion-deinsertion kinetics, rather than the slow SO42- doping-dedoping process, the PANI-LS nanocomposite delivers specific capacitance of 1200 F g-1 at 1 A g-1 surpassing the best conducting polymer-lignin supercapacitors known. A symmetric PANI-LS||PANI-LS device delivers a high specific energy of 21.2 W h kg-1, an outstanding specific power of 26.0 kW kg-1, along with superb flexibility and excellent cycling stability. Thus, combining charge storage attributes of polyaniline and lignosulfonate enables a waste-to-wealth approach to improve the supercapacitive performance of polyaniline.

The ongoing surge in demand for sustainable energy technologies with little to no environmental impacts calls for the exploration of advanced energy storage materials. Inspiration from nature is undoubtedly a promising approach to comply with environmental legislations. Herein, we describe a facile and green electrosynthesis approach to fabricate a polydopamine (PDA) nanofilm supported on oxygen-functionalized carbon cloth (FCC). The surface functionalization of carbon cloth facilitates the PDA nanofilm adhesion and endows the as-prepared PDA-FCC electrode with excellent flexibility, good electrical conductance (22.6 mS), and outstanding wettability to the aqueous electrolyte. Owing to these merits, the PDA-FCC electrode delivers a favorable capacitance of 626 F g−1 at 1.0 A g−1 (617 mF cm−2 at 2.2 mA cm−2, and 1296 mF cm−3 at 5.3 mA cm−3), in which the catechol, amine, and imine moieties of PDA are responsible for its excellent pseudocapacitive behavior. The symmetric all-solid-state flexible PDA-FCC||PDA-FCC device covers almost the entire thermodynamic stability window of aqueous electrolytes (1.2 V), delivers a high specific energy of 11.7 W h kg−1, superb specific power of up to 6.4 kW kg−1, and excellent flexibility along with outstanding cycling stability (81% retention of the initial capacitance after 10 000 cycles). These performance characteristics are in part due to the binder-free PDA biopolymer film that adopts the inherent texture of the carbon cloth, enabling the pores to play the role of temporary ion-buffering reservoirs that facilitate effective mass transport. This new approach to fabricate electrodes from green sources is considered an important step toward environmentally-benign energy storage technologies.

Gut microbiota such as Faecalibacterium prausnitzii play a major role in the regulation of gut barrier, inflammation and metabolic functions. Microbiota–derived extracellular vehicles (EVs) have been recently introduced as functional units mediating the eukaryotic and prokaryotic cell-microbiota interactions. In this paper, the effect of F. prausnitzii and its EVs on mRNA expression levels of tight junction genes (ZO1 and OCLN) as well as PPARs and ANGPTL4 genes in the human epithelial colorectal adenocarcinoma (Caco-2) cell line was evaluated. F. prausnitzii was cultured on the Brain Heart Infusion (BHI) broth medium under anaerobic conditions, and its EVs were extracted by ultracentrifugation. This bacterium and its EVs were treated on the Caco-2 cells. After 24 h, the expression of the genes encoding TJ proteins such as ZO1 and OCLN, PPARs and ANGPTL4 was evaluated by quantitative real-time PCR. Unlike F. prausnitzii, its EVs significantly increased the expression of ZO1 and OCLN genes, and PPARα, PPARγ and PPARβ/δ genes (except at a concentration of 100 µg/ml) as well as ANGPTL4 gene. The results of this study demonstrated that F. prausnitzii–derived EVs increased the intestinal barrier permeability via TJs (ZO1 and OCLN) as well as PPAR-α, PPAR-γ and PPAR β/δ genes and their targeted gene (ANGPTL4) in the Caco-2 cell line. Accordingly, it is suggested that F. prausnitzii–derived EVs can be considered as a new bacterial postbiotic to cure dysbiosis-associated diseases including obesity and its related metabolic dysfunctions, according to the leaky gut hypothesis.

Introduction. Streptococcus pneumoniae is a significant bacterial pathogen in humans. Currently, there are two types of pneumococcal vaccines, but there are concerns regarding their application. Aim. Since many pneumococcal proteins are serotype-independent, polyhistidine triad protein D (PhtD) has been selected as a vaccine candidate. Methodology. We prepared recombinant PhtD and its C-terminal fragment (PhtD-C) using alum and outer-membrane vesicles (OMVs) as adjuvants. The combinations were injected intraperitoneally into mice, and then total immunoglobulin G (IgG) and specific IgG, IgG1 and IgG2a were measured. A serum bactericidal assay and opsonophagocytosis were also performed as complementary tests. Meningococcal OMVs were used as an adjuvant. Results. The levels of specific IgG and IgG1 against combinations of PhtD and its C-terminal with OMVs and alum as adjuvants increased at the time of the third mouse immunization on day 35. Forty per cent and 60% of S. pneumoniae ATCC 6303 (serotype 3) as a virulent pneumococcal strain, respectively, were killed in the opsonophagocytosis test and these results could also be observed in the serum bactericidal assay. Mice mmunized iwith PhtD and its C-terminal with OMVs and alum as adjuvants survived after 10 days of pneumococcal challenge. Conclusion. The combination of PhtD and PhtD-C with alum produced optimal results, but the combination of PhtD and PhtD-C with OMVs produced minimal results by comparison. The survival rates were also measured, and these corresponded with the results of the immunological assessments. Our findings showed that mice receiving PhtD and PhtD-C plus OMV and alum had higher survival rates than the mice in the other groups.

