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Hepatocellular carcinoma (HCC) is one of the leading causes of cancer deaths worldwide. Significantly activated uridine nucleotide and fatty acid metabolism in HCC cells promote malignant proliferation and immune evasion. Herein, it is demonstrated that the tripartite motif 65 (TRIM65) E3 ubiquitin‐protein ligase, O‐GlcNAcylated via O‐GlcNAcylation transferase, is highly expressed in HCC and facilitated metabolic remodeling to promote the accumulation of products related to uracil metabolism and palmitic acid, driving the progression of HCC. Mechanistically, it is showed that TRIM65 mediates ubiquitylation at the K44 residue of neurofibromatosis type 2 (NF2), the key protein upstream of classical Hippo signaling. Accelerated NF2 degradation inhibits yes‐associated protein 1 phosphorylation, inducing aberrant activation of related metabolic enzyme transcription, and orchestrating metabolic and immune advantages. In conclusion, these results reveal a critical role for the TRIM family molecule TRIM65 in supporting HCC cell survival and highlight the therapeutic potential of targeting its E3 ligase activity to alter the regulation of proteasomal degradation. [ABSTRACT FROM AUTHOR]

Macrophages are highly heterogeneous immune cells that fulfill tissue-specific functions. Tissue-derived signals play a critical role in determining macrophage heterogeneity. However, these signals remain largely unknown. The BMP receptor activin receptor-like kinase 1 (ALK1) is well known for its role in blood vessel formation; however, its role within the immune system has never been revealed to our knowledge. Here, we found that BMP9/BMP10/ALK1 signaling controlled the identity and self-renewal of Kupffer cells (KCs) through a Smad4-dependent pathway. In contrast, ALK1 was dispensable for the maintenance of macrophages located in the lung, kidney, spleen, and brain. Following ALK1 deletion, KCs were lost over time and were replaced by monocyte-derived macrophages. These hepatic macrophages showed significantly reduced expression of the complement receptor VSIG4 and alterations in immune zonation and morphology, which is important for the tissue-specialized function of KCs. Furthermore, we found that this signaling pathway was important for KC-mediated Listeria monocytogenes capture, as the loss of ALK1 and Smad4 led to a failure of bacterial capture and overwhelming disseminated infections. Thus, ALK1 signaling instructs a tissue-specific phenotype that allows KCs to protect the host from systemic bacterial dissemination., Introduction Kupffer cells (KCs) are resident macrophages in the liver and constitute 80%-90% of the tissue macrophages present in the body. They are predominantly derived from fetal liver monocytes (1-4). [...]

The study aims to investigate and compare the success rate of concentrated growth factor (CGF) and blood clot (BC) as scaffolds in regenerative endodontic procedures (REPs). Immature permanent necrotic teeth treated by REPs with at least a 6‐month follow‐up were included. These teeth were divided into the CGF (53 teeth) and BC (68 teeth) groups. Treatment outcomes were assessed using a combined clinical and radiographic scoring system. The total success rate was 91.74% over a mean follow‐up period of 23.15 months. There was no significant difference between the CGF group (86.79%) and BC group (95.59%). The success rate of traumatic teeth (84.31%) was significantly lower than that of teeth with developmental dental anomalies (98.39%) (p < 0.05). CGF may be a suitable alternative scaffold in REPs when adequate bleeding cannot be achieved. Moreover, compared to developmental dental anomalies, traumatic teeth treated by REPs may be more vulnerable to failure. [ABSTRACT FROM AUTHOR]

Background: The COVID‐19 pandemic posed a great challenge to paediatric dentistry, which confronted with the restriction of service and resource shortage. Aim: To retrospectively analyse the information of children's dental online health consultation during the COVID‐19 pandemic in China, and to provide methods to distinguish between dental emergencies and non‐emergencies as well as their management. Design: We collected all the online consultation information in Dept. of Paediatric dentistry, School & Hospital of Stomatology, Wuhan University, from 2 February to 31 March 2020, and extracted the information of age, gender, reason for consultation, description of symptom, and preliminary diagnosis of the children. Results: A total of 474 online consultations of paediatric dentistry were included within 59 days during lockdown, and 190 (40.1%) were dental emergencies and 284 (59.9%) non‐emergencies. Of 190 emergency consultations, 186 (97.9%) showed swelling, pain, and trauma with or without systemic symptoms. Among 284 non‐emergency consultations, retained primary teeth (n = 126) and orthodontic consultation (n = 53) were the most common reasons for consultation. Conclusion: The paediatric emergency and non‐emergency problems should be clearly distinguished and sufficient instructions provided in the special period of COVID‐19. Priorities also should be set to deal with urgent conditions after the release of lockdown. [ABSTRACT FROM AUTHOR]

Macrophages are highly heterogeneous immune cells that fulfill tissue-specific functions. Tissue-derived signals play a critical role in determining macrophage heterogeneity. However, these signals remain largely unknown. The BMP receptor activin receptor-like kinase 1 (ALK1) is well known for its role in blood vessel formation; however, its role within the immune system has never been revealed to our knowledge. Here, we found that BMP9/BMP10/ALK1 signaling controlled the identity and self-renewal of Kupffer cells (KCs) through a Smad4-dependent pathway. In contrast, ALK1 was dispensable for the maintenance of macrophages located in the lung, kidney, spleen, and brain. Following ALK1 deletion, KCs were lost over time and were replaced by monocyte-derived macrophages. These hepatic macrophages showed significantly reduced expression of the complement receptor VSIG4 and alterations in immune zonation and morphology, which is important for the tissue-specialized function of KCs. Furthermore, we found that this signaling pathway was important for KC-mediated Listeria monocytogenes capture, as the loss of ALK1 and Smad4 led to a failure of bacterial capture and overwhelming disseminated infections. Thus, ALK1 signaling instructs a tissue-specific phenotype that allows KCs to protect the host from systemic bacterial dissemination. [ABSTRACT FROM AUTHOR]

Thioredoxin peroxidase (TPx) protein from the excretory-secretory antigens (ESAs) of Cysticercus cellulosae (C. cellulosae) has been shown to regulate the differentiation of host Treg and Th17 cells, resulting in an immunosuppressive response dominated by Treg cells. However, the molecular mechanism by which TPx protein from the ESAs of C. cellulosae regulates the imbalance of host Treg/Th17 cell differentiation has not been reported. TPx protein from porcine C. cellulosae ESAs was used to stimulate Jurkat cells activated with PMA and ionomycin at 0, 24, 48, and 72 h. Transcriptomic analysis was performed to investigate the signaling pathways associated with Jurkat cells differentiation regulated by TPx protein from C. cellulosae ESAs. Gene Set Enrichment Analysis (GSEA) revealed that TPx protein from porcine C. cellulosae ESAs could induce upregulation of the TGF-β signaling pathway and downregulation of Th17 cell differentiation in Jurkat cells. TPx protein from porcine C. cellulosae ESAs can activate the TGF-β signaling pathway in Jurkat cells, thereby regulating the differentiation of Treg/Th17 cells and leading to an immunosuppressive response dominated by Treg cells, enabling evasion of the host immune attack. This study provides a foundation for further validation of these pathways and further elucidates the molecular mechanisms underlying immune evasion caused by porcine C. cellulosae., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)