Development Of Reproductive Structures Research Articles

The perspective of ceRNA regulation of circadian rhythm on choroidal neovascularization

Abnormal growth of blood vessels (choroidal neovascularization) can lead to age-related macular degeneration (AMD) and eventually cause vision loss due to detachment of the retinal pigmented epithelium. This indicates that choroidal neovascularization is important for the treatment of AMD. The circadian clock in the mammalian retina is responsible for controlling various functions of the retina, enabling it to adjust to changes in light and darkness. Recent studies have revealed a potential connection between the circadian clock and eye diseases, although a cause-and-effect relationship has not been definitively established. C57BL/6J male mice (aged 6 weeks) were randomly divided into two groups (Control group: 9:00–21:00 light period (300 lx); Jet lag group: 8-hour phase advance once every 4 days). A laser-induced CNV model was created after 2 weeks of feeding in a controlled or jet-lagged environment. Then, full transcriptome sequencing was performed. The pathways regulated by differentially expressed mRNAs were identified by GO analysis and GSEA. Further protein networks were constructed with the STRING database and Cytoscape software. WGCNA was used to further explore the co-expression modules of these differential genes and the correlation between these differential genes and phenotypes. ceRNA networks were constructed with miRanda and TargetScan. The pathways associated with the overlapping differentially expressed mRNAs in the ceRNA network were identified, and the hub genes were validated by qPCR. A total of 661 important DEGs, 31 differentially expressed miRNAs, 106 differentially expressed lncRNAs and 87 differentially expressed circRNAs were identified. GO and GSEA showed that the upregulated DEGs were mainly involved in reproductive structure development and reproductive system development. The STRING database and Cytoscape were used to determine the protein interaction relationships of these DEGs. WGCNA divided the expression of these genes into several modules and screened the hub genes of each module separately. Furthermore, a ceRNA network was constructed. GO analysis and GSEA showed that these target DEmRNAs mainly function in wound healing, cell spreading, epiboly involved in wound healing, epiboly, and morphogenesis of an epithelial sheet. Finally, ten key genes were identified, and their expression patterns were confirmed by real-time qPCR. In this study, we investigated the regulatory mechanism of ceRNAs in choroidal neovascularization according to different light-dark cycles in the eyeball.

Proteomic and Phosphoproteomic Analyses during Plant Regeneration Initiation in Cotton (Gossypium hirsutum L.).

Somatic embryogenesis (SE) is a biotechnological tool used to generate new individuals and is the preferred method for rapid plant regeneration. However, the molecular basis underlying somatic cell regeneration through SE is not yet fully understood, particularly regarding interactions between the proteome and post-translational modifications. Here, we performed association analysis of high-throughput proteomics and phosphoproteomics in three representative samples (non-embryogenic calli, NEC; primary embryogenic calli, PEC; globular embryos, GE) during the initiation of plant regeneration in cotton, a pioneer crop for genetic biotechnology applications. Our results showed that protein accumulation is positively regulated by phosphorylation during SE, as revealed by correlation analyses. Of the 1418 proteins that were differentially accumulated in the proteome and the 1106 phosphoproteins that were differentially regulated in the phosphoproteome, 115 proteins with 229 phosphorylation sites overlapped (co-differential). Furthermore, seven dynamic trajectory patterns of differentially accumulated proteins (DAPs) and the correlated differentially regulated phosphoproteins (DRPPs) pairs with enrichment features were observed. During the initiation of plant regeneration, functional enrichment analysis revealed that the overlapping proteins (DAPs-DRPPs) were considerably enriched in cellular nitrogen metabolism, spliceosome formation, and reproductive structure development. Moreover, 198 DRPPs (387 phosphorylation sites) were specifically regulated at the phosphorylation level and showed four patterns of stage-enriched phosphorylation susceptibility. Furthermore, enrichment annotation analysis revealed that these phosphoproteins were significantly enriched in endosomal transport and nucleus organization processes. During embryogenic differentiation, we identified five DAPs-DRPPs with significantly enriched characteristic patterns. These proteins may play essential roles in transcriptional regulation and signaling events that initiate plant regeneration through protein accumulation and/or phosphorylation modification. This study enriched the understanding of key proteins and their correlated phosphorylation patterns during plant regeneration, and also provided a reference for improving plant regeneration efficiency.

