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Despite having superior transport properties, lack of mechanical flexibility is a major drawback of crystalline molecular semiconductors as compared to their polymer analogues. Here single crystals of an organic semiconductor are reported that are not only flexible but exhibit systematic tuning of bandgaps, fluorescence lifetime, and emission wavelengths upon elastically bending. Spatially resolved fluorescence lifetime imaging and confocal fluorescence microscopy reveals systematic trends in the lifetime decay across the bent crystal region along with shifts in the emission wavelength. From the outer arc to the inner arc of the bent crystal, a significant decrease in the lifetime of ≈1.9 ns is observed, with a gradual bathochromic shift of ≈10 nm in the emission wavelength. For the crystal having a bandgap of 2.73 eV, the directional stress arising from bending leads to molecular reorientation effects and variations in the extent of intermolecular interactions- which are correlated to the lowering of bandgap and the evolution of the projected density of states. The systematic changes in the interactions quantified using electron density topological analysis in the compressed inner arc and elongated outer arc region are correlated to the non-radiative decay processes, thus rationalizing the tuning of fluorescence lifetime.
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INTRODUCTION: Artificial intelligence (AI) is becoming an important part of our lives owing to increased data availability and improved power of computing. One of the recently launched modalities of AI, ChatGPT, is being enormously used worldwide for different types of tasks. In medical context, its use is being explored for clinical queries, academia, research help, etc. Further, literature suggests that parents seek information about health of their children using different Internet resources and would surely turn toward ChatGPT for the same, as this chatbot model is easy to use, generates "one" response, and is available without any subscription. ChatGPT generates a response using text cues and applying different algorithms on prepublished literature but is still in its naïve state; hence, it is imperative to validate the generated responses. Accordingly, we planned this study to determine the clarity, correctness, and completeness of some Frequently asked questions (FAQs) about child's oral health, from a mother's perspective. METHODS: The study design was a vignette-based survey and included a set of 23 questions, for which ChatGPT was interviewed from the perspective of an imaginary parent. The answers responded by ChatGPT were copied "verbatim," and a Google survey form was designed. The survey form was validated and then sent to 15 pediatric dentists, and the responses were mainly collected on the Likert's scale with a provision of one open-ended question aiming to determine "what they would have added" to this generated response as an expert in the field. RESULTS: The responses on Likert's scale were condensed and values ≥4 were considered 'adequate and acceptable' while scores ≤3, were considered 'inadequate'. The generated responses and comments mentioned by different respondents in the open-ended question were critiqued in reference to the existing literature. CONCLUSION: Overall, the responses were found to be complete and logical and in clear language, with only some inadequacies being reported in few of the answers.
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Internet , Oral Health , Parents , Humans , Child , Parents/psychology , Artificial Intelligence , Surveys and Questionnaires , Female , Male , Information Seeking BehaviorABSTRACT
BACKGROUND: Stem cells from human exfoliated deciduous teeth (SHED) hold promise in regenerative medicine owing to their multipotent capabilities resembling mesenchymal stem cells (MSCs). Despite their potential, SHED have not been extensively investigated because their limited lifespan and unavailability of cell-lines pose challenges for therapeutic applications. This study investigated the effect of ectopic human telomerase reverse transcriptase (hTERT) expression on SHEDs' proliferation while preserving stemness and genomic integrity. METHODS: Deciduous teeth were collected from children aged 6-10 years. After isolation and characterization, the SHED were transduced with pBabe-puro-hTERT retrovirus to establish SHED cell-line, which was evaluated and compared with pBabe-puro (mock control) for stemness, multipotency and growth attributes through flow cytometry, trilineage differentiation, and growth kinetics. We also estimated hTERT gene expression, genomic integrity, and validated cell-line through STR analysis. RESULTS: Following hTERT transduction, SHED displayed elevated hTERT gene expression while retaining fibroblast-like morphology and mesenchymal stem cell markers. Moreover, after hTERT transduction cellular shape remained same along with increased replicative lifespan and proliferation potential. SHED-hTERT cells exhibited multi-potency and maintained stemness, as evidenced by surface marker expression and multilineage differentiation. Furthermore, genomic integrity was not affected by hTERT integration, as confirmed by STR analysis and CDKN2A gene assessment. CONCLUSION: Ectopic hTERT expression in SHED successfully prolonged their replicative lifespan and improved their ability to proliferate and migrate, while preserving their stemness, multipotency and genomic integrity, suggesting minimal carcinogenic risk. Establishment of SHED cell-line holds potential in regenerative medicine applications, especially in cell-based drugs and tissue engineering experiments.
