C/EBPε and its acetylation in PMN enhance the tolerance to trauma.

Severe trauma can lead to numerous serious complications, threating the well-being and vitality of the afflicted. The quantity and functionality of PMNs undergo rapid transformations in response to severe trauma, playing a pivotal role in the trauma response. The absence of CCAAT/enhancer-binding protein ε (C/EBPε) profoundly impairs the functionality of polymorphonuclear neutrophils (PMNs), a function of paramount importance in trauma. In this study, by generating mice with C/EBPε knocked out or overexpressed, we substantiate that C/EBPε ensures the restoration of PMN function, enhancing the expression of antimicrobial proteins and thereby promoting trauma recovery. Furthermore, diminished expression of C/EBPε is observed in trauma patients, with levels displaying a negative correlation with ISS and APACHE II scores, suggesting its potential as a prognostic indicator for clinical treatment. Mechanistically, we uncover the upregulation of SIRT1 and the inhibition of P300 participating in the suppression of C/EBPε acetylation, consequently reducing the resilience of mice to trauma. As therapeutic interventions, whether through the sole administration of PMN, NAM treatment, or their combination, all result in an increased survival rate in traumatic mice. In conclusion, our study elucidates the role of C/EBPε in enhancing the resilience to trauma and identifies C/EBPε acetylation as a critical regulatory mechanism, offering potential therapeutic approaches involving PMN transfusion and NAM treatment.

Punicalagin promotes mincle-mediated phagocytosis of macrophages via the NF-κB and MAPK signaling pathways.

Punicalagin (PUN) is a polyphenol derived from the pomegranate peel. It has been reported to have many beneficial effects, including anti-inflammatory, anti-oxidant, and anti-proliferation. However, the role of PUN in macrophage phagocytosis is currently unknown. In this study, we found that pre-treatment with PUN significantly enhanced phagocytosis by macrophages in a time- and dose-dependent manner in vitro. Moreover, KEGG enrichment analysis by RNA-sequencing showed that differentially expressed genes following PUN treatment were significantly enriched in phagocyte-related receptors, such as the C-type lectin receptor signaling pathway. Among the C-type lectin receptor family, Mincle (Clec4e) significantly increased at the mRNA and protein level after PUN treatment, as shown by qRT-PCR and western blotting. Small interfering RNA (siRNA) mediated knockdown of Mincle in macrophages resulted in down regulation of phagocytosis. Furthermore, western blotting showed that PUN treatment enhanced the phosphorylation of nuclear factor kappa-B (NF-κB) and mitogen-activated protein kinase (MAPK) in macrophages at the early stage. Mincle-mediated phagocytosis by PUN was inhibited by PDTC (a NF-κB inhibitor) and SB203580 (a p38 MAPK inhibitor). In addition, PUN pre-treatment enhanced phagocytosis by peritoneal and alveolar macrophages in vivo. After intraperitoneal injection of Escherichia coli (E.coli), the bacterial load of peritoneal lavage fluid and peripheral blood in PUN pre-treated mice decreased significantly. Similarly, the number of bacteria in the lung tissue significantly reduced after intranasal administration of Pseudomonas aeruginosa (PAO1). Taken together, our results reveal that PUN enhances bacterial clearance in mice by activating the NF-κB and MAPK pathways and upregulating C-type lectin receptor expression to enhance phagocytosis by macrophages.

Deep learning-based control framework for dynamic contact processes in humanoid grasping.

Humanoid grasping is a critical ability for anthropomorphic hand, and plays a significant role in the development of humanoid robots. In this article, we present a deep learning-based control framework for humanoid grasping, incorporating the dynamic contact process among the anthropomorphic hand, the object, and the environment. This method efficiently eliminates the constraints imposed by inaccessible grasping points on both the contact surface of the object and the table surface. To mimic human-like grasping movements, an underactuated anthropomorphic hand is utilized, which is designed based on human hand data. The utilization of hand gestures, rather than controlling each motor separately, has significantly decreased the control dimensionality. Additionally, a deep learning framework is used to select gestures and grasp actions. Our methodology, proven both in simulation and on real robot, exceeds the performance of static analysis-based methods, as measured by the standard grasp metric Q1. It expands the range of objects the system can handle, effectively grasping thin items such as cards on tables, a task beyond the capabilities of previous methodologies.

Transplantation of Cold-Stimulated Subcutaneous Adipose Tissue Improves Fat Retention and Recipient Metabolism.