Exploring the effect of Gouqi Nuzhen Liuhe decoction on the PI3K/mTOR signaling pathway for premature ovarian insufficiency based on system pharmacology

ObjectiveTo explore the effect of Gouqi Nuzhen Liuhe Decoction (GNLHD) on the PI3K/mTOR Signaling Pathway for Premature Ovarian Insufficiency (POI) based on system pharmacology. MethodsFirst, the system pharmacology approach was used to predict the mechanism of GNLHD. Then, mice were randomly divided into model group, positive group, GNLHD high-dose group, GNLHD medium-dose group, and GNLHD low-dose group. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of ovarian tissue under light microscope. The expression levels of estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were detected by enzyme-linked immunosorbent assay. The expressions of PI3K, AKT1 and mTOR proteins in ovarian tissue were detected by immunohistochemistry. ResultsThe results of system pharmacology showed that GNLHD may regulate biological processes and signaling pathways such as: reproductive structure development, reproductive system development, Oocyte meiosis and so on. Compared with the model group, the levels of E2 in the GNLHD group were increased, and the levels of FSH and LH were decreased (P < 0.05). Compared with the model group, the number of mature follicles in the GNLHD group was significantly increased, the number of atretic follicles was relatively decreased, and the expressions of PI3K, AKT1, and MTOR proteins in the GNLHD group were significantly increased (P < 0.05). ConclusionGNLHD may improve the ovarian function of POI mice by affecting the expression of PI3K, AKT1 and mTOR proteins, promote the growth and development of follicles, increase the E2 level, reduce FSH and LH level, and maintain the stability of the ovarian internal environment.

Whole-genome sequencing identified candidate genes associated with high and low litter size in Chuanzhong black goats.

The reproductive performance of goats significantly influences breeding efficiency and economic returns, with litter size serving as a comprehensive indicator. Despite this, research on the genetic control of litter size remains limited. Therefore, we aimed to explore the candidate genes affecting fecundity and compared the whole-genome sequences (WGS) of 15 high-litter (HL) and 15 low-litter (LL) size in Chuanzhong black goats. Then genetic diversity and genomic variation patterns were analyzed by phylogenetic, principal component and population genetic structure analysis, it was found that HL and LL subpopulations diverged. Population evolutionary selection elimination analysis was performed by Fst and θπ resulted in 506 genes were annotated in HL and 528 genes in LL. These genes were mainly related to Hippo signaling pathway, G protein-coupled signaling pathway, G protein-coupled receptor activity, cell surface receptor signaling pathway, gonadal and reproductive structure development. According to the significantly selected genomic regions and important pathways, we found that the g.89172108T > G variant locus in the exon of the AMH gene was significantly associated with litter size (P < 0.05), which could be used as an auxiliary selection gene for the high fertility of Chuanzhong black Goat.

Climate warming disturbances periodicity of Siberian stone pine seed production (Pinus sibirica Du Tour)

Siberian stone pine is one of the main edificator plants of taiga forests of Western Siberia. Sustainable functioning of forest ecosystems depends on its successful cone crops, as its seeds are the basis for the diet of many forest animals. A cone crop in this species is characterized by pronounced interannual variability, manifested in the formation of high seed yields once in 3-4 years. However, in the last 20 years, high yields have been rare, replaced by years with average and low yields. To establish the reasons for these changes, the dynamics of seeding in the period from 1990 to 2023 and weather conditions in spring in the pollination year during the same period were analyzed. It was found that the number of mature cones in the crown largely depended on spring weather in the year of pollination and was negatively correlated with the sum of active temperatures above +5°C accumulated before the late spring frost. If frost occurred at SAT above 300°C, the following year’s crop was minimized. Analysis of weather conditions showed that, on average, there is a tendency to shift the dates of the last frosts to later dates, and even a short-term decrease in temperature to -1 °C leads to complete death of the future crop of cones. Despite the growth of heat availability in the spring period due to active temperature increase in April, the expected shift of frosts to earlier dates is not observed in the south of Western Siberia. For Siberian stone pine, such situation is fraught with strengthening of negative trend in seeding dynamics. It is supposed that at further climate warming the beginning of spring development of reproductive structures will occur at earlier dates, so reproductive structures will be more damaged by late spring frosts, since the latter remain within the same time frames.

