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1.
Expert Rev Pharmacoecon Outcomes Res ; 24(2): 285-292, 2024 Feb.
Article in English | MEDLINE | ID: mdl-37855081

ABSTRACT

BACKGROUND: The aim of the current analysis was to evaluate the cost-effectiveness of toripalimab plus chemotherapy compared with chemotherapy alone as the first-line option for patients with advanced esophageal squamous cell carcinoma (ESCC) from the perspective of Chinese health-care system. METHODS: A partitioned survival model was conducted to track 3-week patients' transition and evaluate the health and economic outcomes in 10-year horizon of the two competing first-line treatment among toripalimab plus chemotherapy and chemotherapy alone. The survival data were gathered from the JUPITER-06 trial, and cost and utility values were obtained from the local charges and published studies. Total costs, life-years, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio (ICER) were the model outcomes. Sensitivity and subgroup analyses were conducted. RESULTS: Treatment with toripalimab plus chemotherapy yields marginal cost of $8,639.74 and additional 0.65 QALYs, resulting in an ICER of $13,280.97 per additional QALY gained, which was lower than the willingness-to-pay (WTP) threshold of $38,224 in China. Sensitivity and subgroup analyses confirmed the robustness of the model outcomes. CONCLUSIONS: Toripalimab plus chemotherapy was likely to be the cost-effective first-line option for patients with advanced ESCC compared with chemotherapy alone with the WTP threshold of $38,224 per additional QALY gained from the perspective of the Chinese health-care system.


Subject(s)
Antibodies, Monoclonal, Humanized , Esophageal Neoplasms , Esophageal Squamous Cell Carcinoma , Humans , Esophageal Squamous Cell Carcinoma/drug therapy , Cost-Effectiveness Analysis , Esophageal Neoplasms/drug therapy , Cost-Benefit Analysis , Antineoplastic Combined Chemotherapy Protocols
2.
Article in English | MEDLINE | ID: mdl-37936507

ABSTRACT

OBJECTIVE: The aim of the current study was to evaluate the cost-effectiveness of serplulimab plus chemotherapy compared chemotherapy alone as first-line strategy for patients with ES-SCLC in China. METHODS: A decision-analytic model that based on the Chinese health-care system perspective was conducted to evaluate the economic benefits for the two competing first-line treatment. The clinical survival and safety data were obtained from the ASTRUM-005 trial, cost and utility values were gathered from the local charges and previously published study. Both cost and utility values were discounted at an annual rate of 5%. Sensitivity analyses and subgroup analyses were performed to examine the robustness of the model results. RESULTS: Serplulimab plus chemotherapy could bring additional 0.25 QALYs with the marginal cost of $37,569.32, resulting in an ICER of $147,908.74 per additional QALY gained. Sensitivity analyses confirmed that model results were robust. Subgroup analyses revealed that adding serplulimab to first-line chemotherapy were unlikely to be the cost-effective option for all subgroup patients. CONCLUSIONS: Serplulimab plus chemotherapy was unlikely to be the cost-effective first-line strategy compared with chemotherapy alone for patients with ES-SCLC in China. Reduced the price of serplulimab could increase its cost-effective.

3.
BMC Pharmacol Toxicol ; 23(1): 24, 2022 04 15.
Article in English | MEDLINE | ID: mdl-35428330

ABSTRACT

BACKGROUND: Inflammation plays a major role in the pulmonary artery hypertension (PAH) and the acute lung injury (ALI) diseases. The common feature of these complications is the dysfunction of pulmonary microvascular endothelial cells (PMVECs). Fasudil, the only Rho kinase (ROCK) inhibitor used in clinic, has been proved to be the most promising new drug for the treatment of PAH, with some anti-inflammatory activity. Therefore, in the present study, the effect of fasudil on lipopolysaccharide (LPS)-induced inflammatory injury in rat PMVECs was investigated. METHODS: LPS was used to make inflammatory injury model of rat PMVECs. Thereafter, the mRNA and protein expression of pro-inflammatory factors was evaluated by reverse transcription-polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) assay respectively. Intracellular reactive oxygen species (ROS) levels were measured by the confocal laser scanning system. The activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and the content of malondialdehyde (MDA) were determined by using commercial kits according to the manufacturer's instructions. Western blot assay was used to detect the protein expression of nuclear factor kappa B (NF-κB) p65. RESULTS: Fasudil effectively prevented inflammatory injury induced by LPS, which is manifested by the decrease of pro-inflammatory cytokines interleukin-6 (IL-6) and monocyte chenotactic protein-1 (MCP-1). Meanwhile, fasudil dramatically reduced the levels of ROS and MDA, and also elevated the activities of SOD and GSH-Px. Furthermore, the nuclear translocation of NF-κB p65 induced by LPS was also suppressed by fasudil. Additionally, the ROS scavengers N-Acetylcysteine (N-Ace) was also found to inhibit the nuclear translocation of NF-κB and the mRNA expression of IL-6 and MCP-1 induced by LPS, which suggested that ROS was essential for the nuclear translocation of NF-κB. CONCLUSIONS: The present study revealed that fasudil reduced the expression of inflammatory factors, alleviated the inflammatory and oxidative damage induced by LPS in rat PMVECs via ROS-NF-κB signaling pathway.


