Unveiling the Promotion of Fe in Ni3S2 Catalyst on Charge Transfer for the Oxygen Evolution Reaction.

In recent years, catalysts based on transition metal sulfides have garnered extensive attention due to their low cost and excellent electrocatalytic activity in the alkaline oxygen evolution reaction. Here, the preparation of Fe-doped Ni3S2 via a one-step hydrothermal approach is reported by utilizing inexpensive transition metals Ni and Fe. In an alkaline medium, Fe-Ni3S2 exhibits outstanding electrocatalytic activity and stability for the OER, and the current density can reach 10 mA cm-2 with an overpotential of 163 mV. In addition, Pt/C||Fe-Ni3S2 is used as the membrane electrode of the anion exchange membrane water electrolyzer, which is capable of providing a current density of 650 mA cm-2 at a cell voltage of 2.0 V, outperforming the benchmark Ir/C. The principle is revealed that the doping of Fe enhances the electrocatalytic water decomposition ability of Ni3S2 by in situ Raman and in situ X-ray absorption fine structure. The results indicate that the doping of Fe decreases the charge density near Ni atoms, which renders Fe-Ni3S2 more favorable for the adsorption of OH- and the formation of *OO- intermediates. This work puts forward an effective strategy to significantly improve both the alkaline OER activity and stability of low-cost electrocatalysts.

Wet Conformation of Prion-Like Domain and Intimate Correlation of Hydration and Conformational Fluctuations.

Proteins with prion-like domains (PLDs) are involved in neurodegeneration-associated aggregation and are prevalent in liquid-like membrane-less organelles. These PLDs contain amyloidogenic stretches but can maintain dynamic disordered conformations, even in the condensed phase. However, the molecular mechanism underlying such intricate conformational properties of PLDs remains elusive. Here we employed molecular dynamics simulations to investigate the conformational properties of a prototypical PLD system (i.e., FUS PLD). According to our simulation results, PLD adopts a wet collapsed conformation, wherein most residues maintain sufficient hydration with the abundance of internal water. These internal water molecules can rapidly exchange between the protein interior and the bulk, enabling intensive coupling of the entire protein with its hydration environment. The dynamic exchange of water molecules is intimately correlated to the overall conformational fluctuations of PLD. Furthermore, the abundance of dynamic internal water suppresses the formation of aggregation-prone ordered structures. These results collectively elucidate the crucial role of internal water in sustaining the dynamic disordered conformation of the PLD and inhibiting its aggregation propensity.

Predicting the Dynamic Interaction of Intrinsically Disordered Proteins.

Intrinsically disordered proteins (IDPs) participate in various biological processes. Interactions involving IDPs are usually dynamic and are affected by their inherent conformation fluctuations. Comprehensive characterization of these interactions based on current techniques is challenging. Here, we present GSALIDP, a GraphSAGE-embedded LSTM network, to capture the dynamic nature of IDP-involved interactions and predict their behaviors. This framework models multiple conformations of IDP as a dynamic graph, which can effectively describe the fluctuation of its flexible conformation. The dynamic interaction between IDPs is studied, and the data sets of IDP conformations and their interactions are obtained through atomistic molecular dynamic (MD) simulations. Residues of IDP are encoded through a series of features including their frustration. GSALIDP can effectively predict the interaction sites of IDP and the contact residue pairs between IDPs. Its performance in predicting IDP interactions is on par with or even better than the conventional models in predicting the interaction of structural proteins. To the best of our knowledge, this is the first model to extend the protein interaction prediction to IDP-involved interactions.

LncRNA CARMN inhibits abdominal aortic aneurysm formation and vascular smooth muscle cell phenotypic transformation by interacting with SRF.

Phenotypic transformation of vascular smooth muscle cells (VSMCs) plays a crucial role in abdominal aortic aneurysm (AAA) formation. CARMN, a highly conserved, VSMC-enriched long noncoding RNA (lncRNA), is integral in orchestrating various vascular pathologies by modulating the phenotypic dynamics of VSMCs. The influence of CARMN on AAA formation, particularly its mechanisms, remains enigmatic. Our research, employing single-cell and bulk RNA sequencing, has uncovered a significant suppression of CARMN in AAA specimens, which correlates strongly with the contractile function of VSMCs. This reduced expression of CARMN was consistent in both 7- and 14-day porcine pancreatic elastase (PPE)-induced mouse models of AAA and in human clinical cases. Functional analyses disclosed that the diminution of CARMN exacerbated PPE-precipitated AAA formation, whereas its augmentation conferred protection against such formation. Mechanistically, we found CARMN's capacity to bind with SRF, thereby amplifying its role in driving the transcription of VSMC marker genes. In addition, our findings indicate an enhancement in CAMRN transcription, facilitated by the binding of NRF2 to its promoter region. Our study indicated that CARMN plays a protective role in preventing AAA formation and restrains the phenotypic transformation of VSMC through its interaction with SRF. Additionally, we observed that the expression of CARMN is augmented by NRF2 binding to its promoter region. These findings suggest the potential of CARMN as a viable therapeutic target in the treatment of AAA.

