Monthly Archives: September 2023

Trace Elements and Consequent Ecological Risks in Mining‐Influenced Streams of Appalachia

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Abstract

Appalachian (eastern USA) coal surface mines fracture geologic materials, causing release of both major ions and trace elements to water via accelerated weathering. When elevated above natural background, trace elements in streams may produce adverse effects on biota via direct exposure from water and sediment and via dietary exposure in food sources. Other studies have found elevated water concentrations of multiple trace elements in Appalachia's mining-influenced streams. Except for Se, trace-element concentrations in abiotic and biotic media of Appalachian mining-influenced streams are less well known. We analyzed environmental media of headwater streams receiving alkaline waters from Appalachian coal mines for eight trace elements (Al, As, Cd, Cu, Ni, Sr, V, and Zn) and assessed the potential consequent ecological risks. Streamwater, particulate media (sediment, biofilm, leaf detritus), and benthic macroinvertebrates (primary consumers, secondary consumers, crayfish) were sampled from six mining-influenced and three reference streams during low-flow conditions in two seasons. Dissolved Cu, Ni, and Sr were higher in mining-influenced streams than in reference streams; Ni, Sr, and Zn in fine sediments and Ni in macroinvertebrates were also elevated relative to reference-stream levels in samples from mining-influenced streams. Seasonal ratios of mining-influenced stream concentrations to maximum concentrations in reference streams also demonstrated mining-influenced increases for several elements in multiple media. In most media, concentrations of several elements including Ni were correlated positively. All water-column dissolved concentrations were below protective levels, but fine-sediment concentrations of Ni approached or exceeded threshold-effect concentrations in several streams. Further study is warranted for several elements (Cd, Ni, and Zn in biofilms, and V in macroinvertebrates) that approached or exceeded previously established dietary-risk levels. Environ Toxicol Chem 2023;00:1–15. © 2023 SETAC.

Meta‐Analysis Comparing Nominal and Measured Concentrations of Perfluorooctanoic Acid and Perfluorooctane Sulfonate in Aquatic Toxicity Studies Across Various Experimental Conditions

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Abstract

Perfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are among the most frequently detected chemicals among the per- and polyfluoroalkyl substances in aquatic environments. Because of their high detection frequency, persistence, and potential toxicity, interest in both PFOA and PFOS has increased in recent years. However, a substantial number of PFOA and PFOS toxicity tests only report nominal, or unmeasured, treatment concentrations, which may complicate the determination of protective values. In addition, previous literature has indicated that differences between nominal and measured concentrations of both PFOA and PFOS could be linked to experimental conditions (e.g., feeding regimes for test organisms, test vessel material [glass or plastic], use of solvent, and the presence of substrate). Therefore, this critical review examined whether nominal and measured concentrations were in close agreement with each other among the current PFOA and PFOS aquatic toxicity literature and if experimental conditions were associated with any observed differences. Nominal and measured concentrations in the current PFOA and PFOS aquatic toxicity literature generally displayed a high degree of linear correlation and relatively low median percent differences. Correlations between measured and nominal concentrations were >0.98 for PFOA and >0.95 for PFOS in freshwater tests across experimental conditions. For saltwater tests, correlations of >0.84 were observed for PFOA and PFOS (separate and combined) across experimental conditions. While measured PFOA and PFOS toxicity tests are generally preferred, the present meta-analysis demonstrated that experimental conditions had little influence on observed discrepancies between nominal and measured concentrations, with the exception of PFOS saltwater tests and PFOA and PFOS freshwater studies that contained substrate. Unmeasured tests with these conditions should be considered carefully based on project needs, with the caveat that the data sets for these two experimental conditions were limited. Environ Toxicol Chem 2023;00:1–13. Published 2023. This article is a U.S. Government work and is in the public domain in the USA.

