Chronic Exposure to Diquat Causes Reproductive Toxicity in Female Mice

Diquat is a bipyridyl herbicide that has been widely used as a model chemical for in vivo studies of oxidative stress due to its generation of superoxide anions, and cytotoxic effects. There is little information regarding the toxic effects of diquat on the female reproductive system, particularly ovarian function. Thus, we investigated the reproductive toxic effects of diquat on female mice. Chronic exposure to diquat reduced ovary weights, induced ovarian oxidative stress, resulted in granulosa cell apoptosis, and disrupted oocyte developmental competence, as shown by reactive oxygen species (ROS) accumulation, decreased polar body extrusion rates and increased apoptosis-related genes expression. Additionally, after diquat treatment, the numbers of fetal mice and litter sizes were significantly reduced compared to those of control mice. Thus, our results indicated that chronic exposure to diquat induced reproductive toxicity in female mice by promoting the ROS production of gruanousa cells and ooctyes, impairing follicle development, inducing apoptosis, and reducing oocyte quality. In conclusion, our findings indicate that diquat can be used as a potent and efficient chemical for in vivo studies of female reproductive toxicity induced by oxidative stress. Moreover, the findings from this study will further enlarge imitative research investigating the effect of ovarian damage induced by oxidative stress on reproductive performance and possible mechanisms of action in large domestic animals.     

LINC01128 regulates the development of osteosarcoma by sponging miR‐299‐3p to mediate MMP2 expression and activating Wnt/β‐catenin signalling pathway

Osteosarcoma (OS) is one of the most common metastatic bone cancers, which results in significant morbidity and mortality. The important role of long non‐coding RNAs (lncRNAs) in the biological processes of OS has been demonstrated through several studies. In the current study, we evaluated the role of the lncRNA, LINC01128, in OS. We analysed the expression of LINC01128 in three OS gene expression omnibus (GEO) data sets {"type":"entrez-geo","attrs":{"text":"GSE21257","term_id":"21257"}}GSE21257, {"type":"entrez-geo","attrs":{"text":"GSE36001","term_id":"36001"}}GSE36001 and {"type":"entrez-geo","attrs":{"text":"GSE42352","term_id":"42352"}}GSE42352. The expression of LINC01128 in OS tissues and matched non‐tumour tissues obtained from 50 OS patients was detected using qRT‐PCR. The association between LINC01128 expression and overall survival of OS patients was evaluated using the Kaplan‐Meier method. The effects of LINC01128 knockdown and overexpression were evaluated through in vitro and in vivo assays. The LINC01128/miR‐299‐3p/ MMP2 axis was verified using dual‐luciferase reporter assay and qRT‐PCR assays. GEO data sets analysis revealed that the expression of LINC01128 was increased in OS. Elevated LINC01128 expression was accompanied by shorter overall survival in OS patients. Functional studies revealed that LINC01128 knockdown reduced the proliferation, migration and invasion of OS cells both in vitro and in vivo. Mechanistically, LINC01128 sponged miR‐299‐3p to increase MMP2 expression. Rescue assays determined the role of the LINC01128/miR‐299‐3p/MMP2 axis in the proliferation, migration and invasion of OS cells. Additionally, the Wnt/β‐catenin signalling pathway was activated by LINC01128 and MMP2 in OS cell lines. In summary, this study demonstrates that LINC01128 facilitates OS by functioning as a sponge of miR‐299‐3p, thus promoting MMP2 expression and activating the Wnt/β‐catenin signalling pathway.     

Multiple species of wild tree peonies gave rise to the ‘king of flowers’, Paeonia suffruticosa Andrews

The origin of cultivated tree peonies, known as the ‘king of flowers'' in China for more than 1000 years, has attracted considerable interest, but remained unsolved. Here, we conducted phylogenetic analyses of explicitly sampled traditional cultivars of tree peonies and all wild species from the shrubby section Moutan of the genus Paeonia based on sequences of 14 fast-evolved chloroplast regions and 25 presumably single-copy nuclear markers identified from RNA-seq data. The phylogeny of the wild species inferred from the nuclear markers was fully resolved and largely congruent with morphology and classification. The incongruence between the nuclear and chloroplast trees suggested that there had been gene flow between the wild species. The comparison of nuclear and chloroplast phylogenies including cultivars showed that the cultivated tree peonies originated from homoploid hybridization among five wild species. Since the origin, thousands of cultivated varieties have spread worldwide, whereas four parental species are currently endangered or on the verge of extinction. The documentation of extensive homoploid hybridization involved in tree peony domestication provides new insights into the mechanisms underlying the origins of garden ornamentals and the way of preserving natural genetic resources through domestication.     

