Genome-Wide Identification of GAST Family Members and Their Potential Roles in Epicotyl Dormancy in Chinese Cork Oak (Quercus variabilis).

Chinese cork oak (Quercus variabilis Blume) is a widespread tree species with high economic and ecological values. Chinese cork oak exhibits epicotyl dormancy, causing emergence heterogeneity and affecting the quality of seedling cultivation. Gibberellic acid-stimulated transcript (GAST) is a plant-specific protein family that plays a crucial regulatory role in plant growth, development, and seed germination. However, their evolution in Chinese cork oak and roles in epicotyl dormancy are still unclear. Here, a genome-wide identification of the GAST gene family was conducted in Chinese cork oak. Ten QvGAST genes were identified, and nine of them were expressed in seed. The physicochemical properties and promoter cis-acting elements of the selected Chinese cork oak GAST family genes indicated that the cis-acting elements in the GAST promoter are involved in plant development, hormone response, and stress response. Germinated seeds were subjected to gibberellins (GAs), abscisic acid (ABA), and fluridone treatments to show their response during epicotyl dormancy release. Significant changes in the expression of certain QvGAST genes were observed under different hormone treatments. QvGAST1, QvGAST2, QvGAST3, and QvGAST6 exhibited upregulation in response to gibberellin. QvGAST2 was markedly upregulated during the release of epicotyl dormancy in response to GA. These findings suggested that QvGAST2 might play an important role in epicotyl dormancy release. This study provides a basis for further analysis of the mechanisms underlying the alleviation of epicotyl dormancy in Chinese cork oak by QvGASTs genes.

miR-34b-3p-mediated regulation of STC2 and FN1 enhances chemosensitivity and inhibits proliferation in cervical cancer.

Dysregulation of microRNA (miRNA) expression in cancer is a significant factor contributing to the progression of chemoresistance. The objective of this study is to explore the underlying mechanisms by which miR-34b-3p regulates chemoresistance in cervical cancer (CC). Previous findings have demonstrated low expression levels of miR-34b-3p in both CC chemoresistant cells and tissues. In this study, we initially characterize the behavior of SiHa/DDP cells which are CC cells resistant to the chemotherapeutic drug cisplatin (DDP). Subsequently, miR-34b-3p mimics are transfected into SiHa/DDP cells. It is observed that overexpression of miR-34b-3p substantially inhibits the proliferation, migration, and invasion abilities of SiHa/DDP cells and also enhances their sensitivity to DDP-induced cell death. Quantitative RT-PCR and western blot analysis further reveal elevated expression levels of STC2 and FN1 in SiHa/DDP cells, contrary to the expression pattern of miR-34b-3p. Moreover, STC2 and FN1 contribute to DDP resistance, proliferation, migration, invasion, and decreased apoptosis in CC cells. Through dual-luciferase assay analysis, we confirm that STC2 and FN1 are direct targets of miR-34b-3p in CC. Finally, rescue experiments demonstrate that overexpression of either STC2 or FN1 can partially reverse the inhibitory effects of miR-34b-3p overexpression on chemoresistance, proliferation, migration and invasion in CC cells. In conclusion, our findings support the role of miR-34b-3p as a tumor suppressor in CC. This study indicates that targeting the miR-34b-3p/STC2 or FN1 axis has potential therapeutic implications for overcoming chemoresistance in CC patients.

Machine learning predictor PSPire screens for phase-separating proteins lacking intrinsically disordered regions.

The burgeoning comprehension of protein phase separation (PS) has ushered in a wealth of bioinformatics tools for the prediction of phase-separating proteins (PSPs). These tools often skew towards PSPs with a high content of intrinsically disordered regions (IDRs), thus frequently undervaluing potential PSPs without IDRs. Nonetheless, PS is not only steered by IDRs but also by the structured modular domains and interactions that aren't necessarily reflected in amino acid sequences. In this work, we introduce PSPire, a machine learning predictor that incorporates both residue-level and structure-level features for the precise prediction of PSPs. Compared to current PSP predictors, PSPire shows a notable improvement in identifying PSPs without IDRs, which underscores the crucial role of non-IDR, structure-based characteristics in multivalent interactions throughout the PS process. Additionally, our biological validation experiments substantiate the predictive capacity of PSPire, with 9 out of 11 chosen candidate PSPs confirmed to form condensates within cells.

Genomic basis of the distinct biosynthesis of ß-glucogallin, a biochemical marker for hydrolyzable tannin production, in three oak species.

