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A novel n-MgFe2O4–n-ZnS heterojunction catalyst was employed via two step approach for photodegradation of organic dyes such as Methylene Blue (MB) and Crystal Violet (CV) dyes under visible light irradiation. The synthesized MgFe2O4/ZnS NCs were characterized using PXRD, FTIR, UV–Visible spectroscopy, PL and FESEM analysis which reveals the formation of flake like structure with size as to be ~ 50 nm. The photocatalytic experimental result demonstrates that the MgFe2O4/ZnS nanocomposites (NCs) improve photodegradation performance with 98.0% and 91% decomposition of MB and CV dyes within 120 min illumination during simulated visible light irradiation. From the result, MgFe2O4/ZnS NCs has higher photocatalytic performance than that of MgFe2O4, and ZnS due to efficient separation of the photo-induced electron–hole pairs and effective electron–hole generation transfer by the formation of n-MgFe2O4–n-ZnS heterojunction. Hence, photodegradation performance implies that the synthesized MgFe2O4/ZnS NCs can be effectively utilized in waste water purification systems. [ABSTRACT FROM AUTHOR]

Oral rotavirus vaccine (ORV) efficacy varies between countries, but underlying reasons aren’t fully understood. In this prospective cohort study, authors show that maternal rotavirus-specific antibodies in serum and breastmilk and pre-vaccination microbiota diversity are negatively correlated with ORV response in India and Malawi but not in the UK.

Background: In preclinical models of prostate cancer (PC), disulfiram (DSF) reduced tumor growth only when co-administered with copper (Cu), and Cu uptake in tumors is partially regulated by androgen-receptor signaling. However, prior trials of DSF in PC used DSF as monotherapy., Objective: To assess the safety and efficacy of concurrent administration of DSF with Cu, we conducted a phase 1b clinical trial of patients with metastatic castration-resistant prostate cancer (mCRPC) receiving Cu with DSF., Design, Setting, and Participants: Patients with mCRPC were treated in two cohorts: mCRPC with nonliver/peritoneal metastases (A), and mCRPC with liver and/or peritoneal metastases (B). Baseline Cu avidity was measured by 64 CuCl 2 PET scan. Intravenous (IV) CuCl 2 was given weekly for three doses with oral daily DSF followed by daily oral Cu gluconate and DSF until disease progression. DSF and metabolite diethyldithiocarbamic acid methyl ester (Me-DDC) levels in plasma were measured. DSF and Me-DDC were then assessed for cytotoxicity in vitro., Results: We treated nine patients with mCRPC (six on cohort A and three on cohort B). Bone and nodal metastases showed differential and heterogeneous Cu uptake on 64 CuCl 2 PET scans. No confirmed PSA declines or radiographic responses were observed. Median PFS was 2.8 months and median OS was 8.3 months. Common adverse events included fatigue and psychomotor depression; no Grade 4/5 AEs were observed. Me-DDC was measurable in all samples (LOQ = 0.512 ng/ml), whereas DSF was not (LOQ = 0.032 ng/ml, LOD = 0.01 ng/ml); Me-DDC was not cytotoxic in vitro., Conclusions: Oral DSF is not an effective treatment for mCRPC due to rapid metabolism into an inactive metabolite, Me-DDC. This trial has stopped enrollment and further work is needed to identify a stable DSF formulation for treatment of mCRPC., (© 2022 Wiley Periodicals LLC.)

Alkyne functional groups have Raman signatures in a region (1800 cm -1 to 2800 cm -1 ) that is free from interference from cell components, known as the "silent region", and alkyne signals in this region were first utilized a decade ago to visualize the nuclear localization of a thymidine analogue EdU. Since then, the strategy of Raman imaging of biological samples by using alkyne functional groups, called alkyne-tag Raman imaging (ATRI), has become widely used. This article reviews the applications of ATRI in biological samples ranging from organelles to whole animal models, and briefly discusses the prospects for this technique., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

Disulfiram in conjunction with copper has been shown to be a potent anticancer agent. However, disulfiram's therapeutic potential in prostate cancer is hindered by off-target effects due to its reactive and nucleophilic thiol-containing component, diethyldithiocarbamate (DTC). To minimize undesirable reactivity, we have strategically blocked the thiol moiety in DTC with a cleavable p-aminobenzyl (pAB) group linked to peptide substrates recognized by prostate specific antigen (PSA). Here we report the synthesis and evaluation in cancer cell models of two PSA-activatable prodrugs: HPD (Ac-HSSKLQL-pAB-DTC and RPD (RSSYYSL-pAB-DTC). In vitro exposure to PSA was found to trigger activation of HPD and RPD to release diethyldithiocarbamate, and both prodrugs were found to induce toxicity in prostate cancer cells, with HPD showing the most promising selectivity. With copper supplementation, the IC 50 of HPD was 1.4 µM in PSA-expressing LNCaP cells, and 11 µM in PC3 cells that do not express PSA. These studies demonstrate the utility of using peptide recognition handles to direct the activity of dithiocarbamate prodrugs for selective cytotoxicity of cancer cells., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Recent developments in Mn biology have added new physiological and pathophysiological roles of this essential metal ion to the already existing repertoire of indispensable biological roles of Mn ions. Notably, the discovery of Mn 2+ specific transporters, maladies related to mutations in these transporters, and evidence of the role of labile Mn 2+ species as anti-oxidants have initiated studies targeted at elucidating Mn ion regulation and pathways implicated in pathological conditions. Closely inter-linked with the quest for understanding metal ion homeostasis are basic questions like "How are metal ions installed in their correct biological addresses where they need to function?" and "Are dynamic changes in metal ion distribution functionally relevant?" These questions become more critical in the context of Mn 2+ ions, which have inherently low binding affinities toward most ligands and hence would always face competing metal ions in the biological milieu. In the emerging context of functional roles of the labile Mn 2+ ion pool, the development of chemical tools and techniques that can provide information on the location, distribution and dynamic changes in these parameters under physiological and pathophysiological conditions becomes imperative. In this frontier article, we discuss the challenges that had left Mn 2+ ions lagging behind in the race for the development of chemical tools and recent approaches that addressed these challenges to develop tools and techniques that can illuminate Mn ions in living systems.