Aquatic macroinvertebrate assemblages in wetlands of Northeastern China

Hydrobiologia - Lake Malaŵi cichlids have evolved rapidly, extensively, and in some cases iteratively to fill an array of ecological niches; however, neither species richness nor trophic...     

Designing Commensurate and Incommensurate Resonances for Enhanced Dipole Emission in Coupled Plasmonic Nanorods

Plasmonic nanorods and their clusters are the fundamental units in plasmonic nanoantenna engineering. A theory that can predict the resonance of single nanorod already exists but is in lack for a heterodimer. Here, we propose a model combining the effective circuit theory for the response of spherical nanoparticles together with standard transmission line theory for hemispherically capped nanorod antennas. The resonances of multiple orders are predictable by defining the reflection phase at the terminals of such antennas, in both symmetric and asymmetric coupled nanorods. The theoretical results compare favorably with full-wave finite element numerical calculations. By the analytical formula, it is easy to control the length of the antennas for regulating the cooperative resonant properties and consequently the radiation characteristics of a nearby electric dipole. Consequently, we obtain both commensurate and incommensurate resonance features in such nanorod-based heterodimer antennas, showing respectively cumulative and selective responses from the individual nanorods.     

iTRAQ‐Based Proteomics Reveals that the Tomato ms1035 Gene Causes Male Sterility through Compromising Fat Acid Metabolism

So far, over 50 spontaneous male sterile mutants of tomato have been described and most of them are categorized as genetic male sterility. To date, the mechanism of tomato genetic male sterility remained unclear. In this study, differential proteomic analysis is performed between genetic male sterile line (2‐517), which carries the male sterility (ms10³⁵) gene, and its wild‐type (VF‐11) using isobaric tags for relative and absolute quantification‐based strategy. A total of 8272 proteins are quantified in the 2–517 and VF‐11 lines at the floral bud and florescence stages. These proteins are involved in different cellular and metabolic processes, which express obvious functional tendencies toward the hydroxylation of the ω‐carbon in fatty acids, the tricarboxylic acid cycle, the glycolytic, and pentose phosphate pathways. Based on the results, a protein network explaining the mechanisms of tomato genetic male sterility is proposed, finding the compromising fat acid metabolism may cause the male sterility. These results are confirmed by parallel reaction monitoring, quantitative Real‐time PCR (qRT‐PCR), and physiological assays. Taken together, these results provide new insights into the metabolic pathway of anther abortion induced by ms10³⁵ and offer useful clues to identify the crucial proteins involved in genetic male sterility in tomato.     

Split Nano luciferase complementation for probing protein‐protein interactions in plant cells

Deciphering protein‐protein interactions (PPIs) is fundamental for understanding signal transduction pathways in plants. The split firefly luciferase (Fluc) complementation (SLC) assay has been widely used for analyzing PPIs. However, concern has risen about the bulky halves of Fluc interfering with the functions of their fusion partners. Nano luciferase (Nluc) is the smallest substitute for Fluc with improved stability and luminescence. Here, we developed a dual‐use system enabling the detection of PPIs through the Nluc‐based SLC and co‐immunoprecipitation assays. This was realized by coexpression of two proteins under investigation in fusion with the HA‐ or FLAG‐tagged Nluc halves, respectively. We validated the robustness of this system by reproducing multiple previously documented PPIs in protoplasts or Agrobacterium‐transformed plants. We next applied this system to evaluate the homodimerization of Arabidopsis CERK1, a coreceptor of fungal elicitor chitin, and its heterodimerization with other homologs in the absence or presence of chitin. Moreover, split fragments of Nluc were fused to two cytosolic ends of Arabidopsis calcium channels CNGC2 and CNGC4 to help sense the allosteric change induced by the bacterial elicitor flg22. Collectively, these results demonstrate the usefulness of the Nluc‐based SLC assay for probing constitutive or inducible PPIs and protein allostery in plant cells.     

