Nuclear factor OsNF-YC5 modulates rice seed germination by regulating synergistic hormone signaling.

Regulation of seed dormancy/germination is of great importance for seedling establishment and crop production. Nuclear factor-Y (NF-Y) transcription factors regulate plant growth and development, as well as stress responses; however, their roles in seed germination remain largely unknown. In this study, we reported that NF-Y gene OsNF-YC5 knockout increased, while its overexpression reduced, the seed germination in rice (Oryza sativa L.). ABA-induced seed germination inhibition assays showed that the osnf-yc5 mutant was less sensitive but OsNF-YC5-overexpressing lines were more sensitive to exogenous ABA than the wild type. Meanwhile, MeJA treatment substantially enhanced the ABA sensitivity of OsNF-YC5-overexpressing lines during seed germination. Mechanistic investigations revealed that the interaction of OSMOTIC STRESS/ABA-ACTIVATED PROTEIN KINASE 9 (SAPK9) with OsNF-YC5 enhanced the stability of OsNF-YC5 by protein phosphorylation, while the interaction between JASMONATE ZIM-domain protein 9 (OsJAZ9) and OsNF-YC5 repressed OsNF-YC5 transcriptional activity and promoted its degradation. Furthermore, OsNF-YC5 transcriptionally activated ABA catabolic gene OsABA8ox3, reducing ABA levels in germinating seeds. However, the transcriptional regulation of OsABA8ox3 by OsNF-YC5 was repressed by addition of OsJAZ9. Notably, OsNF-YC5 improved seed germination under salinity conditions. Further investigation showed that OsNF-YC5 activated the high-affinity K+ transporter gene (OsHAK21) expression, and addition of SAPK9 could increase the transcriptional regulation of OsHAK21 by OsNF-YC5, thus substantially reducing the ROS levels to enhance seed germination under salt stress. Our findings establish that OsNF-YC5 integrates ABA and JA signaling during rice seed germination, shedding light on the molecular networks of ABA-JA synergistic interaction.

The adverse effect of anticancer drug toremifene on vascular smooth muscle cells is an important aspect of its tumor growth inhibition.

PURPOSE: Toremifene (TOR) is widely used as an antineoplastic drug and has an inhibitory effect on angiogenesis in mesenteric desmoid tumors and vascular intracranial solitary fibrous tumors. However, no study has investigated the direct effect of TOR on vascular cells. This study aimed at exploring the effect of TOR on the behaviors of vascular smooth muscle cells (VSMCs). METHODS: Human aortic umbilical vascular smooth muscle cells (HAVSMCs) were treated by TOR. Cell morphology, migration, adhesion, and proliferation assay were investigated. The cell cycle, apoptosis, mitochondrial membrane potential, and reactive oxygen species were assessed using flow cytometry. Caspase-3 and 9 activities were assayed using Caspase-3 and Caspase-9 Activity Assay kits, respectively. Immunofluorescence and Western blot assays were carried out to characterize protein expressions of PCNA, p53, and Rho/ROCK signaling pathway. RESULTS: TOR damaged cytoskeleton, inhibited VSMC proliferation, migration, and adhesion, and induced abnormal cell morphology and apoptosis. The antiproliferative activity of TOR was associated with the induction of G0/G1 phase arrest, blocking the cell cycle. TOR disrupted intracellular reactive oxygen species and mitochondrial membrane potential, and enhanced p53 expression and the activities of caspase-3 and caspase-9. Thus, TOR-induced apoptosis by the mitochondrial signaling pathway. Additionally, TOR induced decreased Rho, ROCK, MLC, and pMLC proteins. Collectively, TOR may affect multiple behaviors of VSMCs by damaging cytoskeleton through the Rho/ROCK pathway. CONCLUSION: The adverse effect of TOR on VSMCs could be considered as an important aspect of tumor growth inhibition.

SYP-3343 drives abnormal vascularization in zebrafish through regulating endothelial cell behavior.

