A Julolidine Aldehyde Dansyl Hydrazine Schiff Base as Fluorescence Chemosensor for Zn2+ ions Recognition and its Application.

The Schiff base fluorescent probe (Dz-Jul), containing julolidine aldehyde and dansyl hydrazine, was derived using a simple condensation. This chemosensor showed high selectivity towards Zn2+ and quick response (170 s) in DMSO/H2O solutions (8/2, v/v, pH 7.2 buffer). A fluorometric titration determined that Dz-Jul-Zn2+ has a binding ratio of 1:1, and the association constant (Ka) is 1.03 × 105 M-1. The Dz-Jul detection limit of Zn2+ ions was 15 nM, much lower than the WHO standard (76.0 nM). DFT, ESI mass, and FTIR spectral demonstrated a plausible complexation mode between Dz-Jul and Zn2+ ions. In actual water samples, Zn2+ has been detected with good detection performance using Dz-Jul. Additionally, Dz-Jul-coated test strips allowed for rapid and qualitative monitoring of Zn2+ ions in a visible manner.

3D Lumerical simulation of silicon photodiodes with microholes for high-speed short-reach intra-datacenter interconnects.

3D simulations are conducted using Lumerical software to study the performance of surface illuminated silicon positive-intrinsic-negative photodiodes with microholes. Drift-diffusion equations are solved including the effects of carrier lifetime due to Shockley-Read-Hall and Auger recombination mechanisms, as well as high field mobility. Lumerical's FDTD tool is used to determine the light absorption in the device. The generation profile is imported to Lumerical's CHARGE tool to determine the transient-limited impulse response. An equivalent circuit of the photodiode with microholes is developed for the simulation of an end-to-end high-speed system. Simulation results show an open eye diagram at 50 Gbps for 20µm×20µm devices.

Hepatocellular Carcinoma: Understanding the Inflammatory Implications of the Microbiome.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide. It is well known that repeated inflammatory insults in the liver can cause hepatic cellular injury that lead to cirrhosis and, ultimately, hepatocellular carcinoma. Furthermore, the microbiome has been implicated in multiple inflammatory conditions which predispose patients to malignancy. With this in mind, we explore the inflammatory implications of the microbiome on pathways that lead to HCC. We also focus on how an understanding of these underlying inflammatory principles lead to a more wholistic understanding of this deadly disease, as well as potential therapeutic implications.

CRAMER: a lightweight, highly customizable web-based genome browser supporting multiple visualization instances.

SUMMARY: In recent years, the ability to generate genomic data has increased dramatically along with the demand for easily personalized and customizable genome browsers for effective visualization of diverse types of data. Despite the large number of web-based genome browsers available nowadays, none of the existing tools provides means for creating multiple visualization instances without manual set up on the deployment server side. The Cranfield Genome Browser (CRAMER) is an open-source, lightweight and highly customizable web application for interactive visualization of genomic data. Once deployed, CRAMER supports seamless creation of multiple visualization instances in parallel while allowing users to control and customize multiple tracks. The application is deployed on a Node.js server and is supported by a MongoDB database which stored all customizations made by the users allowing quick navigation between instances. Currently, the browser supports visualizing a large number of file formats for genome annotation, variant calling, reads coverage and gene expression. Additionally, the browser supports direct Javascript coding for personalized tracks, providing a whole new level of customization both functionally and visually. Tracks can be added via direct file upload or processed in real-time via links to files stored remotely on an FTP repository. Furthermore, additional tracks can be added by users via simple drag and drop to an existing visualization instance. AVAILABILITY AND IMPLEMENTATION: CRAMER is implemented in JavaScript and is publicly available on GitHub on https://github.com/FadyMohareb/cramer. The application is released under an MIT licence and can be deployed on any server running Linux or Mac OS. CONTACT: f.mohareb@cranfield.ac.uk. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Identification of a new type of haematopoietic progenitor kinase-interacting protein (HIP-55) in Aedes aegypti mosquito haemocytes and its involvement in immunity-like functions in mosquito: a molecular study.

