Lysosomal cyst(e)ine storage potentiates tolerance to oxidative stress in cancer cells.

Cyst(e)ine is a key precursor for the synthesis of glutathione (GSH), which protects cancer cells from oxidative stress. Cyst(e)ine is stored in lysosomes, but its role in redox regulation is unclear. Here, we show that breast cancer cells upregulate major facilitator superfamily domain containing 12 (MFSD12) to increase lysosomal cyst(e)ine storage, which is released by cystinosin (CTNS) to maintain GSH levels and buffer oxidative stress. We find that mTORC1 regulates MFSD12 by directly phosphorylating residue T254, while mTORC1 inhibition enhances lysosome acidification that activates CTNS. This switch modulates lysosomal cyst(e)ine levels in response to oxidative stress, fine-tuning redox homeostasis to enhance cell fitness. MFSD12-T254A mutant inhibits MFSD12 function and suppresses tumor progression. Moreover, MFSD12 overexpression correlates with poor neoadjuvant chemotherapy response and prognosis in breast cancer patients. Our findings reveal the critical role of lysosomal cyst(e)ine storage in adaptive redox homeostasis and suggest that MFSD12 is a potential therapeutic target.

Efficient Homojunction Tin Perovskite Solar Cells Enabled by Gradient Germanium Doping.

P-type self-doping is known to hamper tin-based perovskites for developing high-performance solar cells by increasing the background current density and carrier recombination processes. In this work, we propose a gradient homojunction structure with germanium doping that generates an internal electric field across the perovskite film to deplete the charge carriers. This structure reduces the dark current density of perovskite by over 2 orders of magnitude and trap density by an order of magnitude. The resultant tin-based perovskite solar cells exhibit a higher power conversion efficiency of 13.3% and excellent stability, maintaining 95% and 85% of their initial efficiencies after 250 min of continuous illumination and 3800 h of storage, respectively. We reveal the homojunction formation mechanism using density functional theory calculations and molecular level characterizations. Our work provides a reliable strategy for controlling the spatial energy levels in tin perovskite films and offers insights into designing intriguing lead-free perovskite optoelectronics.

Microplastics increase the microbial functional potential of greenhouse gas emissions and water pollution in a freshwater lake: A metagenomic study.

Aquatic ecosystems are being increasingly polluted by microplastics (MPs), which calls for an understanding of how MPs affect microbially driven biogenic element cycling in water environments. A 28-day incubation experiment was conducted using freshwater lake water added with three polymer types of MPs (i.e., polyethylene, polypropylene, polystyrene) separately or in combination at a concentration of 1 items/L. The effects of various MPs on microbial communities and functional genes related to carbon, nitrogen, phosphorus, and sulfur cycling were analyzed using metagenomics. Results showed that Sphingomonas and Novosphingobium, which were indicator taxa (genus level) in the polyethylene treatment group, made the largest functional contribution to biogenic element cycling. Following the addition of MPs, the relative abundances of genes related to methane oxidation (e.g., hdrD, frhB, accAB) and denitrification (napABC, nirK, norB) increased. These changes were accompanied by increased relative abundances of genes involved in organic phosphorus mineralization (e.g., phoAD) and sulfate reduction (cysHIJ), as well as decreased relative abundances of genes involved in phosphate transport (phnCDE) and the SOX system. Findings of this study underscore that MPs, especially polyethylene, increase the potential of greenhouse gas emissions (CO2, N2O) and water pollution (PO43-, H2S) in freshwater lakes at the functional gene level.

Transcriptional profiling of exosomes derived from plasma of canine with mammary tumor by RNA-seq analysis.

