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Abstract Objectives The pathophysiology of diabetic cardiomyopathy (DCM) is a phenomenon of great interest, but its clinical problems have not yet been effectively addressed. Recently, the mechanism of ferroptosis in the pathophysiology of various diseases, including DCM, has attracted widespread attention. Here, we explored the role of PACS2 in ferroptosis in DCM through its downregulation of PACS2 expression. Methods and results Cardiomyocytes were treated with high glucose and palmitic acid (HGPA), and the detection of cardiomyocyte iron ions, lipid peroxides, and reactive oxygen species (ROS) revealed clear ferroptosis during these treatments. Silencing PACS2 downregulated CPT1A expression and upregulated DHODH expression significantly, reversing HGPA-induced ferroptosis. Further silencing of PACS2 with a CPT1A agonist exacerbated cardiomyocyte ferroptosis while promoting mitochondrial damage in cardiomyocytes. Using a mouse model of type 2 diabetes induced by streptozotocin (STZ) and a high-fat diet (HFD), we found that PACS2 deletion reversed these treatment-induced increases in cellular iron ions, impaired cardiac function, mitochondrial damage and ferroptosis in cardiac muscle tissues. Conclusions The PACS2/CPT1A/DHODH signalling pathway may be involved in ferroptosis in DCM by regulating cardiomyocyte mitochondrial function.

The western edge fault of the Maoyaba Basin, a branch of the Litang fault zone in western Sichuan, is the western boundary fault controlling the Great Maoyaba Basin. There have been no reports on its geometric distribution and deep structure. This article uses high-density electrical method and shallow seismic exploration technology to conduct geophysical exploration on the northern and southern sections of the western edge fault of the Maoyaba Basin, respectively. The response characteristics of the western edge fault of the Maoyaba Basin revealed by the high-density electrical method and shallow seismic exploration profiles are analyzed. The western edge fault of the Maoyaba Basin shows lateral displacement of the marker layer on the shallow seismic reflection profile, with the presence of fault diffraction waves and other phenomena. The tomographic inversion velocity profile reflects significant changes in the lateral velocity on both sides of the fault, suggesting that the depth of the upper breakpoint is shallower than 15 m. The low resistance strip characteristics on the apparent resistivity profile inverted by the high-density electrical method are preliminarily determined by combining field investigation and regional geological data to determine the production of the fault, shape, geometric structure, and planar layout. Advantages, disadvantages, and application prerequisites of the two geophysical methods in active fault detection are also explored in this article. Based on similar cases domestically and internationally, a combination of multiple methods is proposed to more effectively detect fault structures.

The expansion of the rural middle-income group has been a global focus as it contributes to narrowing income gaps and reducing social inequality. Using data from the China Family Panel Studies (CFPS), this study examines the impact of Internet use on the mobility of rural low-income groups to the middle-income group from the perspective of income mobility. Controlling for household and provincial-level variables, the results of this study indicate that Internet use significantly promotes the mobility of rural low-income groups to the middle-income group, thereby facilitating the expansion of the rural middle-income group. These conclusions hold even after conducting endogeneity and robustness tests. Mechanism analysis shows that household entrepreneurship and non-agricultural employment are crucial pathways through which Internet use facilitates the mobility of rural low-income groups to middle-income groups. Further investigation shows that mobility from rural low-income to middle-income groups is more difficult in central-western regions and among those with lower levels of education. Internet use exacerbates the “digital divide” between different areas and education groups. In particular, the effect of Internet use in promoting mobility from rural low-income to middle-income groups is more pronounced in the eastern regions and among those with higher levels of education. The results of this study provide new evidence on the role of Internet use in expanding the rural middle-income group.