Immunological Exploration of Helicobacter pylori Serotype O2 O‐antigen by Using A Synthetic Glycan Library

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Comprehensive Summary

Helicobacter pylori (H. pylori) infection is a threat to human health. The lipopolysaccharide (LPS) O-antigen holds promise for developing vaccines. It is meaningful to explore the immunological activity of oligosaccharides with different lengths and frameshifts for antigen development. Herein, a glycan library of H. pylori O2 O-antigen containing eight fragments is constructed. After screening with anti-H. pylori O2 LPS sera and patients’ sera by glycan microarray, the disaccharide HPO2G-2b and trisaccharide HPO2G-3a show strong antigenicity and then are separately conjugated with carrier protein CRM197. Both glycoconjugates elicit a robust immunoglobulin G (IgG) immune response in rabbits. The anti-HPO2G-3a IgG antibodies possess a much stronger binding affinity with the LPS and bacteria of H. pylori O2 than the anti-HPO2G-2b IgG antibodies. There is no cross-reaction between both sera IgG antibodies with LPS and bacteria of H. pylori O1, O6, and E. coli. The results demonstrate the trisaccharide HPO2G-3a is a promising candidate for H. pylori vaccine development.

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Fluorine Substitution of TCNQ Alters the Redox‐Driven Catalytic Pathway for the Ferricyanide‐Thiosulfate Reaction

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Fluorine Substitution of TCNQ Alters the Redox-Driven Catalytic Pathway for the Ferricyanide-Thiosulfate Reaction

Fluorination of TCNQ tunes the redox potential and can alter catalytic mechanisms. Accordingly, TCNQF4 1− and TCNQF2 1− can act as catalysts for the ferrocyanide-thiosulfate reaction via the same mechanism, which differs from that found for TCNQ. CuTCNQFn (n=0, 4) coordination polymers have sufficient solubility in water to act as catalysts via homogeneous pathways. This study challenges perceptions of insolubility being correlated with heterogeneous pathways.


Abstract

Mechanistic variation in catalysis through substituent-based redox tuning is well established. Fluorination of TCNQ (TCNQ=tetracyanoquinodimethane) provides ~850 mV variation in the redox potentials of the and (n=0, 2, 4) processes. With , catalysis of the kinetically very slow ferrocyanide-thiosulfate redox reaction in aqueous solution occurs via a mechanism in which the catalyst is reduced to when reacting with which is oxidised to . Subsequently, reacts with to form and reform the catalyst, in another thermodynamically favoured process. An analogous mechanism applies with as a catalyst. In contrast, since the reaction of with is thermodynamically unfavourable, an alternative mechanism is required to explain the catalytic activity observed in this non-fluorinated system. Here, upon addition of , reduction of to occurs with concomitant oxidation of to , which then acts as the catalyst for oxidation. Thermodynamic data explain the observed differences in the catalytic mechanisms. (n=0, 4) also act as catalysts for the ferricyanide-thiosulfate reaction in aqueous solution. The present study shows that homogeneous pathways are available following addition of these dissolved materials. Previously, these (n=0, 4) coordination polymers have been regarded as insoluble in water and proposed as heterogeneous catalysts for the ferricyanide-thiosulfate reaction. Details and mechanistic differences were established using UV-visible spectrophotometry and cyclic voltammetry.

Impact of Top Electrodes (Cu, Ag, and Al) on Resistive Switching behaviour of Cu‐rich Cu2ZnSnS4 (CZTS) Ideal Kesterite

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Impact of Top Electrodes (Cu, Ag, and Al) on Resistive Switching behaviour of Cu-rich Cu2ZnSnS4 (CZTS) Ideal Kesterite

The resistive switching behaviour of Cu2ZnSnS4 material on ITO substrate with three different top electrodes (Cu, Ag, and Al) and work function is demonstrated. The Ag top electrode-based resistive random-access memory device shows more stable resistive switching than the ones with Cu and Al top electrode.


