Integrated virtual screening and in vitro studies for exploring the mechanism of triterpenoids in Chebulae Fructus alleviating mesaconitine-induced cardiotoxicity via TRPV1 channel.

Background: In traditional Mongolian or Tibetan medicine in China, Chebulae Fructus (CF) is widely used to process or combine with aconitums to decrease the severe toxicity of aconitums. Researches in this area have predominantly focused on tannins, with few research on other major CF components for cardiotoxicity mitigation. The present study aimed to clarify whether triterpenoids can attenuate the cardiotoxicity caused by mesaconitine (MA) and investigate the mechanism of cardiotoxicity attenuation. Methods: Firstly, the pharmacophore model, molecular docking, and 3D-QSAR model were used to explore the mechanism of CF components in reducing the toxicity of MA mediated by the TRPV1 channel. Then three triterpenoids were selected to verify whether the triterpenoids had the effect of lowering the cardiotoxicity of MA using H9c2 cells combined with MTT, Hoechst 33258, and JC-1. Finally, Western blot, Fluo-3AM, and MTT assays combined with capsazepine were used to verify whether the triterpenoids reduced H9c2 cardiomyocyte toxicity induced by MA was related to the TRPV1 channel. Results: Seven triterpenoids in CF have the potential to activate the TRPV1 channel. And they exhibited greater affinity for TRPV1 compared to other compounds and MA. However, their activity was relatively lower than that of MA. Cell experiments revealed that MA significantly reduced H9c2 cell viability, resulting in diminished mitochondrial membrane potential and nuclear pyknosis and damage. In contrast, the triterpenoids could improve the survival rate significantly and counteract the damage of MA to the cells. We found that MA, arjungenin (AR), and maslinic acid (MSA) except corosolic acid (CRA) upregulated the expression of TRPV1 protein. MA induced a significant influx of calcium, whereas all three triterpenoids alleviated this trend. Blocking the TRPV1 channel with capsazepine only increased the cell viability that had been simultaneously treated with MA, and AR, or MSA. However, there was no significant difference in the CRA groups treated with or without capsazepine. Conclusion: The triterpenoids in CF can reduce the cardiotoxicity caused by MA. The MSA and AR function as TRPV1 agonists with comparatively reduced activity but a greater capacity to bind to TRPV1 receptors, thus antagonizing the excessive activation of TRPV1 by MA.

Angle-Resolved Optical Imaging of Interlayer Rotations in Twisted Bilayer Graphene.

Twisted bilayer graphene (TBG) is a prototypical layered material whose properties are strongly correlated to interlayer coupling. The two stacked graphene layers with distinct orientations are investigated to generate peculiar optical and electronic phenomena. Thus, the rapid, reliable, and nondestructive twist angle identification technique is of essential importance. Here, we integrated the white light reflection spectra (WLRS), the Raman spectroscopy, and the transmission electron microscope (TEM) to propose a facile RGB optical imaging technique that identified the twist angle of the TBG in a large area intuitively with high efficiency. The RGB technique established a robust correlation between the interlayer rotation angle and the contrast difference in the RGB color channels of a standard optical image. The angle-resolved optical behavior is attributed to the absorption resonance matching with the separation of van Hove singularities in the density of states of the TBG. Our study thus developed a route to identify the rotation angle of stacked bilayer graphene by means of a straightforward optical method, which can be further applied in other stacked van der Waals layered materials.

Controllable CVD Growth of 2D Cr5Te8 Nanosheets with Thickness-Dependent Magnetic Domains.

As a unique 2D magnetic material with self-intercalated structure, Cr5Te8 exhibits many intriguing magnetic properties. While its ferromagnetism of Cr5Te8 has been previously reported, the research on its magnetic domain remains unexplored. Herein, we have successfully fabricated 2D Cr5Te8 nanosheets with controlled thickness and lateral size by chemical vapor deposition (CVD). Then magnetic property measurement system revealed Cr5Te8 nanosheets exhibiting intense out-of-plane ferromagnetism with a Curie temperature (TC) of 176 K. Significantly, we reported for the first time two magnetic domains: magnetic bubbles and thickness-dependent maze-like magnetic domains in our Cr5Te8 nanosheets by cryogenic magnetic force microscopy (MFM). The domain width of the maze-like magnetic domains increases rapidly with decreasing sample thickness; meanwhile, the domain contrast decreases. This indicates the dominant role of ferromagnetism shifts from dipolar interactions to magnetic anisotropy. Our research not only establishes a pathway for the controllable growth of 2D magnetic materials but also points toward novel avenues for regulating magnetic phases and methodically tuning domain characteristics.