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Given the fact that the cellular interior is crowded by many different kinds of macromolecules, it is important that in vitro studies be carried out in the presence of mixed crowder systems. In this regard, we have used binary crowders formed by the combination of some of the commonly used crowding agents, namely, Ficoll 70, Dextran 70, Dextran 40, and PEG 8000 (PEG 8), to study how these affect enzyme activity, dynamics, and crowder diffusion. The enzyme chosen is AK3L1, an isoform of adenylate kinase. To investigate its dynamics, we have carried out three single point mutations (A74C, A132C, and A209C) with the cysteine residues being labeled with a coumarin-based solvatochromic probe [CPM: (7-diethylamino-3-(4-maleimido-phenyl)-4-methylcoumarin)]. Both enzyme activity and dynamics decreased in the binary mixtures as compared with the sum of the individual crowders, suggesting a reduction in excluded volume (in the mixture). To gain deeper insights into the binary mixtures, fluorescence correlation spectroscopy studies were carried out using fluorescein isothiocyanate-labeled Dextran 70 and tetramethylrhodamine-labeled AK3L1 as the diffusion probes. Diffusion in binary mixtures was observed to be much more constrained (relative to the sum of the individual crowders) for the labeled enzyme as compared to the labeled crowder showing different environments being faced by the two species. This was further confirmed during imaging of the phase-separated droplets formed in the binary mixtures having PEG as one of the crowding agents. The interior of these droplets was found to be rich in crowders and densely packed, as shown by confocal and digital holographic microscopy images, with the enzymes predominantly residing outside these droplets, that is, in the relatively less crowded regions. Taken together, our data provide important insights into various aspects of the simplest form of mixed crowding, that is, composed of just two components, and also hint at the enhanced complexity that the cellular interior presents toward having a detailed and comprehensive understanding of the same.
Subject(s)
Adenylate Kinase , Polyethylene Glycols , Diffusion , Adenylate Kinase/metabolism , Adenylate Kinase/chemistry , Adenylate Kinase/genetics , Polyethylene Glycols/chemistry , Ficoll/chemistry , Dextrans/chemistry , Dextrans/metabolism , Spectrometry, Fluorescence , Point Mutation , Coumarins/chemistry , Coumarins/metabolismABSTRACT
ABSTRACT: Cleidocranial dysplasia (CCD) is a developmental anomaly of the skeleton and teeth which may be inherited, be transmitted as dominant characteristics in either male or female or even appear spontaneously. A case was reported in the department of oral medicine and radiology of two sisters age 17 and 19 years old with a chief complaint of milk teeth not falling since childhood. They presented specific physical and oral findings in common which suggested the idea of an undiagnosed syndrome. The sisters showed CCD characteristics including short stature (4 feet) and frontal bone resorption indicating delayed closure of fontanels. The stature is moderately shortened with the neck appearing long and narrow and the shoulders markedly dropped. Dental abnormalities such as retention of primary dentition, multiple supernumerary teeth, and delayed eruption of permanent dentition. OPG showed the presence of multiple impacted permanent and supernumerary teeth with radiolucency involving the crowns of impacted teeth revealing a cystic lesion. Lateral cephalogram also revealed the presence of multiple impacted teeth. The provisional diagnosis of CCD with dentigerous cyst was given. The enucleation of cyst was done and submitted for histopathological examination. Histopathologically, the soft tissue section suggested the features of dentigerous cyst. The final diagnosis of CCD associated with dentigerous cyst was confirmed.