Abstract

Cu2ZnSnS4 (CZTS) active material-based resistive random-access memory (RRAM) devices are investigated to understand the impact of three different Cu, Ag, and Al top electrodes. The dual resistance switching (RS) behaviour of spin coated CZTS on ITO/Glass is investigated up to 102 cycles. The stability of all the devices (Cu/CZTS/ITO, Ag/CZTS/ITO, and Al/CZTS/ITO) is investigated up to 103 sec in low- (LRS) and high- (HRS) resistance states at 0.2 V read voltage. The endurance up to 102 cycles with 30 msec switching width shows stable write and erase current. Weibull cumulative distribution plots suggest that Ag top electrode is relatively more stable for set and reset state with 33.61 and 25.02 shape factors, respectively. The charge carrier transportation is explained by double logarithmic plots, Schottky emission plots, and band diagrams, substantiating that at lower applied electric field intrinsic copper ions dominate in Cu/CZTS/ITO, whereas, at higher electric filed, top electrodes (Cu and Ag) dominate over intrinsic copper ions. Intrinsic Cu+ in CZTS plays a decisive role in resistive switching with Al electrode. Further, the impedance spectroscopy measurements suggest that Cu+ and Ag+ diffusion is the main source for the resistive switching with Cu and Ag electrodes.

Identification of in situ generated iron‐vacancy induced oxygen evolution reaction kinetics on cobalt iron oxyhydroxide

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Comprehensive Summary

Developing highly efficient and low-cost electrocatalysts towards oxygen evolution reaction (OER) is essential for the practical application in water electrolyzers and rechargeable metal-air batteries. Although Fe-based oxyhydroxides are regarded as the state-of-the-art non-noble OER electrocatalysts, the origin of performance enhancement derived from Fe doping still remains a hot topic of considerable discussion. Herein, we demonstrate that in situ generated Fe vacancies in the pristine CoFeOOH catalyst through a pre-conversion process during alkaline OER results from dynamic Fe dissolution, identifying the origin of Fe-vacancy-induced enhanced OER kinetics. Density functional theory (DFT) calculations and experimental results including X-ray absorption fine-structure spectroscopy, in situ UV-Vis spectroscopy, and in situ Raman spectroscopy reveal that the Fe vacancies could significantly promote the d-band center and valence states of adjacent Co sites, alter the active site from Fe atom to Co atom, accelerate the formation of high-valent active Co4+ species, and reduce the energy barrier of the potential-determining step, thereby contribute to the significantly enhanced OER performance.

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One‐pot Stereoselective Synthesis of Different Fused Multicyclic Iminosugars Based on the Iminium‐ion Intermediate

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Comprehensive Summary

Different novel fused multicyclic iminosugars were synthesized from D-ribose tosylate, aniline and vinyl ethyl ether by one-pot three-component stereoselective [4+2] reaction at different temperatures. The iminium-ion is the key intermediate for the reaction. As a result, several complex fused iminosugars 3a were obtained by aza-Diels-Alder mechanism at 60 oC, while a series of aza-C-glycosides 5a were prepared by Mannich reaction at room temperature accompanied by another tetrahydroquinoline-fused iminosugars 4a (tricyclic derivatives) through aza-Diels-Alder cycloaddition. This strategy will help to construct structurally diverse and bioactive iminosugar analogues.

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Chemical Probes for Profiling of MALT1 Protease Activity

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Chemical Probes for Profiling of MALT1 Protease Activity

MALT1 is a cysteine protease and the only human paracaspase. It is implicated in various human diseases. Here, an overview of the currently available molecular tools is given. Furthermore, their application and future possibilities are discussed. We expect that future research with these and improved tools will provide novel insights into MALT1’s pathobiological roles and enable use as diagnostic tools.