Heat shock factor binding protein BrHSBP1 regulates seed and pod development in Brassica rapa.

Plant heat shock factor binding proteins (HSBPs) are well known for their implication in the negative regulation of heat stress response (HSR) pathways. Herein, we report on the hitherto unknown functions of HSBP1 in Brassica rapa (BrHSBP1). BrHBSP1 was found to be predominant in flower buds and young leaves, while its segmental duplicate, BrHSBP1-like, was abundant in green siliques. Exposure to abiotic stress conditions, such as heat, drought, cold, and H2O2, and to phytohormones was found to differentially regulate BrHSBP1. The activity of BrHSBP1-GFP fusion proteins revealed their cellular localization in nuclei and cytosols. Transgenic overexpression of BrHSBP1 (BrHSBP1OX) improved pod and seed sizes, while CRISPR-Cas BrHSBP1 knock-out mutants (Brhsbp1_KO) were associated with aborted seed and pod development. The transcriptomic signatures of BrHSBP1OX and Brhsbp1_KO lines revealed that 360 and 2381 genes, respectively, were differentially expressed (Log2FC≥2, padj<0.05) expressed relative to control lines. In particular, developmental processes, including plant reproductive structure development (RSD)-related genes, were relatively downregulated in Brhsbp1_KO. Furthermore, yeast two-hybrid assays confirmed that BrHSBP1 can physically bind to RSD and other genes. Taking the findings together, it is clear that BrHSBP1 is involved in seed development via the modulation of RSD genes. Our findings represent the addition of a new regulatory player in seed and pod development in B. rapa.

Large-scale analysis of de novo mutations identifies risk genes for female infertility characterized by oocyte and early embryo defects

BackgroundOocyte maturation arrest and early embryonic arrest are important reproductive phenotypes resulting in female infertility and cause the recurrent failure of assisted reproductive technology (ART). However, the genetic etiologies of these female infertility-related phenotypes are poorly understood. Previous studies have mainly focused on inherited mutations based on large pedigrees or consanguineous patients. However, the role of de novo mutations (DNMs) in these phenotypes remains to be elucidated.ResultsTo decipher the role of DNMs in ART failure and female infertility with oocyte and embryo defects, we explore the landscape of DNMs in 473 infertile parent–child trios and identify a set of 481 confident DNMs distributed in 474 genes. Gene ontology analysis reveals that the identified genes with DNMs are enriched in signaling pathways associated with female reproductive processes such as meiosis, embryonic development, and reproductive structure development. We perform functional assays on the effects of DNMs in a representative gene Tubulin Alpha 4a (TUBA4A), which shows the most significant enrichment of DNMs in the infertile parent–child trios. DNMs in TUBA4A disrupt the normal assembly of the microtubule network in HeLa cells, and microinjection of DNM TUBA4A cRNAs causes abnormalities in mouse oocyte maturation or embryo development, suggesting the pathogenic role of these DNMs in TUBA4A.ConclusionsOur findings suggest novel genetic insights that DNMs contribute to female infertility with oocyte and embryo defects. This study also provides potential genetic markers and facilitates the genetic diagnosis of recurrent ART failure and female infertility.

Reproductive maturity and sexual dimorphism of a population of Amerotyphlops brongersmianus from a Restinga area in southeastern Brazil (Serpentes: Typhlopidae).