Objectives Staphylococcus epidermidis is the primary causative agent of infections associated with indwelling biomaterials. Antibiotic susceptibility patterns, Biofilm formation capability, and screening of responsible genes in biofilm formation procedure in clinical isolates (icaA, icaB, icaC, icaD, sdrG, and atlE) were assigned as the main objectives in this study. The clinical samples were analyzed via standard biochemical assays for identifying different bacteria which were confirmed using the multiplex colony PCR method. Subsequently, biofilm-formation capability, antibiotic susceptibility testing, and the frequency of genes responsible for biofilm formation in the confirmed strains were checked. Results Out of 183 clinical specimens 54 S. epidermidis isolates were detected by targeting a housekeeping gene (sesc) taking advantage of the PCR procedure. All of the strains were Biofilm forming producers. The in vitro biofilm formation assays determined that 45 (83.33%), 5 (9.26%), 4 (7.41%) were strong, moderate, and weak biofilm former strains respectively. Among the isolated strains, the specific frequencies of the biofilm-forming genes were specified to be (98%) for sdrG, (84%) for atlE, (80%) for icaC, and (70%) for icaD. Cefamandole and Amikacin are the most effective antibiotics in isolated strains. All strains were ascertained to be methicillin and amoxicillin/clavulanic acid resistant.

Introduction: Streptococcus pneumoniae causes invasive and non-invasive diseases in children and adults. Currently, there are two types of pneumococcal vaccines: 23-valent pneumococcal polysaccharide vaccine and 13-valent pneumococcal conjugate vaccine which have caused many failures. Therefore, a new generation of pneumococcal vaccines is being pursued. Methods: An improved version of our previous study was performed using recombinant C-terminal of pneumococcal polyhistidine triad protein D (PhtD-C) as a vaccine antigen. The antigen was combined with meningococcal outer membrane vesicle (OMV) and alum as adjuvants to immunize BALB/c mice intraperitoneally. The generated total IgG, specific IgG, IgG1 and IgG2a antibodies and the killing ability of pneumococci by an opsonophagocytosis assay were then assayed. Results: Immunization by 30 µg PhtD-C and 50 µg OMV as an adjuvant, induced higher amounts of functional antibodies compared to our previous study while killing 50-55% of pneumococci cells. Conclusion: At optimized concentrations, PhtD-C and meningococcal OMV could be considered as a potent immunogens and the induced specific IgGs were effective and functional for killing pneumococci.

The pursuit of new negative electrode materials for redox supercapacitors with a high capacitance, boosted energy, and high rate capability is still a tremendous challenge. Herein, we report a Nile Blue conjugated graphene aerogel (NB–GA) as a negative electrode material with excellent pseudocapacitive performance (with specific capacitance of up to 483 F g–1 at 1 A g–1) in all acidic, neutral, and alkaline aqueous electrolytes. The contribution from capacitive charge storage represents 93.4% of the total charge, surpassing the best pseudocapacitors known. To assess the feasibility of NB–GA as a negative electrode material across the full pH range, we fabricated three devices, namely, a symmetric NB–GA||NB–GA device in an acidic (1.0 M H2SO4) electrolyte, an NB–GA||MnO2 device in a pH-neutral (1.0 M Na2SO4) electrolyte, and an NB–GA||LDH (LDH = Ni–Co–Fe layered double hydroxide) device in an alkaline (1.0 M KOH) electrolyte. The NB–GA||NB–GA device exhibits a maximum specific energy of 22.1 Wh kg–1 and a ...

Major technological challenges in point-of-care diagnostics are in the development of simple, fast, and inexpensive methods for high-throughput and multiplexed genotyping of single-nucleotide polymorphisms (SNPs). Herein, we develop a facile SNP detection platform based on platinum nanoparticles–induced etching of gold nanorods (AuNRs) by H2O2. The IVS-II-1 (G>A) β-thalassemia mutation, as one of the most prevalent mutations in the Middle East, was used as a model disease. In the presence of H2O2, ferrous ion (Fe2+) triggers a Fenton reaction with the catalytic decomposition of H2O2 into highly reactive hydroxyl (HO·) and hydroperoxyl (HOO·) radicals. These species etch AuNRs along the longitudinal axes to short AuNRs or even Au nanoparticles. For signaling SNPs, monobase-modified platinum nanoparticles (M-PtNPs) are hybridized to mutated sites of the duplex DNA. PtNPs catalyze the decomposition of H2O2 to water and oxygen, thus reducing the amount of H2O2 available for oxidative etching of AuNRs, and generating a series of distinct colors depending on the frequency of SNP in the target DNA. The frequency of SNP can be detected with the naked-eye or with UV-vis spectroscopy. The naked-eye detection limits of G–T and A–C mismatches are 17 and 15 pM, whereas UV-vis method responds linearly to these mismatches in the ranges from 10 to 200 pM and 5 to 120 pM with detection limits of 4 and 2 pM (3σ/slope), respectively. The present genosensor demonstrates a straightforward and easy-to-interpret method for naked-eye discrimination between PCR products of normal, heterozygous, and homozygous β-thalassemia-related mutation of β-hemoglobin.

ObjectivesPharyngeal carriers such asH.influenzaeseem to constitute the only reservoir and probably the only transmission vehicle of the invasive disease. The aims of this study were to estimate the prevalence ofH. influenzaecarriage, to characterize antibiotic susceptibility, and to explore genetic diversity ofH. influenzaeisolates. Sampling was carried out as nasopharynx swabs among children less than 6 years old volunteers. After traditional biochemical tests, isolates were confirmed by targetingomp6sequence. Following the susceptibility tests, genomic diversity of strains was analyzed by Pulsed-Field Gel Electrophoresis procedure.ResultsOut of 328 nasopharynx swabs, 73 strains were identified as H.influenzae. AmongH. influenzaeisolates, resistance to chloramphenicol (42%) and ampicillin (43%) was observed. Levofloxacin is the most effective antibiotic and the least effect belonged to tetracycline. By genomic analysis of selectedH.influenza, 28 PFGE patterns were achieved among which 11 patterns included at least 2 strains. All strains clustered into 25 different clones. The dendrogram analysis of the isolatedH.influenzaestrains showed that some of these strains had a clonal relationship and common genetic origin. According to our results, antibiotic resistance didn’t show any significant correlation with the clonality of strains.

