Glycyrrhizin arginine salt protects against cisplation-induced acute liver injury by repressing BECN1-mediated ferroptosis

The study aimed to investigate the protective effects and biological mechanisms of glycyrrhizin arginine salt (Gly-Arg) against cisplatin (Cis)-induced liver injury. Our data showed that Gly-Arg improved Cis-induced liver injury. Further study showed that BECN1 (beclin1) and LC3-II/LC3-I protein expression was significantly increased in primary hepatocytes and mouse liver tissues after Cis treatment, but Gly-Arg reduced the protein levels of BECN1 and LC3-II/LC3-I in primary hepatocytes and mouse liver tissues. Also, Gly-Arg improved indicators related to Cis-induced ferroptosis. Furthermore, Cis increased colocalization of lysosomal membrane-associated protein 1A (LAMP1) with ferritin heavy chain 1 (FTH1) in primary mouse hepatocytes, while Gly-Arg intervention attenuated this colocalization in primary hepatocytes. More improtantly, Cis enhanced the formation of the BECN1-xCT complex, thus inhibiting solute carrier family 7 member 11 (SLC7A11, xCT) and glutathione peroxidase-4 (GPX4) activity. In contrast, Gly-Arg intervention disrupted the formation of this complex. However, Gly-Arg alleviated Cis-induced liver injury in mice by preventing autophagic death and ferroptosis through the inhibition of BECN1-xCT complex formation

Recent Progress in Phage Therapy to Modulate Multidrug-Resistant Acinetobacter baumannii, Including in Human and Poultry

Acinetobacter baumannii is a multidrug-resistant and invasive pathogen associated with the etiopathology of both an increasing number of nosocomial infections and is of relevance to poultry production systems. Multidrug-resistant Acinetobacter baumannii has been reported in connection to severe challenges to clinical treatment, mostly due to an increased rate of resistance to carbapenems. Amid the possible strategies aiming to reduce the insurgence of antimicrobial resistance, phage therapy has gained particular importance for the treatment of bacterial infections. This review summarizes the different phage-therapy approaches currently in use for multiple-drug resistant Acinetobacter baumannii, including single phage therapy, phage cocktails, phage–antibiotic combination therapy, phage-derived enzymes active on Acinetobacter baumannii and some novel technologies based on phage interventions. Although phage therapy represents a potential treatment solution for multidrug-resistant Acinetobacter baumannii, further research is needed to unravel some unanswered questions, especially in regard to its in vivo applications, before possible routine clinical use

Rif1 Maintains Telomere Length Homeostasis of ESCs by Mediating Heterochromatin Silencing

SummaryTelomere length homeostasis is essential for genomic stability and unlimited self-renewal of embryonic stem cells (ESCs). We show that telomere-associated protein Rif1 is required to maintain telomere length homeostasis by negatively regulating Zscan4 expression, a critical factor for telomere elongation by recombination. Depletion of Rif1 results in terminal hyperrecombination, telomere length heterogeneity, and chromosomal fusions. Reduction of Zscan4 by shRNA significantly rescues telomere recombination defects of Rif1-depleted ESCs and associated embryonic lethality. Further, Rif1 negatively modulates Zscan4 expression by maintaining H3K9me3 levels at subtelomeric regions. Mechanistically, Rif1 interacts and stabilizes H3K9 methylation complex. Thus, Rif1 regulates telomere length homeostasis of ESCs by mediating heterochromatic silencing

DeePMD-kit v2: A software package for Deep Potential models

DeePMD-kit is a powerful open-source software package that facilitates molecular dynamics simulations using machine learning potentials (MLP) known as Deep Potential (DP) models. This package, which was released in 2017, has been widely used in the fields of physics, chemistry, biology, and material science for studying atomistic systems. The current version of DeePMD-kit offers numerous advanced features such as DeepPot-SE, attention-based and hybrid descriptors, the ability to fit tensile properties, type embedding, model deviation, Deep Potential - Range Correction (DPRc), Deep Potential Long Range (DPLR), GPU support for customized operators, model compression, non-von Neumann molecular dynamics (NVNMD), and improved usability, including documentation, compiled binary packages, graphical user interfaces (GUI), and application programming interfaces (API). This article presents an overview of the current major version of the DeePMD-kit package, highlighting its features and technical details. Additionally, the article benchmarks the accuracy and efficiency of different models and discusses ongoing developments.Comment: 51 pages, 2 figure

Coupling Relationship between Urban Expansion and Lake Change—A Case Study of Wuhan

With the development of urbanisation, the contradiction between urban expansion and lake protection becomes increasingly evident. Particularly, lake reclamation of urban construction causes serious damage to the water system and further affects the ecological environment of urban areas. On the basis of the interpretation and analysis of long time-series remote sensing images, this study evaluated the spatial pattern and dynamic changes of urban built-up areas and lakes in Wuhan from 1987–2018 and analysed the role of urban policies in this process. A coupling coordination degree model was used to analyse the correlation between them. Results show that with the continuous advancement of urban construction and renewal of urban policies, the coupling degree between urban expansion and lake change in Wuhan has been on the rise in the past 30 years. Moreover, the antagonistic relationship between urban construction and lake protection has gradually eased from severe imbalance to slightly balanced, and the negative impact of urban development on lake change has gradually decreased. The findings underscore the need for Wuhan to adhere to policies that promote lake protection. Lake supervision should be strengthened, and ecological restoration should be actively promoted. Furthermore, sustainable urban development policies should be maintained to improve the quality of urban development