SYP-3343 is a novel strobilurin fungicide with excellent and broad-spectrum antifungal activity, and its potential toxicity raises public health concerns. However, the vascular toxicity of SYP-3343 to zebrafish embryos is still not well understood. In the present study, we investigated the effects of SYP-3343 on vascular growth and its potential mechanism of action. SYP-3343 inhibited zebrafish endothelial cell (zEC) migration, altered nuclear morphology, and triggered abnormal vasculogenesis and zEC sprouting angiogenesis, resulting in angiodysplasia. RNA sequencing showed that SYP-3343 exposure altered the transcriptional levels of vascular development-related biological processes in zebrafish embryos including angiogenesis, sprouting angiogenesis, blood vessel morphogenesis, blood vessel development, and vasculature development. Whereas, the addition of NAC exerted an improvement effect on zebrafish vascular defects owing to SYP-3343 exposure. Additionally, SYP-3343 altered cell cytoskeleton and morphology, obstructed migration and viability, disrupted cell cycle progression, and depolarized mitochondrial membrane potential, as well as promoted apoptosis and reactive oxygen species (ROS) in HUVEC. SYP-3343 also caused an imbalance of the oxidation and antioxidant systems and irritated the alterations in the cell cycle- and apoptosis-related genes in HUVECs. Collectively, SYP-3343 has high cytotoxicity, possibly by up-regulating p53 and caspase3 expressions and bax/bcl-2 ratio via ROS, leading to malformed vascular development.

The toxicity of 4-tert-butylphenol in early development of zebrafish: morphological abnormality, cardiotoxicity, and hypopigmentation.

Endocrine disrupting effects of 4-tert-butylphenol (4-t-BP) are well described in literature. However, the evidence regarding developmental toxic effect of 4-t-BP is still vague. The present study used zebrafish as a model organism to investigate the toxic effect of 4-t-BP. The results showed that 4-t-BP exposure at 3, 6, and 12 µM induced developmental toxicity in zebrafish, such as reduced embryo hatchability and abnormality morphological. Flow cytometry analysis showed that 4-t-BP also induced intracellular ROS production. 4-t-BP induced changes in the expression of genes related to cardiac development and melanin synthesis, resulting in cardiotoxicity and hypopigmentation. 4-t-BP also caused oxidative stress, and initiated apoptosis through p53-bcl-2/bax-capase3 pathway. Integrative biomarker response analysis showed time- and dose-dependent effects of 4-t-BP on oxidative damage and developmental toxicity in zebrafish embryos. Overall, this study contributed to a comprehensive evaluation of the toxicity of 4-t-BP, and the findings provided new evidence for early warning of residues in aquatic environments.

Spiromesifen contributes vascular developmental toxicity via disrupting endothelial cell proliferation and migration in zebrafish embryos.

Spiromesifen (SPF) is a specific contact pesticide, which has been widely used to control the growth of sucking insects like mites and whiteflies on crops. Although its residues in crops and effects on organisms has been extensively reported, its impact on the vasculature is still not being reported. In the present study, using human umbilical vein endothelial cells (HUVECs) and zebrafish embryos, we investigated the effects of SPF on blood vessel development and its mechanism of action. SPF exposure triggered abnormal blood vessel development, including vascular deletions and malformations, inhibition of CCV remodeling, and decrease of SIV areas. SPF exposure also obstructed the migration of endothelial cell from caudal hematopoietic tissue in zebrafish embryos. SPF damaged cytoskeleton, caused cell cycle arrest, inhibited the viability and migration of HUVECs. In addition, SPF also inhibited the expression of the VEGF/VEGFR pathway-related genes (hif1a, vegfa, flt1, and kdrl), cell cycle-related genes (ccnd1, ccne1, cdk2, and pcna), and Rho/ROCK pathway-related genes (itgb1, rho, rock, mlc-1, and vim-1). Taken together, SPF may inhibit the proliferation and migration of vascular endothelial cells through disturbing cytoskeleton via the Rho/ ROCK pathway, resulting in vascular malformation. Our study contributes to potential insight into the mechanism of SPF toxicity in angiocardiopathy.

Spiromesifen conferred abnormal development in zebrafish embryos by inducing embryonic cytotoxicity via causing oxidative stress.

