Individual olfactory sensory neurons (OSNs) in the mouse main olfactory epithelium express a single odorant receptor (OR) gene from the repertoire of either class I or class II ORs. The transcription factor Bcl11b determines the OR class to be expressed in OSNs. The septal organ (SO), a small neuroepithelium located at the ventral base of the nasal septum, is considered as an olfactory subsystem because it expresses a specific subset of ORs. However, the mechanisms underlying the generation and differentiation of SO-OSN remain unknown. In the present study, we show that the generation and differentiation of SO-OSN employ the same genetic pathway as in the OSN lineage, which is initiated by the neuronal fate determinant factor Ascl1. Additionally, the key role of Bcl11b in the SO is demonstrated by the abnormal phenotypes of Bcl11b-deficient mice significant reduction in the expression of OR genes and in the number of mature SO-OSNs. Although SO-OSNs are specified to express a subset of class II OR genes in wild-type mice, the Bcl11b deletion led to the expression of class I OR genes, while the expression of class II OR genes was significantly decreased, with one exception of Olfr15. These results indicate that Bcl11b is necessary for proper OR expression in SO-OSNs.NUCB2/nesfatin-1 is expressed in variety of tissues. Treatment with nesfatin-1 reduces inflammation in rat models of subarachnoid hemorrhage-induced oxidative brain damage and traumatic brain injury as well as myocardial injury. learn more There is only one study showing anti-inflammatory actions of nesfatin-1 on acute lung inflammation. To more precisely determine the role of NUCB2/nesfatin-1 in acute lung inflammation, we conducted a study using NUCB2/nesfatin-1 knockout (NKO) mice as well as neutrophils isolated from the bone marrows of WT and NKO mice. Our findings suggest that the absence of NUCB2/nesfatin-1 significantly increases the accumulation of adherent neutrophils by approximately 3 times compared with WT within LPS-treated lungs. Integrating this with observations from both BALF and neutrophil cytokine expression, we propose that although neutrophils lacking NUCB2/nesfatin-1 individually secrete less pro-inflammatory cytokines compared with stimulated WT cells, the result of knocking out NUCB2/nesfatin-1 is net pro-inflammatory. No change was found in NUCB2/nesfatin-1 mRNA or protein expression comparing WT LPS and PBS-treated samples. Taken together, our results show that NUCB2/nesfatin-1 is constitutively expressed in mouse lungs and neutrophils and demonstrates anti-inflammatory properties in mouse lungs during acute lung injury, by inhibiting adherent neutrophil accumulation and inflammatory cytokine expression.The occurrence of osteoarthritis is closely related to chondrocyte dysfunction caused by cellular inflammatory response and matrix degradation, which seriously affect the quality of life of patients. Therefore, this study aimed to investigate the role of potassium voltage-gated channel subfamily Q member 1 overlapping transcript 1 (KCNQ1OT1), a member of the lncRNA voltage-gated channel subfamily Q, in the development of osteoarthritis. In this study, RT-qPCR results showed that KCNQ1OT1 expression was downregulated in osteoarthritic chondrocytes compared with normal chondrocytes. In addition, upregulation of KCNQ1OT1 significantly enhanced the viability of osteoarthritic chondrocytes, inhibited cell apoptosis, and reduced the release of inflammatory cytokines and metal matrix enzymes. Next, bioinformatics analysis and luciferase reporter gene analysis predicted and validated the targeting relationship between KCNQ1OT1 and miR-218-5p. We found that the expression of miR-218-5p was significantly upregulated in osteoarthritic chondrocytes, and knockdown of miR-218-5p significantly enhanced the viability of osteoarthritic chondrocytes, inhibited apoptosis, and decreased the abundance of inflammatory cytokines and metal matrix enzymes. Furthermore, the targeting relationship between miR-218-5p and recombinant phosphoinositide-3-kinase class-2-alpha polypeptide (PIK3C2A) was identified, and overexpression of PIK3C2A enhanced cell viability, and reduced apoptosis and secretion of inflammatory factors. Finally, we found that miR-218-5p overexpression reversed the protective effect of overexpression of KCNQ1OT1 or PIK3C2A on osteoarthritic chondrocytes. In conclusion, our results demonstrated that KCNQ1OT1 upregulated PIK3C2A and activated the PI3K/AKT/mTOR pathway to reduce chondrocyte dysfunction by targeting miR-218-5p, providing new insights into the pathogenesis of osteoarthritis.Phospholipase D6 (PLD6) plays pivotal roles in mitochondrial dynamics and spermatogenesis, but the cellular and subcellular localization of endogenous PLD6 in testis germ cells is poorly defined. We examined the distribution and subcellular localization of PLD6 in mouse testes using validated specific anti-PLD6 antibodies. Ectopically expressed PLD6 protein was detected in the mitochondria of PLD6-transfected cells, but endogenous PLD6 expression in mouse testes was localized to the perinuclear region of pachytene spermatocytes, and more prominently, to the round (Golgi and cap phases) and elongating spermatids (acrosomal phase); these results suggest that PLD6 is localized to the Golgi apparatus. The distribution of PLD6 in the round spermatids partially overlapped with that of the cis-Golgi marker GM130, indicating that the PLD6 expression corresponded to the GM130-positive subdomains of the Golgi apparatus. Correlative light and electron microscopy revealed that PLD6 expression in developing spermatids was localized almost exclusively to several flattened cisternae, and these structures might correspond to the medial Golgi subcompartment; neither the trans-Golgi networks nor the developing acrosomal system expressed PLD6. Further, we observed that PLD6 interacted with tesmin, a testis-specific transcript necessary for successful spermatogenesis in mouse testes. To our knowledge, these results provide the first evidence of PLD6 as a Golgi-localized protein of pachytene spermatocytes and developing spermatids and suggest that its subcompartment-specific distribution within the Golgi apparatus may be related to the specific functions of this organelle during spermatogenesis.