Subject(s)
Lipopolysaccharides , NF-kappa B , 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine/analogs & derivatives , Animals , Endothelial Cells , Interleukin-6/genetics , Interleukin-6/metabolism , Lipopolysaccharides/toxicity , NF-kappa B/metabolism , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/therapeutic use , RNA, Messenger/metabolism , Rats , Reactive Oxygen Species/metabolism , Superoxide Dismutase/metabolism , rho-Associated Kinases/metabolism , rho-Associated Kinases/pharmacology
4.
Front Genet ; 13: 1081478, 2022.
Article in English | MEDLINE | ID: mdl-36685868

ABSTRACT

Aim: Osteosarcoma is the most common primary malignant tumor of bone. However, our understanding of the prognostic indicators and the genetic mechanisms of the disease progression are still incomplete. The aim of this study was to identify a long noncoding RNA (lncRNA) risk signature for osteosarcoma survival prediction. Methods: RNA sequencing data and relevant clinical information of osteosarcoma patients were downloaded from the database of Therapeutically Applicable Research to Generate Effective Treatments (TARGET). We analyzed the differentially expressed lncRNAs between deceased and living patients by univariate and multivariate Cox regression analysis to identify a risk signature. We calculated a prognostic risk score for each sample according to this prognosis signature, and divided patients into high-risk and low-risk groups according to the median value of the risk score (0.975). Kaplan-Meier analysis and receiver operating characteristic (ROC) curve statistics were used to evaluate the performance of the signature. Next, we analyzed the signature's potential function through Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and gene-set enrichment analysis (GSEA). Lastly, qRT-PCR was used to validate the expression levels of the four lncRNAs in clinical samples. Results: Twenty-six differentially expressed lncRNAs were identified between deceased and living patients. Four of these lncRNAs (CTB-4E7.1, RP11-553A10.1, RP11-24N18.1, and PVRL3-AS1) were identified as independent prognostic factors, and a risk signature of these four lncRNAs for osteosarcoma survival prediction was constructed. Kaplan-Meier analysis showed that the five-year survival time in high-risk and low-risk groups was 33.1% and 82.5%, and the area under the curve (AUC) of the ROC was 0.784, which demonstrated that the prognostic signature was reliable and had the potential to predict the survival of patients with osteosarcoma. The expression level of the four lncRNAs in osteosarcoma tissues and cells was determined by qRT-PCR. Functional enrichment analysis suggested that the signature might be related to osteosarcoma through regulation of the MAPK signaling pathway, the PI3K-Akt signaling pathway, and the extracellular matrix and also provided new insights into the study of osteosarcoma, including the role of papillomavirus infection, olfactory receptor activity, and olfactory transduction in osteosarcoma. Conclusion: We constructed a novel lncRNA risk signature that served as an independent biomarker for predicting the prognosis of osteosarcoma patients.

5.
Plant Cell Rep ; 40(10): 1971-1987, 2021 Oct.
Article in English | MEDLINE | ID: mdl-34392380

ABSTRACT

KEY MESSAGE: PeTCP10 can be induced by salt stresses and play important regulation roles in salt stresses response in transgenic Arabidopsis. Salt stress is one of the major adverse environmental factors that affect normal plant development and growth. PeTCP10, a Class I TCP member, was markedly expressed in moso bamboo mature leaf, root and stem under normal conditions and also induced by salt stress. Overexpressed PeTCP10 was found to enhance salt tolerance of transgenic Arabidopsis at the vegetative growth stage. It was also found capable to increase relative water content, while decreasing relative electrolyte leakage and Na+ accumulation of transgenic Arabidopsis versus wild-type (WT) plants at high-salt conditions. In addition, it improved antioxidant capacity of transgenic Arabidopsis plants by promoting catalase activity and enhanced their H2O2 tolerance. In contrast to WT plants, transcriptome analysis demonstrated that multiple genes related to abscisic acid, salt and H2O2 response were induced after NaCl treatment in transgenic plants. Meanwhile, overexpressed PeTCP10 improved the tolerance of abscisic acid. Moreover, luciferase reporter assay results showed that PeTCP10 is able to directly activate the expression of BT2 in transgenic plants. In contrary, the germination rates of transgenic plants were significantly lower than those of WT plants under high-NaCl conditions. Both primary root length and survival rate at the seedling stage are also found lower in transgenic plants than in WT plants. It is concluded that overexpressed PeTCP10 enhances salt stress tolerance of transgenic plants at the vegetative growth stage, and it also improves salt sensitiveness in both germination and seedling stages. These research results will contribute to further understand the functions of TCPs in abiotic stress response.


