High temperature is a significant environmental stress that limits plant growth and agricultural productivity. GDSL lipase is a hydrolytic enzyme with a conserved GDSL sequence at the N-terminus, which has various biological functions, such as participating in plant growth, development, lipid metabolism, and stress resistance. However, little is known about the function of the GDSL lipase gene in the heat tolerance of rice. Here, we characterized a lipase family protein coding gene HTA1, which was significantly induced by high temperature in rice. Rice seedlings in which the mutant hta1 was knocked out showed enhanced heat tolerance, whereas the overexpressing HTA1 showed more sensitivity to heat stress. Under heat stress, hta1 could reduce plant membrane damage and reactive oxygen species (ROS) levels and elevate the activity of antioxidant enzymes. Moreover, real-time quantitative PCR (RT-qPCR) analysis showed that mutant hta1 significantly activated gene expression in antioxidant enzymes, heat response, and defense. In conclusion, our results suggest that HTA1 negatively regulates heat stress tolerance by modulating the ROS accumulation and the expression of heat-responsive and defense-related genes in rice seedlings. This research will provide a valuable resource for utilizing HTA1 to improve crop heat tolerance.
The multifunctional molecule chondroitin sulfate proteoglycan 4 (CSPG4/NG2) plays key roles in organogenesis and tumorigenesis. However, its roles in placentation remain unclear. In this study, CSPG4 expression in human and mouse placentas was investigated through immunohistochemistry (IHC), qPCR and western blotting. The theoretical structure and function of CSPG4 were assessed using bioinformatic tools, and the functions of CSPG4 in fetal and placental development were investigated using a mouse model established by trophoblast-specific CSPG4 knockdown and a trophoblast cell line with CSPG4 knockout by lentivirus infection. The results showed that CSPG4 was mainly located in trophoblasts in both human placentas and mouse placentas, with a higher level in preeclampsia (PE) placentas than in healthy control placentas. Furthermore, there was a trend of increasing expression in mouse placentas during pregnancy. The 3D structure of CSPG4 was visualized using an M model composed of two chains, and the structure implied that CSPG4 was a multifunctional molecule containing multiple pockets with multiligand binding sites and enzyme active sites. Trophoblast-specific CSPG4 knockdown caused frequent fetal loss, and viable fetal development was restricted by poor placentation, with mice placentas having reduced weight and width. The proliferation and invasion of CSPG4-knockout trophoblasts were significantly inhibited, and as such, the molecular signaling of AKT and ERK phosphorylation was inhibited, and the expression of MMP2 and MMP9 was reduced. In summary, CSPG4 deficiency inhibited trophoblast proliferation and invasion, which was associated with AKT, ERK and MMP signaling. CSPG4 deficiency also caused pregnancy complications with poor placentation in mice.
Cold stress significantly constrains the growth, development, productivity, and distribution of rice, particularly the indica cultivar, known for its susceptibility to cold, limiting its cultivation to specific regions. This study investigated the genes associated with cold responsiveness in the roots of two indica cultivars, SQSL (cold-tolerant) and XZX45 (cold-susceptible), through transcriptome dynamics analysis during the seedling stage. The analysis identified 8144 and 6427 differentially expressed genes (DEGs) in XZX45 and SQSL, respectively. Among these DEGs, 4672 (G2) were shared by both cultivars, while 3472 DEGs (G1) were specific to XZX45, and 1755 DEGs (G3) were specific to SQSL. Additionally, 572 differentially expressed transcription factors (TFs) from 48 TF families, including WRKY, NAC, bHLH, ERF, bZIP, MYB, C2H2, and GRAS, were identified. Gene Ontology (GO) enrichment analysis revealed significant enrichment of DEGs in the G3 group, particularly in the "response to cold" category, highlighting the crucial role of these specific genes in response to cold stress in SQSL. Furthermore, Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated pronounced enrichment of DEGs in the G3 group in metabolic pathways such as "Pyruvate metabolism", "Glycolysis/Gluconeogenesis", and "Starch and sucrose metabolism", contributing to cold tolerance mechanisms in SQSL. Overall, this study provides comprehensive insights into the molecular mechanisms underlying cold responses in the indica cultivar, informing future genetic improvement strategies to enhance cold tolerance in susceptible indica rice cultivars.
