Effect of rheological heterogeneities on the lithospheric deformation of the Tibetan Plateau and neighbouring regions

The Tibetan Plateau, induced by the India-Eurasian collision, has the highest average altitude in the world. During its uplift vertically, the Tibetan Plateau has been considered to expand laterally. However, there are several strong and almost non-deformable cratons on its periphery, such as the Tarim, North China craton, and South China block. The present landform features show that these cratons limit the expansion of the Tibetan Plateau. However, there is still much controversy over whether the deformation can be transmitted to periphery orogens or reactivate ancient orogens in the cratons. This study used numerical models to investigate the effect of rheological heterogeneities on the lithospheric deformation of the Tibetan Plateau and its neighbouring regions. The results show that the lateral heterogeneities of the lithosphere have an important influence on the deformation or strain partitioning. Generally, during the lateral expansion of the Tibetan Plateau, its peripheral cratons can transmit the deformation or high strain to neighbouring weak orogens. This case can be used to understand the Tian Shan orogen, which was reactivated by the India-Eurasian collision. However, when the orogens inside the cratons have high lithospheric strength, high strain is difficult to distribute on them and the expanding Tibetan Plateau is constrained by its peripheral cratons. These results can be used to explain the ancient orogens that are not strongly deformed, such as the Jiangnan orogen in the South China block. Because these orogens formed at the same time as the cratons and have relatively high lithospheric strength. In addition, the large lithospheric thickness difference and low crustal rheological contrast favor high strain rates localized on the lithosphere of the ancient orogen in the craton, such as the Trans-North China orogen in the North China craton

Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis

BackgroundSynovial macrophages play important roles in the formation and progression of osteoarthritis (OA). This study aimed to explore the biological and clinical significance of macrophage-associated genes (MAGs) in OA.MethodsThe OA synovial gene expression profiles GSE89408 and GSE82107 were obtained from the GEO database. Single-sample gene set enrichment analysis (ssGSEA) and GSEA were employed to decipher differences in immune infiltration and macrophage-associated biological pathways, respectively. Protein–protein interaction (PPI) network analysis and machine learning were utilized to establish a macrophage-associated gene diagnostic signature (MAGDS). RT-qPCR was performed to test the expression of key MAGs in murine models.ResultsOA synovium presented high levels of immune infiltration and activation of macrophage-associated biological pathways. A total of 55 differentially expressed MAGs were identified. Using PPI analysis and machine learning, a MAGDS consisting of IL1B, C5AR1, FCGR2B, IL10, IL6, and TYROBP was established for OA diagnosis (AUC = 0.910) and molecular pathological evaluation. Patients with high MAGDS scores may possess higher levels of immune infiltration and expression of matrix metalloproteinases (MMPs), implying poor biological alterations. The diagnostic value of MAGDS was also validated in an external cohort (AUC = 0.886). The expression of key MAGs was validated in a murine model using RT-qPCR. Additionally, a competitive endogenous RNA network was constructed to reveal the potential posttranscriptional regulatory mechanisms.ConclusionsWe developed and validated a MAGDS model with the ability to accurately diagnose and characterize biological alterations in OA. The six key MAGs may also be latent targets for immunoregulatory therapy

Assessment of the optimal rebound effects from energy intensity reduction

Energy efficiency improvement is widely recognized as a cost-effective measure for clean production. In literature, the rebound effects of energy efficiency improvement represented by energy intensity reductions, potential energy savings and actual energy savings are not well defined and properly clarified. To address this issue, this study comprehensively discusses and clarifies how to define and estimate potential and actual energy savings in the assessment. We focus on the well-known concept of rebound effect and propose a new notion of the optimal rebound effect, which avoids the counter-intuitive values in cases of energy intensity increases in neighboring years. The optimal rebound effect must be assessed by an optimization approach, while the traditional rebound effect assumes the observed next-year data as the case of energy intensity reduction. For illustration, a non-radical data envelopment analysis model is used to estimate the potential energy intensity reduction, which serves to assess the optimal rebound effects in four Asian countries including China, India, Japan and Korea, during the period 1973–2017. The findings indicate that neither backfire nor super-conservation appears in the estimated optimal rebound effects

Threshold Effect of Economic Growth on Energy Intensity — Evidence from 21 Developed Countries

Based on threshold regression models, this paper analyzes the effect of economic growth on energy intensity by using panel data from 21 developed countries from 1996 to 2015. Results show that a 1% increase in GDP per capita can lead to a 0.62–0.78% reduction in energy intensity, implying economic growth can significantly reduce energy intensity. The extent of the reduction in energy intensity varies depending on the economic development stages represented by key influencing factors including energy mix in consumption, urbanization, industrial structure, and technological progress. Specifically, the reduction in energy intensity due to economic growth can be enhanced with relatively more renewable energy consumption and more urban population until a threshold point, where the enhancement disappears. On the other hand, the extent of the energy intensity reduction due to economic growth can be weakened with relatively more tertiary industry activities and more research and development (R&D) investment in an economy until a threshold point, where the weakening cannot continue. However, compared to the early stages represented by the low ends of renewable energy consumption, urban population, tertiary industry activities, and R&D investment, the later stages represented by the high ends of these key factors after a threshold show the weakened effect of economic growth on the decline of energy intensity. Hence, when an economy is well-developed, policy makers are advised to put fewer expectations on the role of economic growth to reduce energy intensity, while pursuing relatively cleaner energy, greater urbanization, more tertiary industry activities, and advanced technologie

