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Probing nuclear quantum effects in HCl clusters with high accuracy machine learning potentials

Nuclear quantum effects (NQEs) in hydrogen chloride (HCl) clusters up to the trimer are investigated using a combination of robust path integral simulations and highly accurate machine-learning potential energy surfaces (PESs). Fundamental-invariant neural network PESs, which inherently enforce permutational symmetry, are constructed from over 110 000 CCSD(T)-F12a/AVTZ level data points. Intra- and inter-molecular interactions are described using the many-body expansion approach, achieving remarkable accuracy for the 1-body, 2-body, and 3-body interactions, with root-mean-square errors of 0.003, 0.021, and 0.094 meV, respectively. Our PESs reveal new configurations of the HCl trimer, enhancing our understanding of its structural landscape and interconversion pathways. Employing our neural network potentials, path integral molecular dynamics simulations reveal that NQEs weaken the binding of HCl clusters at temperatures of 100 K and below, significantly destabilizing the trimer (by 50 meV) at 30 K. Ground state tunneling splitting of (H35Cl)2 is computed with the recently developed Eckart spring path-integral molecular dynamics method, agreeing with the experimental value within 10% difference. Our study provides quantitative insights into the influences of NQEs in these hydrogen-bonded clusters. In addition, the highly accurate many-body potentials developed herein lay the groundwork for future studies of HCl in the condensed phase.

The FKF1–ELF3–PRC2 module regulates flowering time in response to light in temperate grasses

The precise timing of flowering is critical to ensure reproductive success in plants. This process is coordinated by both endogenous and environmental cues. Light is a pivotal environmental cue fundamentally regulating plant growth and development. In temperate grasses, how light regulates flowering time remains largely unknown. Here, we characterize a blue-light photoreceptor, FLAVIN-BINDING, KELCH REPEAT, F-BOX 1 (FKF1), which functions as a flowering promoter in Brachypodium distachyon . Loss-of-function mutations in FKF1 result in delayed flowering under long-day conditions, whereas overexpression of FKF1 strongly accelerates flowering. We show that FKF1 controls the stability of floral repressor EARLY FLOWERING 3 (ELF3) in response to blue light. FKF1 directly interacts with and catalyzes the ubiquitination of ELF3, leading to protein degradation of ELF3 via the 26S proteasome pathway. Blue light can strengthen the interaction between FKF1 and ELF3, thereby accelerating degradation of ELF3. Moreover, ELF3 physically interacts with SWINGER and CURLY LEAF, two core subunits of Polycomb repressive complex 2 (PRC2), and mediates the subsequent deposition of histone H3 lysine 27 trimethylation (H3K27me3) for stable transcriptional silencing of the flowering activator PHOTOPERIOD 1 . Remarkably, the FKF1–ELF3–PRC2 regulatory module-mediated flowering time control in response to light is likely conserved across temperate grasses. Our study elucidates the mechanism by which light modulates H3K27me3 deposition to regulate flowering time in temperate grasses. This mechanism also allows plants to adapt to dynamically changing environments.

Conformational switch upon substrate binding informs the rational design of CCoAOMT enzymes

Abstract Poplar is a deciduous tree belonging to the willow family, whose wood has the characteristics of light texture and toughness. It can be used to produce pulp, and is one of the main raw materials in the paper industry. A large amount of lignin is produced during pulping and papermaking process, where the generated waste liquid and pollutants are one of the main sources of industrial pollution. Regulating lignin content not only enables factories to process more pulp, but also greatly reduces the use of chemical reagents and the production of pollutants. Caffeoyl coenzyme A O-methyltransferase (CCoAOMT) is a class of S-adenosyl methionine (SAM) methyltransferases, which can effectively regulate the total amount of lignin biosynthesis. At present, molecular recognition mechanism of CCoAoMT with the substrate caffeoyl coenzyme A (CCoA) and corresponding conformational change both remain unclear, significantly restricting the design of weakly active enzymes. In this work, the overall conformational changes of CCoAOMT after binding CCoA were firstly explored by comparative molecular dynamics (MD) simulations. The results show that the four regions of α1, α2, α6 and α8 located outside binding pocket show greater flexibility, which is conducive to substrate binding. Through free energy landscape (FEL) and conformation cluster analyses, the representative functional motion modes were investigated, with the regions involved being β5, α2 and α8. According to adaptive steered molecular dynamics (ASMD) simulations, the complete recognition process of the receptor by SAM and CCoA, and allostery in the transport channel of substrates both were observed. With the binding of substrates, the structure of CCoAOMT gradually becomes more compact, accompanied by its transport channel from open to closed state. By binding free energy prediction and energy decomposition, a series of key residues favoring the receptor-substrate mutual recognition were proposed. Specifically, CCoA exhibits H-bonds with N170, D218, T42, Y188, N39, R186, N174 and R30, as well as hydrophobic interactions with K1 and I40. In particular, Y188 and D218 both anchor CCoA caffeoyl group to the Ca2+ active site by forming stable H-bonds. Based on exhaustive single mutation and folding entropy calculation, six mutants (K1L, N39G, I40P, T42N, N174D and D218V) may be candidates for low-activity CCoAOMT.