A natural indirect-to-direct band gap transition in artificially fabricated MoS2 and MoSe2 flowers.

Twisted bilayer (tB) transition metal dichalcogenide (TMD) structures formed from two pieces of a periodic pattern overlaid with a relative twist manifest novel electronic and optical properties and correlated electronic phenomena. Here, twisted flower-like MoS2 and MoSe2 bilayers were artificially fabricated by the chemical vapor deposition (CVD) method. Photoluminescence (PL) studies demonstrated that an energy band structural transition from the indirect gap to the direct gap happened in the region away from the flower center in tB MoS2 (MoSe2) flower patterns, accompanied by an enhanced PL intensity. The indirect-to-direct-gap transition in the tB-MoS2 (MoSe2) flower dominantly originated from a gradually enlarged interlayer spacing and thus, interlayer decoupling during the spiral growth of tB flower patterns. Meanwhile, the expanded interlayer spacing resulted in a decreased effective mass of the electrons. This means that the charged exciton (trion) population was reduced and the neutral exciton density was increased to obtain the upgraded PL intensity in the off-center region. Our experimental results were further evidenced by the density functional theory (DFT) calculations of the energy band structures and the effective masses of electrons and holes for the artificial tB-MoS2 flower with different interlayer spacings. The single-layer behavior of tB flower-like homobilayers provided a viable route to finely manipulate the energy band gap and the corresponding exotic optical properties by locally tuning the stacked structures and to satisfy the real requirement in TMD-based optoelectronic devices.

Twist angle-dependent work functions in CVD-grown twisted bilayer graphene probed by Kelvin probe force microscopy.

Tailoring the interlayer twist angle of bilayer graphene (BLG) significantly affects its electronic properties, including its superconductivity, topological transitions, ferromagnetic states, and correlated insulating states. These exotic electronic properties are sensitive to the work functions of BLG samples. In this study, the twist angle-dependent work functions of chemical vapour deposition-grown twisted bilayer graphene (tBLG) were investigated in detail using Kelvin probe force microscopy (KPFM) in combination with Raman spectroscopy. The thickness-dependent surface potentials of Bernal-stacked multilayer graphene were measured. It is found that with the increase in the number of layers, the work function decreases and tends to saturate. Bernal-stacked BLG and tBLG were determined via KPFM due to their twist angle-specific surface potentials. The detailed relationship between the twist angle and surface potential was determined via in situ KPFM and Raman spectral measurements. With the increase in the twist angle, the work function of tBLG will increase rapidly and then increase slowly when it is greater than 5°. The thermal stability of tBLG was investigated through a controlled annealing process. tBLG will become Bernal-stacked BLG after annealing at 350 °C. Our work provides the twist angle-dependent surface potentials of tBLG and provides the relevant conditions for the stability of the twist angle, which lays the foundation for further exploration of its twist angle-dependent electronic properties.

Gallic Acid Inhibits Mesaconitine-Activated TRPV1-Channel-Induced Cardiotoxicity.

Aconiti Kusnezoffii Radix (Caowu) is often combined or processed with Chebulae Fructus (Hezi) to achieve attenuation purposes in Mongolian medicine. Mesaconitine (MA), a main bioactive ingredient of Caowu, is also famous for its high cardiotoxicity while exerting good anti-inflammatory and analgesic properties. Gallic acid (GA), one of the leading chemical components in Hezi, possesses cardiac protection. This study aimed to clarify the detoxification effects of GA from Hezi on MA-induced cardiotoxicity and whether the detoxification mechanism is related to the TRPV1 channel. Cell viability was determined by methyl thiazol tetrazolium (MTT), and lactate dehydrogenase (LDH) leakage rate was determined by ELISA. Hoechst 33258, JC-1, DCFH-DA, and Fluo-3 AM staining were conducted to detect apoptosis, mitochondrial membrane potential, reactive oxygen species (ROS), and Ca2+ respectively; TRPV1 channel current was recorded by whole-cell patch-clamp technology to observe the effect of GA and MA alone or in combination on TRPV1 channel. The results showed that GA exhibited pronounced detoxification effects on MA-induced cardiotoxicity. GA significantly inhibited the MA-induced decrease in cell viability; suppressed the MA-induced LDH leakage rate, apoptosis, and the release of ROS and Ca2+; and alleviated the reduction of mitochondrial membrane potential. We found that MA-induced cardiotoxicity was significantly attenuated in H9c2 cells pretreated with the TRPV1 antagonist BCTC. In the whole-cell patch-clamp experiment, the TRPV1 channel current increase was caused by the GA and MA treatment, whereas it was reduced by the cotreatment of GA and MA. Our data demonstrate that GA in Hezi can reduce MA-induced cardiotoxicity by inhibiting intracellular Ca2+ influx, restoring mitochondrial membrane potential, and reducing apoptosis. The detoxification mechanism may be related to the desensitization of the TRPV1 channel by the combined application of MA and GA.

