Breaking the size limitation of nonadiabatic molecular dynamics in condensed matter systems with local descriptor machine learning.

Nonadiabatic molecular dynamics (NA-MD) is a powerful tool to model far-from-equilibrium processes, such as photochemical reactions and charge transport. NA-MD application to condensed phase has drawn tremendous attention recently for development of next-generation energy and optoelectronic materials. Studies of condensed matter allow one to employ efficient computational tools, such as density functional theory (DFT) and classical path approximation (CPA). Still, system size and simulation timescale are strongly limited by costly ab initio calculations of electronic energies, forces, and NA couplings. We resolve the limitations by developing a fully machine learning (ML) approach in which all the above properties are obtained using neural networks based on local descriptors. The ML models correlate the target properties for NA-MD, implemented with DFT and CPA, directly to the system structure. Trained on small systems, the neural networks are applied to large systems and long timescales, extending NA-MD capabilities by orders of magnitude. We demonstrate the approach with dependence of charge trapping and recombination on defect concentration in MoS2. Defects provide the main mechanism of charge losses, resulting in performance degradation. Charge trapping slows with decreasing defect concentration; however, recombination exhibits complex dependence, conditional on whether it occurs between free or trapped charges, and relative concentrations of carriers and defects. Delocalized shallow traps can become localized with increasing temperature, changing trapping and recombination behavior. Completely based on ML, the approach bridges the gap between theoretical models and realistic experimental conditions and enables NA-MD on thousand-atom systems and many nanoseconds.

Brain structural and functional signatures of multi-generational family history of suicidal behaviors in preadolescent children.

Parent-child transmission of suicidal behaviors has been extensively studied, but the investigation of a three-generation family suicide risk paradigm remains limited. In this study, we aimed to explore the behavioral and brain signatures of multi-generational family history of suicidal behaviors (FHoS) in preadolescents, utilizing a longitudinal design and the dataset from Adolescent Brain and Cognitive DevelopmentSM Study (ABCD Study®), which comprised 4 years of data and includes a total of 9,653 preadolescents. Our findings revealed that multi-generational FHoS was significantly associated with an increased risk of problematic behaviors and suicidal behaviors (suicide ideation and suicide attempt) in offspring. Interestingly, the problematic behaviors were further identified as a mediator in the multi-generational transmission of suicidal behaviors. Additionally, we observed alterations in brain structure within superior temporal gyrus (STG), precentral/postcentral cortex, posterior parietal cortex (PPC), cingulate cortex (CC), and planum temporale (PT), as well as disrupted functional connectivity of default mode network (DMN), ventral attention network (VAN), dorsal attention network (DAN), fronto-parietal network (FPN), and cingulo-opercular network (CON) among preadolescents with FHoS. These results provide compelling longitudinal evidence at the population level, highlighting the associations between multi-generational FHoS and maladaptive behavioral and neurodevelopmental outcomes in offspring. These findings underscore the need for early preventive measures aimed at mitigating the familial transmission of suicide risk and reducing the global burden of deaths among children and adolescents.

Genomic and transcriptomic characteristics of 12 novel primary cell lines derived from three patients with cholangiocarcinoma.

Cholangiocarcinoma (CCA) is an aggressive bile duct malignancy with poor prognosis. To improve our understanding of the biological characteristics of CCA and develop effective therapies, appropriate preclinical models are required. Here, we established and characterized 12 novel patient-derived primary cancer cell (PDPC) models using multi-region sampling. At the genomic level of PDPCs, we observed not only commonly mutated genes, such as TP53, JAK3, and KMT2C, consistent with the reports in CCA, but also specific mutation patterns in each cell line. In addition, specific expression patterns with distinct biological functions and pathways involved were also observed in the PDPCs at the transcriptomic level. Furthermore, the drug-sensitivity results revealed that the PDPCs exhibited different responses to the six commonly used compounds. Our findings indicate that the established PDPCs can serve as novel in vitro reliable models to provide a crucial molecular basis for improving the understanding of tumorigenesis and its treatment.

Identification of whole-genome mutations and structural variations of bile cell-free DNA in cholangiocarcinoma.

