Characterization of polyamine metabolism predicts prognosis, immune profile, and therapeutic efficacy in lung adenocarcinoma patients.

Background: Polyamine modification patterns in lung adenocarcinoma (LUAD) and their impact on prognosis, immune infiltration, and anti-tumor efficacy have not been systematically explored. Methods: Patients from The Cancer Genome Atlas (TCGA) were classified into subtypes according to polyamine metabolism-related genes using the consensus clustering method, and the survival outcomes and immune profile were compared. Meanwhile, the geneCluster was constructed according to the differentially expressed genes (DEGs) of the subtypes. Subsequently, the polyamine metabolism-related score (PMRS) system was established using the least absolute shrinkage and selection operator (LASSO) multivariate regression analysis in the TCGA training cohort (n = 245), which can be applied to characterize the prognosis. To verify the predictive performance of the PMRS, the internal cohort (n = 245) and the external cohort (n = 244) were recruited. The relationship between the PMRS and immune infiltration and antitumor responses was investigated. Results: Two distinct patterns (C1 and C2) were identified, in which the C1 subtype presented an adverse prognosis, high CD8+ T cell infiltration, tumor mutational burden (TMB), immune checkpoint, and low tumor immune dysfunction and exclusion (TIDE). Furthermore, two geneClusters were established, and similar findings were observed. The PMRS, including three genes (SMS, SMOX, and PSMC6), was then constructed to characterize the polyamine metabolic patterns, and the patients were divided into high- and low-PMRS groups. As confirmed by the validation cohort, the high-PMRS group possessed a poor prognosis. Moreover, external samples and immunohistochemistry confirmed that the three genes were highly expressed in tumor samples. Finally, immunotherapy and chemotherapy may be beneficial to the high-PMRS group based on the immunotherapy cohorts and low half-maximal inhibitory concentration (IC50) values. Conclusion: We identified distinct polyamine modification patterns and established a PMRS to provide new insights into the mechanism of polyamine action and improve the current anti-tumor strategy of LUAD.

Ultrafast vibrational energy redistribution in cyclotrimethylene trinitramine (RDX).

The microscopic mechanism of the energy transfer in cyclotrimethylene trinitramine (RDX) is of particular importance for the study of the energy release process in high-energy materials. In this work, an effective vibrational Hamiltonian based on normal modes (NMs) has been introduced to study the energy transfer process of RDX. The results suggest that the energy redistribution in RDX can be characterized as an ultrafast process with a time scale of 25 fs, during which the energy can be rapidly localized to the -NNO2 twisting mode (vNNO2), the N-N stretching mode (vN-N), and the C-H stretching mode (vC-H). Here, the vNNO2 and vN-N modes are directly related to the cleavage and dissociation of the N-N bond in RDX and, therefore, can be referred to as "active modes." More importantly, we found that the energy can be rapidly transferred from the vC-H mode to the vNNO2 mode due to their strong coupling. From this perspective, the vC-H mode can be regarded as an "energy collector" that plays a pivotal role in supplying energy to the "active modes." In addition, the bond order analysis shows that the dissociation of the N-N bonds of RDX follows a combined twisting and stretching path along the N-N bond. This could be an illustration of the further exothermic decomposition triggered by the accumulation of vibrational energy. The present study reveals the microscopic mechanism for the vibrational energy redistribution process of RDX, which is important for further investigation of the energy transfer process in high-energy materials.

Discriminative Mechanical and Thermal Response of the H-N Bonds for the Energetic LLM-105 Molecular Assembly.

Molecular interactions in energetic materials form the key not only to the "structure stability, energy storage, ignition, and detonation" dynamics but also to the sensitivity to the loading of perturbation and the power intensity of radiation for the energetic substance, with the nature of the interactions remaining elusive. With the aid of perturbative Raman spectroscopy and the pressure-resolved density functional theory, we uncovered that the H-N bond of the intermolecular O:H-N bonds for LLM-105 shares the same negative compressibility and thermal expansivity of the H-O bond for the coupling O:H-O bond of water [Phys. Rep. 2023, 998, 1-68]. In contrast, the dangling H-N bond vibrating at a 3440 cm-1 high frequency does otherwise due to the absence of coupling interaction and the undercoordination-driven bond contraction. These findings should deepen our insight into interactions involving electron lone pairs and offer an efficient means for discriminating the performance of individual bonds.

