Transient ischemia is a leading cause of cognitive dysfunction. Postischemic ROS generation and an increase in the cytosolic Zn2+ level ([Zn2+]c) are critical in delayed CA1 pyramidal neuronal death, but the underlying mechanisms are not fully understood. Here we investigated the role of ROS-sensitive TRPM2 (transient receptor potential melastatin-related 2) channel. Using in vivo and in vitro models of ischemia–reperfusion, we showed that genetic knockout of TRPM2 strongly prohibited the delayed increase in the [Zn2+]c, ROS generation, CA1 pyramidal neuronal death and postischemic memory impairment. Time-lapse imaging revealed that TRPM2 deficiency had no effect on the ischemia-induced increase in the [Zn2+]c but abolished the cytosolic Zn2+ accumulation during reperfusion as well as ROS-elicited increases in the [Zn2+]c. These results provide the first evidence to show a critical role for TRPM2 channel activation during reperfusion in the delayed increase in the [Zn2+]c and CA1 pyramidal neuronal death and identify TRPM2 as a key molecule signaling ROS generation to postischemic brain injury.

Pre-eclampsia is a serious multisystem disorder and causes significant increase in both maternal and foetal morbidity and perinatal mortality globally. Due to the limited understanding of the molecular mechanism of pre-eclampsia, the current study conducted bioinformatic analyses to screen key regulators involved in pre-eclampsia. The gene expression profiling dataset GSE44711 containing 8 early-onset pre-eclampsia placentas and 8 gestational-age-matched control placentas was downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) were screened by limma software package, which were then subjected to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analysis on the Database for Annotation, Visualization, and Integrated Discovery website. Finally, protein-protein interaction network was constructed using the Search Tool for the Retrieval of Interacting Genes database. In total, 192 DEGs including 106 upregulated and 86 downregulated genes were obtained. Proteoglycan 2 and podoplanin were the most significantly up- and downregulated genes, respectively. In addition, three potential pathways and their related DEGs: spermidine/spermine N1-acetyltransferase 1, amiloride-binding protein 1 and adenosylmethionine decarboxylase 1 were associated with arginine and proline metabolism. Vascular endothelial growth factor C; phosphatidylinositol-4, 5-bisphosphate 3-kinase, catalytic subunit beta; collagen, type I, alpha 1 (COL1A1); and fibronectin 1 (FN1) were associated with focal adhesion. COL6A1 as well as COL1A1 and FN1 were involved in extra-cellular matrix-receptor interaction. The current study identified several potential genes and three pathways which may be considered as candidate targets for diagnosis and therapy of pre-eclampsia.

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FEAT protein is uniformly overexpressed in a variety of human cancers but weakly expressed in normal tissue. FEAT has antiapoptotic activity and plays a role in carcinogenesis; however, the correlation between FEAT and clinicopathologic characteristics in cancer has not been reported. Our study explores the expression of FEAT protein and its clinicopathologic significance in breast cancer. We examined the expression of FEAT in tissues from 131 cases of breast cancer by immunohistochemistry and analyzed the correlation between FEAT expression and clinicopathologic parameters. The difference in FEAT expression between normal breast tissues and breast cancer tissues was also investigated. Finally, we analyzed the association between FEAT expression and disease-free survival or overall survival. Our data showed that FEAT was expressed in the cytoplasm. The expression of FEAT protein was significantly higher in breast cancer tissues than in normal breast tissues. Moreover, the expression of FEAT protein was higher in breast cancer with a larger tumor size (>2 cm), negative PR, positive HER2, or higher Ki67 index (≥14%) than in breast cancer with a smaller tumor size (≤2 cm), positive PR, negative HER2, or lower Ki67 index (<14%) (P<0.05). In addition, the expression of FEAT protein was associated with tumor size, PR status, HER2 expression, Ki67 index, and molecular subtype. Survival analysis showed that disease-free survival and overall survival were significantly shorter in breast cancer patients with high FEAT expression than in those with low expression of FEAT (P<0.05). COX regression analysis showed that FEAT was an independent prognostic factor for recurrence in breast cancer, but not for survival. In conclusion, FEAT may be a potential biomarker for recurrence of breast cancer.

Generating chromosome-scale haplotype resolved assembly is important for functional studies. However, current de novo assemblers are either haploid assemblers that discard allelic information, or diploid assemblers that can only tackle genomes of low complexity. Here, we report a diploid assembler, gcaPDA (gamete cells assisted Phased Diploid Assembler), which exploits haploid gamete cells to assist in resolving haplotypes. We generate chromosome-scale phased diploid assemblies for the highly heterozygous and repetitive genome of a maize F1 hybrid using gcaPDA and evaluate the assembly result thoroughly. With applicability of coping with complex genomes and fewer restrictions on application than other diploid assemblers, gcaPDA is likely to find broad applications in studies of eukaryotic genomes.

2q13 CNV was associated with various diseases, with a lack of consensus. By CMA analysis, we found that four fetuses had deletion in the proximal region of 2q13, one had duplication, and one had duplication in the distal region of 2q13; however, they had variable outcomes.

VWD is reported as the most common inherited bleeding disorder worldwide, found in approximately 1% population [1-4]. It can be divided into 3 subtypes: type 1, type 2 and type 3, caused by quantitative or qualitative defects of VWF. VWF is a complex plasma protein essential for primary hemostasis and coagulation. VWF helps to bind and stabilize blood clotting FVIII from rapid breakdown within the blood stream. Any defect in VWF can also cause reduction of FVIII levels [5]. Type 3 VWD is the rarest and most severe type due to virtual absence of VWF and very low levels of FVIII, another protein involved in blood clotting. Hemophilia A is another type of genetic bleeding disorder characterized by deficiency in clotting FVIII, usually affecting males. Type 3 VWD can be difficult to diagnose due to its rarity. Symptoms, hemostatic challenge and bleeding history may become more apparent with increasing age. Since type 3 VWD also exhibits very low levels of FVIII resembles hemophilia A and it can be misdiagnosed if based on FVIII levels only.