Abstract Background Cardiovascular health (CVH) and abdominal aortic calcification (AAC) are closely linked to cardiovascular disease (CVD) and related mortality. However, the relationship between CVH metrics via Life’s Essential 8 (LE8) and AAC remains unexplored. Methods The study analyzed data from the 2013–2014 National Health and Nutrition Examination Survey (NHANES) cohort, which included adults aged 40 or above. The research used the LE8 algorithm to evaluate CVH. Semi-quantitative AAC-24 scoring techniques were employed to assess AAC, categorized into no calcification, mild to moderate calcification, and severe calcification. Results The primary analysis involved 2,478 participants. Following adjustments for multiple factors, the LE8 score exhibited a significant association with ACC risk (Mild-moderate ACC: 0.87, 95% CI: 0.81,0.93; Severe ACC: 0.77, 95% CI: 0.69,0.87, all P

Tofu is a widely consumed protein gel, which is the denaturation of soybean protein (specifically the 7S and 11S globulin), under heat treatment, and the aggregation by salt ions, hydrogen ions or enzymes, forming a dense and uniform protein gel with a network structure. The formation of tofu gel and quality of tofu are affected by many factors. In this paper, a comprehensive review of the impact factors on tofu gel formation and quality is presented. The types of coagulants including salts, acids, and enzymatic coagulants, together with processing conditions such as the processing raw material, pulping method, pH value, and heat treatment are all discussed. The research progress on the effects of coagulants and processing conditions on the formation and quality of tofu gel is reviewed, to provide a theoretical guidance for industrial tofu production and a scientific basis for research and development of tofu food and quality control.

Abstract Objective This study aimed to evaluate the association of triglyceride-glucose (TyG) index with all-cause and cardiovascular mortality risk among patients with cardiometabolic syndrome (CMS). Methods We performed a cohort study of 5754 individuals with CMS from the 2001–2018 National Health and Nutrition Examination Survey. The TyG index was calculated as Ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multivariate Cox proportional hazards regression models assessed the associations between TyG index and mortality . Non-linear correlations and threshold effects were explored using restricted cubic splines and a two-piecewise Cox proportional hazards model. Results Over a median follow-up of 107 months, 1201 all-cause deaths occurred, including 398 cardiovascular disease-related deaths. The multivariate Cox proportional hazards regression model showed a positive association between the TyG index and all-cause and cardiovascular mortality. Each one-unit increase in the TyG index was associated with a 16% risk increase in all-cause mortality (HR: 1.16, 95% CI 1.03, 1.31, P = 0.017) and a 39% risk increase in cardiovascular mortality (HR: 1.39, 95% CI 1.14, 1.71, P = 0.001) after adjusting for confounders. The restricted cubic splines revealed a U-shaped association between the TyG index and all-cause (P for nonlinear

Abstract Obesity is often accompanied by metabolic disorder and insulin resistance, resulting in type 2 diabetes. Based on previous findings, FYGL, a natural hyperbranched proteoglycan extracted from the G. lucidum fruiting body, can decrease blood glucose and reduce body weight in diabetic mice. In this article, the underlying mechanism of FYGL in ameliorating obesity-induced diabetes was further investigated both in vivo and in vitro. FYGL upregulated expression of metabolic genes related to fatty acid biosynthesis, fatty acid β-oxidation and thermogenesis; downregulated the expression of insulin resistance-related genes; and significantly increased the number of beige adipocytes in db/db mice. In addition, FYGL inhibited preadipocyte differentiation of 3T3-L1 cells by increasing the expression of FABP-4. FYGL not only promoted fatty acid synthesis but also more significantly promoted triglyceride degradation and metabolism by activating the AMPK signalling pathway, therefore preventing fat accumulation, balancing adipocyte production and lipid metabolism, and regulating metabolic disorders and unhealthy obesity. FYGL could be used as a promising pharmacological agent for the treatment of metabolic disorder-related obesity.

