Search

Neural tube defects (NTDs) constitute the second most common congenital malformation of the central nervous system. The pathogenesis of NTDs is not entirely clear. In recent years, microRNAs (miRNAs) have become a hot spot in genetic and developmental biology research. The present study aimed to explore the potential role of miRNA-26a in NTDs and the underlying pathogenesis thereof. First, we found significantly increased miRNA-26a expression in fetuses with NTDs (p < 0.0001), which significantly downregulated EphA2 and ERK1 mRNA and protein expression levels in fetuses with NTDs compared to normal controls (p < 0.01). In addition, a dual-luciferase reporter assay showed that miR-26a negatively regulated EphA2 by directly binding with the 3′-untranslated region of EphA2. Second, the upregulation of miRNA-26a expression increased caspase 3 and 9 protein expression levels (p < 0.01) and decreased EphA2 mRNA and protein expression levels (p < 0.01), as well as ERK1 and SRF protein expression levels (p < 0.01) in mouse neural stem cells (NE-4C) and human astroblastoma cells (U87MG). Furthermore, the upregulation of miRNA-26a inhibited cell proliferation and enhanced apoptosis of NE-4C and U87MG cells (p < 0.05). Similar results were observed with the MAPK inhibitor PD98059 (p < 0.01). These results suggest that miR-26a targets EphA2, modulates phosphorylation of the MAPK/ERK (MEK) pathway, regulates SRF, and participates in regulating nervous cell proliferation and apoptosis. Dysregulation of the aforementioned mechanism may be involved in the pathogenesis of NTDs. [ABSTRACT FROM AUTHOR]

BACKGROUND: Bemisia tabaci (Gennadius) is a major damaging agricultural pest that exhibits high resistance to pyrethroid insecticides. L925I (TTA to ATA) and T929V (ACT to GTT) mutations in the para‐type voltage‐gated sodium channel (VGSC) are associated with resistance of B. tabaci to pyrethroids. Amplicon sequencing is a reliable and highly efficient method to detect the frequency of mutations linked with insecticide resistance. RESULTS: Similar frequencies of L925I and T929V mutations were obtained by amplicon sequencing and Sanger sequencing (L925I: 0.3548 vs 0.3619; T929V: 0.6140 vs 0.6381) with overlap of 95% confidence interval in the SX population of B. tabaci. In five populations of B. tabaci from China, the maximum and minimum frequencies of the two mutations were found in the LN (L925I: 0.1126; T929V: 0.8834) and JS (L925I: 0.8776; T929V: 0.1166) populations by amplicon sequencing. However, there was no significant difference in frequencies between the L925I and T929V mutations. The sum frequency of L925I and T929V exceeded 0.9688 in all populations. In addition, a combining mutation, L925 + T929V (L925I and T929V located in same allele), was found in five populations by amplicon sequencing even though its highest frequency was only 0.0157. CONCLUSION: We established an efficient approach for detecting frequency of mutation by amplicon sequencing. The frequencies of L925I and T929V in VGSC associated with pyrethroid resistance were detected in this study, which could provide foundational data for resistance management of B. tabaci. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

Introduction: Idiopathic polyhydramnios (IPH) is an abnormal increase in amniotic fluid volume (AFV). This condition has unknown etiologies and is associated with various adverse pregnancy outcomes including maternal and fetal complication. This study aims to establish a comparative proteome profile for the human amniotic fluid (AF) of IPH and normal pregnancies and identify the responsible mediators and pathways that regulate AFV.Methods: We first employed coupled isobaric tags for relative and absolute quantitation (iTRAQ) proteomics and bioinformatics analysis to examine the differentially expression proteins (DEPs) in the AF of IPH and normal pregnancies. Second, CUL5, HIP1, FSTL3, and LAMP2 proteins were selected for verification in amnion, chorion, and placental tissues by Western blot analysis.Results: We identified 357 DEPs with 282 upregulated and 75 downregulated. Bioinformatics analysis revealed that cell, cellular process, and binding were the most enriched Gene Ontology terms. Amoebiasis, hematopoietic cell lineage, and NF-kappa B signaling pathway were the top significant pathways. In the verification procedure, FSTL3 protein had a highly significant expression in the amnion, chorion, and placentas of IPH and normal AFV groups (p < 0.05).Discussion: Our results provide new insights into idiopathic polyhydramnios and offer fundamental points for future studies on AFV. [ABSTRACT FROM AUTHOR]