DataSheet1_Effect of rheological heterogeneities on the lithospheric deformation of the Tibetan Plateau and neighbouring regions.PDF

The Tibetan Plateau, induced by the India-Eurasian collision, has the highest average altitude in the world. During its uplift vertically, the Tibetan Plateau has been considered to expand laterally. However, there are several strong and almost non-deformable cratons on its periphery, such as the Tarim, North China craton, and South China block. The present landform features show that these cratons limit the expansion of the Tibetan Plateau. However, there is still much controversy over whether the deformation can be transmitted to periphery orogens or reactivate ancient orogens in the cratons. This study used numerical models to investigate the effect of rheological heterogeneities on the lithospheric deformation of the Tibetan Plateau and its neighbouring regions. The results show that the lateral heterogeneities of the lithosphere have an important influence on the deformation or strain partitioning. Generally, during the lateral expansion of the Tibetan Plateau, its peripheral cratons can transmit the deformation or high strain to neighbouring weak orogens. This case can be used to understand the Tian Shan orogen, which was reactivated by the India-Eurasian collision. However, when the orogens inside the cratons have high lithospheric strength, high strain is difficult to distribute on them and the expanding Tibetan Plateau is constrained by its peripheral cratons. These results can be used to explain the ancient orogens that are not strongly deformed, such as the Jiangnan orogen in the South China block. Because these orogens formed at the same time as the cratons and have relatively high lithospheric strength. In addition, the large lithospheric thickness difference and low crustal rheological contrast favor high strain rates localized on the lithosphere of the ancient orogen in the craton, such as the Trans-North China orogen in the North China craton.</p

GSDMD suppresses keratinocyte differentiation by inhibiting FLG expression and attenuating KCTD6-mediated HDAC1 degradation in atopic dermatitis

Background Recent studies have shown that activated pyroptosis in atopic dermatitis (AD) switches inflammatory processes and causes abnormal cornification and epidermal barrier dysfunction. Little research has focused on the interaction mechanism between pyroptosis-related genes and human keratinocyte differentiation. Methods The AD dataset from the Gene Expression Omnibus (GEO) was used to identify differently expressed pyroptosis-related genes (DEPRGs). Hub genes were identified and an enrichment analysis was performed to select epithelial development-related genes. Lesions of AD patients were detected via immunohistochemistry (IHC) to verify the hub gene. Human keratinocytes cell lines, gasdermin D (GSDMD) overexpression, Caspase1 siRNA, Histone Deacetylase1 (HDAC1) siRNA, and HDAC1 overexpression vectors were used for gain-and-loss-of-function experiments. Regulation of cornification protein was determined by qPCR, western blot (WB), immunofluorescence (IF), dual-luciferase reporter assay, co-immunoprecipitation (Co-IP), and chromatin immunoprecipitation (ChIP). Results A total of 27 DEPRGs were identified between either atopic dermatitis non-lesional skin (ANL) and healthy control (HC) or atopic dermatitis lesional skin (AL) and HC. The enrichment analysis showed that these DEPRGs were primarily enriched in the inflammatory response and keratinocytes differentiation. Of the 10 hub genes identified via the protein-protein interaction network, only GSDMD was statistically and negatively associated with the expression of epithelial tight junction core genes. Furthermore, GSDMD was upregulated in AD lesions and inhibited human keratinocyte differentiation by reducing filaggrin (FLG) expression. Mechanistically, GSDMD activated by Caspase1 reduced FLG expression via HDAC1. HDAC1 decreased FLG expression by reducing histone acetylation at the FLG promoter. In addition, GSDMD blocked the interaction of Potassium Channel Tetramerization Domain Containing 6 (KCTD6) and HDAC1 to prohibit HDAC1 degradation. Conclusion This study revealed that GSDMD was upregulated in AD lesions and that GSDMD regulated keratinocytes via epigenetic modification, which might provide potential therapeutic targets for AD

Hypoxia Molecular Characterization in Hepatocellular Carcinoma Identifies One Risk Signature and Two Nomograms for Clinical Management

Hypoxia is a universal feature in the tumor microenvironment (TME). Nonetheless, the heterogeneous hypoxia patterns of TME have still not been elucidated in hepatocellular carcinoma (HCC). Using consensus clustering algorithm and public datasets, we identified heterogeneous hypoxia subtypes. We also revealed the specific biological and clinical characteristics via bioinformatic methods. The principal component analysis algorithm was employed to develop a hypoxia-associated risk score (HARS). We identified the two hypoxia subtypes: low hypoxia pattern (C1) and high hypoxia pattern (C2). C1 was less sensitive to immunotherapy compared to C2, consistent with the lack of immune cells and immune checkpoints (ICPs) in C1, whereas C2 was the opposite. C2 displayed worse prognosis and higher sensitivity to obatoclax relative to C1, while C1 was more sensitive to sorafenib. The two subtypes also demonstrated subtype-specific genomic variations including mutation, copy number alteration, and methylation. Moreover, we developed and validated a risk signature: HARS, which had excellent performance for predicting prognosis and immunotherapy. We revealed two hypoxia subtypes with distinct biological and clinical characteristics in HCC, which enhanced the understanding of hypoxia pattern. The risk signature was a promising biomarker for predicting prognosis and immunotherapy