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The L1 cell adhesion molecule (L1) has demonstrated a range of beneficial effects in animal models of spinal cord injury, neurodegenerative disease, and ischemia; however, the role of L1 in TBI has not been fully examined. Mutations in the L1 gene affecting the extracellular domain of this type 1 transmembrane glycoprotein have been identified in patients with L1 syndrome. These patients suffer from hydrocephalus, MASA (mental retardation, adducted thumbs, shuffling gait, aphasia) symptoms, and corpus callosum agenesis. Clinicians have observed that recovery post-traumatic brain injury (TBI) varies among the population. This variability may be explained by the genetic differences present in the general population. In this study, we utilized a novel mouse model of L1 syndrome with a mutation at aspartic acid position 201 in the extracellular domain of L1 (L1-201). We assessed the impact of this specific single nucleotide polymorphism (SNP) localized to the X-chromosome L1 gene on recovery outcomes following TBI by comparing the L1-201 mouse mutants with their wild-type littermates. We demonstrate that male L1-201 mice exhibit significantly worse learning and memory outcomes in the Morris water maze after lateral fluid percussion (LFP) injury compared to male wild-type mice and a trend to worse motor function on the rotarod. However, no significant changes were observed in markers for inflammatory responses or apoptosis after TBI.

In female mammals, the proliferation and apoptosis of granulosa cells (GCs) have been shown to determine the fate of follicles. DNA methyltransferases (DNMTs) and SLCO3A1 have been reported to be involved in the survival of GCs and follicular growth. However, the molecular mechanisms enabling DNMTs to regulate the expression of SLCO3A1 to participate in follicular growth are unclear. In this study, we found that the knockdown of DNMT1 enhanced the mRNA and protein levels of SLCO3A1 by regulating the chromatin accessibility probably. Moreover, SLCO3A1 upregulated the mRNA and protein levels of MCL1, PCNA, and STAR to promote the proliferation of GCs and facilitated cell cycle progression by increasing the mRNA and protein levels of CCNE1, CDK2, and CCND1, but it decreased apoptosis by downregulating the mRNA and protein levels of CASP3 and CASP8. Moreover, SLCO3A1 promoted the growth of porcine follicles and development of mice follicles. In conclusion, the knockdown of DNMT1 upregulated the mRNA and protein levels of SLCO3A1, thereby promoting the proliferation of GCs to facilitate the growth and development of ovarian follicles, and these results provide new insights into investigations of female reproductive diseases.

Heat stress severely affects the annual agricultural production. Heat stress transcription factors (HSFs) represent a critical regulatory juncture in the heat stress response (HSR) of plants. The HsfA1-dependent pathway has been explored well, but the regulatory mechanism of the HsfA1-independent pathway is still under-investigated. In the present research, HsfA4, an important gene of the HsfA1-independent pathway, was isolated from lilies (Lilium longiflorum) using the RACE method, which encodes 435 amino acids. LlHsfA4 contains a typical domain of HSFs and belongs to the HSF A4 family, according to homology comparisons and phylogenetic analysis. LlHsfA4 was mainly expressed in leaves and was induced by heat stress and H2O2 using qRT-PCR and GUS staining in transgenic Arabidopsis. LlHsfA4 had transactivation activity and was located in the nucleus and cytoplasm through a yeast one hybrid system and through transient expression in lily protoplasts. Over expressing LlHsfA4 in Arabidopsis enhanced its basic thermotolerance, but acquired thermotolerance was not achieved. Further research found that heat stress could increase H2O2 content in lily leaves and reduced H2O2 accumulation in transgenic plants, which was consistent with the up-regulation of HSR downstream genes such as Heat stress proteins (HSPs), Galactinol synthase1 (GolS1), WRKY DNA binding protein 30 (WRKY30), Zinc finger of Arabidopsis thaliana 6 (ZAT6) and the ROS-scavenging enzyme Ascorbate peroxidase 2 (APX2). In conclusion, these results indicate that LlHsfA4 plays important roles in heat stress response through regulating the ROS metabolism in lilies.

