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At least 1,279 records · Page 71
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

Molecular analysis and essentiality of Aro1 shikimate biosynthesis multi-enzyme in Candida albicans

In the human fungal pathogen Candida albicans, ARO1 encodes an essential multi-enzyme that catalyses consecutive steps in the shikimate pathway for biosynthesis of chorismate, a precursor to folate and the aromatic amino acids. We obtained the first molecular image of C. albicans Aro1 that reveals the architecture of all five enzymatic domains and their arrangement in the context of the full-length protein. Aro1 forms a flexible dimer allowing relative autonomy of enzymatic function of the individual domains. Our activity and in cellulo data suggest that only four of Aro1’s enzymatic domains are functional and essential for viability of C. albicans, whereas the 3-dehydroquinate dehydratase (DHQase) domain is inactive because of active site substitutions. We further demonstrate that in C. albicans, the type II DHQase Dqd1 can compensate for the inactive DHQase domain of Aro1, suggesting an unrecognized essential role for this enzyme in shikimate biosynthesis. In contrast, in Candida glabrata and Candida parapsilosis, which do not encode a Dqd1 homolog, Aro1 DHQase domains are enzymatically active, highlighting diversity across Candida species.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Density functional modeling of the binding energies between aluminosilicate oligomers and different metal cations

Interactions between negatively charged aluminosilicate species and positively charged metal cations are critical to many important engineering processes and applications, including sustainable cements and aluminosilicate glasses. In an effort to probe these interactions, here we have calculated the pair-wise interaction energies (i.e., binding energies) between aluminosilicate dimer/trimer and 17 different metal cations M n+ (M n+ = Li + , Na + , K + , Cu + , Cu 2+ , Co 2+ , Zn 2+ , Ni 2+ , Mg 2+ , Ca 2+ , Ti 2+ , Fe 2+ , Fe 3+ , Co 3+ , Cr 3+ , Ti 4+ and Cr 6+ ) using a density functional theory (DFT) approach. Analysis of the DFT-optimized structural representations for the clusters (dimer/trimer + M n+ ) shows that their structural attributes (e.g., interatomic distances) are generally consistent with literature observations on aluminosilicate glasses. The DFT-derived binding energies are seen to vary considerably depending on the type of cations (i.e., charge and ionic radii) and aluminosilicate species (i.e., dimer or trimer). A survey of the literature reveals that the difference in the calculated binding energies between different M n+ can be used to explain many literature observations associated with the impact of metal cations on materials properties (e.g., glass corrosion, mineral dissolution, and ionic transport). Analysis of all the DFT-derived binding energies reveals that the correlation between these energy values and the ionic potential and field strength of the metal cations are well captured by 2nd order polynomial functions ( R 2 values of 0.99–1.00 are achieved for regressions). Given that the ionic potential and field strength of a given metal cation can be readily estimated using well-tabulated ionic radii available in the literature, these simple polynomial functions would enable rapid estimation of the binding energies of a much wider range of cations with the aluminosilicate dimer/trimer, providing guidance on the design and optimization of sustainable cements and aluminosilicate glasses and their associated applications. Finally, the limitations associated with using these simple model systems to model complex interactions are also discussed.

Gong, Kai↗
DOE OSTI2022

Overview of Diverse Methyl/Alkyl-Coenzyme M Reductases and Considerations for Their Potential Heterologous Expression

Methyl-coenzyme M reductase (MCR) is an archaeal enzyme that catalyzes the final step of methanogenesis and the first step in the anaerobic oxidation of methane, the energy metabolisms of methanogens and anaerobic methanotrophs (ANME), respectively. Variants of MCR, known as alkyl-coenzyme M reductases, are involved in the anaerobic oxidation of short-chain alkanes including ethane, propane, and butane as well as the catabolism of long-chain alkanes from oil reservoirs. MCR is a dimer of heterotrimers (encoded by mcrABG) and requires the nickel-containing tetrapyrrole prosthetic group known as coenzyme F430. MCR houses a series of unusual post-translational modifications within its active site whose identities vary depending on the organism and whose functions remain unclear. Methanogenic MCRs are encoded in a highly conserved mcrBDCGA gene cluster, which encodes two accessory proteins, McrD and McrC, that are believed to be involved in the assembly and activation of MCR, respectively. The requirement of a unique and complex coenzyme, various unusual post-translational modifications, and many remaining questions surrounding assembly and activation of MCR largely limit in vitro experiments to native enzymes with recombinant methods only recently appearing. Production of MCRs in a heterologous host is an important step toward developing optimized biocatalytic systems for methane production as well as for bioconversion of methane and other alkanes into value-added compounds. This review will first summarize MCR catalysis and structure, followed by a discussion of advances and challenges related to the production of diverse MCRs in a heterologous host.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

