Enhancing the accuracy of XPS calculations: Exploring hybrid basis set schemes for CVS-EOMIP-CCSD calculations.

Reliable computational methodologies and basis sets for modeling x-ray spectra are essential for extracting and interpreting electronic and structural information from experimental x-ray spectra. In particular, the trade-off between numerical accuracy and computational cost due to the size of the basis set is a major challenge, since molecular orbitals undergo extreme relaxation in the core-hole state. To gain clarity on the changes in electronic structure induced by the formation of a core-hole, the use of sufficiently flexible basis for expanding the orbitals, particularly for the core region, has been shown to be essential.

Uncovering dissipation from coarse observables: A case study of a random walk with unobserved internal states.

Inferring underlying microscopic dynamics from low-dimensional experimental signals is a central problem in physics, chemistry, and biology. As a trade-off between molecular complexity and the low-dimensional nature of experimental data, mesoscopic descriptions such as the Markovian master equation are commonly used. The states in such descriptions usually include multiple microscopic states, and the ensuing coarse-grained dynamics are generally non-Markovian.

Retrieving the Stability and Practical Performance of Activation-Unstable Mesoporous Zr(IV)-MOF for Highly Efficient Self-Calibrating Acidity Sensing.

The practical applications of activation-unstable mesoporous metal-organic frameworks (MOFs) are often constrained by their structural instability. However, enhancing their stability could unlock valuable functionalities. Herein, we stabilized the otherwise unstable, post-activated structure of a novel mesoporous Zr(IV)-MOF, NKM-809, which uses a pyridine-containing amphiprotic linker (PPTB).

Combining Fourier Transform Ion Mobility with Charge Detection Mass Spectrometry for the Analysis of Multimeric Protein Complexes.

Charge detection mass spectrometry (CDMS) allows direct mass measurement of heterogeneous samples by simultaneously determining the charge state and the mass-to-charge ratio (/) of individual ions, unlike conventional MS methods that use large ensembles of ions. CDMS typically requires long acquisition times and the collection of thousands of spectra, each containing tens to hundreds of ions, to generate sufficient ion statistics, making it difficult to interface with the time scales of online separation techniques such as ion mobility. Here, we demonstrate the application of Fourier transform multiplexing and drift tube ion mobility joined with Orbitrap-based CDMS for the analysis of multimeric protein complexes.

Modular Construction of Multivariate Metal-Organic Frameworks for Luminescent Sensing.

Metal-organic frameworks (MOFs) have played a pivotal role as rapid and effective luminescent sensing materials. Numerous MOFs with diverse characteristics have been meticulously designed for target analytes. Previous studies have highlighted the factors of spectral characteristics, energy levels, interaction forces, and sensor stabilities for the luminescent sensing performance in response to a specific analyte.

Brain-derived tau oligomer polymorphs: distinct aggregations, stability profiles, and biological activities.

Aggregation of microtubule-associated tau protein is a distinct hallmark of several neurodegenerative disorders such as Alzheimer's disease (AD), dementia with Lewy bodies (DLB), and progressive supranuclear palsy (PSP). Tau oligomers are suggested to be the primary neurotoxic species that initiate aggregation and propagate prion-like structures. Furthermore, different diseases are shown to have distinct structural characteristics of aggregated tau, denoted as polymorphs.

Injectable ionic hydrogel conductors: Advancing material design to transform cardiac pacing.

Direct pacing of the mid myocardium where re-entry originates can be used to prevent ventricular arrhythmias and circumvent the need for painful defibrillation or cardiac ablation. However, there are no pacing electrodes small enough to navigate the coronary veins that cross these culprit scar regions. To address this need, we have developed an injectable ionically conductive hydrogel electrode that can fill the epicardial coronary veins and transform them into flexible electrodes.

Stereospecific Resistance to N2-Acyl Tetrahydro-β-carboline Antimalarials Is Mediated by a PfMDR1 Mutation That Confers Collateral Drug Sensitivity.

Half the world's population is at risk of developing a malaria infection, which is caused by parasites of the genus . Currently, resistance has been identified to all clinically available antimalarials, highlighting an urgent need to develop novel compounds and better understand common mechanisms of resistance. We previously identified a novel tetrahydro-β-carboline compound, PRC1590, which potently kills the malaria parasite.

Rational Electrolyte Design for Elevated-Temperature and Thermally Stable Lithium-Ion Batteries with Nickel-Rich Cathodes.

As the energy density of lithium-ion batteries (LIBs) increases, the shortened cycle life and the increased safety hazards of LIBs are drawing increasing concerns. To address such challenges, a series of localized high-concentration electrolytes (LHCEs) based on a solvating-solvent mixture of tetramethylene sulfone and trimethyl phosphate and a high flash-point diluent 1H,1H,5H-octafluoropentyl 1,1,2,2-tetrafluoroethyl ether were designed. The LHCEs exhibited nonflammability and greatly suppressed heat release at elevated temperatures, which would potentially improve the safety performance of the LIBs.