Bile cell-free DNA (cfDNA) has been reported as a promising liquid biopsy tool for cholangiocarcinoma (CCA), however, the whole-genome mutation landscape and structural variants (SVs) of bile cfDNA remains unknown. Here we performed whole-genome sequencing on bile cfDNA and analyzed the correlation between mutation characteristics of bile cfDNA and clinical prognosis. TP53 and KRAS were the most frequently mutated genes, and the RTK/RAS, homologous recombination (HR), and HIPPO were top three pathways containing most gene mutations. Ten overlapping putative driver genes were found in bile cfDNA and tumor tissue. SVs such as chromothripsis and kataegis were identified. Moreover, the hazard ratio of HR pathway mutations were 15.77 (95% CI: 1.571-158.4), patients with HR pathway mutations in bile cfDNA exhibited poorer overall survival (P = 0.0049). Our study suggests that bile cfDNA contains genome mutations and SVs, and HR pathway mutations in bile cfDNA can predict poor outcomes of CCA patients.

Epitope screening and vaccine molecule design of PRRSV GP3 and GP5 protein based on immunoinformatics.

Porcine reproductive and respiratory syndrome (PRRS) is a respiratory disease in pigs that causes severe economic losses. Currently, live PRRSV vaccines are commonly used but fail to prevent PRRS outbreaks and reinfection. Inactivated PRRSV vaccines have poor immunogenicity, making PRRSV a significant threat to swine health globally. Therefore, there is an urgent need to develop an effective PRRSV vaccine. This study used immunoinformatics to predict, screen, design and construct a candidate vaccine that fused B-cell epitopes, CTL- and HTL-dominant protective epitopes of PRRSV strain's GP3 and GP5 proteins. The study identified 12 B-cell epitopes, 6 CTL epitopes and 5 HTL epitopes of GP3 and GP5 proteins. The candidate vaccine was constructed with 50S ribosomal protein L7/L1 molecular adjuvant, which has antigenicity, solubility, stability, non-allergenicity and a high affinity for its target receptor, TLR-3. The C-ImmSim immunostimulation results showed significant increases in cellular and humoral responses (B cells and T cells) and production of TGF-ß, IL-2, IL-10, IFN-γ and IL-12. The constructed vaccine was stable and immunogenic, and it can effectively induce strong T-cell and B-cell immune responses against PRRSV. Therefore, it is a promising candidate vaccine for controlling and preventing PRRSV outbreaks.

MOF-Derived CoSe2 Nanoparticles/Carbonized Melamine Foam as Catalytic Cathode Enabling Flexible Li-CO2 Batteries with High Energy Efficiency and Stable Cycling.

Rechargeable aprotic Li-CO2 batteries have aroused worldwide interest owing to their environmentally friendly CO2 fixation ability and ultra-high specific energy density. However, its practical applications are impeded by the sluggish reaction kinetics and discharge product accumulation during cycling. Herein, a flexible composite electrode comprising CoSe2 nanoparticles embedded in 3D carbonized melamine foam (CoSe2/CMF) for Li-CO2 batteries is reported. The abundant CoSe2 clusters can not only facilitate CO2 reduction/evolution kinetics but also serve as Li2CO3 nucleation sites for homogeneous discharge product growth. The CoSe2/CMF-based Li-CO2 battery exhibits a large initial discharge capacity as high as 5.62 mAh cm-2 at 0.05 mA cm-2, a remarkably small voltage gap of 0.72 V, and an ultrahigh energy efficiency of 85.9% at 0.01 mA cm-2, surpassing most of the noble metal-based catalysts. Meanwhile, the battery demonstrates excellent cycling stability of 1620 h (162 cycles) at 0.02 mA cm-2 with an average overpotential of 0.98 V and energy efficiency of 85.4%. Theoretical investigations suggest that this outstanding performance is attributed to the suitable CO2/Li adsorption and low Li2CO3 decomposition energy. Moreover, flexible Li-CO2 pouch cell with CoSe2/CMF cathode displays stable power output under different bending deformations, showing promising potential in wearable electronic devices.

Multiregion WES of metastatic pancreatic neuroendocrine tumors revealed heterogeneity in genomic alterations, immune microenvironment and evolutionary patterns.