BACKGROUND: Induction of beige fat for grafting is an emerging transplantation strategy. However, safety concerns associated with pharmaceutical interventions limit its wider application. Moreover, because beige fat is a special type of fat with strong metabolic functions, its effect on the metabolism of recipients after grafting has not been explored in the plastic surgery domain. OBJECTIVES: The aim of this study was to explore whether cold-induced inguinal white adipose tissue (iWAT) transplantation has a higher retention rate and beneficial effects on recipient metabolism. METHODS: C57/BL6 mice were subjected to cold stimulation for 48 hours to induce the browning of iWAT and harvested immediately. Subsequently, each mouse received a transplant of 0.2 mL cold-induced iWAT or normal iWAT. Fat grafts and recipients' iWAT, epididymal adipose tissue, and brown adipose tissue were harvested at 8 weeks after operation. Immunofluorescence staining, real-time polymerase chain reaction, and western blot were used for histological and molecular analysis. RESULTS: Cold-induced iWAT grafting had a higher mean [standard error of the mean] retention rate (67.33% [1.74%] vs 55.83% [2.94%], P < .01) and more satisfactory structural integrity than normal iWAT. Histological changes identified improved adipose tissue homeostasis after cold challenge, including abundant smaller adipocytes, higher levels of adipogenesis, angiogenesis, and proliferation, but lower levels of fibrosis. More importantly, cold-induced iWAT grafting suppressed the inflammation of epididymal adipose tissue caused by conventional fat grafting, and activated the glucose metabolism and thermogenic activity of recipients' adipose tissues. CONCLUSIONS: Cold-induced iWAT grafting is an effective nonpharmacological intervention strategy to improve the retention rate and homeostasis of grafts. Furthermore, it improves the adverse effects caused by traditional fat grafting, while also conferring metabolic benefits.

Systematic analysis of MASP-1 serves as a novel immune-related biomarker in sepsis and trauma followed by preliminary experimental validation.

Background: Dysregulated immune response in trauma and sepsis leads to the abnormal activation of the complement and coagulation systems. Mannose-binding lectin (MBL)-associated serine protease-1 (MASP-1) activates the lectin pathway of the complement system and mediates proinflammatory and procoagulant reactions. However, the potential effects of MASP-1 in trauma and sepsis have not yet been explored. Methods: We obtained five sepsis, two trauma, and one sepsis and trauma RNA-sequencing dataset from the Gene Expression Omnibus (GEO) database and conducted a comprehensive evaluation of the expression pattern, biological functions, and diagnostic value of MASP-1 in trauma and sepsis. Additionally, we investigated the association between MASP-1 expression and clinicopathological characteristics of trauma and sepsis. Furthermore, we collected clinical specimens to preliminarily validate the expression level and diagnostic efficacy of MASP-1 as well as the correlation of MASP-1 with clinical features of trauma and sepsis. Subsequently, we conducted a correlation analysis among MASP-1, immune cell infiltration, and immune and molecular pathways. Finally, we mechanistically analyzed the relationship among MASP-1, specific immune cells, and pivotal molecular pathways. Results: MASP-1 expression was significantly upregulated in the trauma/sepsis samples compared to the control samples in the GEO datasets. MASP-1 exhibited excellent diagnostic values (AUC > 0.7) in multiple datasets and at multiple time points and could efficiently distinguish trauma/sepsis samples from the control samples. Moreover, MASP-1 expression was significantly positively correlated with the severity of the disease (APACHE-II, CRP, and neutrophil levels). These results were further validated by real-time quantitative polymerase chain reaction and enzyme-linked immunosorbent assay. Functional enrichment analysis revealed that MASP-1 primarily promotes trauma and sepsis via the immune-related signaling pathway. MASP-1 was significantly correlated with the infiltration of specific immune cells (such as B cells, CD8 T cells, neutrophils, macrophages, and infiltrating lymphocytes) and immune and molecular pathways (such as checkpoint, HLA, IL6/JAK/STAT3 signaling, necrosis, T-cell co-inhibition, and T-cell co-stimulation). Finally, analysis of the transcription and single-cell data revealed that MASP-1 was specifically expressed in T cells, and further correlation analysis revealed a close correlation between MASP-1 expression, proportion of CD8 T cells, and IL6/JAK/STAT3 signaling scores. Conclusion: Our results suggest that MASP-1 can serve as an immune-related biomarker for the diagnosis and disease severity of trauma and sepsis. It may activate the IL6 JAK-STAT3 signaling pathway and promote CD8 T-cell depletion to trigger traumatic sepsis.

Near-Infrared Fluorescence Probe for Indication of the Pathological Stages of Wound Healing Process and Its Clinical Application.

Chronic wound healing is one of the most complicated biological processes in human life, which is also a serious challenge for human health. During the healing process, multiple biological pathways are activated, and various kinds of reactive oxygen species participate in this process. Hydrogen peroxide (H2O2) involves in chronic wounds and its concentration is fluctuated in different pathological stages during the wound healing process. Therefore, H2O2 may be recognized as a powerful biomarker to indicate the wound healing process. However, the pathological roles of H2O2 cannot be fully understood yet. Herein, we proposed a near-infrared fluorescent probe DCM-H2O2 for highly sensitive and rapid detection of H2O2 in living cells and scald and incision wound mice models. DCM-H2O2 exhibited a low detection limit and high specificity with low cytotoxicity for H2O2, which had great potential for its application in vivo. The probe was successfully utilized to monitor the fluctuation of endogenous H2O2 in the proliferation process of human immortalized epidermal (HACAT) cells, which confirmed that H2O2 participated in the cells' proliferation activity through a growth factor signaling pathway. In the scald and incision wound mice models, H2O2 concentration fluctuations at different pathological stages during the wound healing process could be obtained by in vivo fluorescence imaging. Finally, H2O2 concentrations in different stages of human diabetic foot tissues were also confirmed by the proposed probe. We expect that H2O2 could be a sensitive biomarker to indicate the wound healing process.