The thermoelectric transport properties in strongly correlated single quantum dot with splitting spin

We study properties of thermocurrent through a single quantum dot (QD) system, which has an energy difference between levels of the spin-up and the spin-down as well as a Coulomb interaction between them under the temperature settings both with and without the Kondo effect. Two additional sign-changings of the thermocurrent with changing the energy level of QD is observed. Due to the Coulomb interaction between the electrons with different spins, only changing the energy level of one spin will cause significant variations for the thermocurrent of the two spins. Depending on the temperature, namely, whether the Kondo effect takes place, the Coulomb interaction exhibits different influences on thermocurrent. At high temperatures, the thermocurrent simply changes from positive to negative as the energy level of one spin increases. The lower temperatures trigger the Kondo effect and make the influence of the Coulomb interaction stand out. In this case, the thermocurrent undergoes extra multiple sign-changings and it can be explained by the changing of the electron states and hole states within the temperature bias window. Meanwhile, the splitting of energy levels leads to an obvious spin-polarized thermocurrent in the system. The spin-polarized thermocurrent changes from positive to negative as the energy level of one spin increases and the changing behavior depends on the temperature. In addition, the Coulomb interaction between two spins also profoundly affects the sign-changing phenomenon of thermocurrent at low temperatures.

High-resolution geostationary satellite observations of free tropospheric NO ₂ over North America and implications for lightning emissions

Free tropospheric (FT) nitrogen dioxide (NO 2 ) plays a critical role in atmospheric oxidant chemistry as a source of tropospheric ozone and of the hydroxyl radical (OH). It also contributes significantly to satellite-observed tropospheric NO 2 columns, which should be considered when using these columns to quantify surface emissions of nitrogen oxide radicals (NO x ≡ NO + NO 2 ). But large uncertainties remain in the sources and chemistry of FT NO 2 because observations are sparse. Here, we construct a cloud-sliced FT NO 2 (700 to 300 hPa) product from the Tropospheric Emissions: Monitoring of Pollution (TEMPO) geostationary satellite instrument over North America. This product provides higher data density and quality than previous products from low Earth orbit instruments, including the first observations of the FT NO 2 diurnal cycle in different seasons. Combined with coincident observations from the Geostationary Lightning Mapper, the TEMPO data imply that lightning is the dominant source of FT NO x in nonwinter seasons. Comparison of TEMPO FT NO 2 data with the Goddard Earth Observation System-Composition Forecasts (GEOS-CF) atmospheric chemistry model shows overall consistent magnitudes, seasonality, and diurnal variation, with a midday minimum in nonwinter seasons from photochemical loss. However, there are major discrepancies that we attribute to GEOS-CF’s use of a standard cloud-top-height-based scheme for the lightning NO x source. We find that this scheme underestimates offshore lighting flash density and misrepresents the diurnal cycle of lightning over land. Our FT NO 2 product provides a unique resource for improving the lightning NO x parameterization in atmospheric models and the ability to use NO 2 observations from space to quantify surface NO x emissions.