Cryo-EM structure of the diapause chaperone artemin

The protein artemin acts as both an RNA and protein chaperone and constitutes over 10% of all protein in Artemia cysts during diapause. However, its mechanistic details remain elusive since no high-resolution structure of artemin exists. Here we report the full-length structure of artemin at 2.04 Å resolution. The cryo-EM map contains density for an intramolecular disulfide bond between Cys22-Cys61 and resolves the entire C-terminus extending into the core of the assembled protein cage but in a different configuration than previously hypothesized with molecular modeling. We also provide data supporting the role of C-terminal helix F towards stabilizing the dimer form that is believed to be important for its chaperoning activity. We were able to destabilize this effect by placing a tag at the C-terminus to fully pack the internal cavity and cause limited steric hindrance.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2023

Cinnamon essential oil vapor alleviates the reduction of aroma-related volatiles in cold-stored “Feicheng” peach using HS-GC-IMS

“Feicheng” peach is popular for its unique aroma, but its defect of being highly sensitive to chilling injury (CI) often leads to aroma loss and internal browning. Essential oils (EOs) are often used to enhance the antioxidant capacity of plants and fruits, as well as to trigger their defense against biotic/abiotic stresses. This study aimed to examine the effect of cinnamon essential oil (CEO) vapor treatment on the aroma quality of peach fruit during cold storage using HS-GC-IMS. The results showed that 50 μL/L CEO vapor reduced the severity of internal browning (IB) in peaches at the stage of 7 ~ 21 d during refrigeration (Significantly, the L * value was higher and the IB index was lower than that of control, p < 0.05). Meanwhile, the evident reduction or loss of aroma content caused by CI was restored to a higher level than the control ( p < 0.05). Furthermore, CEO treatment promoted the release of aroma-related volatiles as evidenced by more propyl acetate, and the dimer of amyl acetate, isoamyl acetate, butyl acetate detected than that on harvest day and no-treated group after 21 d of cold storage plus 2 d of shelf life. Genes of PpLOX1 , PpLOX2 , PpHPL1 and PpADH1 associated with aroma-related volatile biosynthesis revealed higher transcript abundance in peach fruits treated with CEO than the control ( p < 0.05). Overall, our study demonstrated that CEO in vapor phase may be beneficial to alleviate the quality deterioration in aroma and flesh color of “Feicheng” peaches caused by CI, which lays a theoretical reference for maintaining postharvest quality of peach fruits.

Wang, Dan↗
DOE OSTI2021

Early Drug Discovery and Development of Novel Cancer Therapeutics Targeting DNA Polymerase Eta (POLH)

Polymerase eta (or Pol η or POLH) is a specialized DNA polymerase that is able to bypass certain blocking lesions, such as those generated by ultraviolet radiation (UVR) or cisplatin, and is deployed to replication foci for translesion synthesis as part of the DNA damage response (DDR). Inherited defects in the gene encoding POLH (a.k.a., XPV) are associated with the rare, sun-sensitive, cancer-prone disorder, xeroderma pigmentosum, owing to the enzyme’s ability to accurately bypass UVR-induced thymine dimers. In standard-of-care cancer therapies involving platinum-based clinical agents, e.g., cisplatin or oxaliplatin, POLH can bypass platinum-DNA adducts, negating benefits of the treatment and enabling drug resistance. POLH inhibition can sensitize cells to platinum-based chemotherapies, and the polymerase has also been implicated in resistance to nucleoside analogs, such as gemcitabine. POLH overexpression has been linked to the development of chemoresistance in several cancers, including lung, ovarian, and bladder. Co-inhibition of POLH and the ATR serine/threonine kinase, another DDR protein, causes synthetic lethality in a range of cancers, reinforcing that POLH is an emerging target for the development of novel oncology therapeutics. Using a fragment-based drug discovery approach in combination with an optimized crystallization screen, we have solved the first X-ray crystal structures of small novel drug-like compounds, i.e., fragments, bound to POLH, as starting points for the design of POLH inhibitors. The intrinsic molecular resolution afforded by the method can be quickly exploited in fragment growth and elaboration as well as analog scoping and scaffold hopping using medicinal and computational chemistry to advance hits to lead. An initial small round of medicinal chemistry has resulted in inhibitors with a range of functional activity in an in vitro biochemical assay, leading to the rapid identification of an inhibitor to advance to subsequent rounds of chemistry to generate a lead compound. Importantly, our chemical matter is different from the traditional nucleoside analog-based approaches for targeting DNA polymerases.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

