Aldehyde-Functionalized Magnetic Particles to Capture Off-Target Chemotherapeutic Agents

Drug capture is a promising technique to prevent off-target chemotherapeutic agents from reaching systemic circulation and causing severe side effects. The current work examines the viability of using immobilized aldehydes for drug-capture applications via Schiff base formation between doxorubicin (DOX) and aldehydes. Commercially available pyridoxal-5′-phosphate (VB6) was immobilized on iron oxide nanoparticles (IONPs) to capture DOX from human serum. Leaching of VB6 persisted as a primary issue and thus various aldehydes with anchoring groups such as catechol, silatrane, and phosphonate esters have been studied. The phosphonate group-based anchor was the most stable and used for further capture studies. To improve the hydrophilic nature of the aldehydes, sulfonate-containing aldehydes and polyethylene glycols (PEGs) were investigated. Finally, the optimized functionalized iron oxide particles, PEGylated-IONP, were used to demonstrate doxorubicin capture from human serum at biologically relevant temperature (37 °C), time (30 min), and concentrations (μM). The current study sets the stage for the development of potential compact dimension capture device based on surface-anchorable polymers with aldehyde groups

Variation in the Biomolecular Interactions of Nickel(Ii) Hydrazone Complexes Upon Tuning the Hydrazide Fragment

Three new bivalent nickel hydrazone complexes have been synthesised from the reactions of [NiCl2(PPh3)(2)] with H2L {L = dianion of the hydrazones derived from the condensation of o-hydroxynaphthaldehyde with furoic acid hydrazide (H2L1) (1)/thiophene-2-acid hydrazide (H2L2) (2)/isonicotinic acid hydrazide (H2L3) (3)} and formulated as [Ni(L-1)(PPh3)] (4), [Ni(L-2)(PPh3)] (5) and [Ni(L-3)(PPh3)] (6). Structural characterization of these compounds 4-6 were accomplished by using various physico-chemical techniques. Single crystal X-ray diffraction data of complexes 4 and 5 proved their distorted square planar geometry. In order to ascertain the potential of the above synthesised compounds towards biomolecular interactions, additional experiments involving interaction with calf thymus DNA (CT DNA) and bovine serum albumin (BSA) were carried out. All the ligands and corresponding nickel(II) chelates have been screened for their scavenging effect towards O-2(-), OH and NO radicals. The efficiency of complexes 4-6 to arrest the growth of HeLa, HepG-2 and A431 tumour cell lines has been studied along with the cell viability test against the non-cancerous NIH 3T3 cells under in vitro conditions.University Grants Commission, New Delhi under the UGC-SAP-DRSRobert A. Welch Foundation F-0003Chemistr

Topological Transitions in Metamaterials

The ideas of mathematical topology play an important role in many aspects of modern physics - from phase transitions to field theory to nonlinear dynamics (Nakahara M (2003) in Geometry, Topology and Physics, ed Brewer DF (IOP Publishing Ltd, Bristol and Philadelphia), Monastryskiy M (1987) in Riemann Topology and Physics, (Birkhauser Verlag AG)). An important example of this is the Lifshitz transition (Lifshitz IM (1960) Anomalies of electron characteristics of a metal in the high-pressure region, Sov Phys JETP 11: 1130-1135), where the transformation of the Fermi surface of a metal from a closed to an open geometry (due to e.g. external pressure) leads to a dramatic effect on the electron magneto-transport (Kosevich AM (2004) Topology and solid-state physics. Low Temp Phys 30: 97-118). Here, we present the optical equivalent of the Lifshitz transition in strongly anisotropic metamaterials. When one of the components of the dielectric permittivity tensor of such a composite changes sign, the corresponding iso-frequency surface transforms from an ellipsoid to a hyperboloid. Since the photonic density of states can be related to the volume enclosed by the iso-frequency surface, such a topological transition in a metamaterial leads to a dramatic change in the photonic density of states, with a resulting effect on every single physical parameter related to the metamaterial - from thermodynamic quantities such as its equilibrium electromagnetic energy to the nonlinear optical response to quantum-electrodynamic effects such as spontaneous emission. In the present paper, we demonstrate the modification of spontaneous light emission from quantum dots placed near the surface of the metamaterial undergoing the topological Lifshitz transition, and present the theoretical description of the effect

Computational Study of Halide Perovskite-Derived A2_2BX6_6 Inorganic Compounds: Chemical Trends in Electronic Structure and Structural Stability

The electronic structure and energetic stability of A$_2$BX$_6$ halide compounds with the cubic and tetragonal variants of the perovskite-derived K$_2$PtCl$_6$ prototype structure are investigated computationally within the frameworks of density-functional-theory (DFT) and hybrid (HSE06) functionals. The HSE06 calculations are undertaken for seven known A$_2$BX$_6$ compounds with A = K, Rb and Cs, and B = Sn, Pd, Pt, Te, and X = I. Trends in band gaps and energetic stability are identified, which are explored further employing DFT calculations over a larger range of chemistries, characterized by A = K, Rb, Cs, B = Si, Ge, Sn, Pb, Ni, Pd, Pt, Se and Te and X = Cl, Br, I. For the systems investigated in this work, the band gap increases from iodide to bromide to chloride. Further, variations in the A site cation influences the band gap as well as the preferred degree of tetragonal distortion. Smaller A site cations such as K and Rb favor tetragonal structural distortions, resulting in a slightly larger band gap. For variations in the B site in the (Ni, Pd, Pt) group and the (Se, Te) group, the band gap increases with increasing cation size. However, no observed chemical trend with respect to cation size for band gap was found for the (Si, Sn, Ge, Pb) group. The findings in this work provide guidelines for the design of halide A$_2$BX$_6$ compounds for potential photovoltaic applications