Background & Aims Clostridioides difficile (C. difficile) has been identified as the leading cause of antibiotic associated diarrhea (AAD). Co-carriage of an intact pathogenicity locus (PaLoc) with binary toxin genes in C. difficile strains seems to be linked with severe disease outcomes in the infected patients. Epidemiology of C. difficile infection (CDI) in hospital setting and knowledge about their genetic context help us to decrease the morbidity, mortality, and costs associated with Clostridioides difficile infection. In the present study was aimed to characterize genetic diversity of PaLoc among different C. difficile strains isolated from hospitalized patients and carriage of cytolethal distending toxin gene (cdt) in different hospitals. Method C. difficile strains were isolated from stool samples of inpatients referred to a reference laboratory from different hospitals and also outpatients with diarrhea, during 2008–2011. DNA was extracted from pure culture of the bacterium and PCR was performed for tcdA, tcdB, tcdE, tcdC, tcdD, and cdu2 genes. Carriage of two binary toxin genes cdtA, cdtB was also determined in these strains. To find clonal strains, similarity of genotypes and integrity of PaLoc among the isolates was compared in each hospital. Results The intact PaLoc was found most frequently among the isolates in the outpatients (19/51, 37.2%, Group I), while incomplete PaLoc found mostly in patients who were hospitalized in the infectious diseases and internal diagnosis wards. tcdA and tcdB genes were detected in different combinations among the studied strains. These strains showed tcdA+B+, tcdA+B−, and tcdA−B+ genotypes in a frequency of 76.4% (39/51), 7.8% (4/51), and 17.6% (9/51), respectively. Analysis of gene composition of the PaLoc showed 19 distinct genotypes among the 51 strains. Accordingly, 38 strains were classified mainly into 6 regular groups, while the remaining strains showed heterogeneous patterns. tcdC−/tcdD− constituted the most common genotypic group among the strains with partial PaLoc (7/51, 13.7%). A hypertoxigenic genotype, tcdC−/tcdA+/tcdB+, was detected in 2 strains (2/51, 3.9%). The intact genotype was also detected in a C. difficile isolate from outpatients. Cdt encoding genes toxins was observed in low numbers of the strains (7/52, 13.5%). All of cdtA+B+ strains were belonged to PaLoc group 1 (intact genotype). Statistical analyses showed no correlation between particular genotypes and special wards of the hospitals (p value>0.05). Conclusion Collectively, our results showed diversity of C. difficile strains in most wards of the studied hospitals. Diversity of PaLoc genotypes in the strains that isolated from the same wards proposed endogenous routes of the infection, as common cause of CDI in these patients.

High power performance with the ability to be charged in a matter of seconds have made supercapacitors the technology of choice for cutting-edge applications. However, improving the energy content of supercapacitors is necessary to contribute to the technological advancement of energy storage devices. Herein, we report the synthesis of two transition metal spinel oxide-reduced graphene oxide (rGO) nanocomposites; namely CuCo2O4-rGO and CoFe2O4-rGO. The CuCo2O4-rGO nanocomposite as a positive electrode exhibits an extremely high specific capacitance of 2064.0 F g−1 at 2 A g−1, whereas the CoFe2O4-rGO nanocomposite as a negative electrode shows a specific capacitance of 261.0 F g−1 at 2 A g−1. The asymmetric CoFe2O4-rGO//CuCo2O4-rGO device exhibits an ultrahigh specific energy of 77.2 Wh kg−1 at 953.0 W kg−1, maintains 8.3 Wh kg−1 under the outstanding specific power of 21.0 kW kg−1, and displays excellent cycling stability (96% capacitance retention after 5000 cycles). We also fabricated an asymmetric AC//CuCo2O4-rGO device (AC = activated carbon) as a control, and realized that the CoFe2O4-rGO nanocomposite not only outperforms AC in terms of specific energy, but also contributes to a higher specific power. The results indicate that these nanocomposites are promising materials for the fabrication of high performance supercapacitors.

The oxidation states of polymers and their stabilities are of great importance for their application in energy storage systems. In this paper, we report an air-stable triphenylamine–triazine-based conjugated microporous polymer (pTTPATA) with the smart function of changing color by simply changing the applied voltage. Uniquely, the yellow colored neutral polymer switches to a red color upon oxidation (p-doping) and the red color remains stable even for ten hours after removal of the applied potential, which allows an in-depth analysis of the pTTPATA in the oxidized state. X-ray photoelectron spectroscopy (XPS) confirms that large amounts of radical cations from the triazine groups as well as a small proportion of those from oxidized triphenylamine are present in the stable red-colored oxidized state of the pTTPATA film. Electrochemistry and density functional theory (DFT) calculations demonstrate that only the triphenylamine group is oxidized in the pTTPATA polymer under the applied voltages. Thus, we conclude that most of the oxidation of the pTTPATA polymer occurs from the structural resonance from the oxidation of the triphenylamine group to the relatively more stable radical cation of the triazine group, which results in a stable red colored oxidation state. More importantly, the structural resonance in the special oxidation state induces the charge storage of triazine except the charge storage of triphenylamine, which results in a high specific capacity of ∼81 mA h g−1, among the best reported values for conducting polymers-based energy storage systems. The combination of these fascinating properties results in an intelligent energy storage device that changes its color based on its charged state so that the state of charge can be monitored by simple visual inspection.