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Bioactive cobalt (II) macrocyclic complexes [Co(N4O4ML1)Cl2]-[Co(N4O4ML3)Cl2] have been synthesized by using the macrocyclic ligands [N4O4ML1], [N4O4ML2], and [N4O4ML3] that have an N4O4 core. These three macrocyclic ligands were all isolated in pure form, together with their complexes. Microanalytical investigations, FT-IR NMR, Mass, magnetic moments, electronic, PXRD, TGA, and EPR spectrum studies were used to analyse their structures. For these complexes, an octahedral geometry is proposed for the metal ion. By using molecular weights and conductivity measurements the monomeric and non-electrolytic nature has been confirmed. The Coats-Redfern and FWO methods are used to determine the thermodynamic characteristics of the ligands and their Co(II) complexes. The molecular modelling using the DFT technique displays the bond angle, bond lengths and quantum chemical properties. To determine their ability to prevent the growth of harmful fungus and bacteria, the ligands [N4O4ML1]- [N4O4ML3] and their complexes were tested in vitro against A. Niger, C. albicans and B. subtilis, S. aureus, E. coli and S. typhi fungal and bacterial organisms, respectively. By using DPPH free radical scavenger assays, the in vitro antioxidant capabilities of each compound were evaluated. The [Co(N4O4ML3)Cl2] antioxidative capabilities revealed significant radical scavenging power. The MTT assay was used to assess the toxicity of all the synthesised compounds under inquiry on MCF-7, HeLa, and A549 cancer cells. The findings revealed that the ligand and the compounds gave outstanding IC50 values in the range of 9.07-36.25 (uM) at a concentration of 25â¯ppm. Among all the substances evaluated, [Co(N4O4ML3)Cl2] complex was discovered to be the most active and least cytotoxic. Additionally, docking investigations of the produced compounds were carried out in order to validate the biological outcomes.
Subject(s)
Antioxidants , Cobalt , Coordination Complexes , Density Functional Theory , Drug Design , Microbial Sensitivity Tests , Molecular Docking Simulation , Cobalt/chemistry , Cobalt/pharmacology , Ligands , Humans , Coordination Complexes/chemistry , Coordination Complexes/pharmacology , Coordination Complexes/chemical synthesis , Antioxidants/chemistry , Antioxidants/pharmacology , Antioxidants/chemical synthesis , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/chemical synthesis , Antifungal Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/chemical synthesis , Macrocyclic Compounds/chemistry , Macrocyclic Compounds/pharmacology , Macrocyclic Compounds/chemical synthesis , Molecular Structure , Cell Survival/drug effects , Drug Screening Assays, Antitumor , Biocompatible Materials/chemistry , Biocompatible Materials/chemical synthesis , Biocompatible Materials/pharmacology , Picrates/antagonists & inhibitors , Picrates/chemistry , Anti-Infective Agents/pharmacology , Anti-Infective Agents/chemistry , Anti-Infective Agents/chemical synthesis , Biphenyl Compounds/antagonists & inhibitors , Biphenyl Compounds/chemistry , Cell Proliferation/drug effects , Bacteria/drug effects , Fungi/drug effects , Cell Line, TumorABSTRACT
De novo Aspergillus infections of the appendicular skeleton are rare. A 72-year-old female presented with pain and deformity in her left lower limb and an inability to bear weight that had persisted for the last six months. A femur biopsy confirmed the diagnosis of extensive Aspergillus osteomyelitis, and the patient was treated with amphotericin B and oral voriconazole. The patient died of COVID-19 after 2.5 months of treatment. A diagnosis of Aspergillus osteomyelitis may be delayed because of its varied clinical presentation. To the best of our knowledge, this is the first known case of de novo neglected and extensive (multisite, multibone) Aspergillus osteomyelitis in an immunocompetent patient. This case highlights the importance of awareness in patients and treating physicians of this rare infection and its early diagnosis to prevent extensive spread.