Pancreatic neuroendocrine tumors (PanNETs), though uncommon, have a high likelihood of spreading to other body parts. Previously, the genetic diversity and evolutionary patterns in metastatic PanNETs were not well understood. To investigate this, we performed multiregion sampling whole-exome sequencing (MRS-WES) on samples from 10 patients who had not received prior treatment for metastatic PanNETs. This included 29 primary tumor samples, 31 lymph node metastases, and 15 liver metastases. We used the MSK-MET dataset for survival analysis and validation of our findings. Our research indicates that mutations in the MEN1/DAXX genes might trigger the early stages of PanNET development. We categorized the patients based on the presence (MEN1/DAXXmut, n = 7) or absence (MEN1/DAXXwild, n = 3) of these mutations. Notable differences were observed between the two groups in terms of genetic alterations and clinically relevant mutations, confirmed using the MSK-MET dataset. Notably, patients with mutations in MEN1/DAXX/ATRX genes had a significantly longer median overall survival compared to those without these mutations (median not reached vs. 43.63 months, p = 0.047). Multiplex immunohistochemistry (mIHC) analysis showed a more prominent immunosuppressive environment in metastatic tumors, especially in patients with MEN1/DAXX mutations. These findings imply that MEN1/DAXX mutations lead PanNETs through a unique evolutionary path. The disease's progression pattern indicates that PanNETs can spread early, even before clinical detection, highlighting the importance of identifying biomarkers related to metastasis to guide personalized treatment strategies.

Adolescent anxiety and depression: perspectives of network analysis and longitudinal network analysis.

BACKGROUND: Anxiety and depression often co-occur, exhibiting high comorbidity, with their trends evolving over time. However, the specific pathways through which comorbid symptoms of anxiety and depression evolve and interact remain unclear. To investigate these questions, this study employed Network Analysis (NA) and Longitudinal Network Analysis (LNA) to explore the central symptoms of anxiety and depression, as well as the temporal evolution of these central symptoms. METHODS: The study focused on 606 high school students who were not in their final year in Shandong of China, with assessments conducted from March to September 2022. The bootnet package in R was used for establishing NA and LNA models, as well as for conducting accuracy analysis and node stability analysis. RESULTS: The results of the NA indicated that adolescent highly susceptible to anxiety and depression. And uncontrollable worry was a common central symptom, while irritability emerged as a central bridging symptom across all three NAs. The LNA results revealed that suicidal ideation and worthlessness were key central symptoms in the LNA. Furthermore, worthlessness played a pivotal role in the developmental pathway of "suicidal ideation → worthlessness → anxiety and uncontrollable worry." A reduction in suicidal ideation was associated with decreased severity in other symptoms. CONCLUSIONS: The findings suggest that adolescent anxiety and depression are in a state of vulnerability, and that irritability, worthlessness, and suicidal ideation are potential targets for interventions to address adolescent anxiety and depression.

Decoherence ensures convergence of non-adiabatic molecular dynamics with number of states.

Non-adiabatic (NA) molecular dynamics (MD) is a powerful approach for studying far-from-equilibrium quantum dynamics in photophysical and photochemical systems. Most NA-MD methods are developed and tested with few-state models, and their validity with complex systems involving many states is not well studied. By modeling intraband equilibration and interband recombination of charge carriers in MoS2, we investigate the convergence of three popular NA-MD algorithms, fewest switches surface hopping (FSSH), global flux surface hopping (GFSH), and decoherence induced surface hopping (DISH) with the number of states. Only the standard DISH algorithm converges with the number of states and produces Boltzmann equilibrium. Unitary propagation of the wave function in FSSH and GFSH violates the Boltzmann distribution, leads to internal inconsistency between time-dependent Schrödinger equation state populations and trajectory counts, and produces non-convergent results. Introducing decoherence in FSSH and GFSH by collapsing the wave function fixes these problems. The simplified version of DISH that omits projecting out the occupied state and is applicable to few-state systems also causes problems when the number of states is increased. We discuss the algorithmic application of wave function collapse and Boltzmann detailed balance and provide detailed FSSH, GFSH, and DISH flow charts. The use of convergent NA-MD methods is highly important for modeling complicated quantum processes involving multiple states. Our findings provide the basis for investigating quantum dynamics in realistic complex systems.

