Lysine catabolism reprograms tumour immunity through histone crotonylation.

Cancer cells rewire metabolism to favour the generation of specialized metabolites that support tumour growth and reshape the tumour microenvironment1,2. Lysine functions as a biosynthetic molecule, energy source and antioxidant3-5, but little is known about its pathological role in cancer. Here we show that glioblastoma stem cells (GSCs) reprogram lysine catabolism through the upregulation of lysine transporter SLC7A2 and crotonyl-coenzyme A (crotonyl-CoA)-producing enzyme glutaryl-CoA dehydrogenase (GCDH) with downregulation of the crotonyl-CoA hydratase enoyl-CoA hydratase short chain 1 (ECHS1), leading to accumulation of intracellular crotonyl-CoA and histone H4 lysine crotonylation. A reduction in histone lysine crotonylation by either genetic manipulation or lysine restriction impaired tumour growth. In the nucleus, GCDH interacts with the crotonyltransferase CBP to promote histone lysine crotonylation. Loss of histone lysine crotonylation promotes immunogenic cytosolic double-stranded RNA (dsRNA) and dsDNA generation through enhanced H3K27ac, which stimulates the RNA sensor MDA5 and DNA sensor cyclic GMP-AMP synthase (cGAS) to boost type I interferon signalling, leading to compromised GSC tumorigenic potential and elevated CD8+ T cell infiltration. A lysine-restricted diet synergized with MYC inhibition or anti-PD-1 therapy to slow tumour growth. Collectively, GSCs co-opt lysine uptake and degradation to shunt the production of crotonyl-CoA, remodelling the chromatin landscape to evade interferon-induced intrinsic effects on GSC maintenance and extrinsic effects on immune response.

Research on Global Optimization Algorithm of Integrated Energy and Thermal Management for Plug-In Hybrid Electric Vehicles.

Power distribution and battery thermal management are important technologies for improving the energy efficiency of plug-in hybrid electric vehicles (PHEVs). In response to the global optimization of integrated energy thermal management strategy (IETMS) for PHEVs, a dynamic programming algorithm based on adaptive grid optimization (AGO-DP) is proposed in this paper to improve optimization performance by reducing the optimization range of SOC and battery temperature, and adaptively adjusting the grid distribution of state variables according to the actual feasible region. The simulation results indicate that through AGO-DP optimization, the reduction ratio of the state feasible region is more than 30% under different driving conditions. Meanwhile, the algorithm can obtain better global optimal driving costs more rapidly and accurately than traditional dynamic programming algorithms (DP). The computation time is reduced by 33.29-84.67%, and the accuracy of the global optimal solution is improved by 0.94-16.85% compared to DP. The optimal control of the engine and air conditioning system is also more efficient and reasonable. Furthermore, AGO-DP is applied to explore IETMS energy-saving potential for PHEVs. It is found that the IETMS energy-saving potential range is 3.68-23.74% under various driving conditions, which increases the energy-saving potential by 0.55-3.26% compared to just doing the energy management.

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.

Enhancement of the photocurrents injected in gapped graphene by the orthogonally polarized two-color laser field.

We theoretically investigate the photocurrents injected in gapped graphene by the orthogonally polarized two-color laser field. Depending on the relative phase, the photocurrents can be coherently controlled by deforming the electron trajectory in the reciprocal space. Under the same field strength, the peak photocurrent in the orthogonally polarized two-color field is about 20 times larger than that for linearly polarized light, and about 3.6 times for elliptically polarized light. The enhancement of the photocurrent can be attributed to an obvious asymmetric distribution of the real population in the reciprocal space, which is sensitive to the waveform of the laser field and related to the quantum interference between the electron trajectories. Our work provides a noncontact method to effectively enhance the injected current in graphene.

The interaction between lipocalin 2 and dipyridine ketone hydrazone dithiocarbamte may influence respective function in proliferation and metastasis-related gene expressions in HepG2 cell.

