A
bstract
With the hypothesis of minimal flavor violation, we find that there exists a power-aligned relation between the Yukawa couplings of the two scalar doublets in the two-Higgs-doublet model ...with Hermitian Yukawa matrices. Within such a power-aligned framework, it is found that a simultaneous explanation of the anomalies observed in the electron and muon anomalous magnetic moments can be reached with TeV-scale quasi-degenerate Higgs masses, and the resulting parameter space is also phenomenologically safer under the B-physics,
Z
and
τ
decay data, as well as the current LHC bounds. Furthermore, the flavor-universal power that enhances the charged-lepton Yukawa couplings prompts an interesting correlation between the two anomalies, which makes the model distinguishable from the (generalized) linearly aligned and the lepton-specific two-Higgs-doublet models that address the same anomalies but in a non-correlative manner, and hence testable by future precise measurements.
MYC transcriptional factors are members of the bHLH (basic helix-loop-helix) superfamily, and play important roles in plant growth and development. Recent studies have revealed that some MYCs are ...involved in the crosstalk between Jasmonic acid regulatory pathway and light signaling in Arabidopsis, but such kinds of studies are rare in wheat, especially in photo-thermo-sensitive genic male sterile (PTGMS) wheat line.
27 non-redundant MYC gene copies, which belonged to 11 TaMYC genes, were identified in the whole genome of wheat (Chinese Spring). These gene copies were distributed on 13 different chromosomes, respectively. Based on the results of phylogenetic analysis, 27 TaMYC gene copies were clustered into group I, group III, and group IV. The identified TaMYC genes copies contained different numbers of light, stress, and hormone-responsive regulatory elements in their 1500 base pair promoter regions. Besides, we found that TaMYC3 was expressed highly in stem, TaMYC5 and TaMYC9 were expressed specially in glume, and the rest of TaMYC genes were expressed in all tissues (root, stem, leaf, pistil, stamen, and glume) of the PTGMS line BS366. Moreover, we found that TaMYC3, TaMYC7, TaMYC9, and TaMYC10 were highly sensitive to methyl jasmonate (MeJA), and other TaMYC genes responded at different levels. Furthermore, we confirmed the expression profiles of TaMYC family members under different light quality and plant hormone stimuli, and abiotic stresses. Finally, we predicted the wheat microRNAs that could interact with TaMYC family members, and built up a network to show their integrative relationships.
This study analyzed the size and composition of the MYC gene family in wheat, and investigated stress-responsive and light quality induced expression profiles of each TaMYC gene in the PTGMS wheat line BS366. In conclusion, we obtained lots of important information of TaMYC family, and the results of this study was supposed to contribute novel insights and gene and microRNA resources for wheat breeding, especially for the improvement of PTGMS wheat lines.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Dysregulated extravillous trophoblast invasion and proliferation are known to increase the risk of recurrent spontaneous abortion (RSA); however, the underlying mechanism remains unclear. Herein, in ...our retrospective observational case-control study we show that villous samples from RSA patients, compared to healthy controls, display reduced succinate dehydrogenase complex iron sulfur subunit (SDHB) DNA methylation, elevated SDHB expression, and reduced succinate levels, indicating that low succinate levels correlate with RSA. Moreover, we find high succinate levels in early pregnant women are correlated with successful embryo implantation. SDHB promoter methylation recruited MBD1 and excluded c-Fos, inactivating SDHB expression and causing intracellular succinate accumulation which mimicked hypoxia in extravillous trophoblasts cell lines JEG3 and HTR8 via the PHD2-VHL-HIF-1α pathway; however, low succinate levels reversed this effect and increased the risk of abortion in mouse model. This study reveals that abnormal metabolite levels inhibit extravillous trophoblast function and highlights an approach for RSA intervention.
