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A bstract On two subspaces of the Bruhat-Tits tree, effective actions are calculated. The limits of these effective field theories are found to be the same conformal field theory over p-adic numbers when subspaces are taken to the boundary of the tree. Their relations to the p-adic version of AdS/CFT are also discussed.

This paper presents a case study of the first shamanic organization in China and argues that organizational shamanism in Northeast China is characterized by the double identities of the shaman and the dualistic attitudes of the national authorities. The analyses in this paper reveal how the shamanic organization created a modernized and globalized space for traditional shamans and specialists to connect with the outside world, enabling them to gain empowerment, legitimacy, and agency. Chinese authorities hold dualistic attitudes towards shamanism: the positive attitude of seeing shamanism as part of cultural heritage has always been coupled with the negative attitude of seeing shamanism as superstition. The studies in this paper demonstrate that organizational shamanism in Northeast China has played a crucial role in negotiating with political authorities and linking local traditions with global discourse. In this sense, the traditional eco-cosmological way of maintaining relationships with natural forces and nonhuman beings has been irrevocably transformed into a cosmopolitical form for the shaman, where the animistic world engages with the outside world, global currency, and political forces.

Social trends and historical contexts have popularized Eliade’s trance model in shamanism studies and have contributed to a famous academic debate. A case study on Manchu shamanism conducted in this article shows that a Manchu shaman functions primarily as a sacrificial specialist rather than a mental state adept. Three types of Manchu shamanism—court shamanism, clan shamanism, and wild shamanism—are examined based on historical and ethnographic analyses. This study deconstructs the trance model and demonstrates that shamanism among Manchus has a dynamic, reactive, constitutive, and unstable historical process.

The case study in this paper is on the Daur (as well as the Evenki, Buriat, and Bargu Mongols) in Hulun Buir, Northeast China. The aim of this research is to examine how shamanic rituals function as a conduit to actualize communications between the clan members and their shaman ancestors. Through examinations and observations of Daur and other Indigenous shamanic rituals in Northeast China, this paper argues that the human construction of the shamanic landscape brings humans, other-than-humans, and things together into social relations in shamanic ontologies. Inter-human metamorphosis is crucial to Indigenous self-conceptualization and identity. Through rituals, ancestor spirits are active actors involved in almost every aspect of modern human social life among these Indigenous peoples.

PurposeDiabetic cardiomyopathy (DCM), a common complication of diabetes mellitus and is characterized by myocardial hypertrophy and myocardial fibrosis. Pyrroloquinoline quinone (PQQ), a natural nutrient, exerts strong protection against various myocardial diseases. Pyroptosis, a type of inflammation-related programmed cell death, is vital to the development of DCM. However, the protective effects of PQQ against DCM and the associated mechanisms are not clear. This study aimed to investigate whether PQQ protected against DCM and to determine the underlying molecular mechanism.MethodsDiabetes was induced in mice by intraperitoneal injection of streptozotocin, after which the mice were administered PQQ orally (10, 20, or 40 mg/kg body weight/day) for 12 weeks. AC16 human myocardial cells were divided into the following groups and treated accordingly: control (5.5 mmol/L glucose), high glucose (35 mmol/L glucose), and HG + PQQ groups (1 and 10 nmol/L PQQ). Cells were treated for 24 h.ResultsPQQ reduced myocardial hypertrophy and the area of myocardial fibrosis, which was accompanied by an increase in antioxidant function and a decrease in inflammatory cytokine levels. Moreover, myocardial hypertrophy—(ANP and BNP), myocardial fibrosis—(collagen I and TGF-β1), and pyroptosis-related protein levels decreased in the PQQ treatment groups. Furthermore, PQQ abolished mitochondrial dysfunction and the activation of NF-κB/IκB, and decreased NLRP3 inflammation-mediated pyroptosis in AC16 cells under high-glucose conditions.ConclusionPQQ improved DCM in diabetic mice by inhibiting NF-κB/NLRP3 inflammasome-mediated cell pyroptosis. Long-term dietary supplementation with PQQ may be greatly beneficial for the treatment of DCM.Diagram of the underlying mechanism of the effects of PQQ on DCM. PQQ inhibits ROS generation and NF-κB activation, which stimulates activation of the NLRP3 inflammasome and regulates the expression of caspase-1, IL-1β, and IL-18. The up-regulated inflammatory cytokines trigger myocardial hypertrophy and cardiac fibrosis and promote the pathological process of DCM.