The origin of broadband blue emission in zero-dimensional organic lead iodine perovskites: A first-principles study.

Broadband blue emission in zero-dimensional perovskites has received considerable attention, which is very important for the realization of stable blue-light emitters; however, the underlying formation mechanism remains unclear. Based on first-principles calculations, we have systematically studied the self-trapped excitons (STEs) behavior and luminescence properties in 0D-(DMA)4PbI6 perovskite. Our calculations show that there is a significant difference between the intrinsic STE luminescence mechanism (∼2.51 eV) and experimental observations (∼2.70 eV). In contrast, we found that the iodine vacancy (VI) is energetically accessible and exhibits a shallow charge transition level at ∼2.69 eV (0/+1) above the valence band maximum, which provides the initial local well for the STEs formation. Moreover, the low electronic dimension synergistic Jahn-Teller distortion facilitates the formation of extrinsic excitons self-trapping. Further excited state electronic structure analysis and configuration coordinate diagram calculations confirmed that the broadband blue emission in 0D-(DMA)4PbI6 is the origin of VI-induced extrinsic STEs instead of intrinsic STEs. Therefore, our simulation results rationalize the experimental phenomena and provide important insights into the formation mechanism of STEs in low-dimensional perovskite systems.

Polystyrene microplastics induce pulmonary fibrosis by promoting alveolar epithelial cell ferroptosis through cGAS/STING signaling.

Polystyrene microplastics (PS-MPs) are new types of environmental pollutant that have garnered significant attention in recent years since they were found to cause damage to the human respiratory system when they are inhaled. The pulmonary fibrosis is one of the serious consequences of PS-MPs inhalation. However, the impact and underlying mechanisms of PS-MPs on pulmonary fibrosis are not clear. In this study, we studied the potential lung toxicity and PS-MPs-developed pulmonary fibrosis by long-term intranasal inhalation of PS-MPs. The results showed that after exposing to the PS-MPs, the lungs of model mouse had different levels of damage and fibrosis. Meanwhile, exposing to the PS-MPs resulted in a markedly decrease in glutathione (GSH), an increase in malondialdehyde (MDA), and iron overload in the lung tissue of mice and alveolar epithelial cells (AECs). These findings suggested the occurrence of PS-MP-induced ferroptosis. Inhibitor of ferroptosis (Fer-1) had alleviated the PS-MPs-induced ferroptosis. Mechanically, PS-MPs triggered cell ferroptosis and promoted the development of pulmonary fibrosis via activating the cGAS/STING signaling pathway. Inhibition of cGAS/STING with G150/H151 attenuated pulmonary fibrosis after PS-MPs exposure. Together, these data provided novel mechanistic insights of PS-MPs-induced pulmonary fibrosis and a potential therapeutic paradigm.

1G6-D7 Inhibits Homologous Recombination Repair by Targeting Extracellular HSP90α to Promote Apoptosis in Non-Small Cell Lung Cancer.

Despite recent advances in treatment, non-small cell lung cancer (NSCLC) continues to have a high mortality rate. Currently, NSCLC pathogenesis requires further investigation, and therapeutic drugs are still under development. Homologous recombination repair (HRR) repairs severe DNA double-strand breaks. Homologous recombination repair deficiency (HRD) occurs when HRR is impaired and causes irreparable double-strand DNA damage, leading to genomic instability and increasing the risk of cancer development. Poly(ADP-ribose) polymerase (PARP) inhibitors can effectively treat HRD-positive tumors. Extracellular heat shock protein 90α (eHSP90α) is highly expressed in hypoxic environments and inhibits apoptosis, thereby increasing cellular tolerance. Here, we investigated the relationship between eHSP90α and HRR in NSCLC. DNA damage models were established in NSCLC cell lines (A549 and H1299). The activation of DNA damage and HRR markers, apoptosis, proliferation, and migration were investigated. In vivo tumor models were established using BALB/c nude mice and A549 cells. We found that human recombinant HSP90α stimulation further activated HRR and reduced DNA damage extent; however, eHSP90α monoclonal antibody, 1G6-D7, effectively inhibited HRR. HRR inhibition and increased apoptosis were observed after LRP1 knockdown; this effect could not be reversed with hrHSP90α addition. The combined use of 1G6-D7 and olaparib caused significant apoptosis and HRR inhibition in vitro and demonstrated promising anti-tumor effects in vivo. Extracellular HSP90α may be involved in HRR in NSCLC through LRP1. The combined use of 1G6-D7 and PARP inhibitors may exert anti-tumor effects by inhibiting DNA repair and further inducing apoptosis of NSCLC cells.

