Functional divergence of the rapidly evolving miR-513 subfamily in primates

BACKGROUND: The miR-513 subfamily belongs to an X-linked primate-specific miR506-514 cluster. Across primate species, there have been several duplication events and different species each possess a variety of miR-513 copies, indicating it underwent rapid evolution. Evidence suggests that this subfamily is preferentially expressed in the testis, but otherwise, to date, the evolutionary history and functional significance of this miRNA subfamily has remained largely unexplored. RESULTS: We analyzed the evolutionary pattern of gene duplications and their functional consequence for the miR-513 subfamily in primates. Sequence comparisons showed that the duplicated copies of miR-513 were derived from transposable element (MER91C). Moreover, duplication events of the miR-513 subfamily seem to have occurred independently in Platyrrhini (New World monkeys) and Catarrhini (Old World monkeys, apes and humans) after they diverged. Different copies of the miR-513 subfamily (miR-513a/b/c) have different seed sequences, due to after-duplication sequence divergences, which eventually led to functional divergences. The results of functional assays indicated that miR-513b could inhibit the expression of its target gene, the down-regulator of transcription 1 (DR1) at both the mRNA and protein levels. In the developing testis of rhesus macaques, we observed a temporal coupling of expression levels between miR-513b and DR1, suggesting that miR-513b could affect male sexual maturation by negatively regulating the development-stage related functioning of DR1. CONCLUSIONS: The miR-513 subfamily underwent multiple independent gene duplications among five different lineages of primates. The after-duplication sequence divergences among the different copies of miR-513 led to functional divergence of these copies in primates

Metabolic profile, bioavailability and toxicokinetics of zearalenone-14-glucoside in rats after oral and intravenous administration by liquid chromatography high-resolution mass spectrometry and tandem mass spectrometry

Zearalenone-14-glucoside (ZEN-14G), a key modified mycotoxin, has attracted a great deal of attention due to the possible conversion to its free form of zearalenone (ZEN) exerting toxicity. In this study, the toxicokinetics of ZEN-14G were investigated in rats after oral and intravenous administration. The plasma concentrations of ZEN-14G and its major five metabolites were quantified using a validated liquid chromatography tandem mass spectrometry (LC-MS/MS) method. The data were analyzed via non-compartmental analysis using software WinNonlin 6.3. The results indicated that ZEN-14G was rapidly hydrolyzed into ZEN in vivo. In addition, the major parameters of ZEN-14G following intravenous administration were: area under the plasma concentration-time curve (AUC), 1.80 h.ng/mL; the apparent volume of distribution (V-Z), 7.25 L/kg; and total body clearance (CL), 5.02 mL/h/kg, respectively. After oral administration, the typical parameters were: AUC, 0.16 h.ng/mL; V-Z, 6.24 mL/kg; and CL, 4.50 mL/h/kg, respectively. The absolute oral bioavailability of ZEN-14G in rats was about 9%, since low levels of ZEN-14G were detected in plasma, which might be attributed to its extensive metabolism. Therefore, liquid chromatography high-resolution mass spectrometry (LC-HRMS) was adopted to clarify the metabolic profile of ZEN-14G in rats' plasma. As a result, eight metabolites were identified in which ZEN-14-glucuronic acid (ZEN-14GlcA) had a large yield from the first time-point and continued accumulating after oral administration, indicating that ZEN-14-glucuronic acid could serve a potential biomarker of ZEN-14G. The obtained outcomes would prompt the accurate safety evaluation of ZEN-14G

Maternal control of axial–paraxial mesoderm patterning via direct transcriptional repression in zebrafish

