Unraveling the underlying pathogenic factors driving nonalcoholic steatohepatitis and hepatocellular carcinoma: an in-depth analysis of prognostically relevant gene signatures in hepatocellular carcinoma.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) is a progressive manifestation of nonalcoholic fatty liver disease (NAFLD) that can lead to fibrosis, cirrhosis, and hepatocellular carcinoma (HCC). Despite the growing knowledge of NASH and HCC, the association between the two conditions remains to be fully explored. Bioinformatics has emerged as a valuable approach for identifying disease-specific feature genes, enabling advancements in disease prediction, prevention, and personalized treatment strategies. MATERIALS AND METHODS: In this study, we utilized CellChat, copy number karyotyping of aneuploid tumors (CopyKAT), consensus Non-negative Matrix factorization (cNMF), Gene set enrichment analysis (GSEA), Gene set variation analysis (GSVA), Monocle, spatial co-localization, single sample gene set enrichment analysis (ssGSEA), Slingshot, and the Scissor algorithm to analyze the cellular and immune landscape of NASH and HCC. Through the Scissor algorithm, we identified three cell types correlating with disease phenotypic features and subsequently developed a novel clinical prediction model using univariate, LASSO, and multifactor Cox regression. RESULTS: Our results revealed that macrophages are a significant pathological factor in the development of NASH and HCC and that the macrophage migration inhibitory factor (MIF) signaling pathway plays a crucial role in cellular crosstalk at the molecular level. We deduced three prognostic genes (YBX1, MED8, and KPNA2), demonstrating a strong diagnostic capability in both NASH and HCC. CONCLUSION: These findings shed light on the pathological mechanisms shared between NASH and HCC, providing valuable insights for the development of novel clinical strategies.

Dynamics studies for the multi-well and multi-channel reaction of OH with C2H2 on a full-dimensional global potential energy surface.

The C2H2 + OH reaction is an important acetylene oxidation pathway in the combustion process, as well as a typical multi-well and multi-channel reaction. Here, we report an accurate full-dimensional machine learning-based potential energy surface (PES) for the C2H2 + OH reaction at the UCCSD(T)-F12b/cc-pVTZ-F12 level, based on about 475 000 ab initio points. Extensive quasi-classical trajectory (QCT) calculations were performed on the newly developed PES to obtain detailed dynamic data and analyze reaction mechanisms. Below 1000 K, the C2H2 + OH reaction produces H + OCCH2 and CO + CH3. With increasing temperature, the product channels H2O + C2H and H + HCCOH are accessible and the former dominates above 1900 K. It is found that the formation of H2O + C2H is dominated by a direct reaction process, while other channels belong to the indirect mechanism involving long-lived intermediates along the reaction pathways. At low temperatures, the C2H2 + OH reaction behaves like an unimolecular reaction due to the unique PES topographic features, of which the dynamic features are similar to the decomposition of energy-rich complexes formed by C2H2 + OH collision. The classification of trajectories that undergo different reaction pathways to generate each product and their product energy distributions were also reported in this work. This dynamic information may provide a deep understanding of the C2H2 + OH reaction.

Formation Mechanisms of Electronically Excited Nitrogen Molecules from N + N2 and N + N + N Collisions Revealed by Full-Dimensional Potential Energy Surfaces.

This work reports six new full-dimensional adiabatic potential energy surfaces (PESs) of the N3 system (four 4A″ states and two 2A″ states) at the MRCI + Q/AVQZ level of theory that correlated to N2(X1Σg+) + N(4S), N2(X1Σg+) + N(2D), N2(A3Σu+) + N(4S), N2(B3Πg) + N(4S), N2(W3Δu) + N(4S), and N(4S) + N(4S) + N(4S) channels. The neural networks with a proper account of the nuclear permutation invariant symmetry of N3 were employed to fit the PESs based on about 4000 ab initio points. The accuracy of the PESs was validated by excellent agreement on the equilibrium bond length, vertical excitation energy, and dissociation energy with experimental values. Two possible mechanisms of the formation of N2(A) were found. One is that the collision occurs between N2(X) and N(4S) in the 14A″ state, followed by a nonadiabatic transition through the conical intersection with the 24A″ PES, resulting in the formation of the N2(A) + N(4S) product. The other takes place in the collision among three N(4S) atoms in the adiabatic 24A″ state, and then, N2(A) + N(4S) is formed. This is the first systematical research of the N3 system focusing on the formation of the excited states of N2 via both adiabatic and nonadiabatic pathways.