Spiromesifen (SPF) is widely used in agriculture to protect against herbivorous mites, whose residues may be harmful to the environment. However, the toxicity assessment of SPF is insufficient. Here, we investigated the toxicological effects of SPF using zebrafish embryos as an animal model. The results showed that SPF exposure solutions at 10, 20, 30, and 40 µM caused cytotoxicity in zebrafish embryos such as reactive oxygen species (ROS) accumulation, mitochondrial membrane potential decrease, cell division arrest, and apoptosis, which further led to developmental toxicity in zebrafish embryos including delayed hatching, decreased survival rate and spontaneous curling rate, and severe morphological deformities. SPF also induced apoptosis via changes in the expressions of apoptosis-related marker genes, caused immunotoxicity by reducing the number of macrophages and the activity of AKP/ALP and increasing inflammatory factors, and disturbed endogenous antioxidant systems via changes SOD, CAT, and GST activities as well as MDA and GSH contents. Therefore, the potential mechanism that caused embryonic developmental toxicity appeared to be related to the generation of oxidative stress by an elevation in ROS and changes in apoptosis-, immune-, antioxidant-related markers. The antioxidant system and inflammatory response simultaneously participated in and resisted the threat of SPF to prevent tissue damage. Taken together, spiromesifen induced oxidative stress to contribute to developmental toxicity in zebrafish embryos by inducing embryonic cytotoxicity. Our study provides new insight into the toxicity assessment of SPF to non-target organisms.

Microcystin-leucine arginine exhibits adverse effects on human aortic vascular smooth muscle cells in vitro.

Microcystin-leucine arginine (MC-LR) is a kind of toxin produced by cyanobacteria, which can do harm to human and livestock health. MC-LR can easily enter tissues and organs through the blood circulation and accumulate in certain target organs. Vessels are prone to contact with MC-LR during growth and development. Previous study had demonstrated that MC-LR had potential vascular toxicity. However, it is not clear whether MC-LR has adverse effects on vascular smooth muscle cells. In this study, we evaluated the cytotoxicity of MC-LR exposure (0.01, 0.05, 0.1, 0.5, and 1 µM) on human aortic vascular smooth muscle cells (HAVSMCs) in vitro. The data showed that MC-LR exposure inhibited the HAVSMC proliferation and migration, induced HAVSMC apoptosis, cytoskeleton destruction, S-phase arrest, mitochondrial transmembrane potential (MMP) loss, and reactive oxygen species (ROS) production. In addition, MC-LR exposure resulted in the imbalance between oxidants and antioxidants, increased the caspase-3 and caspase-9 activities, and down-regulated the gene expressions (integrin ß1, Rho, ROCK, MLC). Taken together, MC-LR could induce the generation of ROS in HAVSMCs, leading to apoptosis by the mitochondrial signaling pathway. MC-LR could also induce cytoskeletal disruption by integrin-mediated FAK/ROCK signaling pathway, leading to cell cycle arrest and the inhibition of HAVSMCs proliferation and migration. The current findings facilitate an understanding of the mechanism of MC-LR toxicity involved in angiocardiopathy.

Adverse effects of SYP-3343 on zebrafish development via ROS-mediated mitochondrial dysfunction.

As a newly-invented and highly-efficiency strobilurin fungicide, pyraoxystrobin (SYP-3343) has been recognized as a highly poisonous toxin for a variety of aquatic organisms. Nevertheless, the developmental toxicity and potential mechanism of SYP-3343 have not been well-documented. The results showed that SYP-3343 was relatively stable and maintained within the range of 20 % in 24 h, and the LC50 value to embryos at 72 hpf was 17.13 µg/L. The zebrafish embryotoxicity induced by 1, 2, 4, and 8 µg/L SYP-3343 is demonstrated by repressive embryo incubation, enhancive mortality rate, abnormal heart rate, malformed morphological characteristic, and impaired spontaneous coiling, indicating SYP-3343 mostly exerted its toxicity in a dose- and time-dependent manner. Besides SYP-3343 was critically involved in regulating cell cycle, mitochondrial membrane potential, and reactive oxygen species production as well as zebrafish primary cells apoptosis, which can be mitigated using antioxidant N-acetyl-L-cysteine. A significant change occurred in total protein content, the biochemical indices, and antioxidant capacities owing to SYP-3343 exposure. Additionally, SYP-3343 altered the mRNA levels of heart development-, mitochondrial function-, and apoptosis-related genes in zebrafish embryos. These results indicated that SYP-3343 induced apoptosis accompanying reactive oxygen species-initiated mitochondrial dysfunction in zebrafish embryos.