In this study, we characterize the HIP-55 protein in the mosquito Aedes aegypti for the first time. HIP-55 is a 55-kDa HPK1-interacting protein that is also called SH3P7. HIP-55 constitutively binds HPK1 'via' an HPK1 proline-rich motif 2(PR2) through its C-terminal SH3 domain. HIP-55 critically interacts with ZAP-70, and this interaction was induced by TCR signalling. ZAP-70 phosphorylated HIP-55 at Tyr-334 and Tyr-344 in vitro and in vivo. In our previous findings, AaZAP gene expression strongly proved that AaZAP-70 was involved in immunity-like functions in mosquito. Northern blot analysis of HIP-55 mRNA expression confirmed that it is only expressed in the abdomen and haemocyte tissues; this prediction correlates 100% and a polyclonal antibody also confirmed its localization in haemocytes and the abdomen. We prepared extracts to show the cytoplasmic expression (CE) of this protein. Previous results had proven that this protein is secreted from the cytoplasm; thus, we confirmed here that the protein is a cytoplasmic adaptor protein in mosquitoes and mammalian systems. Furthermore, our polyclonal antibody against HIP-55 also demonstrated that this protein is found in haemocytes and abdomen tissues, which assumes that the protein may be involved in phagocytic-like functions. RNAi (siRNA) silencing studies were used to degrade mosquito HIP-55; however, silencing only slightly affected the HIP-55 sequence and the gene transcriptional level. To characterize this protein, we cloned 609 bp from the 1.6-kb full-length cDNA using a pET28 vector for polyclonal antibody production. Graphical abstract.

Activation of the Integrated Stress Response and Metabolic Dysfunction in a Murine Model of Sleep Apnea.

Intermittent hypoxia (IH) induces activation of the integrated stress response (ISR), but its role in IH-induced visceral white adipose tissue (vWAT) insulin resistance is unknown. CHOP is activated by chronic ISR, whereas GADD34 dephosphorylates the subunit of translation initiation factor 2 (eIF2α), leading to termination of the ISR. We hypothesized that CHOP/Gadd34 null mice would not manifest evidence of insulin resistance after IH exposures. Eight-week-old CHOP/GADD34-/- (double mutant [DM]) and wild-type (WT) littermates were randomly assigned to IH or room air (RA) exposures for 6 weeks. Glucose and insulin tolerance tests were performed, and regulatory T cells (Tregs) and macrophages in vWAT were assessed. Phosphorylated eIF2α:total eIF2α, ATF4, XBP1 expression, and insulin-induced pAKT/AKT expression changes were examined in vWATs. Single GADD34-/- and PERK+/- mice were also evaluated. Body weight and vWAT mass were reduced in DM and WT mice after IH. M1/M2 macrophages and inflammatory macrophages (Ly-6chigh) were significantly increased in WT vWAT but remained unchanged in DM mice. Tregs were significantly decreased in WT vWAT but not in DM mice. Systemic insulin and glucose tolerance tests revealed insulin resistance in IH-WT but not in IH-DM mice. Similarly, decreased pAKT/AKT responses to exogenous insulin emerged in IH-WT compared with RA-WT mice, whereas no significant differences emerged in IH-DM compared with DM-RA. Chronic ISR activation appears to contribute to the insulin resistance and vWAT inflammation that characteristically emerge after long-term IH exposures in a murine model of obstructive sleep apnea.

Visceral White Adipose Tissue after Chronic Intermittent and Sustained Hypoxia in Mice.

