ABSTRACT
BACKGROUND: Previous epidemiologic investigations have consistently demonstrated a strong association between the ratio of cholesterol to total lipids in medium very-low-density lipoprotein (VLDL) and the occurrence of peptic ulcers (PU). However, the precise causal relationship between these factors remains ambiguous. Consequently, this study aims to elucidate the potential correlation between the ratio of cholesterol to total lipids in medium VLDL and the incidence of peptic ulcer. AIM: To investigate the ratio of cholesterol to total lipids in medium very-low-density lipoprotein (VLDL) association with PU via genetic methods, guiding future clinical research. METHODS: Genome-wide association study (GWAS) datasets for the ratio of cholesterol to total lipids in intermediate VLDL and peptic ulcer were retrieved from the IEU OpenGWAS project (https://gwas.mrcieu.ac.uk). For the forward Mendelian randomization (MR) analysis, 72 single nucleotide polymorphisms (SNPs) were identified as instrumental variables. These SNPs were selected based on their association with the ratio of cholesterol to total lipids in intermediate VLDL, with peptic ulcer as the outcome variable. Conversely, for the inverse MR analysis, no SNPs were identified with peptic ulcer as the exposure variable and the ratio of cholesterol to total lipids in intermediate VLDL as the outcome. All MR analyses utilized inverse variance weighted (IVW) as the primary analytical method. Additionally, weighted median and MR-Egger methods were employed as supplementary analytical approaches to assess causal effects. Egger regression was used as a supplementary method to evaluate potential directional pleiotropy. Heterogeneity and multiplicity tests were conducted using the leave-one-out method to evaluate result stability and mitigate biases associated with multiple testing. RESULTS: The genetically predicted ratio of cholesterol to total lipids in medium VLDL was significantly associated with an elevated risk of peptic ulcer (IVW: OR = 2.557, 95%CI = 1.274-5.132, P = 0.008). However, no causal association of peptic ulcer with the ratio of cholesterol to total lipids in medium VLDL was observed in the inverse Mendelian randomization analysis. CONCLUSION: In conclusion, our study reveals a significant association between the ratio of cholesterol to total lipids in medium VLDL and an elevated risk of peptic ulcers. However, further validation through laboratory investigations and larger-scale studies is warranted to strengthen the evidence and confirm the causal relationship between these factors.
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Phosphate deficiency and drought are significant environmental constraints that impact both the productivity and quality of wheat. The interaction between phosphorus and water facilitates their mutual absorption processes in plants. Under conditions of both phosphorus deficiency and drought stress, we observed a significant upregulation in the expression of wheat MYB-CC transcription factors through the transcriptome analysis. 52 TaMYB-CC genes in wheat were identified and analyzed their evolutionary relationships, structures, and expression patterns. The TaMYB-CC5 gene exhibited specific expression in roots and demonstrated significant upregulation under phosphorus deficiency and drought stress compared to other TaMYB-CC genes. The overexpression of TaMYB-CC5A in Arabidopsis resulted in a significant increase of root length under stress conditions, thereby enhancing tolerance to phosphate starvation and drought stress. The wheat lines with silenced TaMYB-CC5 genes exhibited reduced root length under stress conditions and increased sensitivity to phosphate deficiency and drought stress. In addition, silencing the TaMYB-CC5 genes resulted in altered phosphorus content in leaves but did not lead to a reduction in phosphorus content in roots. Enrichment analysis the co-expression genes of TaMYB-CC5 transcription factors, we found the zinc-induced facilitator-like (ZIFL) genes were prominent associated with TaMYB-CC5 gene. The TaZIFL1, TaZIFL2, and TaZIFL5 genes were verified specifically expressed in roots and regulated by TaMYB-CC5 transcript factor. Our study reveals the pivotal role of the TaMYB-CC5 gene in regulating TaZIFL genes, which is crucial for maintaining normal root growth under phosphorus deficiency and drought stress, thereby enhanced resistance to these abiotic stresses in wheat.