X-ray Crystallographic Study of Preferred Spacing by the NF-κB p50 Homodimer on κB DNA

Though originally characterized as an inactive or transcriptionally repressive factor, the NF-κB p50 homodimer has become appreciated as a physiologically relevant driver of specific target gene expression. By virtue of its low affinity for cytoplasmic IκB protein inhibitors, p50 accumulates in the nucleus of resting cells, where it is a binding target for the transcriptional co-activator IκBζ. In this study, we employed X-ray crystallography to analyze the structure of the p50 homodimer on κB DNA from the promoters of human interleukin-6 (IL-6) and neutrophil-gelatinase-associated lipocalin (NGAL) genes, both of which respond to IκBζ. The NF-κB p50 homodimer binds 11-bp on IL-6 κB DNA, while, on NGAL κB DNA, the spacing is 12-bp. This begs the question: what DNA binding mode is preferred by NF-κB p50 homodimer? To address this, we engineered a “Test” κB-like DNA containing the core sequence 5'-GGGGAATTCCCC-3' and determined its X-ray crystal structure in complex with p50. This revealed that, when presented with multiple options, NF-κB p50 homodimer prefers to bind 11-bp, which necessarily imposes asymmetry on the complex despite the symmetry inherent in both the protein and its target DNA, and that the p50 dimerization domain can contact DNA via distinct modes.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Mechanistic Insights Revealed by YbtPQ in the Occluded State

Recently, several ATP-binding cassette (ABC) importers have been found to adopt the typical fold of type IV ABC exporters. Presumably, these importers would function under the transport scheme of “alternating access” like those exporters, cycling through inward-open, occluded, and outward-open conformations. Understanding how the exporter-like importers move substrates in the opposite direction requires structural studies on all the major conformations. To shed light on this, here we report the structure of yersiniabactin importer YbtPQ from uropathogenic Escherichia coli in the occluded conformation trapped by ADP-vanadate (ADP-Vi) at a 3.1 Å resolution determined by cryo-electron microscopy. The structure shows unusual local rearrangements in multiple helices and loops in its transmembrane domains (TMDs). In addition, the dimerization of the nucleotide-binding domains (NBDs) promoted by the vanadate trapping is highlighted by the “screwdriver” action at one of the two hinge points. These structural observations are rare and thus provide valuable information to understand the structural plasticity of the exporter-like ABC importers.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

An Engineered Laccase from Fomitiporia mediterranea Accelerates Lignocellulose Degradation

Laccases from white-rot fungi catalyze lignin depolymerization, a critical first step to upgrading lignin to valuable biodiesel fuels and chemicals. In this study, a wildtype laccase from the basidiomycete Fomitiporia mediterranea (Fom_lac) and a variant engineered to have a carbohydrate-binding module (Fom_CBM) were studied for their ability to catalyze cleavage of β-O-4′ ether and C–C bonds in phenolic and non-phenolic lignin dimers using a nanostructure-initiator mass spectrometry-based assay. Fom_lac and Fom_CBM catalyze β-O-4′ ether and C–C bond breaking, with higher activity under acidic conditions (pH < 6). The potential of Fom_lac and Fom_CBM to enhance saccharification yields from untreated and ionic liquid pretreated pine was also investigated. Adding Fom_CBM to mixtures of cellulases and hemicellulases improved sugar yields by 140% on untreated pine and 32% on cholinium lysinate pretreated pine when compared to the inclusion of Fom_lac to the same mixtures. Adding either Fom_lac or Fom_CBM to mixtures of cellulases and hemicellulases effectively accelerates enzymatic hydrolysis, demonstrating its potential applications for lignocellulose valorization. We postulate that additional increases in sugar yields for the Fom_CBM enzyme mixtures were due to Fom_CBM being brought more proximal to lignin through binding to either cellulose or lignin itself.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2024

Completing the Ba–As Compositional Space: Synthesis and Characterization of Three New Binary Zintl Arsenides, Ba3As4, Ba5As4, and Ba16As11