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Objective Pterion is an "H" shaped formation of sutures located in the temporal fossa of the skull. It is an important anatomical landmark and a craniometric point. The thinness of the skull and its inner relation with the middle meningeal artery make this anatomical landmark clinically significant. Variations in the pterion are imperative, especially for neurosurgeons in order to have the most suitable craniometric point to be minimally invasive. Materials and Methods One hundred pterions were studied to report the variations in the type and location of the pterion. Murphy's classification was used to classify the pterion into four types on the basis of bone articulation-sphenoparietal, frontotemporal, stellate, and epipteric. Results All four types of pterions were observed, sphenoparietal being the most common. No significant gender difference was observed in terms of type and laterality of various pterions. The mean distance between the center of pterion to the superolateral point of zygomaticotemporal (PZT) suture and the anterolateral point of the frontozygomatic (PFZ) suture were 3.91 ± 3.79 cm and 3.68 ± 3.79 mm, respectively. Correlation analysis showed a strong positive relation between PZT and PFZ sutures. Conclusion Accurate data on the morphology and morphometry of bony anatomical points are crucial, while performing intracranial surgery using them as recognizable landmarks. The morphometric parameters may help in determining the soundness of the pterion as an identifiable landmark for performing interventions like burr hole and other neurosurgical procedures in this area.
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Primary signet ring cell carcinoma (PSRCC) of the prostate is an extremely rare variant of prostatic adenocarcinoma. A PubMed search of the English language literature from January 2000 to June 2020 using the keywords "signet ring cell carcinoma" and "prostate," identified 20 cases of PSRCC of the prostate. On the basis of the combined data from this study and the literature review, 21 such patients were evaluated for clinical characteristics, histologic diagnoses, special and immunohistochemical staining, and treatment. The mean age at the diagnosis was 68.47 years (range 50-85 years). The prostate-specific antigen (PSA) levels varied from 0.19 to 6658 ng/mL, with a mean of 509.15 ng/mL. Most (50%) presented with Stage 3 cancer. The most common Gleason grade group was 5 (Gleason score 9 to 10), seen in 61.5%. The extent of signet ring cell involvement of the specimen when reported was documented as more than 20% of the tumor-containing signet ring cells, with a range of 25%-90%. For pathologic diagnosis, the most common special stains performed were periodic acid-Schiff and Alcian blue, and among the immunohistochemical stains, the most common were PSA, CK20, and prostate-specific acid phosphatase. A detailed clinicoradiological and pathological workup is essential to rule out primary from other common sites, in view of its grave prognosis and lack of an established treatment protocol.
Subject(s)
Carcinoma, Signet Ring Cell , Prostatic Neoplasms , Male , Humans , Middle Aged , Aged , Aged, 80 and over , Prostate/pathology , Prostate-Specific Antigen , Prostatic Neoplasms/diagnosis , Prostatic Neoplasms/pathology , Carcinoma, Signet Ring Cell/diagnosis , Carcinoma, Signet Ring Cell/pathology , Pelvis/pathologyABSTRACT
Four new room-temperature nematic liquid-crystalline (LC) dimers consisting of a wedge-shaped 3,4,5-tridecyloxy gallic ester molecule linked to either cyanobiphenyl, cholesteryl, pentaalkynylbenzene or triphenylene based moieties are reported. Dimers with pentaalkynylbenzene and triphenylene moieties in their room-temperature discotic nematic (ND) mesophase show ambipolar charge carrier mobilities of the order of 10-5 cm2 V-1 s-1 and 10-3 cm2 V-1 s-1, respectively, as measured using a time-of-flight (ToF) technique.
