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Previous studies have shown that mitochondrial dysfunction plays an important role in high- glucose(HG)-induced podocyte injury and thus contributes to the progression of diabetic nephropathy(DN). The histone deacetylase Sirtuin6 (Sirt6) has been revealed to have an essential role in the regulation of mitochondrial function in skeletal muscle and cardiomyocytes. However, its specific role in mitochondrial homeostasis in podocytes is undetermined. Here, we aimeds to explore the physiological function of Sirt6 in podocyte mitochondria and apoptosis under HG conditions and explore the possible mechanism. Herein, we observed that Sirt6-WT-1 colocalization was suppressed in the glomeruli of patients with DN. In addition, diabetic mice exhibited reduced Sirt6 expression and AMP kinase (AMPK) dephosphorylation accompanied by mitochondrial morphological abnormalities. , podocytes exposed to HG presented with mitochondrial morphological alterations and podocyte apoptosis accompanied by Sirt6 and p-AMPK downregulation. In addition, HG promoted a decrease in mitochondrial number and an increase in mitochondrial superoxide production as well as a decreased mitochondrial membrane potential. ROS production was also increased in HG-treated podocytes. Conversely, all these mitochondrial defects induced by HG were significantly alleviated by Sirt6 plasmid transfection. Sirt6 overexpression simultaneously alleviated HG-induced podocyte apoptosis and oxidative stress, as well as increased AMPK phosphorylation. Increased levels of H3K9ac and H3K56ac induced by HG were attenuated in podocytes transfected with Sirt6 plasmids. Therefore, these results elucidated that Sirt6 protects mitochondria of podocytes and exerts anti-apoptotic effects via activating AMPK pathway. The present findings provide key insights into the pivotal role of mitochondria regulation by SIRT6 in its protective effects on podocytes.

HighlightsFour main strategies for improving the hydrogen evolution reaction (HER) performance of Ru-based catalysts were summarized.The source of HER activity of Ru-based catalysts is discussed in terms of catalytic mechanism.The current states, challenges and prospects were specifically provided for Ru-based catalysts.The investigation of highly effective, durable, and cost-effective electrocatalysts for the hydrogen evolution reaction (HER) is a prerequisite for the upcoming hydrogen energy society. To establish a new hydrogen energy system and gradually replace the traditional fossil-based energy, electrochemical water-splitting is considered the most promising, environmentally friendly, and efficient way to produce pure hydrogen. Compared with the commonly used platinum (Pt)-based catalysts, ruthenium (Ru) is expected to be a good alternative because of its similar hydrogen bonding energy, lower water decomposition barrier, and considerably lower price. Analyzing and revealing the HER mechanisms, as well as identifying a rational design of Ru-based HER catalysts with desirable activity and stability is indispensable. In this review, the research progress on HER electrocatalysts and the relevant describing parameters for HER performance are briefly introduced. Moreover, four major strategies to improve the performance of Ru-based electrocatalysts, including electronic effect modulation, support engineering, structure design, and maximum utilization (single atom) are discussed. Finally, the challenges, solutions and prospects are highlighted to prompt the practical applications of Ru-based electrocatalysts for HER.

Recent studies have shown that crustal body wave phases, such as PmP or SmS, can be effectively retrieved from ambient noise cross‐correlations. However, few studies have used these phases to constrain crustal structures. In this study, we successfully retrieve SmS signals from ambient noise data and observe SmS splitting caused by crustal radial anisotropy. Furthermore, through simulations of synthetic tests and application to field data, we demonstrate that these SmS signals can be used to constrain crustal radial anisotropy structures through joint inversion with surface waves. Our findings suggest that SmS signals obtained from noise data can significantly enhance the understanding of fine crustal radial anisotropic structures. Plain Language Summary By cross‐correlating ambient noise data, seismologists can extract the empirical Green's function between a pair of stations. Theoretically, both body and surface waves can be retrieved from these cross‐correlations. However, in practice, retrieving body wave signals from field data remains challenging. In this study, we successfully observe SmS signals, and their splitting caused by crustal radial anisotropy. By combining these SmS phases with surface wave dispersions, we can constrain the fine radial anisotropic structure of the crust. Using these body‐wave signals will enhance our understanding of the structure of the lower crust. Key Points SmS phases extracted from ambient noise show splitting due to radial anisotropy of the crust SmS signals can be used to constrain the radial anisotropy of the lower crust Joint inversion of SmS signals and surface waves provides an advantage in constructing the radial anisotropy of the crust