Three novel binary barium arsenides, Ba3As4, Ba5As4, and Ba16As11, were synthesized and their crystal and electronic structures were investigated. Structural data collected via the single-crystal X-ray diffraction method indicate that the anionic substructures of all three novel compounds are composed of structural motifs based on the homoatomic As–As contacts, with [As2]4− dimers found in Ba5As4 and Ba16As11, and an [As4]6− tetramer found in Ba3As4. Ba3As4 and Ba5As4 crystallize in the orthorhombic crystal system—with the non-centrosymmetric space group Fdd2 (a = 15.3680(20) Å, b = 18.7550(30) Å, c = 6.2816(10) Å) for the former, and the centrosymmetric space group Cmce (a = 16.8820(30) Å, b = 8.5391(16) Å, and c = 8.6127(16) Å) for the latter—adopting Eu3As4 and Eu5As4 structure types, respectively. The heavily disordered Ba16As11 structure was solved in the tetragonal crystal system with the space group P4¯21m (a = 12.8944(12) Å and c = 11.8141(17) Å). The Zintl concept can be applied to each of these materials as follows: Ba3As4 = (Ba2+)3[As4]6−, Ba5As4 = (Ba2+)5(As3−)2[As2]4−, and 2 × Ba16As11 = (Ba2+)32(As3−) ≈ 20[As2]4− ≈ 1, pointing to the charge-balanced nature of these compounds. Electronic structure calculations indicate narrow bandgap semiconducting behavior, with calculated bandgaps of 0.47 eV for Ba3As4, 0.34 eV for Ba5As4, and 0.33 eV for Ba16As11.

Crystallography↗
DOE OSTI2020

Mathematical Model of ATM Activation and Chromatin Relaxation by Ionizing Radiation

We propose a comprehensive mathematical model to study the dynamics of ionizing radiation induced Ataxia-telangiectasia mutated (ATM) activation that consists of ATM activation through dual mechanisms: the initiative activation pathway triggered by the DNA damage-induced local chromatin relaxation and the primary activation pathway consisting of a self-activation loop by interplay with chromatin relaxation. The model is expressed as a series of biochemical reactions, governed by a system of differential equations and analyzed by dynamical systems techniques. Radiation induced double strand breaks (DSBs) cause rapid local chromatin relaxation, which is independent of ATM but initiates ATM activation at damage sites. Key to the model description is how chromatin relaxation follows when active ATM phosphorylates KAP-1, which subsequently spreads throughout the chromatin and induces global chromatin relaxation. Additionally, the model describes how oxidative stress activation of ATM triggers a self-activation loop in which PP2A and ATF2 are released so that ATM can undergo autophosphorylation and acetylation for full activation in relaxed chromatin. In contrast, oxidative stress alone can partially activate ATM because phosphorylated ATM remains as a dimer. The model leads to predictions on ATM mediated responses to DSBs, oxidative stress, or both that can be tested by experiments.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Alicyclobacillus mali FL18 as a Novel Source of Glycosyl Hydrolases: Characterization of a New Thermophilic β-Xylosidase Tolerant to Monosaccharides

A thermo-acidophilic bacterium, Alicyclobacillus mali FL18, was isolated from a hot spring of Pisciarelli, near Naples, Italy; following genome analysis, a novel putative β-xylosidase, AmβXyl, belonging to the glycosyl hydrolase (GH) family 3 was identified. A synthetic gene was produced, cloned in pET-30a(+), and expressed in Escherichia coli BL21 (DE3) RIL. The purified recombinant protein, which showed a dimeric structure, had optimal catalytic activity at 80 °C and pH 5.6, exhibiting 60% of its activity after 2 h at 50 °C and displaying high stability (more than 80%) at pH 5.0–8.0 after 16 h. AmβXyl is mainly active on both para-nitrophenyl-β-D-xylopyranoside (K M 0.52 mM, k cat 1606 s -1 , and k cat /K M 3088.46 mM -1 ·s -1 ) and para-nitrophenyl-α-L-arabinofuranoside (K M 10.56 mM, k cat 2395.8 s -1 , and k cat /K M 226.87 mM -1 ·s -1 ). Thin-layer chromatography showed its ability to convert xylooligomers (xylobiose and xylotriose) into xylose, confirming that AmβXyl is a true β-xylosidase. Furthermore, no inhibitory effect on enzymatic activity by metal ions, detergents, or EDTA was observed except for 5 mM Cu 2+ . AmβXyl showed an excellent tolerance to organic solvents; in particular, the enzyme increased its activity at high concentrations (30%) of organic solvents such as ethanol, methanol, and DMSO. Lastly, the enzyme showed not only a good tolerance to inhibition by xylose, arabinose, and glucose, but was activated by 0.75 M xylose and up to 1.5 M by both arabinose and glucose. The high tolerance to organic solvents and monosaccharides together with other characteristics reported above suggests that AmβXyl may have several applications in many industrial fields.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2021