Natural history data are important for a better understanding of distinct aspects of snake biology, and this information in scarce on Scolecophidia. Here we focus on sexual maturity and sexual dimorphism within a population of Amerotyphlops brongersmianus from the Restinga de Jurubatiba National Park, Rio de Janeiro state, Brazil. The smallest sexually active male and female showed snout-vent length of 117.5 and 158.4 mm, respectively. Females had statistically significant larger body and head length sizes, whereas males had longer tails. Juveniles showed no sexual dimorphism for any analyzed feature. Secondary vitellogenic follicles had a more opaque, yellowish/darker aspect, being larger than 3.5 mm. We reinforce that in addition to traditional features for determining sexual maturity, morphological and histological characteristics of kidneys should be evaluated in males, as well as the morphology of the infundibulum in females. Histological data show development of seminiferous tubules and presence of spermatozoa in males, and infundibulum receptacles and uterine glands in females as a sign of sexual maturity. This type of information is essential for a more accurate description of data on sexual maturity, allowing access to information on the development of reproductive structures that are not available macroscopically.

Mutation analysis of WNT4 gene in SRY negative 46,XX DSD patients with Mullerian agenesis and/or gonadal dysgenesis- An Indian study

Developmental disruption of the Mullerian duct and gonads in females leads to Mullerian agenesis and gonadal dysgenesis, respectively. These two structural abnormalities are coming under the 46,XX DSD (Disorders of Sexual Development) classification, the majority of cases the aetiology remains elusive. Without the SRY gene, WNT4 plays a key role in female reproductive structure development. Since there are no studies that explored the involvement of the WNT4 gene in Indian 46,XX DSD patients, we analysed the role of WNT4 in Indian 46,XX DSD patients with Mullerian agenesis and/or Gonadal dysgenesis. In our study, we recruited 103 adolescent girls with primary amenorrhea. After the cytogenetic and SRY gene analysis, we included thirty-two 46,XX DSD patients with Mullerian agenesis and/or gonadal dysgenesis for WNT4 gene mutation analysis. PCR sequencing was performed for all the coding exons of the WNT4 gene. Bioinformatic tools like Mutation Taster, Human Splicing Finder, and miRDB were used. We observed single nucleotide variations in three patients. One patient showed a known synonymous polymorphism (c.861C > T; p.G287G, rs544988174). miRDB data revealed the absence of microRNA regulatory sites in this region. The other two cases carried a nucleotide substitution in intronic regions and did not affect the normal splicing mechanism. In conclusion, we could not find any indication about WNT4 involvement in the disease condition. In the future, WNT4 promoter analysis in these patients and molecular characterization of the WNT4 coding and promoter region in more patients are needed to link WNT4 variants with these structural abnormalities.

Natural history and ecological effects on the establishment and fate of Florida carpenter ant cadavers infected by the parasitic manipulator Ophiocordyceps camponoti‐floridani

Abstract Ophiocordyceps fungi manipulate the behaviour of their ant hosts to produce a summit disease phenotype, thereby establishing infected ant cadavers onto vegetation at elevated positions suitable for fungal growth and transmission. Multiple environmental and ecological factors have been proposed to shape the timing, positioning and outcome of these manipulations. We conducted a long‐term field study of Ophiocordyceps camponoti‐floridani infections of Camponotus floridanus ants—the Florida zombie ants. We propose and refine hypotheses on the factors that shape infection outcomes by tracking the occurrence of and fungal growth from hundreds of ant cadavers. We modelled and report these data in relation to weather, light, vegetation and attack by hyperparasites. We investigated environmental factors that could affect the occurrence and location of newly manipulated ant cadavers. New cadaver occurrence was preferentially biased towards epiphytic Tillandsia bromeliads, canopy openness and summer weather conditions (an interactive effect of temperature, humidity and precipitation). Furthermore, we suggest that incident light at the individual cadaver level reflects microhabitat choice by manipulated ants or selective pressure on cadaver maintenance for conditions that improve fungal survival. We also asked which environmental conditions affect fungal fitness. Continued fungal development of reproductive structures and putative transmission increased with moist weather conditions (interaction of humidity and precipitation) and canopy openness, while being reduced by hyperparasitic mycoparasite infections. Moreover, under the most open canopy conditions, we found an atypical Ophiocordyceps growth morphology that could represent a plastic response to conditions influenced by high light levels. Taken together, we explore general trends and the effects of various ecological conditions on host and parasite disease outcomes in the Florida zombie ant system. These insights from the field can be used to inform experimental laboratory setups that directly test the effects of biotic and abiotic factors on fungus–ant interactions or aim to uncover underlying molecular mechanisms. Read the free Plain Language Summary for this article on the Journal blog.

