Mechanism for the Decision of Ovarian Surface Epithelial Stem Cells to Undergo Neo-Oogenesis or Ovarian Tumorigenesis

The ovary is surrounded by a whitish layer of mesodermally derived ovarian surface epithelium (OSE) that lines the intraembryonic celom and comprises simple squamous to cuboidal to low pseudostratified columnar epithelial cells. Its integrity is maintained by simple desmosomes, incomplete tight junctions, several integrins and cadherins. Recent research has found that ovarian stem cells (OSCs) exist within the OSE and may be responsible for both neo-oogenesis and ovarian cancer during adult life. The factors determining whether OSCs undergo neo-oogenesis or ovarian cancer are of great interest to researchers and clinicians. Accumulating evidence suggests the mechanism for the decision of ovarian surface epithelial stem cells to undergo either neo-oogenesis or ovarian cancer transformation may comprise both internal and external factors. Here, we review recent progress on how the internal factors, including genes, signaling pathways and lncRNA: OSE stem cells mediate the development and progression of ovarian cancer through various genes such as p53, KRAS, BRAF, and PTEN, and mutations in PIK3CA, and through various signaling pathways, including TGF-B pathway, Wnt signaling pathway, Notch signaling pathway, NF-kB signal transducer and transcriptional activator 3 (STAT3) pathway and Hedghog (HH) pathway. A series of expressions of IncRNA have changed in epithelial ovarian cancer tissues and cell lines compared to normal ovarian tissues and cell lines. As well as external factors, including incessant ovulation, gonadotropin and chronicinflammation: Frequent ovulation, without long-term dormancy, increases the risk of illness, because repeated rupture and repair at the ovulation site provides an opportunity for the accumulation of genetic aberrations; FSH affects all aspects of ovarian cancer metastasis, such as inhibition of apoptosis, through Induction of increased expression of VEGFA (VEGF) to support tumor growth, promote vascular growth, and possibly alter certain oncogenic pathways, thereby promoting proliferation and invasive phenotypic inflammation contributes to tumorigenesis, which help determine whether OSCs undergo neo-oogenesis or ovarian tumorigenesis. Understanding this issue is critical for developing novel strategies for premature ovarian failure and ovarian cancer prevention and therapy

Distinct lesion features and underlying mechanisms in patients with acute multiple infarcts in multiple cerebral territories

ObjectiveTo determine the etiology spectrum and lesion distribution patterns of patients with acute multiple infarcts in multiple cerebral territories (AMIMCT) and provide guidance for treatment and prevention strategies in these patients.MethodsPatients with acute ischemic stroke diagnosed using diffusion-weighted imaging (DWI) were consecutively included in this study between June 2012 and Apr 2022. AMIMCT was defined as non-contiguous focal lesions located in more than one cerebral territory with acute neurological deficits. We retrospectively analyzed the clinical and imaging characteristics, etiology spectra and underlying mechanisms in patients with and without AMIMCT. Infarct lesion patterns on DWI and their relevance to etiology were further discussed.ResultsA total of 1,213 patients were enrolled, of whom 145 (12%) were diagnosed with AMIMCT. Patients with AMIMCT tended to be younger (P = 0.016), more often female (P = 0.001), and exhibited less common conventional vascular risk factors (P < 0.05) compared to those without AMIMCT. The constitution of the Trial of Org 10,172 in Acute Stroke Treatment classification was significantly different between patients with and without AMIMCT (P = 0.000), with a higher proportion of stroke of other determined causes (67.6% vs. 12.4%). For detailed etiologies, autoimmune or hematologic diseases were the most common (26.2%) etiologies of AMIMCT, followed by periprocedural infarcts (15.2%), cardioembolism (12.4%), tumor (12.4%), large artery atherosclerosis (10.3%), and sudden drop in blood pressure (8.3%). Hypercoagulability and systemic hypoperfusion are common underlying mechanisms of AMIMCT. Distinctive lesion distribution patterns were found associated with stroke etiologies and mechanisms in AMIMCT. Most of patients with large artery atherosclerosis (73.3%), autoimmune/hematologic diseases (57.9%) manifested the disease as multiple infarct lesions located in bilateral supratentorial regions. However, 66.7% of cardioembolism and 83.8% of cardiovascular surgery related stroke presented with both supratentorial and infratentorial infarct lesions.ConclusionThe etiologies and mechanisms of patients with AMIMCT were more complex than those without AMIMCT. The distribution characteristics of infarct lesions might have important implications for the identification of etiology and mechanism in the future, which could further guide and optimize clinical diagnostic strategies

Burden of dilated perivascular spaces in patients with moyamoya disease and moyamoya syndrome is related to middle cerebral artery stenosis