Isotope Effects on State-to-State Photodissociation Dynamics of D2S in Its First Absorption Band.

State-to-state photodissociation dynamics of D2S in its first absorption band were explored by utilizing recently developed diabatic potential energy surfaces (PESs). Quantum dynamics calculations, involving the first two strongly coupled 1A″ states, were executed employing a Chebyshev real wavepacket method. The nonadiabatic channel via the conical intersection (CI) is facile, direct, and fast, leading to the production of rotationally and vibrationally cold SD(X̃2Π). The calculated absorption spectrum, product state distributions, and angular distributions are in reasonable agreement with the experimental results, although some discrepancies exist at 193.3 nm. Compared with H2S, there are obvious isotope effects on rotational state distributions for D2S photodissociation in its first absorption band. Moreover, we scrutinize the variation of product state distributions as a function of photon energy and the vibrational mediated photodissociation of the parent molecule. Due to the diverse shapes of the three fundamental vibrational wave functions, photoexcited wavepackets access distinct segments of the upper-state PES, resulting in a disparate absorption spectrum and ro-vibrational distributions via the nonadiabatic transition. This study provides a comprehensive figure of the isotopic effect and wavelength dependence on the photofragmentation behaviors from D2S photodissociation, which should attract more experimental and theoretical attention to this prototypical system.

ABLRI: A program for calculating the long-range interaction energy between two monomers in their non-degenerate states.

An accurate description of the long-range (LR) interaction is essential for understanding the collision between cold or ultracold molecules. However, to our best knowledge, there lacks a general approach to construct the intermolecular potential energy surface (IPES) between two arbitrary molecules and/or atoms in the LR region. In this work, we derived analytical expressions of the LR interaction energy, using the multipole expansion of the electrostatic interaction Hamiltonian and the non-degenerate perturbation theory. To make these formulae practical, we also derived the independent Cartesian components of the electrostatic properties, including the multipole moments and polarizabilities, of the monomer for a given symmetry using the properties of these components and the group-theoretical methods. Based on these newly derived formulae, we developed a FORTRAN program, namely ABLRI, which is capable of calculating the interaction energy between two arbitrary monomers both in their non-degenerate electronic ground states at large separations. To test the reliability of this newly developed program, we constructed IPESs for the electronic ground state of H2O-H2 and O2-H systems in the LR region. The interaction energy computed by our program agreed well with the ab initio calculation, which shows the validity of this program.

Highly sensitive optical fiber pressure sensor based on the FPI and Vernier effect via femtosecond laser plane-by-plane writing technology.

In this paper, a highly sensitive pressure sensor based on fiber-optic Fabry-Perot interferometers (FPIs) and the Vernier effect (VE) is proposed and experimentally demonstrated. We employ a closed capillary-based F P I s for the sensing cavity, and an F P I r created through femtosecond laser refractive index modulation for the reference cavity, which remains impervious to pressure changes. Connecting these two FPIs in series produces a VE-based cascaded sensor with a clear spectral envelope. The femtosecond laser micromachining technique provides precise control over the length of F P I r and facilitates adjustments to the VE's amplification degree. Experimental results reveal significant pressure sensitivities of -795.96p m/M P a and -3219.91p m/M P a, respectively, representing a 20-fold and 80-fold improvement compared to F P I s (-39.80p m/M P a). This type of sensor has good sensitivity amplification and, due to its all-fiber structure, can be a promising candidate for high-temperature and high-pressure sensing, especially in harsh environments.

New accurate diabatic potential energy surfaces for the two lowest 1A'' states of H2S and photodissociation dynamics in its first absorption band.