LCN2 (Lipocalins) was first identified as iron transporter through associating with its siderophores and also involved in many cancer metastases, but its function is still paradoxical. We questioned that whether LCN2 might also associate exogenous iron chelator as does in inherent way and the association may influence their respective function. To address this issue, we investigated the effect of LCN2 on action of DpdtC (2,2'-dipyridine ketone hydrazone dithiocarbamte), an iron chelator in proliferation and metastasis-related gene expression. The results showed that exogenous LCN2 and DpdtC could inhibit growth of HepG2 cells, while the combination treatment enhanced their inhibitory effect both in proliferation and colony formation. This encouraged us to investigate the effect of the interaction on metastasis-related gene expression. The results revealed that both LCN2 and DpdtC impaired the wound healing of HepG2, but the inhibitory effect of DpdtC was significantly enhanced upon association with LCN2. Undergoing epithelium-mesenchymal transition (EMT) is a crucial step for cancer metastasis, LCN2 and DpdtC had opposite effects on EMT markers, the binding of DpdtC to LCN2 significantly weakened the regulation of it (or its iron chelate) on EMT markers. To insight into the interaction between LCN2 and DpdtC-iron, fluorescence titration and molecular docking were performed to obtain the association constant (~ 104 M-1) and thermodynamic parameters (ΔG = - 26.10 kJ/mol). Importantly this study provided evidence that siderophores-loading state of LCN2 may influence its function, which be helpful for understanding the contradictory role of LCN2 in the metastasis of cancer.

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.

Activation of CO2 by Alkaline-Earth Metal Hydrides: Matrix Infrared Spectra and DFT Calculations of HM(O2CH) and (MH2)(HCOOH) Complexes (M = Sr, Ba).

Reactions of MH2 (M = Sr, Ba) with CO2 were explored in pure parahydrogen at 3.5 K using matrix isolation infrared spectroscopy and quantum chemical calculations. The formate complex HM(η2-O2CH) and formic acid complex (MH2)(HCOOH) were trapped and identified by isotopic substitutions and density functional theory (DFT) frequency calculations. Natural population analysis and the CO2 reduction mechanism demonstrate that hydride ion transfer from a metal hydride to a CO2 moiety facilitates the stabilization of such complexes.

M←NCCH3, M-η2-(NC)-CH3, and CN-M-CH3 Prepared by Reactions of Ce, Sm, Eu, and Lu Atoms with Acetonitrile: Matrix Infrared Spectra and Theoretical Calculations.

The reactions of laser-ablated Ce, Sm, Eu, and Lu atoms with acetonitrile were studied by matrix infrared spectra in a neon matrix, and M←NCCH3, M-η2-(NC)-CH3, and CN-M-CH3 were identified with isotopic substitution and quantum chemical calculations. The major product is the insertion complex (CN-M-CH3), while the end-on and side-on complexes (M←NCCH3 and M-η2-(NC)-CH3) are also trapped in the matrix. The CCN antisymmetric stretching mode for Ce-η2-(NC)-CH3 was observed at 1536.9 cm-1, which is much lower than the same modes observed for other lanthanides. NBO analysis reveals that Ce exhibits a remarkable 4f-orbital contribution in bonding to N and to C, reconfirming an active 4f-orbital contribution of cerium in bonding in the side-on complex, while the 4f contributions of Sm and Eu to the M-N and M-C bonds are much lower and the 4f orbital of Lu is not involved in bonding.

Metal Oxo-Fluoride Molecules OnMF2 (M = Mn and Fe; n = 1-4) and O2MnF: Matrix Infrared Spectra and Quantum Chemistry.

On reacting laser-ablated manganese or iron difluorides with O2 or O3 during codeposition in solid neon or argon, infrared absorptions of several new metal oxo-fluoride molecules, including OMF2, (η1-O2)MF2, (η2-O3)MF2, (η1-O2)2MF2 (M = Mn and Fe), and O2MnF, have been observed. Quantum chemical density functional and multiconfiguration wavefunction calculations have been applied to characterize these new products by their geometric and electronic structures, vibrations, charges, and bonding. The assignment of the main vibrational absorptions as dominant symmetric or antisymmetric M-F or M-O stretching modes is confirmed by oxygen isotopic shifts and quantum chemical calculations of frequencies and thermal stabilities. The tendency of Fe to form polyoxygen complexes in lower oxidation states than the preceding element Mn is affirmed experimentally and supported theoretically. The M-F stretching frequencies of the isolated metal oxo-fluorides may provide a scale for the local charge on the MF2 sites in active energy conversion systems. The study of these species provides insights for understanding the trend of oxidation state changes across the transition-metal series.