Entangled X-Ray Photon Pair Generation by Free-Electron Lasers.

We investigate entangled x-ray photon pair emissions in a free-electron laser (FEL) and establish a quantum electrodynamical theory for coherently amplified entangled photon pair emission from microbunched electron pulses in the undulator. We provide a scheme to generate highly entangled x-ray photon pairs and numerically demonstrate the properties of entangled emission, which is of great importance in x-ray quantum optics. Our work shows a unique advantage of FELs in entangled x-ray photon pair generation.

From Molecular to Behavior: Higher Order Occipital Cortex in Major Depressive Disorder.

Medial prefrontal cortex (MPFC) and other regions like the occipital cortex (OC) exhibit abnormal neural activity in major depressive disorder (MDD). Their relationship to specific biochemical, psychophysical, and psychopathological changes remains unclear, though. For that purpose, we focus on a particular subregion in OC, namely middle temporal (MT) visual area that is known to mediate the perception of visual motion. Using high-field 7 T magnetic resonance imaging (MRI), including resting state functional MRI and proton magnetic resonance spectroscopy, the amplitude of low-frequency fluctuations (ALFF) of the blood oxygen level-dependent signal in MT, MT-seeded functional connectivity (FC), and gamma-aminobutyric acid (GABA) in MT were investigated. Applying the vision motion psychophysical task, the motion suppression index of subjects was also examined. We demonstrate significantly elevated neural variability (as measured by ALFF) in MT together with decreases in both MT GABA and motion suppression in our MDD sample. Unlike in healthy subjects, MT neural variability no longer modulates the relationship of MT GABA and motion suppression in MDD. MT also exhibits reduction in global inter-regional FC to MPFC in MDD. Finally, elevated MT ALFF relates to specifically retardation in behavior as measured by the Hamilton subscore. Together, MT provides a strong candidate for biomarker in MDD.

Calcium phytate reverses high glucose-inhibited osteogenesis of BMSCs via the MAPK/JNK pathway.

OBJECTIVES: Diabetes mellitus (DM) induces oxidative tissue impairment and suppresses bone formation. Some studies have shown that phytic acid has antioxidant and anti-diabetic properties. This study aimed to investigate the potential of calcium phytate (Ca-phytate) to reverse inhibited osteogenesis of human bone marrow mesenchymal stem cells (hBMSCs) in a high glucose (HG) environment and to determine the underlying mechanism. MATERIALS AND METHODS: hBMSCs were exposed to HG and palmitic acid to simulate DM in vitro. Osteogenic differentiation was measured using alkaline phosphatase staining and activity assay, alizarin red S staining, qRT-PCR, Western blot and immunofluorescence staining. A critical-size cranial defect model of type 2 diabetes mellitus (T2DM) rats was established to evaluate bone regeneration. A specific pathway inhibitor was used to explore whether the MAPK/JNK pathway was involved. RESULTS: Treatment with 34 µM Ca-phytate had the highest effect on osteogenic differentiation in HG. Ca-phytate improved cranial bone defect healing in T2DM rats. The long-term HG environment inhibited the activation of the MAPK/JNK signalling pathway, which was restored by Ca-phytate. Blocking the JNK pathway reduced the Ca-phytate-mediated osteogenic differentiation of hBMSCs. CONCLUSION: Ca-phytate induced bone regeneration in vivo and reversed HG-inhibited osteogenesis of hBMSCs in vitro via the MAPK/JNK signalling pathway.

Reduction of higher-order occipital GABA and impaired visual perception in acute major depressive disorder.