Hydrolyzable tannins (HTs), predominant polyphenols in oaks, are widely used in grape wine aging, feed additives, and human healthcare. However, the limited availability of a high-quality reference genome of oaks greatly hampered the recognition of the mechanism of HT biosynthesis. Here, high-quality reference genomes of three Asian oak species (Quercus variabilis, Quercus aliena, and Quercus dentata) that have different HT contents were generated. Multi-omics studies were carried out to identify key genes regulating HT biosynthesis. In vitro enzyme activity assay was also conducted. Dual-luciferase and yeast one-hybrid assays were used to reveal the transcriptional regulation. Our results revealed that ß-glucogallin was a biochemical marker for HT production in the cupules of the three Asian oaks. UGT84A13 was confirmed as the key enzyme for ß-glucogallin biosynthesis. The differential expression of UGT84A13, rather than enzyme activity, was the main reason for different ß-glucogallin and HT accumulation. Notably, sequence variations in UGT84A13 promoters led to different trans-activating activities of WRKY32/59, explaining the different expression patterns of UGT84A13 among the three species. Our findings provide three high-quality new reference genomes for oak trees and give new insights into different transcriptional regulation for understanding ß-glucogallin and HT biosynthesis in closely related oak species.

Incorporation of Decidual Stromal Cells Derived Exosomes in Sodium Alginate Hydrogel as an Innovative Therapeutic Strategy for Advancing Endometrial Regeneration and Reinstating Fertility.

Intrauterine adhesion (IUA) stands as a prevalent medical condition characterized by endometrial fibrosis and scar tissue formation within the uterine cavity, resulting in infertility and, in severe cases, recurrent miscarriages. Cell therapy, especially with stem cells, offers an alternative to surgery, but concerns about uncontrolled differentiation and tumorigenicity limit its use. Exosomes, more stable and immunogenicity-reduced than parent cells, have emerged as a promising avenue for IUA treatment. In this study, a novel approach has been proposed wherein exosomes originating from decidual stromal cells (DSCs) are encapsulated within sodium alginate hydrogel (SAH) scaffolds to repair endometrial damage and restore fertility in a mouse IUA model. Current results demonstrate that in situ injection of DSC-derived exosomes (DSC-exos)/SAH into the uterine cavity has the capability to induce uterine angiogenesis, initiate mesenchymal-to-epithelial transformation (MET), facilitate collagen fiber remodeling and dissolution, promote endometrial regeneration, enhance endometrial receptivity, and contribute to the recovery of fertility. RNA sequencing and advanced bioinformatics analysis reveal miRNA enrichment in exosomes, potentially supporting endometrial repair. This finding elucidates how DSC-exos/SAH mechanistically fosters collagen ablation, endometrium regeneration, and fertility recovery, holding the potential to introduce a novel IUA treatment and offering invaluable insights into the realm of regenerative medicine.

Melatonin alleviates valproic acid-induced neural tube defects by modulating Src/PI3K/ERK signaling and oxidative stress.

Neural tube defects (NTDs) represent a developmental disorder of the nervous system that can lead to significant disability in children and impose substantial social burdens. Valproic acid (VPA), a widely prescribed first-line antiepileptic drug for epilepsy and various neurological conditions, has been associated with a 4-fold increase in the risk of NTDs when used during pregnancy. Consequently, urgent efforts are required to identify innovative prevention and treatment approaches for VPA-induced NTDs. Studies have demonstrated that the disruption in the delicate balance between cell proliferation and apoptosis is a crucial factor contributing to NTDs induced by VPA. Encouragingly, our current data reveal that melatonin (MT) significantly inhibits apoptosis while promoting the restoration of neuroepithelial cell proliferation impaired by VPA. Moreover, further investigations demonstrate that MT substantially reduces the incidence of neural tube malformations resulted from VPA exposure, primarily by suppressing apoptosis through the modulation of intracellular reactive oxygen species levels. In addition, the Src/PI3K/ERK signaling pathway appears to play a pivotal role in VPA-induced NTDs, with significant inhibition observed in the affected samples. Notably, MT treatment successfully reinstates Src/PI3K/ERK signaling, thereby offering a potential underlying mechanism for the protective effects of MT against VPA-induced NTDs. In summary, our current study substantiates the considerable protective potential of MT in mitigating VPA-triggered NTDs, thereby offering valuable strategies for the clinical management of VPA-related birth defects.

Allele-specific H3K9me3 and DNA methylation co-marked CpG-rich regions serve as potential imprinting control regions in pre-implantation embryo.

Parental DNA methylation and histone modifications undergo distinct global reprogramming in mammalian pre-implantation embryos, but the landscape of epigenetic crosstalk and its effects on embryogenesis are largely unknown. Here we comprehensively analyse the association between DNA methylation and H3K9me3 reprogramming in mouse pre-implantation embryos and reveal that CpG-rich genomic loci with high H3K9me3 signal and DNA methylation level (CHM) are hotspots of DNA methylation maintenance during pre-implantation embryogenesis. We further profile the allele-specific epigenetic map with unprecedented resolution in gynogenetic and androgenetic embryos, respectively, and identify 1,279 allele-specific CHMs, including 19 known imprinting control regions (ICRs). Our study suggests that 22 ICR-like regions (ICRLRs) may regulate allele-specific transcription similarly to known ICRs, and five of them are confirmed to be important for mouse embryo development. Taken together, our study reveals the widespread existence of allele-specific CHMs and largely extends the scope of allele-specific regulation in mammalian pre-implantation embryos.