The microstructure and micro-mechanics around the repaired interface, and the tensile properties of laser additive repaired (LARed) Inconel 625 alloy were investigated. The results showed that the microstructure around the repaired interface was divided into three zones: the substrate zone (SZ), the heat-affected zone (HAZ), and the repaired zone (RZ). The microstructure of the SZ had a typical equiaxed crystal structure, displaying simultaneously precipitated block-shaped MC-type carbides (NbC, TiC), with bimodal sizes of approximately 10 μm and 0.5 μm and an irregularly shaped flocculent Laves phase. Recrystallization occurred in the HAZ, and led to significant grain growth; a portion of the second phase dissolved in the original grain boundaries. In the RZ, there was a columnar crystal structure, and the size increased with increasing deposition thickness. Moreover, the microstructure between the layer interface and layer interior was quite different, presenting an overlapping transition zone (OTZ), in which the dendritic structure coarsened and more Laves phase were precipitated, compared to in the layer interior. The hardness and tensile properties of the LARed samples were equivalent to those of the wrought substrate, which indicates that laser additive repairing (LAR) is a reliable repair solution for damaged and mis-machined components comprising Inconel 625 alloy. [ABSTRACT FROM AUTHOR]

Abstract: The effects of Mn substitution for Mg on the microstructure, mechanical properties, and corrosion behavior of Mg69−xZn27Ca4Mnx (x=0, 0.5 and 1at.%) alloys were investigated using X-ray diffraction, compressive tests, electrochemical treatments, and immersion tests, respectively. Microstructural observations showed that the Mg69Zn27Ca4 alloy was mainly amorphous. The addition of Mn decreases the glass-forming ability, which results in a decreased strength from 545MPa to 364MPa. However, this strength is still suitable for implant application. Polarization and immersion tests in the simulated body fluid at 37°C revealed that the Mn-doped Mg–Zn–Ca alloys have significantly higher corrosion resistance than traditional ZK60 and pure Mg alloys. Cytotoxicity test showed that cell viabilities of osteoblasts cultured with Mn-doped Mg–Zn–Ca alloys extracts were higher than that of pure Mg. Mg68.5Zn27Ca4Mn0.5 exhibits the highest bio-corrosion resistance, biocompatibility and has desirable mechanical properties, which could suggest to be used as biomedical materials in the future. [Copyright &y& Elsevier]

Background: Uterine Corpus Endometrial Carcinoma (UCEC) stands as one of the prevalent malignancies impacting women globally. Given its heterogeneous nature, personalized therapeutic approaches are increasingly significant for optimizing patient outcomes. This study investigated the prognostic potential of cellular senescence genes(CSGs) in UCEC, utilizing machine learning techniques integrated with large-scale genomic data., Methods: A comprehensive analysis was conducted using transcriptomic and clinical data from 579 endometrial cancer patients sourced from the Cancer Genome Atlas (TCGA). A subset of 503 CSGs was assessed through weighted gene co-expression network analysis (WGCNA) alongside machine learning algorithms, including Gaussian Mixture Model (GMM), support vector machine - recursive feature elimination (SVM-RFE), Random Forest, and eXtreme Gradient Boosting (XGBoost), to identify key differentially expressed cellular senescence genes. These genes underwent further analysis to construct a prognostic model., Results: Our analysis revealed two distinct molecular clusters of UCEC with significant differences in tumor microenvironment and survival outcomes. Utilizing cellular senescence genes, a prognostic model effectively stratified patients into high-risk and low-risk categories. Patients in the high-risk group exhibited compromised overall survival and presented distinct molecular and immune profiles indicative of tumor progression. Crucially, the prognostic model demonstrated robust predictive performance and underwent validation in an independent patient cohort., Conclusion: The study emphasized the significance of cellular senescence genes in UCEC progression and underscored the efficacy of machine learning in developing reliable prognostic models. Our findings suggested that targeting cellular senescence holds promise as a strategy in personalized UCEC treatment, thus warranting further clinical investigation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Wei, Lin, Huang, Wei, Mao and Fan.)