ABSTRACT
BACKGROUND: Autoimmune pancreatitis (AIP) is a rare form of autoimmune-mediated pancreatitis, which is easily misdiagnosed as pancreatic cancer and thus treated surgically. We studied the diagnosis and treatment of a patient with type 1 AIP recently admitted to our hospital, and reviewed the literature to provide a reference for clinical diagnosis of AIP. CASE SUMMARY: The chief complaint was yellowing of the body, eyes and urine for 21 d. The patient's clinical presentation was obstructive jaundice and imaging suggested pancreatic swelling. It was difficult to distinguish between inflammation and tumor. Serum immunoglobulin G4 (IgG4) was markedly elevated. IgG4 is an important serological marker for type 1 AIP. The patient was diagnosed with AIP, IgG4-related cholangitis, acute cholecystitis and hepatic impairment. After applying hormonal therapy, the patient's symptoms improved significantly. At the same time, imaging suggested that pancreatic swelling subsided, and liver function and other biochemical indicators decreased. The treatment was effective. CONCLUSION: In patients with pancreatic swelling, the possibility of AIP should be considered.
ABSTRACT
Adaptation to drought and salt stresses is a fundamental part of plant cell physiology and is of great significance for crop production under environmental stress. Heat shock proteins (HSPs) are molecular chaperones that play a crucial role in folding, assembling, translocating, and degrading proteins. However, their underlying mechanisms and functions in stress tolerance remain elusive. Here, we identified the HSP TaHSP17.4 in wheat by analyzing the heat stress-induced transcriptome. Further analysis showed that TaHSP17.4 was significantly induced under drought, salt, and heat stress treatments. Intriguingly, yeast-two-hybrid analysis showed that TaHSP17.4 interacts with the HSP70/HSP90 organizing protein (HOP) TaHOP, which plays a significant role in linking HSP70 and HSP90. We found that TaHSP17.4- and TaHOP-overexpressing plants have a higher proline content and a lower malondialdehyde content than wild-type plants under stress conditions and display strong tolerance to drought, salt, and heat stress. Additionally, qRT-PCR analysis showed that stress-responsive genes relevant to reactive oxygen species scavenging and abscisic acid signaling pathways were significantly induced in TaHSP17.4- and TaHOP-overexpressing plants under stress conditions. Together, our findings provide insight into HSP functions in wheat and two novel candidate genes for improvement of wheat varieties.
Subject(s)
Plant Proteins , Triticum , Triticum/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Heat-Shock Proteins/genetics , Heat-Shock Proteins/metabolism , Heat-Shock Response , Stress, Physiological/genetics , Plants, Genetically Modified/metabolism , Sodium Chloride/pharmacology , Gene Expression Regulation, Plant , DroughtsABSTRACT
Bacterial wilt, caused by Ralstonia solanacearum, one of the most destructive phytopathogens, leads to significant annual crop yield losses. Type III effectors (T3Es) mainly contribute to the virulence of R. solanacearum, usually by targeting immune-related proteins. Here, we clarified the effect of a novel E3 ubiquitin ligase (NEL) T3E, RipAW, from R. solanacearum on pathogen-associated molecular pattern (PAMP)-triggered immunity (PTI) and further explored its action mechanism. In the susceptible host Arabidopsis thaliana, we monitored the expression of PTI marker genes, flg22-induced ROS burst, and callose deposition in RipAW- and RipAWC177A-transgenic plants. Our results demonstrated that RipAW suppressed host PTI in an NEL-dependent manner. By Split-Luciferase Complementation, Bimolecular Fluorescent Complimentary, and Co-Immunoprecipitation assays, we further showed that RipAW associated with three crucial components of the immune receptor complex, namely FLS2, XLG2, and BIK1. Furthermore, RipAW elevated the ubiquitination levels of FLS2, XLG2, and BIK1, accelerating their degradation via the 26S proteasome pathway. Additionally, co-expression of FLS2, XLG2, or BIK1 with RipAW partially but significantly restored the RipAW-suppressed ROS burst, confirming the involvement of the immune receptor complex in RipAW-regulated PTI. Overall, our results indicate that RipAW impairs host PTI by disrupting the immune receptor complex. Our findings provide new insights into the virulence mechanism of R. solanacearum.