Bioactive glasses (BGs) are ideal biomaterials in the field of bio-restoration due to their excellent biocompatibility. Titanium alloys are widely used as a bone graft substitute material because of their excellent corrosion resistance and mechanical properties; however, their biological inertness makes them prone to clinical failure. Surface modification of titanium alloys with bioactive glass can effectively combine the superior mechanical properties of the substrate with the biological properties of the coating material. In this review, the relevant articles published from 2013 to the present were searched in four databases, namely, Web of Science, PubMed, Embase, and Scopus, and after screening, 49 studies were included. We systematically reviewed the basic information and the study types of the included studies, which comprise in vitro experiments, animal tests, and clinical trials. In addition, we summarized the applied coating technologies, which include pulsed laser deposition (PLD), electrophoretic deposition, dip coating, and magnetron sputtering deposition. The superior biocompatibility of the materials in terms of cytotoxicity, cell activity, hemocompatibility, anti-inflammatory properties, bioactivity, and their good bioactivity in terms of osseointegration, osteogenesis, angiogenesis, and soft tissue adhesion are discussed. We also analyzed the advantages of the existing materials and the prospects for further research. Even though the current research status is not extensive enough, it is still believed that BG-coated Ti implants have great clinical application prospects.

Reactive oxygen species (ROS) and salicylic acid (SA) are essential signaling molecules in plant cells that participate in responses to biotic and abiotic stresses. Changes in ROS and SA signals during interactions between pear and the pear scab pathogen Venturia nashicola remain unclear. Herein, we analyzed the roles of ROS in the signal transduction pathway of pear scab resistance using the highly resistant Huangguan and susceptible Xuehua cultivars of pear (Pyrus bretschneideri Rehd). Protoplasts, calluses, and leaves were obtained from 14-year-old pear trees and treated with V. nashicola for different periods. The results showed that ROS rapidly accumulated in protoplasts of both cultivars within a 120-min treatment period, but the fluorescence intensity of ROS differed between cultivars. The H2O2 content in fruit-derived calluses of Huangguan peaked at 48 h post-infection at levels 1.85 times higher than those in Xuehua. Induction of H2O2 by V. nashicola in Huangguan was more intense than in Xuehua over a 96-h treatment period. At 96 h post-infection, the malondialdehyde content in leaves of Huangguan was significantly lower than in Xuehua, while the activities of superoxide dismutase, peroxidase, and catalase, and the relative expression levels of PbMnSOD, PbPOD, and PbCAT genes were higher in Huangguan than Xuehua. V. nashicola infection also caused a continuous increase in the leaf SA content of Huangguan, which was 6.76 times higher than in Xuehua at 96 h post-infection, and V. nashicola exposure upregulated the expression of PbPAL, PbICS, PbPR1, and PbPR5. In summary, both ROS and SA participated in the responses of pear trees to V. nashicola infection and played vital roles in the signal transduction pathway of pear scab resistance.

Magnesium alloys have great application prospects as ideal bone implant materials. However, their poor corrosion resistance limits their clinical orthopedic application. Surface modification promotes the corrosion resistance of magnesium. Conversion coatings, such as calcium phosphate (Ca-P) coating, microarc oxidation (MAO) treatment, and fluoride (FLU) treatment, have been extensively investigated in in vivo studies. This systematic review and network meta-analysis compared the influence of different conversion coatings on bone repair, material properties, and systemic host response in orthopedic applications. Using the PICOS model, the inclusion criteria for biodegradable magnesium and its alloys were determined for in vivo studies. Four databases were used. The standard and weight mean differences with 95% confidence intervals were used to analyze new bone formation and degradation rate. Network structure and forest plots were created, and ranking probabilities were estimated. The risk of bias and quality of evidence were assessed using SYRCLE, CERQual, and GRADE tools. In the qualitative analysis, 43 studies were selected, and the evaluation of each outcome indicator was not entirely consistent from article to article. In the quantitative analysis, 21 articles were subjected to network meta-analysis, with 16 articles on implant degradation and 8 articles for new bone formation. Additionally, SUCRA indicated that Ca-P coating exhibited the highest corrosion resistance, followed by FLU treatment. MAO demonstrated the best capability for new bone formation, followed by Ca-P coating. Ca-P coating exhibited the highest overall performance. To conclude, coated Mg can promote better new bone formation than bare Mg and has considerable biocompatibility. Ca-P-coated Mg and MAO-coated Mg have the greatest potential to significantly promote corrosion resistance and bone regeneration, respectively. The findings of this study will provide a theoretical basis for the investigation of composite coatings and guidance for the orthopedic application of Mg bone implants.