Host-Induced Gene Silencing of a G Protein α Subunit Gene CsGpa1 Involved in Pathogen Appressoria Formation and Virulence Improves Tobacco Resistance to Ciboria shiraiana.

Hypertrophy sorosis scleroteniosis caused by Ciboria shiraiana is the most devastating disease of mulberry fruit. However, few mulberry lines show any resistance to C. shiraiana. An increasing amount of research has shown that host-induced gene silencing (HIGS) is an effective strategy for enhancing plant tolerance to pathogens by silencing genes required for their pathogenicity. In this study, two G protein α subunit genes, CsGPA1 and CsGPA2, were identified from C. shiraiana. Silencing CsGPA1 and CsGPA2 had no effect on hyphal growth but reduced the number of sclerotia and increased the single sclerotium weight. Moreover, silencing CsGpa1 resulted in increased fungal resistance to osmotic and oxidative stresses. Compared with wild-type and empty vector strains, the number of appressoria was clearly lower in CsGPA1-silenced strains. Importantly, infection assays revealed that the virulence of CsGPA1-silenced strains was significantly reduced, which was accompanied by formation of fewer appressoria and decreased expression of several cAMP/PKA- or mitogen-activated protein-kinase-related genes. Additionally, transgenic Nicotiana benthamiana expressing double-stranded RNA targeted to CsGpa1 through the HIGS method significantly improved resistance to C. shiraiana. Our results indicate that CsGpa1 is an important regulator in appressoria formation and the pathogenicity of C. shiraiana. CsGpa1 is an efficient target to improve tolerance to C. shiraiana using HIGS technology.

Cylindrospermopsin impairs vascular smooth muscle cells by P53-mediated apoptosis due to ROS overproduction.

Cylindrospermopsin (CYN) is a toxic secondary metabolite from cyanobacteria that can cause cardiovascular disease. However, the study of CYN-induced cardiovascular toxicity in vitro is very limited and the mechanism is remain to be clarified. Vascular smooth muscle cells (VMSCs) have an important function in maintaining the structural and functional integrity of the aortic wall, and are an important in vitro model for cardiovascular research. Thus, the effects of CYN exposure (2, 20, 200, and 2000 nM) on VMSCs were analyzed. In vitro study, results showed that CYN exposure decreased VMSCs viability, inhibited VMSCs migration, induced DNA damage, destroyed cytoskeleton, changed cell morphology, promoted VMSCs apoptosis, and increased intracellular reactive oxygen species (ROS) levels. In addition, CYN could induce the activities of SOD, CAT and GPX, and promote the expressions of SOD1, CAT, GPx1, p53 and Bax genes and inhibit the expression of Bcl-2 gene, leading to a higher ratio of Bax/Bcl-2. Taken together, CYN may induce ROS overproduction, leading to increased p53 expression and ultimately promoting VSMC apoptosis. Therefore, the present study demonstrates that CYN could impair VMSCs, leading to vascular developmental defects and angiocardiopathy.

Microcystin-leucine arginine blocks vasculogenesis and angiogenesis through impairing cytoskeleton and impeding endothelial cell migration by downregulating integrin-mediated Rho/ROCK signaling pathway.

The main characteristic of eutrophication is cyanobacteria harmful algae blooms. Microcystin-leucine arginine (MC-LR) is considered to be the most toxic and most commonly secondary metabolite produced by cyanobacteria. It has been reported that MC-LR had potential vascular toxicity. However, the mechanism that MC-LR-induced vascular toxicity is very limited and remains to be clarified. The aim of this study was to evaluate the toxic hazard toward the vasculogenesis and angiogenesis of MC-LR. Its effects on vasculogenesis, sprouting angiogenesis, and endothelial cell tube formation were studied. The study showed that MC-LR exposure blocked vasculogenesis in zebrafish embryos, sprouting angiogenesis from rat aorta, and tube formation of human umbilical vein endothelial cells (HUVECs). In addition, MC-LR exposure also induced the disruption of cytoskeletal structures and markedly inhibited endothelial cell (EC) migration from caudal hematopoietic tissue in zebrafish and HUVEC migration. Western blot analysis showed that MC-LR exposure downregulated the expressions of integrin ß1, FAK, Rho, and ROCK. Combined with these results, MC-LR could induce disruption of cytoskeleton via downregulating integrin-mediated FAK/ROCK signaling pathway, leading to the inhibition of EC migration, which finally blocked vasculogenesis and angiogenesis.