Background: Endoplasmic reticulum (ER) stress arises from the accumulation of misfolded or unfolded proteins within the cell and is intricately linked to the initiation and progression of various tumors and their therapeutic strategies. However, the precise role of ER stress in uterine corpus endometrial cancer (UCEC) remains unclear., Methods: Data on patients with UCEC and control subjects were obtained from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Using differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA), we identified pivotal differentially expressed ER stress-related genes (DEERGs). Further validation of the significance of these genes in UCEC was achieved through consensus clustering and bioinformatic analyses. Using Cox regression analysis and several machine learning algorithms (least absolute shrinkage and selection operator [LASSO], eXtreme Gradient Boosting [XGBoost], support vector machine recursive feature elimination [SVM-RFE], and Random Forest), hub DEERGs associated with patient prognosis were effectively identified. Based on the four identified hub genes, a prognostic model and nomogram were constructed. Additionally, a drug sensitivity analysis and in vitro validation experiments were performed., Results: A total of 94 DEERGs were identified in patients with UCEC and healthy controls. Consensus clustering analysis revealed significant differences in prognosis, typical immune checkpoints, and tumor microenvironments between the subtypes. Using Cox regression analysis and machine learning, four hub DEERGs, MYBL2, RADX, RUSC2, and CYP46A1, were identified to construct a prognostic model. The reliability of the model was validated using receiver operating characteristic (ROC) curves. Decision curve analysis (DCA) demonstrated the superior predictive ability of the nomogram in terms of 3- and 5-year survival, compared with that of other clinical indicators. Drug sensitivity analysis revealed increased sensitivity to dactinomycin, docetaxel, selumetinib, and trametinib in the low-risk group. The expressions of RADX, RUSC2, and CYP46A1 were downregulated, whereas that of MYBL2 was upregulated in UCEC tissues, as demonstrated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and immunofluorescence assays., Conclusion: This study developed a stable and accurate prognostic model based on multiple bioinformatics analyses, which can be used to assess the prognosis of UCEC. This model may contribute to future research on the risk stratification of patients with UCEC and the formulation of novel treatment strategies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lin, Wei, Wei and Fan.)

Due to the increased crewed spaceflights in recent years, it is vital to understand how the space environment affects human health. A lack of gravitational force is known to risk multiple physiological functions of astronauts, particularly damage to the central nervous system (CNS). As innate immune cells of the CNS, microglia can transition from a quiescent state to a pathological state, releasing pro-inflammatory cytokines that contribute to neuroinflammation. There are reports indicating that microglia can be activated by simulating microgravity or exposure to galactic cosmic rays (GCR). Consequently, microglia may play a role in the development of neuroinflammation during spaceflight. Prolonged spaceflight sessions raise concerns about the chronic activation of microglia, which could give rise to various neurological disorders, posing concealed risks to the neural health of astronauts. This review summarizes the risks associated with neural health owing to microglial activation and explores the stressors that trigger microglial activation in the space environment. These stressors include GCR, microgravity, and exposure to isolation and stress. Of particular focus is the activation of microglia under microgravity conditions, along with the proposal of a potential mechanism., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wu, Zhao, Wei, Xu, Liu, Li and Chen.)