Cost effectiveness and pricing strategy of first line benmelstobart combination treatment for extensive stage small cell lung cancer in China

Ligand effects on the angular momentum fine structure of CdTe quantum dots

Ligand effects on the angular momentum fine structure of 3.2 nm diameter CdTe quantum dots have been studied using room temperature static spectroscopy and lifetime measurements. This study focuses on the comparison of particles having charged (octadecylphosphonic acid) and uncharged (octanethiol) ligands. In both cases, polarized photoluminescence excitation spectroscopy provides a measure of the extent to which fine structure states with orthogonal polarizations can be selectively excited, and the photoluminescence Stokes shift provides a measure of the amount of luminescence coming from fine structure states with different energies. Radiative lifetime measurements provide a measure of the relative oscillator strengths of fine structure states with different energies. We demonstrate that the changes in the nature of the surface ligands (charged or uncharged) measurably change the polarized photoluminescence excitation spectrum, Stokes shift, and radiative lifetimes. We suggest that this is due to large internal electric fields associated with the charged ligands that alter the angular momentum fine structure mixings and energetics. The results are analyzed in terms of a simple two-parameter effective mass approximation model for quasi-spherical II–VI quantum dots [Efros et al., Phys. Rev. B 54, 4843–4856 (1996)], which is the most commonly used model of angular momentum fine structure states. We find that this model qualitatively explains the results. However, quantitative analysis of these results gives a significant deviation from the model predictions; it requires that the fine structure splittings are smaller and/or more complicated and that the lower energy states have more oscillator strength than predicted by the Efros model.

Protein disulfide isomerases regulate androgen receptor stability and promote prostate cancer cell growth and survival

Cancer cells exhibit accelerated protein production to accommodate their high rates of growth and proliferation. Elevated protein synthesis creates a dependency on endoplasmic reticulum (ER)-resident proteins and chaperones, which are required to maintain proteostasis. In this study, we identified the protein disulfide isomerases (PDIs) PDIA1 and PDIA5, which play a critical role in folding of client proteins in the ER, as important regulators of prostate cancer growth and response to therapy. PDIA1 and PDIA5 are upregulated in prostate cancer and induced by the androgen receptor (AR) signaling axis. Genetic or pharmacological disabling of PDIA1/PDIA5 caused redox stress, mitochondrial dysfunction, growth inhibition, and death of prostate cancer cells in vitro and in vivo. The critical functions of these enzymes in redox homeostasis and cell survival were observed in both AR-driven and AR-independent models of prostate cancer. Loss of PDIA1/PDIA5 activity led to ubiquitination and degradation of the AR, revealing a feedback loop between these chaperones and the AR pathway. Mechanistically, PDIA1/PDIA5 regulated AR stability by mediating disulfide bond formation, an activity that required cysteines 669 and 844 in AR’s ligand-binding domain. Importantly, targeting PDIAs sensitized prostate cancer cells to the AR antagonist, enzalutamide. This study reveals a mechanism governing AR proteostasis in prostate cancer and positions PDIA1/5 as viable therapeutic targets.

Investigation on process optimization and kinetics for leaching of rare earth elements from red mud using citric acid

Optimizing thermoelectric efficiency in Sn-doped Sb2Te3 alloys through Se alloying by modulating carrier and phonon transport

Sb2Te3-based alloys have attracted considerable attention owing to their favorable thermoelectric transport properties in the mid-temperature range. Herein, the thermoelectric transport properties of pristine Sb2Te3 and Sn0.03Sb1.97Te3–ySey (y = 0, 0.05, 0.10, 0.15, 0.20, and 0.25) alloys were systematically investigated by combining Sn doping with Se alloying. The 1.5 at. % Sn doping in Sb2Te3 as Sn0.03Sb1.97Te3 increased the density-of-states effective mass (md*) and reduced lattice thermal conductivity (κlatt) compared with those of Sb2Te3, thereby enhancing the maximum thermoelectric figure of merit to 0.58 from 0.46. However, it also significantly increased the carrier concentration (nH) to 1.46 × 1020 cm−3, thereby limiting further enhancement of the thermoelectric figure of merit (zT). Se alloying was introduced to reduce nH by suppressing the native antisite defects. With Se alloying, nH gradually decreased, as expected; however, a concurrent slight reduction in md* was observed and, therefore, further increase in power factor was limited. Nevertheless, Se alloying led to a rather large reduction in total thermal conductivity owing to reductions in both electronic and lattice thermal conductivities induced by nH decrease and additional phonon scattering, respectively. Consequently, the overall zT increased with a small amount of Se alloying up to y = 0.10, with a maximum zT of 0.67 at 650 K, compared with 0.46 of Sb2Te3 and 0.59 of Sn0.03Sb1.97Te3. This study demonstrated that the dual doping or further alloying of the doped compositions could be effective, as it leads to a rather large reduction in thermal conductivity despite a potential slight decrease in enhanced md* owing to mobility degradation.