Background and Objectives: Cutaneous candidiasis is a multipicture fungal infection caused by members of the genus Candida which is considered as a public health problem all over the world with urgency of effective treatment and control. This study was performed to analyze the clinical epidemiology and molecular aspects of cutaneous candidiasis in Tehran-Iran in relation to antifungal susceptibility and virulence factors of etiologic Candida species. Materials and Methods: Candida species were isolated from skin (27.3%) and nail scrapings (72.7%) of suspected patients and identified by ITS sequencing. Phylogeny of the isolates was evaluated using multilocus sequence typing (MLST) and antifungal susceptibility and virulence factors of the isolates were determined in relation to clinical presentation. Results: Candida albicans was the most prevalent species (39.8%), followed by C. parapsilosis (32.9%), C. orthopsilosis (10.4%), C. tropicalis (7.9%), C. glabrata and C. guilliermondii, each (4.5%). Molecular typing of 35 C. albicans isolates by MLST revealed 28 novel sequence types with 11 singletons with 80.0% new diploid sequence types (DSTs). Majority of the isolates were susceptible to amphotericin B (91.5%), followed by posaconazole (90.3%), fluconazole (84.3%), itraconazole (74.1%), caspofungin (53.6%), and voriconazole (26.8%). Biofilm formation, yeast-to-hyphae transformation and phospho- lipase activity were reported species-dependent. Conclusion: Our results demonstrated clinical epidemiology of various Candida species from cutaneous candidiasis dis- tributed in new molecular types with increasing importance of drug resistant of non-albicans Candida species. Our results showed that drug susceptibility and genetic variability of Candida species may be attributed to their clinical features and source of isolation.

Consumption of very hot beverages and foods increases the incidence of oral and esophageal cancer but the mechanisms are not known and the critical temperature is not well defined. We realized a study with exfoliated cells from the oral cavity of individuals (n = 73) that live in an area in Iran which has the highest incidence of EC worldwide. Consumption of beverages at very high temperatures is a characteristic feature of this population. We analyzed biomarkers which are (i) indicative for genetic instability (micronuclei that are formed as a consequence of chromosomal damage, nuclear buds which are a consequence of gene amplifications and binucleated cells which reflect mitotic disturbances), (ii) markers that reflect cytotoxic effects (condensed chromatin, karyorrhectic, karyolitic and pyknotic cells), (iii) furthermore, we determined the number of basal cells which is indicative for the regenerative capacity of the buccal mucosa. The impact of the drinking temperature on the frequencies of these parameters was monitored with thermometers. We found no evidence for induction of genetic damage but an increase of the cytotoxic effects with the temperature was evident. This effect was paralleled by an increase of the cell division rate of the mucosa which was observed when the temperature exceeded 60 °C. Our findings indicate that cancer in the upper digestive tract in drinkers of very hot beverages is not caused by damage of the genetic material but by an increase of the cell division rate as a consequence of cytotoxic effects which take place at temperatures over 60 °C. It is known from earlier experiments with rodents that increased cell divisions lead to tumor promotion in the esophagus. Our findings provide a mechanistic explanation and indicate that increased cancer risks can be expected when the drinking temperature of beverages exceeds 60 °C.

BackgroundMagnetospirillum gryphiswaldense (MSR-1), a type of magnetotactic bacteria are capable of forming magnetosomes, which are nanometer-sized particles and membrane-enclosed organelles containing crystals of magnetite (Fe3O4). For the synthesis of magnetosomes, bacteria require a significant amount of iron. Iron is an essential element for most life on earth; however, the elevation of iron level leads to hemochromatosis.This research aimed to investigate whether MSR-1 has an impact on the alteration of iron levels in mammalian cells in vivo.Female BALB/c were received intraperitonealinjections of iron-dextran (100mg/kg b.w.) 2 times per week for four consecutive weeks, and the iron was allowed to equilibrate for 15 days. The MSR-1 (109 in 200 µl PBS)were injected into healthy (C+MSR-1) and iron overloaded (IO+MSR-1) mice. The control healthy (C+ no MSR-1) and control iron overloaded (IO+ no MSR-1) mice received PBS. After the administration of bacteria, the viable bacterial numbers were evaluated in mice. Iron levels in serum and liver, as well as urinary iron exertion, were detected.ResultsBacteria were not detected in the liver, spleen, and lymph nodes of mice after 72 hours of post-injection. Serum iron and total liver iron levels in C+MSR-1 were reduced compare to C-MSR-1 (by 42.1% and 34.1%), respectively. Moreover, similar patterns were observed in IO+MSR-1 compare to IO+ no MSR-1, 42.1% iron reduction in serum, and 32.1% in the liver after 24h of post-injection. The urinary iron exertion was dramatically increased (by 3-fold) compared to groups with no MSR-1. ConclusionOur results suggest that MSR-1 can reduce the iron in iron-overloaded mice and, therefore, may inhibit the organ damage caused by excess iron. Our research on optimizing the biological magnetic system is continuing.

Background: After cardiovascular diseases, cancer is the main cause of death in the United States, and its prevalence is continually increasing. Ovarian cancer is a fetal and common cancer among women and is the eighth common cancer in Iran. Colorectal cancer is known as the second and fourth common cancer in Iranian women and men, respectively. Arazyme is a metalloprotease with strong antitumor effects on tumor cells. Objectives: This study aimed at studying the effect of metalloprotease arazyme in vitro on the expression of MMP2 and MMP9 genes, causing metastasis in ovarian and colon cancer. Methods: Bacterial strains and cell lines, the construction of an expression vector, and preparation of recombinant protein were done. Then, they were evaluated by Western blot, cell culture, cell viability assay, and reverse transcriptase-polymerase chain reaction. Results: The effects of arazyme on ovarian and colon cell lines were assessed by the MTT assay showing that the viability of cancer cells treated with arazyme decreased significantly in comparison with control cells. Also, RT-PCR showed that the expression of MMP2 and MMP9 genes decreased after treatment with arazyme, which was significant when compared to the results of pre-treatment. Conclusions: In this study, the results showed that the use of arazyme protein as a bacterial anti-protease can play a significant role in reducing the expression of metastatic genes. According to numerous studies on the role of bacterial proteases in the process of metastasis in recent years, this method can be considered as a therapeutic approach in reducing the metastatic process.