Mycofactocin Is Associated with Ethanol Metabolism in Mycobacteria

Tuberculosis is caused by Mycobacterium tuberculosis, and the increasing emergence of multidrug-resistant strains renders current treatment options ineffective. Although new antimycobacterial drugs are urgently required, their successful development often relies on complete understanding of the metabolic pathways—e.g., cholesterol assimilation—that are critical for persistence and for pathogenesis of M. tuberculosis. In this regard, mycofactocin (MFT) function appears to be important because its biosynthesis genes are predicted to be essential for M. tuberculosisin vitro growth in cholesterol. In determining the metabolic basis of this genetic requirement, our results unexpectedly revealed the essential function of MFT in ethanol metabolism. The metabolic dysfunction thereof was found to affect the mycobacterial growth in cholesterol which is solubilized by ethanol. This knowledge is fundamental in recognizing the bona fide function of MFT, which likely resembles the pyrroloquinoline quinone-dependent ethanol oxidation in acetic acid bacteria exploited for industrial production of vinegar.Mycofactocin (MFT) belongs to the class of ribosomally synthesized and posttranslationally modified peptides conserved in many Actinobacteria. Mycobacterium tuberculosis assimilates cholesterol during chronic infection, and its in vitro growth in the presence of cholesterol requires most of the MFT biosynthesis genes (mftA, mftB, mftC, mftD, mftE, and mftF), although the reasons for this requirement remain unclear. To identify the function of MFT, we characterized MFT biosynthesis mutants constructed in Mycobacterium smegmatis, M. marinum, and M. tuberculosis. We found that the growth deficit of mft deletion mutants in medium containing cholesterol—a phenotypic basis for gene essentiality prediction—depends on ethanol, a solvent used to solubilize cholesterol. Furthermore, functionality of MFT was strictly required for growth of free-living mycobacteria in ethanol and other primary alcohols. Among other genes encoding predicted MFT-associated dehydrogenases, MSMEG_6242 was indispensable for M. smegmatis ethanol assimilation, suggesting that it is a candidate catalytic interactor with MFT. Despite being a poor growth substrate, ethanol treatment resulted in a reductive cellular state with NADH accumulation in M. tuberculosis. During ethanol treatment, mftC mutant expressed the transcriptional signatures that are characteristic of respirational dysfunction and a redox-imbalanced cellular state. Counterintuitively, there were no differences in cellular bioenergetics and redox parameters in mftC mutant cells treated with ethanol. Therefore, further understanding of the function of MFT in ethanol metabolism is required to identify the cause of growth retardation of MFT mutants in cholesterol. Nevertheless, our results establish the physiological role of MFT and also provide new insights into the specific functions of MFT homologs in other actinobacterial systems

Prognostic scoring system and risk stratification in patients with emphysematous pyelonephritis: an 11‐year prospective study at a tertiary referral centre

Objectives: To define pre‐morbid, clinical, laboratory, and imaging features and identify prognostic factors associated with morbidity and mortality in patients with emphysematous pyelonephritis (EPN) and develop a prognostic scoring system for improving management outcomes. / Patients and Methods: From January 2009 to December 2019, we performed a prospective study of all patients with a suspected diagnosis of EPN referred to a specialist tertiary centre in South India. All patients who underwent non‐contrast computed tomography of the abdomen and those diagnosed with EPN were included in this study. Demographic parameters, imaging, haematological and microbiology results were recorded. Patients were divided into three groups: Group 1, patients who survived without any intervention; Group 2, those who survived with surgical intervention; and Group 3, those who died with or without intervention. A prognostic scoring system was developed from 18 different parameters and risk stratification was developed. The scores were correlated with overall prognosis. / Results: Data from 131 patients with EPN enrolled in the study were analysed: Group 1 (n = 22), Group 2 (n = 102) and Group 3 (n = 7). By using univariate analysis, 10 factors were identified to be significantly associated with prognosis. Diabetes mellitus was the most common comorbidity. Shock at initial admission indicated a poor prognosis and warranted immediate attention (P < 0.001). / Conclusions: A multi‐disciplinary approach, a high index of clinical suspicion, an early diagnosis and administration of culture‐specific antibiotics with identification of prognostic indicators and risk stratification, allows prompt and appropriate medical and surgical treatments that could improve EPN management outcomes

New limit for the half-life of double beta decay of 94^{94}Zr to the first excited state of 94^{94}Mo

Neutrinoless Double Beta Decay is a phenomenon of fundamental interest in particle physics. The decay rates of double beta decay transitions to the excited states can provide input for Nuclear Transition Matrix Element calculations for the relevant two neutrino double beta decay process. It can be useful as supplementary information for the calculation of Nuclear Transition Matrix Element for the neutrinoless double beta decay process. In the present work, double beta decay of $^{94}$Zr to the $2^{+}_{1}$ excited state of $^{94}$Mo at 871.1 keV is studied using a low background $\sim$ 230 cm$^3$ HPGe detector. No evidence of this decay was found with a 232 g.y exposure of natural Zirconium. The lower half-life limit obtained for the double beta decay of $\rm^{94}Zr$ to the $2^{+}_{1}$ excited state of $\rm^{94}Mo$ is $T_{1/2} (0\nu + 2\nu)> 3.4 \times 10^{19}$ y at 90% C.L., an improvement by a factor of $\sim$ 4 over the existing experimental limit at 90\% C.L. The sensitivity is estimated to be $T_{1/2} (0\nu + 2\nu) > 2.0\times10^{19}$ y at 90% C.L. using the Feldman-Cousins method.Comment: 11 pages, 7 figures, Accepted in Eur. Phys. J.