Genome-wide analysis of long non-coding RNAs under diel light exhibits role in floral development and the circadian clock in Arabidopsis thaliana

The circadian clock is regulated by signaling networks that enhance a plant's ability to coordinate internal events with the external environment. In this study, we examine the rhythmic expression of long non-coding RNAs (lncRNAs) using multiple transcriptomes of Arabidopsis thaliana in the diel light cycle and integrated this information to have a better understanding of the functions of lncRNAs in regulating the circadian clock. We identified 968, 1050, and 998 lncRNAs at 8 h light, 16 h light and 8 h dark conditions, respectively. Among these, 423, 486, and 417 lncRNAs were uniquely present at 8 h light, 16 h light, and 8 h dark, respectively, whereas 334 lncRNAs were common under the three conditions. The specificity of identified lncRNAs under different light conditions was verified using qRT-PCR. The identified lncRNAs were less GC-rich and expressed at a significantly lower level than the mRNAs of protein-coding genes. In addition, we identified enriched motifs in lncRNA transcribing regions that were associated with light-responsive genes (SORLREP and SORLIP), flower development (AGAMOUS), and circadian clock (CCA1) under all three light conditions. We identified 10 and 12 different lncRNAs targeting different miRNAs with perfect and interrupted complementarity (endogenous target mimic). These predicted lncRNA-interacting miRNAs govern the function of a set of genes involved in the developmental process, reproductive structure development, gene silencing and transcription regulation. We demonstrated that the lncRNA transcribing regions were enriched for epigenetic marks such as H3.3, H3K4me2, H3K4me3, H4K16ac, H3K36ac, H3K56ac and depleted for heterochromatic (H3K9me2 and H3K27me1) and repressive (H3K27me3) histone modifications. Further, we found that hypermethylated genomic regions negatively correlated with lncRNA transcribing regions. Overall, our study showed that lncRNAs expressed corresponding to the diel light cycle are implicated in regulating the circadian rhythm and governing the developmental stage-specific growth.

Identification of functional TF-miRNA-hub gene regulatory network associated with ovarian endometriosis.

Endometriosis (EMs), one of the most common gynecological diseases, seriously affects the health and wellness of women; however, the underlying pathogenesis remains unclear. This study focused on dysregulated genes and their predicted transcription factors (TFs) and miRNAs, which may provide ideas for further mechanistic research. The microarray expression dataset GSE58178, which included six ovarian endometriosis (OE) samples and six control samples, was downloaded from the Gene Expression Omnibus (GEO) to identify differentially expressed genes (DEGs). Gene Ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were performed to study the cellular and organism-level functions of DEGs. The protein-protein interaction (PPI) network was built and visualized using Cytoscape, and modules and hub genes were explored using various algorithms. Furthermore, we predicted miRNAs and TFs of hub genes using online databases, and constructed the TF-miRNA-hub gene network. There were 124 upregulated genes and 66 downregulated genes in EMs tissues. GO enrichment analysis showed that DEGs were concentrated in reproductive structure development and collagen-containing extracellular matrix, while KEGG pathway analysis showed that glycolysis/gluconeogenesis and central carbon metabolism in cancer require further exploration. Subsequently, HIF1A, LDHA, PGK1, TFRC, and CD9 were identified as hub genes, 22 miRNAs and 34 TFs were predicted to be upstream regulators of hub genes, and these molecules were pooled together. In addition, we found three key feedback loops in the network, MYC-miR-34a-5p-LDHA, YY1-miR-155-5p-HIF1A, and RELA-miR-93-5p-HIF1A, which may be closely related to OE development. Taken together, our study structured a TF-miRNA-hub gene network to decipher the molecular mechanism of OE, which may provide novel insights for clinical diagnosis and treatment.

Transcriptional Regulation of Pine Male and Female Cone Initiation and Development: Key Players Identified Through Comparative Transcriptomics.