AbstractAxial–paraxial mesoderm patterning is a special dorsal–ventral patterning event of establishing the vertebrate body plan. Though dorsal–ventral patterning has been extensively studied, the initiation of axial–paraxial mesoderm pattering remains largely unrevealed. In zebrafish, spt cell-autonomously regulates paraxial mesoderm specification and flh represses spt expression to promote axial mesoderm fate, but the expression domains of spt and flh initially overlap in the entire marginal zone of the embryo. Defining spt and flh territories is therefore a premise of axial–paraxial mesoderm patterning. In this study, we investigated why and how the initial expression of flh becomes repressed in the ventrolateral marginal cells during blastula stage. Loss- and gain-of-function experiments showed that a maternal transcription factor Vsx1 is essential for restricting flh expression within the dorsal margin and preserving spt expression and paraxial mesoderm specification in the ventrolateral margin of embryo. Chromatin immunoprecipitation and electrophoretic mobility shift assays in combination with core consensus sequence mutation analysis further revealed that Vsx1 can directly repress flh by binding to the proximal promoter at a specific site. Inhibiting maternal vsx1 translation resulted in confusion of axial and paraxial mesoderm markers expression and axial–paraxial mesoderm patterning. These results demonstrated that direct transcriptional repression of the decisive axial mesoderm gene by maternal ventralizing factor is a crucial regulatory mechanism of initiating axial–paraxial mesoderm patterning in vertebrates

Bufalin Induces Lung Cancer Cell Apoptosis via the Inhibition of PI3K/Akt Pathway

Bufalin is a class of toxic steroids which could induce the differentiation and apoptosis of leukemia cells, and induce the apoptosis of gastric, colon and breast cancer cells. However, the anti-tumor effects of bufalin have not been demonstrated in lung cancer. In this study we used A549 human lung adenocarcinoma epithelial cell line as the experimental model to evaluate the potential of bufalin in lung cancer chemotherapy. A549 cells were treated with bufalin, then the proliferation was detected by MTT assay and apoptosis was detected by flow cytometry analysis and Giemsa staining. In addition, A549 cells were treated by Akt inhibitor LY294002 in combination with bufalin and the activation of Akt and Caspase-3 as well as the expression levels of Bax, Bcl-2 and livin were examined by Western blot analysis. The results showed that Bufalin inhibited the proliferation of A549 cells and induced the apoptosis of A549 cells in a dose and time dependent manner. Mechanistically, we found that bufalin inhibited the activation of Akt. Moreover, bufalin synergized with Akt inhibitor to induce the apoptosis of A549 cells and this was associated with the upregulation of Bax expression, the downregulation of Bcl-2 and livin expression, and the activation of Caspase-3. In conclusion, our findings demonstrate that bufalin induces lung cancer cell apoptosis via the inhibition of PI3K/Akt pathway and suggest that bufalin is a potential regimen for combined chemotherapy to overcome the resistance of lung cancer cells to chemotherapeutics induced apoptosis

Energy Costs of Chair Sitting and Standing Video Exercises in Chinese Older Adults, Ages 60 to 89 years

International Journal of Exercise Science 16(7): 814-827, 2023. Home-based video exercise interventions improve older adults’ physiological performance and functional capacity. Little is known about the energy costs of video exercises in older adults. The Compendium of Physical Activities (PAs) has few items with PA metabolic equivalents (METs) in older adults. This study measured the energy costs of four chair and two standing exercises (sitting Tai Chi, Yoga, mobility ball, aerobics: standing, slow aerobics, and fast aerobics). Fifteen females and 14 males, 62-87 years (M ± SD, 73 ± 7.7 years), were categorized into three age groups (60-69, 70-79, 80-89). Oxygen uptake (VO2, ml.min-1.kg-1) and heart rate (HR, b.min-1) were measured by indirect calorimetry and heart rate monitor. MET values were calculated as standard- (activity VO2/3.5), rounded- (significant digit rounded to 0, 3, 5, 8), and corrected METs (individual resting metabolism). Results showed chair Yoga, Tai Chi, and mobility ball ranged from 2.0 to 2.8 rounded METs (light intensity). Chair- and standing aerobics ranged from 3.0 to 4.3 rounded METs (moderate intensity). Averaged HR ranged from 91.9 ± 12.7 b.min-1 to 115.4 ± 19.1 b.min-1 for all PAs. Corrected METs were higher than standard METs (P \u3c .05). Standard METs were similar between age groups (P \u3e .05). In conclusion, this study is unique as it measures the energy costs of sitting and standing video exercises that can be performed by older adults at home or in an exercise facility. Knowing the energy costs of PAs for older adults can provide exercises interventions to prevent sedentary lifestyles