Subject(s)
Arabidopsis Proteins , Arabidopsis , Ralstonia solanacearum , Antigen-Antibody Complex , Innate Immunity Recognition , Reactive Oxygen Species , Immunoprecipitation , Receptors, Immunologic , Protein Serine-Threonine Kinases , Arabidopsis Proteins/geneticsABSTRACT
Background: Yiqi Huoxue Decoction (YQHXD) is a traditional Chinese medicine that promotes blood circulation, removes blood stasis, facilitates diuresis, and alleviates edema. It is composed of 10 herbal medicines and has extensive application in treating nephrotic syndrome (NS). However, the active components and the potential mechanism of YQHXD for treating NS remain unclear. Methods: We set up a sensitive and rapid method based on Ultra-High Performance Liquid Chromatograph-Mass (UPLC-MS) to identify the compounds in YQHXD and constituents absorbed into the blood. Disease genes were collected through GeneCards, DisGeNET, and OMIM database. Genes of compounds absorbed into blood were predicted by the TCMSP database. We constructed Disease-Drug-Ingredient-Gene (DDIG) network using Cytoscape, established a Protein-protein interaction (PPI) network using String, Gene biological process (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was performed using DAVID. Cellular experiments were performed to validate the results of network pharmacology. Result: A total of 233 compounds in YQHXD and 50 constituents absorbed into the blood of rats were identified. The 36 core targets in the PPI network were clustered in the phosphatidylinositol 3 kinase-RAC serine/threonine-protein kinase (PI3K-AKT) and nuclear factor kappa-B (NF-κB) signaling pathways. Luteolin, Wogonin, Formononetin, and Calycosin were top-ranking components as potentially active compounds. Conclusion: The results of our studies show that YQHXD is able to enhance renal function, alleviate podocyte injury, and improve adriamycin nephrotic syndrome.
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Haploid induction is one of the main techniques for breeding new varieties of major crops, and its key steps are improving the haploid induction rate and simplifying the induction procedure. With the development and innovation of plant haploid induction technologies, haploid breeding has been widely used in varietal improvement of important crops, showing the advantages of rapid homozygosity of heterozygous genes, shortening breeding period, and improving breeding efficiency. The combination of haploid breeding with crossing breeding, mutation breeding, reverse breeding, and molecular marker-assisted selection will greatly improve the effectiveness of crop breeding. Haploids and doubled haploids have demonstrated their usefulness in production of genetic populations, characterization of gene functions, and transgenic and cytological studies in plants. In this review, we summarize the progress of haploid induction technologies in view of various haploid induction techniques and applications of haploids and double haploids. In particular, the advances on the haploid induction in several major crops by genome editing were briefly described. Finally, we discuss current issues and future perspectives in this field, so as to promote the application of the haploid induction techniques, especially the techniques of creating haploid inducer lines by genome editing in crop breeding.
Subject(s)
Crops, Agricultural/genetics , Haploidy , Plant Breeding/methods , Gene EditingABSTRACT
YABBY family is a plant specific transcription factor family, with the typical N-terminal C2C2 type zinc finger domain and the C-terminal YABBY conservative structure domain, which plays important biological roles in plant growth, development and morphogenesis. In this study, a total of 17 YABBY genes were identified in the soybean genome. The results of this research showed that 17 soybean YABBY genes were located on 11 chromosomes. Analysis of putative cis-acting elements showed that soybean YABBY genes contained lots of MYB and MYC elements. Quantitative Real-time PCR (qRT-PCR) showed that the expressions of GmYABBY3, GmYABBY10 and GmYABBY16 were more highly sensitive in drought, NaCl and ABA stresses. And the transient expression in Arabidopsis protoplasts showed that GmYABBY3 protein distributed uniformly the whole cells, while GmYABBY10 protein was mainly localized in the membranes and cytoplasm and GmYABBY16 protein was localized the nucleus and membranes. To further identify the function of GmYABBY10, we obtained the transgenic Arabidopsis overexpression GmYABBY10. Based on germination and seedling root arrays in transgenic Arabidopsis, we found that the rates of wild type seeds was a litter higher than that of GmYABBY10 transgenic seeds under both PEG and NaCl treatment. While the root length and root surface of wild type seedlings were bigger than those of GmYABBY10 transgenic seedlings. When seedlings were grown in soil, the survival rates of wild type were higher than those of transgenic plants under both PEG and NaCl treatment, which indicated that GmYABBY10 may be a negatively regulator in plant resistances to drought and salt stresses. This study provided valuable information regarding the classification and functions of YABBY genes in soybean.
