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Background: The liver's regenerative capacity allows it to repair itself after injury. Extracellular vesicles and particles (EVPs) in the liver's interstitial space are crucial for signal transduction, metabolism, and immune regulation. Understanding the role and mechanism of liver-derived EVPs in regeneration is significant, particularly after partial hepatectomy, where the mechanisms remain unclear. Methods: A 70% hepatectomy model was established in mice, and EVPs were isolated and characterized using electron microscopy, nanocharacterization, and Western blot analysis. Combined metabolomic and transcriptomic analyses revealed ß-sitosterol enrichment in EVPs and activation of the Hedgehog signaling pathway during regeneration. The role of ß-sitosterol in EVPs on the Hedgehog pathway and its targets were identified using qRT-PCR, Western blot analysis. The regulation of carnitine synthesis by this pathway was determined using a dual luciferase assay. The effect of a ß-sitosterol diet on liver regeneration was verified in mice. Results: After 70% hepatectomy, the liver successfully regenerated without liver failure or death. At 24 hours post-surgery, tissue staining showed transient regeneration-associated steatosis (TRAS), with increased Ki67 positivity at 48 hours. EVPs displayed a spherical lipid bilayer structure with particle sizes of 70-130 nm. CD9, CD63, and CD81 in liver-derived EVPs were confirmed. Transcriptomic and metabolomic analyses showed EVPs supplementation significantly promoted carnitine synthesis and fatty acid oxidation. Tissue staining confirmed accelerated TRAS resolution and enhanced liver regeneration with EVP supplementation. Mass spectrometry identified ß-sitosterol in EVPs, which binds to Smo protein, activating the Hedgehog pathway. This led to the nuclear transport of Gli3, stimulating Setd5 transcription and inducing carnitine synthesis, thereby accelerating fatty acid oxidation. Mice with increased ß-sitosterol intake showed faster TRAS resolution and liver regeneration compared to controls. Conclusion: Liver-derived EVPs promote regeneration after partial hepatectomy. ß-sitosterol from EVPs accelerates fatty acid oxidation and promotes liver regeneration by activating Hedgehog signaling pathway.

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Changes in soil microbial activity and ecological function can be used to assess the level of soil fertility and the stability of ecosystems. To assess the fertility and safety of organic fertilizer of kitchen waste (OFK), soils containing 0% (CK), 1%, 3%, and 5% OFK were cultured, and the physical, chemical, and microbial properties of the soils were measured dynamically with routine agrochemical analysis measures and amplicon sequencing. The results showed that compared with those in CK, the contents of organic matter, available phosphorus, available potassium, NH4+-N, and NO3--N in soils with OFK increased by 23.80%-35.13%, 13.29%-29.72%, 16.91%-39.37%, 164.7%-340.2%, and 28.56%-32.71%, respectively. The activities of hydrolases related to the cycle of carbon, nitrogen, and phosphorus (α-glucosidase, leucine aminopeptidase, acid phosphatase, etc.) were also significantly higher than those of the CK treatment. OFK stimulated the growth of soil microorganisms and increased the carbon content of the microbial biomass. The amplicon sequencing analysis found that the microbial community structures of different treatments were significantly different at both the class and genus levels. In addition, it was found that the abundance of beneficial microbes in the soils with OFK increased, whereas pathogenic microbes decreased. RDA results confirmed that soil properties (including soil pH, organic matter, available nutrients, and microbial biomass) had a significant impact on microbial community structure. The results of investing bacterial community based on PICRUSt and FAPROTAX revealed that the function of the soil bacterial community was similar in the four treatments, but OFK supply significantly improved the microbial carbon utilization and metabolic ability. Moreover, by using the FUNGuild software, we found that the application of OFK increased the proportion of saprotroph-symbiotroph and symbiotroph and stimulated the growth of ectomycorrhizal fungi-undefined saprophytic fungi but inhibited plant and animal pathogenic fungi in soil. These results implied that OFK could promote the establishment of symbiotic relationships and inhibit the growth of pathogenic fungi. In summary, OFK could improve soil fertility and hydrolase activity, stimulate the growth of beneficial microorganisms, and defend against pathogens, indicating a promising use as safe and efficient organic fertilizer.