The formation of large igneous provinces (LIPs) has been widely believed to be linked to mantle plume activity. However, how the plume modifies the overlying lithosphere, particularly its compositional structure, remains uncertain. Here, we characterize the deep thermochemical structure beneath the Emeishan LIP (ELIP), which is a well‐known Permian plume‐related LIP in China, by taking a multi‐observable probabilistic inversion. Our results find a clear correlation between the lithospheric composition with the ELIP's concentric zones. We infer that the fertile feature of the lithospheric mantle in the ELIP's inner zone was caused by the plume‐derived fertile magmas which infiltrated into and chemically refertilized the ambient depleted lithosphere. This plume‐modified lithospheric compositional structure is likely to be preserved after the plume event, while the present lithospheric thermal structure has been mainly influenced by the subsequent thermal‐tectonic activity. Our results improve our understanding of the physicochemical interactions between the lithosphere and ancient plume. Plain Language Summary Gaining insights into the nature of large igneous provinces (LIPs) helps understand mass extinction and climate change in the past, since the outpouring of large accumulations of igneous rocks associated with LIPs could alter ancient climates and environments. Here, we focus on a well‐known plume‐related LIP during the Permian in China, Emeishan LIP (ELIP), to construct its deep thermochemical structure based on a multi‐observable probabilistic inversion method. Our results suggest that the bulk fertile feature (not depleted by melt extraction) of the lithospheric mantle in the vicinity of the ELIP's inner zone was caused by the plume‐derived fertile magmas which infiltrated into the ambient depleted (deficient in minerals extracted by partial melting of the rock) lithospheric mantle and chemically refertilized it by melt‐rock interaction. However, the imaged thermal structure shows a large ongoing asthenospheric upwelling and small‐scale thermal convection, implying that the present‐day lithospheric thickness has been mainly influenced by the subsequent tectonic events. Our results improve the understanding of the physicochemical interactions between the lithosphere and ancient plume and contribute to the knowledge of the nature of LIPs. Key Points Image the thermochemical structure beneath the Emeishan Large Igneous Province via novel joint inversions Reveal plume refertilization of the lithosphere beneath the Emeishan Large Igneous Province's inner zone Image complex mantle circulation patterns beneath the Emeishan Large Igneous Province region

Angiotensin II (Ang II) is a risk factor for the initiation and progression of chronic kidney disease (CKD), as elevated Ang II levels can lead to podocyte injury. However, there have been no studies on the role of Ang II in lipid metabolism or on podocyte injury caused by lipid dysfunction. Our study showed that Ang II induced lipid droplet (LD) accumulation and expression of the LD marker adipose differentiation-related protein (ADRP) in podocytes, and the extent of lipid deposition could be alleviated by losartan. Our study also demonstrated that Ang II increased the content of cholesterol in podocytes, which is an LD component, and this change was accompanied by decreased expression of the cholesterol efflux-related molecule ATP-binding cassette transporter-1 (ABCA1) and increased expression of the cholesterol uptake-related molecule LDL receptor (LDLR) and the cholesterol synthesis-related molecules sterol regulatory element-binding protein (SREBP1 and SREBP2) and 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR). Pretreating podocytes with methyl-β-cyclodextrin (CD), which induces cholesterol efflux, decreased Ang II-mediated cholesterol accumulation and Ang II-induced podocyte apoptosis and maintained the podocyte cytoskeleton and spreading. These results suggested that Ang II induced podocyte cholesterol accumulation by regulating the expression of cholesterol metabolism-related molecules and that the subsequent cholesterol metabolism dysfunction resulted in podocyte injury.

Based on 1–2 years of continuous observations of seismic ambient noise data obtained at more than 600 stations in and around Tibet, Rayleigh wave phase velocity maps are constructed from 10 s to 60 s period. A 3‐D Vsv model of the crust and uppermost mantle is derived from these maps. The 3‐D model exhibits significant apparently inter‐connected low shear velocity features across most of the Tibetan middle crust at depths between 20 and 40 km. These low velocity zones (LVZs) do not conform to surface faults and, significantly, are most prominent near the periphery of Tibet. The observations support the internal deformation model in which strain is dispersed in the deeper crust into broad ductile shear zones, rather than being localized horizontally near the edges of rigid blocks. The prominent LVZs are coincident with strong mid‐crustal radial anisotropy in western and central Tibet and probably result at least partially from anisotropic minerals aligned by deformation, which mitigates the need to invoke partial melt to explain the observations. Irrespective of their cause in partial melt or mineral alignment, mid‐crustal LVZs reflect deformation and their amplification near the periphery of Tibet provides new information about the mode of deformation across Tibet. Key Points A 3D Vsv model of the Tibetan crust is constructed from ambient noise tomography It exhibits inter‐connected LVZs in the mid‐crust, strong near the periphery Mid‐crustal LVZs and their distribution provides new information about deformation

Atmospheric Lamb waveforms are useful for reconstructing large air events, but the propagation of Lamb waves is significantly affected by varying atmospheric conditions. The detailed dispersion of Lamb waves remains vague due to lack of data, but also to simplifications inherent in existing models. Here, we investigate the pressure perturbations induced by the 2022 Hunga‐Tonga eruption at both global and regional barometric arrays. After correction of the influence of wind and temperature, the group velocity dispersion curves, measured by tracking energy arrival times across different frequencies, show a decreasing trend with frequency which is superimposed by two low‐velocity bands. Regarding the synthetic results, we interpret these low‐velocity bands as the coupling effect between Lamb waves in the lower atmosphere and gravity or acoustic waves in the upper atmosphere, offering profound understandings of surface‐to‐space observations for hazard management and mitigation after extreme atmospheric events.