Background and objectiveThe correlation between intracranial large artery disease and cerebral small vessel disease (CSVD) has become a noteworthy issue. Dilated perivascular spaces (dPVS) are an important marker of CSVD, of which cerebral atrophy has been regarded as one of the pathological mechanisms. DPVS has been found to be associated with vascular stenosis in patients with moyamoya disease (MMD), but the underlying mechanism remains unclear. The purpose of our study was to explore the correlation between the middle cerebral artery (MCA) stenosis and dPVS in the centrum semiovale (CSO-dPVS) in patients with MMD/moyamoya syndrome (MMS) and to determine whether brain atrophy plays a mediating role in this relationship.MethodsA total of 177 patients were enrolled in a single-center MMD/MMS cohort. Images of their 354 cerebral hemispheres were divided into three groups according to dPVS burden: mild (dPVS 0–10), moderate (dPVS 11–20), and severe (dPVS > 20). The correlations among cerebral hemisphere volume, MCA stenosis, and CSO-dPVS were analyzed, adjusting for the confounding factors of age, gender, and hypertension.ResultsAfter adjustment for age, gender, and hypertension, the degree of MCA stenosis was independently and positively associated with ipsilateral CSO-dPVS burden (standardized coefficient: β = 0.247, P < 0.001). A stratified analysis found that the subgroup with a severe CSO-dPVS burden exhibited a significantly higher risk of severe stenosis of the MCA [p < 0.001, OR = 6.258, 95% CI (2.347, 16.685)]. No significant correlation between CSO-dPVS and ipsilateral hemisphere volume was found (p = 0.055).ConclusionIn our MMD/MMS cohort, there was a clear correlation between MCA stenosis and CSO-dPVS burden, which may be a direct effect of large vessel stenosis, without a mediating role of brain atrophy

Overexpression of MsSAG113 gene promotes leaf senescence in alfalfa via participating in the hormone regulatory network

IntroductionAlfalfa (Medicago sativa) is a kind of high quality leguminous forage species, which was widely cultivated in the world. Leaf senescence is an essential process in plant development and life cycle. Here, we reported the isolation and functional analysis of an alfalfa SENESCENCE-ASSOCIATED GENE113 (MsSAG113), which belongs to the PP2C family and mainly plays a role in promoting plant senescence.MethodsIn the study, Agrobacterium-mediated, gene expression analysis, next generation sequencing, DNA pull-down, yeast single hybridization and transient expression were used to identify the function of MsSAG113 gene.ResultsThe MsSAG113 gene was isolated from alfalfa, and the transgenic plants were obtained by Agrobacterium-mediated method. Compared with the wildtype, transgenic plants showed premature senescence in leaves, especially when cultivated under dark conditions. Meanwhile, application of exogenous hormones ABA, SA, MeJA, obviously acclerated leaf senescence of transgenic plants. Furthermore, the detached leaves from transgenic plants turned yellow earlier with lower chlorophyll content. Transcriptome analysis identified a total of 1,392 differentially expressed genes (DEGs), involving 13 transcription factor families. Of which, 234 genes were related to phytohormone synthesis, metabolism and transduction. Pull-down assay and yeast one-hybrid assay confirmed that alfalfa zinc finger CCCH domain-containing protein 39 (MsC3H-39) could directly bind the upstream of MsSAG113 gene. In conclusion, the MsSAG113 gene plays a crucial role in promoting leaf senescence in alfalfa via participating in the hormone regulatory network.DiscussionThis provides an essential basis for further analysis on the regulatory network involving senescence-associated genes in alfalfa

Foxtail Mosaic Virus-induced Flowering Assays in Monocot Crops

Virus-induced flowering (VIF) exploits RNA or DNA viruses to express flowering time genes to induce flowering in plants. Such plant virus-based tools have recently attracted widespread attention for their fundamental and applied uses in flowering physiology and in accelerating breeding in dicotyledonous crops and woody fruit-trees. We now extend this technology to a monocot grass and a cereal crop. Using the Foxtail mosaic virus-based VIF system, dubbed FoMViF, we showed that expression of florigenic Flowering Locus T (FT) genes can promote early flowering and spikelet development in proso millet, a C4 grass species with potential for nutritional food and biofuel resources, and in non-vermalized C3 wheat, a major food crop worldwide. Floral and spikelet/grain induction in the two monocot plants was caused by the virally expressed untagged or FLAG-tagged FT orthologues, and the florigenic activity of rice Hd3a was more pronounced than its dicotyledonous counterparts in proso millet. The FoMViF system is easy to perform and its efficacy to induce flowering and early spikelet/grain production is high. In addition to proso millet and wheat, we envisage that FoMViF will be also applicable to many economically important monocotyledonous food and biofuel crops