Low frequency lattice mode dynamics of cyclotrimethylene trinitramine (RDX) crystal studied by femtosecond time-resolved impulsive stimulated Raman scattering.

The femtosecond time-resolved impulsive stimulated Raman scattering (fs-ISRS) has been performed to study the low frequency lattice mode dynamics of the RDX crystal. Through Fourier filtering, four lattice mode dynamics is distinguished from the time-resolved spectrum. And the wavenumbers and time constants of these four lattice modes are determined by fitting their dynamic curves. The energy dispersion paths of these four lattice modes are deduced from these fitting parameters. Compared with the other three lattice modes, the lattice mode with wavenumber 30 cm-1 has a very longer life time. We consider that the excitation of this lattice mode more likely to cause the damage of the intermolecular interaction under the strong external stimulation.

Femtosecond coherent anti-Stokes Raman spectroscopy study of vibrational dynamics of liquid chloroform.

Femtosecond time-resolved coherent anti-Stokes Raman spectroscopy (CARS) was used to study the dynamics of the vibrational modes of liquid chloroform. The vibrational modes were selectively excited and their coherent vibrational dynamics were obtained. Some subtle features that are difficult to distinguish in the ordinary spontaneous Raman spectrum, such as overtones and combinations of some fundamental vibrational modes, were recognized from the CARS transients. Combined with theoretical calculations, the contributions of chlorine isotopes were also confirmed from the CARS transients of the vibrational modes involving the motion of chlorine atoms.

Solution structures and ultrafast vibrational energy dissipation dynamics in cyclotetramethylene tetranitramine.

Steady-state and time-resolved infrared (IR) studies of cyclotetramethylene tetranitramine (HMX) were carried out, using the asymmetric nitro-stretch as probe, to investigate its solution structures and vibrational energy transfer processes in pure dimethyl sulfoxide (DMSO) and in a DMSO/water mixture. A linear IR spectrum in the nitro-stretching mode region shows two major bands and one minor band in DMSO but changes to the two major bands mainly picture when adding water as an antisolvent of HMX, suggesting a transition from well-solvated and less perfect ß-conformation to a less-solvated and close-to-perfect ß-conformation. The latter bears a similar asymmetric nitro-stretch vibration profile to the ß-polymorph in the crystal form. Density functional theory computations of the nitro-stretching vibrations suggest that HMX in DMSO may be in a NO2 group rotated ß-conformation. Two-dimensional IR cross-peak intensity reveals intramolecular energy transfer between the axial and equatorial nitro-groups in the ß-HMX on the ps time scale, which is slightly faster in the mixed solvent case. The importance of water as an antisolvent in influencing the equilibrium solvation structure, as well as the vibrational and orientational relaxation dynamics of HMX, is discussed.

The geometrical analysis of localization error characteristic in stereo vision systems.

The parameters of a stereo camera directly determine the accuracy of a stereo vision positioning system. In this paper, the relationship between camera parameter error and positioning error is established by using the geometric analysis method with a clear physical meaning. The error models of the relative position error and camera resolution error of the stereo camera are established. The relative position error of the stereo camera is represented by the rotation and translation of the coordinate system, and the positioning error is derived from image coordinates through the pinhole camera model. For the camera resolution error, the two pixels of the stereo camera are projected into an octahedral uncertain region in space. We use geometric methods to derive the maximum size of the octahedron in the three-axis direction. The maximum size in the three-axis direction is used to evaluate the impact of camera resolution errors. The depth of field and angle of view are used to represent the measured area. The effects of resolution error and camera parameters on the measurement error of each axis are analyzed. Finally, a large number of simulations verified our conclusion. By comparing the effects of the magnitude of the error, we can conclude that the baseline and pixel size of the camera have a greater impact on the positioning accuracy.

Vibrational energy redistribution in crystalline nitromethane simulated by ab initio molecular dynamics.

Ab initio molecular dynamics simulations (AIMD) are systematically performed to study the Vibrational Energy Redistribution (VER) in solid nitromethane (NM) by combining normal mode decomposition and short-time Fourier transform technique. After the selective excitations of all fourteen intramolecular vibrational modes above 400 cm-1, four three-dimensional (3D) excitation and detected vibrational spectra are obtained. The evolution of the kinetic energy proportion of all vibrations are also given and discussed quantitatively. These results show that, as the daughter modes, NO2 symmetric stretches, CH3 stretches and bends are usually excited quickly and relatively conspicuously compared with the other vibrations. Interestingly, we found that, although the stretching vibration of the CN bond which is a bridge between the methyl and nitro group can not respond immediately to the selective excitations, it always accumulates the vibrational energy slowly and steadily. Then, the underlying mechanisms are discussed based on the response of vibrational modes in both the time and frequency domain. As a result, we found that anharmonic transfers following symmetry rules which involve the couplings assisted by the overtones and rotations, as well as the transfers among the adjacent modes, play important roles in the VER of solid NM.