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Myocardial infarction (MI) is one of the leading causes of death worldwide. Danlou tablet (Dan) is an effective traditional Chinese medicine for cardiac protection, although the underlying mechanism was not fully understood. In this study, we used a murine MI model and demonstrated that Dan administration effectively attenuated myocardial apoptosis, cardiac remodeling, and heart failure post MI. Dan increased CD31-positive capillaries in MI hearts, and reduced the apoptosis and oxidative stress in human umbilical vein endothelial cells after oxygen-glucose deprivation stress, simultaneously with the activated HIF-1α/VEGFA/eNOS signaling. Moreover, inhibition of eNOS by L-NAME attenuated Dan-induced protection against MI, and abolished its effect in promoting angiogenesis and reducing endothelial apoptosis and oxidative stress. Collectively, Dan is beneficial to promote eNOS-dependent endothelial protection and angiogenesis thus protecting against MI. A deep understanding of Dan-induced protection might help promote clinical usage of Dan in MI treatment.

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Background: Gliomas are the most common intracranial nervous system tumours that are highly malignant and aggressive, and mitochondria are an important marker of metabolic reprogramming of tumour cells, the prognosis of which cannot be accurately predicted by current histopathology. Therefore, Identify a mitochondrial gene with immune-related features that could be used to predict the prognosis of glioma patients. Methods: Gliomas data were downloaded from the TCGA database and mitochondrial-associated genes were obtained from the MITOCARTA 3.0 dataset. The CGGA, kamoun and gravendeel databases were used as external datasets. LASSO(Least absolute shrinkage and selection operator) regression was applied to identify prognostic features, and area and nomograms under the ROC(Receiver Operating Characteristic) curve were used to assess the robustness of the model. Single sample genomic enrichment analysis (ssGSEA) was employed to explore the relationship between model genes and immune infiltration, and drug sensitivity was used to identify targeting drugs. Cellular studies were then performed to demonstrate drug killing against tumours. Results: COX assembly mitochondrial protein homolog (CMC1), Cytochrome c oxidase protein 20 homolog (COX20) and Cytochrome b-c1 complex subunit 7 (UQCRB) were identified as prognostic key genes in glioma, with UQCRB, CMC1 progressively increasing and COX20 progressively decreasing with decreasing risk scores. ROC curve analysis of the TCGA training set model yielded AUC (Area Under The Curve) values >0.8 for 1-, 2- and 3-year survival, and the model was associated with both CD8+ T cells and immune checkpoints. Finally, using cellMiner database and molecular docking, it was confirmed that UQCRB binds covalently to Amonafide via lysine at position 78 and threonine at position 82, while cellular assays showed that Amonafide inhibits glioma migration and invasion. Conclusion: Our three mitochondrial genomic composition-related features accurately predict Survival in glioma patients, and we also provide glioma chemotherapeutic agents that may be mitochondria-related targets.

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OBJECTIVE: Studies have shown that obesity has a significant impact on poor surgical outcomes. However, the relationship between obesity and pediatric epilepsy surgery has not been reported. This study aimed to explore the relationship between obesity and complications of pediatric epilepsy surgery and the effect of obesity on the outcome of pediatric epilepsy surgery, and to provide a reference for weight management of children with epilepsy. METHODS: A single-center retrospective analysis of complications in children undergoing epilepsy surgery was conducted. Body mass index (BMI) percentiles were adjusted by age and used as a criterion for assessing obesity in children. According to the adjusted BMI value, the children were divided into the obese group (n = 16) and nonobese group (n = 20). The intraoperative blood loss, operation time, and postoperative fever were compared between the two groups. RESULTS: A total of 36 children were included in the study, including 20 girls and 16 boys. The mean age of the children was 8.0 years old, ranging from 0.8 to 16.9 years old. The mean BMI was 18.1 kg/m2, ranging from 12.4 kg/m2 to 28.3 kg/m2. Sixteen of them were overweight or obese (44.4%). Obesity was associated with higher intraoperative blood loss in children with epilepsy (p = 0.04), and there was no correlation between obesity and operation time (p = 0.21). Obese children had a greater risk of postoperative fever (56.3%) than nonobese children (55.0%), but this was statistically nonsignificant (p = 0.61). The long-term follow-up outcomes showed that 23 patients (63.9%) were seizure-free (Engel grade I), 6 patients (16.7%) had Engel grade II, and 7 patients (19.4%) had Engel grade III. There was no difference in long-term seizure control outcomes between obese and nonobese groups (p = 0.682). There were no permanent neurological complications after surgery. CONCLUSION: Compared with nonobese children with epilepsy, obese children with epilepsy had a higher intraoperative blood loss. It is necessary to conduct early weight management of children with epilepsy as long as possible.

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