OsLEA1a overexpression enhances tolerance to diverse abiotic stresses by inhibiting cell membrane damage and enhancing ROS scavenging capacity in transgenic rice.

Late embryogenesis abundant (LEA) proteins are involved in diverse abiotic stresses tolerance in many different organisms. Our previous studies have shown that the heterologous expression of OsLEA1a interfered with the resistance of Escherichia coli to abiotic stresses. However, in the present study, based on growth status and physiological indices of rice plant, the overexpression of OsLEA1a in rice conferred increased resistance to abiotic stresses compared with the wild-type (WT) plants. Before applying abiotic stresses, there were no significant differences in physiological indices of rice seedlings. After NaCl, sorbitol, CuSO4 and H2O2 stresses, the transgenic lines had lower relative electrical conductivity, malondialdehyde and lipid peroxidation, greater the contents of proline, soluble sugar and glutathione, and higher the activities of superoxide dismutase, catalase and peroxidase than the WT plants. The results indicate that the OsLEA1a gene is involved in the protective response of plants to various abiotic stresses by inhibiting cell membrane damage and enhancing reactive oxygen species scavenging capacity. It was speculated that post-translational modification causes OsLEA1a functional differences in E. coli and rice. The present study shows that OsLEA1a could be a useful candidate gene for engineering abiotic stress tolerance in cultivated plants.

Comprehensive insights into the occurrence and toxicological issues of nodularins.

The occurrence of cyanobacterial toxins is being increasingly reported. Nodularins (NODs) are one of the cyanotoxins group mainly produced by Nodularia spumigena throughout the world. NODs may exert adverse effects on animal and human health, and NOD-R variant is the most widely investigated. However, research focused on them is still limited. In order to understand the realistic risk well, the aim of this review is to compile the available information in the scientific literature regarding NODs, including their sources, distribution, structural characteristics, physicochemical properties, biosynthesis and degradation, adverse effects in vitro and vivo, and toxicokinetics. More data is urgently needed to integrate the cumulative or synergistic effects of NODs on different species and various cells to better understand, anticipate and aggressively manage their potential toxicity after both short- and long-term exposure in ecosystem, and to minimize or prevent the adverse effects on human health, environment and the economy.

Effect of acute exposure of saxitoxin on development of zebrafish embryos (Danio rerio).

As a type of cyanobacterial toxins, saxitoxin (STX) is receiving great interest due to its increasing presence in waterbodies. However, the underlying mechanism of STX-induced adverse effect is poorly understood. Here, we examined the developmental toxicity and molecular mechanism induced by STX using zebrafish embryos as an animal model. The embryonic toxicity induced by STX was demonstrated by inhibition of embryo hatching, increase in mortality rate, abnormal heart rate, abnormalities in embryo morphology as well as defects in angiogenesis and common cardinal vein remodeling. STX induced embryonic DNA damage and cell apoptosis, which would be alleviated by antioxidant N-acetyl-L-cysteine. Additionally, STX significantly increased reactive oxygen species level, catalase activity and malondialdehyde content and decreased the activity of superoxide dismutase and glutathione content. STX also promoted the expression of vascular development-related genes DLL4 and VEGFC, and inhibited VEGFA expression. Furthermore, STX altered the transcriptional regulation of apoptosis-related genes (BAX, BCL-2, P53 and CASPASE 3). Taken together, STX induced adverse effect on development of zebrafish embryos, which might be associated with oxidative stress-induced apoptosis.

Nodularin induced oxidative stress contributes to developmental toxicity in zebrafish embryos.