Elucidating the Coupling Mechanisms of Rapid Intramolecular Vibrational Energy Redistribution in Nitromethane: Ab Initio Molecular Dynamics Simulation.

Ab initio molecular dynamics simulations are presented to investigate the intramolecular vibrational energy redistribution (IVR) of an isolated nitromethane molecule. A number of IVR processes are simulated by monitoring the kinetic energy of vibrational modes under selective low-lying vibrational excitations from their ground states (Δν = 1 or 2). Evolution of the normal-mode kinetic energy gives the ultrafast energy transfer processes from parent modes to daughter modes intuitively. From the ultrafast vibrational transfer made by Fourier transformation of the time-dependent normal-mode kinetic energy, we can capture that the symmetry of the normal modes plays an important role in the anharmonic coupling between the vibrational modes. The results show three symmetry-dependent coupling mechanisms: direct symmetric coupling, overtone-assisted coupling, and rotation-assisted coupling. Furthermore, the calculated efficiencies of IVR also coincide with these mechanisms.

Thermochemistry and Initial Decomposition Pathways of Triazole Energetic Materials.

A thorough investigation of the initial decomposition pathways of triazoles and their nitro-substituted derivatives has been conducted using the MP2 method for optimization and DLPNO-CCSD(T) method for energy. Different initial thermolysis mechanisms are proposed for 1,2,4-triazole and 1,2,3-triazole, the two kinds of triazoles. The higher energy barrier of the primary decomposition path of 1,2,4-triazole (H-transfer path, ∼52 kcal/mol) compared with that of 1,2,3-triazole (ring-open path, ∼45 kcal/mol) shows that 1,2,4-triazole is more stable, consistent with experimental observations. For nitro-substituted triazoles, more dissociation channels associated with the nitro group have been obtained and found to be competitive with the primary decomposition paths of the triazole skeleton in some cases. Besides, the effect of the nitro group on the decomposition pattern of the triazole skeleton has been explored, and it has been found that the electron-withdrawing nitro group has an opposite effect on the primary dissociation channels of 1,2,4-triazole derivatives and 1,2,3-triazole derivatives.

Ab initio molecular dynamics simulation of vibrational energy redistribution of selective excitation of C-H stretching vibrations for solid nitromethane.

Vibrational energy redistribution (VER) of energetic materials plays an important role in transferring the injected energy to the hot spots, but it is extremely challenging to understand the mechanism of VER from experimental or theoretical studies. Here, we combined nonequilibrium molecular dynamics with density functional theory to study the processes of VER for solid nitromethane after the selective excitation of the C-H stretching vibration. The VER processes are traced by monitoring the normal-mode kinetic energies of both excited and unexcited vibrations. To explore the underlying VER mechanism, we also analyzed the spectral energy density for the normal mode, obtained from the squared modulus of the short-time Fourier transition of their normal mode momentum. The results showed that the simulated VER progress was reproduced well compared with the previous 3D IR-Raman experiments of liquid nitromethane. Interestingly, the symmetric dependence of the coupling mechanism between the normal modes has been found.

Development of a deep eutectic solvent-based matrix solid phase dispersion methodology for the determination of aflatoxins in crops.

A novel and sensitive deep eutectic solvent-based matrix solid phase dispersion (DES-MSPD) method for the determination of aflatoxins (AFB1, AFB2, AFG1, AFG2) in various crops was established using high-performance liquid chromatography with fluorescence detection (HPLC-FLD). The DES-MSPD sample preparation procedure was optimized. Based on the optimal conditions, the intra-day and inter-day variability for AFs in all crop samples was less than 7.5%. Linearity was observed with R2 values (>0.994). Using the present method, HPLC-FLD gave the limits of detection (LODs) of 0.03-0.10 µg/kg and the limits of quantification (LOQs) of 0.10-0.33 µg/kg for AFs. This work represents the first attempt of using DESs as a green extraction medium for the extraction of AFs in MSPD. Compared with conventional MSPD methods, the DES-MSPD procedure looks promising as a relatively simple and low cost process to build an assay that can be used for monitoring concentrations of AFs in crops.