Canine mammary tumor (CMT) are the second most common tumor in dogs. Exosomes can act as biomarkers for the early diagnosis of tumors, and also be involved in the pathogenesis and metastasis mechanism of tumors. The expression profile of exosomal RNA revealed that there were a total of 5547 differentially expressed mRNAs, and 196 differentially expressed lncRNAs. GO and KEGG enrichment analysis found that the differentially expressed mRNAs and lncRNA target genes were associated with metabolic processes, DNA replication, cell proliferation, cell junction, and cell adhesion. In conclusion, this study revealed lncRNA and mRNA expression profiles in exosomes derived from plasma of CMT and further annotated their potential functions. The data obtained in this study will also provide valuable resources for understanding lncRNA information in plasma exosomes of dogs with CMT, and contribute to the study of early diagnostic markers and pathogenesis of CMT.

Rapid quantification of the surface overflow and underground infiltration in sewer pipes based on computer vision and continuous optimization.

The overloading of the sewer network caused by unwarranted infiltration of stormwater may lead to waterlogging and environmental pollution. The accurate identification of infiltration and surface overflow is essential to predict and reduce these risks. To retrieve the limitations of infiltration estimation and the failure of surface overflow perception using the common stormwater management model (SWMM), a surface overflow and underground infiltration (SOUI) model is proposed to estimate the infiltration and overflow. First, the precipitation, water level of the manhole, surface water depth and images of the overflowing point, and volume at the outfall are collected. Then, the surface waterlogging area is identified based on computer vision to reconstruct the local digital elevation model (DEM) by spatial interpolation, and the relationship between the waterlogging depth, area and volume is established to identify the real-time overflow. Next, a continuous genetic algorithm optimization (CT-GA) model is proposed for the underground sewer system to determine the inflow rapidly. Finally, surface and underground flow estimations are combined to perceive the state of the urban sewer network accurately. The results show that, compared with the common SWMM simulation, the accuracy of the water level simulation is improved by 43.5% during the rainfall period, and the time cost of the computational optimization is reduced by 67.5%. The proposed method can effectively diagnose the operation state and overflow risk of the sewer networks in real time during rainfall seasons.

Rotational echo spectroscopy for accurate measurement of molecular alignment.

We measure the molecular alignment induced in gas using molecular rotational echo spectroscopy. Our results show that the echo intensity and the time interval between the local extremas of the echo responses depend sensitively on the pump intensities and the initial molecular rotational temperature, respectively. This allows us to accurately extract these experimental parameters from the echo signals and then further determine the molecular alignment in experiments. The accuracy of our method has been verified by comparing the simulation with the extracted parameters from the molecular alignment experiment performed with a femtosecond pump pulse.

Fingerprint of the Interbond Electron Hopping in Second-Order Harmonic Generation.

We experimentally explore the fingerprint of the microscopic electron dynamics in second-order harmonic generation (SHG). It is shown that the interbond electron hopping induces a novel source of nonlinear polarization and plays an important role even when the driving laser intensity is 2 orders of magnitude lower than the characteristic atomic field. Our model predicts anomalous anisotropic structures of the SHG yield contributed by the interbond electron hopping, which is identified in our experiments with ZnO crystals. Moreover, a generalized second-order susceptibility with an explicit form is proposed, which provides a unified description in both the weak and strong field regimes. Our work reveals the nonlinear responses of materials at the electron scale and extends the nonlinear optics to a previously unexplored regime, where the nonlinearity related to the interbond electron hopping becomes dominant. It paves the way for realizing controllable nonlinearity on an ultrafast time scale.

Reproducibility of Hybrid Density Functional Calculations for Equation-of-State Properties and Band Gaps.

Hybrid density functional (HDF) approximations usually deliver higher accuracy than local and semilocal approximations to the exchange-correlation functional, but this comes with drastically increased computational cost. Practical implementations of HDFs inevitably involve numerical approximations─even more so than their local and semilocal counterparts due to the additional numerical complexity arising from treating the exact-exchange component. This raises the question regarding the reproducibility of the HDF results yielded by different implementations. In this work, we benchmark the numerical precision of four independent implementations of the popular Heyd-Scuseria-Ernzerhof (HSE) range-separated HDF on describing key materials' properties, including both properties derived from equations of state (EOS) and band gaps of 20 crystalline solids. We find that the energy band gaps obtained by the four codes agree with each other rather satisfactorily. However, for lattice constants and bulk moduli, the deviations between the results computed by different codes are of the same order of magnitude as the deviations between the computational and experimental results. On the one hand, this means that the HSE functional is rather accurate for describing the cohesive properties of simple insulating solids. On the other hand, this also suggests that the numerical precision achieved with current major HSE implementations is not sufficiently high to unambiguously assess the physical accuracy of HDFs. It is found that the pseudopotential treatment of the core electrons is a major factor that contributes to this uncertainty.