Subject(s)
Arabidopsis/physiology , Salt Tolerance/genetics , Sasa/genetics , Transcription Factors/genetics , Abscisic Acid/pharmacology , Arabidopsis/drug effects , Arabidopsis/genetics , Chlorophyll/genetics , Chlorophyll/metabolism , Gene Expression Regulation, Plant , Germination/genetics , Malondialdehyde/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plant Roots/genetics , Plants, Genetically Modified , Potassium/metabolism , Seedlings/genetics , Seeds/genetics , Sodium/metabolism , Transcription Factors/metabolism , Two-Hybrid System Techniques
6.
Cell Death Dis ; 12(5): 487, 2021 05 13.
Article in English | MEDLINE | ID: mdl-33986259

ABSTRACT

Myocarditis (MC) is a common, potentially life-threatening inflammatory disease of the myocardium. A growing body of evidence has shown that mitogen-activated protein kinase 14 (MAPK14) participates in the pathogenesis of MC. However, the upstream regulators of MAPK14 remain enigmatic. Circular RNAs (circRNAs) have been identified to play vital roles in the pathophysiology of cardiovascular diseases. Nevertheless, the clinical significance, biological function, and regulatory mechanisms of circRNAs in MC remain poorly understood. In this study, we determined a novel circRNA, circACSL1 (ID: hsa_circ_0071542), which was significantly upregulated in the acute phase of MC, and its dynamic change in expression was related to the progression of MC. We used lipopolysaccharide (LPS) to induce the inflammatory responses in the human cardiomyocytes (HCM) line for in vitro and in cellulo experiments. The pro-inflammatory factors (IL-1ß, IL-6, and TNF-α), myocardial injury markers (cTnT, CKMB, and BNP), cell viability, and cell apoptosis were measured to evaluate the extent of myocardial inflammation and myocardial injury level. Functional experiments, including gain-of-function and loss-of-function, were then performed to investigate the pro-inflammatory roles of circACSL1. The results revealed that circACSL1 could aggravate inflammation, myocardial injury, and apoptosis in HCM. Mechanistically, circACSL1 acted as a sponge for miR-8055-binding sites to regulate the downstream target MAPK14 expression. Furthermore, overexpression of miR-8055 rescued the pro-inflammatory effects of circACSL1 on HCM, and the upregulation of MAPK14 induced by circACSL1 was attenuated by miR-8055 overexpression. Knockdown of circACSL1 or overexpression of miR-8055 reduced myocardial inflammation and myocardial injury level and these effects were rescued by overexpression of MAPK14. In summary, our study demonstrated that circACSL1 could aggravate myocardial inflammation and myocardial injury through competitive absorption of miR-8055, thereby upregulating MAPK14 expression. Moreover, circACSL1 may represent a potential novel biomarker for the precise diagnosis of MC and offer a promising therapeutic target for MC treatment.


Subject(s)
Coenzyme A Ligases/genetics , MicroRNAs/genetics , Myocarditis/metabolism , RNA, Circular/metabolism , Adult , Aged , Case-Control Studies , Humans , Middle Aged , Mitogen-Activated Protein Kinase 14/metabolism , Myocarditis/genetics , RNA, Circular/genetics , Up-Regulation
7.
Plant Physiol Biochem ; 164: 205-221, 2021 Jul.
Article in English | MEDLINE | ID: mdl-34004558