Genetic polymorphisms of MDM2 and TP53 genes are associated with risk of nasopharyngeal carcinoma in a Chinese population

<p>Abstract</p> <p>Background</p> <p>The tumor suppressor TP53 and its negative regulator MDM2 play crucial roles in carcinogenesis. Previous case-control studies also revealed <it>TP53 </it>72Arg>Pro and <it>MDM2 </it>309T>G polymorphisms contribute to the risk of common cancers. However, the relationship between these two functional polymorphisms and nasopharyngeal carcinoma (NPC) susceptibility has not been explored.</p> <p>Methods</p> <p>In this study, we performed a case-control study between 522 NPC patients and 722 healthy controls in a Chinese population by using PCR-RFLP.</p> <p>Results</p> <p>We found an increased NPC risk associated with the <it>MDM2 </it>GG (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 2.08-3.96) and TG (OR = 1.49, 95% CI = 1.16-2.06) genotypes. An increased risk was also associated with the <it>TP53 </it>Pro/Pro genotype (OR = 2.22, 95% CI = 1.58-3.10) compared to the Arg/Arg genotype. The gene-gene interaction of <it>MDM2 </it>and <it>TP53 </it>polymorphisms increased adult NPC risk in a more than multiplicative manner (OR for the presence of both <it>MDM2 </it>GG and <it>TP53 </it>Pro/Pro genotypes = 7.75, 95% CI = 3.53-17.58).</p> <p>Conclusion</p> <p>The findings suggest that polymorphisms of <it>MDM2 </it>and <it>TP53 </it>genes may be genetic modifier for developing NPC.</p

Protein–protein interaction site prediction by model ensembling with hybrid feature and self-attention

Abstract Background Protein–protein interactions (PPIs) are crucial in various biological functions and cellular processes. Thus, many computational approaches have been proposed to predict PPI sites. Although significant progress has been made, these methods still have limitations in encoding the characteristics of each amino acid in sequences. Many feature extraction methods rely on the sliding window technique, which simply merges all the features of residues into a vector. The importance of some key residues may be weakened in the feature vector, leading to poor performance. Results We propose a novel sequence-based method for PPI sites prediction. The new network model, PPINet, contains multiple feature processing paths. For a residue, the PPINet extracts the features of the targeted residue and its context separately. These two types of features are processed by two paths in the network and combined to form a protein representation, where the two types of features are of relatively equal importance. The model ensembling technique is applied to make use of more features. The base models are trained with different features and then ensembled via stacking. In addition, a data balancing strategy is presented, by which our model can get significant improvement on highly unbalanced data. Conclusion The proposed method is evaluated on a fused dataset constructed from Dset186, Dset_72, and PDBset_164, as well as the public Dset_448 dataset. Compared with current state-of-the-art methods, the performance of our method is better than the others. In the most important metrics, such as AUPRC and recall, it surpasses the second-best programmer on the latter dataset by 6.9% and 4.7%, respectively. We also demonstrated that the improvement is essentially due to using the ensemble model, especially, the hybrid feature. We share our code for reproducibility and future research at https://github.com/CandiceCong/StackingPPINet

Century-scale high-resolution black carbon records in sediment cores from the South Yellow Sea, China

Black carbon (BC) has received increasing attention in the last 20 years because it is not only an absorbent of toxic pollutants but also a greenhouse substance, preserving fire-history records, and more importantly, acting as an indicator of biogeochemical cycles and global changes. By adopting an improved chemothermal oxidation method (WXY), this study reconstructed the century-scale high-resolution records of BC deposition from two fine-grained sediment cores collected from the Yellow Sea Cold Water Mass in the South Yellow Sea. The BC records were divided into five stages, which exhibited specific sequences with three BC peaks at approximately 1891, 1921, and 2007 AD, representing times at which the first heavy storms appeared just after the termination of long-term droughts. The significant correlation between the times of the BC peaks in the cores and heavy storms in the area of the Huanghe (Yellow) River demonstrated that BC peaks could result from markedly strengthened sedimentation due to surface runoff, which augmented the atmospheric deposition. Stable carbon isotope analysis indicated that the evident increase in carbon isotope ratios of BC in Stage 5 might have resulted from the input of weathered rock-derived graphitic carbon cardinally induced by the annual anthropogenic modulation of water-borne sediment in the Huanghe River since 2005 AD. Numerical calculations demonstrated that the input fraction of graphitic carbon was 22.97% for Stage 5, whereas no graphitic carbon entered during Stages 1 and 3. The obtained data provide new and important understanding of the source-sink history of BC in the Yellow Sea