With long reproductive timescales, large complex genomes, and a lack of reliable reference genomes, understanding gene function in conifers is extremely challenging. Consequently, our understanding of which genetic factors influence the development of reproductive structures (cones) in monoecious conifers remains limited. Genes with inferred roles in conifer reproduction have mostly been identified through homology and phylogenetic reconstruction with their angiosperm counterparts. We used RNA-sequencing to generate transcriptomes of the early morphological stages of cone development in the conifer species Pinus densiflora and used these to gain a deeper insight into the transcriptional changes during male and female cone development. Paired-end Illumina sequencing was used to generate transcriptomes from non-reproductive tissue and male and female cones at four time points with a total of 382.82 Gbp of data generated. After assembly and stringent filtering, a total of 37,164 transcripts were retrieved, of which a third were functionally annotated using the Mercator plant pipeline. Differentially expressed gene (DEG) analysis resulted in the identification of 172,092 DEGs in the nine tissue types. This, alongside GO gene enrichment analyses, pinpointed transcripts putatively involved in conifer reproductive structure development, including co-orthologs of several angiosperm flowering genes and several that have not been previously reported in conifers. This study provides a comprehensive transcriptome resource for male and early female cone development in the gymnosperm species Pinus densiflora. Characterisation of this resource has allowed the identification of potential key players and thus provides valuable insights into the molecular regulation of reproductive structure development in monoecious conifers.

Evolution and expression of LEAFY genes in ferns and lycophytes

BackgroundThe LEAFY (LFY) transcription factors are present in algae and across land plants. The available expression and functional data of these genes in embryophytes suggest that LFY genes control a plethora of processes including the first zygotic cell division in bryophytes, shoot cell divisions of the gametophyte and sporophyte in ferns, cone differentiation in gymnosperms and floral meristem identity in flowering plants. However, their putative plesiomorphic role in plant reproductive transition in vascular plants remains untested.ResultsWe perform Maximum Likelihood (ML) phylogenetic analyses for the LFY gene lineage in embryophytes with expanded sampling in lycophytes and ferns. We recover the previously identified seed plant duplication that results in LEAFY and NEEDLY paralogs. In addition, we recover multiple species-specific duplications in ferns and lycophytes and large-scale duplications possibly correlated with the occurrence of whole genome duplication (WGD) events in Equisetales and Salviniales. To test putative roles in diverse ferns and lycophytes we perform LFY expression analyses in Adiantum raddianum, Equisetum giganteum and Selaginella moellendorffii. Our results show that LFY genes are active in vegetative and reproductive tissues, with higher expression in early fertile developmental stages and during sporangia differentiation.ConclusionsOur data point to previously unrecognized roles of LFY genes in sporangia differentiation in lycophytes and ferns and suggests that functions linked to reproductive structure development are not exclusive to seed plant LFY homologs.

FOXF1 Was Identified as a Novel Biomarker of Infantile Hemangioma by Weighted Coexpression Network Analysis and Differential Gene Expression Analysis.

Background The most frequent benign tumor in newborns is infantile hemangioma. The majority of infantile hemangiomas has a favorable prognosis and generally fades away on their own. Some people, however, do experience major consequences. Transcriptome alterations in infantile hemangiomas are yet unclear. The use of transcriptome analysis to uncover diagnostic markers for infantile hemangioma has clinical implications. Methods The dataset GSE127487 for infantile hemangioma was obtained from the GEO database. The gene set most related with infantile hemangioma was investigated using weighted coexpression network analysis. Differential expression analysis was performed to see whether genes were up or downregulated in infantile hemangiomas. The enrichment of gene sets in pathways or functions is determined via enrichment analysis. Hub genes were discovered via protein-protein interaction network analysis. The relationship between hub genes and immune cells was investigated using immunomicroenvironment analysis. Results Turquoise and Pink modules were revealed to be the most linked with infantile hemangioma in a weighted coexpression network analysis (p < 0.001). The genes in the two modules were mostly concentrated in actin filament organization, embryonic organ development, reproductive structure development, cell substrate adhesion, extracellular matrix organization, and so on, according to GO enrichment analysis (p < 0.05). These gene enrichment pathways comprised the PI3K-Akt signaling pathway, human papillomavirus infection, focal adhesion, and hepatitis C pathways, according to KEGG enrichment analyzes (p < 0.05). Differential expressed gene analysis showed 43 upregulated and 21 downregulated genes in infantile hemangiomas. We found the gene set most associated to infantile hemangioma by intersecting the elevated genes with the genes acquired by WGCNA, with FOXF1 serving as the hub gene. FOXF1 was linked to the degree of monocyte infiltration, according to immunocorrelation analysis (p < 0.05). B cell memory, dendritic cells resting, macrophage M0, neutrophils, and T cells helper are all negatively connected (p < 0.05). In the FOXF1 hyperexpression group, GSEA analysis revealed that cholesterol homeostasis and cell cycle-associated pathways G2M checkpoint were primarily activated (p < 0.05). Conclusion FOXF1 was found to be a reliable biomarker of infantile hemangiomas in our research of transcriptome changes in infantile hemangiomas.

