INDQ/NO, a Bioreductively Activated Nitric Oxide Prodrug

The design, synthesis, and development of INDQ/NO, a novel nitric oxide (NO) prodrug targeted by a bioreductive trigger, are described. INDQ/NO, an indolequinone-diazeniumdiolate is found to be metabolized to produce NO by DT-diaphorase, a bioreductive enzyme that is overexpressed in certain cancers and hypoxic tumors. Cell-based assays revealed that INDQ/NO induces DNA damage and is a potent inhibitor of cancer cell proliferation

Soft X‑ray Spectromicroscopic Evidence for Site-Specific Nanoscale Phase Segregation of Polyurethane onto a Confined Surface

Synchrotron-based small-angle X-ray scattering and near-edge X-ray absorption fine structure spectromicroscopy have been used to study the phase separation of thermoplastic polyurethane in a confined thin-film geometry. The functional nanomaterials were introduced in a polymer matrix, where the shape and nature of the functional surface were varied to gain insight into the mechanism of aggregation of polyurethane segments enriched with functional moieties. Using soft X-ray scattering it has been established that the two-dimensional flat functional surface displayed higher phase-segregated geometries with a wider distribution of interdomain spacing in comparison to the one-dimensional contour shaped nanofillers. A strong chemical environment dependence has been observed for π–π or electrostatic interactions during the nanoscale phase separation of the polyurethane matrix by X-ray absorption spectromicroscopy. Our results support the fact that soft X-ray-based spectromicroscopy can be exclusively used as a powerful noninvasive technique for the structure–property analysis of polymer nanocomposites

Structural and functional alterations of nitric oxide synthase 3 due to missense variants associate with high-altitude pulmonary edema through dynamic study

The human endothelial nitric oxide synthase (NOS3) is 28 Kbp at 7q36.1 and encodes protein comprising of 1280 amino acids. Being a major source of nitric oxide, the enzyme is crucial to the vascular homeostasis and thereby to be an important pharmaceutical target. We hence have been investigating this molecule in a high-altitude disorder namely, high-altitude pulmonary edema (HAPE). We performed a genome-wide association study (GWAS) in a case-control design of sojourners that included healthy controls and HAPE patients (n = 200) each. Four NOS3 missense SNPs i.e. rs1799983 (E298D), rs3918232 (V827M), rs3918201 (R885M) and rs3918234 (Q982L), were associated significantly with HAPE (P-value in silico analyses were performed to predict the detrimental effect of the four variant types and their three most relevant co-factors namely, heme, flavin adenine dinucleotide (FAD) and flavin mononucleotide (FMN) that are accountable for amendment of protein stability leading to structural de-construction. Subsequently, we validated the findings in a larger sample size of the two study groups. HAPE patients had a higher frequency of the four variants and significantly decreased levels of circulating nitric oxide (NO) (P-value in silico and human subjects findings complement each other. This study explored the impact of HAPE-associated NOS3 variants with its protein structure stability and holds promise to be current and future drug targets. Communicated by Ramaswamy H. Sarma</p

Additional file 1 of Differential methylation in EGLN1 associates with blood oxygen saturation and plasma protein levels in high-altitude pulmonary edema

Additional file 1. Fig. S1 Levels of SpO2 % in HAPE-p, HAPE-f and HLs. Fig. S2 Dot plot of CpG methylation in EGLN1 in the three study groups, i.e., HAPE-p, HLs and HAPE-f. It revealed 97 CpG sites in EGLN1 CpG island 179. Fig. S3 Dot plot of CpG methylation in HIF1AN in the three study groups, i.e., HAPE-f, HAPE-p and HLs. It revealed 46 CpG sites in HIF1AN CpG island 47. Table S1 Methylation distribution of CpG sites of EGLN1 and HIF1AN in each subject of the three study groups i.e., HAPE-f, HAPE-p and HLs. Table S2 Real-time PCR conditions for EGLN1 and HIF1AN. Table S3 Sodium bisulfite-conversion-based methylation PCR Primers and conditions for EGLN1 and HIF1AN

Supplementary document for Direct time-of-flight distributed analysis of nonlinear forward scattering - 5735335.pdf

Supplementary analysisa and measurement

Observation of anti-parity-time-symmetry, phase transitions and exceptional points in an optical fibre

The exotic physics emerging in non-Hermitian systems with balanced distributions of gain and loss has drawn a great deal of attention in recent years. These systems exhibit phase transitions and exceptional point singularities in their spectra, at which eigen-values and eigen-modes coalesce and the overall dimensionality is reduced. Among several peculiar phenomena observed at exceptional points, an especially intriguing property, with relevant practical potential, consists in the inherently enhanced sensitivity to small-scale perturbations. So far, however, these principles have been implemented at the expenses of precise fabrication and tuning requirements, involving tailored nano-structured devices with controlled distributions of optical gain and loss. In this work, anti-parity-time symmetric phase transitions and exceptional point singularities are demonstrated in a single strand of standard single-mode telecommunication fibre, using a setup consisting of entirely of off-the-shelf components. Two propagating signals are amplified and coupled through stimulated Brillouin scattering, which makes the process non-Hermitian and enables exquisite control over gain and loss. Singular response to small variations around the exceptional point and topological features arising around this singularity are experimentally demonstrated with large precision, enabling robustly enhanced spectral response to small-scale changes in the Brillouin frequency shift. Our findings open exciting opportunities for the exploration of non-Hermitian phenomena over a table-top setup, with straightforward extensions to higher-order Hamiltonians and applications in quantum optics, nanophotonics and sensing

DABCO-catalyzed synthesis of 3-substituted-3-hydroxyindolin-2-ones in aqueous media

<p>An efficient and greener protocol for easy access to 3-susbstituted-3-hydroxy-2-oxindoles by the reaction with various substituted isatins and acetophenones is described. This protocol is widely applicable for a variety of isatins and acetophenones using water as a reaction media and 1,4-diazabicyclo[2.2.2]octane (DABCO) as catalyst with shorter reaction time and good to excellent yield of products.</p

sj-docx-1-opp-10.1177_10781552231212926 - Supplemental material for Outcomes of weight-based vs. fixed dose of Pembrolizumab among patients with non-small cell lung cancer

Supplemental material, sj-docx-1-opp-10.1177_10781552231212926 for Outcomes of weight-based vs. fixed dose of Pembrolizumab among patients with non-small cell lung cancer by Lena Chaitesipaseut, Nina Shah, Thach-Giao Truong, Fang Niu, Patrick Shin, Kavita Sharma, Joshua Smith and Rita L Hui in Journal of Oncology Pharmacy Practice</p

Correlation between different drought adaptive traits and grain yield.

<p>Traits used are biomass, Canopy Temperature (at vegetative and reproductive stages), HI,NDVI and chlorophyll content. The highlighted values indicate significant correlation at 5% level.</p

Scheme of recurrent selection.

<p>At the end of each cycle the progenies with higher yield and physiological attributes were selected as the base material for next cycle.</p