Derivation of Rhesus Monkey Parthenogenetic Embryonic Stem Cells and Its MicroRNA Signature

Parthenogenetic embryonic stem cells are considered as a promising resource for regeneration medicine and powerful tools for developmental biology. A lot of studies have revealed that embryonic stem cells have distinct microRNA expression pattern and these microRNAs play important roles in self-renewal and pluripotency of embryonic stem cells. However, few studies concern about microRNA expression pattern in parthenogenetic embryonic stem cells, especially in non-human primate—the ideal model species for human, largely due to the limited rhesus monkey parthenogenetic embryonic stem cells (rpESCs) available and lack of systematic analysis of the basics of rpESCs. Here, we derived two novel rpESCs lines and characterized their microRNA signature by Solexa deep sequencing. These two novel rpESCs shared many properties with other primate ESCs, including expression of pluripotent markers, capacity to generate derivatives representative of all three germ layers in vivo and in vitro, maintaining of euploid karyotype even after long culture. Additionally, lack of some paternally expressed imprinted genes and identity of Single-nucleotide Polymorphism (SNP) compare to their oocyte donors support their parthenogenesis origin. By characterizing their microRNA signature, we identified 91 novel microRNAs, except those are also detected in other primate ESCs. Moreover, these two novel rpESCs display a unique microRNA signature, comparing to their biparental counterpart ESCs. Then we analyzed X chromosome status in these two novel rpESCs; results suggested that one of them possesses two active X chromosomes, the other possesses only one active X chromosome liking biparental female embryonic stem cells. Taken together, our novel rpESCs provide a new alternative to existing rhesus monkey embryonic stem cells, microRNA information expands rhesus monkey microRNA data and may help understanding microRNA roles in pluripotency and parthenogenesis

Nitrogen-doped carbon nanospheres-modified graphitic carbon nitride with outstanding photocatalytic activity

Metals and metal oxides are widely used as photo/electro-catalysts for environmental remediation. However, there are many issues related to these metal-based catalysts for practical applications, such as high cost and detrimental environmental impact due to metal leaching. Carbon-based catalysts have the potential to overcome these limitations. In this study, monodisperse nitrogen-doped carbon nanospheres (NCs) were synthesized and loaded onto graphitic carbon nitride (g-C3N4, GCN) via a facile hydrothermal method for photocatalytic removal of sulfachloropyridazine (SCP). The prepared metal-free GCN-NC exhibited remarkably enhanced efficiency in SCP degradation. The nitrogen content in NC critically influences the physicochemical properties and performances of the resultant hybrids. The optimum nitrogen doping concentration was identified at 6.0 wt%. The SCP removal rates can be improved by a factor of 4.7 and 3.2, under UV and visible lights, by the GCN-NC composite due to the enhanced charge mobility and visible light harvesting. The mechanism of the improved photocatalytic performance and band structure alternation were further investigated by density functional theory (DFT) calculations. The DFT results confirm the high capability of the GCN-NC hybrids to activate the electron–hole pairs by reducing the band gap energy and efficiently separating electron/hole pairs. Superoxide and hydroxyl radicals are subsequently produced, leading to the efficient SCP removal

The fast light of CsI(Na) crystals

The responds of different common alkali halide crystals to alpha-rays and gamma-rays are tested in our research. It is found that only CsI(Na) crystals have significantly different waveforms between alpha and gamma scintillations, while others have not this phenomena. It is suggested that the fast light of CsI(Na) crystals arises from the recombination of free electrons with self-trapped holes of the host crystal CsI. Self-absorption limits the emission of fast light of CsI(Tl) and NaI(Tl) crystals.Comment: 5 pages, 11 figures Submit to Chinese Physics