Angiogenesis, a process induced by hypoxia in visceral white adipose tissues (vWAT) in the context of obesity, mediates obesity-induced metabolic dysfunction and insulin resistance. Chronic intermittent hypoxia (IH) and sustained hypoxia (SH) induce body weight reductions and insulin resistance of different magnitudes, suggesting different hypoxia inducible factor (HIF)-1α-related activity. Eight-week-old male C57BL/6J mice (n = 10-12/group) were exposed to either IH, SH, or room air (RA). vWAT were analyzed for insulin sensitivity (phosphorylated (pAKT)/AKT), HIF-1α transcription using chromatin immunoprecipitation (ChIP)-sequencing, angiogenesis using immunohistochemistry, and gene expression of different fat cell markers and HIF-1α gene targets using quantitative polymerase chain reaction or microarrays. Body and vWAT weights were reduced in hypoxia (SH > IH > RA; P < 0.001), with vWAT in IH manifesting vascular rarefaction and increased proinflammatory macrophages. HIF-1α ChIP-sequencing showed markedly increased binding sites in SH-exposed vWAT both at 6 hours and at 6 weeks compared with IH, the latter also showing decreased vascular endothelial growth factor, endothelial nitric oxide synthase, P2RX5, and PAT2 expression, and insulin resistance (IH > > > SH = RA; P < 0.001). IH induces preferential whitening of vWAT, as opposed to prominent browning in SH. Unlike SH, IH elicits early HIF-1α activity that is unsustained over time and is accompanied by concurrent vascular rarefaction, inflammation, and insulin resistance. Thus, the dichotomous changes in HIF-1α transcriptional activity and brown/beige/white fat balance in IH and SH should enable exploration of mechanisms by which altered sympathetic outflow, such as that which occurs in apneic patients, results in whitening, rather than the anticipated browning of adipose tissues that occurs in SH.

Circulating Plasma Extracellular Microvesicle MicroRNA Cargo and Endothelial Dysfunction in Children with Obstructive Sleep Apnea.

RATIONALE: Obese children are at increased risk for developing obstructive sleep apnea (OSA), and both of these conditions are associated with an increased risk for endothelial dysfunction (ED) in children, an early risk factor for atherosclerosis and cardiovascular disease. Although weight loss and treatment of OSA by adenotonsillectomy improve endothelial function, not every obese child or child with OSA develops ED. Exosomes are circulating extracellular vesicles containing functional mRNA and microRNA (miRNA) that can be delivered to other cells, such as endothelial cells. OBJECTIVES: To investigate whether circulating exosomal miRNAs of children with OSA differentiate based on endothelial functional status. METHODS: Obese children (body mass index z score >1.65) and nonobese children were recruited and underwent polysomnographic testing (PSG), and fasting endothelial function measurements and blood draws in the morning after PSG. Plasma exosomes were isolated from all subjects. Isolated exosomes were then incubated with confluent endothelial cell monolayer cultures. Electric cell-substrate impedance sensing systems were used to determine the ability of exosomes to disrupt the intercellular barrier formed by confluent endothelial cells. In addition, immunofluorescent assessments of zonula occludens-1 tight junction protein cellular distribution were conducted to examine endothelial barrier dysfunction. miRNA and mRNA arrays were also applied to exosomes and endothelial cells, and miRNA inhibitors and mimics were transfected for mechanistic assays. MEASUREMENTS AND MAIN RESULTS: Plasma exosomes isolated from either obese children or nonobese children with OSA were primarily derived from endothelial cell sources and recapitulated ED, or its absence, in naive human endothelial cells and also in vivo when injected into mice. Microarrays identified a restricted signature of exosomal miRNAs that readily distinguished ED from normal endothelial function. Among the miRNAs, expression of exosomal miRNA-630 was reduced in children with ED and normalized after therapy along with restoration of endothelial function. Conversely, transfection of exosomes from subjects without ED with an miRNA-630 inhibitor induces the ED functional phenotype. Gene target discovery experiments further revealed that miRNA-630 regulates 416 gene targets in endothelial cells that include the Nrf2, AMP kinase, and tight junction pathways. CONCLUSIONS: These observations elucidate a novel role of exosomal miRNA-360 as a putative key mediator of vascular function and cardiovascular disease risk in children with underlying OSA and/or obesity, and identify therapeutic targets.

Extracellular microvesicle microRNAs in children with sickle cell anaemia with divergent clinical phenotypes.