Due to their unprecedented ability to flexibly manipulate the parameters of light, metasurfaces offer a new approach to integrating multiple functions in a single optical element. In this paper, based on a single-celled metasurface composed of chiral umbrella-shaped metal–insulator–metal (MIM) unit cells, a strategy for simultaneous multiple polarization generation and wavefront shaping is proposed. The unit cells can function as broadband and high-performance polarization-preserving mirrors. In addition, by introducing a chiral-assisted Aharonov–Anandan (AA) geometric phase, the phase profile and phase retardation of two spin-flipped orthogonal circular polarized components can be realized simultaneously and independently with a single-celled metasurface via two irrelevant parameters. Benefiting from this flexible phase manipulation ability, a vectorial hologram generator and metalens array with spatially varying polarizations were demonstrated. This work provides an effective approach to avoid the pixel and efficiency losses caused by the intrinsic symmetry of the PB geometric phase, and it may play an important role in the miniaturization and integration of multipolarization-involved displays, real-time imaging, and spectroscopy systems.

Oligomerization of the mixed-lineage kinase domain-like protein (MLKL) is essential for its cation channel function in necroptosis. Here we show that the MLKL channel is an octamer comprising two previously identified tetramers most likely in their side-by-side position. Intermolecule disulfide bonds are present in the tetramer but are not required for octamer assembly and necroptosis. MLKL forms oligomers in the necrosome and is then released from the necrosome before or during its membrane translocation. We identified two MLKL mutants that could not oligomerize into octamers, although they formed a tetramer, and also, one MLKL mutant could spontaneously form a disulfide bond-linked octamer. Subsequent analysis revealed that the tetramers fail to translocate to the plasma membrane and that the MLKL octamer formation depends on α-helices 4 and 5. While MLKL could be detected from outside the cells, its N- and C-terminal ends could not be detected, indicating that the MLKL octamer spans across the plasma membrane, leaving its N and C termini inside the cell. These data allowed us to propose a 180° symmetry model of the MLKL octamer and conclude that the fully assembled MLKL octamers, but not the previously described tetramers, act as effectors of necroptosis. [ABSTRACT FROM AUTHOR]

Receptor interacting protein 3 (RIP3) is a protein kinase essential for TNF-induced necroptosis. Phosphorylation on Ser-227 in human RIP3 (hRIP3) is required for its interaction with human mixed lineage kinase domain-like (MLKL) in the necrosome, a signaling complex induced by TNF stimulation. RIP1 and RIP3 mediate necrosome aggregation leading to the formation of amyloid-like signaling complexes. We found that TNF induces Thr-231 and Ser-232 phosphorylation in mouse RIP3 (mRIP3) and this phosphorylation is required for mRIP3 to interact with mMLKL. Ser-232 in mRIP3 corresponds to Ser- 227 in hRIP3, whereas Thr-231 is not conserved in hRIP3. Although the RIP3-MLKL interaction is required for necroptosis in both human and mouse cells, hRIP3 does not interact with mMLKL and mRIP3 cannot bind to hMLKL. The species specificity of the RIP3-MLKL interaction is primarily determined by the sequence differences in the phosphorylation sites and the flanking sequence around the phosphorylation sites in hRIP3 and mRIP3. It appears that the RIP3-MLKL interaction has been selected as an evolutionarily conserved mechanism in mediating necroptosis signaling despite that differing structural and mechanistic bases for this interaction emerged simultaneously in different organisms. In addition, we further revealed that the interaction of RIP3 with MLKL prevented massive abnormal RIP3 aggregation, and therefore should be crucial for formation of the amyloid signaling complex of necrosomes. We also found that the interaction between RIP3 and MLKL is required for the translocation of necrosomes to mitochondria-associated membranes. Our data demonstrate the importance of the RIP3- MLKL interaction in the formation of functional necrosomes and suggest that translocation of necrosomes to mitochondria associated membranes is essential for necroptosis signaling. [ABSTRACT FROM AUTHOR]