In this work, state-to-state photodissociation dynamics of H2S in its first absorption band has been studied quantum mechanically with a new set of coupled potential energy surfaces (PESs) for the first two 1A'' excited states, which were developed at the explicitly correlated internally contracted multi-reference configuration interaction level with the cc-pVQZ-F12 basis set and a large active space. The calculated absorption spectrum, product state distributions, and angular distributions are in excellent agreement with available experimental data, validating the accuracy of the PESs and the non-adiabatic couplings. Detailed analysis of the dynamics reveals that there are strong non-adiabatic couplings between the bound 11B1 and dissociative 11A2 states around the Franck-Condon region, leading to very fast predissociation to ro-vibrationally cold SH(X̃) fragments, during which marginal angular anisotropy of the PESs is involved. This study provides quantitatively accurate characterization of the electronic structure and detailed fragmentation dynamics of this prototypical photodissociation system, which is desirable for improving astrochemical modelling.

Dissection of the Multichannel Reaction O(3P) + C2H2: Differential Cross-Sections and Product Energy Distributions.

The O(3P) + C2H2 reaction plays an important role in hydrocarbon combustion. It has two primary competing channels: H + HCCO (ketenyl) and CO + CH2 (triplet methylene). To further understand the microscopic dynamic mechanism of this reaction, we report here a detailed quasi-classical trajectory study of the O(3P) + C2H2 reaction on the recently developed full-dimensional potential energy surface (PES). The entrance barrier TS1 is the rate-limiting barrier in the reaction. The translation of reactants can greatly promote reactivity, due to strong coupling with the reaction coordinate at TS1. The O(3P) + C2H2 reaction progress through a complex-forming mechanism, in which the intermediate HCCHO lives at least through the duration of a rotational period. The energy redistribution takes place during the creation of the long-lived high vibrationally (and rotationally) excited HCCHO in the reaction. The product energy partitioning of the two channels and CO vibrational distributions agree with experimental data, and the vibrational state distributions of all modes of products present a Boltzmann-like distribution.

Theoretical H + O3 rate coefficients from ring polymer molecular dynamics on an accurate global potential energy surface: assessing experimental uncertainties.

Thermal rate coefficients and kinetic isotope effects have been calculated for an important atmospheric reaction H/D + O3 → OH/OD + O2 based on an accurate permutation invariant polynomial-neural network potential energy surface, using ring polymer molecular dynamics (RPMD), quasi-classical trajectory (QCT) and variational transition-state theory (VTST) with multidimensional tunneling. The RPMD approach yielded results that are generally in better agreement with experimental rate coefficients than the VTST and QCT ones, especially at low temperatures, attributable to its capacity to capture quantum effects such as tunneling and zero-point energy. The theoretical results support one group of existing experiments over the other. In addition, rate coefficients for the D + O3 → OD + O2 reaction are also reported using the same methods, which will allow a stringent assessment of future experimental measurements, thus helping to reduce the uncertainty in the recommended rate coefficients of this reaction.

Full-Dimensional Global Potential Energy Surface for the KRb + KRb → K2Rb2* → K2 + Rb2 Reaction with Accurate Long-Range Interactions and Quantum Statistical Calculation of the Product State Distribution under Ultracold Conditions.

A full-dimensional global potential energy surface (PES) for the KRb + KRb → K2Rb2* → K2 + Rb2 reaction is reported based on high-level ab initio calculations. The short-range part of the PES is fit with the permutationally invariant polynomial-neural network method, while the long-range parts of the PES in both the reactant and product asymptotes are represented by an asymptotically correct form. The long- and short-range parts are connected with intermediate-range parts to make them smooth. Within a statistical quantum model, this PES reproduces both the measured loss rates of ultracold KRb molecules and the K2 and Rb2 product state distributions, underscoring the important role of tunneling in ultracold chemistry. The PES also correctly predicts the lifetime of the K2Rb2* intermediate complex within the Rice-Ramsperger-Kassel-Marcus limit. It thus provides a reliable platform for future dynamical studies of the prototypical reaction.