ABSTRACT

Plant monovalent cation/proton antiporters (CPAs), types of transmembrane transporters, play important roles in resistance to salt stress. In this study, 37 CPA genes from moso bamboo (Phyllostachys edulis) were identified and characterised. The expression profiles of 10 CPA1 genes (PheNHXs) of moso bamboo were detected by qRT-PCR, which showed that they were specifically expressed in six tissues. In addition, the expression of 10 PheNHXs in leaves and roots changed significantly under 150/200 mM NaCl and 100 µM ABA treatments. In particular, the expression of PheNHX2 in leaves and roots was significantly upregulated under NaCl treatment, thus, we cloned PheNHX2 and analysed its function. Subcellular localisation analysis showed that PheNHX2 was located on the vacuolar membrane. Overexpression of PheNHX2 reduced seed germination and root growth of Arabidopsis thaliana under salt stress, as well as severely affecting cellular Na+ and K+ content, which in turn reduced the salt tolerance of transgenic Arabidopsis. Measurements of physiological indicators, including chlorophyll content, malondialdehyde content, peroxidase and catalase enzyme activities and relative electrical conductivity, all supported this conclusion. Under salt stress, PheNHX2 also inhibited the expression of some stress-related and ion transport-related genes in transgenic Arabidopsis. Overall, these results indicate that overexpression of PheNHX2 reduces the salt tolerance of transgenic Arabidopsis. This investigation establishes a foundation for subsequent functional studies of moso bamboo CPA genes, and it provides a deeper understanding of PheNHX2 regulation in relation to the salt tolerance of moso bamboo.


Subject(s)
Arabidopsis , Antiporters/genetics , Arabidopsis/genetics , Arabidopsis/metabolism , Cations, Monovalent , Gene Expression Regulation, Plant , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/metabolism , Poaceae/genetics , Poaceae/metabolism , Protons
8.
Physiol Plant ; 171(3): 309-327, 2021 Mar.
Article in English | MEDLINE | ID: mdl-32134494

ABSTRACT

In the past few years, many studies have reported that the transcription factor Nuclear Factor Y (NF-Y) gene family plays important roles in embryonic development, photosynthesis, flowering time regulation and stress response, in various plants. Although the NF-Y gene family has been systematically studied in many species, little is known about NF-Y genes in Populus. In this study, the NF-Y gene family in the Populus genome was identified and its structural characteristics were described. Fifty-two NF-Y genes were authenticated in the Populus trichocarpa genome and categorized into three subfamilies (NF-YA/B/C) by phylogenetic analysis. Chromosomal localization of these genes revealed that they were distributed randomly across 17 of the 19 chromosomes. Segmental duplication played a vital role in the amplification of Populus NF-Y gene family. Moreover, microsynteny analysis indicated that, among Populus trichocarpa, Arabidopsis thaliana, Vitis vinifera and Carica papaya, NF-Y duplicated regions were more conserved between Populus trichocarpa and Vitis vinifera. Redundant stress-related cis-elements were also found in the promoters of most 13 NF-YA genes and their expression levels varied widely following drought, salt, ABA and cold treatments. Subcellular localization experiments in tobacco showed that PtNF-YA3 was localized in nucleus and cytomembrane, while PtNF-YA4 was only in the nucleus in tobacco. According to the transcriptional activity experiments, neither of them had transcriptional activity in yeast. In summary, a comprehensive analysis of the Populus NF-Y gene family was performed to establish a theoretical basis for further functional studies on this family.


Subject(s)
Populus , CCAAT-Binding Factor , Gene Expression Profiling , Gene Expression Regulation, Plant/genetics , Multigene Family , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Populus/genetics , Populus/metabolism , Transcription Factors/metabolism
9.
Physiol Plant ; 172(1): 91-105, 2021 May.
Article in English | MEDLINE | ID: mdl-33280114

ABSTRACT

Moso bamboo (Phyllostachys edulis), a high-value bamboo used to produce food (young shoots), building, and industrial goods. To explore key candidate genes regulating signal transduction and metabolic processes during the initiation of stem elongation in moso bamboo, a transcriptome analysis of the shoots during three successive early elongation stages was performed. From cluster and differential expression analyses, 2984 differentially expressed genes (DEGs) were selected for an enrichment analysis. The DEGs were significantly enriched in the plant hormone signal transduction, sugar and starch metabolism, and energy metabolism pathways. Consequently, the DEG expression patterns of these pathways were analyzed, and the plant endogenous hormone and carbon metabolite (including sucrose, total soluble sugar, and starch) contents for each growth stage, of the shoot, were determined. The cytokinin-signaling pathway was continuously active in the three successive elongation stages, in which several cytokinin-signaling genes played indispensable roles. Additionally, many key DEGs regulating sugar, starch metabolism, and energy conversion, which are actively involved in energy production and substrate synthesis during the continuous growth of the shoots, were found. In summary, our study lays a foundation for understanding the mechanisms of moso bamboo growth and provides useful gene resources for breeding through genetic engineering.


