As rate-limiting enzymes of β-oxidation of fatty acids in mitochondria, the carnitine palmitoyltransferase (CPT) played an important role in regulating energy homeostasis of aquatic animals. However, ...there was very little research on β-oxidation of fatty acids in crustaceans. In the present study, the full-length cDNA sequences of cpt-1a , cpt-1b and cpt-2 were isolated from the hepatopancreas of Scylla paramamosain , and contained 4206, 5303 and 3486 bp respectively. Sequence analysis showed that the CPT-1A, CPT-1B and CPT-2 encoded proteins with 777, 775 and 672 amino acids respectively, and only the CPT-1A possessed a transmembrane region. In addition, both the CPT-1B and CPT-2 contained conservative functional domains like N-terminal domain and acyltransferases choActase 2, while the CPT-1A lacked. The results of phylogenetic tree indicated that the CPT-1A, CPT-1B and CPT-2 of S. paramamosain gathered together with their corresponding orthologues from crustaceans. The tissue distribution exhibited that the cpt-1a was highly expressed in hepatopancreas, followed by muscle, eyestalk and cranial ganglia, and the muscle, eyestalk and heart were main expressed tissues of cpt-1b . Furthermore, the high expression levels of cpt-2 were mainly detected in hepatopancreas, muscle and heart. The transcriptional levels of cpt-1a , cpt-1b and cpt-2 were significantly up-regulated under chronic low salinity stress. Besides, at the acute low salinity stress condition, the expression levels of cpt-1a , cpt-1b and cpt-2 in hepatopancreas were dramatically increased in 14‰ and 4‰ salinity groups at the 6h and 48h, while the transcriptional levels of cpt-1a , cpt-1b and cpt-2 in muscle were signally up-regulated in 14‰ and 4‰ salinity groups at the 12h and 24h, showing an alternate response pattern. Similarly, the present study found that fasting could markedly increase the expression levels of cpt-1a , cpt-1b and cpt-2 in hepatopancreas and muscle, especially cpt-1a in hepatopancreas as well as cpt-1a and cpt-1b in muscle. The results above indicated that the cpt-1a , cpt-1b and cpt-2 played a crucial part in providing energy for coping with fasting and salinity stress. These results would contribute to enhancing the knowledge of cpt phylogenetic evolution and their roles in energy metabolism of crustaceans.
Immunotherapies such as immune checkpoint blockade have achieved remarkable success in treating cancer. Unfortunately, response rates have been limited in multiple cancers including hepatocellular ...carcinoma (HCC). The critical function of epigenetics in tumor immune evasion and antitumor immunity supports harnessing epigenetic regulators as a potential strategy to enhance the efficacy of immunotherapy. Here, we discovered a tumor-promoting function of FTSJ3, an RNA 2'-O-methyltransferase, in HCC by suppressing antitumor immune responses. FTSJ3 was upregulated in hepatocellular carcinoma, and high FTSJ3 expression correlated with reduced patient survival. Deletion of FTSJ3 blocked HCC growth and induced robust antitumor immune responses. Mechanistically, FTSJ3 suppressed double-stranded RNA (dsRNA)-induced IFNβ signaling in a 2'-O-methyltransferase manner. Deletion of RNA sensors in HCC cells or systemic knockout of type I IFN receptor IFNAR in mice rescued the in vivo tumor growth defect caused by FTSJ3 deficiency, indicating that FTSJ3 deletion suppresses tumor growth by activating the RNA sensor-mediated type I IFN pathway. Furthermore, FTSJ3 deletion significantly enhanced the efficacy of programmed cell death protein 1 (PD-1) immune checkpoint blockade. The combination of FTSJ3 deficiency and anti-PD-1 antibody treatment effectively eradicated tumors and increased the survival time. In conclusion, this study reveals an epigenetic mechanism of tumor immune evasion and, importantly, suggests FTSJ3-targeting therapies as potential approach to overcome immunotherapy resistance in patients with HCC.
Hepatocellular carcinoma cells use 2'-O-methylation catalyzed by FTSJ3 for immune evasion by suppressing abnormal dsRNA-mediated type I IFN responses, providing a potential target to activate antitumor immunity and enhance immunotherapy efficacy.
Moesin has been proved to be implicated in invasiveness and metastasis in many other cancers, but unclear in HCC. Thus, this study was performed to investigate the clinical significance of moesin and ...its biological functions in HCC. The results showed that moesin was significantly up-regulated in HCC tissues and was an independent prognostic factor for predicting the recurrence of HCC patients, postoperatively. Furthermore, we also demonstrated that moesin promoted the migration and invasion of HCC cells in vitro and in vivo. And the mechanism studies indicated that moesin overexpression increased the formation of invadopodia and improved the activation of β-catenin/MMP9 axis. Taken together, our findings revealed that moesin acted as an important onco-protein participating in the metastasis of HCC.
•We found the expression of moesin is increased in HCC tissues comparing to non-tumor tissues, for the first time.•Moesin has been identified as an independent prognostic factor for predicting the recurrence of HCC patients.•Invadopodia formation or β-catenin/MMP9 axis modulated by moesin cause promoting the migration and invasion of HCC cells..
•Ku80 physically interacted with SALL4.•Ku80-SALL4 interaction competitively disrupts the SALL4-OCT4 complex and result in OCT4 lysosomal degradation.•Ku80 inhibits self-renew and metastasis of HCC ...through breaking SALL4-OCT4 interactions and downregulating OCT4expression.
SALL4 and OCT4, along with other pluripotency-associated transcription factors, play critical roles in maintaining embryonic stem cell pluripotency and self-renewal. Ku80 is a component of the protein complex called DNA-dependent protein kinase, which mainly involved in DNA double-strand break repair. In this study, we show evidence that Ku80 physically interacted with SALL4. The interaction competitively disrupts the SALL4-OCT4 complex and result in OCT4 lysosomal degradation. Finally, Ku80 inhibits self-renewal and metastasis of hepatocellular carcinoma cells through breaking the SALL4-OCT4 interactions and down-regulating the expression of OCT4. Our study reveal novel function of Ku80 in stemness maintaining of cancer stem cells via its interaction with SALL4 and highlight the double-sidedness of Ku80 as an anti-cancer target.
Effective feature representation is crucial for improving short-term wind power prediction accuracy. While previous studies commonly utilize a point-wise attention mechanism, this approach treats ...each time step of the wind power time series independently, neglecting semantic information that connects different time steps. To address this limitation, we propose a short-term wind power prediction strategy based on a patch attention mechanism. This approach segments historical time series data, encodes positions, and utilizes the Transformer's multi-head attention mechanism to calculate position weights. High-dimensional feature vectors are obtained through residual connection networks and feedforward neural networks, and future wind power is predicted using a linear layer. Case study results show that wind power prediction with the patch attention mechanism achieves higher accuracy compared to Transformer and Informer models.
The interactions in multiple D-PMSGs-gridding systems are quite complex, and it is difficult to determine the oscillation paths and dominant oscillation sources. To solve this problem, the transfer ...function method of multiple input and multiple output is adopted, and the interactions in multiple D-PMSGs-gridding systems are analyzed. First, a system example of 4 D-PMSGs and 5 nodes is established, and the transfer matrix model is obtained. Secondly, the interaction between D-PMSGs and grid and the interaction between different D-PMSGs is analyzed. Then, the oscillation path and oscillation source are determined. Finally, targeted optimization measures are proposed, which are optimization of cutting D-PMSG and optimization of parameters, and it is verified by using eigenvalue method and time-domain simulation method.