Sickle cell anaemia (SCA) is the most frequent genetic haemoglobinopathy, which exhibits a highly variable clinical course characterized by hyper-coagulable and pro-inflammatory states, as well as endothelial dysfunction. Extracellular microvesicles are released into biological fluids and play a role in modifying the functional phenotype of target cells. We hypothesized that potential differences in plasma-derived extracellular microvesicles (EV) function and cargo from SCA patients may underlie divergent clinical trajectories. Plasma EV from SCA patients with mild, intermediate and severe clinical disease course were isolated, and primary endothelial cell cultures were exposed. Endothelial cell activation, monocyte adhesion, barrier disruption and exosome cargo (microRNA microarrays) were assessed. EV disrupted the endothelial barrier and induced expression of adhesion molecules and monocyte adhesion in a SCA severity-dependent manner compared to healthy children. Microarray approaches identified a restricted signature of exosomal microRNAs that readily distinguished severe from mild SCA, as well as from healthy children. The microRNA candidates were further validated using quantitative real time polymerase chain reaction assays, and revealed putative gene targets. Circulating exosomal microRNAs may play important roles in predicting the clinical course of SCA, and in delineation of individually tailored, mechanistically-based clinical treatment approaches of SCA patients in the near future.

I2-TBHP-catalyzed one-pot highly efficient synthesis of 4,3-fused 1,2,4-triazoles from N-tosylhydrazones and aromatic N-heterocycles via intermolecular formal 1,3-dipolar cycloaddition.

I2-TBHP-catalyzed azomethine imine generation and subsequent regioselective 1,3-dipolar cycloaddition (DC) with aromatic N-heterocycles was developed to afford various 4,3-fused 1,2,4-triazoles in excellent yields. The method is operationally simple and highly efficient with broad functional group tolerance.

DNA barcoding based on plastid matK and RNA polymerase for assessing the genetic identity of date (Phoenix dactylifera L.) cultivars.

The cultivated date palm is the most agriculturally important species of the Arecaceae family. The standard chloroplast DNA barcode for land plants recommended by the Consortium for the Barcode of Life plant working group needs to be evaluated for a wide range of plant species. Therefore, we assessed the potential of the matK and rpoC1 markers for the authentication of date cultivars. There is not one universal method to authenticate date cultivars. In this study, 11 different date cultivars were sequenced and analyzed for matK and rpoC1 genes by using bioinformatic tools to establish a cultivar-specific molecular monogram. The chloroplast matK marker was more informative than the rpoC1 chloroplast DNA markers. Phylogenetic trees were constructed on the basis of the matK and rpoC1 sequences, and the results suggested that matK alone or in combination with rpoC1 can be used for determining the levels of genetic variation and for barcoding.

Sequential decarboxylative azide-alkyne cycloaddition and dehydrogenative coupling reactions: one-pot synthesis of polycyclic fused triazoles.

Herein, we describe a one-pot protocol for the synthesis of a novel series of polycyclic triazole derivatives. Transition metal-catalyzed decarboxylative CuAAC and dehydrogenative cross coupling reactions are combined in a single flask and achieved good yields of the respective triazoles (up to 97% yield). This methodology is more convenient to produce the complex polycyclic molecules in a simple way.

Comparative Evaluation of Volume and Homogeneity of Obturation with Four Different Obturation Systems Using Micro-Computed Tomography: An In vitro Study.

Aim: To evaluate and compare volume and homogeneity of the three different root canal obturation systems. Materials and Methods: Single-rooted premolar (n = 24) teeth samples were selected, and crowns were removed for standardization. Four groups are divided randomly as (n = 6), namely: For group I (single-cone gutta-percha obturation), group II (Beefill 2 in 1 obturation), group III (GuttaCore obturation), group IV (GuttaFlow bioseal obturation) and the root canal were subjected to prepare till X3 (protaper next) and subjected to micro-CT imaging. After completion of obturation, the image was taken by using micro-CT imaging. This is to evaluate the volume of filled obturation material in the canal space and the voided area sections, viz. the apical, middle, coronal, and third sections. Results: Group III (GuttaCore obturation) showed the least significant mean of the difference in relation to the volume of the canal obturation (81.148). The least mean significant difference in area of voids in the canal region for apical (0.00133), middle (0.00233), and coronal thirds (0.00533). The most statistically significant difference is in the apical and middle thirds root canal space. Conclusion: All the experimental groups showed significant differences in volume and voids in the obturation at three different levels, and the GuttaCore obturation systems occupied more of the volume with less voids in the prepared root canal space.

