Guang-Fu Ji

Phosphorylation of the regulator (R) domain underlies the basis for gating in the human cystic fibrosis transmembrane conductance regulator (CFTR), malfunction or down regulation of CFTR leads to defective apical chloride transport. The biophysical mechanism that underlies the regulatory effect of R domain is still unclear. Here, we utilize a combination of molecular dynamics simulations and theoretically calculated two-dimensional infrared (2D IR) spectra to probe both the structure and spectral signature of phosphorylated and unphosphorylated CFTR. We uncover an ATP-independent asymptotic movement of nucleotide binding domains (NBDs) driven by phosphorylated R domain. Utilizing non-rephasing cross ground-state bleach infrared (GB IR) spectra simulation, we overcome the interpretation hurdle caused by overlaps of multiple vibrational modes, and find distinct vibrational couplings induced by phosphorylation. By calculating exciton eigenfrequencies, we pinpoint specific vibrational couplings to individual amide I modes (carbonyl stretches), unveiling a critical role of serine residues in modulating the coupling state of neighboring amino acids. Our findings offer a bond-specific perspective on how intramolecular interactions within the R domain translate into its broader regulatory function.

The external electric field (E-field), which is an important stimulus, can change the decomposition mechanism and sensitivity of energetic materials. As a result, understanding the response of energetic materials to external E-fields is critical for their safe use. Motivated by recent experiments and theories, the two-dimensional infrared (2D IR) spectra of 3,4-bis (3-nitrofurazan-4-yl) furoxan (DNTF), which has a high energy, a low melting point, and comprehensive properties, were theoretically investigated. Cross-peaks were observed in 2D IR spectra under different E-fields, which demonstrated an intermolecular vibration energy transfer; the furazan ring vibration was found to play an important role in the analysis of vibration energy distribution and was extended over several DNTF molecules. Measurements of the non-covalent interactions, with the support of the 2D IR spectra, indicated that there were obvious non-covalent interactions among different DNTF molecules, which resulted from the conjugation of the furoxan ring and the furazan ring; the direction of the E-field also had a significant influence on the strength of the weak interactions. Furthermore, the calculation of the Laplacian bond order, which characterized the C-NO₂ bonds as trigger bonds, predicted that the E-fields could change the thermal decomposition process of DNTF while the positive E-field facilitates the breakdown of the C-NO₂ in DNTFⅣ molecules. Our work provides new insights into the relationship between the E-field and the intermolecular vibration energy transfer and decomposition mechanism of the DNTF system.

Introduction: The COVID-19 pandemic has posed a major burden on healthcare and economic systems across the globe for over 3 years. Even though vaccines are available, the pathogenesis is still unclear. Multiple studies have indicated heterogeneity of immune responses to SARS-CoV-2, and potentially distinct patient immune types that might be related to disease features. However, those conclusions are mainly inferred by comparing the differences of pathological features between moderate and severe patients, some immunological features may be subjectively overlooked.Methods: In this study, the relevance scores(RS), reflecting which features play a more critical role in the decision-making process, between immunological features and the COVID-19 severity are objectively calculated through neural network, where the input features include the immune cell counts and the activation marker concentrations of particular cell, and these quantified characteristic data are robustly generated by processing flow cytometry data sets containing the peripheral blood information of COVID-19 patients through PhenoGraph algorithm.Results: Specifically, the RS between immune cell counts and COVID-19 severity with time indicated that the innate immune responses in severe patients are delayed at the early stage, and the continuous decrease of classical monocytes in peripherial blood is significantly associated with the severity of disease. The RS between activation marker concentrations and COVID-19 severity suggested that the down-regulation of IFN-γ in classical monocytes, Treg, CD8 T cells, and the not down-regulation of IL_17a in classical monocytes, Tregs are highly correlated with the occurrence of severe disease. Finally, a concise dynamic model of immune responses in COVID-19 patients was generalized.Discussion: These results suggest that the delayed innate immune responses in the early stage, and the abnormal expression of IL-17a and IFN-γ in classical monocytes, Tregs, and CD8 T cells are primarily responsible for the severity of COVID-19.

