"On-the-Fly" Nonadiabatic Dynamics Simulation on the Ultrafast Photoisomerization of a Molecular Photoswitch Iminothioindoxyl: An RMS-CASPT2 Investigation.

Iminothioindoxyl (ITI) is a new class of photoswitch that exhibits many excellent properties including well-separated absorption bands in the visible region for both conformers, ultrafast Z to E photoisomerization as well as the millisecond reisomerization at room temperature for the E isomer, and switchable ability in both solids and various solvents. However, the underlying ultrafast photoisomerization mechanism at the atomic level remains unclear. In this work, we have employed a combination of high-level RMS-CASPT2-based static electronic structure calculations and nonadiabatic dynamics simulations to investigate the ultrafast photoisomerization dynamics of ITI. Based on the minimum-energy structures, minimum-energy conical intersections, linear interpolation internal coordinate paths, and nonadiabatic dynamics simulations, the overall photoisomerization scenario of ITI upon excitation is established. Upon excitation around 416 nm, the molecule will be excited to the S2 state considering its close energy to the experimentally measured absorption maximum and larger oscillator strength, from which ultrafast decay of S2 to S1 state can take place efficiently with a time constant of 62 fs. However, the photoisomerization is not likely to complete in the S2 state since the dihedral associated with the Z to E isomerization changes little during the relaxation. Upon relaxing to the S1 state, the molecule will decay to the S0 state ultrafast with a time constant of 232 fs. In contrast, the decay of the S1 state is important for the isomerization considering that the dihedral related to the isomerization of the hopping structures is close to 90°. Therefore, the S1/S0 intersection region should be important for the isomerization of ITI. Arriving at the S0 state, the molecule can either go back to the original Z reactant or isomerize to the E products. At the end of the 500 fs simulation time, the E configuration accounts for nearly 37% of the final structures. Moreover, the photoisomerization mechanism is different from the isomerization mechanism in the ground state; i.e., instead of the inversion mechanism in the ground state, the photoisomerization prefers the rotation mechanism. Our results not only agree well with previous experimental studies but also provide some novel insights that could be helpful for future improvements in the performance of the ITI photoswitches.

Irritable bowel syndrome: Epidemiology, overlap disorders, pathophysiology and treatment.

Irritable bowel syndrome (IBS) is a common chronic gastrointestinal disease with a significant impact on patients' quality of life and a high socioeconomic burden. And the understanding of IBS has changed since the release of the Rome IV diagnosis in 2016. With the upcoming Rome V revision, it is necessary to review the results of IBS research in recent years. In this review of IBS, we can highlight future concerns by reviewing the results of IBS research on epidemiology, overlap disorders, pathophysiology, and treatment over the past decade and summarizing the latest research.

Adsorption characteristics of sulfonamide antibiotic molecules on carbon nanotube and the effects of environment.

CONTEXT: In this paper, the adsorption characteristics of five sulfonamide antibiotic molecules on carbon nanotubes were investigated using density functional theory (DFT) calculations. The adsorption configurations of different adsorption sites were optimized, and the most stable adsorption configuration of each sulfonamide molecule was determined by adsorption energy comparison, and the relative adsorption stability of five sulfonamide molecules on carbon nanotubes was determined by comparing their adsorption energies, i.e., sulfamethazine > sulfadiazine > sulfamerazine > sulfamethoxazole > sulfanilamide. The electron densities of the adsorption configurations were then calculated to confirm that the adsorption of five sulfonamide drug molecules on carbon nanotubes should be physical adsorption. Moreover, the adsorption energy of five sulfonamide molecules on carbon nanotubes in the aqueous environment was larger than that in the vacuum even though the adsorption process remain to be physical adsorption. The adsorption characteristics of the five sulfonamide molecules in various acid-base environments were finally investigated. In contrast, the adsorption energies of the five drug molecules in acid-base environments were significantly reduced, indicating that carbon nanotubes may need to have a suitable pH range to achieve the optimal adsorption effect when they are used for the treatment of sulfonamide antibiotics. METHODS: In this paper, we use density functional theory (DFT) with PBE functional to study the adsorption properties of five sulfonamides on carbon nanotubes. The structural optimization and the calculation of electronic structural properties are carried out by CP2K package (version 7.1), adopting the DZVP-MOLOPT-SR-GTH basis set and Goedeck-Teter-Hutter (GTH) pseudo potential. Grimme's D3 correction is used to during all the calculations to correctly capture the influence of the van der Waals interactions.

3-Bromopyruvate Attenuates Experimental Pulmonary Hypertension via Inhibition of Glycolysis.

BACKGROUND: The shift of metabolism from mitochondrial oxidative phosphorylation to glycolysis and mitochondria binding partner of hexokinase are features common to cancer. These have been seen in pulmonary hypertension (PH) as well. An inhibitor of hexokinase 2 (HK 2), the small molecule 3-bromopyruvate (3-BrPA) is an incredibly powerful and swift-acting anticancer agent. However, whether it could be of potential benefit to PH has still been unknown. METHODS: Sprague-Dawley rats with monocrotaline (MCT)-induced PH were administered 2 oral doses of 3-BrPA (15 and 30 mg/kg/day, respectively) for 14 days. Hemodynamic parameters were obtained by right heart catheterization. Histopathology, immunohistochemistry, transmission electron microscopy, flow cytometry, and assessments of relative protein expressions were conducted. RESULTS: Compared with MCT treatment, 3-BrPA decreased mean pulmonary arterial pressure and pulmonary vascular resistance, and increased cardiac output. 3-BrPA significantly suppressed proliferation in addition to enhancing apoptosis of pulmonary artery smooth muscle cells, attenuating small pulmonary artery remodeling and right ventricular hypertrophy. Treatment with 3-BrPA markedly reduced the mitochondrial membrane potential and restored mitochondrial structure. Furthermore, 3-BrPA significantly inhibited HK 2 expression but not HK 1. The expression of both pyruvate dehydrogenase kinase and lactate dehydrogenase was decreased whereas that of pyruvate dehydrogenase and cytosolic cytochrome c was upregulated with 3-BrPA administration. CONCLUSION: This study demonstrates the reversal of PH by 3-BrPA is related to alteration in glycolysis and improved mitochondria function, indicating the "metabolic targeting" as a rational therapeutic strategy for PH.