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"Xia, Xi"
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MicroRNA‐488 inhibits endometrial glandular epithelial cell proliferation, migration, and invasion in endometriosis mice via Wnt by inhibiting FZD7
Endometriosis is a chronic inflammatory syndrome and nearly 6%‐10% of women are affected by it during the reproductive period. Previous studies have proved that microRNAs (miRNAs) are implicated in the pathogenesis of ovarian endometriosis. In this study, we aimed to investigate that restored miR‐488 would effectively inhibit the development of endometriosis. The microarray‐based data analysis was performed to screen endometriosis‐related differentially expressed genes (DEGs). The mouse model in endometriosis syndrome was established by being subcutaneously injected with Estradiol benzoate, and the ectopic endometrial tissues and normal endometrial tissues were collected. Additionally, the endometrial glandular epithelial cells were extracted from the endometrial glandular epithelial tissues from normal and endometriosis mice. In order to examine the role of miR‐488 in mice with endometriosis, we measured miR‐488 expression and expression levels of Frizzled‐7 (FZD7), cyclinD1, β‐catenin, and c‐Myc in vivo and in vitro. Finally, we detected the effect of miR‐488 on cell proliferation, apoptosis, migration and invasion in vitro. FZD7 was upregulated in human endometriosis. The data showed higher expression levels of FZD7, β‐catenin, c‐Myc and cyclinD1, and lower miR‐488 expression in mouse endometrial tissues. FZD7 was the target gene of miR‐488. Furthermore, elevated miR‐488 in isolated mouse endometrial glandular endometrial cells inhibited FZD7, the translocation of β‐catenin to nucleus, the activation of Wnt pathway, and the cell proliferation, migration and invasion. Collectively, these findings indicated that up‐regulated miR‐488 may reduce the proliferation, migration and invasion of endometrial glandular epithelial cells through inhibiting the activation of Wnt pathway by down‐regulating FZD7.
Journal Article
A vortex-dynamical scaling theory for flickering buoyant diffusion flames
The flickering of buoyant diffusion flames is associated with the periodic shedding of toroidal vortices that are formed under gravity-induced shearing at the flame surface. Numerous experimental investigations have confirmed the scaling,
$f\\propto D^{-1/2}$
, where
$f$
is the flickering frequency and
$D$
is the diameter of the fuel inlet. However, the connection between the toroidal vortex dynamics and the scaling has not been clearly understood. By incorporating the finding of Gharib et al. (J. Fluid Mech., vol. 360, 1998, pp. 121–140) that the detachment of a continuously growing vortex ring is inevitable and can be dictated by a universal constant that is essentially a non-dimensional circulation of the vortex, we theoretically established the connection between the periodicity of the toroidal vortices and the flickering of a buoyant diffusion flame with small Froude number. The scaling theory for flickering frequency was validated by the existing experimental data of pool flames and jet diffusion flames.
Journal Article
COCO enhances the efficiency of photoreceptor precursor differentiation in early human embryonic stem cell-derived retinal organoids
Background
Significant progress has been made in cell replacement therapy for neural retinal diseases using retinal cells differentiated from human pluripotent stem cells. Low tumorigenicity and the ability to mature to form synaptic junctions make precursor cells a promising donor source. Here, we attempted to improve the yield of photoreceptor precursor cells in three-dimensional retinal organoids from human embryonic stem cells (hESCs).
Methods
A CRX-tdTomato-tagged hESC line was generated to track retinal precursors in 3D retinal organoids. COCO, a multifunctional antagonist of the Wnt, TGF-β, and BMP pathways, was employed to 3D organoid differentiation schemes for enhanced photoreceptor precursor cells. Organoid fluorescence intensity measurement was used to monitor retinalization tendency with the number of precursors further checked by flow cytometry. Signature gene expression during organoid differentiation were assessed by qPCR and immunocytochemistry after COCO supplementation.
Results
CRX-positive cells can be spatiotemporally tracked by tdTomato without affecting retinalization during retinal organoid differentiation. Fluorescence intensity of organoids, which turned out highly consistent with flow cytometry measurement, allowed us to determine the differentiation efficiency of precursors during organoid culturing directly. Using COCO as an auxiliary supplement, rather than alone, can yield an increased number of photoreceptor precursors in the early stage of organoid differentiation. Over a longer time-frame, photoreceptor precursors enhanced their fate of cones and decreased fate of rods after treatment with COCO.
Conclusions
Tracing with the CRX-reporter system showed that in retinal organoids derived from human pluripotent stem cells, COCO increased the differentiation efficiency of photoreceptor precursors and cones.