Background: Recurrent pregnancy loss defined as the occurrence of two or more pregnancy losses before 20-24 weeks of gestation, is a prevalent and significant pathological condition that impacts human reproductive health. However, the underlying mechanism of RPL remains unclear. This study aimed to investigate the biomarkers and molecular mechanisms associated with RPL and explore novel treatment strategies for clinical applications., Methods: The GEO database was utilized to retrieve the RPL gene expression profile GSE165004. This profile underwent differential expression analysis, WGCNA, functional enrichment, and subsequent analysis of RPL gene expression using LASSO regression, SVM-RFE, and RandomForest algorithms for hub gene screening. ANN model were constructed to assess the performance of hub genes in the dataset. The expression of hub genes in both the RPL and control group samples was validated using RT-qPCR. The immune cell infiltration level of RPL was assessed using CIBERSORT. Additionally, pan-cancer analysis was conducted using Sangerbox, and small-molecule drug screening was performed using CMap., Results: A total of 352 DEGs were identified, including 198 up-regulated genes and 154 down-regulated genes. Enrichment analysis indicated that the DEGs were primarily associated with Fc gamma R-mediated phagocytosis, the Fc epsilon RI signaling pathway, and various metabolism-related pathways. The turquoise module, which showed the highest relevance to clinical symptoms based on WGCNA results, contained 104 DEGs. Three hub genes, WBP11, ACTR2, and NCSTN, were identified using machine learning algorithms. ROC curves demonstrated a strong diagnostic value when the three hub genes were combined. RT-qPCR confirmed the low expression of WBP11 and ACTR2 in RPL, whereas NCSTN exhibited high expression. The immune cell infiltration analysis results indicated an imbalance of macrophages in RPL. Meanwhile, these three hub genes exhibited aberrant expression in multiple malignancies and were associated with a poor prognosis. Furthermore, we identified several small-molecule drugs., Conclusion: This study identifies and validates hub genes in RPL, which may lead to significant advancements in understanding the molecular mechanisms and treatment strategies for this condition., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Wei, Wei, Cheng, Tan, Zhou, Lin and Pang.)

The cotton bollworm Helicoverpa armigera (Hübner) is one of the most damaging cotton pests worldwide. In China, control of this pest has been dependent on transgenic cotton producing a single Bacillus thuringiensis (Bt) protein Cry1Ac since 1997. A small, but significant, increase in H. armigera resistance to Cry1Ac was detected in field populations from Northern China. Since Vip3Aa has a different structure and mode of action than Cry proteins, Bt cotton pyramids containing Vip3Aa are considered as ideal successors of Cry1Ac cotton in China. In this study, baseline susceptibility of H. armigera to Vip3Aa was evaluated in geographic field populations collected in 2014 from major cotton-producing areas of China. The LC 50 values of 12 field populations ranged from 0.053 to 1.311 μg/cm², representing a 25-fold range of natural variation among populations. It is also demonstrated that four laboratory strains of H. armigera with high levels of resistance to Cry1Ac or Cry2Ab have no cross-resistance to Vip3Aa protein. The baseline susceptibility data established here will serve as a comparative reference for detection of field-evolved resistance to Vip3Aa in H. armigera after future deployment of Bt cotton pyramids in China.

Evolution of resistance by insect pests threatens the long-term benefits of transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt). Previous work has detected increases in the frequency of resistance to Bt toxin Cry1Ac in populations of cotton bollworm, Helicoverpa armigera, from northern China where Bt cotton producing Cry1Ac has been grown extensively for more than a decade. Confirming that trend, we report evidence from 2011 showing that the percentage of individuals resistant to a diagnostic concentration of Cry1Ac was significantly higher in two populations from different provinces of northern China (1.4% and 2.3%) compared with previously tested susceptible field populations (0%). We isolated two resistant strains: one from each of the two field-selected populations. Relative to a susceptible strain, the two strains had 460- and 1200-fold resistance to Cry1Ac, respectively. Both strains had dominant resistance to a diagnostic concentration of Cry1Ac in diet and to Bt cotton leaves containing Cry1Ac. Both strains had low, but significant cross-resistance to Cry2Ab (4.2- and 5.9-fold), which is used widely as the second toxin in two-toxin Bt cotton. Compared with resistance in other strains of H. armigera, the resistance in the two strains characterized here may be especially difficult to suppress.