Subject(s)
Gene Expression Regulation, Plant , Transcriptome , Gene Expression Profiling , Metabolic Networks and Pathways/genetics , Poaceae/genetics , Signal Transduction/genetics
10.
Plant Cell Rep ; 40(1): 187-204, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33098450

ABSTRACT

KEY MESSAGE: 78 HD-Zip family genes in Phyllostachys edulis were analyzed. Overexpression of Phehdz1 can improve the drought tolerance of transgenic rice and affect its secondary metabolism. Many studies suggested homeodomain-leucine zipper (HD-Zip) transcription factors are important regulators of plant growth and development, signal transduction, and responses to environmental stresses. In this study, 78 moso bamboo (Phyllostachys edulis) HD-Zip genes were investigated and classified into four subfamilies (HD-Zip I-IV). Additionally, Phehdz1 (HD-Zip I gene) was isolated and confirmed to be highly expressed in the roots. A quantitative real-time PCR analysis indicated Phehdz1 expression was significantly induced by drought, high salinity, and abscisic acid (ABA). A transient expression assay proved that Phehdz1 was localized in the nucleus of tobacco cells. Moreover, it could bind to the core region encoded by the H-box sequence (CAATAATTG) in yeast. In response to mannitol treatments, the Phehdz1-overexpressing transgenic rice had a higher germination rate and longer shoots than the wild-type controls. Moreover, Phehdz1-overexpressing rice plants had a higher survival rate as well as higher relative water and proline contents, but a lower malondialdehyde content, than the WT plants after a 30% polyethylene glycol 6000 treatment. Accordingly, the overexpression of Phehdz1 enhances the drought tolerance of transgenic rice. Many of the differentially expressed genes identified by a transcriptome analysis are involved in MAPK signal transduction and the biosynthesis of secondary metabolites. Thus, the overexpression of Phehdz1 enhances the drought stress tolerance of transgenic rice, while also potentially modulating the expression of metabolism-related genes.


Subject(s)
Droughts , Oryza/physiology , Plant Proteins/genetics , Poaceae/genetics , Transcription Factors/genetics , Abscisic Acid/metabolism , Abscisic Acid/pharmacology , DNA, Plant/metabolism , Dehydration/genetics , Gene Expression Regulation, Plant , Germination/drug effects , Mannitol/pharmacology , Multigene Family , Oryza/drug effects , Oryza/genetics , Phylogeny , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/physiology , Salinity , Transcription Factors/metabolism
11.
Front Plant Sci ; 11: 579255, 2020.
Article in English | MEDLINE | ID: mdl-33240298

ABSTRACT

CCCH zinc finger proteins are a class of important zinc-finger transcription factors and have functions in various plant growth and stress responses, but their functions in moso bamboo (Phyllostachys edulis) are unclear. In this current study, we main investigated the structures, phylogenetic relationships, promoter elements and microsynteny of PeC3Hs. In this research, 119 CCCH zinc finger proteins (PeC3H1-119) identified genes in moso bamboo were divided into 13 subfamilies (A-M) based on phylogenetic analysis. Meanwhile, moso bamboo were treated with abscisic acid (ABA), methyl jasmonate (Me-JA) and gibberellic acid (GA) and 12 CCCH genes expression levels were assayed using qRT-PCR. In the three hormone treatments, 12 genes were up-regulated or down-regulated, respectively. In addition, PeC3H74 was localized on the cytomembrane, and it had self-activation activities. Phenotypic and physiological analysis showed that PeC3H74 (PeC3H74-OE) conferred drought tolerance of transgenic Arabidopsis, including H2O2 content, survival rate, electrolyte leakage as well as malondialdehyde content. Additionally, compared with wild-type plants, transgenic Arabidopsis thaliana seedling roots growth developed better under 10 µM ABA; Moreover, the stomatal of over-expressing PeC3H74 in Arabidopsis changed significantly under ABA treatment. The above results suggest that PeC3H74 was quickly screened by bioinformatics, and it may enhanced drought tolerance in plants through the ABA-dependent signaling pathway.

12.
Plant Sci ; 299: 110605, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32900443

ABSTRACT

Drought-induced 19 (Di19) proteins play crucial roles in regulating stress responses, but the exact mechanisms underlying their involvement in moso bamboo are not fully understood. In this study, PheDi19-8 of moso bamboo (Phyllostachys edulis) was isolated and characterized. PheDi19-8 was a nuclear protein and has a high expression under various abiotic stresses, including drought and salt. As revealed by phenotypic and physiological analyses, ectopic overexpression of PheDi19-8 in Arabidopsis and rice enhanced drought tolerance. Under drought stress, the PheDi19-8-overexpressing lines showed smaller stomatal apertures and higher survival rate in comparison to the wild-type plants, as well as the PheDi19-8-overexpressing lines had higher biomass and souble sugar, but lower relative electrolyte leakage and malondialdehyde. Further investigation revealed that PheDi19-8 interacted with PheCDPK22, and their interaction decreased the DNA-binding activity of PheDi19-8. However, overexpression of PheCDPK22 enhanced Arabidopsis sensitivity to drought stress. Moreover, the expression of marker genes, including LEA, RD22, DREB2A and RD29A, was up-regulated in the PheDi19-8-overexpressing lines but down-regulated in the PheCDPK22-overexpressing. Further yeast one-hybrid and EMSA assays indicated that PheDi19-8 directly binds to the promoter of DREB2A. These results provided new insight into the interaction of PheCDPK22 and PheDi19-8 that functions oppositely to regulate drought stress in plants.