LINC00324 affects non-small cell lung cancer cell proliferation and invasion through regulation of the miR-139-5p/IGF1R axis.

Long non-coding RNAs (lncRNAs) are proved to perform critical function in regulating cancer cell behavior. It is reported that LINC00324 promotes lung adenocarcinoma development by regulating miR-615-5p/AKT1 axis. This study aimed to demonstrate whether LINC00324 participates in non-small cell lung cancer (NSCLC) pathogenesis through other molecular mechanism. Relative mRNA, lncRNA, and microRNA levels were analyzed using quantitative real-time-polymerase chain reaction (qRT-PCR). Western blot was used to detect protein level. MTT assay shown proliferation ability and transwell assay shown invasive ability. Luciferase reporter assay illustrated the interaction between RNA molecules. In NSCLC, the high expression of LINC00324 had correlation with the poor prognosis. LINC00324 promoted the proliferation and invasion of NSCLC cells while miR-139-5p inhibited these behaviors. LINC00324 overexpression promoted insulin-like growth factor 1 receptor (IGF1R) expression via absorbing miR-139-5p. The tumor-promoting effects of LINC00324 were attenuated through miR-139-5p overexpression. Highly expressed LINC00324 in NSCLC through sponged miR-139-5p to elevate IGF1R expression and promoted cell proliferation and invasion. This research demonstrated that LINC00324 is a potential NSCLC diagnosis and therapy target.

Channel-closing effects of electronic excitation in solids.

We investigate the electronic excitation of solids in strong fields by solving the time-dependent Schrödinger equation. The excitation probability exhibits a strong modulation as a function of laser intensity when the initial states fill in the whole valence band. To have a clear insight into the modulation, we further study the electronic excitation from a single eigenstate in solids. A series of resonance-like enhancements of excitation probability are produced by changing the laser intensity and wavelength. We attribute the resonance-like enhancements to the channel-closing effects in solids. It is shown that the excitation probability exhibits enhancements when the value of channel is odd for intracycle interference and an integer for intercycle interference. This is different from the atom that the enhancement occur in the integer channels. We also reveal that the channel-closing effects can be observed by solid high-order harmonic generation.

Reciprocal-Space-Trajectory Perspective on High-Harmonic Generation in Solids.

We revisit the mechanism of high-harmonic generation (HHG) from solids by comparing HHG in laser fields with different ellipticities but a constant maximum amplitude. It is shown that the cutoff of HHG is strongly extended in a circularly polarized field. Moreover, the harmonic yield with large ellipticity is comparable to or even higher than that in the linearly polarized field. To understand the underlying physics, we develop a reciprocal-space-trajectory method, which explains HHG in solids by a trajectory ensemble from different ionization times and different initial states in the reciprocal space. We show that the cutoff extension is related to an additional preacceleration step prior to ionization, which has been overlooked in solids. By analyzing the trajectories and the time-frequency spectrogram, we show that the HHG in solids cannot be interpreted in terms of the classical recollision picture alone. Instead, the radiation should be described by the electron-hole interband polarization, which leads to the unusual ellipticity dependence. We propose a new four-step model to understand the mechanism of HHG in solids.

Matrix infrared spectroscopy of F2BMF and FB[triple bond, length as m-dash]WF2 (M = Cr, Mo and W) complexes and quantum chemistry calculations.

Laser-ablated group 6 transition metal atoms react with BF3 to yield typical transition metal inserted complexes F2B-MF (M = Cr, Mo, and W) and terminal borylene complex FB[triple bond, length as m-dash]WF2. These products are investigated by using infrared spectroscopy, isotopic substitution and theoretical frequency calculations. The inserted complexes F2B-MF (M = Cr, Mo, and W) were identified by antisymmetric and symmetric stretching modes of F-B-F. The FB[triple bond, length as m-dash]WF2 molecule has a 11B-F (10B-F) stretching frequency at 1453.2 (1505.0) cm-1 and the triple bond between boron and tungsten is confirmed by EDA-NOCV calculations, CASSCF calculation and NBO analysis. Furthermore, the bonding for tungsten complexes is compared with that of molybdenum and chromium complexes, which reveals interesting differences in their chemistries.

