Concentration- and Solvent-Induced Chiral Tuning by Manipulating Non-Proteinogenic Amino Acids in Glycoconjugate Supra-Scaffolds: Interaction with Protein, and Streptomycin Delivery.

We showed solvent- and concentration-triggered chiral tuning of the fibrous assemblies of two novel glycoconjugates Z-P(Gly)-Glu and Z-F(4-N)-Glu made by chemical attachment of Cbz-protected [short as Z)] non-proteinogenic amino acids L-phenylglycine [short as P(Gly)] and 4-Nitro-L-phenylalanine [short as F(4-N)] with D-glucosamine [short as Glu]. Both biomimetic gelators can form self-healing and shape-persistent gels with a very low critical gelator concentration in water as well as in various organic solvents, indicating they are ambidextrous supergelators. Detailed spectroscopic studies suggested ß-sheet secondary structure formation during anisotropic self-aggregation of the gelators which resulted in the formation of hierarchical left-handed helical fibers in acetone with an interlayer spacing of 2.4 nm. After the physical characterization of the gels, serum protein interaction with the gelators was assessed, indicating they may be ideal for biomedical applications. Further, both gelators are benign, non-immunogenic, non-allergenic, and non-toxic in nature, which was confirmed by performing the blood parameters and liver function tests on Wister rats. Streptomycin-loaded hydrogels showed efficacious antibacterial activity in vitro and in vivo as well. Finally, cell attachment and biocompatibility of the hydrogels were demonstrated which opens a newer avenue for promising biomedical and therapeutic applications.

Information-dependent enrichment analysis reveals time-dependent transcriptional regulation of the estrogen pathway of toxicity.

The twenty-first century vision for toxicology involves a transition away from high-dose animal studies to in vitro and computational models (NRC in Toxicity testing in the 21st century: a vision and a strategy, The National Academies Press, Washington, DC, 2007). This transition requires mapping pathways of toxicity by understanding how in vitro systems respond to chemical perturbation. Uncovering transcription factors/signaling networks responsible for gene expression patterns is essential for defining pathways of toxicity, and ultimately, for determining the chemical modes of action through which a toxicant acts. Traditionally, transcription factor identification is achieved via chromatin immunoprecipitation studies and summarized by calculating which transcription factors are statistically associated with up- and downregulated genes. These lists are commonly determined via statistical or fold-change cutoffs, a procedure that is sensitive to statistical power and may not be as useful for determining transcription factor associations. To move away from an arbitrary statistical or fold-change-based cutoff, we developed, in the context of the Mapping the Human Toxome project, an enrichment paradigm called information-dependent enrichment analysis (IDEA) to guide identification of the transcription factor network. We used a test case of activation in MCF-7 cells by 17ß estradiol (E2). Using this new approach, we established a time course for transcriptional and functional responses to E2. ERα and ERß were associated with short-term transcriptional changes in response to E2. Sustained exposure led to recruitment of additional transcription factors and alteration of cell cycle machinery. TFAP2C and SOX2 were the transcription factors most highly correlated with dose. E2F7, E2F1, and Foxm1, which are involved in cell proliferation, were enriched only at 24 h. IDEA should be useful for identifying candidate pathways of toxicity. IDEA outperforms gene set enrichment analysis (GSEA) and provides similar results to weighted gene correlation network analysis, a platform that helps to identify genes not annotated to pathways.

Fabrication of water-resistant fluorescent ink using the near-unity photoluminescence quantum yield of CsPbBr3 doped with NiBr2.

Doping with transition and alkaline earth metal ions into all-inorganic perovskite nanocrystals (NCs) has attracted attention recently for tuning the photoluminescence quantum yield (PLQY). We report on the hot injection synthesis of nickel ion-doped CsPbBr3 NCs with near-unity PLQYs. Nickel ions were successfully incorporated into the octahedral environment of CsPbBr3 NCs, replacing the lead ions. The introduction of nickel ions into CsPbBr3 NCs substantially eliminates intrinsic defects and halide vacancies for improved structural order and near-unity PLQYs. Benefiting from these unique properties, nickel ion-doped CsPbBr3 NCs were dispersed in a polymer to prepare an efficient fluorescent ink. The fluorescent ink shows excellent thermal and water stability under harsh environmental conditions. Moreover, the usefulness of the fluorescent ink for security purposes was demonstrated by designing and recognizing a fluorescent QR code. This study reveals that doped CsPbBr3 NCs can be used to prepare efficient water-resistant fluorescent ink for anti-counterfeiting applications, widening the usefulness of doped all-inorganic perovskite NCs.