Dear Editor, TrophoblasticCD147, also knownas basigin (BSG), regulates the differentiation and spiral artery remodelling functions of extravillous trophoblasts (EVCTs), and its deficiency contributes to the pathophysiology of preeclampsia (PE). The biological activities of CD147 are mediated by its interaction with integrin β1 and Wnt/β-catenin signalling. The reduced serum and villous CD147 levels in PE are worth further investigation in a clinical trial as an early biomarker of PE. PE is a multifactorial gestational complication affecting 4.6% of pregnancies worldwide.1 It is the top cause of prenatal morbidity/mortality and is associated with a high incidence of maternal and perinatal complications, causing a heavy burden to the healthcare system.1 The aetiology of PE is associated with defective trophoblast differentiation and functions causing abnormal placental development, insufficient placental perfusion, and maternal– foetal exchange defects.1,2 Our limited knowledge of the pathogenesis of the disease has hindered the development of a reliable approach for the prediction and treatment of PE. CD147 is a component of several of the most abundant protein complexes in human and mouse placentas3 (Figure S1). It has been linked to the physiology and pathology of various reproductive processes.4 Systematic CD147 knockout leads to perinatal lethality before day 12.5 of gestation in mice.5 The observations could be due to deficiency of CD147 in the foetus and/or the placenta. To circumvent the limitation of the knockout model, we employed our nanoparticle model6 to specifically knockdown CD147 expression in mouse trophoblasts (Figure S2). Our results showed that trophoblastic CD147 knockdown caused PE-like symptoms in mice, including placental haemorrhage (Figure 1A), reduction of alive litter size (Figure 1B), reduction of body, placental and foetal weight (Figure 1C-E), and elevation of blood pressure
High temperature is one of the main constraints affecting plant growth and development. It has been reported that abscisic acid (ABA) synthesis gene 9-cis-epoxycarotenoid dioxygenase (NCED) positively regulates plant resistance to salt, cold, and drought stresses. However, little is known about the function of the NCED gene in heat tolerance of rice. Here, we found that OsNCED1 was a heat stress inducible gene. Rice seedlings overexpressing OsNCED1 showed enhanced heat tolerance with more abundant ABA content, whereas the knockout mutant osnced1 accumulated less ABA and showed more sensitive to heat stress. Under heat stress, increased expression of OsNCED1 could reduce membrane damage and reactive oxygen species (ROS) level of plants, and elevate the activity of antioxidant enzymes. Moreover, real time-quantitative PCR (RT-qPCR) analysis showed that overexpression of OsNCED1 significantly activated the expression of genes involved in antioxidant enzymes, ABA signaling pathway, heat response, and defense. Together, our results indicate that OsNCED1 positively regulates heat tolerance of rice seedling by raising endogenous ABA contents, which leads to the improved antioxidant capacity and activated expression of heat and ABA related genes.
Triple-negative breast cancer (TNBC) is the most aggressive type of breast cancer. Currently, targeting therapy makes great advances for the treatment of TNBC, whereas more effective therapeutic targets are urgently needed. Cyclin B2 (CCNB2), which belongs to B-type cyclins, is known as a cell cycle regulator. CCNB2 is synthesized at G1 phase in cancer cells and downregulated at anaphase. The defects of CCNB2 led to the abnormal cell cycle and tumorigenesis. Though there are wide effects of CCNB2 on multiple types of tumors, the potential role of CCNB2 in TNBC progression is still unclear. Herein, we found that CCNB2 was highly expressed in human TNBC tissues and correlated with the prognosis and clinical pathological features including tumor size (p=0.022∗) and pTNM stage (p=0.021∗) of patients with TNBC. CCNB2 could promote the proliferation of TNBC cells in vitro and in mice. Our findings therefore confirmed the involvement of CCNB2 in TNBC progression and provided the evidence that CCNB2 could serve as a promising molecular target of TNBC.
猪圆环病毒2型(Porcine circovirus type 2,PCV2)是引起猪圆环病毒相关系统疾病的主要病原体,给全球的养猪业造成了巨大的经济损失.PCV2含有11个开放阅读框(Open reading frame,ORF),当前对其ORF1~ORF4所编码的相关蛋白研究较多,了解这4个主要蛋白在PCV2复制中的功能及其与宿主细胞间的相互作用,有助于揭示PCV2复制和致病的分子机制.文中对PCV2 0RF1~ORF4基因所编码蛋白的结构及在病毒生命周期中所发挥的作用进行了综述.
R-spondin3 (RSPO3), an activator of Wnt/β-catenin signaling, plays a key role in tumorigenesis of various cancers, but its role in choriocarcinoma remains unknown. To investigate the effect of RSPO3 on the tumor growth of choriocarcinoma JEG-3 cells, the expression of RSPO3 in human term placenta was detected, and a stable RSPO3-overexpressing JEG-3 cell line was established via lentivirus-mediated transduction. The expression of biomarkers involved in tumorigenicity was detected in the RSPO3-overexpressing JEG-3 cells, and cell proliferation, invasion, migration, and apoptosis were investigated. Moreover, soft agar clonogenic assays and xenograft tumorigenicity assays were performed to assess the effect of RSPO3 on tumor growth in vitro and in vivo. The results showed that RSPO3 was widely expressed in human term placenta and overexpression of RSPO3 promoted the proliferation and inhibited the migration, invasion, and apoptosis of the JEG-3 cells. Meanwhile, RSPO3 overexpression promoted tumor growth both in vivo and in vitro. Further investigation showed that the phosphorylation levels of Akt, phosphatidylinositol 3-kinase (PI3K), and ERK as well the expression of β-catenin and proliferating cell nuclear antigen (PCNA) were increased in the RSPO3-overexpressing JEG-3 cells and tumor xenograft. Taken together, these data indicate that RSPO3 promotes the tumor growth of choriocarcinoma via Akt/PI3K/ERK signaling, which supports RSPO3 as an oncogenic driver promoting the progression of choriocarcinoma.