Nodularin (NOD) is a kind of cyanobacterial toxins. It is of concern due to elicit severe genotoxicity in humans and animals. The comprehensive evaluation of NOD-induced adverse effects in living organisms is urgently needed. This study is aimed to report the developmental toxicity and molecular mechanism using zebrafish embryos exposed to NOD. The embryonic toxicity induced by NOD is demonstrated by inhibition of embryo hatching, increase in mortality rate, abnormal heart rate, embryonic malformation as well as defects in angiogenesis and common cardinal vein remodeling. NOD triggered a decreased rate of angiogenesis through inhibiting endothelial cells migration. NOD induced embryonic cell apoptosis and DNA damage, which can be alleviated by antioxidant N-acetyl-L-cysteine. NOD significantly caused oxidative damage as indicated by changes in reactive oxygen species, superoxide dismutase, catalase, glutathione and malondialdehyde. NOD also altered the expression of vascular development-genes (DLL4, CDH5, VEGFA, VEGFC) and apoptosis-related genes (BAX, BCL-2, P53, CASPASE 3). Taken together, NOD induced adverse effect on zebrafish embryos development, which may be associated with oxidative stress and apoptosis through the activation of P53-BAX/BCL-2-CASPASE 3-mediated pathway.

Cylindrospermopsin induces abnormal vascular development through impairing cytoskeleton and promoting vascular endothelial cell apoptosis by the Rho/ROCK signaling pathway.

Cylindrospermopsin (CYN) is a widely distributed cyanobacterial toxin in water bodies and is considered to pose growing threats to human and environmental health. Although its potential toxicity has been reported, its effects on the vascular system are poorly understood. In this study, we examined the toxic effects of CYN on vascular development and the possible mechanism of vascular toxicity induced by CYN using zebrafish embryos and human umbilical vein endothelial cells (HUVECs). CYN exposure induced abnormal vascular development and led to an increase in the growth of common cardinal vein (CCV), in which CCV remodeling was delayed as reflected by the larger CCV area and wider ventral diameter. CYN decreased HUVECs viability, inhibited HUVECs migration, promoted HUVECs apoptosis, destroyed cytoskeleton, and increased intracellular ROS levels. Additionally, CYN could promote the expression of Bax, Bcl-2, and MLC-1 and inhibit the expression of ITGB1, Rho, ROCK, and VIM-1. Taken together, CYN may induce cytoskeleton damage and promote vascular endothelial cell apoptosis by the Rho/ROCK signaling pathway, leading to abnormal vascular development. The current results provide potential insight into the mechanism of CYN toxicity in angiocardiopathy and are beneficial for understanding the environmental risks of CYN for aquatic organisms and human health.

Adverse effect of cylindrospermopsin on embryonic development in zebrafish (Danio rerio).

Eutrophication of freshwater bodies increases the occurrence of toxic cyanobacterial blooms. The cyanobacterial toxin cylindrospermopsin (CYN) is receiving great interest due to its increasing presence in waterbodies. However, the toxic effects of CYN on zebrafish development are poorly understood, especially the toxicological mechanism, which is still unclear. In this study, we examined the adverse effects of CYN on embryonic development in zebrafish. CYN (2-2000 nM) exposure decreased embryos survival rate, hatching rate, body length and eye size in a concentration-dependent manner and caused abnormalities in embryo morphology, including pericardial edema, spinal curvature, tail deformity, uninflated swim bladder, cardiac and vascular defects. CYN at concentrations of 20 nM or higher significantly increased ROS level and promoted cell apoptosis in zebrafish embryos. To preliminarily elucidate the potential mechanism of zebrafish developmental toxicity caused by CYN, we examined the expression of oxidative stress- and apoptotic-related genes. CYN could promote the expression of oxidative stress-related genes (SOD1, CAT and GPx1) and induce changes in transcriptional levels of apoptotic-related genes (p53, Bax and Bcl-2). Taken together, CYN induced adverse effects on zebrafish embryos development, which may associate with oxidative stress and apoptosis. These outcomes will advance our understanding of CYN toxicity, environmental problems and health hazards caused by climate changes and eutrophication.

Systematical evolution on a Zn-Mg alloy potentially developed for biodegradable cardiovascular stents.