Journal Article
Fusion and expansion of vitellogenin vesicles during Caenorhabditis elegans intestinal senescence
Some of the most conspicuous aging phenotypes of C. elegans are related to post‐reproductive production of vitellogenins (Vtg), which form yolk protein (YP) complexes after processing and lipid loading. Vtg/YP levels show huge increases with age, and inhibition of this extends lifespan, but how subcellular and organism‐wide distribution of these proteins changes with age has not been systematically explored. Here, this has been done to understand how vitellogenesis promotes aging. The age‐associated changes of intestinal vitellogenin vesicles (VVs), pseudocoelomic yolk patches (PYPs), and gonadal yolk organelles (YOs) have been characterized by immuno‐electron microscopy. We find that from reproductive adult day 2 (AD 2) to post‐reproductive AD 6 and AD 9, intestinal VVs expand from 0.2 to 3–4 μm in diameter or by >3000 times in volume, PYPs increase by >3 times in YP concentration and volume, while YOs in oocytes shrink slightly from 0.5 to 0.4 μm in diameter or by 49% in volume. In AD 6 and AD 9 worms, mislocalized YOs found in the hypodermis, uterine cells, and the somatic gonadal sheath can reach a size of 10 μm across in the former two tissues. This remarkable size increase of VVs and that of mislocalized YOs in post‐reproductive worms are accompanied by extensive fusion between these Vtg/YP‐containing vesicular structures in somatic cells. In contrast, no fusion is seen between YOs in oocytes. We propose that in addition to the continued production of Vtg, excessive fusion between VVs and mislocalized YOs in the soma worsen the aging pathologies seen in C. elegans. On the left is a young wild‐type C. elegans of adult day 1 or 2, and on the right is an older worm of adult day 6 or 9. The orange‐colored structures are: in the intestine, vitellogenin vesicles (VVs), of a median diameter of 200 nm on the left and 3‐4 μm on the right, with a frequent fusion between VVs in the older worm; in the pseudocoelom, pseudocoelomic yolk patches, greatly expanded in the older worm; in oocytes and eggs, yolk organelles (YOs), of a median diameter of 500 nm on the left and 400 nm on the right; in the hypodermis, sheath or uterine cells of the older worm, mislocalized YOs.
Journal Article
Depletion of Arabidopsis SC35 and SC35-like serine/arginine-rich proteins affects the transcription and splicing of a subset of genes
Serine/arginine-rich (SR) proteins are important splicing factors which play significant roles in spliceosome assembly and splicing regulation. However, little is known regarding their biological functions in plants. Here, we analyzed the phenotypes of mutants upon depleting different subfamilies of Arabidopsis SR proteins. We found that loss of the functions of SC35 and SC35-like (SCL) proteins cause pleiotropic changes in plant morphology and development, including serrated leaves, late flowering, shorter roots and abnormal silique phyllotaxy. Using RNA-seq, we found that SC35 and SCL proteins play roles in the pre-mRNA splicing. Motif analysis revealed that SC35 and SCL proteins preferentially bind to a specific RNA sequence containing the AGAAGA motif. In addition, the transcriptions of a subset of genes are affected by the deletion of SC35 and SCL proteins which interact with NRPB4, a specific subunit of RNA polymerase II. The splicing of FLOWERING LOCUS C (FLC) intron1 and transcription of FLC were significantly regulated by SC35 and SCL proteins to control Arabidopsis flowering. Therefore, our findings provide mechanistic insight into the functions of plant SC35 and SCL proteins in the regulation of splicing and transcription in a direct or indirect manner to maintain the proper expression of genes and development.
Journal Article
Integrative analysis of transcriptome and metabolome reveals flavonoid biosynthesis regulation in Rhododendron pulchrum petals
Background
Color is the major ornamental feature of the
Rhododendron
genus, and it is related to the contents of flavonoid in petals. However, the regulatory mechanism of flavonoid biosynthesis in
Rhododendron pulchrum
remains unknown. The transcriptome and metabolome analysis of
Rhododendron pulchrum
with white, pink and purple color in this study aimed to reveal the mechanism of flavonoid biosynthesis and to provide insight for improving the petal color.
Results
Flavonoids and flavonols are the major components of flavonoid metabolites in
R.pulchrum
, such as laricitrin, apigenin, tricin, luteolin, isoorientin, isoscutellarein, diosmetin and their glycosides derivatives. With transcriptome and metabolome analysis, we found
CHS, FLS, F3’H, F3′5’H, DFR, ANS
,
GT, FNS
,
IFR
and
FAOMT
genes showed significantly differential expression in cultivar ‘Zihe'.
FNS and IFR
were discovered to be associated with coloration in
R.pulchrum
for the first time. The
FNS
gene existed in the form of
FNSI.