Recent research underscores a potential correlation between chronic obstructive pulmonary disease (COPD) and frailty, suggesting a shared genetic foundation. However, specific genetic factors and mechanisms underlying this association remain unclear. This study aimed to explore genetic connections between COPD and frailty using genome-wide association studies to enhance our understanding and improve clinical management and prevention strategies for these conditions. We utilised summary statistics for genome-wide association studies to examine the genetic correlations between COPD and frailty using linkage disequilibrium score regression. Local genetic correlations were evaluated using the ρ-heritability estimates from summary statistics method. Using the established two-sample Mendelian randomization approach, causal relationships have been identified. Shared genetic variants were quantified using a bivariate causal mixture model. Shared loci and single nucleotide polymorphisms were identified by conjoint false discovery rate (conjFDR). Gene enrichment and transcriptome-wide association studies (TWAS) were conducted to explore potential transcriptomic associations across tissues. We observed a significant genetic correlation between COPD and frailty (Rg =  0.4324, P =  6.09 ×  10 - 26). MiXeR estimated 3,200-shared causal variants. Additionally, we discovered 16 shared loci linked to 91 genes, offering novel insights into gene expression across diverse tissues. The TWAS revealed 25 shared genes, representing a significant advance in understanding the genetic overlap between COPD and frailty. Furthermore, out of the 25 SNPs identified through TWAS, 4 overlapped with the lead SNPs, specifically [HLA-DRB1, PBX3, SLC22A5/OCTN2, SLMAP]. Our study shows a common genetic foundation for COPD and frailty, identifying multiple shared loci and offering insights into their underlying causal connections. These findings enhance our understanding of the biological mechanisms linking these conditions and may guide future research and treatment strategies for related diseases.

Aims Acyl‐CoA synthetase long chain family member 4 (ACSL4) is closely related to tumor genesis and development in certain tissues. However, the function of ACSL4 in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) is unclear. In this study, we investigated the expression patterns and role of ACSL4 in SAH and post‐SAH EBI using a rat model of SAH. Methods The rat model of SAH was induced by autologous blood injection into the prechiasmatic cistern of rats. We also used two specific inhibitors of ferroptosis (Ferrostatin‐1 and Liproxstatin‐1) to investigate the role of ferroptosis in EBI. Results We found that ACSL4 levels in brain tissue increased significantly in post‐SAH EBI. Inhibiting the expression of ACSL4 using small interfering RNAs alleviated inflammation, blood‐brain barrier (BBB) impairment, oxidative stress, brain edema, and behavioral and cognitive deficits, and increased the number of surviving neurons, after SAH. Similar effects were obtained by suppressing ferroptosis. Conclusions ACSL4 exacerbated SAH‐induced EBI by mediating ferroptosis. These findings may provide a theoretical basis for potential therapy aimed at alleviating post‐SAH EBI. ACSL4 levels in brain tissue of rats increase significantly in EBI and brain damage after SAH could be reduced by down‐regulation of ACSL4. ACSL4 could trigger ferroptosis and aggravate brain damage via catalyzing lipid metabolism. It may provide a theoretical basis for potential therapy to alleviate EBI after SAH