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Parkinson's disease is caused by the deficiency of striatal dopamine and the accumulation of aggregated α-synuclein in the substantia nigra pars compacta (SNpc). Neuroinflammation associated with oxidative stress is a key factor contributing to the death of dopaminergic neurons in SNpc and advancement of Parkinson's disease. Two molecular targets, i.e., nuclear factor kappa-light-chain-enhancer (NF-kB) and α-synuclein play a substantial role in neuroinflammation progression. Therefore, the compounds targeting these neuroinflammatory targets hold a great potential to combat Parkinson's disease. Thereby, in this study, molecular docking and Connectivity Map (CMap) based gene expression profiling was utilized to reposition the approved drugs as neuroprotective agents for Parkinson's disease. With in silico screening, two drugs namely theophylline and propylthiouracil were selected for anti-neuroinflammatory activity evaluation in in vivo models of chronic neuroinflammation. The neuroinflammatory effect of the identified compounds was confirmed by quantifying the expression of three important neuroinflammatory mediators, i.e. IL-6, TNF-alpha, and IL-1 beta on brain tissue using ELISA assay. The ELISA experiment demonstrated that both compounds significantly decreased the expression of neuroinflammatory mediators, highlighting the compounds' potential in neuroinflammation management. Furthermore, the drug and disease interaction network of the two identified drugs and diseases (neuroinflammation and Parkinson's disease) suggested that the two drugs might interact with various targets namely adenosine receptors, Poly [ADP-ribose] polymerase-1, myeloperoxidase (MPO) and thyroid peroxidase through multiple pathways associated with neuroinflammation and Parkinson's disease. Computational studies suggest that a particular drug may be effective in managing Parkinson's disease associated with neuroinflammation. However, further research is needed to confirm this in biological experiments.
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Caesarean scar endometriosis (CSE) is a rare type of abdominal wall endometriosis and is frequently missed on initial presentation. A case of CSE diagnosed and treated by surgical excision is presented. Although rare, CSE should be considered a possibility in the differential diagnoses of pain and mass at scar site.
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Introduction: Dental caries has been the most common disease affecting the human population. Once cavitated, the disease requires restoration. Dental adhesives used to bond composite resins to tooth structure have evolved over the last several decades. Composites were developed to meet the requirements of durable esthetics restorative material. The process of bonding occurred due to micromechanical interlocking between hydroxyapatite of enamel and resin. Over a period of time, bonding to enamel has become a reliable procedure. However, bonding to dentin has proven to be less predictable. In order to overcome the challenges, dental adhesive systems have evolved through several generations with changes in chemistry, mechanism, number of bottles, application techniques, and clinical effectiveness. Case details: The "self-etch" system is especially attractive to pediatric dentistry because of its "fewer steps" and "lesser time." One product launched as a self-etching self-adhesive flowable composite Constic (DMG, Germany), a new three- in -one flowable composite that combines etching gel, bonding agent, and flowable composite in one single product which has multiple benefits over conventional products. Such a material can be of true advantage as it allows for single-step application, less technique sensitivity, and reduced chair time. In light of this knowledge, this paper will focus on two commonly performed procedures in the general practitioner's office, that is, the placement of small class I composite resin restorations and the placement of pit and fissure sealants on permanent molars in pediatric patients. Clinical significance: The advantage of this material is less technique sensitivity and reduced chair time. How to cite this article: Pruthi T, Pandit IK, Gugnani N, et al. Bonding Technologies in Young Permanent Molars: A Case Series. Int J Clin Pediatr Dent 2023;16(1):159-161.
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NET-1 is a key chemotropic ligand that signals commissural axon migration and change in direction. NET-1 and its receptor UNC-5B switch axon growth cones from attraction to repulsion. The biophysical properties of the NET-1 + UNC-5B complex have been poorly characterized. Using multi-wavelength-AUC by adding a fluorophore to UNC-5B, we were able to separate the UNC-5B sedimentation from NET-1. Using both multi-wavelength- and single-wavelength AUC, we investigated NET-1 and UNC-5B hydrodynamic parameters and complex formation. The sedimentation velocity experiments show that NET-1 exists in a monomer-dimer equilibrium. A close study of the association shows that NET-1 forms a pH-sensitive dimer that interacts in an anti-parallel orientation. UNC-5B can form equimolar NET-1 + UNC-5B heterocomplexes with both monomeric and dimeric NET-1.
Subject(s)
Netrin Receptors , Netrin-1 , Protein Interaction Domains and Motifs , Animals , Ultracentrifugation , Netrin-1/chemistry , HumansABSTRACT
Netrin-1 is a bifunctional chemotropic guidance cue that plays key roles in diverse cellular processes including axon pathfinding, cell migration, adhesion, differentiation, and survival. Here, we present a molecular understanding of netrin-1 mediated interactions with glycosaminoglycan chains of diverse heparan sulfate proteoglycans (HSPGs) and short heparin oligosaccharides. Whereas interactions with HSPGs act as platform to co-localise netrin-1 close to the cell surface, heparin oligosaccharides have a significant impact on the highly dynamic behaviour of netrin-1. Remarkably, the monomer-dimer equilibrium of netrin-1 in solution is abolished in the presence of heparin oligosaccharides and replaced with highly hierarchical and distinct super assemblies leading to unique, yet unknown netrin-1 filament formation. In our integrated approach we provide a molecular mechanism for the filament assembly which opens fresh paths towards a molecular understanding of netrin-1 functions.