Comparative Evaluation of Antibacterial Efficacy, Molecular Docking of Ethanolic Extract of Blackseed, Seaweed and Calcium Hydroxide Intracanal Medicament with Enterococcus Faecalis Antigens.

Aim: To evaluate the inhibitory effect of ethanolic extract blackseed, seaweed, and calcium hydroxide intracanal medicament with Enterococcus faecalis biofilm. To study the binding interaction between the active components of blackseed and seaweed against the enterococcal surface protein of (E. faecalis) by molecular docking. Materials and Methods: The ethanolic extracts of blackseed and seaweed were prepared using the Soxhlet apparatus. They were divided into three groups, namely, |Group I: Calcium hydroxide, Group II: Blackseed, and Group III: Seaweed. The antibacterial activity of the three groups was detected employing various concentrations ranging from 250, 125, and 62.5 µg/ml and based on the zone of inhibition. The inhibitory potential of medicaments to inhibit E. faecalis growth at various stages and kinetics plate were assessed following biofilm architecture evaluation by crystal violet biofilm assay. With the Swissdock suite, the molecular docking procedure was carried out. PyMOL version 4.1.5 was the program used for visualization. Since enterococcal surface protein (Esp) is primarily involved in the formation of biofilms, it was chosen as the target protein of E. faecalis. Based on their chromatographic investigations, Group II Thymoquinone (TQ) and Group III Ledenoxide were chosen as ligands. Results: The percentage of inhibition of E. faecalis biofilm was analyzed as statistically significant observed within groups. On post-hoc analysis, significant differences were present between the groups (P < 0.05). Molecular docking reveals binding energies of thymoquinone (Group II) and ledenoxide (Group III) against the enterococcal surface protein of E. faecalis were -6.90 Kcal/mol and -6.44 Kcal/mol, respectively. Conclusion: Compared to seaweed, black seed extract exhibited higher antibacterial activity against the E. faecalis biofilm in microbial inhibition and molecular interaction.

Genetic variance in nitric oxide synthase and endothelin genes among children with and without endothelial dysfunction.

BACKGROUND: The presence of endothelial dysfunction (ED) constitutes an early risk factor for cardiovascular disease (CVD) in children. Nitric oxide (NO) and endothelin (EDN) are generated in endothelial cells and are critical regulators of vascular function, with ED resulting from an imbalance between these two molecules. We hypothesized that genetic variants in NO synthase and EDN isoforms and its receptors (EDNRA and EDNRB) may account for a proportion of the risk for ED in developing children. METHODS: Consecutive children (ages 5-10 years) were prospectively recruited from the community. Time to peak post-occlusive reperfusion (Tmax) was considered as the indicator of either normal endothelial function (NEF; Tmax < 45 sec) or ED (Tmax ≥ 45 sec). Lipid profiles, high sensitivity C-reactive protein (hsCRP), fasting glucose and insulin were assayed using ELISA. Genomic DNA from peripheral blood was extracted and genotyped for NOS1 (209 SNPs), NOS2 (122 SNPs), NOS3 (50 SNPs), EDN1 (43 SNPs), EDN2 (48 SNPs), EDN3 (14 SNPs), EDNRA (27 SNPs), and EDNRB (23 SNPs) using a custom SNPs array. Linkage disequilibrium was analyzed using Haploview version 4.2 software. RESULTS: The relative frequencies of SNPs were evaluated in 122 children, 84 with NEF and 38 with ED. The frequencies of NOS1 (11 SNPs), and EDN1 (2 SNPs) were differentially distributed between NEF vs. ED, and no significant differences emerged for all other genes. Significant SNPs for NOS1 and EDN1 SNPs were further validated with RT-PCR. CONCLUSIONS: Genetic variants in the NOS1 and EDN1 genes appear to account for important components of the variance in endothelial function, particularly when concurrent risk factors such as obesity exist. Thus, analysis of genotype-phenotype interactions in children at risk for ED will be critical for more accurate formulation of categorical CVD risk estimates.

Characterization of bioactive compound isolated from Micromonospora marina KPMS1 and its activity against emerging antibiotics resistant strains of Klebsiella pneumoniae HAUTI7 and Proteus vulgaris HAUTI14.