Two novel polyoxometalate (POM)-based metal–organic frameworks (MOFs), TBA3ε-PMoV 8MoVI 4O36(OH)4Zn4BTB4/3·xGuest (NENU-500, BTB = benzene tribenzoate, TBA+ = tetrabutylammonium ion) and TBA3ε-PMoV ...8MoVI 4O37(OH)3Zn4BPT (NENU-501, BPT = 1,1′-biphenyl-3,4′,5-tricarboxylate), were isolated. In these compounds, the POM fragments serving as nodes were directly connected with organic ligands giving rise to three-dimensional (3D) open frameworks. The two anionic frameworks were balanced by TBA+ ions residing inside the open channels. They exhibit not only good stability in air but also tolerance to acidic and basic media. Furthermore, they were employed as electrocatalysts for the hydrogen evolution reaction (HER) owing to the combination of the redox activity of a POM unit and the porosity of a MOF. Meanwhile, the HER activities of ε(trim) 4/3 , NENU-5, and HKUST-1 were also studied for comparison. Remarkably, as a 3D hydrogen-evolving cathode operating in acidic electrolytes, NENU-500 exhibits the highest activity among all MOF materials. It shows an onset overpotential of 180 mV and a Tafel slope of 96 mV·dec–1, and the catalytic current density can approach 10 mA·cm–2 at an overpotential of 237 mV. Moreover, NENU-500 and NENU-501 maintain their electrocatalytic activities after 2000 cycles.
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IJS, KILJ, NUK, PNG, UL, UM
The methyltransferase like 3 （METTL3）-containing methyltransferase complex catalyzes the N6-methyladenosine （m6A） formation, a novel epitranscriptomic marker; however, the nature of this complex ...remains largely unknown. Here we report two new components of the human m6A methyltransferase complex, Wilms＇ tumor 1-associating protein （WTAP） and methyltransferase like 14 （METTL14）. WTAP interacts with METTL3 and METTL14, and is required for their localization into nuclear speckles enriched with pre-mRNA processing factors and for catalytic ac- tivity of the m6A methyltransferase in vivo. The majority of RNAs bound by WTAP and METTL3 in vivo represent mRNAs containing the consensus m6A motif. In the absence of WTAP, the RNA-binding capability of METTL3 is strongly reduced, suggesting that WTAP may function to regulate recruitment of the m6A methyltransferase complex to mRNA targets. Furthermore, transcriptomic analyses in combination with photoactivatable-ribonucleoside-en- hanced crosslinking and immunoprecipitation （PAR-CLIP） illustrate that WTAP and METTL3 regulate expression and alternative splicing of genes involved in transcription and RNA processing. Morpholino-mediated knockdown targeting WTAP and/or METTL3 in zebrafish embryos caused tissue differentiation defects and increased apoptosis. These findings provide strong evidence that WTAP may function as a regulatory subunit in the m6A methyltransferase complex and play a critical role in epitranscriptomic regulation of RNA metabolism.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Leucine-rich repeat receptor-like protein kinases (LRR-RLKs) are the largest group of receptor-like kinases in plants and play crucial roles in development and stress responses. The evolutionary ...relationships among LRR-RLK genes have been investigated in flowering plants; however, no comprehensive studies have been performed for these genes in more ancestral groups. The subfamily classification of LRR-RLK genes in plants, the evolutionary history and driving force for the evolution of each LRR-RLK subfamily remain to be understood.
We identified 119 LRR-RLK genes in the Physcomitrella patens moss genome, 67 LRR-RLK genes in the Selaginella moellendorffii lycophyte genome, and no LRR-RLK genes in five green algae genomes. Furthermore, these LRR-RLK sequences, along with previously reported LRR-RLK sequences from Arabidopsis thaliana and Oryza sativa, were subjected to evolutionary analyses. Phylogenetic analyses revealed that plant LRR-RLKs belong to 19 subfamilies, eighteen of which were established in early land plants, and one of which evolved in flowering plants. More importantly, we found that the basic structures of LRR-RLK genes for most subfamilies are established in early land plants and conserved within subfamilies and across different plant lineages, but divergent among subfamilies. In addition, most members of the same subfamily had common protein motif compositions, whereas members of different subfamilies showed variations in protein motif compositions. The unique gene structure and protein motif compositions of each subfamily differentiate the subfamily classifications and, more importantly, provide evidence for functional divergence among LRR-RLK subfamilies. Maximum likelihood analyses showed that some sites within four subfamilies were under positive selection.