Major depressive disorder (MDD) is a complex state-dependent psychiatric illness for which biomarkers linking psychophysical, biochemical, and psychopathological changes remain yet elusive, though. Earlier studies demonstrate reduced GABA in lower-order occipital cortex in acute MDD leaving open its validity and significance for higher-order visual perception, though. The goal of our study is to fill that gap by combining psychophysical investigation of visual perception with measurement of GABA concentration in middle temporal visual area (hMT+) in acute depressed MDD. Psychophysically, we observe a highly specific deficit in visual surround motion suppression in a large sample of acute MDD subjects which, importantly, correlates with symptom severity. Both visual deficit and its relation to symptom severity are replicated in the smaller MDD sample that received MRS. Using high-field 7T proton Magnetic resonance spectroscopy (1H-MRS), acute MDD subjects exhibit decreased GABA concentration in visual MT+ which, unlike in healthy subjects, no longer correlates with their visual motion performance, i.e., impaired SI. In sum, our combined psychophysical-biochemical study demonstrates an important role of reduced occipital GABA for altered visual perception and psychopathological symptoms in acute MDD. Bridging the gap from the biochemical level of occipital GABA over visual-perceptual changes to psychopathological symptoms, our findings point to the importance of the occipital cortex in acute depressed MDD including its role as candidate biomarker.

RBF Neural Network Sliding Mode Control for Passification of Nonlinear Time-Varying Delay Systems with Application to Offshore Cranes.

This paper is devoted to studying the passivity-based sliding mode control for nonlinear systems and its application to dock cranes through an adaptive neural network approach, where the system suffers from time-varying delay, external disturbance and unknown nonlinearity. First, relying on the generalized Lagrange formula, the mathematical model for the crane system is established. Second, by virtue of an integral-type sliding surface function and the equivalent control theory, a sliding mode dynamic system can be obtained with a satisfactory dynamic property. Third, based on the RBF neural network approach, an adaptive control law is designed to ensure the finite-time existence of sliding motion in the face of unknown nonlinearity. Fourth, feasible easy-checking linear matrix inequality conditions are developed to analyze passification performance of the resulting sliding motion. Finally, a simulation study is provided to confirm the validity of the proposed method.

Carbon-Confined Indium Oxides for Efficient Carbon Dioxide Reduction in a Solid-State Electrolyte Flow Cell.

Developing robust electrocatalysts and advanced devices is important for electrochemical carbon dioxide (CO2 ) reduction toward the generation of valuable chemicals. We present herein a carbon-confined indium oxide electrocatalyst for stable and efficient CO2 reduction. The reductive corrosion of oxidative indium to the metallic state during electrolysis could be prevented by carbon protection, and the applied carbon layer also optimizes the reaction intermediate adsorption, which enables both high selectivity and activity for CO2 reduction. In a liquid-phase flow cell, the formate selectivity exceeds 90 % in a wide potential window from -0.8 V to -1.3 V vs. RHE. The continuous production of ca. 0.12 M pure formic acid solution is further demonstrated at a current density of 30 mA cm-2 in a solid-state electrolyte mediated reactor. This work provides significant concepts in the parallel development of electrocatalysts and devices for carbon-neutral technologies.

Sub-Rayleigh second-order correlation imaging using spatially distributive colored noise speckle patterns.

We present a novel method, to our knowledge, to synthesize non-trivial speckle patterns that can enable sub-Rayleigh second-order correlation imaging. The speckle patterns acquire a unique anti-correlation in the spatial intensity fluctuation by introducing the blue noise distribution on spatial Fourier power spectrum to the input light fields through amplitude modulation. Illuminating objects with the blue noise speckle patterns can lead to a sub-diffraction limit imaging system with a resolution more than three times higher than first-order imaging, which is comparable to the resolving power of ninth order correlation imaging with thermal light. Our method opens a new route towards non-trivial speckle pattern generation by tailoring amplitudes in spatial Fourier power spectrum of the input light fields and provides a versatile scheme for constructing sub-Rayleigh imaging and microscopy systems without invoking complicated higher-order correlations.

Copper(II)-Catalyzed Tandem Reaction: Synthesis of Furo[3,2-c]coumarin Derivatives and Evaluation for Photophysical Properties.

An efficient protocol for synthesizing furo[3,2-c]coumarin derivatives is described. The novel reaction could afford the desired furocoumarins with good to excellent yields in a mild and rapid manner. Large substrate scope screening and scale-up preparation have also been accomplished, and selected compounds were evaluated for their photophysical properties.