H2MBH2 and M(µ-H)2BH2 Molecules Isolated in Solid Argon: Interelement M-B and M-H-B Bonds (M = Ge, Sn).

Laser-ablated boron atoms react with GeH4 molecules to form novel germylidene borane H2GeBH2, which undergoes a photochemical rearrangement to the germanium tetrahydroborate Ge(µ-H)2BH2 upon irradiation with light of λ = 405 nm. For comparison, the boron atom reactions with SnH4 only gave the tin tetrahydroborate Sn(µ-H)2BH2. Infrared matrix-isolation spectroscopy with deuterium substitution and the state-of-the-art quantum-chemical calculations are used to identify these species in solid argon. A planar structure of H2GeBH2 with an electron-deficient B-Ge bond with a partial multiple bond character (bond order = 1.5) is predicted by quantum-chemical calculations. In the case of M(µ-H)2BH2 (M = Ge, Sn) two 3c-2e B-H-M hydrogen bridged bonds are formed by donation of electrons from the B-H σ-bonds into empty p-orbitals of M.

M-S Multiple Bond in HMSH, H2MS, and HMS Molecules (M = B, Al, Ga): Matrix Infrared Spectra and Theoretical Calculations.

Reaction products of B, Al, and Ga atoms with H2S have been identified in solid argon using matrix isolation infrared absorption spectroscopy. The results show that the ground state B atom reaction with H2S gives the H2BS molecule while for the Al atom the HAlSH molecule forms first, which then further isomerizes to H2AlS upon >500 nm irradiation. The reaction of the Ga atom with H2S only takes place upon photolysis to produce HGaSH in the matrix. The assignments of the major modes for these products were confirmed by appropriate 10B, 11B, D2S, and H234S isotopic shifts and theoretical frequency calculations. Topological analysis of the electron density suggests that both HBSH and H2BS molecules possess covalent B-S bond with significant double bond character, while the M-S bond in the heavier group 13 homologues (Al, Ga) was characterized as a polar covalent strong interaction.

Matrix Infrared Spectra and Theoretical Calculations of Fluoroboryl Complexes F2B-MF (M = C, Si, Ge, Sn and Pb).

The reactions of laser-ablated C, Si, Ge, Sn, and Pb atoms with BF3 have been studied using matrix isolation Fourier transform infrared (FTIR) spectroscopy and density functional theoretical (DFT) calculations. All atoms generate the inserted complex F2B-MF, which were trapped in inert gas and identified by the isotopic substitutions and DFT frequency calculations. DFT and CCSD(T) calculations show that triplet F2B-CF is the most stable isomer with two singly occupied molecular orbitals, while singlet F2B-MF (M= Si, Ge, Sn and Pb) molecules possess a near right angle B-M-F moiety with lone pair electrons on the M atom. The bonding difference between C and other group 14 atoms is mainly caused by relativistic effect, which is that, for heavier metal atom valences, s and p orbitals have a lower tendency to form hybrid orbitals.

OMS, OM(η2-SO), and OM(η2-SO)(η2-O2S) Molecules (M = Ce, Th) with Chiral Structure: Matrix Infrared Spectra and Theoretical Calculations.

Infrared absorptions of the matrix isolated OMS, OM(η2-SO), and OM(η2-SO)(η2-O2S) (M = Ce, Th) molecules were observed following reactions of laser-ablated Ce and Th metal atoms with SO2 during condensation in excess argon and neon. Band assignments for the main vibrational modes were confirmed by appropriate 34SO2 and S18O2 isotopic shifts. B3LYP, BPW91 density functional, and CASSCF/CASPT2 calculations were performed to characterize these new reaction products and to explore the admixture of f orbitals into the bonding giving stronger M≡O triple bonds. It is very interesting that both OM(η2-SO) and OM(η2-SO)(η2-O2S) molecules show chiral structure.

Electronic Systems Diagnosis Fault in Gasoline Engines Based on Multi-Information Fusion.