Much of the diversity of plant LRR-RLK genes was established in early land plants. Positive selection contributed to the evolution of a few LRR-RLK subfamilies.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Environmental ultrafine particulate matter (PM) is capable of inducing airway injury, while the detailed molecular mechanisms remain largely unclear. Here, we demonstrate pivotal roles of autophagy ...in regulation of inflammation and mucus hyperproduction induced by PM containing environmentally persistent free radicals in human bronchial epithelial (HBE) cells and in mouse airways. PM was endocytosed by HBE cells and simultaneously triggered autophagosomes, which then engulfed the invading particles to form amphisomes and subsequent autolysosomes. Genetic blockage of autophagy markedly reduced PM-induced expression of inflammatory cytokines, e.g. IL8 and IL6, and MUC5AC in HBE cells. Mice with impaired autophagy due to knockdown of autophagy-related gene Becn1 or Lc3b displayed significantly reduced airway inflammation and mucus hyperproduction in response to PM exposure in vivo. Interference of the autophagic flux by lysosomal inhibition resulted in accumulated autophagosomes/amphisomes, and intriguingly, this process significantly aggravated the IL8 production through NFKB1, and markedly attenuated MUC5AC expression via activator protein 1. These data indicate that autophagy is required for PM-induced airway epithelial injury, and that inhibition of autophagy exerts therapeutic benefits for PM-induced airway inflammation and mucus hyperproduction, although they are differentially orchestrated by the autophagic flux.
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BFBNIB, GIS, IJS, KISLJ, NUK, PNG, UL, UM, UPUK
Functional constipation (FC) in children affects their growth, development and quality of life. L-pipecolic acid (L-PA) was decreased in FC children based on gut microbiome and serum metabolomic. In ...this study, loperamide-induced constipation in mice was used to evaluate the effects of L-PA on constipated mice.
26 FC and 28 healthy children were recruited. Stool samples and serum samples were subjected to 16S rDNA sequencing and ultra-performance liquid chromatography/quadrupole time of flight (UPLC-Q/TOF-MS) approach, respectively. A loperamide-induced mouse constipation model was developed, and all mice were randomly divided into control (Con), loperamide (Lop) and L-PA (Lop + L-PA) treatment groups (6 mice per group). The mice in the Lop + L-PA group were given L-PA (250 mg/kg, once a day) and loperamide; the Lop group was given loperamide for 1 week, and the Con group was given saline. The fecal parameters and intestinal motility of mice in each group were detected. serum 5-HT levels and colon 5-HT expression were detected by ELISA and immunohistochemistry, respectively; qRT-PCR was used to detect the expression of AQP3 and 5-HT4R mRNA in each group.
45 differential metabolites and 18 significantly different microbiota were found in FC children. The α and β diversity of gut microbiota in FC children was significantly reduced. Importantly, serum L-PA was significantly reduced in FC children. The KEGG pathway enrichment were mainly enriched in fatty acid biosynthesis, lysine degradation, and choline metabolism. L-PA was negatively associated with Ochrobactrum, and N6, N6, N6-trimethyl-l-lysine was positively associated with Phascolarcrobacterium. In addition, L-PA improved the fecal water content, intestinal transit rate, and increased the serum 5-HT levels in constipated mice. Moreover, L-PA increased the expression of 5-HT4R, reduced AQP3, and regulated constipation-associated genes.