DFT+U within the framework of linear combination of numerical atomic orbitals.

We present a formulation and implementation of the density functional theory (DFT)+U method within the framework of linear combination of numerical atomic orbitals (NAO). Our implementation not only enables single-point total energy and electronic-structure calculations but also provides access to atomic forces and cell stresses, hence allowing for full structure relaxations of periodic systems. Furthermore, our implementation allows one to deal with non-collinear spin texture, with the spin-orbit coupling (SOC) effect treated self-consistently. The key aspect behind our implementation is a suitable definition of the correlated subspace when multiple atomic orbitals with the same angular momentum are used, and this is addressed via the "Mulliken charge projector" constructed in terms of the first (most localized) atomic orbital within the d/f angular momentum channel. The important Hubbard U and Hund J parameters can be estimated from a screened Coulomb potential of the Yukawa type, with the screening parameter either chosen semi-empirically or determined from the Thomas-Fermi screening model. Benchmark calculations are performed for four late transition metal monoxide bulk systems, i.e., MnO, FeO, CoO, and NiO, and for the 5d-electron compounds IrO2. For the former type of systems, we check the performance of our DFT+U implementation for calculating bandgaps, magnetic moments, electronic band structures, as well as forces and stresses; for the latter, the efficacy of our DFT+U+SOC implementation is assessed. Systematic comparisons with available experimental results, especially with the results from other implementation schemes, are carried out, which demonstrate the validity of our NAO-based DFT+U formalism and implementation.

Multilevel quantum interference in the formation of high-order fractional molecular alignment echoes.

We theoretically investigate the formation of the high-order fractional alignment echo in OCS molecule and systematically study the dependence of echo intensity on the intensities and time delay of the two excitation pulses. Our simulations reveal an intricate dependence of the intensity of high-order fractional alignment echo on the laser conditions. Based on the analysis with rotational density matrix, this intricate dependence is further demonstrated to arise from the interference of multiple quantum pathways that involve multilevel rotational transitions. Our result provides a comprehensive multilevel picture of the quantum dynamics of high-order fractional alignment echo in molecular ensembles, which will facilitate the development of "rotational echo spectroscopy."

Dynamic Core Polarization in High Harmonic Generation from Solids: The Example of MgO Crystals.

Previously, the strong field processes in solids have always been explained by the single-active-electron (SAE) model with a frozen core excluding the fluctuation of background electrons. In this work, we demonstrate the strong field induced dynamic core polarization effect and propose a model for revealing its role in high harmonic generation (HHG) from solids. We show that the polarized core induces an additional polarization current beyond the SAE model based on the frozen cores. It gives a new mechanism for HHG and leads to new anisotropic structures, which are experimentally observed with MgO. Our experiments indicate that the influences of dynamic core polarization on HHG are obvious for both linearly and elliptically polarized laser fields. Our work establishes the bridge between the HHG and the dynamic changes of the effective many-electron interaction in solids, which paves the way to probe the ultrafast electron dynamics.

Rhophilin-associated tail protein 1 promotes migration and metastasis in triple negative breast cancer via activation of RhoA.