Colorectal cancer is a lethal and prevalent type of cancer in both men and women worldwide, which can develop resistance to cancer chemotherapy. Developing an effective therapeutic agent is the most promising method for this life-threatening disease. The present study aimed to identify, clone, express and purify the recombinant arazyme (r-arazyme) of Serratia proteomaculans and evaluate the antitumor effect of r-arazyme in vitro.Bacterial strains and cell line, construction of expression vector and preparation of recombinant protein were prepared and then evaluated by western blot, cell culture, cell viability assay, lactate dehydrogenase release assay, cell apoptosis assay, caspase-3 and -9 activation assay, adhesion assay, matrigel invasion assay and reverse transcriptase-polymerase chain reaction (RT-PCR).R-arazyme caused a great cytotoxic effect against human colorectal adenocarcinoma (HT29) cells in a dose-dependent manner, without any cytotoxic effect on human embryonic kidney cells 293 (HEK 293). In addition, r-arazyme could induce apoptosis in colorectal cancer cell lines via caspase-3 activation and the elevation of the Bax/Bcl-2 ratio. Further, r-arazyme inhibited cancer cells angiogenesis by significantly reducing the expression of angiogenesis-related genes such as VEGF, VEGFR-1, and VEGFR-2. Furthermore, r-arazyme could prevent invasion and adhesion of cancer cells. In general, the results may support the evidence that r-arazyme is a promising therapeutic candidate against cancer.R-arazyme may play an important role in developing effective therapies against colorectal adenocarcinoma in humans, which results in reducing the overall morbidity and mortality related to colorectal cancer.

BACKGROUND AND OBJECTIVES: Gut microbiota such as Faecalibacterium prausnitzii play a major role in the regulation of gut barrier, inflammation and metabolic functions. Microbiota–derived extracellular vehicles (EVs) have been recently introduced as functional units mediating the eukaryotic and prokaryotic cell-microbiota interactions. In this paper, the effect of F. prausnitzii and its EVs on mRNA expression levels of tight junction genes (ZO1 and OCLN) as well as PPARs and ANGPTL4 genes in the human epithelial colorectal adenocarcinoma (Caco-2) cell line was evaluated. METHODS: F. prausnitzii was cultured on the Brain Heart Infusion (BHI) broth medium under anaerobic conditions, and its EVs were extracted by ultracentrifugation. This bacterium and its EVs were treated on the Caco-2 cells. After 24 h, the expression of the genes encoding TJ proteins such as ZO1 and OCLN, PPARs and ANGPTL4 was evaluated by quantitative real-time PCR. RESULTS: Unlike F. prausnitzii, its EVs significantly increased the expression of ZO1 and OCLN genes, and PPARα, PPARγ and PPARβ/δ genes (except at a concentration of 100 µg/ml) as well as ANGPTL4 gene. CONCLUSIONS: The results of this study demonstrated that F. prausnitzii–derived EVs increased the intestinal barrier permeability via TJs (ZO1 and OCLN) as well as PPAR-α, PPAR-γ and PPAR β/δ genes and their targeted gene (ANGPTL4) in the Caco-2 cell line. Accordingly, it is suggested that F. prausnitzii–derived EVs can be considered as a new bacterial postbiotic to cure dysbiosis-associated diseases including obesity and its related metabolic dysfunctions, according to the leaky gut hypothesis. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s40200-020-00605-1) contains supplementary material, which is available to authorized users.

Herein, we report the one-pot co-synthesis of a novel water-stable nickel-based metal-organic framework (Ni-MOF) with a Co-MOF, as well as the dual Ni/Co-MOF-reduced graphene oxide (rGO) nanocomposite in the same reaction vessel. Introduction of the two metal precursors along with the organic linker in the same reaction vessel guarantees in situ homogeneously distributed MOF particles in the nanoscale level that cannot be obtained by physical mixing of the MOFs synthesized individually. The Ni/Co-MOF-rGO nanocomposite demonstrates a high specific capacitance of 860 F/g at 1.0 A/g. The asymmetric activated carbon//Ni/Co-MOF-rGO device delivers specific energy of 72.8 Wh/kg at 850 W/kg, and still holds 15.1 Wh/kg under the high specific power of 42.5 kW/kg, as well as a long cycle life (91.6% capacitance retention after 6000 charge-discharge cycles at 1 A/g). Two 1.0 cm2 devices connected in series run a clock for about 2 h, and also sequentially power a blue light emitting diode (LED) for 25 min, then a green LED for 25 min, and finally a red LED for more than 140 min, demonstrating that the nanocomposite is a very promising active material for practical applications.

