Evaluation of post-operative dry eye in upper and lower eyelid reconstruction: A cross-sectional study.

Purpose: In cases of eyelid malignancies requiring full thickness excisional biopsy followed by reconstruction of the created defect, the Meibomian glands are lost. Post-operative varying degrees of dry eye disease (DED) are expected in such patients. The aim was to evaluate the objective and subjective statuses of DED in cases of full thickness eyelid reconstruction following excisional biopsy because of malignancies. Methods: This was a cross-sectional pilot study. Objective and subjective dry eye parameters are assessed in cases of full thickness eyelid reconstruction following excisional biopsy because of malignancies in 37 eyes at 6 months post-operative follow-up. Analysis of variance and Chi square test were used for statistical analysis. Results: When compared with fellow eye, all the parameters were found to be statistically significant (P < 0.0). Subjective assessment of dry eye by ocular surface disease index (OSDI) scoring did not corroborate with the objective data (p 0.00). Lower eyelid reconstruction showed a minimum number of dry eye cases (P > 0.05). Conclusion: Prevalence of post-operative dry eye is more with increasing percentage of full thickness upper eyelid reconstruction. Disparity was found between objective and subjective parameters of dry eye in patients requiring varying percentages of upper eyelid reconstruction because of malignancies.

MODOMICS: a database of RNA modification pathways. 2021 update.

The MODOMICS database has been, since 2006, a manually curated and centralized resource, storing and distributing comprehensive information about modified ribonucleosides. Originally, it only contained data on the chemical structures of modified ribonucleosides, their biosynthetic pathways, the location of modified residues in RNA sequences, and RNA-modifying enzymes. Over the years, prompted by the accumulation of new knowledge and new types of data, it has been updated with new information and functionalities. In this new release, we have created a catalog of RNA modifications linked to human diseases, e.g., due to mutations in genes encoding modification enzymes. MODOMICS has been linked extensively to RCSB Protein Data Bank, and sequences of experimentally determined RNA structures with modified residues have been added. This expansion was accompanied by including nucleotide 5'-monophosphate residues. We redesigned the web interface and upgraded the database backend. In addition, a search engine for chemically similar modified residues has been included that can be queried by SMILES codes or by drawing chemical molecules. Finally, previously available datasets of modified residues, biosynthetic pathways, and RNA-modifying enzymes have been updated. Overall, we provide users with a new, enhanced, and restyled tool for research on RNA modification. MODOMICS is available at https://iimcb.genesilico.pl/modomics/.

DNA-enabled rational design of fluorescence-Raman bimodal nanoprobes for cancer imaging and therapy.

Recently, surface-enhanced Raman scattering nanoprobes have shown tremendous potential in oncological imaging owing to the high sensitivity and specificity of their fingerprint-like spectra. As current Raman scanners rely on a slow, point-by-point spectrum acquisition, there is an unmet need for faster imaging to cover a clinically relevant area in real-time. Herein, we report the rational design and optimization of fluorescence-Raman bimodal nanoparticles (FRNPs) that synergistically combine the specificity of Raman spectroscopy with the versatility and speed of fluorescence imaging. DNA-enabled molecular engineering allows the rational design of FRNPs with a detection limit as low as 5 × 10-15 M. FRNPs selectively accumulate in tumor tissue mouse cancer models and enable real-time fluorescence imaging for tumor detection, resection, and subsequent Raman-based verification of clean margins. Furthermore, FRNPs enable highly efficient image-guided photothermal ablation of tumors, widening the scope of the NPs into the therapeutic realm.

A comparison of four different conformations adopted by human telomeric G-quadruplex using computer simulations.

The telomeric G-quadruplexes for their unique structural features are considered as potential anticancer drug targets. These, however, exhibit structural polymorphism as different topology types for the intra-molecular G-quadruplexes from human telomeric G-rich sequences have been reported based on NMR spectroscopy and X-ray crystallography. These techniques provide detailed atomic-level information about the molecule but relative conformational stability of the different topologies remains unsolved. Therefore, to understand the conformational preference, we have carried out quantum chemical calculations on G-quartets; used all-atom molecular dynamics (MD) simulations and steered molecular dynamics (SMD) simulations to characterize the four human telomeric G-quadruplex topologies based on its G-tetrad core-types, viz., parallel, anti-parallel, mixed-(3 + 1)-form1 and mixed-(3 + 1)-form2. We have also studied a non-telomeric sequence along with these telomeric forms giving a comparison between the two G-rich forms. The structural properties such as base pairing, stacking geometry and backbone conformations have been analyzed. The quantum calculations indicate that presence of a sodium ion inside the G-tetrad plane or two potassium ions on both sides of the plane give it an overall planarity which is much needed for good stacking to form a helix. MD simulations indicate that capping of the G-tetrad core by the TTA loops keep the terminal guanine bases away from water. The SMD simulations along with equilibrium MD studies indicate that the parallel and non-telomeric forms are comparatively less stable. We could come to the conclusion that the anti-parallel form and also the mixed-(3 + 1)-form1 topology are most likely to represent the major conformation., 2016. © 2015 Wiley Periodicals, Inc. Biopolymers 105: 83-99, 2016.