CpG island reconfiguration for the establishment and synchronization of polycomb functions upon exit from naive pluripotency.

Polycomb group (PcG) proteins are essential for post-implantation development by depositing repressive histone modifications at promoters, mainly CpG islands (CGIs), of developmental regulator genes. However, promoter PcG marks are erased after fertilization and de novo established in peri-implantation embryos, coinciding with the transition from naive to primed pluripotency. Nevertheless, the molecular basis for this establishment remains unknown. In this study, we show that the expression of the long KDM2B isoform (KDM2BLF), which contains the demethylase domain, is specifically induced at peri-implantation and that its H3K36me2 demethylase activity is required for PcG enrichment at CGIs. Moreover, KDM2BLF interacts with BRG1/BRM-associated factor (BAF) and stabilizes BAF occupancy at CGIs for subsequent gain of accessibility, which precedes PcG enrichment. Consistently, KDM2BLF inactivation results in significantly delayed post-implantation development. In summary, our data unveil dynamic chromatin configuration of CGIs during exit from naive pluripotency and provide a conceptual framework for the spatiotemporal establishment of PcG functions.

ncHMR detector: a computational framework to systematically reveal non-classical functions of histone modification regulators.

Recently, several non-classical functions of histone modification regulators (HMRs), independent of their known histone modification substrates and products, have been reported to be essential for specific cellular processes. However, there is no framework designed for identifying such functions systematically. Here, we develop ncHMR detector, the first computational framework to predict non-classical functions and cofactors of a given HMR, based on ChIP-seq data mining. We apply ncHMR detector in ChIP-seq data-rich cell types and predict non-classical functions of HMRs. Finally, we experimentally reveal that the predicted non-classical function of CBX7 is biologically significant for the maintenance of pluripotency.

The Alterations of Biofilm Formation and EPS Characteristics of a Diatom by a Sponge-Associated Bacterium Psychrobacter sp.

A sponge-associated bacterium, which was identified as Psychrobacter sp. in this study, was found with high activity against biofilm formation of benthic diatoms, including Amphora sp., Nitzschia closterium, Nitzschia frustulum, and Stauroneis sp. The activity against diatom biofilm formation by the tested strain was confirmed mostly in the culture supernatant and could be extracted using organic solvents. Treatment with its supernatant crude extract significantly reduced the cells of Stauroneis sp. forming biofilm and slightly increased the cells floating in the culture medium, which results in the ratio of biofilm cell/floating cell altering from 0.736 in control to 0.414 in treatment. Use of the supernatant crude extract led to increased production of extracellular polymeric substances (EPSs) by diatom Stauroneis sp. from 16.66 to 41.59 (g/g cell dry weight). The increase in EPS production was mainly contributed by soluble EPS (SL-EPS) and followed by the EPS that was tightly bound to biofilm cells (BF-TB-EPS). In addition, the supernatant crude extract caused significant changes in the monosaccharides composition of the EPS of Stauroneis sp. Specifically, glucuronic acid (Glc-A) and N-acetyl-D-glucosamine (Glc-NAc) in BF-TB-EPS were 55% fold decreased and 1219% fold increased, respectively. Based on our findings, we proposed that these changes in monosaccharides composition might lead to a decreased biofilm formation efficiency of diatom.

The characterization and comparison of exopolysaccharides from two benthic diatoms with different biofilm formation abilities.

Exopolysaccharide (EPS) of two benthic diatoms, Amphora sp. and Stauroneis sp., with different biofilm formation abilities were investigated. The ratio of suspension-cells/biofilm-cells was employed to indicate the diatom biofilm formation abilities. The soluble EPS from the supernatant of whole culture, tightly bound EPS from floating cells, loosely and tightly bound EPS from biofilm cells were fractionated as SL-EPS, F-TB-EPS, BF-LB-EPS and BF-TB-EPS, respectively. The analysis for productions and monosaccharide compositions indicated that EPS from two diatoms were different in terms of the productions, distributions, and monomer compositions. Amphora sp. produced more (1.5-fold) total exopolysaccharides, but less (<0.4-fold) BF-TB-EPS than Stauroneis sp. The monosaccharides of the EPS from Amphora sp. were more diverse than those of Stauroneis sp., with 13 and 10 monomers, respectively. Neutral sugars, Glc, Xyl and Man, were abundant in Stauroneis sp., while Gal, Glc and Xyl were rich in Amphora sp. Uronic acid and hexosamine were present in all fractions of two diatoms, especially Glc-A being the most abundant monomer in SL-EPS of Amphora sp. It was proposed that the high content of uronic acid (especially Glc-A) might be crucial for the strong biofilm formation abilities of Amphora sp.