A prodrug approach is presented to direct copper-dependent cytotoxicity to prostate cancer cells. The prochelator GGTDTC requires activation by γ-glutamyl transferase (GGT) to release the metal chelator diethyldithiocarbamate from a linker that masks its thiol reactivity and metal binding properties. In vitro studies demonstrated successful masking of copper binding as well as clean liberation of the chelator by GGT. GGTDTC was stable to non-specific degradation when incubated with a series of prostate cancer and normal cell lines, with selective release of diethyldithiocarbamate only occurring in cells with measurable GGT activity. The antiproliferative efficacy of the prochelator correlated with cellular GGT activity, with 24 h inhibitory concentrations ranging from 800 nm in prostate cancer lines 22Rv1 and LNCaP to over 15 μm in normal prostate PWR-1E cells. These findings underscore a new strategy to leverage the amplified copper metabolism of prostate cancer by conditional activation of a metal-binding pharmacophore., (© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

We tune the coordination environment of macrocyclic ligands to design two novel fluorescence sensors for Mn(2+). The BODIPY-based Mn(2+) sensor M1 affords an excellent, 52 fold, fluorescence 'turn-on' response despite the paramagnetic nature of Mn(2+). The lipophilic probe is cell-permeable and confocal imaging demonstrates that the sensor distinctly detects Mn(2+) within live cells.

Manganese (manganese ion; referred to as Mn) is essential for neuronal function, yet it is toxic at high concentrations. Environmental and occupational exposure to high concentrations of Mn causes manganism, a well-defined movement disorder in humans, with symptoms resembling Parkinson's disease (PD). However, manganism is distinct from PD and the neural basis of its pathology is poorly understood. To address this issue, we generated a zebrafish model of manganism by incubating larvae in rearing medium containing Mn. We find that Mn-treated zebrafish larvae exhibit specific postural and locomotor defects. Larvae begin to float on their sides, show a curved spine and swim in circles. We discovered that treatment with Mn causes postural defects by interfering with mechanotransduction at the neuromasts. Furthermore, we find that the circling locomotion could be caused by long-duration bursting in the motor neurons, which can lead to long-duration tail bends in the Mn-treated larvae. Mn-treated larvae also exhibited fewer startle movements. Additionally, we show that the intensity of tyrosine hydroxylase immunoreactivity is reversibly reduced after Mn-treatment. This led us to propose that reduced dopamine neuromodulation drives the changes in startle movements. To test this, when we supplied an external source of dopamine to Mn-treated larvae, the larvae exhibited a normal number of startle swims. Taken together, these results indicate that Mn interferes with neuronal function at the sensory, motor and modulatory levels, and open avenues for therapeutically targeted studies on the zebrafish model of manganism., (© 2014. Published by The Company of Biologists Ltd.)

Two-dimensional (13)C-(13)C correlation experiments are widely employed in structure determination of protein assemblies using solid-state nuclear magnetic resonance. Here, we investigate the process of (13)C-(13)C magnetisation transfer at a moderate magic-angle-spinning frequency of 30 kHz using some of the prominent second-order dipolar recoupling schemes. The effect of isotropic chemical-shift difference and spatial distance between two carbons and amplitude of radio frequency on (1)H channel on the magnetisation transfer efficiency of these schemes is discussed in detail.

Leucine dehydrogenase has been purified to homogeneity from a moderate thermophilic actinomycete, Thermoactinomyces intermedius IFO 14230. The enzyme can be stored without loss of its activity at a low temperature (e.g., 4 degrees C) for over two years. The enzyme was more thermostable at higher concentrations of salts such as NaCl and KCl. It retained about 90% of activity on incubation at 70 degrees C for at least 40 min in the presence of 3 M NaCl. The Michaelis constants for NAD, L-leucine, NADH, 2-oxoisocaproate and ammonia were determined to be 0.36, 2.0, 0.042, 0.63 and 118 mM, respectively, from initial-velocity analyses. The enzyme showed pro-S stereospecificity for hydrogen transfer of NADH in the reductive amination. The enzyme gene was cloned into Escherichia coli and its complete DNA sequence was determined. The leucine dehydrogenase gene (leudh) consists of a 1098-bp open reading frame and encodes 366 amino acid residues corresponding to a subunit (M(r) 40586) of the octameric enzyme. The amino acid sequence of the enzyme showed 80.7% similarity with that of the Bacillus stearothermophilus enzyme. The enzyme was overproduced in E. coli JM 109 having a recombinant plasmid, pULDH2, which was constructed from pUC18 and the leudh gene. The enzyme was purified from the cell extract to homogeneity in one day, with 78% recovery.