The
IFR
gene and its related metabolites of medicarpin derivatives were highly expressed in purple petal. In cultivar ‘Fenhe', up-regulation of
F3’H
and
F3′5’H
and down-regulation of
4CL, DFR, ANS,
and
GT
were associated with pink coloration. With the transcription factor analysis, a subfamily of
DREBs
was found to be specifically enriched in pink petals. This suggested that the
DREB
family play an important role in pink coloration. In cultivars ‘Baihe', flavonoid biosynthesis was inhibited by low expression of
CHS
, while pigment accumulation was inhibited by low expression of
F3′5'H, DFR
, and
GT
, which led to a white coloration.
Conclusions
By analyzing the transcriptome and metabolome of
R.pulchrum
, principal differential expression genes and metabolites of flavonoid biosynthesis pathway were identified. Many novel metabolites, genes, and transcription factors associated with coloration have been discovered. To reveal the mechanism of the coloration of different petals, a model of the flavonoid biosynthesis pathway of
R.pulchrum
was constructed. These results provide in depth information regarding the coloration of the petals and the flavonoid metabolism of
R.pulcherum
. The study of transcriptome and metabolome profiling gains insight for further genetic improvement in
Rhododendron
.
Journal Article
Normal foot loading parameters and repeatability of the Footscan® platform system
Background
The Footscan® platform system is one of the most commonly used clinical tools for the measurement of the foot pressure. The present study was designed to assess the repeatability of the system and identify the range of loading parameters observed in the normal foot.
Methods
Measurements were collected from 32 healthy participants, 15 females and 17 males, twice at an interval of 1 week. Peak pressure (PP), contact time (CT), contact area (CA), pressure-time integral (PTI), and maximum force (MaF) were recorded; these parameters were investigated in 10 areas of the foot: medial heel, lateral heel, midfoot, first to fifth metatarsals, hallux, and toes 2–5. The intra-session repeatability was evaluated by calculating the intraclass correlation coefficients (ICCs) and coefficients of variation (CVs) across the three repeated trials within the same session. The inter-session repeatability was assessed using the average of the three trials in each session to determine the ICCs and CVs.
Results
The ICCs showed moderate to good repeatability for every variable of interest, and the CVs were all <28%. The highest zones of PP were found under the second and third metatarsals, followed by the medial heel. The CT was 68.5–82.8% of the total stance time under the metatarsal heads. CA was highest under the midfoot, PTI was highest under the second metatarsal, and MaF was highest under the medial heel.
Conclusions
Footscan® platform system was found to be repeatable. Thus, it can be used as a valuable tool in the assessment of plantar pressure distribution, and the normal values of the foot loading parameters identified in this study can be employed to provide a reference range for the gait analysis performed by the Footscan® system.
Journal Article
Revisited Globalization’s Impact on Total Environment: Evidence Based on Overall Environmental Performance Index
This study aims to examine the impact of globalization on environmental performance by employing panel data for 148 countries from 2001 to 2018, via the indicator of Environmental Performance Index to capture the overall environmental quality and KOF index to measure the multi dimensions of globalization. The empirical results suggest that globalization is critical to environmental performance, which is reliable while we conduct several robustness tests. Furthermore, if globalization increases, it would be beneficial for the environmental performance; moreover, among specific dimensions of globalization, economic globalization, social globalization and political globalization would bring about better environmental performance. Besides, the improvement of globalization, social globalization and political globalization would bring about better environmental performance, while that of economic globalization cannot change the overall environmental performance. Our study offers more insight into the relationship between globalization and environmental performance.
Journal Article
The neurotrophic activities of brain‐derived neurotrophic factor are potentiated by binding with apigenin, a common flavone in vegetables, in stimulating the receptor signaling
We aimed to identify the neurotrophic activities of apigenin (4',5,7-trihydroxyflavone) via its coordination with brain-derived neurotrophic factor (BNDF) and an elevated signaling of tyrosine kinase receptor B (Trk B receptor).
The direct binding of apigenin to BDNF was validated by ultrafiltration and biacore assay. Neurogenesis, triggered by apigenin and/or BDNF, was determined in cultured SH-SY5Y cells and rat cortical neurons. The amyloid-beta (Aβ)
-induced cellular stress was revealed by propidium iodide staining, mitochondrial membrane potential, bioenergetic analysis, and formation of reactive oxygen species levels. Activation of Trk B signaling was tested by western blotting.
Apigenin and BDNF synergistically maintained the cell viability and promoted neurite outgrowth of cultured neurons. In addition, the BDNF-induced neurogenesis of cultured neurons was markedly potentiated by applied apigenin, including the induced expressions of neurofilaments, PSD-95 and synaptotagmin. Moreover, the synergy of apigenin and BDNF alleviated the (Aβ)
-induced cytotoxicity and mitochondrial dysfunction. The synergy could be accounted by phosphorylation of Trk B receptor, and which was fully blocked by a Trk inhibitor K252a.
Apigenin potentiates the neurotrophic activities of BDNF through direct binding, which may serve as a possible treatment for its curative efficiency in neurodegenerative diseases and depression.
Journal Article