Genetic analysis of Caenorhabditis elegans pry-1/Axin suppressors identifies genes involved in reproductive structure development, stress responses, and aging.

The Axin family of scaffolding proteins regulates a wide array of developmental and post-developmental processes in eukaryotes. Studies in the nematode Caenorhabditis elegans have shown that the Axin homolog PRY-1 plays essential roles in multiple tissues. To understand the genetic network of pry-1, we focused on a set of genes that are differentially expressed in the pry-1-mutant transcriptome and are linked to reproductive structure development. Knocking down eight of the genes (spp-1, clsp-1, ard-1, rpn-7, cpz-1, his-7, cdk-1, and rnr-1) via RNA interference efficiently suppressed the multivulva phenotype of pry-1 mutants. In all cases, the ectopic induction of P3.p vulval precursor cell was also inhibited. The suppressor genes are members of known gene families in eukaryotes and perform essential functions. Our genetic interaction experiments revealed that in addition to their role in vulval development, these genes participate in one or more pry-1-mediated biological events. Whereas four of them (cpz-1, his-7, cdk-1, and rnr-1) function in both stress response and aging, two (spp-1 and ard-1) are specific to stress response. Altogether, these findings demonstrate the important role of pry-1 suppressors in regulating developmental and post-developmental processes in C. elegans. Given that the genes described in this study are conserved, future investigations of their interactions with Axin and their functional specificity promises to uncover the genetic network of Axin in metazoans.

Why is phloem sap nitrate kept low?

Since the first description of phloem sap composition nearly 60 years ago, it is generally assumed that phloem sap does not contain nitrate and that there is little or no backflow of nitrate from shoots to roots. While it is true that nitrate can occasionally be absent from phloem sap, there is now substantial evidence that phloem can carry nitrate and furthermore, transporters involved in nitrate redistribution to shoot sink organs and roots have been found. This raises the question of why nitrate may or may not be present in phloem sap, why its concentration is generally kept low, and whether plant shoot-root nutrient cycling also involves nitrate. We propose here that phloem sap nitrate is not only an essential component of plant nutritional signaling but also contributes to physical properties of phloem sap and as such, its concentration must be controlled to ensure proper coordination of plant development and nutrient transport. This article is protected by copyright. All rights reserved.

Revealing the therapeutic targets and molecular mechanisms of emodin-treated coronavirus disease 2019 via a systematic study of network pharmacology.