Quality Characteristics and Anthocyanin Profiles of Different Vitis amurensis Grape Cultivars and Hybrids from Chinese Germplasm.

To evaluate the important Vitis amurensis germplasm, the quality characteristics and anthocyanin profiles of the ripe berries of 20 V. amurensis grapes and 11 interspecific hybrids in two consecutive years were analysed. Compared with the V. vinifera grapes, V. amurensis grapes had small berries with low total soluble solids and high titratable acids, and were richer in phenolic compounds except for flanan-3-ols in their skins but had lower phenolic contents in their seeds and showed lower antioxidant activities. An outstanding feature of the V. amurensis grapes was their abundant anthocyanin contents, which was 8.18-fold higher than the three wine grapes of V. vinifera. The anthocyanin composition of V. amurensis was characterized by an extremely high proportion of diglucoside anthocyanins (91.71%) and low acylated anthocyanins (0.04%). Interestingly, a new type of speculated 3,5,7-O-triglucoside anthocyanins was first identified and only detected in V. amurensis grapes and hybrids. Based on the total phenolic and anthocyanin characteristics, V. amurensis grapes were set apart from V. vinifera cultivars and the interspecific hybrids, for the same qualities, fell between them, as assessed by principal component analysis.

Galactose-Modified PH-Sensitive Niosomes for Controlled Release and Hepatocellular Carcinoma Target Delivery of Tanshinone IIA.

Increasing the drug tumor-specific accumulation and controlling their release is considered one of the most effective ways to increase the efficacy of drugs. Here, we developed a vesicle system that can target hepatoma and release drugs rapidly within tumor cells. This non-ionic surfactant vesicle is biodegradable. Galactosylated stearate has been used to glycosylate the vesicles to achieve liver targeting; replacement of a portion (Chol:CHEMS = 1:1) of cholesterol by cholesteryl hemisuccinate (CHEMS) allows for a rapid release of drugs in an acidic environment. In vitro release experiments confirmed that galactose-modified pH-sensitive niosomes loaded with tanshinone IIA had excellent drug release performance in acid medium. In vitro experiments using ovarian cancer cells (A2780), colon cancer cells (HCT8), and hepatoma cell (Huh7, HepG2) confirmed that the preparation had specific targeting ability to hepatoma cells compared with free drugs, and this ability was dependent on the galactose content. Furthermore, the preparation also had a more substantial inhibitory effect on tumor cells, and subsequent apoptosis assays and cell cycle analyses further confirmed its enhanced anti-tumor effect. Results of pharmacokinetic experiments confirmed that the vesicle system could significantly extend the blood circulation time of tanshinone IIA, and the larger area under the curve indicated that the preparation had a better drug effect. Thus, the results of biodistribution experiments confirmed the in vivo liver targeting ability of this preparation. Niosomes designed in this manner are expected to be a safe and effective drug delivery system for liver cancer therapy.

Theoretical Investigations of Rate Coefficients for H + O3 and HO2 + O Reactions on a Full-Dimensional Potential Energy Surface.

In this work, a machine learning method is used to construct a high-fidelity multichannel global reactive potential energy surface (PES) for the HO3 system from 21452 high-level ab initio calculations at the explicitly correlated multireference configuration interaction (MRCI-F12) level of theory. The permutation invariance of the PES with respect to the three identical oxygen atoms is enforced using permutation invariant polynomials (PIPs) in the input layer of a neural network (NN). This PIP-NN representation is highly faithful to the ab initio points, with a root-mean-square error of 0.20 kcal/mol. Using this PES, the kinetics of H + O3 → OH + O2 (R1) and HO2 + O → OH + O2 (R2) reactions were investigated using a quasi-classical trajectory method over a wide temperature range (200-2000 K). It was found that the calculated thermal rate coefficients of R1 and R2, exhibiting positive and negative temperature dependences, respectively, are in reasonably good agreement with most experimental measured values. These temperature dependences can be attributed to the presence and absence of an entrance channel potential barrier.

