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Renal fibrosis is a common characteristic and the final pathological mechanism of chronic kidney disease (CKD). Although CKD remains incurable, inhibition of renal fibrosis is beneficial to inhibit the CKD process. Relaxin alleviates renal fibrosis in some experimental models, but its mechanism remains unclear. In the following, we studied the regulatory effect of relaxin on epithelial-mesenchymal transition (EMT) after unilateral ureteral obstruction (UUO). Our results demonstrate that relaxin could downregulate Wnt/β-catenin signaling and decrease EMT, thus protecting against loss of transporters in tubular epithelial cells (TECs) and abrogate renal interstitial fibrosis following UUO. We confirmed that relaxin can downregulate Wnt/β-catenin signaling and decrease EMT in NRK52E, thus abrogating G2 cell cycle arrest in vitro experiments. Therefore, a novel mechanism by which relaxin is antifibrotic is that relaxin regulates the EMT program of TECs via Wnt/β-catenin signaling pathway. The inhibition of EMT contributes to protecting the functional capabilities of TECs and promoting the regeneration of TECs.

Shear-coupled grain boundary motion (SCGBM) is an important and efficacious plasticity mechanism in the deformation of metals. In this work, a molecular dynamic (MD) simulation of the interaction between the SCGBM of Σ9[110](221) GB and Cu-rich precipitates in α-iron was carried out. The effects of the size, the temperature, and the composition of the Cu precipitates were also studied. It was found that the precipitates inhibited the GB motion significantly, and the configuration transformation from spheroid to ellipsoid was also investigated in the simulation results. The critical stress of the interaction increased with the size of the precipitates. At higher temperatures, the GB sliding event increased the critical stress of the GB motion, which was higher than that of the interaction, inducing no stress-rise stage in the stress–time curve. The critical stress of the CuNi precipitates on the SCGBM was higher than that of the pure Cu precipitates with the same size, which was one of the reasons for the outstanding strength of the high-strength low-alloy (HSLA) steels compared with the traditional Cu-containing steels. [ABSTRACT FROM AUTHOR]

Purpose: Neuroblastoma (NB) originates from differentiation arrest of sympathoadrenal progenitors in the neural crest. It is necessary to reveal the differentiation mechanism of NB. Previously, we reported that Purkinje cell protein 4 (PCP4) is a well-differentiated marker of NB tissues. Herein, we explored the underlying mechanism of PCP4 induced differentiation in order to find better treatment options for patients., Methods: We screened the interacting proteins of PCP4 by co-immunoprecipitation (Co-IP) and liquid chromatography-mass spectrometry (LC-MS/MS). Then we investigated the relevance between expression of calmodulin-dependent protein kinase II gamma (CAMK2G) and clinical features using R2 platform. We also explored the function of CAMK2G in NB cells by knockdown and RNA sequencing., Results: Here, we verified the binding of PCP4 and calmodulin (CaM) by Co-IP and identified a target kinase of CaM, CAMK2G, by LC-MS/MS. PCP4 overexpression activates the autophosphorylation of CAMK2G. Patients with high CAMK2G expression had better survival while low CAMK2G was associated with unfavorable clinical features including MYCN-amplification, unfavorable histology, progression and high INSS stage. CAMK2G knockdown inhibited neurite outgrowth and down-regulated neuronal differentiation markers (NF-H, MAP2), yet promoted migration, invasion and proliferation. Gene Ontology (GO) analysis showed that knockdown of CAMK2G downregulated the expression of neuronal differentiation-related genes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed that knockdown of CAMK2G upregulated the expression of migration-related genes., Conclusion: These findings indicate that CAMK2G activated by PCP4/CaM complex promotes differentiation and inhibits migration in NB cells., Level of Evidence: Not applicable., Competing Interests: Conflict of interest The authors declare no conflict of interest. There is not any competing financial interest in relation to the work described., (Copyright © 2024 Elsevier Inc. All rights reserved.)