New perspective on the fluorescence and sensing mechanism of TNP chemosensor 2-(4,5-bis(4-chlorophenyl)-1H-imidazol-2-yl)-4-chlorolphenol.

For TNP chemosensor 2-(4,5-Bis(4-Chlorophenyl)-1H-Imidazol-2-yl)-4-Chlorolphenol (HPICI), previous thought with no theoretical basis was that excited-state intramolecular proton transfer (ESIPT) process and the ground-state HPICI-TNP complex are mainly responsible for its fluorescence emission and the detection of TNP. However, this interpretation has been proved to be wrong by the present theoretical DFT/TDDFT explorations. Actually, the strong fluorescence of HPICI is mainly induced by the local excitation of the enol form HPICI(E) without ESIPT, and the fluorescence quenching by TNP is due to the photo-induced electron transfer (PET) process together with the cooperative effect of hydrogen-bonding interaction and π-π stacking interaction coexisting in the HPICI-TNP complex. The strengthened excited-state hydrogen bond promotes the PET process, thus facilitates the fluorescence quenching. This mechanism is proposed on the basis of the theoretical analyses on molecule geometry, binding energy, Gibbs free energy, electronic transitions, and frontier molecular orbitals (FMOs).

Role of electron in intramolecular vibrational energy redistribution: a simulation of time- and frequency-resolved CARS spectrum.

A coupled oscillator model with special attention to the electron is employed to simulate the time- and frequency-resolved coherent anti-Stokes Raman scattering (TFR-CARS) spectrum of benzene, where the electronic contribution is introduced as an oscillator as well as molecular vibration, and both the coupling between molecular vibrations and the coupling between electron and molecular vibration are involved. Through the simulation, the intramolecular vibrational energy redistribution (IVR) process is confirmed to occur more readily between the molecular vibrations with the same vibrational symmetry. Moreover, it is found that the electron plays a mediator role in the IVR process, and the coupling between electron and molecular vibration significantly increases the intramolecular vibrational energy transfer efficiency.

Predicting the Initial Thermal Decomposition Path of Nitrobenzene Caused by Mode Vibration at Moderate-Low Temperatures: Temperature-Dependent Anti-Stokes Raman Spectra Experiments and First-Principals Calculations.

The lack of understanding of the initial decomposition micromechanism of energetic materials subjected to external stimulation has hindered its safe storage, usage, and development. The initial thermal decomposition path of nitrobenzene triggered by molecular thermal motion is investigated using temperature-dependent anti-Stokes Raman spectra experiments and first-principles calculations to clarify the initial thermal decomposition micromechanism. The experiment shows that the symmetric nitro stretching, antisymmetric nitro stretching, and phenyl ring stretching vibration modes are active as increasing temperature below 500 K. The DFT method is used to examine the effects of the three mode vibrations on the initial decomposition of nitrobenzene by relaxed scan for each relevant change in bond lengths and bond angles to obtain the optimal reaction channel leading to initial thermal decomposition of nitrobenzene. The results demonstrate that the initial thermal decomposition is the isomerization of nitrobenzene to phenyl nitrite. The optimal reaction channel leading to the initial isomerization is the increase or decrease of angle O-N-C from the antisymmetric nitro stretching vibration, which causes the torsion of nitro group and the subsequent oxygen atom attacking carbon atom. The scanning energy barrier related to angle O-N-C is about 62.1 kcal/mol, which is very consistent with the calculated activation barrier of isomerization of nitrobenzene. This proves the reliability of our conclusions.

Resonance Rayleigh scattering assay for EGFR using antibody immobilized gold nanoparticles.

A highly selectivity determination of epidermal growth factor receptor (EGFR) has been described in the article. Antibody immobilized cysteamine (Cys) functionalized gold nanoparticles (AuNP) were proposed as immunosensors, and resonance Rayleigh scattering (RRS) was used for detection. First, Cys stabilized AuNPs (Cys-AuNP) were prepared by the reduction of chloroauric acid with sodium borohydride in the presence of Cys. Further, anti-EGFR antibody (Cetuximab, C225) was covalently linked to the Cys-AuNP by carbodiimide-mediated amidation protocol to yield the C225-AuNP immunoprobe. The prepared conjugations were characterized by ultraviolet-visible (UV-vis) spectroscopy, transmission electron microscopy (TEM), Fourier transform infrared (FT-IR) and sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE). Based on the specific binding of C225 to EGFR, an RRS method was established to determine the concentration of EGFR. Under the optimal conditions, the concentration of EGFR was related to the intensity of RRS in the range 30-130 ng ml-1 with a low detection limit of 4.0 ng ml-1 . Meanwhile, the proposed immunosensor exhibited excellent selectivity and anti-interference property. The method was applied to the determination of EGFR in human serum and cancer cell lysate samples with satisfactory results.