A computational study on the effect of structural isomerism on the excited state lifetime and redox energetics of archetype iridium photoredox catalyst platforms [Ir(ppy)2(bpy)]+ and Ir(ppy)3.

This study investigates the impact of structural isomerism on the excited state lifetime and redox energetics of heteroleptic [Ir(ppy)2(bpy)]+ and homoleptic Ir(ppy)3 photoredox catalysts using ground-state and time-dependent density functional theory methods. While the ground- and excited-state reduction potentials differ only slightly among the isomers of these complexes, our findings reveal significant variations in the radiative and non-radiative decay rates of the reactivity-controlling triplet 3MLCT states of these closely related species. The observed differences in radiative decay rates could be traced back to variations in the transition dipole moment, vertical energy gaps, and spin-orbit coupling of the isomers.

Computational Tool for Determining Local Dielectric Constants in Heterogeneous Nanoscale Systems from Molecular Dynamics Trajectories.

In this work, we describe a computational tool designed to determine the local dielectric constants (ε) of charge-neutral heterogeneous systems by analyzing dipole moment fluctuations from molecular dynamics (MD) trajectories. Unlike conventional methods, our tool can calculate dielectric constants for dynamically evolving selections of molecules within a defined region of space, rather than for fixed sets of molecules. We validated our approach by computing the dielectric constants of TIP3P water nanospheres, achieving results consistent with literature values for bulk water.

NADH-bound AIF activates the mitochondrial CHCHD4/MIA40 chaperone by a substrate-mimicry mechanism.

Mitochondrial metabolism requires the chaperoned import of disulfide-stabilized proteins via CHCHD4/MIA40 and its enigmatic interaction with oxidoreductase Apoptosis-inducing factor (AIF). By crystallizing human CHCHD4's AIF-interaction domain with an activated AIF dimer, we uncover how NADH allosterically configures AIF to anchor CHCHD4's β-hairpin and histidine-helix motifs to the inner mitochondrial membrane. The structure further reveals a similarity between the AIF-interaction domain and recognition sequences of CHCHD4 substrates.

Transforming Detrimental Crystalline Zinc Hydroxide Sulfate to Homogeneous Fluorinated Amorphous Solid-Electrolyte Interphase on Zinc Anode.

The formation of non-ion conducting byproducts on zinc anode is notoriously detrimental to aqueous zinc-ion batteries (AZIBs). Herein, we successfully transform a representative detrimental byproduct, crystalline zinc hydroxide sulfate (ZHS) to fast-ion conducting solid-electrolyte interphase (SEI) via amorphization and fluorination induced by suspending CaF nanoparticles in dilute sulfate electrolytes. Distinct from widely reported nonhomogeneous organic-inorganic hybrid SEIs that exhibit structural and chemical instability, the designed single-phase SEI is homogeneous, mechanically robust, and chemically stable.

Organoboron-Functionalized Metal-organic Nanosheets for Highly Efficient CO2 Fixation Mediated by Frustrated Lewis Pairs.

Converting CO2 to high-value fine chemicals represents one of the most promising approaches to combat global warming and subsequently achieve a sustainable carbon cycle. Herein, we contribute an organoboron functionalized ultra-thin metal-organic nanosheet (MON), termed TCPB-Zr-NS, featuring an abundance of exposed Lewis acidic B and formate sites, which can effectively promote CO2 conversion upon the addition of Lewis basic o-phenylenediamines. Compared with the prototypical 3D analogue TCPB-Zr-3D, the resultant TCPB-Zr-NS showcases dramatically improved catalytic activity for the cyclization of o-phenylenediamine as a result of the highly exposed active sites and efficient substrates/products diffusion.

Overcoming the Conductance versus Crossover Trade-off in State-of-the-Art Proton Exchange Fuel-Cell Membranes by Incorporating Atomically Thin Chemical Vapor Deposition Graphene.

Permeance-selectivity trade-offs are inherent to polymeric membranes. In fuel cells, thinner proton exchange membranes (PEMs) could enable higher proton conductance and increased power density with lower area-specific resistance (ASR), smaller ohmic losses, and lower ionomer cost. However, reducing thickness is accompanied by an increase in undesired species crossover harming performance and long-term efficiency.

Gut bacterial sphingolipid production modulates dysregulated skin lipid homeostasis.

Sphingolipids are an essential lipid component of the skin barrier with alterations in skin sphingolipid composition associated with multiple skin disorders including psoriasis, atopic dermatitis, and ichthyosis. Contributions to skin sphingolipid abundance are not well characterized, thus the main method of modulating skin lipid levels is the topical application of creams rich with sphingolipids at the skin surface. Evidence that diet and gut microbiome function can alter skin biology proposes an intriguing potential for the modulation of skin lipid homeostasis through gut microbial metabolism, but potential mechanisms of action are not well understood.

