The function and therapeutic potential of transfer RNA-derived small RNAs in cardiovascular diseases: A review.

Transfer RNA-derived small RNAs (tsRNAs) are a class of small non-coding RNA (sncRNA) molecules derived from tRNA, including tRNA derived fragments (tRFs) and tRNA halfs (tiRNAs). tsRNAs can affect cell functions by participating in gene expression regulation, translation regulation, intercellular signal transduction, and immune response. They have been shown to play an important role in various human diseases, including cardiovascular diseases (CVDs). Targeted regulation of tsRNAs expression can affect the progression of CVDs. The tsRNAs induced by pathological conditions can be detected when released into the extracellular, giving them enormous potential as disease biomarkers. Here, we review the biogenesis, degradation process and related functional mechanisms of tsRNAs, and discuss the research progress and application prospects of tsRNAs in different CVDs, to provide a new perspective on the treatment of CVDs.

Carbazole-based mitochondria-targeted fluorescent probes for in vivo viscosity and cyanide detection in cells and zebrafish.

Cells of most eukaryotic species contain mitochondria, which play a role in physiological processes such as cellular senescence, metabolism, and autophagy. Viscosity is considered a key marker for many illnesses and is involved in several crucial physiological processes. Cyanide (CN-) can target cytochrome-c oxidase, disrupting the mitochondrial electron transport chain and causing cell death through asphyxiation. In this study, a fluorescent probe named HL-1, which targets mitochondria and measures viscosity and CN- levels, was designed and synthesized. HL-1 is viscosity-sensitive, with a linear correlation coefficient of up to 0.992. In addition, HL-1 was found to change color substantially during a nucleophilic addition reaction with CN-, which has a low detection limit of 47 nM. HL-1 not only detects viscosity and exogenous CN- in SKOV-3 cells and zebrafish but also monitors viscosity changes during mitochondrial autophagy in real time. Furthermore, HL-1 has been used successfully to monitor changes in mitochondrial membrane potential during apoptosis. Endogenous CN- in plant samples was quantified. HL-1 provides new ideas for studying viscosity and CN-.

[Density functional theory investigations of the spectroscopic characteristics and luminescent mechanisms of dipterex and dichlorvos].

By using G09 program package, the ground-state structures, infrared spectra, NMR spectra, UV-Vis spectra as well as the excited structures and fluorescence/phosphorescence spectra of dipterex and dichlorvos were investigated systematically, and luminescence principles were analyzed with the molecular orbitals to provide the theoretical foundation for the detection of trace dipterex and dichlorvos. Our theoretical model revealed that the IR spectra of dipterex and dichlorvos bear strong absorptions at about 1107 cm(-1), which belong to the P-O stretch modes, but dipterex has strong absorption peaks involving the O-H bond; for UV-Vis spectra, dichlorvos has a strong absorption peak at 182.03 nm, but dipterex has a weak one at 192.42 nm, which are assigned to pipi* and sigmapi* transitions, respectively; the emission spectra of dichlorvos are very weak, and has double fluorescence/phosphorescence characteristics, which may be attributed to the resonance structures of dichlorvos; the fluorescence of dipterex has a unique broad peak at 1849.22 nm, corresponding to the LUMO-->HOMO transition of S1 state.

Attention-guided context asymmetric fusion networks for the liver tumor segmentation of computed tomography images.