IL‐17A‐producing T cells exacerbate fine particulate matter‐induced lung inflammation and fibrosis by inhibiting PI3K/Akt/mTOR‐mediated autophagy

Fine particulate matter (PM2.5) is the primary air pollutant that is able to induce airway injury. Compelling evidence has shown the involvement of IL‐17A in lung injury, while its contribution to PM2.5‐induced lung injury remains largely unknown. Here, we probed into the possible role of IL‐17A in mouse models of PM2.5‐induced lung injury. Mice were instilled with PM2.5 to construct a lung injury model. Flow cytometry was carried out to isolate γδT and Th17 cells. ELISA was adopted to detect the expression of inflammatory factors in the supernatant of lavage fluid. Primary bronchial epithelial cells (mBECs) were extracted, and the expression of TGF signalling pathway‐, autophagy‐ and PI3K/Akt/mTOR signalling pathway‐related proteins in mBECs was detected by immunofluorescence assay and Western blot analysis. The mitochondrial function was also evaluated. PM2.5 aggravated the inflammatory response through enhancing the secretion of IL‐17A by γδT/Th17 cells. Meanwhile, PM2.5 activated the TGF signalling pathway and induced EMT progression in bronchial epithelial cells, thereby contributing to pulmonary fibrosis. Besides, PM2.5 suppressed autophagy of bronchial epithelial cells by up‐regulating IL‐17A, which in turn activated the PI3K/Akt/mTOR signalling pathway. Furthermore, IL‐17A impaired the energy metabolism of airway epithelial cells in the PM2.5‐induced models. This study suggested that PM2.5 could inhibit autophagy of bronchial epithelial cells and promote pulmonary inflammation and fibrosis by inducing the secretion of IL‐17A in γδT and Th17 cells and regulating the PI3K/Akt/mTOR signalling pathway.     

Use of Tregs as a cell‐based therapy via CD39 for benign prostate hyperplasia with inflammation

Benign prostatic hyperplasia (BPH) occurs most commonly among older men, often accompanied by chronic tissue inflammation. Although its aetiology remains unclear, autoimmune dysregulation may contribute to BPH. Regulatory T cells (Tregs) prevent autoimmune responses and maintain immune homeostasis. In this study, we aimed to investigate Tregs frequency, phenotype, and function in BPH patients and to evaluate adoptive transfer Tregs for immunotherapy in mice with BPH via CD39. Prostate specimens and peripheral blood from BPH patients were used to investigate Treg subsets, phenotype and Treg‐associated cytokine production. Sorted CD39^+/? Tregs from healthy mice were adoptively transferred into mice before or after testosterone propionate administration. The Tregs percentage in peripheral blood from BPH patients was attenuated, exhibiting low Foxp3 and CD39 expression with low levels of serum IL‐10, IL‐35 and TGF‐β. Immunohistochemistry revealed Foxp3+ cells were significantly diminished in BPH prostate with severe inflammatory. Although the Tregs subset was comprised of more effector/memory Tregs, CD39 was still down‐regulated on effector/memory Tregs in BPH patients. Before or after testosterone propionate administration, no alterations of BPH symptoms were observed due to CD39‐ Tregs in mice, however, CD39⁺Tregs existed more potency than Tregs to regulate prostatic hyperplasia and inhibit inflammation by decreasing IL‐1β and PSA secretion, and increasing IL‐10 and TGF‐β secretion. Furthermore, adoptive transfer with functional Tregs not only improved prostate hyperplasia but also regulated muscle cell proliferation in bladder. Adoptive transfer with Tregs may provide a novel method for the prevention and treatment of BPH clinically.     

Methyltransferase like 3 promotes colorectal cancer proliferation by stabilizing CCNE1 mRNA in an m6A-dependent manner

m6A modification is the most prevalent RNA modification in eukaryotes. As the critical N6-methyladenosine (m6A) methyltransferase, the roles of methyltransferase like 3 (METTL3) in colorectal cancer (CRC) are controversial. Here, we confirmed that METTL3, a critical m6A methyltransferase, could facilitate CRC progression in vitro and in vivo. Further, we found METTL3 promoted CRC cell proliferation by methylating the m6A site in 3′-untranslated region (UTR) of CCNE1 mRNA to stabilize it. Moreover, we found butyrate, a classical intestinal microbial metabolite, could down-regulate the expression of METTL3 and related cyclin E1 to inhibit CRC development. METTL3 promotes CRC proliferation by stabilizing CCNE1 mRNA in an m6A-dependent manner, representing a promising therapeutic strategy for the treatment of CRC.