SAR Multi-Angle Observation Method for Multipath Suppression in Enclosed Spaces

Synthetic aperture radar (SAR) is a powerful tool for detecting and imaging targets in enclosed environments, such as tunnels and underground garages. However, SAR performance is degraded by multipath effects, which occur when electromagnetic waves are reflected by obstacles, such as walls, and interfere with the direct signal. This results in the formation of multipath ghost images, which obscure the true target and reduce the image quality. To overcome this challenge, we propose a novel method based on multi-angle observation. This method exploits the fact that the position of ghost images changes depending on the angle of the radar, while the position of the true target remains stable. By collecting and processing multiple data sets from different angles, we can eliminate the ghost images and enhance the target image. In addition, we introduce a center vector distance algorithm to address the complexity and computational intensity of existing multipath suppression algorithms. This algorithm, which defines the primary direction of multi-angle vectors from stable scattering centers as the center vector, processes and synthesizes multiple data sets from multi-angle observations. It calculates the distance of pixel intensity sequences in the composite data image from the center vector. Pixels within a specified threshold are used for imaging, and the final result is obtained. Simulation experiments and real SAR data from underground garages confirm the effectiveness of this method in suppressing multipath ghost images

Idiopathic Ventricular Arrhythmias Originating from Different Portions of the Coronary Venous System: Prevalence, Electrocardiographic Characteristics, Catheter Ablation, and Complications

(1) Background: To determine the prevalence, electrocardiographic characteristics, mapping, and ablation of IVAs arising from the CVS. (2) Methods: Detailed activation and pace mapping of the CVS IVAs was performed before attempted radiofrequency ablation (RFCA). (3) Results: The IVAs originating from the vicinity of the CVS represented approximately 5.27% (164/3113) of all IVAs; 94.51% (155/164) cases were accessed at the earliest identified site and 83.54% (137/164) IVAs were successfully ablated. The main coronary vein group had a relatively short procedure time, short fluoroscopy time, fewer radiofrequency lesions prior to success, and less Swartz sheath support. IVAs originating from the CVS had distinct ECG characteristics: Rs, RS or rS (with s or S) wave in lead V1 indicate the Vas arising from the proximal portion of the anterior interventricular vein (AIV) and summit-CV; Rs (with s or S) wave in leads V5–V6 indicate the Vas arising from the adjacent regions of the distal great cardiac vein 1 (DGCV1); positive wave (R, Rs or r) In lead I indicate the VAs ori”inat’ng from Summit-CV and posterior wall subgroup (including middle cardiac vein [MCV], posterior lateral vein [PLV], coronary sinus [CS]). Compared with the IVAs originating from the endocardial mitral annulus, a PdW > 45 ms, an IDT > 74 ms, and an MDI > 0.50 indicate a CVS origin of the IVAs. The common peri-procedure complications were CV dissection (6.45%, 10/155), CV rupture (1.29%, 2/155), coronary artery spasm (1.29%, 2/155), coronary artery stenosis (0.65%, 1/155), pericardial effusion (0.65%, 1/155) and tamponade (1.29%, 2/155). Stenosis of coronary arteries was not observed at the adjacent ablation site in the CVS during follow-up. (4) Conclusions: vAs arising from the CVS are not a rare phenomenon. Several ECG and procedure characteristics could help regionalize, map, and ablate the origin of IVAs from different portions of the CVS. RFCA within the CVS was relatively effective and safe

Zscan4 Contributes to Telomere Maintenance in Telomerase-Deficient Late Generation Mouse ESCs and Human ALT Cancer Cells

Proper telomere length is essential for indefinite self-renewal of embryonic stem (ES) cells and cancer cells. Telomerase-deficient late generation mouse ES cells and human ALT cancer cells are able to propagate for numerous passages, suggesting telomerase-independent mechanisms responding for telomere maintenance. However, the underlying mechanisms ensuring the telomere length maintenance are unclear. Here, using late generation telomerase KO (G4 Terc-/-) ESCs as a model, we show that Zscan4, highly upregulated in G4 Terc-/- ESCs, is responsible for the prolonged culture of these cells with stably short telomeres. Mechanistically, G4 Terc-/- ESCs showed reduced levels of DNA methylation and H3K9me3 at Zscan4 promoter and subtelomeres, which relieved the expression of Zscan4. Similarly, human ZSCAN4 was also derepressed by reduced H3K9me3 at its promoter in ALT U2 OS cells, and depletion of ZSCAN4 significantly shortened telomeres. Our results define a similar conserved pathway contributing to the telomere maintenance in telomerase-deficient late generation mESCs and human ALT U2OS cancer cells