Evolution of Thyroglobulin Loop Kinetics in EpCAM

Epithelial cell-activating molecule (EpCAM) is an important cancer biomarker and therapeutic target given its elevated expression in epithelial cancers. EpCAM is a type I transmembrane protein that forms cis-dimers along the thyroglobulin type-1A-like domain (TYD) in the extracellular region. The thyroglobulin loop (TY loop) within the TYD is structurally dynamic in the monomer state of human EpCAM, binding reversibly to a TYD site. However, it is not known if this flexibility is prevalent across different species. Here, we conduct over 17 μs of all-atom molecular dynamics simulations to study EpCAM TY loop kinetics of five different species, including human, mouse, chicken, frog, and fish. We find that the TY loop remains dynamic across evolution. In addition to the TYD binding site, we discover a second binding site for the TY loop in the C-terminal domain (CTD). Calculations of the dissociation rate constants from the simulation trajectories suggest a differential binding pattern of fish EpCAM and other organisms. Whereas fish TY loop has comparable binding for both TYD and CTD sites, the TY loops of other species preferably bind the TYD site. A hybrid construct of fish EpCAM with human TY loop restores the TYD binding preference, suggesting robust effects of the TY loop sequence on its dynamic behavior. Our findings provide insights into the structural dynamics of EpCAM and its implication in physiological functions.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Protocol for Engineered Compositional Asymmetry Within Nanodiscs

Membrane proteins remain the most challenging targets for structural characterization, yet their elucidation provides valuable insights into protein function, disease mechanisms, and drug specificity. Structural biology platforms have advanced rapidly in recent years, notably through the development and implementation of nanodiscs—discoidal lipid–protein complexes that encapsulate and solubilize membrane proteins within a controlled, native-like environment. While nanodiscs have become powerful tools for studying membrane proteins, faithfully reconstituting the compositional asymmetry intrinsic to nearly all biological membranes has not yet been achieved. Proper membrane leaflet lipid distribution is critical for accurate protein folding, stability, and insertion. Here, we share a protocol for reconstituting tailored compositional asymmetry within nanodiscs through membrane extraction from giant unilamellar vesicles (GUVs) treated with a leaflet-specific methyl-β-cyclodextrin (mβCD) lipid exchange. Nanodisc asymmetry is verified through a geometric approach: biotin-DPPE-preloaded mβCD engages in lipid exchange with the outer leaflet of POPC GUVs solubilized by the lipid-free membrane scaffold protein (MSP) Δ49ApoA-I to form nanodisc structures. Once isolated, nanodiscs are introduced to the biotin-binding bacterial protein streptavidin. High-speed atomic force microscopy imaging depicts nanodisc–dimer complexes, indicating that biotin-DPPE was successfully reconstituted into a single leaflet of the nanodiscs. This finding outlines the first step toward engineering tailored nanodisc asymmetry and mimicking the native environment of integral proteins—a potentially powerful tool for accurately reconstituting and structurally analyzing integral membrane proteins whose functions are modulated by lipid asymmetry.