Modulatory role of copper on hIAPP aggregation and toxicity in presence of insulin.

Aggregation of the human islets amyloid polypeptide, or hIAPP, is linked to ß-cell death in type II diabetes mellitus (T2DM). Different pancreatic ß-cell environmental variables such as pH, insulin and metal ions play a key role in controlling the hIAPP aggregation. Since insulin and hIAPP are co-secreted, it is known from numerous studies that insulin suppresses hIAPP fibrillation by preventing the initial dimerization process. On the other hand, zinc and copper each have an inhibitory impact on hIAPP fibrillation, but copper promotes the production of toxic oligomers. Interestingly, the insulin oligomeric equilibrium is controlled by the concentration of zinc ions when the effect of insulin and zinc has been tested together. Lower zinc concentrations cause the equilibrium to shift towards the monomer and dimer states of insulin, which bind to monomeric hIAPP and stop it from developing into a fibril. On the other hand, the combined effects of copper and insulin have not yet been studied. In this study, we have demonstrated how the presence of copper affects hIAPP aggregation and the toxicity of the resultant conformers with or without insulin. For this purpose, we have used a set of biophysical techniques, including NMR, fluorescence, CD etc., in combination with AFM and cell cytotoxicity assay. In the presence and/or absence of insulin, copper induces hIAPP to form structurally distinct stable toxic oligomers, deterring the fibrillation process. More specifically, the oligomers generated in the presence of insulin have slightly higher toxicity than those formed in the absence of insulin. This research will increase our understanding of the combined modulatory effect of two ß-cell environmental factors on hIAPP aggregation.

Contribution of Weight and Volume of the Extirpated Thyroid Gland on Voice Alterations After Total Thyroidectomy in Patients With Papillary Carcinoma of the Thyroid.

PURPOSE: Voice change after thyroid surgery is common despite preservation of laryngeal nerves. In this study, we sought to find if the change in voice after total thyroidectomy is related to the weight and volume of the removed thyroid gland. METHODS: This is a prospective cohort study of 50 patients of papillary carcinoma of the thyroid treated with total thyroidectomy from December 2016 through May 2018. Both objective and subjective voice parameters were analyzed preoperatively and at 1 and 3 months following surgery. RESULTS: A cohort of 29 patients, with a median age of 31 years (18-64 years), comprising 22 women were eligible for final analysis. Speaking fundamental frequency showed a mean change of 17.21 Hz (SD 34.49) while the mean intensity change was 5.54 dB (SD 18.21). The mean weight and volume of thyroid gland was 18.99 g (SD 8.93) and 15.67 ml (SD 8.70), respectively. On multivariate analysis, both weight and volume affected the range of frequency (P = 0.002 and 0.035, respectively) and range of intensity (P = 0.014 and 0.008, respectively). CONCLUSION: Larger thyroid tumors are more likely to be associated with transient change in voice quality following their surgical removal despite physical preservation of external and recurrent laryngeal nerves, which may persist up to 3 months. This study affirms that perturbations in voice after thyroidectomy can still exist in spite of clinical demonstration of integrity of neuromuscular function.

Postsynthesis Spontaneous Coalescence of Mixed-Halide Perovskite Nanocubes into Phase-Stable Single-Crystalline Uniform Luminescent Nanowires.

All inorganic mixed-halide perovskite, CsPb(Br xI1- x)3 (0 ≤ x ≤ 1), nanocrystals possess tunable photoluminescence with high quantum yield in the visible window. However, the photoluminescence degrades rapidly with postsynthetic aging due to the spontaneous ion separation and phase instability. Here we show that the postsynthetic aging of CsPb(Br xI1- x)3 nanocubes spontaneously forms highly uniform single-crystalline nanowires with a diameter of 9 ± 0.5 nm and length of up to several micrometers. The nanowires show bright photoluminescence with an absolute photoluminescence quantum yield of 41%. Rietveld refinement identifies the stable orthorhombic phase of the nanowires, implying a phase transition from the cubic crystallographic phase of the nanocubes during the morphology evolution. Transient absorption spectroscopy reveals a faster excited-state decay dynamic with a large exciton delocalization length in 1D nanowires. Our findings elucidate the insights into the postsynthesis morphology evolution of mixed-halide perovskite nanocrystals leading to luminescent nanowires with excellent crystal phase stability for potential optoelectronic applications.

Composition-dependent nanoelectronics of amido-phenazines: non-volatile RRAM and WORM memory devices.