Hydralazine inhibits cysteamine dioxygenase to treat preeclampsia and senesce glioblastoma.

The vasodilator hydralazine (HYZ) has been used clinically for ~ 70 years and remains on the World Health Organization's List of Essential Medicines as a therapy for preeclampsia. Despite its longstanding use and the concomitant progress toward a general understanding of vasodilation, the target and mechanism of HYZ have remained unknown. We show that HYZ selectively targets 2-aminoethanethiol dioxygenase (ADO) by chelating its metal cofactor and alkylating one of its ligands.

Plasmon hybridization model in molecules: molecular jackhammers.

We recently demonstrated molecular plasmons in cyanine dyes for the conversion of photon energy into mechanical energy through a whole-molecule coherent vibronic-driven-action. Here we present a model, a molecular plasmon analogue of molecular orbital theory and of plasmon hybridization in metal nanostructures. This model describes that molecular plasmons can be obtained from the combination or hybridization of elementary molecular fragments, resulting in molecules with hybridized plasmon resonances in the electromagnetic spectrum.

Highly versatile small virus-encoded proteins in cellular membranes: A structural perspective on how proteins' inherent conformational plasticity couples with host membranes' properties to control cellular processes.

We investigated several small viral proteins that reside and function in cellular membranes. These proteins belong to the viroporin family because they assemble into ion-conducting oligomers. However, despite forming similar oligomeric structures with analogous functions, these proteins have diverse amino acid sequences.

Drug-Linker Constructs Bearing Unique Dual-Mechanism Tubulin Binding Payloads Tethered through Cleavable and Non-Cleavable Linkers.

Antibody-drug conjugates (ADCs) have advanced as a mainstay among the most promising cancer therapeutics, offering enhanced antigen targeting and encompassing wide diversity in their linker and payload components. Small-molecule inhibitors of tubulin polymerization have found success as payloads in FDA approved ADCs and represent further promise in next-generation, pre-clinical and developmental ADCs. Unique dual-mechanism payloads (previously designed and synthesized in our laboratories) function as both potent antiproliferative agents and promising vascular disrupting agents capable of imparting selective and effective damage to tumor-associated microvessels.

Nanofibrous Peptide Hydrogels Leveraging Histidine to Modulate pH-Responsive Supramolecular Assembly and Antibody Release.

In this work, we investigate the pH-responsive behavior of multidomain peptide (MDP) hydrogels containing histidine. Small-angle X-ray scattering confirmed that MDP nanofibers sequester nonpolar residues into a hydrophobic core surrounded by a shell of hydrophilic residues. MDPs with histidine on the hydrophilic face formed nanofibers at all pH values tested, but the morphology of the fibers was influenced by the protonation state and the location of histidine in the MDP sequence.

Markedly Elevated Citrulline in a Neonate: Citrin Deficiency due to a Previously Unreported Solute Carrier Family 25 Member 13 Variant.

Background: Citrin deficiency (CD) is an autosomal recessive metabolic disorder affecting the urea cycle and energy production. Diagnosis involves measuring ammonia and amino acid levels (eg: citrulline), with confirmation through solute carrier family 25 member 13 (SLC25A13) gene mutation analysis. Herein, we present a case report of a variant in the SLC25A13 gene that has not been previously reported in the literature.

Reversible light-responsive protein hydrogel for on-demand cell encapsulation and release.

The design of biomaterials that can reconfigure on-demand in response to external stimuli is an emerging area in materials research. However, achieving reversible assembly of protein-based biomaterials by light input remains a major challenge. Here, we present the engineering of a new protein material that is capable of switching between liquid and solid state reversibly, controlled by lights of different wavelengths.

PbsNRs: predict the potential binders and scaffolds for nuclear receptors.

Nuclear receptors (NRs) are a class of essential proteins that regulate the expression of specific genes and are associated with multiple diseases. In silico methods for prescreening potential NR binders with predictive binding ability are highly desired for NR-related drug development but are rarely reported. Here, we present the PbsNRs (Predicting binders and scaffolds for Nuclear Receptors), a user-friendly web server designed to predict the potential NR binders and scaffolds through proteochemometric modeling.

Robust Bayesian graphical regression models for assessing tumor heterogeneity in proteomic networks.

Graphical models are powerful tools to investigate complex dependency structures in high-throughput datasets. However, most existing graphical models make one of two canonical assumptions: (i) a homogeneous graph with a common network for all subjects or (ii) an assumption of normality, especially in the context of Gaussian graphical models. Both assumptions are restrictive and can fail to hold in certain applications such as proteomic networks in cancer.