Heart failure (HF) is a major cardiovascular disease with high mortality worldwide, whose pathophysiology is multifaceted. Hypoxia has emerged as a critical factor contributing to the progression of heart failure. We aimed to examine the expression and functions of LncRNA Kcnq1ot1 in hypoxia-induced cardiomyocytes in the process of HF. H9C2 cell model was simulated by hypoxia treatment. TUNEL, ELISA, Western Blot and qRT-PCR assay were carried out to evaluate cell pyroptosis, inflammation and dysfunction. Subsequently, we identified the direct downstream target of Kcnq1ot1 by bioinformatics analysis, RNA pull-down, double Luciferase reporter gene and other functional experiments. Firstly, Kcnq1ot1 levels was revealed to be upregulated in hypoxia cells than in control cells, and miR-27b-3p showed the opposite trend. And as expected, inhibition of Kcnq1ot1 and overexpression of miR-27b-3p both protected H9C2 against hypoxia-induced pyroptosis, inflammation and dysfunction. Moreover, miR-27b-3p was proved to bind with Kcnq1ot1 and participated in Kcnq1ot1-mediated H9C2 injury under hypoxia by regulating the Wnt3a/β-Catenin/NLRP3 signaling pathway. Collectively, our study demonstrated that inhibition of Kcnq1ot1 protected cardiomyocyte against hypoxia-induced injury possibly via sponging miR-27b-3p, which could be useful as biomarkers and therapeutic targets for HF patients.

Cervical cancer is one of the most common gynecological malignancies. Due to the high heterogeneity of cervical cancer accelerating cancer progression, it is necessary to identify new prognostic markers and treatment regimens for cervical cancer to improve patients’ survival rates. We purpose to construct and verify a risk prediction model for cervical cancer patients. Based on the analysis of data from the Gene Expression Omnibus database (GEO) and The Cancer Genome Atlas (TCGA), differences of genes in normal and cancer samples were analyzed and then used analysis of WGCNA along with consistent clustering to construct single-factor + multi-factor risk models. After regression analysis, the target genes were obtained as prognostic genes and prognostic risk models were constructed, and the validity of the risk model was confirmed using the receiver operating characteristic curve (ROC) and Kaplan–Meier curve. Subsequently, the above model was verified on the GSE44001 data validation followed by independent prognostic analysis. Enrichment analysis was conducted by grouping the high and low risks of the model. In addition, differences in immune analysis (immune infiltration, immunotherapy), drug sensitivity, and other levels were counted by the high and low risks groups. In our study, three prognostic genes including APOD, APOC1, and SQLE were obtained, and a risk model was constructed along with validation based on the above-mentioned analysis. According to the model, immune correlation and immunotherapy analyses were carried out, which will provide a theoretical basis and reference value for the exploration and treatment of cervical cancer. Highlights Establishment and Validation of a risk model includes APOD, APOC1 and SQLE; APOD, APOC1 and SQLE are related to immunotherapy; APOD, APOC1 and SQLE associates with prognosis in cervical cancer

The genus Camellia, known for species such as Camellia japonica , is of significant agricultural and ecological importance. However, the genetic diversity and evolutionary relationships among Camellia species remain insufficiently explored. In this study, we successfully sequenced and assembled the complete chloroplast (cp) genomes of nine Camellia accessions, including the species Camellia petelotii , and eight varieties of C. Japonica ( C. Japonica ‘Massee Lane’ , C. Japonica ‘L.T.Dees’ , C. Japonica ‘Songzi’ , C. Japonica ‘Kagirohi’ , C. Japonica ‘Sanyuecha’ , C. Japonica ‘Xiameng Hualin’ , C. Japonica ‘Xiameng Wenqing’ , and C. Japonica ‘Xiameng Xiaoxuan’ ). These genomes exhibited conserved lengths (~ 156,580–157,002 bp), indicating minimal variation in genome size. They consistently predicted 87 protein-coding genes, although variations were observed in the rRNA and tRNA genes. Structural and evolutionary analyses revealed the highly conserved nature of these cp genomes, with no significant inversions or gene rearrangements detected. Consistent codon usage patterns were observed across these accessions. Five hypervariable regions ( rpsbK , psbM , ndhJ , ndhF , and ndhD ) were identified as potential molecular markers for species differentiation. Phylogenetic analysis of 82 accessions from the Camellia genus, along with outgroup accessions revealed close genetic relationships among certain C. japonica varieties, including Songzi, Sanyuecha, L.T.Dees, and Kagirohi, which formed sister groups. Massee Lane was located within Sect. Camellia . Moreover, Xiameng Hualin , Xiameng Wenqing , Xiameng Xiaoxuan , and C. petelotii demonstrated a strong genetic affinity. These findings provide valuable insights into the structural and evolutionary dynamics of Camellia cp genomes, contributing to species identification and conservation.