In roses (Rosa sp.), peduncle morphology is an important ornamental feature. The common physiological abnormality known as the bent peduncle phenomenon (BPP) seriously decreases the quality of rose flowers and thus the commercial value. Because the molecular mechanisms underlying this condition are poorly understood, we analysed the transcriptional profiles and cellular structures of bent rose peduncles. Numerous differentially expressed genes involved in the auxin, cytokinin, and gibberellin signaling pathways were shown to be associated with bent peduncle. Paraffin sections showed that the cell number on the upper sides of bent peduncles was increased, while the cells on the lower sides were larger than those in normal peduncles. We also investigated the large, deformed sepals that usually accompany BPP and found increased expression level of some auxin-responsive genes and decreased expression level of genes that are involved in cytokinin and gibberellin synthesis in these sepals. Furthermore, removal of the deformed sepals partially relieved BPP. In summary, our findings suggest that auxin, cytokinin, and gibberellin all influence the development of BPP by regulating cell division and expansion. To effectively reduce BPP in roses, more efforts need to be devoted to the molecular regulation of gibberellins and cytokinins in addition to that of auxin.

The oral mucosa exhibits exceptional healing capability when compared to skin. Recent studies suggest that intrinsic differences in coding genes and regulatory small non-coding RNA (sncRNA) genes (e.g., microRNAs) may underlie the exceptional healing that occurs in the oral mucosa. Here, we investigate the role of a novel class of sncRNA—Piwi-interacting RNA (piRNA)—in the tissue-specific differential response to injury. An abundance of piRNAs was detected in both skin and oral mucosal epithelium during wound healing. The expression of PIWI genes (the obligate binding partners of piRNAs) was also detected in skin and oral wound healing. This data suggested that PIWI-piRNA machinery may serve an unknown function in the highly orchestrated wound healing process. Furthermore, unique tissue-specific piRNA profiles were obtained in the skin and oral mucosal epithelium, and substantially more changes in piRNA expression were observed during skin wound healing than oral mucosal wound healing. Thus, we present the first clue suggesting a role of piRNA in wound healing, and provide the first site-specific piRNA profile of skin and oral mucosal wound healing. These results serve as a foundation for the future investigation of the functional contribution(s) of piRNA in wound repair and tissue regeneration.

Wounds within the oral mucosa are known to heal more rapidly than skin wounds. Recent studies suggest that differences in the microRNAome profiles may underlie the exceptional healing that occurs in oral mucosa. Here, we test whether skin wound-healing can be accelerating by increasing the levels of oral mucosa-specific microRNAs. A panel of 57 differentially expressed high expresser microRNAs were identified based on our previously published miR-seq dataset of paired skin and oral mucosal wound-healing [Sci. Rep. (2019) 9:7160]. These microRNAs were further grouped into 5 clusters based on their expression patterns, and their differential expression was confirmed by TaqMan-based quantification of LCM-captured epithelial cells from the wound edges. Of these 5 clusters, Cluster IV (consisting of 8 microRNAs, including miR-31) is most intriguing due to its tissue-specific expression pattern and temporal changes during wound-healing. The in vitro functional assays show that ectopic transfection of miR-31 consistently enhanced keratinocyte proliferation and migration. In vivo, miR-31 mimic treatment led to a statistically significant acceleration of wound closure. Our results demonstrate that wound-healing can be enhanced in skin through the overexpression of microRNAs that are highly expressed in the privileged healing response of the oral mucosa.

Cell fusion occurs in development and in physiology and rarely in those settings is it associated with malignancy. However, deliberate fusion of cells and possibly untoward fusion of cells not suitably poised can eventuate in aneuploidy, DNA damage and malignant transformation. How often cell fusion may initiate malignancy is unknown. However, cell fusion could explain the high frequency of cancers in tissues with low underlying rates of cell proliferation and mutation. On the other hand, cell fusion might also engage innate and adaptive immune surveillance, thus helping to eliminate or retard malignancies. Here we consider whether and how cell fusion might weigh on the overall burden of cancer in modern societies.

Cell fusion occurs in development and in physiology and rarely in those settings is it associated with malignancy. However, deliberate fusion of cells and possibly untoward fusion of cells not suitably poised can eventuate in aneuploidy, DNA damage and malignant transformation. How often cell fusion may initiate malignancy is unknown. However, cell fusion could explain the high frequency of cancers in tissues with low underlying rates of cell proliferation and mutation. On the other hand, cell fusion might also engage innate and adaptive immune surveillance, thus helping to eliminate or retard malignancies. Here we consider whether and how cell fusion might weigh on the overall burden of cancer in modern societies. [ABSTRACT FROM AUTHOR]