Statistical quantum mechanical approach to diatom-diatom capture dynamics and application to ultracold KRb + KRb reaction.

A general and rigorous quantum method is proposed for studying capture dynamics between two diatomic molecules in full dimensionality. By solving the time-independent Schrödinger equation with proper boundary conditions, this method is ideally suited for studying quantum dynamics of cold and ultracold reactions. To illustrate its applicability, the capture dynamics between ultracold KRb molecules is characterized in full six dimensions for the first time using a first-principles based long-range interaction potential. The calculated capture rates for collisions involving distinguishable and indistinguishable 40K87Rb molecules are in good agreement with the experiment and exhibit clear Wigner threshold behaviors. Predictions for ultracold collisions between internally excited 40K87Rb suggest minor changes in the loss rate, consistent with experimental observations in similar systems.

Quantum dynamics of vibration-vibration energy transfer for vibrationally excited HF colliding with H2.

The rate constants for H2 -HF energy transfer processes, especially for those in vibrationally excited states, are very demanding in astrophysics and chemical laser engineering, especially for those in vibrationally excited states. Based on our recent potential energy surface, we used the coupled-states approximation including the nearest neighboring Coriolis couplings with energy-based local basis set to perform dynamics calculation for the H2 -HF energy transfer system. Rate constants for vibrational transitions (1; 3) → (0; 4), (1; 3) → (2; 2), and (0; 3) → (1; 2) were obtained. For state-to-state rate constants, transitions that have no internal angular momentum gap dominate at high temperatures. The vibrational-resolved rate constant for (1; 3) → (0; 4) initially decreases and then increases with the temperature, while those for (1; 3) → (2; 2), and (0; 3) → (1; 2) transitions monotonically increase. The calculated rate constants are in good agreement with the available experimental results. These dynamical data can be further applied to the numerical simulation of hydrogen fluoride chemical laser. © 2018 Wiley Periodicals, Inc.

First-principles dynamics of collisional intersystem crossing: resonance enhanced quenching of C(1D) by N2.

Intersystem crossing is a common and important nonadiabatic process in molecular systems, and its first-principles characterization requires accurate descriptions of both the electronic structure and nuclear dynamics. Here, we report an accurate full-dimensional quantum dynamical investigation of collisional quenching of the excited state C(1D) atom to its ground state C(3P) counterpart by N2, which is an important process in both combustion and interstellar media, using full-dimensional ab initio potential energy surfaces and spin-orbit couplings. Satisfactory agreement with experimental rate coefficients is obtained. Despite relatively small spin-orbit couplings, it is shown that intersystem crossing is efficient because of multiple passages via long-lived collisional resonances.

Dissection of the multichannel reaction of acetylene with atomic oxygen: from the global potential energy surface to rate coefficients and branching dynamics.

The O(3P) + C2H2 reaction is the first step in acetylene oxidation. The accurate kinetic data and the understanding of the reaction dynamics is of great importance. To this end, a full-dimensional global potential energy surface (PES) for the ground triplet state of the O(3P) + C2H2 reaction is constructed based on approximately 85 000 ab initio points calculated at the level of explicitly correlated unrestricted coupled cluster single, double, and perturbative triple excitations with the explicitly correlated polarized valence triple zeta basis set (UCCSD(T)-F12b/VTZ-F12). The PES is fit using the permutation invariant polynomial-neural network (PIP-NN) approach with a total root mean square error of 0.21 kcal mol-1. The key topographic features of the PES, including multiple potential wells and saddle points along different reaction pathways, are well represented by this fit PES. The kinetics and dynamics of the O(3P) + C2H2 reaction are investigated using the quasi-classical trajectory (QCT) method. The calculated rate coefficients are in good agreement with experimental data over a wide temperature range, especially when the temperature is lower than 1500 K. The product branch ratio has also been determined, which indicates the H + HCCO channel as the dominant reaction pathway at 298-3000 K, accounting for 80-90% of the overall rate coefficient, in agreement with experimental observations. The dynamics of the reaction is analyzed in detail.