With rising energy consumption in the world and the negative environmental and human health impacts of fossil fuels, the demand for renewable energy sources is increasing. The energy generated by renewable energy sources can be stored either in a chemical (water splitting) or an electrochemical (battery or supercapacitor) form, that are two distinct processes. Here, we introduce an integrated solar-powered system for both electrochemical energy storage and water electrolysis. A nickel-cobalt-iron layered double hydroxide (Ni-Co-Fe LDH) was successfully synthesized on nickel foam as a substrate using a fast, one-step electrodeposition approach. The Ni-Co-Fe LDH exhibited excellent electrochemical properties both as an active electrode material in supercapacitors, and as a catalyst in the oxygen evolution reaction (OER). When employed as the positive electrode in a supercapacitor, along with activated carbon as the negative electrode in an asymmetric configuration, the ultrathin and porous Ni-Co-Fe LDH nanoplatelets delivered an ultrahigh specific energy of 57.5 W h kg −1 with an outstanding specific power of 37.9 kW kg −1 and an excellent cycle life. As an OER electrocatalyst, Ni-Co-Fe LDH exhibited superior electrocatalytic performances with a very low overpotential of 0.207 V versus a reference hydrogen electrode (RHE) at 10.0 mA cm −2 , and a small Tafel slope of 31 mV dec −1 . The superior energy storage and catalytic OER properties of the Ni-Co-Fe LDH nanoplatelet array can be attributed to both the synergistic effects among the metal species and the unique mesoporous structure of the LDH that provides facilitated charge/ion diffusion pathways and more available active sites.

While the market for supercapacitors is rapidly growing due to their high power density, their low energy density compared to batteries represents a great barrier for the future of this technology. The poorly understood chemistry of electrode-electrolyte interfaces implies that there is substantial room for improvement through a careful design of the materials involved. Here we present a unique approach for improving the energy density of supercapacitors through redox additive-assisted electrocatalytic in situ regeneration of the electrode active materials. By utilizing a quinone-based redox electrolyte and a nanostructured conjugated polyaniline electrode, we continually regenerate the reactants, resulting in a redox supercapacitor having an extremely high energy density of 1091 Wh kg−1 (based on the total mass of the electrode active materials and the redox additive) and a high power density up to 196 kW kg−1. Considering the other outstanding properties of the polyaniline-naphthoquinone system, such as extreme flexibility (96% capacity retention after bending at an angle of 180° for 1000 cycles), non-flammability, and excellent cycling stability (84% capacity retention after 7000 cycles at 35 A g−1), such a well designed in situ regeneration of the electrode active materials makes this method a very promising approach towards the development of state-of-the-art energy storage devices.

Aqueous supercapacitors based on neutral solutions have the advantages of high-ionic conductivity, being environmentally friendly, safe, and low cost. However, the operating potential window for most aqueous electrolytes is far lower than that of organic electrolytes that are commonly used in commercial supercapacitors. In this work, we report on the fabrication of a wide potential window, high-energy aqueous asymmetric supercapacitor, without sacrificing power, by using a nanostructured LiMn2O4/reduced graphene oxide (LMO–rGO) nanocomposite. We synthesized the uniformly distributed LMO in the LMO–rGO nanocomposite using a co-precipitation route followed by a low-temperature hydrothermal treatment. In a three-electrode cell setup, the specific capacitance of the LMO–rGO nanocomposite electrode at 1 A/g (1.2 mA/cm2) is 268.75 F/g (258 mF/cm2), which shows a dramatic improvement over the sum of the specific capacitances of pristine LMO (162.5 F/g) and pure rGO (29.94 F/g) electrodes in their relative ratios, when used alone. This finding suggests a synergistic coupling of LMO and rGO in the nanocomposite. We also assembled the LMO–rGO nanocomposite, as the positive electrode, with activated carbon, as the negative electrode, into an asymmetric cell configuration. The device shows an ultra-wide potential window of 2.0 V in a neutral aqueous Li2SO4 electrolyte, with a maximum energy density of 29.6 Wh/kg (which approaches the commercial lead-acid batteries), power density of up to 7408 W/kg, and an excellent cycle life (5% loss after 6000 cycles). These findings confirm that an LMO–rGO nanocomposite is a promising material to meet the demands of real world energy storage.

Supercapacitors (SCs), as high power density energy storage resources, have recently attracted considerable attention. Increasing the energy of supercapacitors is a key parameter to success in achieving far more demanding energy storage applications. There are two approaches to achieve this goal: the first is to widen the operating potential window, and the second is to develop emerging capacitive or pseudocapacitive materials. Polyaniline (PANI) with different morphologies, and hence different supercapacitive performances, has been considered as one of the intriguing active materials due to its high conductivity, intrinsic flexibility, and high redox active specific capacitance. In this work, we report on a simple and convenient method to synthesize PANI nanotubes with rectangular morphology. Then we synthesized PANI/reduced graphene oxide (PANI-rGO) nanocomposite via a convenient electrochemical reduction process. We investigated electrochemical performance of the electrode in the presence and absence of catechol, as a redox-additive molecule incorporated into the electrolyte, by CV, EIS and GCD methods. With incorporation of the catechol in the electrolyte the operating potential window of the electrode increased from 1.0 to 1.2 V, and its capacitance boosted about 5-fold from 429 to 1967 F/g at a current density of 1 A/g. The astonishing supercapacitive performance of the electrode is attributed to; (i) the rectangular nanotube morphology of the PANI, which provides both a better electrical conductivity and a facilitated ion transport pathway, and (ii) the synergetic effect between PANI-rGO and catechol. The electrode showed a superior long cycle life with 81% retention of the initial specific capacitance after 5000 cycles, and demonstrated an excellent rate capability with specific capacitances of 267 and 546 F/g, at a current density of 20 A/g, in the absence and presence of catechol, respectively. Furthermore, we fabricated a symmetric device using the PANI-rGO film on a flexible stainless steel substrate in the catechol-containing electrolyte. The device showed specific capacitance of 409 F/g at 1 A/g, energy density of 81.8 Wh/kg and power density of 7.7 kW/kg. These findings could be beneficial for further development of diverse energy storage devices and open up new prospects for the fabrication of high energy and power supercapacitors.