Gut microbiota and serum metabolites were significantly altered in children with FC. The abundance of Phascolarctobacterium and Ochrobactrum and serum L-PA content were decreased in FC children. L-PA was found to alleviate the fecal water content, increase intestinal transit rate and the first black stool defecation time. L-PA improved constipation by increasing 5-HT and 5-HT4R expression while down-regulating AQP3 expression.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Oral squamous cell carcinoma (OSCC), with high potential for metastasis, is the most common malignant tumor of the head and neck. Cancer‑associated fibroblasts (CAFs) are the main stromal cells in ...the microenvironment and aggravate tumor progression. However, whether CAFs are associated with the progression of OSCC remains unknown and the underlying mechanism remains unclear. In the present study, the role of CAFs in mediating OSCC cell migration and invasion was investigated, and the participation of exosomal miR‑382‑5p in this process was elucidated. In this study, according to the α‑SMA staining with immunohistochemistry, 47 OSCC patients were divided into CAFs‑rich and CAFs poor groups, and association of CAF density and clinicopathologic features of the OSCC patients were analyzed with Pearson χ2 test. Transwell assay was used for evaluating cell migration and invasion ability of OSCC cells after being co‑cultured with NFs or CAFs, or after added exosomes. qPCR was used to detect the expression of miR‑382‑5p. Western blot analysis was used to measure the expression of migration and invasion‑associated proteins. In the present study, the CAF density in tumor tissues was found to be relevant to OSCC lymph node metastasis and TNM stage. Furthermore, we revealed that miR‑382‑5p was overexpressed in CAFs compared with that in fibroblasts of adjacent normal tissue and miR‑382‑5p overexpression was responsible for OSCC cell migration and invasion. Finally, we demonstrated that CAF‑derived exosomes transported miR‑382‑5p to OSCC cells. The present study confirmed a new mechanism of CAF‑facilitated OSCC progression and may be beneficial for identifying new cancer therapeutic targets.
Cancer stem cells (CSCs) are cancer‐initiating cells that are not only a source of tumorigenesis but also the cause of tumour progression, metastasis and therapy resistance. EBV‐associated gastric ...cancer (EBVaGC) is a distinct subtype of gastric cancer with unique clinicopathological and molecular features. However, whether CSCs exist in EBVaGC, and the tumorigenic mechanism of EBV, remains unclear. Here, NOD/SCID mice were injected subcutaneously with the EBVaGC cell line SNU719 and treated with 5‐fluorouracil weekly. Successive generations of xenografts yielded a highly malignant EBVaGC cell line, SNU‐4th, which displays properties of CSCs and mainly consists of CD44+CD24− cells. In SNU‐4th cells, an EBV‐encoded circRNA, ebv‐circLMP2A, expression increased and plays crucial roles in inducing and maintaining stemness phenotypes through targeting miR‐3908/TRIM59/p53 axis. Additionally, high expression of ebv‐circLMP2A is significantly associated with metastasis and poor prognosis in patients with EBVaGC. These findings not only provide evidence for the existence of CSCs in EBVaGC and elucidate the pathogenic mechanism of ebv‐circLMP2A in EBVaGC, but also provide a promising therapeutic target for EBVaGC.
Synopsis
The circRNA LMP2A produced by the Epstein‐Barr virus induces stemness of EBV‐associated gastric cancer cells by attenuating the tumor suppressive effect of the miR‐3908/TRIM59/p53 axis, thereby promoting metastasis and tumor progression.
Cells with properties of cancer stem cells were isolated form EBV‐associated gastric cancer (EBVaGC).
The levels of an EBV‐encoded circRNA (ebv‐circLMP2A) are significantly increased in EBVaGC.
ebv‐circLMP2A has crucial roles in inducing and maintaining cancer stemness in EBVaGC.
High expression of ebv‐circLMP2A is significantly associated with metastasis and poor prognosis in EBVaGC patients.
The circRNA LMP2A produced by the Epstein‐Barr virus induces stemness of EBV‐associated gastric cancer cells by attenuating the tumor suppressive effect of the miR‐3908/TRIM59/p53 axis, thereby promoting metastasis and tumor progression.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
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