New insights into the sensing mechanism of a phosphonate pyrene chemosensor for TNT.

As security needs have increased, mechanism investigation has become of high importance in the development of new sensitive and selective chemosensors for chemical explosives. This study details a theoretical investigation of the sensing mechanism of a new phosphonate pyrene chemosensor for trinitrotoluene (TNT), suggesting a different interaction mode between the probe and TNT from the one previously reported. The invalidity of the mechanism of binding TNT through intermolecular hydrogen bonds was proved using the Gibbs free energy profile and 1H NMR analysis. Frontier molecular orbitals (FMOs) analysis was used to show that photo-induced electron transfer (PET) is the underlying mechanism behind the luminescence quenching of the probe upon exposure to TNT, the rationality of which was further confirmed by the recording of a high charge transfer rate. We also found the existence of an energy level crossing between the local excited (LE) state and charge transfer (CT) state of a complex of the probe and TNT, which was confirmed using energy profile calculations along the linearly interpolated internal coordinate (LIIC) pathway.

Stability, Elastic Properties, and Deformation of LiBN2: A Potential High-Energy Material.

Searching for high-energy-density materials is of great interest in scientific research and for industrial applications. Using an unbiased structure prediction method and first-principles calculations, we investigated the phase stability of LiBN2 from 0 to100 GPa. Two new structures with space groups P4̅21 m and Pnma were discovered. The theoretical calculations revealed that Pnma LiBN2 is stable with respect to a mixture of 1/3Li3N, BN, and 1/3N2 above 22 GPa. The electronic band structure revealed that Pnma LiBN2 has an indirect band gap of 2.3 eV, which shows a nonmetallic feature. The Pnma phase has a high calculated bulk modulus and shear modulus, indicating its incompressible nature. The microscopic mechanism of the structural deformation was demonstrated by ideal tensile shear strength calculations. It is worth mentioning that Pnma LiBN2 is dynamically stable under ambient conditions. The decomposition of this phase is exothermic, releasing an energy of approximately 1.23 kJ/g at the PBE level. The results provide new thoughts for designing and synthesizing novel high-energy compounds in ternary systems.

Reconsideration of the Detection and Fluorescence Mechanism of a Pyrene-Based Chemosensor for TNT.

The rapid detection of chemical explosives is crucial for national security and public safety, and the investigation of sensing mechanisms is important for designing highly efficient chemosensors. This study theoretically investigates the detection and fluorescence mechanism of a newly synthesized pyrene-based chemosensor for the detection of trinitrotoluene (TNT) through density-functional-theory (DFT) and time-dependent density-functional-theory (TDDFT) methods and suggests a different interaction product of the probe and TNT from previously reported ones [ Mosca et al. J. Am. Chem. Soc. 2015 , 137 , 7967 ]. Instead of forming Meisenheimer complexes, the energies of which are beyond those of the reactants, a low-energy product generated by a π-π-stacking interaction is more rational and favorable. The fluorescence-quenching property further confirms that the π-π-stacking product is the predicted one rather than luminescent Meisenheimer complexes. Frontier-molecular-orbital (FMO)-analysis results show that photoinduced electron transfer (PET) is the mechanism underlying the luminescence quenching of the probe upon exposure to TNT.

Tracking intramolecular energy redistribution dynamics in aryl halides: the effect of halide mass.

Selective excitation of C-H, C-C, CX1 and CX2 stretching vibrational modes in an orderly manner, detection of intramolecular energy redistribution and vibrational coupling in the electronic ground state of aryl halides are performed by time- and frequency-resolved Coherent Anti-Stokes Raman Scattering (CARS) spectroscopy. Intramolecular energy flow from parent modes to daughter modes is observed in the experiment. According to the experimental results, it is found that the up-hill vibrational energy flow from lower frequency modes to higher frequency ones is counterintuitive and energy redistribution efficiencies are controlled by the mass of the halide. The selectivity and directionality of energy flow are also discussed in view of vibrational symmetry.