Subject(s)
Glycosaminoglycans , Heparin , Netrin-1 , Axon Guidance , Cell Differentiation , Heparan Sulfate ProteoglycansABSTRACT
Plant diseases are one of the main hurdles for successful crop production and sustainable agriculture development world-wide. Though several chemical measures are available to manage crop diseases, many of them have serious side effects on humans, animals and the environment. Therefore, the use of such chemicals must be limited by using effective and eco-friendly alternatives. In view of the same, we found a Bacillus subtilis BS-58 as a good antagonist towards the two most devastating phytopathogens, i.e., Fusarium oxysporum and Rhizoctonia solani. Both the pathogens attack several agricultural crops (including amaranth) and induce a variety of infections in them. The findings of scanning electron microscopy (SEM) in this study suggested that B. subtilis BS-58 could inhibit the growth of both the pathogenic fungi by various means such as perforation, cell wall lysis, and cytoplasmic disintegration in the fungal hyphae. Thin-layer chromatography, LC-MS and FT-IR data revealed the antifungal metabolite to be macrolactin A with a molecular weight of 402 Da. Presence of the mln gene in the bacterial genome further endorsed that the antifungal metabolite produced by BS-58 was macrolactin A. Pot trial conducted in the present study showed that seed treatment by BS-58 effectively reduced seedling mortality (54.00 and 43.76%) in amaranth, when grown in pathogen infested soil (F. oxysporum and R. solani, respectively), when compared to their respective negative controls. Data also revealed that the disease suppression ability of BS-58 was almost equivalent to the recommended fungicide, carbendazim. SEM analysis of roots of the seedlings recovered from pathogenic attack substantiated the hyphal disintegration by BS-58 and prevention of amaranth crop. The findings of this study conclude that macrolactin A produced by B. subtilis BS-58 is responsible for the inhibition of both the phytopathogens and the suppression of the diseases caused by them. Being native and target specific, such strains under suitable conditions, may result in ample production of antibiotic and better suppression of the disease.
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A series of oxidized cysteinyl peptides ([P-Cys-X-OMe]2; P = Boc or H; X = Trp or Glu) showed vesicular and fibrillar assemblies. The anatomy of the self-assembled vesicles from the water-soluble cystine peptide [Cys-Trp-OMe]2 (1a) has been investigated by using various fluorescent probes such as ammonium 8-anilinonaphthalene-1-sulfonate, Nile Red and pyrene. The morphological characterization was carried out by fluorescence lifetime imaging microscopy (FLIM) and super resolution-structured illumination microscopy (SR-SIM) utilizing the autofluorescence of the vesicles stemming from the self-assembly. The self-assembled structures are also observed in solution as evident from the quantitative phase images obtained using a dual-mode digital holographic microscope (DHM) system. Present investigations show that the self-assembly is enthalpy- and entropy-driven in the aqueous medium. Based on the CD spectral studies, we proposed that 1a organizes into vesicles through the sequestration of indole units. We observed that the solutions of dipeptides 1a-b exhibit autofluorescence in the blue region upon excitation at a wavelength >350 nm. Detailed spectroscopic studies on the peptides lacking tryptophan 2a-b unequivocally showed that the autofluorescence stems exclusively from peptide aggregation. Our experimental results with appropriate controls revealed that the clustering of carbonyl chromophores is central to autofluorescence. Autofluorescence was also used to probe the vesicle formation without using any external fluorescent probe. To the best of our knowledge, this is the first report on autofluorescent vesicles formed by the spontaneous association of dipeptides. We also found that the vesicles formed by 1a can act as a host for guests like C60. The biocompatibility and biodegradability of these peptides along with the autofluorescent nature and guest binding ability of peptide-based vesicles offer numerous applications in the biomedical area.