An ab initio based full-dimensional potential energy surface for OH + O2⇄ HO3 and low-lying vibrational levels of HO3.

To provide an in-depth understanding of the HO3 radical and its dissociation to OH + O2, a six-dimensional potential energy surface (PES) has been constructed by fitting 2087 energy points for the electronic ground state of HO3 (X2A'') using the permutation invariant polynomial-neural network (PIP-NN) approach. The energy points were calculated using an explicitly-correlated and Davidson-corrected multi-reference configuration interaction method with the correlation-consistent polarized valence double zeta basis (MRCI(Q)-F12/VDZ-F12). On the PES, the trans-HO3 isomer is found to be the global minimum, 33.0 cm-1 below the cis-HO3 conformer, which is consistent with previous high-level theoretical investigations. The dissociation to the OH + O2 asymptote from both conformers is shown to be barrierless. As a benchmark from a recently developed high-accuracy thermochemistry protocol, D0 for trans-HO3 is calculated to be 2.29 ± 0.36 kcal mol-1, only slightly deeper than the value of 2.08 kcal mol-1 obtained using the PES, and in reasonable agreement with the experimentally estimated value of 2.93 ± 0.07 kcal mol-1. Using this PES, low-lying vibrational energy levels of HO3 are determined using an exact quantum Hamiltonian and compared with available experimental results.

An interaction-asymptotic region decomposition method for general state-to-state reactive scatterings.

A single set of coordinates, which is optimal for both asymptotic product and reactant, is difficult to find in a state-to-state reactive scattering calculation using the quantum wave packet method. An interaction-asymptotic region decomposition (IARD) method was proposed in this work to solve this "coordinate problem." In the method, the interaction region and asymptotic regions are applied with the local optimal coordinate system, i.e., hyperspherical and corresponding Jacobi coordinates. The IARD method is capable of efficiently and accurately accomplishing a calculation with a grid box for the Jacobi coordinate R extending several hundred bohrs for both reactant and product arrangements. We demonstrate the effectiveness of the IARD method with the reaction of H + HD, which is the simplest direct reaction, and F + HD, which is a typical reaction involving resonances with products of extremely slow translational energy and requires extremely long absorbing potential in all channels.

The preparation, characterization of Lupeol PEGylated liposome and its functional evaluation in vitro as well as pharmacokinetics in rats.

Objective: The objective of this study was to enhance the solubility and bioavailability of Lupeol. Methods: Utilizing a thin-film dispersion method, we prepared Lupeol-loaded PEGylated liposomes and Lupeol-loaded liposomes, which was characterized using SEM, mean diameter, PDI, zeta potential, and entrapment efficiency (EE). The EE, in vitro release, and stability of Lupeol-loaded PEGylated liposomes were detected using HPLC. In addition to the safety evaluation, the evaluation was carried out on HepG2 cells in vitro; the pharmacokinetics were carried out after i.v. in the rats. Results: The size, PDI, zeta potential, and EE of Lupeol-loaded PEGylated liposomes and Lupeol-loaded liposomes were 126.9 nm, 0.246, -1.97 mV, 87%; 97.23 nm, 0.25, 1.6 mV, 86.2%, respectively. Lupeol-loaded PEGylated liposomes showed the slow-release effect in vitro release experiments. Lupeol-loaded PEGylated liposomes offered significant advantages over other experimental groups in vitro studies, such as the highest inhibition rate and the highest apoptosis rate. We also found that Lupeol-loaded PEGylated liposomes blocked cells in the G2M phase. The pharmacokinetics result showed that the AUC of Lupeol-loaded PEGylated liposomes group was 3.2 times higher than free Lupeol group after i.v., the MRT and t1/2 values of Lupeol-loaded PEGylated liposomes (MRT = 6.09 h, t1/2 =12.94 h) showed improvements of 2.5 and 4.1 times compared to free Lupeol (MRT = 2.43 h, t1/2 = 3.16 h). Conclusion: The Lupeol-loaded PEGylated liposomes have successfully solved its poor hydrophilicity, low bioavailability.