Subject(s)
Genome-Wide Association Study , Glycine max , Osmotic Pressure , Plant Proteins , Arabidopsis/genetics , Arabidopsis/growth & development , Dehydration/genetics , Dehydration/metabolism , Plant Proteins/genetics , Plant Proteins/metabolism , Plants, Genetically Modified/genetics , Plants, Genetically Modified/growth & development , Protoplasts/metabolism , Glycine max/genetics , Glycine max/metabolismABSTRACT
High-resolution and wide-swath (HRWS) synthetic aperture radar (SAR) is an essential tool for modern remote sensing. To effectively deal with the contradiction problem between high-resolution and low pulse repetition frequency and obtain an HRWS SAR image, a multi-channel in azimuth SAR system has been adopted in the literature. However, the performance of the Doppler ambiguity suppression via digital beam forming processing suffers the losses from the channel mismatch. In this paper, a robust channel-calibration algorithm based on weighted minimum entropy is proposed for the multi-channel in azimuth HRWS SAR imaging. The proposed algorithm is implemented by a two-step process. 1) The timing uncertainty in each channel and most of the range-invariant channel mismatches in amplitude and phase have been corrected in the pre-processing of the coarse-compensation. 2) After the pre-processing, there is only residual range-dependent channel mismatch in phase. Then, the retrieval of the range-dependent channel mismatch in phase is achieved by a local maximum-likelihood weighted minimum entropy algorithm. The simulated multi-channel in azimuth HRWS SAR data experiment is adopted to evaluate the performance of the proposed algorithm. Then, some real measured airborne multi-channel in azimuth HRWS Scan-SAR data is used to demonstrate the effectiveness of the proposed approach.
ABSTRACT
OBJECTIVE: To explore a method for the treatment of the skin defects at the distal phalanges of 2-5th fingers. METHODS: The island flap at the dorsum of the middle phalange was designed with the pedicle of dorsal branches from the digital proper artery. When the flap was used to repair defect at finger pulp, the dorsal branch of the digital proper nerve in the flap was kept to be anastomosed to the digital proper nerve at the recipient finger. From Feb. 2005 to May. 2010, 54 cases with skin defects at the distal phalanges of 61 fingers were treated with the flap, including 35 defects at finger pulp and 26 defects at finger tip. RESULTS: The maximum size of defects and flaps was 2.2 cm x 2.5 cm and 2.4 cm x 2.7 cm, respectively. 61 flaps survived completely. Blister was happened in 3 flaps 2 days after operation, which healed spontaneously without necrosis. 54 cases were followed up for 5 to 22 months (average, 11 months). The flaps had good texture and color match with normal sensation (grade S4). The 2-point discrimination distance was 6-9 mm. The interphalangeal joint had normal movement. CONCLUSIONS: The island flap at the dorsum of the middle phalange is an ideal method for the skin defect at the distal phalange of finger.
Subject(s)
Arteries , Fingers/blood supply , Surgical Flaps/blood supply , Adolescent , Adult , Aged , Female , Fingers/surgery , Humans , Male , Middle Aged , Plastic Surgery Procedures/methods , Skin Transplantation/methods , Young AdultABSTRACT
OBJECTIVE: To study the therapeutic effect of collapsed and comminuted distal radius fracture. METHODS: Twenty-six patients with collapsed and comminuted distal radius fracture were hospitalized from July 1998 to June 2003. All fractures were treated by the methods of open reduction, sustained bone grafting and passing joint external fixator to restore the anatomic shape of distal radius. RESULTS: All 26 cases were followed up, and the results showed that the fractures have been united radiographically. The joint surfaces were intact and there was no length discrepancy occurred in patient's radius. The average volar tilt was 6 to 15 degrees and the average ulnar tilt was 18 to 25 degrees. According to the Dieust criterion, 19 cases were rated as excellent and 7 as good. CONCLUSIONS: The method that applying passing joint external fixator and bone grafting for the treatment of collapsed and comminuted distal radius fracture could maintain the stability of fracture and restore the length of radius and the intact of joint surface.