PURPOSE: Staphylococcus epidermidis is an opportunistic pathogen and a leading cause of morbidity and premature mortality in patients with medical device-related infections, which is a concern in hospitalized patients. Developing a strategy to raise opsonic antibodies against polysaccharide intracellular adhesin (PIA) could be promising for the elimination of colonizing and biofilm-forming S. epidermidis. Following the purification of truncated rSesC protein and PIA, for the first time, PIA was conjugated to rSesC as a carrier to increase the immunogenicity of PIA and its efficacy in mice was evaluated. The structure of the conjugate was analysed using the Fourier transform infrared spectroscopy (FTIR) and proton nuclear magnetic resonance spectroscopy (H1- NMR) methods. Afterwards, the immune response was evaluated by measuring the total IgG, IgG2a and IgG2b titres. RESULTS: The immunization of mice with the PIA-rSesC conjugate raised the levels of opsonic antibodies, and the vaccinated mice were protected when challenged intravenously by wild-type S. epidermidis strain 1457. Further studies indicated that the conjugated vaccine was able to eliminate S. epidermidis biofilm formation in in vitro or in vivo assays. CONCLUSION: This study confirms the proposal that the immunization of mice with PIA-rSesC conjugate vaccine could protect against S. epidermidis infection. ispartof: JOURNAL OF MEDICAL MICROBIOLOGY vol:68 issue:5 pages:791-802 ispartof: location:England status: published

BACKGROUND: Among hospitalized patients, Staphylococcus aureus (S. aureus) infections pose a serious health threat. The present study investigated the frequency of biofilm forming genes among clinical isolates S. aureus and their susceptibility to antibiotics. METHODS: The clinical samples were analyzed via standard biochemical assays for identifying different bacterium, which was then confirmed using the multiplex colony PCR method. Those samples identified as S. aureus were examined for the presence of the cna, fnbA, fnbB and pvl genes. The antibiotic susceptibility of the S. aureus isolates was then tested. RESULTS: Using the standard biochemical assay approach, 54 S. aureus strains were identified. However, when using the multiplex PCR method 50 S. aureus strains were identified among the clinical samples. The in vitro biofilm formation assays determined 3 (6%) strains of S. aureus to be strong biofilm forming, 15 (30%) of the isolates were determined to be moderate biofilm forming and, 32 (64%) were determined to be weak biofilm forming. Among the isolated strains, the specific frequencies of the biofilm forming genes were determined to be 31 (62%) for cna, 35 (70%) for fnbA, 13 (26%) for fnbB and 1 (2%) for pvl. In 11 (22%) of the isolated strains fnbA, fnbB and cna genes were all present. All strains were determined to be penicillin, amoxicillin and clavulanic acid resistant. CONCLUSION: Due to the increase of the antibiotic resistance in biofilm producing S. aureus strains, rapid identification of antibiotic resistance can help to eliminate the infection effectively.

Over the past decade, electrochemical energy storage (EES) devices have greatly improved, as a wide variety of advanced electrode active materials and new device architectures have been developed. These new materials and devices should be evaluated against clear and rigorous metrics, primarily based on the evidence of real performances. A series of criteria are commonly used to characterize and report performance of EES systems in the literature. However, as advanced EES systems are becoming more and more sophisticated, the methodologies to reliably evaluate the performance of the electrode active materials and EES devices need to be refined to realize the true promise as well as the limitations of these fast-moving technologies, and target areas for further development. In the absence of a commonly accepted core group of metrics, inconsistencies may arise between the values attributed to the materials or devices and their real performances. Herein, we provide an overview of the energy storage devices from conventional capacitors to supercapacitors to hybrid systems and ultimately to batteries. The metrics for evaluation of energy storage systems are described, although the focus is kept on capacitive and hybrid energy storage systems. In addition, we discuss the challenges that still need to be addressed for establishing more sophisticated criteria for evaluating EES systems. We hope this effort will foster ongoing dialog and promote greater understanding of these metrics to develop an international protocol for accurate assessment of EES systems.

The occurred changes in the earth are the most important historical transformations. It is a major opinion that the earth is not going to respond the human beings needs anymore, and we should think about the solutions. During the last decades, several meetings and seminars have been performed in this concern. But, unfortunately, none of the objectives have been achieved. The reason is that there is not any operative protection for the international laws and regulations. Hence, the countries and nations’ authorities should include their accepted obligations within the international meetings in their domestic regulations, which contain a larger operative protection comparing the international ones. Iran is a country which contains special natural and environmental characteristics and is one of the first countries who play an important role in creating international environmental law. So, investigating this country domestic laws in comparison with the international environmental laws transformations will reflex its governors’ viewpoints and strategies and the interaction between the internal and international law in this content. The existing research has been designed based on the results of the field studies which have been fulfilled in 20 provinces of Iran regarding the legal-environmental challenges resulted from the rules and regulation governing the forests, pastures and natural environment and their affected laws, and also, studies the ordinary and program laws of Iran applying the proving, comparative and critical methods. The studies show that, there are a large variety of ordinary law subjects which are not coordinated with international documents. Although, the international coordinated rules are centralized in government organizations which does not attract people participation and will not lead our society to a sustainable development. Therefore, it is necessary to inform people the values of natural resources and their interaction, while revising, improving and integrating the rules in this due to represent them in a unique complex.

Mesoporous carbon nitrides (MCNs) are considered as one of the most fascinating materials for a variety of applications because of their low cost, high specific surface area, abundant functionalities, and ordered porous structures. However, pristine MCNs suffer from a poor electrical conductivity, thus an inferior supercapacitive performance. Herein, we synthesized MCN via a nano hard-templating approach (using SBA-15 template) and then composited it with the graphene aerogel (GA). The highly conductive metal-free MCN-GA nanocomposite, in which MCN is firmly grafted onto GA via covalent bonding, exhibits a hierarchical porous structure, and demonstrates an exceptional supercapacitive performance among the different materials of the carbon family. The structure-/composition-tailored MCN-GA nanocomposite electrode possesses a specific capacitance of ~240 F g−1 at 5 mV s−1 in a 1.0 M H2SO4 electrolyte, which is significantly higher than that of the pristine MCN (142 F g−1) and GA (174 F g−1) electrodes. The symmetric MCN-GA||MCN-GA supercapacitor exhibits an excellent long-term stability with an impressive capacitance retention of >94% after 10,000 charge-discharge cycles, as well as a high specific energy (11.6 W h kg−1) and an outstanding specific power (8.0 kW kg−1). These results indicate the potential of the MCN-GA nanocomposite for future energy storage applications as well as the other related technologies.