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Dipeptides , Peptides , Peptides/chemistry , Microscopy, Fluorescence , Tryptophan/chemistry , Water , Fluorescent DyesABSTRACT
UDP-N-acetylglucosamine enolpyruvyl transferase (MurA) is an important enzyme involved in the first cytosolic step of bacterial cell wall synthesis. In this study a combination of ligand based and structure based in silico virtual screening methods were utilised for screening of more than 50,000 drug-like compounds from CSIR-IIIM in-house compound library in order to identify potent inhibitors of MurA. The identified hits were validated in vitro under various incubation conditions using Malachite green phosphate assay, and two potent hits viz 3772-9534 and D396-0012 were identified. Among these hits, compound 3772-9534 showed significant changes in the activity values in different assay conditions. The MD simulation study of 3772-9534 suggested a novel binding site in MurA enzyme, independent of the two-substrate binding sites. Binding of inhibitors at the allosteric site induces conformational changes in the enzyme, which leads to inhibition of enzymatic activity. Overall, the study offers new insight for targeting MurA, which may promote the discovery of novel MurA allosteric site inhibitors.
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Alkyl and Aryl Transferases , Alkyl and Aryl Transferases/metabolism , Binding Sites , Computer Simulation , Enzyme Inhibitors/chemistryABSTRACT
Low-grade intraductal carcinoma (LG-IDC) is the new World Health Organization designation for tumors previously called "low-grade cribriform cystadenocarcinoma" and "low-grade salivary duct carcinoma". LG-IDC is a rare low grade malignant salivary gland neoplasm. A 56-year old woman presented with a painless swelling on the right posterior part of palate of 2 months duration. Radiographic examination revealed heterogenously enhancing soft tissue mass on right side of palate. A provisional diagnosis of pleomorphic adenoma was executed and local excision was done. The tumor had a typical feature of intraductal growth pattern composed of low grade ductal epithelial cells with cribriform and micropapillary patterns forming true "Roman bridges". Immunohistochemically myoepithelial cells displayed p63 around all tumor islands. The case was diagnosed as LG-IDC. LG-IDC is an extremely rare entity and awareness of this entity is important to avoid erroneous diagnosis and inappropriate treatment.
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Introduction: Biologic aggressiveness of OSCC (Oral Cavity Squamous Cell Carcinoma), has intrigued research in various prognosticating histopathological markers over past few decades. DOI (Depth of Invasion) is one such histopathological factor which affects outcomes and was included in the AJCC 8th edition TNM staging. Pattern of Invasion (POI) has been widely reported as an adverse prognostic factor associated with higher locoregional failure and poor prognosis. However, these factors are not utilized for treatment decision making and for outcome assessment. Materials and methods: This is a retrospective analysis of 320 patients with OSCC who underwent treatment, from October 2018-February 2020. Clinic demographic details were extracted from electronic medical records. Univariate and multivariate analysis was done for the parameters. WPOI (Worst Pattern of Invasion) was correlated with all histopathological prognostic factors. Survival analysis was done using Kaplan Meier for WPOI type's I-V. DFS (Disease free Survival) was evaluated for different grades of WPOI. Results: We analyzed the results comparing, early and advanced T (Tumor) stages, cohesive WPOI I-III, non-cohesive WPOI IV-V. Univariate analysis showed a significant association of T-stage (p = 0.001), N (Nodal) -stage (p = 0.002), DOI (p = 0.008), PNI (Peri-neural invasion) (0.001) and Tumor differentiation Grade (p = 0.001). On multivariate analysis, non-cohesive WPOI (IV & V) showed significant association with grade, PNI, DOI (0.002, 0.033 & 0.033 respectively). Non-cohesive WPOI had significantly higher locoregional failures and short DFS. Conclusion: Presence of invasive WPOI is associated with advanced T stage, poor differentiation, PNI, greater depth of invasion, and higher chances of nodal metastasis. WPOI is associated with poor DFS, treatment intensification in early stage disease with WPOI type IV & V may improve survival.