Subject(s)
Bone Transplantation/methods , External Fixators , Fracture Fixation/instrumentation , Fractures, Comminuted/surgery , Radius Fractures/surgery , Adult , Aged , Cohort Studies , Combined Modality Therapy , Female , Follow-Up Studies , Fracture Fixation/methods , Fracture Healing/physiology , Fractures, Comminuted/diagnostic imaging , Humans , Injury Severity Score , Male , Middle Aged , Radiography , Radius Fractures/diagnostic imaging , Recovery of Function , Retrospective Studies , Risk AssessmentABSTRACT
Mesenchymal stem cells (MSCs), in addition to their multilineage differentiation, have a direct immunosuppressive effect on T-cell proliferation in vitro. However, it is unclear whether they also modulate the immune system by acting on the very first step. In this investigation, we addressed the effects of human MSCs on the differentiation, maturation, and function of dendritic cells (DCs) derived from CD14+ monocytes in vitro. Upon induction with granulocyte-macrophage colony-stimulating factor (GM-CSF) plus interleukin-4 (IL-4), MSC coculture could strongly inhibit the initial differentiation of monocytes to DCs, but this effect is reversible. In particular, such suppression could be recapitulated with no intercellular contact at a higher MSC/monocyte ratio (1:10). Furthermore, mature DCs treated with MSCs were significantly reduced in the expression of CD83, suggesting their skew to immature status. Meanwhile, decreased expression of presentation molecules (HLA-DR and CD1a) and costimulatory molecules (CD80 and CD86) and down-regulated IL-12 secretion were also observed. In consistence, the allostimulatory ability of MSC-treated mature DCs on allogeneic T cells was impaired. In conclusion, our data suggested for the first time that human MSCs could suppress monocyte differentiation into DCs, the most potent antigen-presenting cells (APCs), thus indicating the versatile regulation of MSCs on the ultimate specific immune response.
Subject(s)
Cell Differentiation , Dendritic Cells/cytology , Mesenchymal Stem Cells/cytology , Monocytes/cytology , Cell Proliferation , Coculture Techniques , Dendritic Cells/immunology , Dendritic Cells/metabolism , Humans , Immunophenotyping , Interleukin-12/biosynthesis , Interleukin-12/metabolism , Mesenchymal Stem Cells/metabolism , T-Lymphocytes/cytology , T-Lymphocytes/immunologyABSTRACT
The hematopoietic system of the mouse arises from extraembryonic mesoderm that migrate through primitive streak to the presumptive yolk sac at day 7.0 of gestation. However, the mechanisms regulating mesoderm commitment to hematopoietic lineages remain poorly understood. Previous studies demonstrated that the development kinetics and growth factor responsiveness of hematopoietic precursors derived from embryonic stem cells (ES cells) is similar to that found in the yolk sac, indicating that the onset of hematopoiesis within the embryoid bodies (EBs) parallels that found in the embryo. Furthermore, in vitro differentiation of ES cells to hematopoietic cells is valuable for establishment of therapeutic clone against a variety of hematological disorders. Despite the identification of multipotential hematopoietic progenitors in EBs, a subset of more primitive progenitors, identical to the high proliferative potential colony-forming cells (HPP-CFC) derived from human and murine hematopoietic tissues, have not been clearly identified regarding particular their replating potential in vitro. HPP-CFC is among the most primitive hematopoietic multipotent precursors cultured in vitro. In this study, our aim was to investigate the in vitro and in vivo hematopoietic capacity of HPP-CFC within the day 12 EBs, rather than the expansion of more committed progenitors. In this study the HPP-CFC could be detected within EBs differentiated for 5 to 14 days of murine ES cells, but the development dynamics of the HPP-CFC differed greatly among distinct serum lots. Qualitatively HPP-CFC is capable of forming secondary colonies. As to our expectation the ES cells-derived HPP-CFC demonstrated similar regeneration capacity to those from yolk sac, giving rise to secondary granulocyte, erythrocyte, macrophage and mast cells, however largely differed from the counterparts of adult bone marrow. In addition, by RT-PCR ES cells-derived HPP-CFC were found to express transcription factors associated closely with stem cell proliferation including SCL, GATA-2 and AML1 as well as various receptors of hematopoietic growth factors such as c-kit, GM-CSF receptor and interleukin 3 receptor et al. Finally, in order to understand the in vivo hematopoietic capacity of the ES cells-derived HPP-CFC, spleen colony-forming unit (CFU-S) assay was performed. Nevertheless, typical CFU-S was not observed after transplantation of the day 12 EB cells or HPP-CFC colonies into lethally irradiated adult murine. In conclusion the HPP-CFC differentiated from murine ES cells displayed robust hematopoietic activity in vitro, however their in vivo reconstitution ability was not detected. The difference between in vitro and in vivo hematopoietic activities of ES cells-derived primitive hematopoietic precursors deserves further investigation.