A metal-free three component cyclization reaction with amidation is devised for direct synthesis of DFT-designed amido-phenazine derivative bearing noncovalent gluing interactions to fabricate organic nanomaterials. Composition-dependent organic nanoelectronics for nonvolatile memory devices are discovered using mixed phenazine-stearic acid (SA) nanomaterials. We discovered simultaneous two different types of nonmagnetic and non-moisture sensitive switching resistance properties of fabricated devices utilizing mixed organic nanomaterials: (a) sample-1(8:SA = 1:3) is initially off, turning on at a threshold, but it does not turn off again with the application of any voltage, and (b) sample-2 (8:SA = 3:1) is initially off, turning on at a sharp threshold and off again by reversing the polarity. No negative differential resistance is observed in either type. These samples have different device implementations: sample-1 is attractive for write-once-read-many-times memory devices, such as novel non-editable database, archival memory, electronic voting, radio frequency identification, sample-2 is useful for resistive-switching random access memory application.

Ni(II)-salt catalyzed activation of primary amine-sp(3)Cα-H and cyclization with 1,2-diketone to tetrasubstituted imidazoles.

NiCl2·6H2O and Ni(OAc)2·4H2O were found as efficient catalysts for C-H activation of benzyl and aliphatic amines for an unprecedented multi C-N bond forming cyclization with 1,2-diketones under refluxing toluene to furnish highly substituted and polycyclic imidazoles.

Evaluation of vaginal cytology in female sex-workers: A study in a tertiary hospital of eastern India.

BACKGROUND: Papanicolaou (Pap) test is an important and easy diagnostic tool to detect any abnormalities on vaginal cytology. Pap test is routinely done in women of reproductive age group in many countries. AIM: The aim of this study was to detect spectrum of abnormalities in female sex workers (FSWs) on vaginal cytology. MATERIALS AND METHODS: A total of 60 cases were included over a period of 1 year (July, 2011-June, 2012). The age range of the patients was 14-61 years. Pap stained slides were evaluated by two consultant cytopathologists and reported as normal smear, inflammatory smear, specific infection, low grade squamous intraepithelial lesion (LSIL), high grade squamous intraepithelial lesion (HSIL), atypical squamous cell of undetermined significance (ASCUS), squamous cell carcinoma (SCC) and atypical glandular cell of undetermined significance (AGUS). RESULTS: Most of the smears were abnormal accounting for 86.7% of total cases (52/60). Incidence of HSIL was very high in FSWs. Out of 60 cases, 8 normal smears (13.3%), 12 inflammatory smears (20%), 3 cases of infections (5%), 9 cases of LSIL (15%), 23 cases of HSIL (38.3%), 2 cases (3.3%) each of ASCUS and SCC and 1 case (1.3%) AGUS were encountered. CONCLUSIONS: Close follow-up and histologic examinations are necessary to avoid unnecessary spread of the neoplastic disease and untimely death of the patients. Awareness about diseases in FSWs and diagnostic utility of Pap test are also a must.

The Bethesda system for reporting thyroid fine needle aspirates: A cytologic study with histologic follow-up.

BACKGROUND: The Bethesda system for reporting thyroid cytopathology represents a major step towards standardization, reproducibility, improved clinical significance, and greater predictive value of thyroid fine needle aspirates (FNAs). AIMS: To elucidate the utility of the Bethesda system in reporting thyroid FNAs. MATERIALS AND METHODS: We retrospectively reviewed thyroid FNAs between April 2009 and March 2012, classified them using the Bethesda system, found out the distribution of cases in each Bethesda category, and calculated the malignancy risk for each category by follow-up histopathology. RESULTS: Of the 1020 FNAs, 1.2% were non-diagnostic, 87.5% were benign, 1% were atypical follicular lesion of undetermined significance (AFLUS), 4.2% were suspicious for follicular neoplasm (SFN), 1.4% were suspicious for malignancy (SM), and 4.7% malignant. Of 69 cases originally interpreted as non-diagnostic, 12 remained non-diagnostic after re-aspiration. In 323 cases, data of follow-up histopathologic examination (HPE) were available. Rates of malignancy reported on follow-up HPE were non-diagnostic 0%, benign 4.5%, AFLUS 20%, SFN 30.6%, SM 75%, and malignant 97.8%. CONCLUSIONS: Reviewing the thyroid FNAs with the Bethesda system allowed a more specific cytological diagnosis. In this study, the distribution of cases in the Bethesda categories differed from some studies, with the number of benign cases being higher and the number of non-diagnostic and AFLUS cases being lower. The malignancy risk for each category correlated well with other studies. The Bethesda system thus allows standardization in reporting, improves perceptions of diagnostic terminology between cytopathologists and clinicians, and leads to more consistent management approaches.