Subject(s)
Droughts , Gene Expression Regulation, Plant/physiology , Plant Proteins/genetics , Poaceae/physiology , Arabidopsis/genetics , Arabidopsis/metabolism , Oryza/genetics , Oryza/metabolism , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/metabolism , Poaceae/genetics
13.
Sci Rep ; 9(1): 19407, 2019 Dec 19.
Article in English | MEDLINE | ID: mdl-31857596

ABSTRACT

Perpendicular magnetic anisotropy (PMA) ferromagnetic CoFeB with dual MgO interfaces is an attractive material system for realizing magnetic memory applications that require highly efficient, high speed current-induced magnetic switching. Using this structure, a sub-nanometer CoFeB layer has the potential to simultaneously exhibit efficient, high speed switching in accordance with the conservation of spin angular momentum, and high thermal stability owing to the enhanced interfacial PMA that arises from the two CoFeB-MgO interfaces. However, the difficulty in attaining PMA in ultrathin CoFeB layers has imposed the use of thicker CoFeB layers which are incompatible with high speed requirements. In this work, we succeeded in depositing a functional CoFeB layer as thin as five monolayers between two MgO interfaces using magnetron sputtering. Remarkably, the insertion of Mg within the CoFeB gave rise to an ultrathin CoFeB layer with large anisotropy, high saturation magnetization, and good annealing stability to temperatures upwards of 400 °C. When combined with a low resistance-area product MgO tunnel barrier, ultrathin CoFeB magnetic tunnel junctions (MTJs) demonstrate switching voltages below 500 mV at speeds as fast as 1 ns in 30 nm devices, thus opening a new realm of high speed and highly efficient nonvolatile memory applications.

14.
Front Cell Dev Biol ; 7: 299, 2019.
Article in English | MEDLINE | ID: mdl-31824949

ABSTRACT

Secreted proteins (SPs) play important roles in diverse important biological processes; however, a comprehensive and high-quality list of human SPs is still lacking. Here we identified 6,943 high-confidence human SPs (3,522 of them are novel) based on 330,427 human proteins derived from databases of UniProt, Ensembl, AceView, and RefSeq. Notably, 6,267 of 6,943 (90.3%) SPs have the supporting evidences from a large amount of mass spectrometry (MS) and RNA-seq data. We found that the SPs were broadly expressed in diverse tissues as well as human body fluid, and a significant portion of them exhibited tissue-specific expression. Moreover, 14 cancer-specific SPs that their expression levels were significantly associated with the patients' survival of eight different tumors were identified, which could be potential prognostic biomarkers. Strikingly, 89.21% of 6,943 SPs (2,927 novel SPs) contain known protein domains. Those novel SPs we mainly enriched with the known domains regarding immunity, such as Immunoglobulin V-set and C1-set domain. Specifically, we constructed a user-friendly and freely accessible database, SPRomeDB (www.unimd.org/SPRomeDB), to catalog those SPs. Our comprehensive SP identification and characterization gain insights into human secretome and provide valuable resource for future researches.

15.
PeerJ ; 7: e7510, 2019.
Article in English | MEDLINE | ID: mdl-31579567

ABSTRACT

Growth-regulating factor (GRF), a small plant-specific transcription factor (TF) family, is extensively involved in the regulation of growth and developmental processes. However, the GRF family has not been comprehensively studied in moso bamboo (Phyllostachys edulis), a typical non-timber forest member. Here, 18 GRF genes were identified and characterized from the moso bamboo genome, and they clustered into three subfamilies (A, B and C). PeGRF genes were analyzed to determine their gene structures, conserved motifs and promoter. The non-synonymous/synonymous substitution ratios of paralogous and orthologous were less than 1, indicating that the GRF family mainly experienced purifying selection during evolution. According to the analysis of tissue-specific expression patterns, the participation of moso bamboo GRFs might be required during the formation and development of these five tissues. Moreover, PeGRF proteins might be involved in the regulation of plant development in biological processes. The qRT-PCR analysis demonstrated that PeGRF genes played essential roles in combating hormonal stresses and they might be involved in hormone regulation. PeGRF11, a nuclear localized protein as assessed by a subcellular localization assay, could interact with PeGIF3 in yeast and in planta according to yeast two-hybridization and bimolecular fluorescence complementation assays (BiFC) assays. But PeGRF11, as a TF, had no transcriptional activity in yeast. These results provide useful information for future functional research on the GRF genes in moso bamboo.