Inspired by the recent cocrystallization and theory of energetic materials, we theoretically investigated the intermolecular vibrational energy transfer process and the non-covalent intermolecular interactions between explosive compounds. The intermolecular interactions between 2,4,6-trinitrotoluene (TNT) and 2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane (CL-20) and between 1,3,5,7-tetranitro-1,3,5,7-tetrazocane (HMX) and CL-20 were studied using calculated two-dimensional infrared (2D IR) spectra and the independent gradient model based on the Hirshfeld partition (IGMH) method, respectively. Based on the comparison of the theoretical infrared spectra and optimized geometries with experimental results, the theoretical models can effectively reproduce the experimental geometries. By analyzing cross-peaks in the 2D IR spectra of TNT/CL-20, the intermolecular vibrational energy transfer process between TNT and CL-20 was calculated, and the conclusion was made that the vibrational energy transfer process between CL-20 and TNTII (TNTIII) is relatively slower than between CL-20 and TNTI. As the vibration energy transfer is the bridge of the intermolecular interactions, the weak intermolecular interactions were visualized using the IGMH method, and the results demonstrate that the intermolecular non-covalent interactions of TNT/CL-20 include van der Waals (vdW) interactions and hydrogen bonds, while the intermolecular non-covalent interactions of HMX/CL-20 are mainly comprised of vdW interactions. Further, we determined that the intermolecular interaction can stabilize the trigger bond in TNT/CL-20 and HMX/CL-20 based on Mayer bond order density, and stronger intermolecular interactions generally indicate lower impact sensitivity of energetic materials. We believe that the results obtained in this work are important for a better understanding of the cocrystal mechanism and its application in the field of energetic materials.

As the most promising hydrogen storage material, ammonia borane (NH ₃ BH ₃ , AB) has been the subject of study in a variety of scientific fields.

It is reported that the cis/trans conformation change of the peptide hormone oxytocin plays an important role in its receptors and activation and the cis conformation does not lead to antagonistic activity. Motivated by recent experiments and theories, the quasi-static amide-I 2D IR spectra of oxytocin are investigated using DFT/B3LYP (D3)/6-31G (d, p) in combination with the isotope labeling method under different electric fields. The theoretical amide-I IR spectra and bond length of the disulfide bond are consistent with the experimental values, which indicates that the theoretical modes are reasonable. Our theoretical results demonstrate that the oxytocin conformation is transformed from the cis conformation to the trans conformation with the change of the direction of the electric field, which is confirmed by the distance of the backbone carbonyl oxygen of Cys6 and Pro7, the Ramachandran plot of Cys6 and Pro7, the dihedral angle of C_β-S-S-C_β, and the rmsd of the oxytocin backbone. Moreover, the trans conformation as the result of the turn in the vicinity of Pro7 has a tighter secondary spatial structure than the cis conformation, including stronger hydrogen bonds, longer γ-turn geometry involving five amino acids, and a more stable disulfide bond. Our work provides new insights into the relationship between the conformation, the activation of the peptide hormone oxytocin, and the electric fields.

There are two high-temperature superconductor structures in the ScCaH_2n(n= 1–6) system. Among them, ScCaH₈contains H₁₈-cages and theT_creaches 212 K (200 GPa), while ScCaH₁₂has H₂₄-cages and theT_creaches 182 K (200 GPa).

We studied dependency of toluene oxidation-blended n-decane on blending ratio and temperature using the reactive molecular dynamics (RMD) simulations with the newly developed reactive force field (ReaxFF). Different initial reaction pathways of toluene were observed between pure and blended toluene, while that of n-decane showed little contrast. The differences in toluene oxidation paths are related to radical pool, which is largely influenced by H/C ratio. We analysed the influence of H/C ratio on the consumption of intermediate species, and found different dependencies of HCHO consumption on H/C ratio for different temperatures. The difference is attributed to the large active energy difference between the two main HCHO consumption reactions by OH and O₂. For the production part, the OH producing pathway was analysed carefully and shows H/C ratio influences OH production via H production and H abstract reactions. Our RMD simulations show that H/C ratio plays an important role in the oxidation of fuel.

IR spectra of heme and different O₂-content hemoglobin were studied by the quantum computation method at the molecule level. IR spectra of heme and different O₂-content hemoglobin were quantificationally characterized from 0 to 100 THz. The IR spectra of oxy-heme and de-oxy-heme are obviously different at the frequency regions of 9.08–9.48, 38.38–39.78, 50.46–50.82, and 89.04–91.00 THz. At 24.72 THz, there exists the absorption peak for oxy-heme, whereas there is not the absorption peak for de-oxy-heme. Whether the heme contains Fe–O–O bond or not has the great influence on its IR spectra and vibration intensities of functional groups in the mid-infrared area. The IR adsorption peak shape changes hardly for different O₂-content hemoglobin. However, there exist three frequency regions corresponding to the large change of IR adsorption intensities for containing-O₂ hemoglobin in comparison with de-oxy-hemoglobin, which are 11.08–15.93, 44.70–50.22, and 88.00–96.68 THz regions, respectively. The most differential values with IR intensity of different O₂-content hemoglobin all exceed 1.0 × 10⁴ L mol⁻¹ cm⁻¹. With the increase of oxygen content, the absorption peak appears in the high-frequency region for the containing-O₂ hemoglobin in comparison with de-oxy-hemoglobin. The more the O₂-content is, the greater the absorption peak is at the high-frequency region. The IR spectra of different O₂-content hemoglobin are so obviously different in the mid-infrared region that it is very easy to distinguish the hemoglobin variant by means of IR spectra detector. IR spectra of hemoglobin from quantum computation can provide scientific basis and specific identification of hemoglobin variant resulting from different O₂ contents in medical diagnosis.