Prehistoric hunting megastructures in the Adriatic hinterland

Airborne laser scanning survey of the Karst Plateau in the Adriatic hinterland has revealed four monumental dry-stone structures, characterized by long, low stone alignments converging into concealed enclosures. These features, strategically placed along natural movement corridors, appear to have been designed to guide and trap herds of wild animals. Their architectural scale, complexity, and integration with the terrain suggest a high degree of communal organization, landscape knowledge, and planning. Although direct dating remains inconclusive, associated stratigraphy indicates they were abandoned before the Late Bronze Age, pointing to a potentially earlier origin. These structures may represent the westernmost examples of a broader tradition of large-scale hunting installations previously known only from the arid zones of Southwest Asia and North Africa. Their finding challenges prevailing models of prehistoric subsistence in Europe and opens broad perspectives on social organization, mobility, and human–animal relations in complex landscapes.

Short term demand forecasting of electric vehicle charging stations using context aware temporal transformer model

Realistic vibronic modeling of H and J excitonically coupled dimers benchmarked with femtosecond stimulated Raman spectroscopy

Coupling between vibrations and electronic excitations in molecular aggregates is a critical issue in energy transfer and exciton diffusion dynamics in light-harvesting by photosynthetic proteins and molecular materials used in photovoltaics. In most theoretical treatments of this coupling, the vibrational space is dramatically truncated to just a few vibrational modes that approximate the relative frequencies and reorganization energies of the actual vibrations. In this work, we explicitly determine the vibrational coupling of all the normal modes of two common fluorescent dyes, Bodipy (20 coupled modes) and Rhodamine B (29 coupled modes), to their monomeric electronic absorption. The ground-state resonance Raman (RR) spectra of both monomers and their dimers were collected using femtosecond stimulated Raman spectroscopy. We developed a multi-mode excitonic Hamiltonian, which includes 9 vibrational modes on each molecule, to calculate the vibronic structure of the absorption and RR excitation profile of dimers. This Hamiltonian is used to determine the magnitude of exciton coupling between the two monomers in the end-to-end covalently linked “J” dimer of Bodipy and the non-covalently bound, π-stacked “H” dimer of Rhodamine B. The excitonic Hamiltonian successfully reproduces the spectra of both dimers and reveals that the Bodipy-dimer has a coupling of −267 cm−1 and that the RhB dimer has a coupling of +806 cm−1. The multi-mode excitonic Hamiltonian explains the RR intensity of the dimers, except for a small number of vibrational modes that have a significant enhancement of RR intensity that is unexplained by the exciton model.

Small-molecule allosteric activator of ubiquitin-specific protease 7 (USP7)

Ubiquitin-specific protease 7 (USP7) is a deubiquitylase essential for cell homeostasis, DNA repair, and regulation of both tumor suppressors and oncogenes. Recently, haploinsufficiency of USP7 has been associated with Hao–Fountain syndrome (HAFOUS), a rare neurodevelopmental disorder. Although a range of USP7 inhibitors have been developed over the last decade, in the context of HAFOUS, USP7 activators may represent a more relevant approach. To address this challenge, we report the identification and characterization of a small-molecule activator of USP7 called MS-8. Structural and functional studies show that MS-8 allosterically activates USP7, mimicking the endogenous autoactivation mechanism of the enzyme. We observed that MS-8 engages and activates mutant USP7 in a cellular context, impacting downstream proteins. Taken together, our study provides validation of the USP7 activator that paves the way toward activation-driven USP7 pharmacology.

Visuospatial performance and its neural substrates in Dementia with Lewy Bodies during a pointing task

Ground and excited-state properties of the extended Hubbard dimer from the multichannel Dyson equation

We have recently presented the multichannel Dyson equation as an alternative to the standard single-channel Dyson equation. While the latter involves a single many-body Green’s function, the former uses a multichannel Green’s function in which two or more many-body Green’s functions are coupled. Quasiparticles and satellites are thus naturally treated on equal footing in the multichannel Dyson equation. To assess the accuracy of our approach, we apply it here to the ground- and excited-state properties of the extended Hubbard dimer, an exactly solvable model for H2. In particular, we focus on the potential energy surface as well as the corresponding spectral functions and HOMO-LUMO gaps, which are well-known challenges for many-body approximations such as second Born and GW. We show that the multichannel Dyson equation gives overall very good results for all properties considered and outperforms both GW and second Born. In particular, the multichannel Dyson equation yields the correct ground-state energy and HOMO–LUMO gap in the dissociation limit contrary to GW.