16.
BMC Plant Biol ; 19(1): 154, 2019 Apr 25.
Article in English | MEDLINE | ID: mdl-31023225

ABSTRACT

BACKGROUND: Trihelix transcription factors (TTFs) are photoresponsive proteins that have a representative three-helix structure (helix-loop-helix-loop-helix). Members of this gene family have been reported to play roles in many plant processes. RESULTS: In this study, we performed a functional and evolutionary analysis of the TTFs in Moso bamboo (Phyllostachys edulis). A total of 35 genes were identified and grouped into five subfamilies (GT-1, GT-γ, GT-2, SIP1 and SH4) according to their structural properties. Gene structure analysis showed that most genes in the PeTTF family had fewer introns. A unique motif (Motif 16) to the GT-γ subfamily was identified by conserved motif analysis. Promoter analysis revealed various cis-acting elements related to plant growth and development, abiotic and biotic stresses, and phytohormone responses. Data for the 35 Moso bamboo TTF genes were used to generate heat maps, which indicated that these genes were expressed in different tissues or developmental stages. Most of the TTF genes identified here had high expression in leaves and panicles according to the expression profile analysis. The expression levels of the TTF members in young leaves were studied using quantitative real-time PCR to determine their tissue specificity and stress-related expression patterns to help functionally characterize individual members. CONCLUSIONS: The results indicated that members of the TTF gene family may be involved in plant responses to stress conditions. Additionally, PeTTF29 was shown to be located in the nucleus by subcellular localization analysis and to have transcriptional activity in a transcriptional activity assay. Our research provides a comprehensive summary of the PeTTF gene family, including functional and evolutionary perspectives, and provides a basis for functionally characterizing these genes.


Subject(s)
Evolution, Molecular , Poaceae/genetics , Transcription Factors/genetics , Acetates/pharmacology , Arabidopsis/genetics , Cell Nucleus/drug effects , Cell Nucleus/metabolism , Conserved Sequence , Cyclopentanes/pharmacology , Gene Expression Profiling , Gene Expression Regulation, Plant/drug effects , Gene Ontology , Genes, Plant , Nucleotide Motifs , Oryza/genetics , Oxylipins/pharmacology , Phylogeny , Plant Proteins/genetics , Plant Proteins/metabolism , Promoter Regions, Genetic , Transcription Factors/metabolism , Transcriptional Activation/drug effects , Transcriptional Activation/genetics
17.
Plant Cell Physiol ; 60(7): e1-e14, 2019 Jul 01.
Article in English | MEDLINE | ID: mdl-30452736

ABSTRACT

Here, 10 drought-induced 19 (Di19) proteins from Phyllostachys edulis were analyzed and an important stress-related candidate gene (PeDi19-4) was isolated based on analysis of phylogenetic relationships and expression profiles. PeDi19-4 is a nuclear localization protein that can bind the conserved TACA(A/G)T sequence, as determined using enzyme-linked immunosorbent assay (EMSA). PeDi19-4 has no transcriptional activity in yeast but functions as a transcription activator in plants. Overexpression of PeDi19-4 in rice and Arabidopsis thaliana enhanced drought and salt tolerance as determined through phenotypic analysis and the use of stress-associated physiological indicators. PeDi19-4 transgenic plants showed increased sensitivity to ABA during seed germination and early seedling growth. Additionally, transgenic rice accumulated more ABA than wild-type plants under drought and salt stress conditions. Moreover, the stomata of PeDi19-4-overexpressing plants changed significantly with ABA treatment. RNA sequencing revealed that PeDi19-4 regulated the expression of a wide spectrum of stress-/ABA-responsive differentially expressed genes. The stress-responsive genes (OsZFP252 and OsNAC6) and ABA-responsive genes (OsBZ8 and OsbZIP23) were direct targets of PeDi19-4. Our research indicated that PeDi19-4 enhanced drought and salt tolerance in plants via the ABA-dependent signaling pathway.