Subject(s)
Embryonic Stem Cells/cytology , Hematopoietic Stem Cells/cytology , Animals , Basic Helix-Loop-Helix Transcription Factors/genetics , Cell Differentiation/genetics , Cell Differentiation/physiology , Colony-Forming Units Assay , Core Binding Factor Alpha 2 Subunit/genetics , GATA2 Transcription Factor/genetics , Hematopoietic Stem Cells/metabolism , Humans , Mice , Proto-Oncogene Proteins/genetics , Proto-Oncogene Proteins c-kit/genetics , Receptors, Granulocyte-Macrophage Colony-Stimulating Factor/genetics , Receptors, Interleukin-3/genetics , Reverse Transcriptase Polymerase Chain Reaction , T-Cell Acute Lymphocytic Leukemia Protein 1ABSTRACT
Long-tem culture initiating cells(LTC-IC), and in vitro assay of hematopoietic stem/progenitor cells, still represent a heterogeneous population in terms of proliferative capacity and sensitivity to different growth factors. Human umbilical cord (CB) is rich of hematopoietic progenitor cells measured by clonogenic assays and stem cells capable of reconstituting the marrow after transplantation. The influence of culture conditions on the in vitro behavior of LTC-IC from CB was evaluated. First, by using IRES sequence, FL and TPO cDNA were recombined with retroviral vector pLXSN by gene recombination technology. The recombinant plasmid pLFSN, pLTSN, pLFTSN were transfected into human stromal cell line HFCL. Then, LTC-IC were evaluated in long term cultures, comparing five types of stromal feeder layers: human bone marrow stromal cell, human stromal cell line HFCL, and stromal cell lines HDF tranfected with FL gene, HLT transfected with TPO gene or HFT co-transfected with FL and TPO genes. The results were demonstrated that after 8 weeks of coculture, three types of stromal cell lines that supported the maintenance of CFU-C for up to 3 weeks in vitro were identified. However, cocultivation of human bone marrow stromal cell and CB CD34(+) cells on HFT, CFU-C production continued up to 6 weeks or longer on these stroma. The absolute LTC-IC frequency in CD34(+) cells on human bone marrow stromal cell (2.65 +/- 0.76/1 000 cells) was no significant difference with on HFT (3.65 +/- 0.58/1 000 cells). Thus, HFT acts by direct contact to maintain the phenotype and function of the most primitive and quiescent human progenitors. Furthermore, HFT cell line was selected as the optimal one for supporting long-term culture feeder. It was concluded that LTC-IC progenitors from cord blood maintain growing upon the FL/TPO gene-modified stromal feeder layers in vitro.
ABSTRACT
Endothelial cells are the critical cell component of hematopoietic microenvironment. For the purpose of facilitating the study on modulating effect of endothelial cells in hematopoiesis, a human umbilical vein cell line, IEC, was established. Primary human umbilical vein endothelial cells were transfected with the plasmid pSV(3neo) carried SV40 large T antigen by lipofection. The IEC cells expressed factor VIII and the UEA I-binding ratio was about 97%. The chromosome variation was existed in the cell line, with the karyotype 45, XX, -18, 18q(+). The cell line retained the proliferative capacity at least 25 passages. IEC cells stimulated the growth of granulocyte-macrophage progenitor cells in coculture of cord blood CD34(+) cells with IEC cells. It is concluded that IEC cell line possessed the biological features of endothelial cell and supported hematopoiesis in vitro.