Background: Liver tumor segmentation based on medical imaging is playing an increasingly important role in liver tumor research and individualized therapeutic decision-making. However, it remains a challenging in terms of the accuracy of automatic segmentation of liver tumors. Therefore, we aimed to develop a novel deep neural network for improving the results from the automatic segmentation of liver tumors. Methods: This paper proposes the attention-guided context asymmetric fusion network (AGCAF-Net), combining attention guidance and fusion context modules on the basis of a residual neural network for the automatic segmentation of liver tumors. According to the attention-guided context block (AGCB), the feature map is first divided into multiple small blocks, the local correlation between features is calculated, and then the global nonlocal fusion module (GNFM) is used to obtain the global information between pixels. Additionally, the context pyramid module (CPM) and asymmetric semantic fusion module (AFM) are used to obtain multiscale features and resolve the feature mismatch during feature fusion, respectively. Finally, we used the liver tumor segmentation benchmark (LiTS) dataset to verify the efficiency of our designed network. Results: Our results showed that AGCAF-Net with AFM and CPM is effective in improving the accuracy of liver tumor segmentation, with the Dice coefficient increasing from 82.5% to 84.1%. The segmentation results of liver tumors by AGCAF-Net were superior to those of several state-of-the-art U-net methods, with a Dice coefficient of 84.1%, a sensitivity of 91.7%, and an average symmetric surface distance of 3.52. Conclusions: AGCAF-Net can obtain better matched and accurate segmentation in liver tumor segmentation, thus effectively improving the accuracy of liver tumor segmentation.

HNEAP Regulates Necroptosis of Cardiomyocytes by Suppressing the m5 C Methylation of Atf7 mRNA.

PIWI-interacting RNAs (piRNAs) are highly expressed in various cardiovascular diseases. However, their role in cardiomyocyte death caused by ischemia/reperfusion (I/R) injury, especially necroptosis, remains elusive. In this study, a heart necroptosis-associated piRNA (HNEAP) is found that regulates cardiomyocyte necroptosis by targeting DNA methyltransferase 1 (DNMT1)-mediated 5-methylcytosine (m5 C) methylation of the activating transcription factor 7 (Atf7) mRNA transcript. HNEAP expression level is significantly elevated in hypoxia/reoxygenation (H/R)-exposed cardiomyocytes and I/R-injured mouse hearts. Loss of HNEAP inhibited cardiomyocyte necroptosis and ameliorated cardiac function in mice. Mechanistically, HNEAP directly interacts with DNMT1 and attenuates m5 C methylation of the Atf7 mRNA transcript, which increases Atf7 expression level. ATF7 can further downregulate the transcription of Chmp2a, an inhibitor of necroptosis, resulting in the reduction of Chmp2a level and the progression of cardiomyocyte necroptosis. The findings reveal that piRNA-mediated m5 C methylation is involved in the regulation of cardiomyocyte necroptosis. Thus, the HNEAP-DNMT1-ATF7-CHMP2A axis may be a potential target for attenuating cardiac injury caused by necroptosis in ischemic heart disease.

Emerging roles of ferroptosis in cardiovascular diseases.

The mechanism of cardiovascular diseases (CVDs) is complex and threatens human health. Cardiomyocyte death is an important participant in the pathophysiological basis of CVDs. Ferroptosis is a new type of iron-dependent programmed cell death caused by excessive accumulation of iron-dependent lipid peroxides and reactive oxygen species (ROS) and abnormal iron metabolism. Ferroptosis differs from other known cell death pathways, such as apoptosis, necrosis, necroptosis, autophagy and pyroptosis. Several compounds have been shown to induce or inhibit ferroptosis by regulating related key factors or signalling pathways. Recent studies have confirmed that ferroptosis is associated with the development of diverse CVDs and may be a potential therapeutic drug target for CVDs. In this review, we summarize the characteristics and related mechanisms of ferroptosis and focus on its role in CVDs, with the goal of inspiring novel treatment strategies.

1,5-Dimethyl-4-[(E)-3-phenoxy-benzyl-ideneamino]-2-phenyl-1H-pyrazol-3(2H)-one.

The title Schiff base, C(24)H(21)N(3)O(2), adopts an E configuration with respect to the central C=N bond. The pyrazole ring and the central benzene ring attached to the imino group are almost coplanar. The phenyl ring attached to the pyrazole unit is twisted by 39.3 (2)° with respect to the pyrazole ring plane. The phen-oxy benzene ring makes a dihedral angle of 79.8 (2)° with the central benzene ring.