Biological and medical sciences↗
DOE OSTI2022

Data-Driven and Multiscale Modeling of DNA-Templated Dye Aggregates

Dye aggregates are of interest for excitonic applications, including biomedical imaging, organic photovoltaics, and quantum information systems. Dyes with large transition dipole moments (μ) are necessary to optimize coupling within dye aggregates. Extinction coefficients (ε) can be used to determine the μ of dyes, and so dyes with a large ε (>150,000 M –1 cm –1 ) should be engineered or identified. However, dye properties leading to a large ε are not fully understood, and low-throughput methods of dye screening, such as experimental measurements or density functional theory (DFT) calculations, can be time-consuming. In order to screen large datasets of molecules for desirable properties (i.e., large ε and μ), a computational workflow was established using machine learning (ML), DFT, time-dependent (TD-) DFT, and molecular dynamics (MD). ML models were developed through training and validation on a dataset of 8802 dyes using structural features. A Classifier was developed with an accuracy of 97% and a Regressor was constructed with an R2 of above 0.9, comparing between experiment and ML prediction. Using the Regressor, the ε values of over 18,000 dyes were predicted. The top 100 dyes were further screened using DFT and TD-DFT to identify 15 dyes with a μ relative to a reference dye, pentamethine indocyanine dye Cy5. Two benchmark MD simulations were performed on Cy5 and Cy5.5 dimers, and it was found that MD could accurately capture experimental results. The results of this study exhibit that our computational workflow for identifying dyes with a large μ for excitonic applications is effective and can be used as a tool to develop new dyes for excitonic applications.

77 NANOSCIENCE AND NANOTECHNOLOGY↗
DOE OSTI2022

On the Dynamics of the Carbon–Bromine Bond Dissociation in the 1-Bromo-2-Methylnaphthalene Radical Anion

This paper studies the mechanism of electrochemically induced carbon–bromine dissociation in 1-Br-2-methylnaphalene in the reduction regime. In particular, the bond dissociation of the relevant radical anion is disassembled at a molecular level, exploiting quantum mechanical calculations including steady-state, equilibrium and dissociation dynamics via dynamic reaction coordinate (DRC) calculations. DRC is a molecular-dynamic-based calculation relying on an ab initio potential surface. This is to achieve a detailed picture of the dissociation process in an elementary molecular detail. From a thermodynamic point of view, all the reaction paths examined are energetically feasible. The obtained results suggest that the carbon halogen bond dissociates following the first electron uptake follow a stepwise mechanism. Indeed, the formation of the bromide anion and an organic radical occurs. The latter reacts to form a binaphthalene intrinsically chiral dimer. This paper is respectfully dedicated to Professors Anny Jutand and Christian Amatore for their outstanding contribution in the field of electrochemical catalysis and electrosynthesis.

1-bromo-2-methylnaphthalene↗
DOE OSTI2025

Structure-Based Design of Small-Molecule Inhibitors of Human Interleukin-6

Human Interleukin-6 (hIL-6) is a pro inflammatory cytokine that binds to its receptor, IL-6Rα followed by binding to gp130 and subsequent dimerization to form a hexamer signaling complex. As a critical inflammation mediator, hIL-6 is associated with a diverse range of diseases and monoclonal antibodies in clinical use that either target IL-6Rα or hIL-6 to inhibit signaling. Here, we perform high-throughput structure-based computational screening using ensemble docking for small-molecule antagonists for which the target conformations were taken from 600 ns long molecular dynamics simulations of the apo protein. Prior knowledge of the contact sites from binary complex studies and experimental work was incorporated into the docking studies. The top 20 scoring ligands from the in silico studies after post analysis were subjected to in vitro functional assays. Among these compounds, the ligand with the second-highest calculated binding affinity experimentally showed an ~84% inhibitory effect on IL6-induced STAT3 reporter activity at 10 μM concentration. This finding may pave the way for designing small-molecule inhibitors of hIL-6 of therapeutic significance.

Human Interleukin-6↗
DOE OSTI2025

Rapid and Ultrasensitive Short-Chain PFAS (GenX) Detection in Water via Surface-Enhanced Raman Spectroscopy with a Hierarchical Nanofibrous Substrate

GenX, the trade name of hexafluoropropylene oxide dimer acid (HFPO-DA) and its ammonium salt, is a short-chain PFAS that has emerged as a substitute for the legacy PFAS perfluorooctanoic acid (PFOA). However, GenX has turned out to be more toxic than people originally thought. In order to monitor and regulate water quality according to recently issued drinking water standards for GenX, rapid and ultrasensitive detection of GenX is urgently needed. For the first time, this study reports ultrasensitive (as low as 1 part per billion (ppb)) and fast detection (in minutes) of GenX in water via surface-enhanced Raman spectroscopy (SERS) using a hierarchical nanofibrous SERS substrate, which was prepared by assembling ~60 nm Ag nanoparticles on electrospun nylon-6 nanofibers through a “hot start” method. The findings in this research highlight the potential of the engineered hierarchical nanofibrous SERS substrate for enhanced detection of short-chain PFASs in water, contributing to the improvement of environmental monitoring and management strategies for PFASs.

Ismail, Ali K. (ORCID:0009000005987973)↗