Abstract

The paracaspase MALT1 is a key regulator of the human immune response. It is implicated in a variety of human diseases. For example, deregulated protease activity drives the survival of malignant lymphomas and is involved in the pathophysiology of autoimmune/inflammatory diseases. Thus, MALT1 has attracted attention as promising drug target. Although many MALT1 inhibitors have been identified, molecular tools to study MALT1 activity, target engagement and inhibition in complex biological samples, such as living cells and patient material, are still scarce. Such tools are valuable to validate MALT1 as a drug target in vivo and to assess yet unknown biological roles of MALT1. In this review, we discuss the recent literature on the development and biological application of molecular tools to study MALT1 activity and inhibition.

Current State‐of‐the‐Art Toward Chemoenzymatic Synthesis of Polyketide Natural Products

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Current State-of-the-Art Toward Chemoenzymatic Synthesis of Polyketide Natural Products

Polyketides represent an area of significant interest for drug discovery efforts. Leveraging a combination of chemical synthesis and enzymology, researchers have routinely demonstrated that the best of both strategies are conferred and result in improved outcomes. This review highlights the success of such an approach and provides an outlook for polyketide synthetic biology.


Abstract

Polyketide natural products have significant promise as pharmaceutical targets for human health and as molecular tools to probe disease and complex biological systems. While the biosynthetic logic of polyketide synthases (PKS) is well-understood, biosynthesis of designer polyketides remains challenging due to several bottlenecks, including substrate specificity constraints, disrupted protein-protein interactions, and protein solubility and folding issues. Focusing on substrate specificity, PKSs are typically interrogated using synthetic thioesters. PKS assembly lines and their products offer a wealth of information when studied in a chemoenzymatic fashion. This review provides an overview of the past two decades of polyketide chemoenzymatic synthesis and their contributions to the field of chemical biology. These synthetic strategies have successfully yielded natural product derivatives while providing critical insights into enzymatic promiscuity and mechanistic activity.

Hypoxia Modulates Cellular Endocytic Pathways and Organelles with Enhanced Cell Migration and 3D Cell Invasion

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Hypoxia Modulates Cellular Endocytic Pathways and Organelles with Enhanced Cell Migration and 3D Cell Invasion**

Hypoxia in tumors alters cellular processes, affecting cancer cell behavior. Cobalt chloride-induced hypoxia reduced proliferation but increased migration and invasion in cancer cells. Short hypoxia increased galectin3 endocytosis, but prolonged hypoxia decreased it. Organelle changes indicated adaptation to hypoxic stress. Hypoxia modulates endocytic pathways, reducing proliferation and enhancing cell migration and invasion.


Abstract

Hypoxia, a decrease in cellular or tissue level oxygen content, is characteristic of most tumors and has been shown to drive cancer progression by altering multiple subcellular processes. We hypothesized that the cancer cells in a hypoxic environment might have slower proliferation rates and increased invasion and migration rates with altered endocytosis compared to the cancer cells in the periphery of the tumor mass that experience normoxic conditions. We induced cellular hypoxia by exposing cells to cobalt chloride, a chemical hypoxic mimicking agent. This study measured the effect of hypoxia on cell proliferation, migration, and invasion. Uptake of fluorescently labeled transferrin, galectin3, and dextran that undergo endocytosis through major endocytic pathways (Clathrin-mediated pathway (CME), Clathrin-independent pathway (CIE), Fluid phase endocytosis (FPE)) were analyzed during hypoxia. Also, the organelle changes associated with hypoxia were studied with organelle trackers. We found that the proliferation rate decreased, and the migration and invasion rate increased in cancer cells in hypoxic conditions compared to normoxic cancer cells. A short hypoxic exposure increased galectin3 uptake in hypoxic cancer cells, but a prolonged hypoxic exposure decreased clathrin-independent endocytic uptake of galectin 3. Subcellular organelles, such as mitochondria, increased to withstand the hypoxic stress, while other organelles, such as Endoplasmic reticulum (ER), were significantly decreased. These data suggest that hypoxia modulates cellular endocytic pathways with reduced proliferation and enhanced cell migration and invasion.