Multiple antibiotic resistances have increased gradually in many classes of antibiotics among the gram negative organisms like Klebsiella pneumoniae and Proteus vulgaris which are the major causes of infection among worldwide. Nearly a hundred urine samples were collected, among them 16 urine samples were having plasmid and its resistant to various antibiotics. This present investigation has determined the resistant plasmid pattern of multi drug resistant Klebsiella pneumoniae and Proteus vulgaris from urinary tract site isolated from hospital patients. The detection and characterization of antimicrobial metabolite derived from marine sediments that produce potent activity against multidrug resistant pathogen. The 16S rRNA sequencing results and phylogeny showed that the resistant bacteria belong to the genera of Klebsiella pneumoniae HAUTI7 and Proteus vulgaris HAUTI14. The antibacterial activity and the characterization of bioactive compound like FT-IR and NMR studies were performed to analyze the structural elucidation of active compounds derived from marine source Micromonospora marina KPMS1. The 16S rRNA sequences of Micromonospora marina KPMS1was deposited in the Gen bank with the accession number MH036351. The effective bioactive compound derived from marine sediments are virtually unlimited interest that control the emerging multiple antibiotic resistant strains.

Cemento-Ossifying Fibroid Epulis in the Posterior Maxilla.

Cemento-ossifying fibroma is a benign fibro-osseous lesion arising from the periodontal ligament and has the potential to form cementum and bone in the periodontal ligament. Cemento-ossifying fibroma is a painless, pedunculated, or sessile, smooth exophytic growth arising attached to the gingival tissues. We present a case of cemento-ossifying fibroid epulis in the posterior maxilla attached to the interdental gingiva between the 26 and 27 region buccally in a 52-year-old female patient managed with surgical excision of the lesion, extraction of the involved teeth, curettage, and palatal obturator while under general anesthesia. The patient was followed up post-operatively, healing was satisfactory, there were no signs of infection, and no recurrence was noted in the six-month follow-up period.

Surgical Correction of Post-traumatic Residual Deformity of the Mandible: A Case Report.

Mandibular fractures are the most common trauma cases that we often come across in our day-to-day practice of oral and maxillofacial surgery. Various factors can lead to deformities and make those cases more challenging, which includes a delay in surgical treatment, resulting in non-union or malunion of the fracture site causing occlusal disturbances and functional abnormalities in the temporomandibular joint.

Synthesis, characterization, and molecular modeling of phenylenediamine-phenylhydrazine-formaldehyde terpolymer (PPHF) as potent anti-inflammatory agent.

Inflammation, a characteristic physiological response to infections and tissue damage, commences with processes involving tissue repair and pathogen elimination, contributing to the restoration of homeostasis at affected sites. Hence, this study presents a comprehensive analysis addressing diverse aspects associated with this phenomenon. The investigation encompasses the synthesis, spectral characterizations (FT-IR, 1H NMR, and 13C NMR), and molecular modeling of p-phenylenediamine-phenylhydrazine-formaldehyde terpolymer (PPHF), a potent agent in promoting inflammation. To explore the reactivity, bonding nature, and spectroscopy, as well as perform molecular docking for in-silico biological evaluation, density functional theory (DFT) utilizing the def2svp/B3LYP-D3BJ method was employed. The results reveal significant biological activity of the tested compound in relation to anti-inflammatory proteins, specifically 6JD8, 5TKB, and 4CYF. Notably, upon interaction between PPHF and 6JD8, a binding affinity of -4.5 kcal/mol was observed. Likewise, the interaction with 5TKB demonstrated an affinity of -7.8 kcal/mol. Furthermore, a bonding affinity of -8.1 kcal/mol was observed for the interaction with 4CYF. Importantly, these values closely correspond to those obtained from the interaction between the proteins and the standard drug ibuprofen (IBF), which exhibited binding affinities of -5.9 kcal/mol, -7.0 kcal/mol, and -6.1 kcal/mol, respectively. Thus, these results provide compelling evidence affirming the tremendous potential of p-phenylenediamine-phenylhydrazine-formaldehyde (PPHF) as a highly promising anti-inflammatory agent, owing to the presence of nitrogen-a heteroatom within the compound.