To reduce the long-term side effects of permanent metallic stents, a new generation of cardiovascular stents called "biodegradable stents" is being extensively developed. Zinc has been considered as a promising candidate material for biodegradable cardiovascular stents due to its excellent biocompatibility and appropriate biodegradability. However, weak mechanical properties limit its further clinic application. In this study, hot extruded pure Zn and Zn-0.02 Mg alloy were prepared. Compared with pure Zn, Zn-0.02 Mg alloy showed more homogeneous microstructure, much smaller grain size and higher mechanical strength. Zn-0.02 Mg alloy presented uniform corrosion morphologies during the immersion process, and its corrosion rates was higher than that of pure Zn. Hemocompatibility results showed that the Zn-based alloy had extremely low hemolysis rate (0.74 ± 0.15%) and strong inhibitory effect on blood coagulation, platelet adhesion and aggregation. Zn-0.02 Mg alloy also exhibited excellent cytocompatibility. Its extracts could significantly promote the proliferation of endothelial cells. Moreover, the antibacterial activities of the Zn-based alloy were demonstrated by spread plate assay, live/dead viability assay and bacterial morphology observation. These results indicate that the extruded Zn-0.02 Mg alloy has a potential in biodegradable cardiovascular stents.

Overexpression of OsLea14-A improves the tolerance of rice and increases Hg accumulation under diverse stresses.

The group 5 LEA (late embryogenesis abundant) proteins are an atypical LEA protein group, which is associated with resistance to multiple stresses. In this study, OsLea14-A gene was isolated from Oryza sativa L., which encodes a 5C LEA protein with 151 amino acids. The qPCR analysis showed that OsLea14-A expressed in all tissues and organs at all times. The expression of OsLea14-A in the panicles of plumping stage were dramatically increased. The heterologous expression of OsLea14-A in Escherichia coli improved its growth performance under salinity, desiccation, high temperature, and freeze-thaw stresses. The purified OsLea14-A protein can protect LDH activity from freeze-thaw-, heat-, and desiccation-induced inactivation. The overexpression of OsLea14-A in rice improved tolerance to dehydration, high salinity, CuSO4, and HgCl2, but excluding K2Cr2O7. The analysis of metal contents showed that the accumulation of OsLea14-A protein in transgenic rice could increase the accumulation of Hg, but could not increase the accumulation of Na, Cr, and Cu after HgCl2, NaCl, K2Cr2O7, and CuSO4 treatment, respectively. These results suggested that OsLea14-A conferred multiple stress tolerance and Hg accumulation, which made it a possible gene in genetic improvement for plants to acclimatize itself to multiple stresses and remediate Hg-contaminated soil.

Microcystin-LR induces angiodysplasia and vascular dysfunction through promoting cell apoptosis by the mitochondrial signaling pathway.

The harmful algal blooms are becoming increasingly problematic in the regions that drinking water production depends on surface waters. With a global occurrence, microcystins are toxic peptides produced by multiple cyanobacterial genera in the harmful algal blooms. In this study, we examined the effects of microcystin-LR (MC-LR), a representative toxin of the microcystin family, on vascular development in zebrafish and the apoptosis of human umbilical vein endothelial cells (HUVECs). In zebrafish larvae, MC-LR induced angiodysplasia, damaged vascular structures and reduced lumen size at 0.1 µM and 1 µM, leading to the decrease of the blood flow area in the blood vessels and brain hemorrhage, which showed that MC-LR could dose-dependently inhibit vascular development and cause vascular dysfunction. In MC-LR treated HUVECs, the proportion of early apoptosis and late apoptosis cells increased in a concentration-dependent manner. Different concentrations of MC-LR could also activate caspase 3/9 in HUVECs, increase the level of mitochondrial ROS and reduce mitochondrial membrane potential. Additionally, MC-LR could promote the expression of p53 and inhibit the expression of PCNA. The findings showed that MC-LR could promote apoptosis of HUVECs through the mitochondrial signaling pathway. Combined with these results, MC-LR may promote vascular endothelial cell apoptosis through mitochondrial signaling pathway, leading to angiodysplasia and vascular dysfunction.