18.
Database (Oxford) ; 20182018 01 01.
Article in English | MEDLINE | ID: mdl-30339216

ABSTRACT

A gene family is formed by duplication of a single original gene. Poplar trees (genus Populus) are important, principally because of their ecological and economic benefits, and are one of the most widely distributed and adaptable trees in the world. Systematic identification and annotation of gene family members are primary steps in studying the function and evolution of poplar genomes. Here, we describe the construction of the Gene Family Database in Poplar (GFDP), which contains information that systematically describes 6551 genes distributed in 145 gene families. GFDP is designed to present important biological information, such as gene structure, protein length, isoelectric point and functional and evolutionary information, using highly visual displays. Data and graphs are visualized by a web-based interface. Users can browse and download data through all the major browsers. GFDP provides a comprehensive platform with a solid foundation for further study of poplar gene families. GFDP is free available.


Subject(s)
Databases, Genetic , Genes, Plant , Multigene Family , Populus/genetics , Molecular Sequence Annotation
19.
Front Plant Sci ; 9: 1263, 2018.
Article in English | MEDLINE | ID: mdl-30344527

ABSTRACT

TEOSINTE BRANCHED 1, CYCLOIDEA, and PROLIFERATING CELL FACTORS (T), members of a plant-specific gene family, play significant roles during plant growth and development, as well as in response to environmental stress. However, knowledge about this family in moso bamboo (Phyllostachys edulis) is limited. Therefore, in this study, the first genome-wide identification, classification, characterization, and expression pattern analysis of the TCP transcription factor family in moso bamboo was performed. Sixteen TCP members were identified from the moso bamboo genome using a BLASTP algorithm-based method and verified using the Pfam database. Based on a multiple-sequence alignment, the members were divided into two subfamilies, and members of the same family shared highly conserved motif structures. Subcellular localization and transactivation activity analyses of four selected genes revealed that they were nuclear localized and had self-activation activities. Additionally, the expression levels of several PeTCP members were significantly upregulated under abscisic acid, methyl jasmonate, and salicylic acid treatments, indicating that they play crucial plant hormone transduction roles in the processes of plant growth and development, as well as in responses to environmental stresses. Thus, the current study provides previously lacking information on the TCP family in moso bamboo and reveals the potential functions of this gene family in growth and development.

20.
Mol Med Rep ; 18(5): 4468-4476, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30221717

ABSTRACT

Aconitum plants, which have analgesic, diuretic and anti­inflammatory effects, have been widely used to treat various types of disease. However, the apparent toxicity of Aconitum­derived agents, particularly in the cardiovascular system, has largely limited their clinical use. Thus, the present study investigated whether berberine (Ber), an isoquinoline alkaloid, may reduce myocardial injury induced by aconitine (AC) in rats and the underlying mechanisms. Rats (n=40) were randomly divided into four groups: Control, Chuan­wu and Chuan­wu + Ber (8 and 16 mg/kg doses). Electrocardiograms (ECG) of the rats were recorded and serum biomarkers of cardiac function [lactate dehydrogenase (LDH), creatine kinase (CK) and CK­MB] were assayed. Histopathological changes were assessed using myocardial tissue sectioning and hematoxylin and eosin staining. Additionally, the effects of Ber on AC­induced arrhythmias in rats were observed. The changes in ECG following AC perfusion were observed, and the types and onset time of arrhythmias were analyzed. Furthermore, the effects of Ber and AC on papillary muscle action potentials were observed. The results suggested that Ber ameliorated myocardial injury induced by Chuan­wu, which was indicated by reduced arrhythmias and decreased LDH, CK and CK­MB levels in serum. Furthermore, histological damage, including dilation of small veins and congestion, was also markedly attenuated by Ber. In addition, the occurrence of arrhythmias was significantly delayed, and the dosage of AC required to induce arrhythmias was also increased by Ber pretreatment. Additionally, AC­induced changes in action potential amplitude, duration of 30% repolarization and duration of 90% repolarization in the papillary muscle were attenuated by Ber. All of these results indicate that Ber had a preventive effect on acute myocardial injury induced by Chuan­wu and arrhythmias caused by AC, which may be associated with the inhibition of delayed depolarization and triggered activity caused by AC. Thus, combination treatment of Ber with Aconitum plants may be a novel strategy to prevent AC­induced myocardial injury in clinical practice.


Subject(s)
Aconitum/toxicity , Berberine/administration & dosage , Heart Injuries/drug therapy , Myocardium/pathology , Aconitum/chemistry , Animals , Creatine Kinase, MB Form/blood , Electrocardiography , Heart Injuries/blood , Heart Injuries/chemically induced , Heart Injuries/physiopathology , Humans , L-Lactate Dehydrogenase/blood , Plant Extracts/adverse effects , Plant Extracts/chemistry , Plant Extracts/therapeutic use , Rats
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