The rapid development of electronic techniques in automobile has led to an increase of potential safety hazards, thus, a strong on-board diagnostic (OBD) system is desperately needed. To solve the problem of OBD insensitivity to manufacture errors or aging faults, the paper proposes a novel multi information fusion method. The diagnostic model is composed of a data fusion layer, feature fusion layer, and decision fusion layer. They are based on the back propagation (BP) neural network, support vector machine (SVM), and evidence theory, respectively. Algorithms are mainly focused on the reliability allocation of diagnostic results, which come from the data fusion layer and feature fusion layer. A fault simulator system was developed to simulate bias and drift faults of the intake pressure sensor. The real vehicle experiment was carried out to acquire data that are used to verify the availability of the method. Diagnostic results show that the multi-information fusion method improves diagnostic accuracy and reliability effectively. The study will be a promising approach for the diagnosis bias and drift fault of sensors in electronic control systems.

Palmitic Acid Curcumin Ester Facilitates Protection of Neuroblastoma against Oligomeric Aß40 Insult.

BACKGROUND/AIMS: The generation of reactive oxygen species (ROS) caused by amyloid-ß (Aß) is considered to be one of mechanisms underlying the development of Alzheimer's disease. Curcumin can attenuate Aß-induced neurotoxicity through ROS scavenging, but the protective effect of intracellular curcumin on neurocyte membranes against extracellular Aß may be compromised. To address this issue, we synthesized a palmitic acid curcumin ester (P-curcumin) which can be cultivated on the cell membrane and investigated the neuroprotective effect of P-curcumin and its interaction with Aß. METHODS: P-curcumin was prepared through chemical synthesis. Its structure was determined via nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). An MTT assay was used to assess Aß cytotoxicity and the protective effect of P-curcumin on SH-SY5Y cells. The effect of P-curcumin on Aß-induced ROS production in vitro and in vivo were assessed based on changes in dichlorofluorescein (DCF) fluorescence. A spectrophotometric method was employed to detect lipid peroxidation. To mimic the interaction of P-curcumin on cell membranes with Aß, liposomes were prepared by thin film method. Finally, the interactions between free P-curcumin and P-curcumin cultivated on liposomes and Aß were determined via spectrophotometry. RESULTS: A novel derivative, palmitic acid curcumin ester was prepared and characterized. This curcumin, cultivated on the membranes of neurocytes, may prevent Aß-mediated ROS production and may inhibit the direct interaction between Aß and the cellular membrane. Furthermore, P-curcumin could scavenge Aß-mediated ROS as curcumin in vitro and in vivo, and had the potential to prevent lipid peroxidation. Morphological analyses showed that P-curcumin was better than curcumin at protecting cell shape. To examine P-curcumin's ability to attenuate direct interaction between Aß and cell membranes, the binding affinity of Aß to curcumin and P-curcumin was determined. The association constants for free P-curcumin and curcumin were 7.66 × 104 M-1 and 7.61 × 105 M-1, respectively. In the liposome-trapped state, the association constants were 3.71 × 105 M-1 for P-curcumin and 1.44× 106 M-1 for curcumin. With this data, the thermodynamic constants of P-curcumin association with soluble Aß (ΔH, ΔS, and ΔG) were also determined. CONCLUSION: Cultivated curcumin weakened the direct interaction between Aß and cell membranes and showed greater neuroprotective effects against Aß insult than free curcumin.

Double and Triple Si-H-M Bridge Bonds: Matrix Infrared Spectra and Theoretical Calculations for Reaction Products of Silane with Ti, Zr, and Hf Atoms.

Infrared spectra of matrix isolated dibridged Si(µ-H)2MH2 and tribridged Si(µ-H)3MH molecules (M = Zr and Hf) were observed following the laser-ablated metal atom reactions with SiH4 during condensation in excess argon and neon, but only the latter species was observed with titanium. Assignments of the major vibrational modes, which included terminal MH, MH2 and hydrogen bridge Si-H-M stretching modes, were confirmed by the appropriate SiD4 isotopic shifts and density functional vibrational frequency calculations (B3LYP and BPW91). The Si-H-M hydrogen bridge bond is calculated as weak covalent interaction and compared with the C-H···M agostic interaction in terms of electron localization function (ELF) analysis and noncovalent interaction index (NCI) calculations. Furthermore, the different products of Ti, Zr, and Hf reactions with SiH4 are discussed in detail.