Electron waiting times in hybrid junctions with topological superconductors.

We investigate the waiting time distributions (WTDs) of superconducting hybrid junctions, considering both conventional and topologically nontrivial superconductors hosting Majorana bound states at their edges. To this end, we employ a scattering matrix formalism that allows us to evaluate the waiting times between the transmissions and reflections of electrons or holes. Specifically, we analyze normal-metal-superconductor (NIS) junctions and NISIN junctions, where Cooper pairs are spatially split into different leads. The distribution of waiting times is sensitive to the simultaneous reflection of electrons and holes, which is enhanced by the zero-energy state in topological superconductors. For the NISIN junctions, the WTDs of trivial superconductors feature a sharp dependence on the applied voltage, while for topological ones they are mostly independent of it. This particular voltage dependence is again connected to the presence of topological edge states, showing that WTDs are a promising tool for identifying topological superconductivity.

Improvement of butanol production by the development and co-culture of C. acetobutylicum TSH1 and B. cereus TSH2.

Butanol fermentation comprises two successive and distinct stages, namely acidogenesis and solventogenesis. The current lack of clarity regarding the underlying metabolic regulation of fermentation impedes improvements in biobutanol production. Here, a proteomics study was performed in the acidogenesis phase, the lowest pH point (transition point), and the solventogenesis phase in the butanol-producing symbiotic system TSH06. Forty-two Clostridium acetobutylicum proteins demonstrated differential expression levels at different stages. The protein level of butanol dehydrogenase increased in the solventogenesis phase, which was in accordance with the trend of butanol concentration. Stress proteins were upregulated either at the transition point or in the solventogenesis phase. The cell division-related protein Maf was upregulated at the transition point. We disrupted the maf gene in C. acetobutylicum TSH1, and Bacillus cereus TSH2 was added to form a new symbiotic system. TSH06△maf produced 13.9 ± 1.0 g/L butanol, which was higher than that of TSH06 (12.3 ± 0.9 g/L). Butanol was furtherly improved in fermentation at variable temperature with neutral red addition for both TSH06 and TSH06△maf. The butanol titer of the maf deletion strain was higher than that of the wild type, although the exact mechanism remains to be determined.

Isolation and characterisation of non-anaerobic butanol-producing symbiotic system TSH06.

Butanol-producing microorganisms are all obligate anaerobes. In this study, a unique symbiotic system TSH06 was isolated to be capable of producing butanol under non-anaerobic condition. Denaturing gradient gel electrophoresis (DGGE) analysis of 16S ribosomal RNA (rRNA) revealed that two strains coexist in TSH06. The two strains were identical to Clostridium acetobutylicum and Bacillus cereus, respectively. They were isolated individually and named as C. acetobutylicum TSH1 and B. cereus TSH2. C. acetobutylicum TSH1 is a butanol-producing, obligate anaerobic strain. Facultative anaerobic B. cereus TSH2 did not possess the ability of butanol production; however, it offered C. acetobutylicum TSH1 the viability under non-anaerobic condition. Moreover, B. cereus TSH2 enhanced butanol yield and speed of fermentation. TSH06 produced 12.97 g/L butanol and 15.39 g/L total solvent under non-anaerobic condition, which is 25 and 24 %, respectively, higher than those of C. acetobutylicum TSH1. In addition, TSH06 produced butanol faster under non-anaerobic condition than under anaerobic condition. Butanol accounted for more than 80 % of total solvent, which is higher than the known report. TSH06 was stable during passage. In all, TSH06 is a promising candidate for industrialisation of biobutanol with high yield, high butanol proportion, easy-handling and time-saving system. These results demonstrated the potential advantage of symbiosis. This study also provides a promising strategy for butanol fermentation.

Wigner-Poisson statistics of topological transitions in a Josephson junction.

The phase-dependent bound states (Andreev levels) of a Josephson junction can cross at the Fermi level if the superconducting ground state switches between even and odd fermion parity. The level crossing is topologically protected, in the absence of time-reversal and spin-rotation symmetry, irrespective of whether the superconductor itself is topologically trivial or not. We develop a statistical theory of these topological transitions in an N-mode quantum-dot Josephson junction by associating the Andreev level crossings with the real eigenvalues of a random non-Hermitian matrix. The number of topological transitions in a 2π phase interval scales as √[N], and their spacing distribution is a hybrid of the Wigner and Poisson distributions of random-matrix theory.