The development of efficient drug delivery and imaging approaches is of great importance for both diagnostic and therapeutic purposes. This is especially important for the triple-negative breast cancers for which chemotherapy is often the mainstay of treatment. Metal-organic frameworks (MOFs) have recently attracted tremendous attention as nanocarriers that can be loaded with a wide variety of therapeutic as well as bioimaging agents. Herein, the Fe3O4 core UiO-66-NH2 MOF shell nanostructures, Fe3O4@MOF, were loaded with the anticancer drug doxorubicin (DOX), and the loaded nanostructures were conjugated to highly fluorescent carbon dots (CDs) and then capped with the nucleolin-binding aptamer, AS1411. The Fe3O4@MOF-DOX-CDs-Apt nanocarriers were specifically unlocked in the presence of the nucleolin-overexpressing cancer cells, resulted in the release of the loads. The drug delivery process rendered more efficient by pH-dependent controlled release kinetics that provides an enhanced therapeutic outcome. The stimuli-responsive drug delivery system reveals a rather selective permeation of the Fe3O4@MOF-DOX-CDs-Apt nanocarriers into the triple-negative MDA-MB-231 human breast cancer cells, compared to the normal HUVEC cells. Cytotoxicity experiments revealed that the nanocarriers inhibit cell proliferation and induce selective apoptosis towards the MDA-MB-231 cancer cells (>77% at 24 ​h); whereas, less than 10% apoptosis was induced in the normal HUVEC cells. In addition, we encapsulated CDs into the nanocarriers, thereby, the nanocarriers exhibit fluorescence imaging functionality, thus can effectively contribute to monitoring biodistribution of the nanocarriers in vitro. Based on these findings, the Fe3O4@MOF-DOX-CDs-Apt nanocarriers can serve as a promising multifunctional material for cancer therapy and cellular bioimaging.

We report here a new electrochemical probe for the development of a sensitive, and selective sandwich-type electrochemical immunosensor for the detection of epidermal growth factor receptor (EGFR). The probe is a newly synthesized bovine serum albumin (BSA)-templated Pb nanocluster (PbNC@BSA). For fabrication of the immunosensor, we employed streptavidin-coated magnetic beads (MB) as a platform for immobilization of the biotinylated primary antibody (Ab1), and utilized the PbNC@BSA conjugated to secondary antibody (Ab2) as a signaling probe. After sandwiching the target protein between Ab1 and Ab2, we dissolved PbNC@BSA into an acid, and recorded square wave anodic stripping voltammetric (SWASV) signal of the Pb ions as an analytical signal for quantification of the EGFR. The immunosensor responded linearly towards EGFR within the range of 0.4 ng/mL to 35 ng/mL, with a detection limit of 8 pg/mL. The immunosensor displayed good sensitivity, selectivity, stability, and reproducibility, and proved suitable for direct measurement of EGFR in human serum samples. Moreover, we used the as-synthesized PbNC@BSA as a fluorescence label for in vitro cell viability analysis as well as bioimaging of cancerous HeLa and non-cancerous HUVEC cells. PbNC@BSA exhibited low cytotoxicity and high biocompatibility in living cells, and was a suitable fluorescent probe for live cell imaging, with potential therapeutic applications.

Background and study aim Colitis is a common complication after treatment with antibiotics such as β-lactams, quinolones, and aminoglycosides. Recently, Klebsiella oxytoca has been implicated in this type of diarrhoea. The prevalence and characterisations of K. oxytoca isolated from patients with antibiotic-associated diarrhoea were investigated. The K. oxytoca isolates were also tested for cytotoxin production. Patients and methods This study was conducted from May 2011 to Dec 2013. Faecal samples were collected from hospitalised patients receiving antibiotic treatment. Initial cultivation was performed on specific media. The clinical isolates were confirmed by polymerase chain reaction (PCR) using the specific K. oxytoca polygalacturonase (pehX) gene. The double-disc diffusion test was used to detect extended-spectrum beta-lactamase (ESBL)-producing strains. Tracking of ESBL-encoding genes was performed via PCR. The organism was cultured on Hep-2 cell lines for cytotoxin production. Results Out of 331 samples collected from patients, 40 were confirmed molecularly to be clinical isolates of K. oxytoca . Fourteen (35%) ESBL-producing strains were isolated using the double-disc diffusion method. Among the molecularly confirmed K. oxytoca isolates, seven (17.5%) tested positive for the bla SHV gene, 12 (30%) for bla TEM, 10 (25%) for bla CTX-M, three (7.5%) for bla OXA, nine (22.5%) for bla CTX-M-15, and seven (17.5%) for bla TEM-1. Five (12%) isolates showed cytotoxin activity below 30%, 12 (30%) strains showed moderate cytotoxin activity between 30% and 60%, and 23 (58%) strains showed cytotoxin activity ⩾60%. Conclusions The cytotoxin-producing K. oxytoca is found to be one of the causes of antibiotic-induced colitis. Discontinuing treatment and allowing normal intestinal flora to be established or prescribing appropriate medication after antibiogram can help patients with antibiotic-induced haemorrhagic colitis in a timely manner.