Triple negative breast cancer (TNBC) is the most aggressive breast cancer subtype with high motile and invasive capacity that contributes to metastasis. Understanding the mechanisms for the motility of TNBC might provide novel targetable vulnerabilities of the tumors. Herein, we find that Rhophilin-associated tail protein 1 (ROPN1) is selectively overexpressed in human TNBC cell lines and tissues. Overexpression of ROPN1 promotes, while silencing of ROPN1 inhibits the robust migration, invasion, and in vivo metastasis of TNBC cells. Moreover, we find that ROPN1 activates RhoA signaling via rhophilin-1 (RHPN1), leading to enhanced actin stress fibers formation in TNBC cells. RhoA signaling is demonstrated to be essential for ROPN1-mediated migration and metastasis of TNBC cells. Finally, we find that high levels of ROPN1 are significantly associated distant metastasis and predicted poor prognosis in patients with breast cancer. These findings reveal a novel mechanism for the high motility and metastasis of TNBC cells, suggesting that ROPN1 might be a potential prognostic marker and therapeutic target.

Beryllium and Magnesium Metal Clusters: New Globally Stable Structures and G0W0 Calculations.

We study the structural and electronic properties of beryllium (Be) and magnesium (Mg) clusters for sizes 2-20 using a two-step approach. In the first step, a global search of the stable and low-lying metastable isomer structures is carried out on the basis of first-principles potential energy surfaces at the level of the generalized gradient approximation (GGA) of density functional theory (DFT). In the second step, vertical ionization potentials (VIPs) and energy gaps between the highest occupied molecular orbital (HOMO) and lowest unoccupied molecular orbital (LUMO) are determined using the G0W0 methods for up to the fourth-lowest-energy isomers. Novel globally lowest-energy isomer structures are identified for Be14, Mg14, and Mg16 clusters. The van der Waals interactions are found to have a stronger influence on Mg clusters than on Be clusters. A second-difference analysis for both the binding energies and HOMO-LUMO gaps reveals a close relationship between the structural stability and chemical hardness for both types of clusters.

First-principles study of benzo[a]pyrene-7,8-dione and DNA adducts.

Polycyclic aromatic hydrocarbons (PAHs) are widely distributed in environments, and some of them are causative agents of human cancer. Previous studies concluded that benzo[a]pyrene-7,8-dione (BPQ), which is one kind of carcinogenic PAH metabolites, forms covalently bonded adducts with DNA, and the major adduct formed is a deoxyguanosine adduct. In this work, we investigate the interactions between BPQ and DNA molecules via first-principles calculations. We identify six possible DNA adducts with BPQ. In addition to the four adducts forming covalent bonds, there are two adducts bound purely by van der Waals (vdW) interactions. Remarkably, the two vdW-bound adducts have comparable, if not larger, binding energies as the covalent adducts. The results may help us gain more understanding of the interactions between PAH metabolites and DNA.

Optimizing the Void Size of Yolk-Shell Bi@Void@C Nanospheres for High-Power-Density Sodium-Ion Batteries.

Bismuth (Bi) has been demonstrated as a promising anode for Na-ion batteries (NIBs) because it has high gravimetry (386 mA h g-1) and volumetric capacity (3800 mA h cm-3). However, Bi suffers from large volume expansion during sodiation, leading to poor electrochemical performance. The construction of a nanostructure with sufficient void space to accommodate the volume change has been proven effective for achieving prolonged cycling stability. However the excessive void space will definitely decrease the volumetric energy density of the battery. Herein, we design optimized Bi@Void@C nanospheres (Bi@Void@C-2) with yolk-shell structure that exhibit the best cycling performance and enhanced volumetric energy density. The optimized void space not only could buffer the volume change of the Bi nanosphere but also could keep the high volumetric energy density of the battery. The Bi@Void@C-2 shows an excellent rate capacity of 173 mA h g-1 at ultrahigh current density of 100 A g-1 and long-cycle life (198 mA h g-1 at 20 A g-1 over 10 000 cycles). The origin of the superior performance is achieved through in-depth fundamental studies during battery operation using in situ X-ray diffraction (XRD) and in situ transmission electron microscope (TEM), complemented by theoretical calculations and ex situ TEM observation. Our rational design provides insights for anode materials with large volume variation, especially for conversion type and alloying type mechanism materials for batteries (i.e., Li-ion batteries, Na-ion batteries).

Measuring the rotational temperature and pump intensity in molecular alignment experiments via high harmonic generation.