The NLRP3 molecule is responsible for mediating the pyroptosis of intestinal mucosa cells and plays a crucial role in salmonellosis enteritis in chicks.

Salmonella enteritis in poultry can result in reduced immune function, decreased growth rate, and increased mortality. Many farm salmonella strains have developed severe drug resistance and are less susceptible to multiple antibiotics. In the post-antibiotic era, it is of great significance to identify the mechanism of salmonella-induced enteritis in chicks to protect their health and ensure food safety. This article will elucidate the activation mechanism of NOD-like receptor protein 3 (NLRP3) inflammasomes in Salmonella enteritis and review the research on interventions targeting NLRP3 inflammasomes.

Exploring the micromorphological characteristics of adult lower cervical vertebrae based on micro-computed tomography.

We will use micro-computed tomography to scan 31 sets of the adult lower cervical vertebrae (155 vertebrae) to observe the morphological characteristics and direction of trabeculae in the lower cervical vertebrae by outlining and reconstructing the regions of interest and to calculate the variation laws of the microstructure in the regions of interest to reveal their structural characteristics and weak areas. As a result, the images showed that the trabeculae in the lower cervical pedicle near the medial and lateral cortices were relatively dense, and their bone plates were lamellar. There were cavities between the superior and inferior articular processes where the ossification centers had not been absorbed after ossified. The lamellar trabeculae in the vertebral plates near the cortical bones were only 1-2 layers, extended and transformed into rod-shaped trabeculae in a radial shape toward the medullary space. The lamellar trabeculae of the vertebral plate extend over the spinous process near the cortical bone. The statistical results of the trabeculae's morphological parameters showed significant differences in bone volume fraction values among the four parts (P < 0.05). There were substantial differences in BS/BV, except for no differences between the pedicle and the vertebral plate (P < 0.05). There was a significant difference in trabecular pattern factor values between the articular process, the spinous process, and the vertebral plate (P < 0.05) and a significant difference between the pedicle, the spinous process, and the vertebral plate (P < 0.05). There were no significant differences in trabecular bone thickness and trabecular space values among the four parts (P < 0.05). The anatomical microstructural perspective confirms that the optimal choice is internal fixation via the pedicle. If using pedicle screws, the nail tract needs to be placed into the spinous process to increase its holding power and resistance to extraction.

Examination of the microstructures of the lower cervical facet based on micro-computed tomography: A cadaver study.

The cervical facet has complicated 3D microstructures and inhomogeneities. The cervical facet joint, which also participates in the formation, plays a certain role in regulating and limiting the movement of the spine. Correct identification and evaluation of its microstructure can help in the diagnosis of orthopedic disease and predict early phases of fracture risk. To evaluate the safety of the cervical spine by measuring and analyzing the microstructures and morphometric parameters of bone trabeculae in the normal cervical facet with high-resolution 3D micro-computed tomography. Thirty-one sets of C3 to C7 lower cervical vertebrae (155 vertebrae) were scanned using micro-computed tomography. The morphological characteristics and direction of trabecular bone in the facet of the lower cervical vertebrae were observed by selecting and rebuilding the areas of interest, and the changes in the microstructure of the areas of interest were calculated to reveal the structural characteristics and weak areas. Images indicated an ossified center between the superior and inferior articular processes of the lower cervical spine. The cellular bone trabeculae of the articular process had complex reticular microstructures. The trabecular bone plate near the cortical bone was lamellar and relatively dense, and it extended around and transformed into a network structure, and then into the rod-shaped trabecular bone. The rod-shaped trabeculae converged with the plate-shaped trabeculae with only 1 to 2 layers surrounding the trabeculae cavity. Statistical results of the morphological parameters of the trabecular bone showed that trabecular bone volume fraction values were significantly higher for C7 than for C3 to C6 (P < .05). There were significant differences between C7 and C3 to C5 and between C6 and C4 in bone surface area/bone volume (P < .05). There was a significant difference between C7 and C3 to C6 in trabecular bone thickness values (P < .05). The degree of anisotropy value was significantly smaller for C3 than for C6 and C7 (P < .05). The changes in the C3 to C7 microstructure were summarized in this study. The loading capacity and stress of the C7 articular process tended to be limited, and the risk of injury tended to be higher for the C7 articular process.

Residue-Frustration-Based Prediction of Protein-Protein Interactions Using Machine Learning.