Emodin has shown pharmacological effects in the treatment of infection with severe acute respiratory syndrome coronavirus-2, which leads to coronavirus disease 2019 (COVID-19). Thus, we speculated that emodin may possess anti-COVID-19 activity. In this study, using bioinformatics databases, we screened and harvested the candidate genes or targets of emodin and COVID-19 prior to the determination of pharmacological targets and molecular mechanisms of emodin against COVID-19. We discovered core targets for the treatment of COVID-19, including mitogen-activated protein kinase 1 (MAPK1), tumor protein (TP53), tumor necrosis factor (TNF), caspase-3 (CASP3), epidermal growth factor receptor (EGFR), vascular endothelial growth factor A (VEGFA), interleukin 1B (IL1B), mitogen-activated protein kinase 14 (MAPK14), prostaglandin-endoperoxide synthase 2 (PTGS2), B-cell lymphoma-2-like protein 1 (BCL2L1), interleukin-8 (CXCL8), myeloid cell leukemia-1 (MCL1), and colony stimulating factor 2 (CSF2). The GO analysis of emodin against COVID-19 mainly included cytokine-mediated signaling pathway, response to lipopolysaccharide, response to molecule of bacterial origin, developmental process involved in reproduction, and reproductive structure development. The KEGG results exhibited that the molecular pathways mainly included IL-17 signaling pathway, AGE-RAGE signaling pathway in diabetic complications, TNF signaling pathway, pertussis, proteoglycans in cancer, pathways in cancer, MAPK signaling pathway, NOD-like receptor signaling pathway, NF-kappa B signaling pathway, etc. Also, molecular docking results revealed the docking capability between emodin and COVID-19 and the potential pharmacological activity of emodin against COVID-19. Taken together, these findings uncovered the targets and pharmacological mechanisms of emodin for treating COVID-19 and suggested that the vital targets might be used as biomarkers against COVID-19.

Melatonin: Multi-Target Mechanism Against Diminished Ovarian Reserve Based on Network Pharmacology.

BackgroundDiminished ovarian reserve (DOR) significantly increases the risk of female infertility and contributes to reproductive technology failure. Recently, the role of melatonin in improving ovarian reserve (OR) has attracted widespread attention. However, details on the pharmacological targets and mechanisms of melatonin-improved OR remain unclear.ObjectiveA systems pharmacology strategy was proposed to elucidate the potential therapeutic mechanism of melatonin on DOR at the molecular, pathway, and network levels.MethodsThe systems pharmacological approach consisted of target identification, data integration, network construction, bioinformatics analysis, and molecular docking.ResultsFrom the molecular perspective, 26 potential therapeutic targets were identified. They participate in biological processes related to DOR development, such as reproductive structure development, epithelial cell proliferation, extrinsic apoptotic signaling pathway, PI3K signaling, among others. Eight hub targets (MAPK1, AKT1, EGFR, HRAS, SRC, ESR1, AR, and ALB) were identified. From the pathway level, 17 significant pathways, including the PI3K-Akt signaling pathway and the estrogen signaling pathway, were identified. In addition, the 17 signaling pathways interacted with the 26 potential therapeutic targets to form 4 functional modules. From the network point of view, by regulating five target subnetworks (aging, cell growth and death, development and regeneration, endocrine and immune systems), melatonin could exhibit anti-aging, anti-apoptosis, endocrine, and immune system regulation effects. The molecular docking results showed that melatonin bound well to all hub targets.ConclusionThis study systematically and intuitively illustrated the possible pharmacological mechanisms of OR improvement by melatonin through anti-aging, anti-apoptosis, endocrine, and immune system regulation effects.

Aspects of the reproductive biology of Zingiber spectabile (Zingiberaceae)

Ginger (Zingiber spectabile) is cultivated worldwide as a floriculture and landscaping species. Studies on the biology and floral morphology of this species are important for its improvement; however, they are scarce. We investigated the reproductive biology and floral morphology of gingers grown in a germplasm bank. Floral development was monitored during the pre-anthesis and anthesis periods. Floral morphometry, pollen viability, stigmatic receptivity, volume and concentration of nectar sugar, and performance of possible pollinators were evaluated. Ginger flowers had a 24-h durability. Ginger torch is an allogamous species that exhibits floral hercogamy like other Zingiberaceae. Ginger flowers had a 12-h anthesis. During anthesis, floral structures related to reproduction such as the style, stigma, and anther crest continued to develop, increasing floral herkogamy. Pollen viability was above 70% and the stigma remained receptive throughout the anthesis period. Hummingbirds were the only pollinators recorded in the study area that were able to move the anther crest. Fruiting was determined in a natural pollination system. The occurrence of nocturnal anthesis characterized by an increase in the development of reproductive structures and nectar production suggests that the species is adapted to nocturnal visitors.