We demonstrate a method to simultaneously measure the rotational temperature and pump intensity in laser-induced molecular alignment by the time-resolved high harmonic spectroscopy (HHS). It relies on the sensitive dependence of the arising times of the local minima and maxima of the harmonic yields at the rotational revivals on the pump intensity and rotational temperature. By measuring the arising times of these local extrema from the time-resolved harmonic signals, the rotational temperature and pump intensity can be accurately measured. We have demonstrated our method using N2 molecules. The validity and robustness of our method are tested with different harmonic orders and by changing the gas pressures as well as the distance between the gas exit and the optical axis. Moreover, we have also demonstrated the versatility of our method by applying it to CO2 molecules.

Determination of Electron Band Structure using Temporal Interferometry.

We propose an all-optical method to directly reconstruct the band structure of semiconductors. Our scheme is based on the temporal Young's interferometer realized by high harmonic generation with a few-cycle laser pulse. As a time-energy domain interferometer, temporal interference encodes the band structure into the fringe in the energy domain. The relation between the band structure and the emitted harmonic frequencies is established. This enables us to retrieve the band structure from the spectrum of high harmonic generation with a single-shot measurement. Our scheme paves the way to study matters under ambient conditions and to track the ultrafast modification of band structures.

Autocorrected preconditioning regularization inversion algorithm for an atmospheric turbulence profile.

Atmospheric turbulence profiles have great significance for adaptive optics, astronomical observations, laser propagation in atmospheres, and free space optical communications. The two-aperture differential scintillation method is a recent approach for analyzing remote-sensing atmospheric turbulence profiles that utilizes active beacons to make it suitable for different measurement situations. The relationship between differential scintillation and atmospheric turbulence profiles can be modeled using the Fredholm integral equation. To address this ill-posed integration problem, the discrete forward observation equation is first analyzed to obtain better integration intervals and measurement intervals needed for inversion. Then an autocorrected preconditioning conjugate gradient normal residual (PCGNR) algorithm is proposed to acquire atmospheric turbulence profiles. The algorithm contains a developed autocorrection strategy that incorporates incremental differences, adaptive thresholds, and weighted averages to correct for artefacts and marginal errors that arise from the PCGNR method. Compared with other regularized methods, the proposed autocorrected PCGNR method is more accurate and robust in the presence of noise.

All-optical measurement of high-order fractional molecular echoes by high-order harmonic generation.

An all-optical measurement of high-order fractional molecular echoes is demonstrated by using high-order harmonic generation (HHG). Excited by a pair of time-delayed short laser pulses, the signatures of full and high order fractional (1/2 and 1/3) alignment echoes are observed in the HHG signals measured from CO 2 molecules at various time delays of the probe pulse. By increasing the time delay of the pump pulses, much higher order fractional (1/4) alignment echo is also observed in N 2O molecules. With an analytic model based on the impulsive approximation, the spatiotemporal dynamics of the echo process are retrieved from the experiment. Compared to the typical molecular alignment revivals, high-order fractional molecular echoes are demonstrated to dephase more rapidly, which will open a new route towards the ultrashort-time measurement. The proposed HHG method paves an efficient way for accessing the high-order fractional echoes in molecules.

A DFT study of energetic and structural properties of a full turn of A-form DNA under relaxed and stretching conditions.

We carried out a first-principles quantum-mechanical study of a set of full-turn A-form DNA oligonucleotides using density functional approximations. The structural features of the fully relaxed model DNA molecules and more importantly, the energetic and structural changes of these molecules under stretching conditions are examined in detail. Special attention is paid to the dependence of the structural properties on the stacking sequences of the constituent DNA base pairs. It appears that DNA oligonucleotides are extremely flexible, and structural properties such as the diameter and the widths of the minor and major grooves change regularly as a function of the stretching rate (stretching length in percentage). Additionally, we found that the length of the hydrogen bonds in the DNA base pairs varies with the DNA stacking sequence. This work indicates that rich information and insights can be gained from first principles studies of model DNA molecules of only O(102-103) atoms.