Background and aims The recurrence and metastasis of hepatocellular carcinoma (HCC) are mainly caused by microvascular invasion (MVI). Our study aimed to uncover the cellular atlas of MVI + HCC and investigate the underlying immune infiltration patterns with radiomics features. Methods Three MVI positive HCC and three MVI negative HCC samples were collected for single-cell RNA-seq analysis. 26 MVI positive HCC and 30 MVI negative HCC tissues were underwent bulk RNA-seq analysis. For radiomics analysis, radiomics features score (Radscore) were built using preoperative contrast MRI for MVI prediction and overall survival prediction. We deciphered the metabolism profiles of MVI + HCC using scMetabolism and scFEA. The correlation of Radscore with the level of APOE + macrophages and iCAFs was identified. Whole Exome Sequencing (WES) was applied to distinguish intrahepatic metastasis (IM) and multicentric occurrence (MO). Transcriptome profiles were compared between IM and MO. Results Elevated levels of APOE+ macrophages and iCAFs were detected in MVI + HCC. There was a strong correlation between the infiltration of APOE + macrophages and iCAFs, as confirmed by immunofluorescent staining. MVI positive tumors exhibited increased lipid metabolism, which was attributed to the increased presence of APOE+ macrophages. APOE + macrophages and iCAFs were also found in high levels in IM, as opposed to MO. The difference of infiltration level and Radscore between two nodules in IM was relatively small. Furthermore, we developed Radscore for predicting MVI and HCC prognostication that were also able to predict the level of infiltration of APOE + macrophages and iCAFs. Conclusion This study demonstrated the interactions of cell subpopulations and distinct metabolism profiles in MVI + HCC. Besides, MVI prediction Radscore and MVI prognostic Radscore were highly correlated with the infiltration of APOE + macrophages and iCAFs, which helped to understand the biological significance of radiomics and optimize treatment strategy for MVI + HCC.

Senescence of vascular smooth muscle cells (VSMCs) contributes to aging-related cardiovascular diseases by promoting arterial remodelling and stiffness. Ferroptosis is a novel type of regulated cell death associated with lipid oxidation. Here, we show that pro-ferroptosis signaling drives VSMCs senescence to accelerate vascular NAD + loss, remodelling and aging. Pro-ferroptotic signaling is triggered in senescent VSMCs and arteries of aged mice. Furthermore, the activation of pro-ferroptotic signaling in VSMCs not only induces NAD + loss and senescence but also promotes the release of a pro-senescent secretome. Pharmacological or genetic inhibition of pro-ferroptosis signaling, ameliorates VSMCs senescence, reduces vascular stiffness and retards the progression of abdominal aortic aneurysm in mice. Mechanistically, we revealed that inhibition of pro-ferroptotic signaling facilitates the nuclear-cytoplasmic shuttling of proliferator-activated receptor-γ and, thereby impeding nuclear receptor coactivator 4-ferrtin complex-centric ferritinophagy. Finally, the activated pro-ferroptotic signaling correlates with arterial stiffness in a human proof-of-concept study. These findings have significant implications for future therapeutic strategies aiming to eliminate vascular ferroptosis in senescence- or aging-associated cardiovascular diseases. Ferroptosis is a novel form of regulated cell death associated with lipid oxidation. Here, the authors demonstrate that the proferroptosis signal is activated and drives vascular aging by inducing senescence in vascular smooth muscle cells.

Hepatocellular carcinoma (HCC) is an immunotherapy-resistant malignancy characterized by high cellular heterogeneity. The diversity of cell types and the interplay between tumor and non-tumor cells remain to be clarified. Single cell RNA sequencing of human and mouse HCC tumors revealed heterogeneity of cancer-associated fibroblast (CAF). Cross-species analysis determined the prominent CD36 + CAFs exhibited high-level lipid metabolism and expression of macrophage migration inhibitory factor (MIF). Lineage-tracing assays showed CD36 + CAFs were derived from hepatic stellate cells. Furthermore, CD36 mediated oxidized LDL uptake-dependent MIF expression via lipid peroxidation/p38/CEBPs axis in CD36 + CAFs, which recruited CD33 + myeloid-derived suppressor cells (MDSCs) in MIF- and CD74-dependent manner. Co-implantation of CD36 + CAFs with HCC cells promotes HCC progression in vivo. Finally, CD36 inhibitor synergizes with anti-PD-1 immunotherapy by restoring antitumor T-cell responses in HCC. Our work underscores the importance of elucidating the function of specific CAF subset in understanding the interplay between the tumor microenvironment and immune system.