The study of protein-protein interactions (PPIs) is important in understanding the function of proteins. However, it is still a challenge to investigate the transient protein-protein interaction by experiments. Hence, the computational prediction for protein-protein interactions draws growing attention. Statistics-based features have been widely used in the studies of protein structure prediction and protein folding. Due to the scarcity of experimental data of PPI, it is difficult to construct a conventional statistical feature for PPI prediction, and the application of statistics-based features is very limited in this field. In this paper, we explored the application of frustration, a statistical potential, in PPI prediction. By comparing the energetic contribution of the extra stabilization energy from a given residue pair in the native protein with the statistics of the energies, we obtained the residue pair's frustration index. By calculating the number of residue pairs with a high frustration index, the highly frustrated density, a residue-frustration-based feature, was then obtained to describe the tendency of residues to be involved in PPI. Highly frustrated density, as well as structure-based features, were then used to describe protein residues and combined with the long short-term memory (LSTM) neural network to predict PPI residue pairs. Our model correctly predicted 75% dimers when only the top 2‰ residue pairs were selected in each dimer. Our model, which considers the statistics-based features, is significantly different from the models based on the chemical features of residues. We found that frustration can effectively describe the tendency of residue to be involved in PPI. Frustration-based features can replace chemical features to combine with machine learning and realize the better performance of PPI prediction. It reveals the great potential of statistical potential such as frustration in PPI prediction.

Circular RNA Cdyl promotes abdominal aortic aneurysm formation by inducing M1 macrophage polarization and M1-type inflammation.

Macrophage polarization plays a crucial role in regulating abdominal aortic aneurysm (AAA) formation. Circular RNAs (circRNAs) are important regulators of macrophage polarization during the development of cardiovascular diseases. How-ever, the roles of circRNAs in regulating AAA formation through modulation of macrophage polarization remain unknown. In the present study, we compared circRNA microarray data under two distinct polarizing conditions (M1 and M2 macrophages) and identified an M1-enriched circRNA, circCdyl. Loss- and gain-of-function assay results demonstrated that circCdyl overexpression accelerated angiotensin II (Ang II)- and calcium chloride (CaCl2)-induced AAA formation by promoting M1 polarization and M1-type inflammation, while circCdyl deficiency showed the opposite effects. RNA pulldown, mass spectrometry analysis, and RNA immunoprecipitation (RIP) assays were conducted to elucidate the underlying mechanisms by which circCdyl regulates AAA formation and showed that circCdyl promotes vascular inflammation and M1 polarization by inhibiting interferon regulatory factor 4 (IRF4) entry into the nucleus, significantly inducing AAA formation. In addition, circCdyl was shown to act as a let-7c sponge, promoting C/EBP-δ expression in macrophages to induce M1 polarization. Our results indicate an important role for circCdyl-mediated macrophage polarization in AAA formation and provide a potent therapeutic target for AAA treatment.

MicroRNA-23b prevents aortic aneurysm formation by inhibiting smooth muscle cell phenotypic switching via FoxO4 suppression.

AIMS: Phenotypic switching of vascular smooth muscle cells (VSMCs) is essential for the formation of abdominal aortic aneurysms (AAAs). MicroRNA-23b (miR-23b) has recently been shown to play a vital role in maintaining the VSMC contractile phenotype; however, little is known about the role of miR-23b in the formation of AAAs. Here, we investigated whether miR-23b prevents AAA formation by inhibiting VSMC phenotypic switching. MATERIALS AND METHODS: We administered angiotensin II (Ang II, 1000 ng/kg/min) or vehicle to 10-12-week-old male apolipoprotein E knockout (ApoE-/-) or C57BL/6J mice via subcutaneous osmotic minipumps for 4 weeks. KEY FINDINGS: The expression of miR-23b was significantly reduced in the aorta during the early onset of AAA in angiotensin II-treated ApoE-/- mice and in human AAA samples. In vitro experiments showed that the suppression of SMC contractile marker gene expression induced by Ang II was accelerated by miR-23b inhibitors but inhibited by mimics. In vivo studies revealed that miR-23b deficiency in Ang II-treated C57BL/6J mice aggravated the formation of AAAs in these mice compared with control mice; the opposite results were observed in miR-23b-overexpressing mice. Mechanistically, miR-23b knockdown significantly increased the expression of the transcription factor forkhead box O4 (FoxO4) during VSMC phenotypic switching induced by Ang II. In addition, a luciferase reporter assay showed that FoxO4 is a target of miR-23b in VSMCs. SIGNIFICANCE: Our study revealed a pivotal role for miR-23b in protecting against aortic aneurysm formation by maintaining the VSMC contractile phenotype.