Polycomb Repressive Complex 1 and USP16 localize to the mitochondrion and influence its function

Polycomb Repressive Complex 1 (PRC1) represses gene expression by ubiquitinating histone H2A or physically compacting chromatin. USP16, one of the histone H2A deubiquitinases, antagonizes PRC1-mediated H2A ubiquitination (H2Aub). Here, we report that both PRC1 and USP16 are also localized in mitochondria and influence mitochondrial function directly. Our findings are based on immunofluorescence and proximity ligation assays, cell fractionation, and biochemical analyses of isolated or affinity-purified mitochondria. We further showed that PRC1 and USP16 function with the ubiquitin pathway. Auxin-induced, mitochondria-specific depletion of the PRC1 subunit RING2 altered the ubiquitination status of mitochondrial proteins, including H2Aub. Disruption of PRC1, either through double knockout (KO) of RING1 and RING2 or through mitochondria-specific deletion of RING2 in the RING1 KO background, caused profound alterations in mitochondrial proteome and led to disturbances in mitochondrial integrity and impaired respiratory function. Thus, in addition to their canonical functions in the nucleus, PRC1 and USP16 also translocate into mitochondria and directly impact mitochondrial integrity and function.

Structural analysis of Si-doped amorphous In2O3 based on quantum beam measurements and computer simulations

Abstract The structural properties and thermal stability of Si-doped amorphous indium oxide (ISO) were investigated via experimental characterization and computational modeling techniques. The total structure factors, S ( Q ), and reduced pair distribution functions, G ( r ), were calculated for both annealed and pristine ISO samples, revealing the distinct structural features induced by Si doping and thermal treatment. Although the pristine ISO samples exhibited halo patterns indicative of an amorphous structure, annealing at 600 °C led to pronounced Bragg peaks, suggesting that the sample was crystallized. However, an ISO with a higher Si content (20 at%) retained its amorphous structure even after annealing, highlighting the role of Si-doping in enhancing the thermal stability. Classical molecular dynamics–reverse Monte Carlo simulations were employed to elucidate the structure of pristine ISO samples, revealing good agreement with the experimental data. Furthermore, the partial structure factors, S ij ( Q ), and partial pair distribution functions, g ij ( r ) demonstrate the influence of Si doping on atomic correlations and density changes in the ISO. Polyhedral connectivity analysis suggests that the fraction changes of edge sharing due to Si doping affect the thermal stability of ISO and that SiO 4 tetrahedra play a crucial role in inhibiting crystallization.

Potentials of mean force fail to describe chemical bond-breaking in solution

Many liquid phase studies assume that the potential energy surfaces of reacting molecules are the same as in the gas phase, neglecting complex solvent dynamics that can completely alter the nature of chemical reactivity. Even studies that include solvent effects typically only consider them in an average, equilibrium way as part of a potential of mean force (PMF). In this work, we use mixed quantum/classical simulations to compare how equilibrium and non-equilibrium solvent motions affect the photodissociation of a simple diatomic molecule, NaK+, in liquid tetrahydrofuran. A PMF analysis shows that as the excited-state molecule dissociates with the solvent at equilibrium, the bonding electron remains associated with K+ at short bond distances but eventually localizes on Na+ at the end of dissociation. When we examine non-equilibrium dynamical photodissociation trajectories, however, we find that they fall into three distinct categories: about a quarter of them have the bonding electron mainly associated with Na+, another quarter stay mainly associated with K+, and about half have the bonding electron shared roughly equally between the two ions. The results show that equilibrium PMFs cannot accurately describe the dynamics of bond-breaking chemical reactions in solution because there is insufficient time for the solvent to reach equilibrium on the time scale over which bond dissociation occurs. Our analysis shows that the solvent coupling between the electronic energy surfaces is similar at and away from equilibrium, suggesting that other factors, such as solute velocity-driven solvent memory effects, play a more important role in explaining the failure of the equilibrium PMF to predict the non-equilibrium dynamics.

Local consolidative therapy extends survival in metastatic NSCLC with oligoresidual disease following first-line immunotherapy, irrespective of PD-L1 expression